Asa 2016

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How to Establish a Perioperative Surgical Home in Your Institution
Zeev N. Kain, MD, MBA Orange/CA
The healthcare system in the US is currently undergoing a transformation with a new emphasis on the increased cost
of care and quality of clinical outcomes.
Critiques of the healthcare system in the
US point to the high cost (about $3
Trillion and 18% of our GDP) and
relatively low quality in certain areas (e.g.,
ranking of the US in preventable-death
among the industrialized nations). The
perioperative period is also attracting
critiques because of high cost (about 60%
of all hospital costs) as well as the
disjointed service that it provides to the
patients. Please see the figure below.
The Perioperative Surgical Home (PSH)

is an innovative clinical practice model
that has been proposed as one of the
potential solutions to our fragmented and
costly perioperative system. The PSH is
defined as “a patient-centered and
physician-led multidisciplinary and team-based system of coordinated care that guides the patient throughout the
entire surgical experience”. The overall goal of the PSH is to provide improved clinical outcomes and better
perioperative service at more cost effective cost. Conceptually, this model is based on high level coordination of
care from the moment a case was scheduled by the surgeon until 30 days after discharge from the hospital. Within
that time period, the PSH model aims to reduce variability in care provided. This is of importance given that
variability increases the likelihood for errors and complications as well as result in high cost and non-efficient
service. The much needed coordination of care within the entire perioperative episode, is best achieved by having
one team headed by anesthesiologists, to manage all aspects of this continuum from the time that the patient and
the surgeon make the decision for surgery until 30 days after discharge. During this perioperative episode, the goal
of the PSH is to be based on series clinical pathways and clinical protocols that reflect best evidence/ best practices
that are applied in a standardized way to every patient undergoing surgery. Obviously, the clinical protocol and
pathway needs to be adapted based on the specific needs and underlying clinical condition of the specific patient.
When best evidence/best practice does not exist or is not clear, the PSH team should develop an agreement for
standardization of a particular practice that will be applied to all patients. In this situation, local systems and policies
are highly important in decision making. At each step of this continuum from the decision to undergo surgery
until 30 days. After surgery, patients will be informed, educated, and involved in the decision process making and
planning of the surgical episode. By applying these concepts, anesthesiologists have a unique opportunity improve
outcomes, decrease length of stay and other metrics, and improve patient satisfaction.
The PSH needs to be adapted to the specific environment that exists in the organization that is using this model. For
example, the preoperative period can be managed by a preoperative clinic that manages any and all aspects of
preparation of the patient for surgery or a decentralized preoperative center that works with the surgeon’s offices to
assure that the patient is optimized to undergoing the specific surgical procedure. A second example may be given
for the postoperative period. Some surgical services would prefer the anesthesiologist to provide much of the
postoperative care that is required while other surgical services would like the anesthesiologist to be a ‘consultant’
for the various medical issues that may come up during that time period. More on this topic during the refresher
course itself. The Figure below underlines the major differences between the current and the future perioperative care
under a PSH model:
Refresher Course Lectures Anesthesiology 2016 © American Society of Anesthesiologists. All rights reserved. Note: This
publication contains material copyrighted by others. Individual refresher course lectures are reprinted by ASA with permission.
Reprinting or using individual refresher course lectures contained herein is strictly prohibited without permission from the
authors/copyright holders.
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As a first step there is a need to establish a steering committee and achieve the buy in of the administration as well
as the surgical chair of the department that is involved.
This involves the application of various change
management techniques. Change management is defined
as transformation that occurs as a result of a well-
orchestrated and well-led change strategy and
transition plan. The result is a metamorphosis to the
desired state in which there is a wide adoption of the
changes and the associated values, principles and/or
processes. It is highly important for any organization
that intends to implement the PSH to understand and use
the principles of change management. Experts in change
management are typically found in all organizations
either in the human resources departments or in the
quality and patient safety departments. It is crucial to
understand that only 15% of all organization who
emerge in a major change succeed in all of their
predefined goal and that much of this failure is because
of lack of a unifying vision and under-estimating the
need to manage the process. One of the best available
theorists in this area is John P. Kotter and I strongly
advice to read some of his books about change
management. This is of importance as we as physicians
were never trained in this area.
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Creating the PSH Team (total joint replacement as an example)

One of the first steps in this process is to establish a PSH steering committee. This steering committee is ideally
consists of anesthesiologists, surgeons, nurses, pharmacists,
physical therapist, case manager, social worker, information
technology experts and decision support experts. The steering
committee should meet weekly during the implementation
phase and quarterly once the PSH becomes operational. Ideally,
all team members should undergo training in Lean Six Sigma
and value stream mapping (a lean tool that uses a flow diagram
documenting in high detail every step of a process) for all the
perioperative processes needs to be developed. A daylong
retreat can be held for the steering committee and the process
champions, who can be the chairs of the Departments of
Anesthesiology and Orthopedic Surgery along with the Chief
Operating Officer of the hospital. During this retreat, decisions
can be made regarding who would serve as the various team leaders as well as membership for each of the working
groups that reported to the steering committee.
After receiving a short introduction to the PSH process by the orthopedic nurse practitioner in clinic, patients will be
scheduled to participate in the preoperative joint replacement education class and a Mind-Body Surgical Preparation
class. In addition, all patients will be seen in a preoperative anesthesia center by a nurse practitioner supervised by
an anesthesiologist 2 to 4 weeks before the surgical date and preoperative risk stratification and optimization
processes were followed. Standardized testing and management protocols, including nasal Staphylococcus aureus
screening and nosocomial infection prevention protocol, thromboembolic risk and prevention protocol, blood
conservation strategies, and urinalysis protocol will be instituted. All patients will receive protocol-driven,
standardized pain management based on a preoperative multimodal oral pain medication regimen starting the
morning of the surgery. Fluid management will be standardized and will be
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Protocols w i l l b e developed for the acute postoperative care team to include multimodal pain protocol,
pharmacy-led anticoagulation and thromboembolic event prevention protocols, and intensive physical therapy (PT)
protocols starting on the day of surgery with 2 sessions daily. The coordination of care, as well as the management
of any postoperative medical issues, can be handled by a dedicated anesthesiology-based 24/7 PSH Team.
Decisions about blood transfusion will be made jointly by the surgeon and anesthesiologists based on hemoglobin
levels, symptoms, and patient medical history. As a general guideline, the hemoglobin transfusion trigger will be 10
mg/dL in patients with known coronary artery disease and 7 mg/dL for the other patients. These values will
obviously vary between various institutions. Before discharge, the nursing staff, the orthopedic surgical team, and the
anesthesiology-based PSH team will explain all postoperative discharge instructions. The goal is to avoid
readmissions by developing and implementing guidelines for discharge orders, discharge instructions,
medication prescriptions, wound care, and follow-up clinic visits. Before discharge, patients were scheduled to
attend our coagulation clinic 2 to 3 days after discharge and for a follow-up visit with the orthopedic surgeon 2
weeks after the surgical date.
Collecting metrics is very important, as this is the key to convince the hospital administration and the surgeons that
PSH is a solid innovative clinical model. Prospectively collected data is to include (for example) patient
demographics, hospital length of stay (LOS, defined as postoperative number of nights in the hospital after
surgery), 30-day readmission rate, case start time in the morning, turnover time of the operating room, all
University Health Consortium data as well as Surgical Care Improvement Project (SCIP) data, including
antithrombotic treatment, proper timing, choice and discontinuation of prophylactic antibiotic treatment, early
removal of Foley catheters, and proper hair removal from surgical site. Data on the following perioperative
complications should be collected as well: periprosthetic joint infection, mechanical complications, wound healing
complications, pulmonary embolism, death, acute myocardial infarction, pneumonia, sepsis, deep vein
thrombosis, urinary tract infection, stroke, delirium, atrial fibrillation, acute kidney injury, and nausea and
vomiting.
Summary: To achieve the best results, we suggest that an entire bundle of the PSH is needed, with protocolization
of preoperative, intraoperative, postoperative, and post-discharge care and coordination of care. Moreover, the use of
LSS to reduce variability and increase standardization is a very important component in a PSH program. While we
encountered some challenges at the onset of Total Joint-PSH in our institution, particularly with adherence to the
protocols, the teamwork and coordination of postoperative care by the PSH anesthesia and orthopedic teams allowed
the program to stay on track. A major challenge facing any institution that has conducted an initial ‘proof of
concept’ is how to scale up the PSH to all perioperative services. For example, with the initial Total Joint-PSH in
our institution, the anesthesia regional/acute pain team handled postoperative PSH patient care management. This
model, however, is not viable now that we are moving to implement the PSH throughout all orthopedic surgery.
Other institutions, such as University of Alabama, address this issue by using critical care medicine services. This is
certainly a viable option; however, our current plan is designated anesthesiologists that will supervise dedicated PSH
nurse practitioners. As a field, anesthesiology has an opportunity to dramatically change the culture of care in the
United States through establishing the PSH model in our respective institutions and further expand our practice
outside of the operating rooms. Most indicators suggest that the practice of anesthesia is changing. The PSH model
offers anesthesiologists a concrete way to demonstrate their continued value to their patients and to their hospitals by
influencing better outcomes and decreasing cost.
** The above refresher course outlines is based on two manuscripts that were published in the May 2014 issue of
Anesthesia Analgesia:
Garson L, Schwarzkopf R, Vakharia S, Brenton A, Stead S, Cannesson M, Kain ZN. Implementation of a Total Joint
Replacement-Focused Perioperative Surgical Home: A Management Case Report. Anesth Analg 2014;118:1081-
1089.
Kain ZN, Vakharia S, Garson L, Engwall, S, Schwarzkopf, Gupta R, Cannesson M. The Perioperative Surgical
Home as a Future Perioperative Practice Mode. Anesth Analg 2014;118:1126-1130.
Reading list:
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Vetter TR, Goeddel LA, Boudreaux AM, Hunt TR, Jones KA, Pittet JF. The Perioperative Surgical Home: how can
it make the case so everyone wins? BMC Anesthesiology 2013, 13:6
Cannesson M, Kain ZN. Enhanced recovery after surgery versus perioperative surgical home: is it all in the name?
Anesth Analg 2014;118:901-902.
Vetter TR, Boudreaux AM, Jones KA, Hunter JM, Pittet JF. The Perioperative Surgical Home: How Anesthesiology
Can Collaboratively Achieve and Leverage the Triple Aim in Health Care. Anesth Analg 2014;118: 1131–1136.
Dexter F, Wachtel RE. Strategies for net cost reductions with the expanded role and expertise of anesthesiologists in
the perioperative surgical home. Anesth Analg 2014;118:1062-71.
John Kotter and Holger Rathgeber. Our Iceberg Is Melting: Changing and Succeeding Under Any Conditions. St.
Martin's Press (2006).
John Kotter. A sense of urgency. Harvard Business Press; (2008)
Mark Graban. Lean Hospitals: Improving Quality, Patient Safety, and Employee Engagement. Productivity Press
(2011)
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Common Neonatal Emergencies: You Can Never be Better Prepared
Mary Ellen McCann Boston, MA
Introduction
The first year of life represents the most vulnerable period and approximately two thirds of infant
deaths occurring in the first month of life in the USA .1 The leading cause of mortality in infants in 2011
was congenital anomalies at a rate of 126.1/100,000 births followed by premature births at a rate of
104/100,000 live births.2. Although all organ systems are affected by perioperative alterations in
physiology, the neurologic system in particular may be susceptible to neurotoxic and ischemic damage
during general anesthesia (Table1.). In this Refresher Course, we will discuss some of the relevant
anesthetic concerns in neonates during the perioperative period.
Prematurity
Closed claim analysis studies have revealed that neonates and infants are at higher risk for
morbidity and mortality than any other age group and is the result of respiratory and cardiac related
events.3, 4 When assessing the anesthetic risks of young infants, it is important to classify them as
neonates who are in their first month of life or infants who are in the first year of their life. Furthermore,
the risk of anesthesia is greater in preterm those that are less than 37 weeks postmenstrual age (PMA).
Infants who were born preterm but have reached a chronological age that makes them greater than 37
weeks PMA are considered ex-preterm infants. These distinctions are important when determining which
infants are appropriate for ambulatory cases. The rates of prematurity have risen recently in the United
States and developed world, in part, because of a higher incidence of multiple births and older maternal
age. Premature infants are particularly vulnerable during general anesthesia because of their immature
organ systems. Infants born with congenital anomalies are more likely to require both surgical
procedures and to have concomitant congenital cardiac defects, which can complicate the conduct of
anesthesia.
Cardiac function is limited and is heart rate dependent in healthy newborns because the immature
myocardium has limited compliance.5 Bradycardia, therefore, must be aggressively treated to ensure
adequate systemic and cerebral perfusion. A very common cardiac abnormality in premature infants is
patent ductus arteriosus (PDA), which can lead to either left to right or right to left cardiac shunting
depending on the pulmonary vascular resistance. It is customary to place two pulse oximeters on infants
with a known PDA or who are at risk for a PDA to measure preductal (right upper extremity) and
postductal (left upper and both either lower extremity) oxygen saturations during surgical procedures.
Intraoperative hypoxia, hypercarbia, acidosis, hypothermia, and surgical stress can lead to ductal
reopening. Neonates may need vasopressors such as dopamine or additional fluids to maintain
normotension during general anesthesia. The parasympathetic system is predominant in preterm and term
infants; thus stimulation of the vagus nerve by larygoscopy or the stress of hypoxia can cause profound
and rapidly occurring bradycardia. Many pediatric anesthesiologists will prophylactically administer an
anticholinergic agent before manipulating the airway of a neonate especially in the awake state.
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The respiratory system is also affected by prematurity. Although the type II pneumocytes begin to
differentiate by 24 weeks gestation, adequate surfactant is not created until about 34-36 weeks gestation.
Maternal treatment with betamethasone before birth and the administration of surfactant
immediately after birth improves respiratory mechanics but many preterm infants still require respiratory
assistance such as additional oxygen, continuous positive airway pressure (CPAP) or mechanical
ventilation.6 Preterm infants have a very high rate of high oxygen consumption (more than twice that of
adults per body weight) and low pulmonary functional residual capacity. Therefore they are at high risk
for oxygen desaturation with any interruption of ventilation. Anesthetic inductions can be complicated by
tracheomalacia, which makes mask ventilation difficult. Furthermore indiscriminant mask ventilation can
result in abdominal distension, which in turn impedes diaphragmatic excursion.
Premature infants are at higher risk for postoperative apnea after general anesthesia with a
reported rate between 5-50 % depending on the method of measuring apnea.7 Studies using clinical
measures such as nursing observation with or without impedence pneumonography report rates between
5-10% with anemia, lower gestational age and length of surgery all being risk factors.7 There is some
evidence that regional anesthesia has a lower rate of postoperative apnea but regional anesthesia
supplemented with sedatives has a reported rate of postoperative apnea greater than general anesthesia
alone.8, 9 Since neonates can have obstructive, central or mixed apnea with most episodes occurring in the
first 12 hours postoperatively, most pediatric anesthesiologists recommend at least a 12 hour apnea free
period before discharge for former preterm infants who have undergone surgery.10 The risk of
postoperative apnea may persist until the infants reach a postmenstrual age of 60 weeks.7
Preterm infants are also at risk for retinopathy of prematurity, a progressive overgrowth of retinal
vessels, which can lead to intraocular hemorrhage, retinal detachment and blindness. Although it has
been reported in term infants who were not given supplemental oxygen, it is typically found in preterm
infants exposed to supplemental oxygen.11 It is important for anesthesiologists to limit the inspired
oxygen for infants less than 46 weeks postmenstrual age and aim for oxygen saturation percentage in the
range of low 90s.11
The immature renal and hepatic systems affect fluid and electrolyte management and alter the
metabolism of common anesthetic medications and antibiotics during the perioperative period. Neonates
have a lower glomerular filtration rate and urine concentrating ability. This leads to impaired renal
clearance of solutes and drugs. Drug metabolism and protein binding are also diminished due to immature
hepatic function in the neonate. Therefore it is also important to regulate the fluids and drugs
administration carefully in these patients.
The surface area of neonates is larger per body weight than older patients and thus they are
susceptible to evaporative losses both through surgical wounds as well as their skin. Their renal system is
unable to concentrate urine to compensate for fluid losses. The larger surface area also puts neonates and
premature infants at higher risk for significant temperature fluctuations during surgical procedures.
Hypothermia can stress the infant leading to respiratory failure and the need for postoperative ventilation.
On the other hand, it is important not to overheat premature infants while in the operating rooms. There
are many stressors that may be unavoidable such as episodes of hypotension, hypoxia or hypocarbia that
occur during surgery. The potential for cerebral damage of these stressors is exacerbated by hyperthermia.
Neurotoxicity
General anesthetics in vivo and in vitro experiments have been shown to have neurotoxic effects
on the developing central nervous system. These effects include decreased neurogenesis, abnormal
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dendrite formation, decreased glial cell formation and increased neuroapoptosis in both the brain and
spinal cord.12-14 Neuroapoptosis or programmed cell death occurs normally during fetal development as
part of cerebral and neuronal maturation. It differs histologically from ischemic cell death in that there is
no inflammation and it tends to occur in isolated cells rather than regionally. However, anesthetic
exposure during vulnerable periods in laboratory animal has been shown to lead to a marked increase in
apoptotic cell death and subsequent learning deficits especially in the domain of executive function in
animals allowed to mature. The general anesthetics found to cause this neurotoxicity include most of the
commonly used agents such as those that block N-methyl-D-aspartate (NMDA) glutamate receptors
(ketamine, nitrous oxide) and those that are gamma amino butyric acid (GABA) agonists (volatile
anesthetics, benzodiazepines, barbiturates). The period of maximal vulnerability for the neuroapoptotic
effects of anesthetics in animals seems to correspond with the time of maximal synaptogenesis. For
rodents this is day 7 of life, for rhesus monkeys this is day 122 of gestation up to day 5 of life with no
excessive apoptosis seen on day 35.15, 16 The neurotoxic effects of anesthetics on animals are also dose
and duration dependent. Extrapolations of these preclinical studies to humans are fraught with
uncertainty because of physiological differences between species and difficulties in physiologic
monitoring for glucose, blood pressure and respiration in very young, small mammals.
The issue of anesthetic neurotoxicity is further muddled by the fact that in some circumstances
such as cerebral ischemia, general anesthetics can be protective. Isolated pain or surgical stress can lead to
increased neuroapoptosis in animals. The addition of surgical stimulation has been found to lessen the
amount of apoptosis seen after anesthetic exposure in young animals compared to those animals who
received no painful stimulation.17, 18
The susceptibility of human neonates to the neuroapoptotic effects of general anesthesia is not
been elucidated. The potential period of vulnerability might be the period of maximal synaptogenesis
during fetal and early postnatal development, which in humans occurs between the third trimester of
gestation to about 36 months of age. However, there is controversy in this area, with some researchers
using neuro-informatic analysis of brain development across mammalian species concluding that the
relevant period during human development is 17-20 weeks gestation.19, 20 This is roughly the same time
period of maximal human susceptibility to fetal alcohol syndrome which is caused by in utero exposure to
ethanol which is both a NMDA antagonist and GABA agonist.21 A recent prospective randomized
equivalence trial comparing the neurocognitive outcomes at age 2 years, of infants that received either
sevoflurane or regional bupivacaine anesthesia for inguinal hernia repair found no neurocognitive
differences between the two groups.22
General anesthesia may cause both neurotoxic and ischemic damage in neonates.23 The urgent
nature of many of the surgeries as well as physiological changes that neonates undergo especially in the
first few days of life leave many infants in suboptimal condition for general anesthesia. Difficulties in
accurately measuring end-tidal CO2, blood pressure, pH, blood glucose and oxygen saturation levels can
delay necessary interventions for these fragile patients. In general, these infants have less reserve and thus
small alterations in blood pressure can lead to inadequate cerebral perfusion if the infant becomes
hypotensive or increase the risk of intraventricular hemorrhage if the infant becomes hypertensive.24
Periods of hypocarbia and hyperoxia in infants with hypoxic ischemic injury are associated with increased
morbidity and death and may be a risk factor for outcomes after general anesthesia because of decreased
cerebral perfusion.25-27 Even mild hyperthermia in utero just prior to delivery or after a hypoxic ischemic
injury is associated with poor neurologic outcomes but the risk for anesthetized infants is unknown.28-30
Hypoglycemia and hypoxia in infants under general anesthesia may be a risk factor for poor
development.31
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Specific Conditions: (Table 2)
Tracheoesophageal Fistula (TEF)
The incidence of esophageal atresia with tracheoesphageal fistula (TEF) is approximately 1/3000 live
births. The most common type of presentation occurring 87% of the time is an esophageal atresia with
distal TEF (Table 3). Infants present with copious salivation, and choking/coughing with the onset of
feeding. TEF is also seen as part of the VACTERL association (vertebral anomalies, anal atresia, cardiac
defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities). The mainstay of anesthetic
management of these infants is to isolate and block the fistula prior to positive pressure ventilation. This
can be done with a balloon-tipped catheter insertion by the surgeon while doing a rigid bronchoscopy.
Sometimes it is possible to pass an endotracheal tube past the fistula into the right main stem bronchus if
a bronchial blocker is not feasible. Initial surgical treatment can include gastrostomy, fistula repair, spit
fistula, central line placement and the Foker procedure for long gap esophageal atresia.
Gastroschisis and Omphalocele
These diseases are caused by defects in the abdominal wall leading to the intestines being outside the
abdominal cavity. In the case of omphalocele, the intestines are encased in a thin layer of tissue. The
prevalence of gastroschisis is approximately 1/2000 live births and omphalocele is approximately 1/4000
live births. Gastroschisis is usually an isolated congenital anomaly that is increasing in prevalence.
Infants born with gastroschisis and omphalocele are at high risk for infection, dehydration and
hypothermia and generally are surgically managed emergently. Omphalocele is associated with genetic
abnormalities such as trisomies 13, 18, and 21 and Beckwith-Wiedemann Syndrome. Infants with
Beckwith Wiedemann Syndrome have large tongues that can complicate endotracheal intubation. These
babies are at risk for hypoglycemia secondary to hyperinsulinemia. Infants are either repaired primarily
or the abdominal contents are placed in a silastic silo that is cinched every day to incrementally move the
intestines into the abdominal cavity (Figure1). Very often these infants require postoperative ventilation
with muscle relaxation to allow their abdominal cavity to accommodate their intestines.
Pulmonary Hypoplasia and Congenital Diaphragmatic Hernia (CDH)

Congenital diaphragmatic hernias occur in approximately 1/2000 live births. They are always
accompanied by pulmonary hypoplasia due to a decrease in the cross-sectional area of the pulmonary
vasculature. The mortality rate is very high-approaching 50%. Treatment often consists of endotracheal
intubation and extracorporeal membrane oxygenation (ECMO) initially. Often the diaphragm is repaired
while the infant is on ECMO. Ventilatory strategies for conventional ventilation include permissive
hypercapnia to reduce barotrauma to the lungs. Up to 40% of these infants may have congenital heart
disease, which leads to a poorer prognosis. These infants are often treated with vasopressors to maintain
their blood pressures and vasodilators (nitric oxide) to improve their pulmonary hypertension.
Necrotizing enterocolitis (NEC)
Necrotizing enterocolitis is usually seen in extremely premature infants (less than 1500 g) who are on oral
formula feeds. Radiographic finding may include pneumatosis intestinalis, abdominal free air, distended
loops of bowel and intraperitoneal free fluid. Symptoms may be subtle with an increase in apnea and
bradycardia, anemia and delayed gastric emptying. Later signs include increasing abdominal girth,
diarrhea, respiratory failure and shock. The mortality for this disease is very high. Treatment initially is
bowel rest with intravenous nutrition and antibiotics. Infants with evidence of bowel perforation are
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usually treated surgically but in some cases can be managed with interventional radiologic placement of
drains.
Inguinal Herniorrhaphy
Inguinal hernias are one of the most common surgical conditions seen in neonates occurring in about 1-
5% in full term infants and up to 30% of preterm infants.32 Repair can be done either open,
laparascopically or open with laparascopic view of the side contralateral to the presenting hernia. About
10% of infants with a unilateral hernia are found to have an occult hernia on the contralateral side. All
types of surgical repairs can be accomplished with general anesthesia. Regional anesthesia alone can be
done in open procedures but not in complete laparascopic procedures. Pain management postoperatively
can be accomplished with an intraoperative caudal neuraxial block or ilioinguinal peripheral nerve block.
Pyloric Stenosis
Infantile hypertrophic pyloric stenosis is most commonly seen in first-born male infants between the ages
of 2 and 6 weeks of age. It is characterized by severe non- bilious vomiting which can lead to a
hypochloremic metabolic alkalosis. Physical signs include a palpable mass (“olive”) above the
umbilicus. Surgery (laparoscopic or open) should be done after the electrolyte disturbances and
dehydration have resolved. In rare cases it can be treated medically with intravenous fluids and oral
atropine.
Minimally Invasive Surgery
The advantages of this technique include smaller incisions, shorter postoperative recoveries and
less postoperative pain. However, these cases are highly challenging for anesthesiologists. Thoracic
procedures in newborns include procedures for lung resections and biopsies, congenital diaphragmatic
repair, tracheal esophageal fistula and atresia, patent ductus arteriosis and repair of mediastinal masses.
The incidence of late postoperative scoliosis is increased in neonates who have had open thoracotomies.33
Single lung anesthesia in newborns can be accomplished with placement of a balloon tipped
catheter either passed through or beside an endotracheal tube into the mainstem bronchus of the ipsilateral
lung using bronchoscopy to verify its position. Visualization of the pleural space around the partially
collapsed lung can be augmented by low flow and low pressure insufflations of CO2. Many of these
cases are associated with hypotension, respiratory acidosis, hypercapnia and hypothermia. Rarer
complications include CO2 embolus and pneumoperitoneum.34 A retrospective review of congenital
diaphragmatic hernia repairs done thorascopically in neonates demonstrated a 50% incidence of decrease
in oxygen saturations and rise in endtidal CO2.35 These changes were managed by increasing minute
ventilation, decreasing insufflating CO2 flow rate and pressure and maintaining denser neuromuscular
blockade. A pilot randomized controlled trial in 20 infants >1.6 kg undergoing CDH or esophageal
atresia repair done either by open thoracotomy or thoracopically found that there was significantly more
respiratory acidosis and hypercapnia in CDH patients done thorascopically.36 The esophagael atresia
patients did not have significant changes in endtidal CO2, pH or O2 saturation.
Laparoscopic surgical approaches can be used for pyloromyotomy, gastrostomy, fundoplication,

gut malrotation, duodenal atresia, ovarian pathology, Hirshsprungs Disease pull-through, imperforate
anus and inguinal herniorrhaphy. In neonates, surgeons often must access the umbilicus through an open
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techique because of a retained umbiical stump and the danger of inadvertent tissue damage from blind
trochar insertion into the tiny abdominal cavity. It is necessary to develop a pneumoperitoneum in order
for clear visualization of the abdominal organs. The most commonly used method is low pressure
insufflation of CO2 which typically leads to higher levels of endtidal CO2 and respiratory acidosis in
neonates compared with older individuals. It is advised to maintain the intracavitary pressure at or below
10 mmHg to avoid undue cardiovascular effects in neonates. Higher pressures can lead to reduced
venous return to the heart, hypotension and difficulties in ventilation if the diaphragm is unable to fully
descend into the abdominal cavity. Maintaining adequate hydration is also key in avoiding intraoperative
hypotension and neuromuscular blockade will facilitate ventilation.
Neuroendoscopic procedures for cranial suture synostosis and hydrocephalus have been found to
decrease hospital stays and need for transfusions.37 Endoscopic third ventriculostomy can be
accompanied by acute bradycardia that may be part of a Cushing’s reflex or by direct stimulation of the
ventricular floor. Acute elevations in intracranial pressure even in newborns with open fontanelles can be
caused by a mechanical disturbance of egress of irrigation fluid. Small amounts of intracranial
hemorrhage must be managed by copious amounts of irrigation fluid that can also lead to hypothermia.
Since neonates and preterm infants skulls are too thin for fixation pins, neuromuscular blockade is
essential to prevent movement during delicate neurosurgery.
Regional anesthesia
Regional anesthesia used as an adjunctive agent can reduce the amount of general anesthesia
exposure a neonate receives during major abdominal and thoracic surgery and can also be used to ensure
postoperative analgesia. Pure regional anesthesia (either spinal, spinal with epidural or epidural alone) has
been used for inguinal herniorrhaphies, PDA, gastrostomy, pyloromyotomy, bladder extrophy, anoplasty,
omphalocele, circumcision and orthopedic surgery. The distal end of the spinal cord in neonates is
generally between L2 and L3, so pediatric anesthesiologists place a 22 or 25 gauge needle below this
interspace to achieve spinal anesthesia. Neonates have more spinal fluid per body weight compared to
adults, require a larger dose per body weight and the duration of neuromuscular block is shortened.
Local anesthetic toxicity is a greater concern in neonates because the bound fraction of agent is decreased
secondary to low levels of alpha-1 acid glycoprotein in neonates and because of decreased clearance and
elimination half-life. Ester local anesthetics such as 3-chloroprocaine are metabolized by plasma
pseudocholinesterase rather than the liver and thus may be a safer option for very young neonates that
require ongoing local anesthetic infusions for anesthesia. Lidocaine, ropivacaine and levobupivacaine are
associated with less cardiotoxicity than bupivacaine and thus are preferred by some institutions.38
Intravenous intralipid (20% in a dose of 1 ml/kg given every 3-5 minutes for a total dose of 3 ml/kg) can
be lifesaving in infants manifesting malignant ventricular dysrhymias from local anesthesia toxicity.38
The success rate for spinal anesthesia in neonates varies between 78-89% in single institution
series.39-42 A recent multicenter study comparing the effects of general anesthesia versus regional
anesthesia in infants less than 60 weeks postmenstrual age found that surgical times did not vary between
the two techniques but that the over all operating room time and anesthesia time was greater in the general
anesthesia group.43 Adjunctive single shot caudal or epidural with a catheter can be used in awake or
anesthetized infants to prolong the effects of a spinal anesthetic.
Caudal insertion is the most common approach for epidural anesthesia in anesthetized neonates
undergoing major abdominal or thoracic surgery. Catheters can be threaded into the thoracic epidural
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space for surgeries involving the thorax and abdomen and into the lumbar space for lower pelvic and limb
surgeries either using ultrasonography or epidurography for accurate placement. Advantages of
adjunctive epidural analgesia postoperatively include quicker times to extubation and greater blunting of
postoperative stress responses. Important disadvantages include that the highest success rates in
threading epidural catheters to the thoracic space are with adult size catheters which may be too large for
premature infants. In a study of 20 infants with weights ranging between 520 grams to 2750 grams using
a smaller specially designed 23 guage neonatal catheter, there was a success rate of 85% with
malpositioned catheters ending up in epidural vessels, intrathecally and curled up in the lumbar space.44 In
this same study, 9 of the 20 infants were successfully extubated at the the end of the procedure.
Although there are theoretical benefits to regional anesthesia such as better analgesia, decreased
stress response, earlier postoperative extubation, and less general anesthetic exposure, there is little
published evidence that clearly demonstrates an improvement in care.8, 45, 46 The risks of regional
anesthesia in neonates and premature infants is also not well characterized at this time. The Pediatric
Regional Anesthesia Network database in the US has tracked the outcomes of nearly 15,000 regional
anesthetics since 2007 without significant morbidity or mortality found in neonates although the number
of neonates followed is small.45, 47 There are isolated case reports of meningitis, spinal fluid leak and total
spinal anesthetics in neonates under going spinal anesthetics.48, 49
Summary:
Ongoing advances in the perioperative management of the neonate have undoubtedly decreased
the incidence of morbidity and mortality of this vulnerable group. The introduction of new surgical
techniques and more comprehensive understanding of the effects of anesthetic drugs and techniques on
the surgical neonate present many challenges to surgeons and anesthesiologists. Many conditions are
unique to small children. Thorough preoperative evaluation and open communication between members
of the health care team are important. A basic understanding of age-dependent variables and the
interaction of anesthetic and surgical procedures are essential in minimizing perioperative morbidity and
mortality.
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References
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disparities. In: US Health and Human Services HRaSA, Maternal and Child Health Bureau ed. Rockville,
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2 MacDorman MF HD, Mathews TJ. Recent Declines in infant mortality in the United States 2005-2011.
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3 Cohen MM, Cameron CB, Duncan PG. Pediatric anesthesia morbidity and mortality in the
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4 Bhananker SM, Ramamoorthy C, Geiduschek JM, et al. Anesthesia-related cardiac arrest in children:
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5 Brusseau R, McCann ME. Anaesthesia for urgent and emergency surgery. Early Hum Dev 2010; 86:
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6 Ward RM. Pharmacologic enhancement of fetal lung maturation. Clinics in perinatology 1994; 21: 523-
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7 Cote CJ, Zaslavsky A, Downes JJ, et al. Postoperative apnea in former preterm infants after inguinal
herniorrhaphy. A combined analysis. Anesthesiology 1995; 82: 809-22
8 Craven PD, Badawi N, Henderson-Smart DJ, O'Brien M. Regional (spinal, epidural, caudal) versus
general anaesthesia in preterm infants undergoing inguinal herniorrhaphy in early infancy. The Cochrane
database of systematic reviews 2003: CD003669
9 Welborn LG, Rice LJ, Hannallah RS, Broadman LM, Ruttimann UE, Fink R. Postoperative apnea in
former preterm infants: prospective comparison of spinal and general anesthesia. Anesthesiology 1990;
72: 838-42
10 Kurth CD, LeBard SE. Association of postoperative apnea, airway obstruction, and hypoxemia in
former premature infants. Anesthesiology 1991; 75: 22-6
11 McGregor ML, Bremer DL, Cole C, et al. Retinopathy of prematurity outcome in infants with
prethreshold retinopathy of prematurity and oxygen saturation >94% in room air: the high oxygen
percentage in retinopathy of prematurity study. Pediatrics 2002; 110: 540-4
12 Brambrink AM, Evers AS, Avidan MS, et al. Isoflurane-induced neuroapoptosis in the neonatal rhesus
macaque brain. Anesthesiology 2010; 112: 834-41
13 Loepke AW, Soriano SG. An assessment of the effects of general anesthetics on developing brain
structure and neurocognitive function. Anesth Analg 2008; 106: 1681-707
14 De Roo M, Klauser P, Briner A, et al. Anesthetics rapidly promote synaptogenesis during a critical
period of brain development. PloS one 2009; 4: e7043
15 Jevtovic-Todorovic V, Hartman RE, Izumi Y, et al. Early exposure to common anesthetic agents causes
widespread neurodegeneration in the developing rat brain and persistent learning deficits. J Neurosci
2003; 23: 876-82
16 Slikker W, Jr., Zou X, Hotchkiss CE, et al. Ketamine-induced neuronal cell death in the perinatal rhesus
monkey. Toxicol Sci 2007; 98: 145-58
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following inflammatory pain in newborn rat brain. Pediatr Res 2007; 62: 283-90
18 Ruda MA, Ling QD, Hohmann AG, Peng YB, Tachibana T. Altered nociceptive neuronal circuits after
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19 Clancy B, Finlay BL, Darlington RB, Anand KJ. Extrapolating brain development from experimental
species to humans. Neurotoxicology 2007; 28: 931-7
20 Clancy B, Kersh B, Hyde J, Darlington RB, Anand KJ, Finlay BL. Web-based method for translating
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21 Renwick JH, Asker RL. Ethanol-sensitive times for the human conceptus. Early Hum Dev 1983; 8: 99-
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22 Davidson AJ, Disma N, de Graaff JC, et al. Neurodevelopmental outcome at 2 years of age after
general anaesthesia and awake-regional anaesthesia in infancy (GAS): an international multicentre,
randomised controlled trial. Lancet 2015
23 McCann ME, Schouten AN. Beyond survival; influences of blood pressure, cerebral perfusion and
anesthesia on neurodevelopment. Paediatr Anaesth 2014; 24: 68-73
24 Rhondali O, Mahr A, Simonin-Lansiaux S, et al. Impact of sevoflurane anesthesia on cerebral blood
flow in children younger than 2 years. Paediatr Anaesth 2013
25 Pappas A, Shankaran S, Laptook AR, et al. Hypocarbia and adverse outcome in neonatal hypoxic-
ischemic encephalopathy. J Pediatr 2011; 158: 752-8 e1
26 Fabres J, Carlo WA, Phillips V, Howard G, Ambalavanan N. Both extremes of arterial carbon dioxide
pressure and the magnitude of fluctuations in arterial carbon dioxide pressure are associated with
severe intraventricular hemorrhage in preterm infants. Pediatrics 2007; 119: 299-305
27 Markus T, Hansson S, Amer-Wahlin I, Hellstrom-Westas L, Saugstad OD, Ley D. Cerebral inflammatory
response after fetal asphyxia and hyperoxic resuscitation in newborn sheep. Pediatr Res 2007; 62: 71-7
28 Bissonnette B, Sessler DI. Mild hypothermia does not impair postanesthetic recovery in infants and
children. Anesth Analg 1993; 76: 168-72
29 Shankaran S, Laptook AR, Ehrenkranz RA, et al. Whole-body hypothermia for neonates with hypoxic-
ischemic encephalopathy. N Engl J Med 2005; 353: 1574-84
30 Gunn AJ, Bennet L. Is temperature important in delivery room resuscitation? Seminars in neonatology
: SN 2001; 6: 241-9
31 Inder T. How low can I go? The impact of hypoglycemia on the immature brain. Pediatrics 2008; 122:
440-1
32 Brandt ML. Pediatric hernias. The Surgical clinics of North America 2008; 88: 27-43, vii-viii
33 Roclawski M, Pankowski R, Smoczynski A, et al. Secondary scoliosis after thoracotomy in patients
with aortic coarctation and patent ductus arteriosus. Studies in health technology and informatics 2012;
176: 43-6
34 Olsen M, Avery N, Khurana S, Laing R. Pneumoperitoneum for neonatal laparoscopy: how safe is it?
Paediatr Anaesth 2013; 23: 457-9
35 Parelkar SV, Oak SN, Bachani MK, et al. Minimal access surgery in newborns and small infants; five
years experience. Journal of minimal access surgery 2013; 9: 19-24
36 Bishay M, Giacomello L, Retrosi G, et al. Hypercapnia and acidosis during open and thoracoscopic
repair of congenital diaphragmatic hernia and esophageal atresia: results of a pilot randomized
controlled trial. Ann Surg 2013; 258: 895-900
37 Schulz M, Buhrer C, Spors B, Haberl H, Thomale UW. Endoscopic neurosurgery in preterm and term
newborn infants--a feasibility report. Child's nervous system : ChNS : official journal of the International
Society for Pediatric Neurosurgery 2013; 29: 771-9
38 Bosenberg A, Flick RP. Regional anesthesia in neonates and infants. Clinics in perinatology 2013; 40:
525-38
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39 Frumiento C, Abajian JC, Vane DW. Spinal anesthesia for preterm infants undergoing inguinal hernia
repair. Arch Surg 2000; 135: 445-51
40 Kachko L, Simhi E, Tzeitlin E, et al. Spinal anesthesia in neonates and infants - a single-center
experience of 505 cases. Paediatr Anaesth 2007; 17: 647-53
41 Shenkman Z, Hoppenstein D, Litmanowitz I, et al. Spinal anesthesia in 62 premature, former-
premature or young infants--technical aspects and pitfalls. Canadian journal of anaesthesia = Journal
canadien d'anesthesie 2002; 49: 262-9
42 Williams RK, Adams DC, Aladjem EV, et al. The safety and efficacy of spinal anesthesia for surgery in
infants: the Vermont Infant Spinal Registry. Anesth Analg 2006; 102: 67-71
43 Davidson AJ. GAS. 2014
44 van Niekerk J, Bax-Vermeire BM, Geurts JW, Kramer PP. Epidurography in premature infants.
Anaesthesia 1990; 45: 722-5
45 Bosenberg AT, Johr M, Wolf AR. Pro con debate: the use of regional vs systemic analgesia for
neonatal surgery. Paediatr Anaesth 2011; 21: 1247-58
46 Walker SM, Yaksh TL. Neuraxial analgesia in neonates and infants: a review of clinical and preclinical
strategies for the development of safety and efficacy data. Anesth Analg 2012; 115: 638-62
47 Polaner DM, Taenzer AH, Walker BJ, et al. Pediatric Regional Anesthesia Network (PRAN): a multi-
institutional study of the use and incidence of complications of pediatric regional anesthesia. Anesth
Analg 2012; 115: 1353-64
48 Allee JI, Goins KM, Berde CB, McCann ME. A case of cerebrospinal fluid leak in an infant after spinal
anesthesia. J Clin Anesth 2013; 25: 217-9
49 Easley RB, George R, Connors D, Tobias JD. Aseptic meningitis after spinal anesthesia in an infant.
Anesthesiology 1999; 91: 305-7
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Table 1. Common Prepartum and Perinatal Conditions associated with Neonatal Morbidity
Condition Perioperative Problems
Asphyxia  Depressed myocardial function

 Hypoglycemia
 Electrolyte abnormalities
 Impaired cerebral autoregulation
 Decreased gut perfusion
 Shock
 Coagulopathy
Infants of diabetic mothers  Hypoglycemia

 Hypocalcemia
 Polycythemia
Prematurity  Hypoglycemia
 Respiratory distress syndrome
 Postoperative apnea
 Retinopathy of prematurity
 Temperature instability
Small for gestational age  Hypoglycemia

 Hypocalcemia
 Polycythemia and hyperbilirubinemia
 Temperature instability
 Congenital anomalies
 Increased incidence of pulmonary
aspiration/pneumonia
Large for gestational age  Birth injuries (brachial/phrenic nerve, fractured

clavicle)
 Hypoglycemia
 Hypocalcemia
 Polycythemia and hyperbilirubinemia
 Meconium aspiration
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Figure 1.
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Table 2. Perioperative Considerations for Complex Neonatal Surgery.
Surgical Diagnosis Preoperative Intraoperative Postoperative

Considerations Considerations Considerations
Gastroschisis and RDS if premature Hypovolemia Oxygenation/Ventilation

Omphalocele Cardiac anomalies in Hypothermia problems
omphalocele Hypercarbia Bowel ischemia
Sepsis Hypoxemia Renal Failure
Intestinal atresia Respiratory acidosis Peritonitis
Hypovolemia Metabolic acidosis Sepsis
Hypoglycemia Atelectasis Metabolic acidosis
(Beckwith- Volume Hypothermia
Wiedemann) overload/pulmonary Epidural for post-op
edema analgesia
CDH Over-expanded Epidural or narcotic- Epidural for post-op

contralateral lung based technique analgesia
Hypoplastic ipsilateral PTX PTX
lung Hypovolemia Hypovolemia
PTX Pulmonary HTN Pulmonary HTN
Pulmonary HTN Suprasystemic RVBPs Suprasystemic RVBPs
May be on ECMO Hypoventilation Hypoventilation
Respiratory acidosis Hypothermia Hypothermia
Metabolic acidosis Metabolic acidosis Metabolic acidosis
IVH R-to-L shunting R-to-L shunting
Hypoglycemia Volume overload Volume overload
Hypokalemia if on May require HFOV or
diuretics ECMO after
“honeymoon period”
within 24-48 hrs or
repair
TEF Aspiration Epidural or narcotic- Epidural for postop

Gastric distention based technique analgesia
RDS if premature Aspiration PTX
Cardiac anomalies Hypothermia Apnea
GI anomalies Metabolic acidosis Hypoventilation
Renal anomalies Respiratory acidosis Tracheal leak
PTX Weakness
Atelectasis/hypoxemia RLN injury
Mucus plugging Pneumonia
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Gastric distention
Extubation in OR if
possible
NEC RDS if premature No epidural if septic ROP

Sepsis Minimize FiO2 (ROP) Hypovolemia
ARDS Pressors/ionotropes Metabolic acidosis
CHF with cardiac Hypovolemia Sepsis
anomalies Metabolic acidosis Pulmonary edema with
Pulmonary PTX fluid remobilization
overcirculation/ Hypoglycemia Narcotics for postop
pulmonary HTN Hypocalcemia analgesia
IVH with
prematurity/birth
asphyxia
Renal insufficiency if
on NSAIDs for
PDA
Hypoglycemia
Hypocalcemia
DIC
Table 3. Types of Congenital Tracheoesphageal Fistulas (TEF) and Esophageal Atresia
Anatomic Characteristics Percent of Cases (%)

Esophageal atresia with distal TEF 87
Isolated esophageal atresia without TEF 8
Isolated TEF 4
Esophageal atresia with proximal TEF 1
Esophageal atresia with proximal and distal TEF 1
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Questions:
1. Ventral wall defects

a. Such as gastroschisis are very commonly associated with cardiac defects
b. Are rarely associated with genetic or chromosomal abnormalities
c. Such as omphaloceles are often associated with congenital cardiac disease
d. Are almost always repaired in one stage
2. Pyloric stenosis
a. is most commonly seen in first born girls
b. is most commonly associated with hyperchloremic alkalosis
c. is most commonly associated with hypochloremic acidosis
d. is never a surgical emergency
3. The most common type of tracheoesophageal fistula is:
a. esophageal atresia with distal TEF
b. isolated esophageal atresia
c. H type fistula
d. esophageal atresia with proximal TEF
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Current Controversies in Adult Outpatient Anesthesia

Jeffrey L. Apfelbaum, M.D. Chicago/Illinois
Introduction
The world of ambulatory anesthesiology continues to present anesthesiologists with a rapidly changing
array of challenges, particularly as we continue to focus on quality and safety issues in this face-paced environment.
This Refresher Course will provide an update on current controversial issues in adult outpatient anesthesia,
including fast tracking; preoperative assessment, evaluation, and preparation; the paradoxical relationship between
obesity and risk in patients undergoing non cardiac surgery; and the current status of a new paradigm (computer
assisted personalized sedation or CAPS) of moderate sedation for our patients. Additionally we will consider a
variety of “breaking news” areas of controversy which may include topics such as advances in and
recommendations to enhance perioperative communication; treatment decisions for patients on beta blockers and
those with coronary artery stents; opportunities to incorporate one’s personal outcomes data into your patient care
plan and the potential effect of choice of anesthetic on cancer recurrence rates.
Fast Tracking: Eliminating Intensive Post-Operative Care in Same Day Surgery Patients Using Short Acting
Fast Emergence Anesthetics
Many anesthetics have the pharmacokinetic and pharmacodynamic advantages of a shorter duration of
action and a more rapid rate of recovery that permit a faster emergence from anesthesia compared with their
predecessors. Less than 30 years ago, it was unthinkable that patients would be able to return home on the day of
surgery. Today, advances in surgery and anesthesiology make it routine to perform the vast majority of all surgical
procedures safely and effectively on an ambulatory basis, with many patients ready to be reunited with their families
within minutes of emergence from anesthesia. In today’s cost sensitive healthcare environment, the processes of
ambulatory surgical care must be continually re-evaluated to take advantage of advances in technology and
pharmacology and to optimize efficiency of the ambulatory surgical care without detriment to patient safety or
satisfaction.
Traditionally, ambulatory surgical patients go from the operating room to the postanesthesia care unit
(PACU) or recovery room (a highly specialized intensive care unit) for their immediate postoperative recovery from
anesthesia and then to a second stage recovery unit (SSRU) for preparation for home readiness. By its very nature
as a specialized ICU, the PACU is an expensive, labor-intensive environment. After a set of recovery criteria 1, 2, 3
are met in the PACU, the patient is usually transferred to the SSRU. In the SSRU, the patient-to-nurse ratio is
considerably higher (i.e., nursing care in the SSRU is less labor intensive) than in the PACU. Only basic monitoring
and observation are performed as the patient and his or her escort are prepared for imminent discharge to home.
Because of the rapid recovery of patients undergoing anesthesia with the shorter acting, faster emergence
anesthetics, some have questioned if all ambulatory surgical patients need to receive intensive postoperative care in
the PACU setting or whether “first stage” recovery from anesthesia can be achieved safely while still in the
operating room (at least for some patients), thereby resulting in substantial institutional savings.
The “SAFE” study evaluates the impact of selective patient bypass of the PACU on both the outcomes of
ambulatory surgical patients and the use of resources in the surgical arena. 4 This study was designed to evaluate the
rapid recovery of patients undergoing ambulatory surgery using short-acting, fast emergence anesthetic agents and
to determine if policies and procedures could be developed that would allow patients to safely bypass first stage
post-anesthesia care units (PACU) and whether such changes in the recovery paradigm would result in financial
savings for the surgical center. Five community based facilities (hospitals or surgery centers) participated in this
prospective observational study. While in the operating room at the end of the surgical procedure, anesthesiologists
were asked to assess all ambulatory surgical patients for recovery using standardizing discharge criteria typically
used at the end of a PACU stay (Table 1). If the patient met the discharge criteria, they were transferred from the
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OR directly to the less labor intensive second stage recovery unit (SSRU). Financial data were provided from all
five sites detailing all costs associated with the recovery process. Clinical data on every elective ASA 1, 2 and 3
ambulatory surgical patient were collected over a three month period. During month one, data collected established
a baseline of case mix, time stamps, adverse events, bypass rates, and financial profile. During month two, an
educational intervention was provided on a multi-disciplinary basis to all units in the surgical center discussing the
implications of the fast track paradigm. After implementation of the fast track paradigm (month three) weekly
feedback reports were provided to the site featuring the key outcomes of the study, and these reports were
distributed to the health care providers. Nearly 5,000 patients were entered into the study. The overall bypass rate
increased from 15.9% in the baseline month to 58.9% in the month following the educational intervention (p <
0.0001). The change in process in this study went beyond reducing time spent in the PACU to eliminating the time
spent in the PACU while not increasing the time spent in the operating room or SSRU. In fact, the average (SD)
time spent in the SSRU was significantly shorter for patients who bypassed the PACU than for those who did not
bypass the PACU. There were no significant differences in other parameters of patient outcome. Annualized
savings ranged from $50,000 to $160,000 per site.
The Hows And Whys Of Preoperative Evaluation
The continued growth of outpatient surgery has created new roles for the anesthesiologist that seemingly
demands skills in addition to "giving a good anesthetic." The times from induction to emergence are no longer the
only or even most important role for the perioperative physician. Particularly in the freestanding and office
environments, it is often the anesthesiologist who is most involved in the direct medical care of the patient; we are
the physicians who must insure that the patient is appropriately screened, evaluated, and informed prior to the day of
surgery. Indeed, the anesthesiologist/patient relationship that sometimes develops often takes on a primary care
quality. Although difficult to arrange, the preoperative interview and evaluation by a consultant anesthesiologist
(particularly in high risk patients) can be extraordinarily beneficial. In addition to lessening anxiety about the
surgery and anesthesia, in most cases, the anesthesiologist will be able to identify potential medical problems in
advance, determine their etiology, and if indicated, initiate appropriate corrective measures. Additionally, the
ambulatory anesthesiologist can play a critically important role in assuring that the patient understands and complies
with preoperative instructions. In most facilities, the goal is to resolve preoperative problems well in advance of the
day of surgery, thereby minimizing the numbers of both cancellations and complications.
The Inappropriate Patient - Who's OK And Who's Not
There are few data to reliably categorize the inappropriate adult surgical outpatient. As anesthesiologists
have become more experienced with the anesthetic management of the problem surgical outpatient, the list of
"inappropriate" patients has dwindled. We must individualize our decision with regard to each patient; with few
exceptions, the appropriateness of a case for outpatient surgery is determined by a combination of factors including
patient considerations, surgical procedure, anesthetic technique, facility capabilities, and anesthesiologist's comfort
level.
At the University of Chicago Medical Center, we have distinguished several groups of patients who may
not be appropriate candidates for ambulatory surgery. As one might expect, this list is frequently modified to adapt
to the ever-changing conditions of our social and medicolegal environment.
• Unstable ASA Physical Status 3 and 4: At the present time we are reluctant to proceed with elective
ambulatory surgery in a medically unstable patient. Instead, we use our anesthesia perioperative medicine clinic
(APMC) to screen these patients, and together with the primary care surgeon or interventionalist, establish a plan to
proceed with the surgery or intervention after medical stabilization. Contrary to the original "ground rules" of
ambulatory surgery, studies involving hundreds of thousands of patients seem to suggest that neither increasing age
nor the presence of chronic, stable pre-existing disease affect the incidence of postoperative complications in the
surgical outpatient.
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• Malignant Hyperpyrexia: In our facility, overnight hospitalization and observation is usually indicated
for patients with a history of malignant hyperpyrexia or with identified susceptibility to malignant hyperpyrexia.
However, patients who are well educated, have a good understanding of their disease process, and have ready access
to medical care may be treated as outpatients by some centers.
• Complex Morbid Obesity/Complex Sleep Apnea: Although patients who have a history of sleep apnea or
who are morbidly obese without systemic disease are acceptable candidates for ambulatory surgery, we prefer
overnight hospitalization and postoperative observation for morbidly obese surgical patients with significant pre-
existing cardiac, pulmonary, hepatic or renal compromise or those patients with a history of complex sleep apnea.
Practice guidelines for the perioperative management of patients with obstructive sleep apnea have recently been
updated by the American Society of Anesthesiologists and offer recommendations for preoperative evaluation,
preoperative preparation, intraoperative management, postoperative management, and “site” of surgery (inpatient vs.
outpatient).6
• Acute Substance Abuse: Because of the increased likelihood of acute untoward cardiovascular responses
when one administers an anesthetic to a patient who has recently abused illicit drugs, we preoperatively counsel
these patients and inform them that any sign of recent drug abuse on the day of surgery will result in immediate
cancellation of their anesthetic. We tell them that no elective surgical procedure "is worth dying for" and encourage
their preoperative participation in a rehabilitation program.
Anesthesiology directed perioperative medicine clinics are increasingly used to optimize the medical
condition of a patient in preparation for surgery. These clinics have been shown to enhance patient safety, improve
patient satisfaction7,8, minimize preoperative consultation9, and reduce day of surgery case cancellations and case
postponements.10 In summary, it is clear that geriatric and higher risk (physical status 3 and 4) patients may be
considered acceptable candidates for outpatient surgery if their systemic diseases are well controlled and the
patient’s medical condition is optimized preoperatively.
Changes to the ASA Standards for Basic Anesthesia Monitoring
For the first time in nearly a decade, there has been a significant change to the ASA Standards for Basic
Anesthesia Monitoring.11 The standard for monitoring of ventilation has undergone significant revision:
VENTILATION: 3.2.4: During regional anesthesia (with no sedation) or local anesthesia (with no sedation), the
adequacy of ventilation shall be evaluated by continual observation of qualitative clinical signs. During moderate or
deep sedation the adequacy of ventilation shall be evaluated by continual observation of qualitative clinical signs
and monitoring for the presence of exhaled carbon dioxide unless precluded or invalidated by the nature of the
patient, procedure, or equipment. Many physicians have asked if these standards apply to cases where sedation is
administered in “out of operating room” locations. The Centers for Medicare and Medicaid (CMS) Revised
Hospital Anesthesia Services Interpretative Guidelines seemingly provide guidance on this issue. The first section
in these Interpretative Guidelines is entitled “Types of Anesthesia Services” and the first “bullet” in this section
begins as follows: Anesthesia services, which include both anesthesia and analgesia, are provided along a
continuum, ranging from the application of local anesthetics for minor procedures to general anesthesia for patients
who require loss of consciousness as well as control of vital body functions in order to tolerate invasive operative
procedures. This continuum also includes minimal sedation, moderate sedation/analgesia (“conscious sedation”),
monitored anesthesia care (MAC), and regional anesthesia.
CMS Issues Revised Hospital Anesthesia Services Interpretive Guidelines
CMS has recently issued significant revisions to the Anesthesia Services Interpretive Guidelines.12 These
included significant revisions to the CMS compliance requirements for both pre and post anesthesia evaluations, as
well as a requirement that heretofore, ALL anesthesia and sedation services (including mild, moderate, and deep
sedation), REGARDLESS OF PROVIDERS MUST be organized into a single anesthesia service under the
direction of a qualified doctor of medicine or doctor of osteopathy. The CMS revisions to the Anesthesia Services
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Interpretative Guidelines clearly place responsibility on the shoulders of the Director of Anesthesia Services to
assure that all providers of sedation services (e.g., gastroenterologists, cardiologists, pulmonologists, interventional
radiologists, etc.) are fully compliant with CMS requirements for pre, intra, and post procedure sedation regardless
of where sedation is administered in the facility.
Does Choice of Anesthetic Affect the Rate of Cancer Recurrence?
There is a growing body of literature that suggests that surgery and choice of anesthetic/analgesic may have
an influence on the recurrence rate of malignant tumors.13-20 Tumor manipulation and excision leads to the
dissemination of tumor cells into the vascular circulation. Surgical stress and the inflammatory response to surgery
leads to a significant depression of cell mediated immunity. Multiple recent studies suggest that intraoperative and
postoperative opioids may influence the recurrence and/or metastasis of malignant tumors.21-25 We will dedicate a
portion of this presentation to an update of this topic.
Computer-Assisted Personalized Sedation (CAPS): Dead or Alive?
Ethicon Endo-Surgery, Inc. has developed a computer-assisted personalized sedation system (trade name
SEDASYS®). According to the manufacturer, this device is the first computer-assisted personalized sedation
(CAPS) system designed for physician/nurse teams to provide minimal-to-moderate sedation levels with propofol.
By integrating drug delivery and patient monitoring, this computer-assisted personalized sedation device enables
physician/nurse teams to deliver individualized, personalized sedation. It automatically detects and responds to
signs of over-sedation (oxygen desaturation and low respiratory rate/apnea) by stopping or reducing delivery of
propofol, increasing oxygen delivery and automatically instructing patients to take a deep breath.”
The process of getting this device to market was long and tedious. On May 28, 2009, the Anesthesia and
Respiratory Therapy Devices Advisory Committee of the US Food and Drug Administration (FDA) concluded its
deliberations and recommended to the FDA that the device be approvable for the administration of propofol by
physician/nurse teams for the initiation and maintenance of minimal to moderate sedation during screening and
diagnostic procedures in patients undergoing colonoscopy and esophagoduodenoscopy procedures, but only under
the following conditions:
1) The device may only be used in adult patients (ASA I, II, and III) 70 years old or younger;
2) The device may only be used in the presence of a 3 person clinical team where one person shall have
the sole responsibility of monitoring the patient, the device and managing the patient's airway. This
dedicated person must have advanced training and at least the skills of a nurse;
3) Physicians utilizing the device must complete training in advanced airway management, pharmacology
of propofol and opioids, patient selection, monitor training (such as SpO 2 monitoring), device set-up
and maintenance with the training provided by a clinician with credentials to provide deep sedation to
general anesthesia. In addition, the FDA has mandated that there be a program established for ongoing
maintenance of training;
4) The manufacturer must complete all post-marketing studies as proposed at the time of the Advisory
Panel hearing.
5) The product launch is “controlled.”
The Anesthesia and Respiratory Therapy Devices Advisory Committee of the US FDA (composed primarily
of anesthesiologists) recommended approval of the device in large part because of the demonstrated improvement in
patient safety the implementation of the device appeared to provide compared to the “typical” method of moderate
sedation provided by gastroenterologists (i.e., benzodiazepine/opioid parenteral titration). Nevertheless, In April
2010, Johnson & Johnson, the parent company of Ethicon-Endo Surgery, Inc., announced that the FDA sent the
company a “not approvable” letter for the SEDASYS® Computer Assisted Personalized Sedation System. The
company appealed this decision and on May 10, 2013 the company announced that the FDA had granted approval
for launch of the device. Implementation of the launch occurred in October, 2014. Acceptance and utilization by
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gastroenterologists was much slower than expected and in March, 2016, Ethicon Endo-Surgery, Inc. announced it
was exiting the marketplace, thereby putting an end to the utilization of this first generation device.
It would be foolhardy to believe that such computer assisted personalized sedation devices are “dead”.
Traditionally, anesthesiologists have embraced technological advances in patient safety and CAPS devices will
likely soon be back. Indeed, several such second generation devices are currently under development. During the
session, we will review many of the specifics of the first generation of these devices and strategies for its potential
incorporation into a sedation plan.
Summary
Today there is a continued trend to expand the indications for ambulatory surgery. Because outpatient
anesthesia is a break from our traditional training, we are constantly being confronted with the need for change in
our clinical practice patterns. We have recognized that the needs of the surgical outpatient may be very different
from the inpatient and are now trying to adapt our practice patterns to meet the psychologic and pharmacologic
requirements of the compacted perioperative management the outpatient receives. This Refresher Course has
focused on some of the controversial problems that we as practicing clinicians must deal with every day in our
practice of ambulatory anesthesia for adult patients.
REFERENCES
1. Chung F: Are discharge criteria changing? J Clin Anesth 1993; 5:64S-68S.

2. Chung F: Recovery pattern and home-readiness after ambulatory surgery. Anesth Analg 1995; 80:896-902.
3. Aldrete JA: J Perianes Nurs 1998; 13(3):148-55.
4. Apfelbaum JL, et al: Anesthesiology 2002; 97:66-74.
5. Sandberg et al: Anesthesiology 2012; 117:4: 772-779.
6. Gross JB, et al. Anesthesiology 2014; 120::268-286.
7. Parker BM, et al. J Clin Anesth 2000; 12:350-6.
8. Harnett, et al. Anesthesiology 2010; 112:66
9. Fischer SP. Anesthesiology 1996; 85:190-206.
10. Ferschl MB, et al. Anesthesiology 103(4):855-859.
11. http://www.asahq.org/quality-and-practice-management/standards-and-guidelines ; last accessed 6/15/15
12. http://www.asahq.org/about-asa/newsroom/news-releases/2010/05/cms-issues-additional-clarification-of-the
hospital-interpretive-guidelines-for-anesthesia-services ; last accessed 6/15/15
13. Exadaktylos, et al., Anesthesiology 2006; 105(4): 660-664
14. Christopher, et al. , Anesth Analg, 2008, 107(1); 325-332
15. Forget, et al., Anesth Analg 2010; 110(6): 1630
16. Chen et al.,Plos ONE. 2013;8 (2):e56540
17. Bovill et al Anesth Analg 2010;110:1524-1526
18. Snyder et al., Br J Aneaesth. 2010;105:106-115
19. Yeager et al., Reg Anesth Pain Med. 2010;35:483-484
20. Buggy et. Al., Br. J Anaesth. 2015;114: 2-3
21. Singleton et al., Cancer 4 June 2015 DOI 10.1002/cncr.29460
22. Lennon et. al. Anesthesiology 2012:116:940-945
23. Gupta et., al Cancer Res. 2002;62:4491-4498
24. Cata et al., Cancer Medicine 2014; 3(4): 900-908
25. Lennon et al., PLoS ONE 9(3):e91577. doi:10.1371/journal.pone.0091577
26. Pambianco, et al: GI Endoscopy 2008;68: 542-547
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TABLE 1. DISCHARGE CRITERIA
• Awake, alert, oriented, responsive (or return to baseline)

• Minimal pain
• No active bleeding
• Vital signs stable (not likely to require pharmacologic intervention)
• Minimal nausea
• No vomiting
• If nondepolarizing neuromuscular blocking agent used, patient can perform sustained five second head lift
• Oxygen saturation of 94% on room air (three minutes or longer) OR return of oxygen saturation to baseline
or higher in order to be eligible to bypass Phase I recovery (PACU), the patient must meet ALL of the
above criteria, and in the judgment of the anesthesiologist, be capable of transfer to the step-down unit,
with appropriate care and facility for patient management at that location
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Preventing CNS Complications During Anesthesia & Surgery
James E. Cottrell, M.D. Brooklyn, New York
The assumption that anesthetics and sedatives have no serious adverse CNS consequences is probably true for most patients.
However, for patients younger than 1 year or older than 60 years, that assumption is under challenge from a substantial body of
evidence. Fetuses and infants appear to be at risk because systems that would enable them to fully recover from the effects of
more than 2 hours of anesthesia are still in development. In distinction, seniors may be at risk because systems that once enabled
full recovery have ever-diminishing capacity. Even for some patients between the age of 1 and 60 years, full neurologic recovery
may require replacing apoptosed neurons and pruning dendritic spines, leaving them not quite the same person that they were
prior to surgery.
THE YOUNG BRAIN
After 28 weeks of gestation, fetal neurons develop an acute ability to die from boredom. 1 Given estimates of 40-50 billion
neurons at birth,2 and evidence that at least one proto-neuron, and more likely two, undergo apoptosis for each neuron that
survives,3 a midpoint estimate is that the human brain averages about 8,000 apoptotic neuronal deaths per second during the last
11 weeks in utero. Those cellular suicides are selective, leaving the core material and sculpting the primary architecture for
subsequent CNS development.4-6
The trigger for much of that avalanche of apoptosis is a lack of synaptic feedback. Apoptosis appears to be the default
program of many excitable cell types, with cell-typical activity promoting proteins like anti-apoptotic Bcl-2’s that prevent the
default program from running its course. Put differently, the old saying “Use it or lose it” is not only for the old … synaptic
activity may be as crucial to the survival of fetal neurons as are O2, ATP and CBF. So what happens to fetal neurons that would
be receiving and sending signals were it not for the presence of anesthesia?
In laboratory animals
One of the first animal models to test the effect of anesthesia on fetuses was developed by Chalon in 1981. He exposed pregnant
mice to halothane and found that their offspring, and the offspring of those offspring, learned significantly more slowly than first
and second generation controls.7 see also 7a Analogous findings for offspring exposed in utero have been extended to isoflurane,8,9
sevoflurane10 and propofol11 in rodents and to ketamine12 and isoflurane13 in fetal rhesus macaques. Takaenoki et al also reported
cross-generational effects: neonatal exposure of female mice to sevoflurane causes subsequent deficits in maternal behavior that
lead to decreased survival of their non-exposed offspring.14 That finding comports well with Amrock et al’s finding that “even
brief exposures [to sevoflurane] induce long-lasting alterations in neuronal circuitry and sensitize surviving synapses to
subsequent loss.”15 Recent studies notwithstanding, early laboratory reports indicating a potential problem did not receive the
attention they deserved until 2003 when Jevtovic-Todorovic and colleagues published “Early exposure to common anesthetic
agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits” — a title that says it
all.16 Many subsequent studies have confirmed those findings for neonatal exposure to desflurane, isoflurane, sevoflurane,
propofol, nitrous oxide and ketamine in rodents, with the deleterious effects of ketamine exaggerated by caffeine, which is often
consumed during pregnancy and is sometimes given to premature infants to stimulate respiration.17
Postnatal apoptosis consequent to a clinically relevant depth and duration of general anesthesia also occurs in mammals with
periods of rapid synaptogenesis more analogous to humans, including pigs18,19 and non-human primates.20-22 Potentially relevant
for burn victims, twenty-four hours of “a light surgical plane” of ketamine anesthesia also causes long term cognitive deficits in
Rhesus macaque neonates.23 In addition to apoptosis, Stratmann and colleagues found that exposing 7-day-old rats to four hours
of isoflurane induced a decrease in neurogenesis that contributed to a permanent deficit in hippocampal-dependent learning and
memory.24 Neurogenesis requires neural stem cells, and Culley et al have presented evidence that 1 MAC of isoflurane reduces
the production of neural stem cells by 20% in vitro twenty four hours after exposure.25 Decreased neurogenesis and decreased
neural stem cell proliferation notwithstanding, using 16-day-old rats, Briner and coauthors found that sevoflurane, desflurane,
isoflurane26,27 and propofol28 rapidly increase dendritic spine density, which “could interfere with physiologic patterns of
synaptogenesis and thus might impair appropriate circuit assembly in the developing cerebral cortex” while Mintz et al found that
general anesthetics interfere with axon polarization29 and guidance30 in vitro. Huang and Yang have added “reduction in synaptic
structural plasticity” as a cause of impaired motor learning during adulthood in mice exposed to ketamine-xylazine 3 times
between post-natal days 14-18.31 Many of these mechanisms probably contribute to Raper and colleagues finding that 4 hours of
sevoflurane anesthesia during postnatal day 6 to 10 increases anxiety-related behavior at 6 months of age in Rhesus macaques.32
In humans
Levy reported a significant association between near-term emotional sequelae and younger age at anesthetic exposure in 1945
(p<0.0004, data not statistically analyzed in the original article).33 Subsequent reports support an association between impaired
neuro-cognitive-behavioral development and exposure to surgery and anesthesia34-66 with several supporting the relationship
between younger age and increased detrimental effects,e.g. 47, 50 suggesting that the period of extraordinary vulnerability in
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humans is in utero to twelve months postpartum – similar to that found at analogous developmental stages (as distinct from
chronological ages) in non-humans.
If duration of general anesthesia is as critical in human fetuses and neonates as it is in nonhumans,18 then 30-60 minutes of
exposure is not sufficient to affect currently measurable long-term learning capacity, even in the high-vulnerability age group.
Accordingly, Hansen and colleagues finding of no substantive impairment in children “exposed to a single, brief anesthetic
procedure in infancy,”67 and Davidson et al’s finding of no difference between general anesthesia and awake regional anesthesia
during infancy for a single, brief exposure,68 suggest that measurable deleterious effects start taking affect beyond one hour of
exposure.cf. 69 In distinction to a single brief exposure, Wilder et al45 and Yan et al55 found that repeated brief exposures to
general anesthesia have a measurable deleterious effect on neurodevelopment.
Block and colleagues analyzed achievement test scores of 7-17 year-old children who received general anesthesia for up to
3.75 hours during infancy for procedures that are not associated with cognitive impairment. After excluding children with any of
14 pre-specified CNS problems or medical conditions associated with learning disabilities, they found that a substantial
proportion of children without such risk factors scored below the 5th percentile of the normative population (p<0.01), with
increased duration of anesthesia associating with reduced performance. 50 Bong et al also found increased learning disabilities at
age 12 in healthy children exposed to 30-120 minutes of sevoflurane prior age 1.56 In distinction to Block and Bong’s finding for
children exposed to general anesthesia, Williams et al did not find a significant difference in the percentage of children scoring
below the 5th percentile, nor a correlation between achievement scores and duration of surgery, in children who received spinal
anesthesia during infancy.63
To date, perhaps the most intriguing evidence for separating surgically and/or genetically induced neurodevelopmental
deficits from anesthesia/sedative-induced deficits comes from children anesthetized for craniosynostosis50 and reconstructive
heart surgery,51,54 or sedated for procedures during neonatal care. Naumann et al found a stronger association between anesthesia
duration and neurodevelopmental delays at 36 months of age than between surgical duration and neurodevelopmental delays in
children who had non-saggital, single suture craniosynostosis when they were about 6 months old. 50 “After adjustment for
multiple relevant covariates” Andropoulos et al found “an association between VAA [volatile anesthetic agents] exposure ... and
lower neurodevelopmental outcome” at 12 months of age after complex neonatal cardiac surgery. 51 Diaz and coauthors found a
similar result. They performed a retrospective dose-response study on 96 infants who underwent staged reconstructive surgery
for hypoplastic left heart syndrome. Initial surgery with cardio-pulmonary bypass was performed at less than two months of age.
All subsequent surgical interventions as well as ICU stays, up to neurodevelopment assessment at age 4 years, were included in a
cumulative anesthetic exposure analysis. After adjusting for multiple covariates previously demonstrated to influence
neurodevelopmental outcomes, they demonstrated that greater exposure to VAA is correlated with lower full-scale IQ.59
Particularly telling, Duerden et al also found a dose-response curve between midazolam and lower cognitive scores with reduced
hippocampal volumes at age 18-19 months in preterm neonates sedated for stressful and painful procedures during neonatal
intensive care.60
Just as as preterm infants appear to be more sensitive to harmful effects of anesthesia and sedation than full-term infants,
effects in fetuses may be even stronger than those in post-natal infants. In 1986 Hollenbeck and coauthors reported decreased
cognitive capacity in four-year-olds whose mothers had been anesthetized while they were in utero.61 Several subsequent studies
found analogous associations between pre-natal exposure to anesthetics and developmental problems including autism, 62
hydrocephalus,63 diminished general intelligence,64 impaired spatial ability,65 small head size and mental retardation.66
Ongoing Trial
A prospective study scheduled for completion in 2016, the Pediatric Anesthesia Neuro Development Assessment (PANDA) is
shooting for 1000 participants to compare “Global and Domain-specific Neurocognitive Function” between children exposed to
general anesthesia prior to 3 years of age during hernia repair versus siblings of similar age (within 3 years) who were not
exposed to general anesthesia prior to age three.70 Unfortunately, like the Davidson62 and Hansen studies,61 this investigation is
testing for an effect of exposures that may be too brief to have a measurable effect in a study population that may be substantially
composed of children who are too old to be sufficiently susceptible.
Upcoming Trials
At the SmartTots Workshop on June 20, 2014, McCann and Davidson put forth the null hypothesis that “Infants who undergo the
cleft lip/palate repair with an average of >8 hours of general anesthesia in the first year of life exposed to conventional general
anesthesia with sevoflurane and nitrous oxide will have similar neurocognitive outcomes to infants exposed to an ‘apoptosis
sparing’ general anesthetic.” The core of their “apoptosis sparing” anesthetic is dexmedetomidine with remifentanil, the efficacy
of which is being tested in the “T REX” trial.71 Presumably, if T REX demonstrates feasibility, a trial comparing dex/remi
maintenance to sevo-N2O maintenance on subsequent neurocognitive development will follow. Prospective clinical trials that
compare potentially less neurotoxic anesthetic regimens to conventional alternatives in children who receive sufficient anesthesia
at a young enough age to test the anesthesia-neurodevelopment hypothesis ... children for whom delaying surgery is seldom an
option ... will address the most important question. Such trials are long overdue.
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Have the data already changed clinical practice?

How would you answer the following question?
---------------------------------------------------------
A 27-year-old woman presents with an operable, slow-growing, benign, mildly symptomatic brain tumor. Her neurosurgeon has
scheduled the case and estimates an operation time of 4.5 hours. She is 25 weeks pregnant. Would you:
A. Proceed with the case using state-of-the-art equipment, procedures and a volatile anesthetic for maintenance?
B. Discuss evidence that has emerged or gained renewed recognition since 2003 that 4.5 hours of anesthesia may cause neuro-
degeneration and persistent learning deficits in the developing brain and leave the decision to the neurosurgeon?
C. Discuss the above evidence with the neurosurgeon and the parents and leave the decision in their hands?
D. Discuss the above evidence with the neurosurgeon and the parents and, barring development of substantive symptoms, advise
postponing surgery until after the patient has given birth?
---------------------------------------------------------
My guess is that prior to Jevtovic-Todorovic and coauthors’ 2003 shot-heard-round-the-anesthesia-world,16 most of us were on
the A train. In the absence of survey data, my hope is that most of us would now follow a suggestion from Rappaport et al:
“parents and care providers should be made aware of the potential risks that anesthetics pose to the developing brain ... surgeons,
anesthesiologist, and parents should consider carefully how urgently surgery is needed” 72 ... and opt for C or D because, as put by
Drasner, “If you aren’t concerned, you haven’t been paying attention.”73 see also 74
How might we fix this problem?

Olney and his group have proposed that anesthetic drug effects on fetal and neonatal gamma-aminobutyric acid and N-methyl-D-
aspartic acid receptors cause translocation of pro-apoptotic proteins to mitochondrial membranes, leading to an apoptotic
cascade.75 Perhaps this problem can be alleviated through anesthetic management. Dexmedetomidine has been shown to be non-
neurotoxic in a fetal non-human primate model76 and has been shown to ameliorate the apoptosis caused by ketamine, 77
isoflurane,78 and propofol79 in the developing rodent brain.
Several adjunct pharmaceuticals have also shown promise. L-carnitine, an l-lysine derivative that transports long-chain fatty
acids into mitochondria, appears to have a beneficial effect in N2O/isoflurane-damaged neonatal rats.80 Lithium reduces damage
from ketamine and propofol in neonatal mice81 and Brambrink’s group found that lithium protects against anesthesia
neurotoxicity in the infant primate brain – completely preventing isoflurane-induced neuroapoptosis and significantly reducing
apoptosis of oligodendroglia.82 Clonidine reduces the apoptotic and behavioral effects of ketamine in neonatal mice83 and Patel’s
lab has shown that inhibition of p75 neurotrophin receptors attenuates both isoflurane84,85 and propofol86 neurotoxicity in mice.
Using the early post-natal rat model, Yon and coauthors found that melatonin reduced anesthetic-induced damage in the most
vulnerable brain regions: “Melatonin-induced neuroprotection was mediated, at least in part, via inhibition of the mitochondria-
dependent apoptotic pathway since melatonin caused an up-regulation of the anti-apoptotic protein, bcl-XL, reduction in
anesthesia-induced cytochrome C release into the cytoplasm and a decrease in anesthesia-induced activation of caspase-3
[precursor of apoptosis].”87 More recently, Jevtovic-Todorovic’s lab found that both EUK-134, a synthetic reactive oxygen
species scavenger, and R(+) pramepexole, a synthetic aminobenzothiazol derivative that restores mitochondrial integrity,
“completely prevented general anesthesia-induced cognitive impairment” in rats that had been exposed to 6 hours of
midazolam/isoflurane/N2O anesthesia on post-natal day 7.88 see also 89,90 It would be a perfect circle if the investigator who did so
much to bring this problem to the world’s attention also heads the team that finds a solution.
What about hypothermia and neonatal brain damage? Creeley and Olney reported laboratory evidence that hypothermia
(30º C) attenuates anesthesia-induced apoptosis in neonatal mice,91 and human trials looking at whole-body92,93 and head94
hypothermia in neonates with hypoxic-ischemic encephalopathy have found a decrease in death and/or moderate-to-severe
disability. In distinction, hypothermia after out-of-hospital arrest in children,95 like hypothermia after out-of-hospital arrest in
adults,96 does not look promising.cf. 97 Pellegrini and colleagues have presented evidence that erythropoietin substantially
diminishes neurotoxicity and later learning deficits in rat pups exposed to sevoflurane on post-natal day 7.98 More recently,
O’Gorman et al found evidence of improved white matter development at 12-18 and again at 36-42 hours after birth in preterm
human infants given recombinant erythropoietin within 3 hours of birth. 99
THE OLDER BRAIN
The older brain has less cognitive reserve — less resilience subsequent to neurological challenges. Oxidative phosphorylation
does not work as well. We acquire genetic mutations that can alter outcomes. Genetic alleles that were silent when we were
young manifest themselves as we age. And then there is free radical build-up with reduced levels of scavengers like vitamin C,
melatonin and vitamin E. All of these dreary realities probably contribute to Kline and coauthors’ finding that “Elderly subjects
after surgery experienced an increased rate of brain atrophy,”100 and as found by Silbert et al,101 “subjects with mild cognitive
impairment suffered greater subsequent cognitive effects.”
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POCD After Non-Cardiac Surgery

In 1955 P.D. Bedford published "Adverse cerebral effects of anaesthesia on old people." 102 He reviewed 1,193 (presumably non-
cardiac) patients over 50 years old who had received general anesthesia. Mental deterioration in 10% of patients appeared to be
long-term or permanent — a figure that concurs with subsequent findings. Bedford concluded that cognitive decline is related to
anesthetic agents and hypotension. He recommended that “Operations on elderly people should be confined to unequivocally
necessary cases” and that “postoperative medication should not be a routine matter.” The next major study to report POCD skips
ahead 43 years to 1998 — the first International Study of Postoperative Cognitive Dysfunction (ISPOCD). 103 In non-cardiac
patients more than 59 years old, the incidence of cognitive dysfunction 1 week after surgery was 22% higher than in age-matched
controls and 7% higher 3 months after surgery (p<0.004 for both) with 10% of patients (91/910) evidencing POCD (identical to
Bedford’s finding at a longer postoperative interval). Increasing age, duration of anesthesia, lesser education, a second operation,
postoperative infection, and respiratory complications were risk factors for early postoperative cognitive dysfunction. However,
under a circumstance of significantly reduced statistical power due to a 22% loss of follow-up at 3 months, among the risk factors
that were significant in the early postoperative period, only age remained statistically significant.
Monk and colleagues found that 12.7% of elderly (>59 y o) non-cardiac patients had POCD three months after surgery104 —
again, within a narrow confidence interval around Bedford’s 1955 report. Corroborating earlier work, 105 Monk’s study also
found a substantial relationship between POCD and death within one year of surgery. see also 106,107 Independent risk factors for
sustained POCD included greater age, less education, POCD at hospital discharge and a history of stroke without residual
damage. Consistent with many investigations, more education may indicate greater pre-surgical cognitive reserve, just as prior
stroke may indicate pre-surgical reduction of cognitive reserve.107,108 Notably, Monk’s ‘08 study did not find duration of
anesthesia to be a risk factor. However, the risk of a false negative conclusion is high in that regard, because the sample size of
elderly patients at the 3-month measurement was even smaller (308 with 39 POCD patients105) than in the International Study of
POCD (901 with 91 POCD patients103). The longest follow-up study of POCD patients (median = 8.5 years) was published by
the ISPOCD group in 2009: "Cognitive dysfunction after noncardiac surgery was associated with increased mortality, risk of
leaving the labor market prematurely, and dependency on social transfer. 109
POCD After Cardiac Surgery

Most of us have heard friends or relatives say something like “since he had open-heart surgery, he’s not the same … he can’t
think as well, he’s not as happy.” The New York Times brought attention to this problem with an article entitled “Saving the
Heart Can Sometimes Mean Losing Your Memory.”110 In that article, Juhar explained the basics of extracorporeal circulation
and discussed reasons for memory loss, focusing on a patient who had gone back to work and found that he had difficulty with
his job … a patient who could not perform functions that he had performed for many years. That article raised a great deal of
concern, setting the stage for a paper published a year later in the New England Journal of Medicine by Newman and
colleagues.111 see also 112 They found POCD in 53% of Coronary Artery Bypass Graft (CABG) patients at discharge and in 36% of
patients six weeks later. That proportion went down to 24% six months after surgery, but came back up to 42% five years after
surgery — a pattern of early improvement followed by subsequent decline that was predicted by POCD at discharge. see also 113
More recently, Evered et al found strong associations between POCD at 12 months after CABG surgery and death within 10
years, and dramatically increased incidence of dementia 7.5 years after CABG surgery.114
The factors that cause decline in cognitive capacity among non-CABG patients also affect CABG patients. However, some
of those risk factors, like duration of exposure to anesthetics, may be masked by damage done to CABG patients from increased
liability to cerebral emboli, cerebral ischemia during re-perfusion, and over-warming after bypass.115
Aggravating Factors
- On-pump vs. Off-pump

Does on-pump versus off-pump make a neurocognitive difference? Several trials failed to detect a neurocognitive advantage for
off-pump patients.116-118 Although Shroyer et al did not find a statistically significant difference across their composite test
battery, they did find a significant difference on one important test in favor of off-pump, suggesting the possibility of a false
negative conclusion.116 cf. 119 Both the 1-year follow-up from the CORONARY investigators117 and the GOPCABE study
group118 failed to find a statistically significant advantage of off-pump bypass. Statistical significance aside, both investigations
did find a lower incidence of stroke in off-pump patients. If those results were added to Afilalo and colleague’s recent meta-
analysis, they would increase the statistical significance of an already significant finding of a 30% reduction in relative risk of
stroke for off-pump patients.120 So we are left wondering how patients who experience far more strokes (on-pump patients) did
not evidence statistically significantly worse neurocognitive outcome. One reason is that in the CORONARY study some
surgeons took the liberty of performing off-pump surgery on 102 patients who had been randomly assigned to on-pump surgery
because those patients had calcification of their aortas. In the intention-to-treat analysis, those patients’ results were analyzed as
if they had on-pump surgery.121 These profound protocol violations were accompanied by patient-selected, as distinct from
randomly selected, inclusion in neurocognitive testing.117 Dr. Hartung and I have argued that intention-to-treat analysis should
always be accompanied by on-treatment analysis,122 and calculating a ‘p’ value for non-random samples makes no sense. In this
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case “absence of evidence is not evidence of absence,”123 and unless strokes do not have neuro-cognitive consequences, my best-
guess is that the CORONARY study should be disregarded.
Puskas and colleagues found that “After a mean of 7.5 years of follow-up, patients undergoing off-pump coronary artery
bypass performed better than those undergoing [on-pump] cardiopulmonary bypass in several neuropsychological domains,”124
and in what amounts to a serendipitous positive-control study, Li et al found that preconditioning with hyperbaric oxygen
reduced markers of cerebral injury in patients undergoing on-pump bypass but not in patients having off-pump bypass, reasoning
that “the protective effects of HBO preconditioning may only manifest when there is a relatively severe injury, such as an on-
pump procedure and not in off-pump CABG surgery patients.125 More recently, Brewer and coauthors found more postoperative
complications, including permanent stroke, in 3,898 on-pump patients who were baseline-matched to 3,898 off-pump patients.126
Most recently, Kok et al’s prospective study found substantially less POCD 3 months after CABG surgery in patients randomized
to off-pump.127
Less direct evidence came from a study of over 16,000 patients in whom a greater incidence of delirium occurred after on-
pump cardiopulmonary bypass, with duration of surgery (and so anesthesia) as a significant risk factor. 128 Although these
patients were not followed up for POCD, Girard and coauthors found that in “mechanically ventilated medical intensive care unit
patients, duration of delirium (which is potentially modifiable) was independently associated with long-term [12 month]
cognitive impairment129 and Morandi et al found that “delirium duration in the intensive care unit was associated with white
matter disruption at both discharge and 3 months later with worse cognitive scores up to 12 months after discharge.” 130 In a
prospective study of 225 CABG patients, Saczynski and and coauthors found that “Delirium is associated with a significant
decline in cognitive ability during the first year after cardiac surgery”131 and in 263 Alzheimer’s disease patients, Gross and
colleagues concluded that “Delirium is highly prevalent among persons with Alzheimer’s disease who are hospitalized and is
associated with an increased rate of cognitive deterioration that is maintained for up to 5 years.” 132 Neufeld et al found that post-
op delirium in the PACU “is associated with subsequent delirium on the ward, and ... with a decline in cognitive function and
increased institutionalization at hospital discharge.”133 More recently, Mangusan et al also found that: “Patients with
postoperative delirium had significantly longer stays (P < .001) and greater prevalence of falls (P < .001) than did patients
without delirium. Patients with delirium also had a significantly greater likelihood for discharge to a nursing facility (P < .001)
and need for home health services if discharged to home (P < .001) and a significantly higher need for inpatient physical therapy
(P < .001).”134 Clearly, a relationship between depression, sedation, delirium, poor neurological outcome and POCD should not
be discounted,128-140 such that off-pump patients may be at lesser risk for POCD.
- Inflammation
Inflammation caused by surgical trauma may also aggravate POCD and is associated with the pathogenesis of Alzheimers’
Disease (AD) in a mouse model.141 Evidence that the association is causal comes from Vom Berg and coauthors’ finding that
intracerebroventricular delivery of anit-p40, and inhibitor of inflammatory signaling, significantly reduces the concentration of
amyloid  (A) and reverses cognitive deficits in aged Alzheimer’s mice.142 We know about the up-regulation of IL-1, and this
in turn can affect anesthetic receptors.143 The ensuing cascade of events ultimately affects the anesthetic gamma-aminobutyric
acid and N-methyl-D-aspartic acid receptors and increases production of A … and we know that soluble oligomers of A, even
in non-demented patients, associate with cognitive problems. Genetic predispositions are another aggravating factor. For
example, Matthew and coauthors have shown the contribution of P-selectin and C-reactive protein alleles in modulating
susceptibility to cognitive decline caused by inflammation after cardiac surgery, 144 and Cai et al found an association between
APOE4 and early POCD in elderly patients undergoing inhalation anesthesia.145
- General Anesthetics
Are anesthetics aggravating factors? If so, are some more toxic than others? Xie’s group found greater cognitive decline in
patients 1 week after surgery who received spinal anesthesia with desflurane versus spinal anesthesia with isoflurane or spinal
anesthesia alone.146, cf. 147 Examining autopsy brain tissue, Crary and coauthors found that PKMzeta, an atypical protein kinase C
isoform, accumulates in the neurofibrillary tangles of Alzheimer’s patients, but not in control patients.148 One wonders whether
anesthetics might increase this tangling in both AD and non-AD patients. My lab is currently investigating the effect of
anesthetics on PKMzeta in the adult mouse hippocampus.149,150
- Anesthesia and Neurodegenerative Diseases

Do anesthetics aggravate neurodegenerative diseases? Hydrophobic cavities keep sticky proteins from becoming irreversibly
glued together. Unfortunately, molecules of inhalational anesthetics can fill those cavities and reduce the amount of energy
required to maintain protein assembly.151 This anesthesia-facilitated disinhibition of protein binding helps monomers aggregate
into oligomers, and if those monomers are A, the resulting oligomerization can lead to protofibrils that are small enough to
diffuse into neurons and large enough to be neurotoxic. Soluble A oligomers152 and alpha-Synuclein153 appear to contribute to
the neurodegeneration characterized by Alzheimer in the early 20 th Century. Thirteen million Americans are projected to have
AD by the middle of the 21st Century. Many of them will need to be anesthetized, and many of those will have been anesthetized
before they became demented.
The role of inhalational anesthetics in the above scenario has been verified in vitro by a decade of work from Eckenhoff and
coauthors,154 and is also supported by in vivo mouse models.155,156 In addition to the A-anesthesia connection, Xie's group has
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utilized human neuroglioma cell cultures to add anesthesia-induced apoptosis as a factor contributing to AD155, 157,158 and they
have found that isoflurane, but not desflurane, degrades mitochondrial function and impairs learning and memory in mice. 159 Do
the rodent and cell culture findings apply to humans? Eckenhoff’s group reported that the total-tau/A(1-42) ratio in CSF, the
only biomarker validated for use in the diagnosis of AD by the Alzheimer’s Disease Neuroimaging Initiative (ADNI), elevates
during surgery and anesthesia in healthy patients and rises above ADNI’s threshold for mild cognitive impairment within 48
hours,160 and in an article entitled “Coronary artery bypass surgery provokes Alzheimer’s disease-like changes in the
cerebrospinal fluid,” Palotas and colleagues found an increased tau/A ratio in patients 6 months after surgery.161
Early results from retrospective studies on a possible association between anesthetic exposure and AD were unsettling but
inconclusive.162-164 Now two large studies have found substantial evidence. Matching for age and gender, Pin-Liang Chen and
coauthors compared 1,539 patients who had never been anesthetized to 661 patients who had been anesthetized after age 50.
Even after adjustment for comorbidities, the patients exposed to anesthesia had a nearly 2-fold greater incidence of dementia
(p<0.001).165 Comparing 5,345 patients recently diagnosed with dementia to 21,380 age and gender matched individuals without
dementia, Chia-Wen Chen and colleagues found a substantially higher incidence of anesthesia exposure, in a dose-response
relationship, among the demented patients (p<0.0001).166 Benzodiazepine use also looks like a substantive risk factor, with a
“stronger association observed for long term exposures.”167-170 With regard to anesthesia and neurodegenerative diseases, Shoair
et al hit the trifecta, finding significant associations between POCD and APOE4 (p<0.037), use of highly anticholinergic/
sedative-hypnotic drugs at home prior to surgery (p<0.014) and use of sevoflurane (p<0.010).171
If the association between anesthetic exposure and AD is causal, as evidence indicates for the association between
anesthesia and developmental delay in children,33-66 Bedford’s admonition from 1953 still holds: “Operations on elderly people
should be confined to unequivocally necessary cases”102 ... and BIS should be kept on the high side, with intravenous anesthesia
substituted for inhalational anesthesia when practicable, and with regional anesthesia substituted for general anesthesia when
feasible (see below).
Potential Alleviating Factors
- Deeper vs. Lighter & Regional vs. General Anesthesia

Neuman et al found higher mortality and more pulmonary complications in general anesthesia patients compared to regional
anesthesia patients undergoing hip fracture surgery,172 and Brown and colleagues found that elderly patients with serious
comorbidities receiving light sedation (BIS>80) during spinal anesthesia for hip surgery had reduced 1-year mortality compared
to patients who received deep sedation (BIS≈50).173 Examining results from 980 patients who underwent intra-arterial therapy
for acute ischemic stroke under conscious (light) sedation versus (light) general anesthesia, in addition to finding higher mortality
in the general anesthesia patients, Abou-Chebl and coauthors also found poorer neurological outcome.174 Ancelin found that
“Adding sedation to peridural anesthesia led to a decline in verbal secondary memory”175 and Sieber et al found that lighter
sedation during spine surgery led to less delirium.176 Again, there are empirical and neuropathological reasons to suspect a link
between delirium, deep sedation, poor neurological outcome, and POCD. 128-140
Indeed, presaged by results from a pilot study by Ballard et al,177 an investigation by the CODA Trial Group of 921 elderly
patients undergoing major non-cardiac surgery found that patients with a median BIS of 53 experienced less delirium and had
less POCD 3 months after surgery than a control group maintained at a median BIS of 36.178, see also 179 cf. 180 As put by Green et al,
“The important point about this trial is that the investigators were able to maintain an average BIS in the intervention group vs 36
in the control group. This not only resulted in a significant decrease in POCD, but also in postoperative delirium, which we
acknowledge is a cause of significant postoperative morbidity ... As our population ages, we can no longer be complacent about
how our intraoperative management may affect postoperative outcome, and not only in POCD.”181
It may be the case that regional anesthesia with deep sedation is equivalent to general anesthesia when it comes to POCD.182
Be that as it may, whether the effect is on mortality, morbidity or POCD, a substantial and growing body of evidence indicates
that, ceteris paribus, lighter is better than deeper and regional is better than general.
- Anesthetics & Sedatives

How might we reduce the risk of POCD in older patients? Are some anesthetics less deleterious than others? Crosby’s group has
presented data indicating that “In aged rats, propofol anesthesia is devoid of the persistent memory effects observed with other
general anesthetic agents in this model. Thus, it appears that general anesthesia-induced memory impairment may be a function
of the agent rather than the anesthetic state itself.”183 Complementary in vitro work by Wei and Xie also suggests that sevoflurane
and desflurane are less potent triggers of apoptosis than isoflurane.184
Newman's group at Duke reported a significant reduction in POCD at 6 weeks and 1 year among non-diabetic cardiac
patients who received i.v. lidocaine. This effect was most pronounced in patients who received less than 43 mg/kg (total dose),
while lidocaine appears to have had a deleterious effect in diabetic patients and in patients who received higher total doses. 185
Analysis of a follow-up study is scheduled for July, 2016.186 Meanwhile, Chen et al reported that low dose lidocaine reduced
early POCD and serum levels of IL-6, TNF-, S100 and NSE in elderly non-diabetic spine surgery patients.187
Dexmedetomidine has been reported to reduce delirium compared to midazolam or propofol sedation,188, 189 increase survival
rate in patients undergoing cardiac surgery,190 reduce delirium, ventilator time, tachycardia and hypertension compared to
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midazolam in critically ill ICU patients191 and reduce focal neurologic dysfunction during mild sedation in patients with
supratentorial mass lesions compared to midazolam and propofol.192
- A Grab Bag of Adjuvants , Emboli Protection, Diet & Exercise

What about erythropoietin, melatonin, vitamin E, memantine, insulin, statins, minocycline, edaravone and exercise? Lauretani
and colleagues found that EPO levels are lower in 60-to-98-year-olds with impaired peripheral nerve function and/or clinical
diagnosis of polyneuropathy.193 Haljan et al found a trend toward improved neurocognitive recovery with erythropoietin use in
CABG patients,194 and in post-hoc analyses Tseng et all found EPO to be protective in SAH patients who are younger, non-
septic, and on statin therapy.195 More recently, a double-blind trial by Abrishamkar and colleagues found improved Glasgow
Outcome Scores in patients with diffuse axonal injury who received subcutaneous injections of EPO every other day for two
weeks.196
Cheng and colleagues’ review of the beneficial effects of melatonin in experimental models of AD is encouraging,197 as is
Ni and coauthors’ finding that melatonin premedication attenuates isoflurane-induced A in the hippocampus of aged rats.198 A
clinical trial by Furio et al199 found that melatonin improved cognitive function in elderly outpatients who suffered from mild
cognitive impairment and Wade et al200 found the same in mild to moderate Alzheimer’s patients. More recently, Hatta et al
found that a stronger melatonergic sleep agent, ramelteon, prevented delirium in hospitalized older patients. 201
Laboratory studies have reported evidence that by reducing inflammation, minocycline reduces cognitive impairment
induced by sevoflurane202 and isoflurane203 in aged rats, and one open-label study found neuroprotection after ischemic stroke in
humans.204 Several studies indicate that memantine,205, 206 and insulin therapy,207, 208 improve cognitive function or delay clinical
worsening in AD patients, and vitamin E with other dietary supplements have shown similar promise. 209-211
The jury has looked hard for evidence that statin therapy prevents or ameliorates AD, but a definitive verdict is still
pending.212, 213 In distinction, Blanco et al found that statin withdrawal increased the incidence of poor outcome in ischemic
stroke patients214 and retrospective reviews by Flint and colleagues found that statin use during ischemic stroke hospitalization 215
and after intracerebral hemorrhage216 is strongly associated with improved survival and discharge disposition,”217 even for
patients without prior statin use. Tsivgoulis et al found that statin pretreatment in patients diagnosed with acute large artery
atherosclerosis associates with neurologic improvement and reduced stroke recurrence. 218 Using a prospective design, Al-
Khaled et al found that statin treatment reduced mortality 3 months after acute ischemic stroke,219 Zhang et al found enhanced
recovery with increased brain-derived neurotrophic factor 2 months after ischemic stroke in patients who received atorvastatin 220
and Zheng et al found that adding the free radical scavenger edaravone to atorvastatin increased recovery 2 weeks post-stroke.221
Pharmacological and mechanical approaches notwithstanding, perhaps age-appropriate exercise remains the best all-round
regimen for both prevention and treatment of POCD. 222-227
- Preconditioning & Perconditioning

Although fetuses and the elderly are particularly sensitive to ischemia, hypo-perfusion and hypoxia, “Nietzsche’s Toxicology:
whatever doesn’t kill you might make you stronger”228 could lead to improved clinical management of patients with fragile
brains.
In 1964 Dahl and Balfour published evidence of “prolonged anoxic survival due to anoxia pre-exposure.”229 This
phenomenon was eventually replicated in a model of cerebral ischemia,230 and induction of endogenous proteins of repair and the
genes that code for them are now well documented. Our laboratory has added sevoflurane as a potential preconditioner, 231 and
Maze's group reported that in comparison to sevoflurane,232 nitrous oxide and hypoxia,233 xenon preconditions in a manner that
"might mimic the intrinsic mechanism of ischemic preconditioning most closely."232 But if a limited dose of anesthesia triggers
the same protective mechanisms as a limited bout of hypoxia, how much anesthesia can we give before what would have been a
protective effect becomes a deleterious effect on balance?182
Clinically acceptable means of accomplishing cerebral preconditioning are being sought. Volatile anesthetics
notwithstanding, pharmacological cerebral preconditioning may be eclipsed by mechanical Remote Ischemic Preconditioning
(RIPC). Clinical studies have established that three 5-minute inflations of a blood pressure cuff to 200 mmHg around a patient's
upper arm, followed by 5-minute intervals of reperfusion, improves outcome,234, 235 including near-term POCD,236 after several
cardiovascular procedures and evidence from laboratory investigations indicates that the same technique initiated prior to
neurosurgery may improve outcome.237-240 Investigations of RIPC in neurosurgical patients are underway or have recently been
completed,241 and a study by Hu and colleagues reported reduced biochemical markers of neuronal ischemia and improved rate
of recovery after cervical decompression in patients who received RIPC.242 More recently, Meng and coauthors reported that
daily bilateral arm ischemia reduced recurrent stroke and time to recovery over a 300 day period in patients with atherosclerotic
intracranial arterial stenosis,243 and Hougaard et al found that “perconditioning” ischemic stroke patients in the ambulance on
their way to thrombolysis therapy reduced infarction at one month post-stroke.244
- Neurogenesis
The old adage that neurogenesis is only for the young was shown to be wrong for rodents in 1965,245 is known to be wrong for
non-human primates,246 and has been reported in humans.247, 248 This raises the possibility that negative effects of surgery and
anesthesia on the elderly, as well as the very young, can be compensated by therapies that strengthen the neurogenic response.
Results in rats encourage the conclusion that "neural precursors resident in the brain initiate a compensatory response that results
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in the production of new neurons. Moreover, administration of growth factors can enhance this compensatory response … [and]
we may eventually be able to manipulate these precursors to improve recovery of function." 249, 250 In addition to ischemic
preconditioning,251 granulocyte-colony stimulating factor252 and erythropoietin253, 254 appear to be such manipulators, and
neurogenesis may be the therapeutic mechanism of electroconvulsive therapy in patients with depression. 255, 256
CONCLUSION
Reports of possible adverse cognitive effects of anesthetics on young patients appeared in our literature during the 1940’s, on
elderly patients in the 1950’s, and on fetuses in the 1980’s ... so these problems and some of their potential solutions are not new,
but our awareness of them has experienced a renaissance since 2003. 16 Fortunately, in the vast majority of pediatric cases,
anesthetics last for less than 1 hour in children who are less than 1 year old. For that majority, I agree that the “evidence is most
consistent with the premise that ‘anesthesia per se,’ given to an otherwise healthy child who needs only a ‘routine’ surgical
procedure, is not neurotoxic”257 … or is not toxic enough to cause a currently measurable adverse effect. However, for children
less than 12 months old, fetuses of any age and patients over 60, until and unless we are able to classify substantive anesthetic
neurotoxicity as a rare complication, the conservative first-do-no-harm approach should: 1) add anesthesia to surgery on the cost
side of the cost/benefit equation when making decisions about whether and when to proceed with surgery; 2) avoid nitrous
oxide, isoflurane and ketamine in the young because multiple studies indicate that they are particularly toxic; 3) use non-
ketamine intravenous anesthesia instead of inhalational anesthesia when doing so is a reasonable option; 4) keep BIS on the high
side; 5) limit the duration of continuous anesthesia to less than 2 hours whenever possible; 6) consider the possibility that
regional anesthesia with deep sedation may trigger as much neuronal apoptosis as general anesthesia; and 7) when feasible, use
regional anesthesia with light or no sedation.
At the very least, newfound concerns generated by available data should inspire a great deal of translational research. If that
research is funded, my guess is that we will soon have anesthetic, sedative and adjuvant drugs ranked according to their
deleterious effects … and cerebral preconditioning with augmentation of endogenous processes of regeneration will deliver brain
protection and recovery to the very young, the old, and everyone in between … before the younger among us are too far gone to
benefit!
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Clinical Pathways for Total Joint Arthroplasty: Essential Components for Success
James R. Hebl, M.D. Rochester, MN
Clinical Pathways: An Overview

The term clinical pathway refers to a multidisciplinary process of mutual decision-making that results in
the organized care of a well-defined group of patients during a well-defined period of time.[1, 2] Clinical
pathways were first introduced in the 1980’s when escalating medical costs pressured physicians to
decrease resource utilization without jeopardizing patient safety or clinical outcomes. At that time,
pathways were typically procedure-specific (e.g., coronary artery bypass grafting, total knee arthroplasty)
and tailored to a specific institution.[3, 4] As a result, tremendous variability often existed from one
institutional clinical pathway to another, making clinical comparisons between pathways and formal
scientific study exceedingly difficult.
Despite this variability, it is generally agreed upon that clinical pathways provide several distinct
advantages. These include the ability to (1) provide coordinated care between departments and across
patient care units; (2) standardize patient care and reduce hospital length-of-stay; (3) convert typical
inpatient (i.e., same-day admission) procedures to outpatient (i.e., same-day discharge) procedures; (4)
prompt change in the care process to better emphasize patient outcomes and cost containment; (5) control
hospital costs; and (6) serve as a marketing tool with the public or with third-party payers.[5]
Despite these challenges, this review will summarize the important components of a successful clinical
pathway and attempt to evaluate the impact of differing clinical pathways on major perioperative
outcomes after total joint arthroplasty. Perioperative outcomes that will be evaluated include
postoperative complications, hospital length-of stay, clinical outcomes, and medical costs.
Clinical Pathway Components

Effective clinical pathways for major orthopedic surgery include the coordination and standardization of
several patient care activities during the pre-, intra-, and postoperative period. Essential components of
some of the most effective orthopedic clinical pathways are listed in Table 1.
Preoperative Patient Education

Major orthopedic surgery can be a stressful and anxiety-provoking experience for most patients. Bondy
and colleagues [6] examined the effect of anesthesia patient education on preoperative anxiety and found
that a detailed patient education program may have several beneficial effects. Preoperative patient
education may significantly relieve patient anxiety and emotional stress by providing a better
understanding of the perioperative process (e.g., preoperative evaluation, hospital admission process,
anesthetic options, expected clinical course) and establishing clear expectations with regard to hospital
length-of-stay and the discharge process (e.g., dismissal to home vs. rehabilitation swing-bed vs. nursing
home). Because patients have a better understanding of the perioperative process, they will often present
for surgery with increased confidence in the therapeutic plan and a willingness to more actively
participate in their care. Increased participation often results in greater patient satisfaction and potentially
improved perioperative outcomes. However, the extent to which patient education influences
postoperative outcomes is somewhat unclear.[7-9] McDonald and colleagues [8] demonstrated that
preoperative patient education may result in a modest benefit in preoperative anxiety. However, this
benefit failed to persist on Postoperative Day (POD) 2 or at the time of hospital discharge. A review of
the Cochrane Database on this topic fails to demonstrate that preoperative patient education has a
significant impact on postoperative clinical outcomes (e.g., postoperative pain, functional outcomes,
hospital length-of-stay) in patients undergoing total hip or total knee arthroplasty.
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Table 1. Essential Clinical Pathway Components
Preoperative
 Preoperative patient education program
 Appropriate management of preoperative pain and psychological symptoms (fear, anxiety,
depression)
Intraoperative
 Development of a comprehensive multimodal analgesic regimen
 The use of peripheral nerve blockade and continuous perineural catheters
 Postanesthesia Care Unit (PACU) algorithms for the management of acute postoperative pain
Postoperative
 Standardized method of pain assessment on the nursing floors and pain score documentation within
the medical record
 Early and accelerated rehabilitation regimen
 Development of an integrated and multidisciplinary Acute Pain Service
 Staff education regarding the importance of pain management
 Written protocols for acute postoperative pain management
Multimodal Analgesia
Patients undergoing total knee and total hip arthroplasty experience significant postoperative pain.[10]
Severe pain occurs in 60% of patients and moderate pain in up to 30% of patients undergoing total knee
arthroplasty. Failure to provide adequate analgesia may impede early physical therapy and rapid
rehabilitation,[11] which are both important factors for maintaining joint range of motion and facilitating
hospital discharge.[12] In an effort to avoid many of the side effects commonly associated with opioid-
induced analgesia, clinicians have begun adopting multimodal therapeutic regimens. Multimodal
analgesia has become an important concept in the field of modern pain management.[12-17] The concept
is designed to combat pain perception along several pathways of signal transmission, including the
surgical site and surrounding tissues, local sensory nerves, and central nervous system. Advantages
include superior analgesia secondary to the synergistic effects of multiple agents acting via different
pathways, the ability to limit parenteral opioid administration, and minimizing opioid-related side effects.
Several investigations have demonstrated the beneficial effects of multimodal analgesia,[14-16] including
its value in patients undergoing major orthopedic joint replacement surgery.[17-24]
Several medications may be used as part of a multimodal analgesic pathway. Specifically, the use of
acetaminophen,[25] non-steroidal anti-inflammatory agents,[26] selective cyclooxygenase-2
inhibitors,[18] pregabalin,[21] and ketamine,[22] have all been shown to have analgesic benefits in
patients undergoing joint replacement surgery. Most experts recommend using multiple agents during the
pre- and postoperative period in small quantitative doses to maximize the analgesic effect while
minimizing associated side effects. Documented benefits include superior postoperative analgesia,[18,
22, 25, 26] reduced supplemental opioid requirements, [18, 21, 22, 25, 26] fewer opioid-related side
effects,[13, 18] improved joint range-of-motion,[18, 21] fewer postoperative sleep disturbances,[18]
shorter time to achieve hospital discharge criteria,[21] improved functional mobility,[22] and a lower
incidence of chronic neuropathic pain.[21]
Finally, poorly controlled acute postoperative (i.e., nociceptive) pain may contribute to the development
of chronic neuropathic pain or complex regional pain syndrome after total joint arthroplasty.[27]
Nikolajsen and colleagues examined the Danish Hip Arthroplasty Registry and found that 12% of patients
continue to experience moderate-to-severe pain 12-18 months after surgery.[28] Similarly, up to 13% of
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total knee arthroplasty patients may experience moderate-to-severe pain 12-months after surgery.[29]
Additional risk factors for the development of chronic postoperative pain include preoperative pain for
greater than 1-month, an increased intensity of preoperative pain, and a patient history of preoperative
fear, anxiety or depression.[29, 30] Poorly controlled postoperative pain has also been shown to impede
global recovery and lower the reported quality of life 6-months after surgery.[31] Therefore, clinical
pathways that integrate (1) a comprehensive multimodal analgesic regimen to adequately manage pre-
and postoperative pain; and (2) a comprehensive psychiatric program to manage preoperative
psychological symptoms may have a significant benefit in improving long-term clinical and psychiatric
outcomes.
Peripheral Nerve Blockade and Continuous Perineural Catheters

Many treatment regimens for managing severe postoperative orthopedic pain include significant doses of
parenteral opioids. These treatment regimens are commonly associated with significant opioid-related
side effects such as sedation, nausea, vomiting, ileus, and urinary retention that can adversely effect
patient outcomes and prolong hospital length-of-stay.[19] Therefore, clinical pathways that minimize (or
eliminate) opioid administration may significantly reduce opioid-related side effects and improve
postoperative patient outcomes.
The integration of regional anesthesia and peripheral nerve blockade into clinical pathways for orthopedic
surgery is an essential step to minimize opioid use and improve perioperative outcomes. Both single-
injection [32-35] and continuous [36-40] peripheral nerve block techniques have been shown to provide
superior analgesia, reduce supplemental opioid requirements, decrease opioid-related side effects, and
improve functional outcomes after total joint arthroplasty. In a recent meta-analysis of 19 articles and
603 patients, Richman and colleagues [41] also demonstrated that patients receiving continuous
peripheral nerve blockade have superior analgesia, fewer opioid-related side effects (nausea, vomiting,
pruritus, sedation), and improved patient satisfaction when compared to traditional intravenous opioids
alone. Although single-injection techniques have been shown to be superior to placebo or systemic
analgesia [32-35], comparison studies have shown that single-injection blocks fail to provide the extended
benefits of continuous perineural catheters.[37, 42, 43] Continuous peripheral nerve block techniques
have also been shown to have similar analgesia – but a more desirable side effect profile – when
compared to epidural analgesia.[44] A recent review by Fowler and colleagues [44] demonstrated that
patients receiving peripheral nerve blocks had less urinary retention and fewer episodes of postoperative
hypotension when compared to patients receiving neuraxial techniques.
A primary concern regarding the use of peripheral nerve blockade is the risk of neurologic complications.
Barrington and colleagues [45] recently performed a prospective audit of more than 7,000 peripheral
nerve blocks performed at 9 Australian hospitals. Overall, they identified a neurologic injury rate of
0.5%. However, only 10% of these injuries were attributed to peripheral nerve blockade suggesting that
the vast majority of perioperative nerve injuries have a non-anesthesia related etiology. The nerve injury
rate attributed to peripheral nerve blockade was found to be 0.04%  a rate similar to other large-scale
investigations.[46, 47] Jacob and colleagues [48] have also demonstrated that neither the type of
intraoperative anesthesia (general versus neuraxial) nor the use of peripheral nerve blockade was
associated with an increased risk of perioperative nerve injury in 12,329 patients undergoing total knee
arthroplasty. Rather, bilateral surgical procedures and total tourniquet time were found to be associated
with an increased risk of nerve injury.[48]
Standardized Pain Assessment and Documentation, Pain Management Protocols and Staff Education
In 2001, the Joint Commission declared pain as the “Fifth Vital Sign” and instituted Pain Management
Standards for accredited ambulatory care facilities, behavioral health care organizations, critical access
hospitals, home care providers, hospitals, office-based surgery practices, and long-term care
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providers.[49] The standard requires health care providers to (1) Appropriately assess and manage pain;
(2) Document pain management interventions and subsequent reassessments; (3) Perform pain screenings
during initial patient assessments; and (4) Educate patients and their families about pain management.
Benhamou [50] and Fletcher [51] report that similar guidelines and recommendations have been put
forward by the Royal College of Surgeons, the French Ministry of Health, the French Society of
Anesthesia and Intensive Care, the European Task Force on Pain Management, and the International
Association for the Study of Pain. The overwhelming consensus is that each of these interventions should
be considered essential components to any clinical pathway designed to optimize pain management and
patient care. Despite these recommendations, the literature suggests that pain remains under-treated in
both U.S. [52] and European [53] health care facilities – in part, because of a lack of adherence to
previously published standards and guidelines.
Early and Accelerated Rehabilitation

An early and accelerated rehabilitation program should also be integrated into clinical pathways designed
for total hip and total knee arthroplasty patients. A review of the literature suggests that early and
accelerated rehabilitation may have a major impact on improved perioperative outcomes in orthopedic
patients.[9, 55] Munin and colleagues [55] demonstrated that early inpatient rehabilitation resulted in a
shorter hospital length-of-stay and a more rapid attainment of short-term functional outcomes after joint
replacement surgery when compared to a delayed rehabilitation program. Pour and colleagues [9] also
examined the impact of an accelerated pre- and postoperative rehabilitation program versus a standard
regimen on functional outcomes after total hip arthroplasty. Patients randomized to the accelerated
pathway were seen earlier on the day of surgery and more frequently on subsequent postoperative days
(twice daily versus once daily). There was also a greater emphasis on oral analgesics (versus intravenous
patient-controlled analgesia) in patients receiving accelerated rehabilitation. In addition to a shorter
hospital length-of-stay, accelerated pathway patients were able to walk for longer distances, had improved
pain control, and reported higher patient satisfaction at the time of hospital discharge.[9]
Finally, Mahomed and colleagues [56] have demonstrated that rehabilitation after total hip or total knee
arthroplasty does not need to be restricted to the inpatient setting. Home-based rehabilitation programs
may provide similar degrees of postoperative analgesia, functional outcomes, and patient satisfaction at a
significantly lower cost when compared to hospital-based regimens.[56]
Clinical Pathways and Perioperative Outcomes

The goal of most clinical pathways is to provide standardized, evidence-based care to patients in such a
way as to minimize the variability of care provided by individual providers. This process has the
potential to significantly enhance the quality, improve the safety, and reduce the cost associated with
surgical procedures. Several clinical pathways have been reported in the literature for patients
undergoing total joint arthroplasty [1, 4, 19, 20, 57-59]; with no two pathways being identical. As a
result, comparison of clinical pathways is exceedingly difficult – forcing systematic reviews or meta-
analyses that examine the topic to comment on the “concept” of clinical pathways versus their individual
component parts. Barbieri and colleagues [1] recently performed a systematic review of clinical
pathways used for joint replacement surgery. The review examined 22 studies and included 6,316
patients. The aggregate results demonstrated a significant reduction in postoperative complications (deep
venous thrombosis, pulmonary embolism, manipulation, superficial infection, deep infection, heel
decubitus ulcers), a shorter hospital length-of-stay, and lower hospital costs in patients undergoing
clinical pathways versus standard care.[1] Publications from the University of California – Irvine, the
University of Utah, and the Mayo Clinic are described below; and represent typical examples of clinical
pathways developed for orthopedic surgical patients.
Clinical Pathways for Total Joint Arthroplasty

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Skinner and colleagues [57] performed a retrospective, case-controlled investigation of 102 patients
undergoing total hip or total knee arthroplasty at the University of California – Irvine. They compared a
multimodal clinical pathway that incorporated COX-II inhibitors, tramadol, dexamethasone,
acetaminophen, and intra-articular bupivacaine to patients receiving “standard management” with patient-
controlled analgesia and intravenous opioids. Importantly, the authors did not incorporate regional
anesthesia or peripheral nerve blockade as a component of the clinical pathway. Clinical endpoints were
evaluated during POD 1 through 4. For patients receiving the clinical pathway, opioid requirements were
reduced 66% for total hip arthroplasty (POD 2 only) and 68% for total knee arthroplasty (POD 3 only).
Although VAS pain scores were no different among total hip arthroplasty patients, patients undergoing
total knee arthroplasty reported lower VAS pain scores on POD 2 and at the time of hospital discharge.
Implementation of the clinical pathway resulted in no differences in perioperative complications.
Hospital length-of-stay was reduced in only total knee arthroplasty patients undergoing the clinical
pathway (4.0 vs. 4.9 days; P<0.02). [57]
In contrast to clinical pathways not incorporating regional anesthesia [57] – multimodal regimens
utilizing peripheral nerve blockade have been shown to consistently reduce hospital length-of-stay,
improve perioperative analgesia with fewer opioid medications, facilitate postoperative rehabilitation, and
reduce opioid-related side effects.[19, 20, 58] Peters and colleagues [58] performed a retrospective
analysis of 100 patients undergoing total hip and total knee arthroplasty at the University of Utah.[58]
The clinical pathway included a multimodal analgesic regimen (sustained-release oxycodone, COX-II
inhibitors, and acetaminophen), intraoperative regional anesthesia with intrathecal opioids, and an
ultrasound-guided femoral nerve catheter (total knee arthroplasty patients only) for extended
postoperative analgesia. Prior to wound closure, patients undergoing both total hip and total knee
arthroplasty received <1 mg/kg of 0.25% bupivacaine injected into the deep and subcutaneous tissues by
the orthopedic surgeon. A multimodal oral analgesic regimen was then continued into the postoperative
period. Control patients were managed with intraoperative general or spinal anesthesia (within intrathecal
morphine), continuous femoral nerve blockade (total knee arthroplasty patients only), and postoperative
patient-controlled analgesia with intravenous opioids. Patients receiving the clinical pathway had
significantly lower pain scores at rest on POD 1 and 2, lower opioid requirements, improved ambulation
during rehabilitation sessions, and reduced hospital length-of-stay. There were no differences in
perioperative complications when comparing clinical pathway to control patients. Overall, the
investigators concluded that the development and implementation of a comprehensive clinical pathway
combined with early and aggressive physical therapy improves perioperative outcomes, shortens hospital
length-of-stay, and allows patients to achieved physical therapy goals earlier when compared to non-
clinical pathway patients.[58]
Finally, Hebl and colleagues have described the development and implementation of the Mayo Clinic
Total Joint Regional Anesthesia (TJRA) Clinical Pathway in patients undergoing both minimally-invasive
[19] and traditional [20] total hip and total knee arthroplasty. The TJRA Clinical Pathway incorporates
preoperative patient education, a multimodal analgesic regimen emphasizing peripheral nerve blockade,
standardized PACU algorithms, pain assessments, and medical record documentation, pain management
protocols, and a standardized postoperative physical therapy regimen for patients undergoing total joint
arthroplasty. Similar to most clinical pathways, the TJRA Clinical Pathway was developed by a
multidisciplinary group of Mayo Clinic surgeons, anesthesiologists, pharmacists, nurses, and physical
therapy staff based upon their collective experience and exposure to physicians and practice models
outside the institution. Although the basic principles of the pathway have remained unchanged (e.g.,
preoperative patient education, multimodal analgesia, peripheral nerve blockade, pain management
protocols), its individual components are continually being evaluated and modified as necessary based
upon changes in clinical practice. The current multimodal analgesic and regional anesthesia components
of the TJRA Clinical Pathway are listed in Appendix 1.
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The Mayo Clinic TJRA Clinical Pathway was first used in patients undergoing minimally-invasive total
hip (n=20) and total knee (n=20) arthroplasty.[19] Study patients were prospectively enrolled and
compared to matched historical controls undergoing traditional surgical and anesthetic techniques.
Matching criteria included the type of surgical procedure, age, gender, and American Society of
Anesthesiologists physical status (ASA PS) classification. Patients undergoing minimally-invasive
surgery in combination with the TJRA Clinical Pathway had significantly lower pain scores both at rest
and with physical therapy, required fewer opioid medications, were able to ambulate significantly sooner,
and experienced less urinary retention and postoperative cognitive dysfunction when compared to
matched controls. Cognitive dysfunction was defined as disorientation to person, place, or time,
hallucinations, or any other cognitive condition requiring further assessment by a physician. Based upon
these criteria, approximately 15% of control patients and 1% of TJRA patients experience postoperative
cognitive dysfunction during their hospitalization. Hospital length-of-stay was also significantly shorter
among TJRA patients (2.8 days vs. 5.0 days; P<0.01).[19]
The Mayo Clinic TJRA Clinical Pathways has also been utilized in patients undergoing traditional (i.e.,
non-minimally invasive) total hip and total knee arthroplasty.[20] Patients undergoing joint replacement
surgery with the TJRA Clinical Pathway experience superior analgesia with fewer opioid-related side-
effects when compared to control patients. Verbal analog pain scores (VAS) were significantly lower
among TJRA patients both at rest (P<0.001) and with activity (P<0.001) during their entire hospital stay.
Opioid requirements were significantly less among TJRA patients from the pre-/intra-operative period
until the beginning of Postoperative Day 2 (P=0.04). Opioid related side-effects such as nausea
(P<0.001), vomiting (P=0.01), and urinary retention (P<0.001) were also significantly reduced for TJRA
patients throughout most of the perioperative period. There was no significant difference in the frequency
of pruritus between groups.[20]
Postoperative milestones (bed-to-chair transfer, discharge eligibility, and hospital dismissal) were
achieved significantly sooner in patients receiving the multimodal TJRA protocol. The ability to transfer
from bed to chair occurs a mean of 0.2 ± 0.6 days sooner among TJRA patients when compared to
matched controls (P=0.001). However, nearly all patients were able to accomplish this milestone by the
end of POD 1. Discharge eligibility was also achieved a mean of 1.7 ± 1.9 days sooner among TJRA
patients when compared to matched controls (P<0.0001). Hospital length-of-stay was 3.8 days for TJRA
patients and 5.0 days for controls (P<0.001). At the time of hospital dismissal, joint range-of-motion was
significantly better among TJRA patients (90° vs. 85°; P=0.008). Importantly, the small gains in range-
of-motion observed at hospital dismissal persisted at 6-8 weeks postoperatively (106° vs. 99°;
P=0.03).[20]
Severe postoperative complications (neurologic injury, myocardial infarction, renal dysfunction, localized
bleeding, deep venous thrombosis/pulmonary embolism, joint dislocation, wound infection) are similar
among TJRA patients and patients receiving patient-controlled analgesia (PCA). However, urinary
retention (P<0.001) and postoperative ileus occurred significantly more often among control patients (7%
vs. 1%; P=0.01) resulting in delayed postoperative feedings.[20]
Clinical Pathways and Economic Outcomes

Total hip and total knee arthroplasty are two of the most commonly performed surgical procedures in the
United States and represent the single greatest Medicare procedural expenditure.[60, 61] Recent data
from the United States Healthcare Cost and Utilization Project report that both the number and cost of
total knee and total hip replacement surgeries have increased more than 300% during the past decade.[62,
63] Furthermore, the American Academy of Orthopaedic Surgeons and other independent population-
based studies estimate that the number of total joint replacement surgeries will continue to grow.[64, 65]
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In fact, the number of total hip arthroplasties is expected to increase by as much as 50% per year; and the
number of total knee arthroplasties by 300% per year through the year 2030.[64] Given this trend, and
the fact that Medicare reimbursement continues to decline, orthopedic patients may have a major
economic impact on hospitals and other health care facilities during the next 20 years.[66] Therefore, any
changes in surgical or anesthetic practice that can reduce the cost associated with these procedures –
while maintaining the same degree of high-quality and efficient patient care – may have a significant
impact on overall United States health care expenditures.
Medical costs associated with an episode of care can be classified into three major categories (1) indirect
costs; (2) intangible costs; and (3) direct costs.[67] Indirect costs include the cost of lost productivity
related to the morbidity and mortality of the disease state. Intangible costs include the cost associated
with pain and suffering from the disease state. Direct costs include medical supplies, labor, and time –
and can be further divided into Medicare Part A costs and Medicare Part B costs (Figure 1). Several
cohort studies have linked the use of clinical pathways with lower variable costs.[7, 68-74] Other studies
have demonstrated that the development and implementation of a clinical pathway for patients
undergoing total hip or total knee arthroplasty may significantly reduce both total hospital [4] and direct
medical costs [62] while maintaining or improving perioperative outcomes.
Figure 1. Classification of Episode of Care Costs.
A reduction in hospital length-of-stay is often considered a cost-saving benefit during the perioperative
period. However, cost savings associated with reductions in hospital length-of-stay are directly related to
the total duration of stay; and may not necessarily reflect a significant source of cost savings. For
example, although hospital “room and board” costs remain constant throughout a hospitalization,
treatment costs associated with a hospitalization are often greatest during the initial 48-72 hours of care
(reflecting greater care demands during the patient’s initial illness); with a subsequent decline in daily
direct medical (i.e., treatment) costs (Figure 2).[75] Therefore, a reduction in hospital length-of-stay from
72 hours to 48 hours will result in significantly greater cost savings than a length-of-stay reduction from 7
days to 6 days. As a result, hospital administrators must understand that an isolated reduction in length-
of-stay may (or may not) result in a positive financial impact for the hospital or institution.
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Figure 2. Estimating the cost savings associated with reductions in hospital length-of-stay. Hospital stays
include a daily fixed cost called the “hotel” cost. Additionally, a “treatment” cost is added to each hospital day.
During hospitalization the treatment costs are often greatest during the initial portion of the hospital stay
reflecting greater care demands during the patient’s initial illness (represented above). The result is that
decreasing the length of stay from d1 to d2 at the end of hospitalization will likely not result in the same amount
of Limitations
savings as theofdaily average
Clinical cost (line c) would estimate.
Pathways
Effective perioperative pain management is not without potential consequences. In 2001, the Joint
Commission on Accreditation of Healthcare Organizations (JCAHO) declared pain as the 5 th vital sign
and mandated that pain management become an integral component of all patient care activities as a
condition of hospital accreditation. As a result, many institutions implemented aggressive pain
management protocols that were guided by patient reports of pain intensity as quantified by a numeric
pain scale. Although numeric pains scales may be useful to monitor pain trends within a given patient,
these subjective methods of pain assessment are an extremely poor guide for directed analgesic
management. In fact, because these subjective and often non-reproducible pain scales do not take into
consideration patient comorbidities or associated medication risks, adverse outcomes such as oversedation
and respiratory depression may lead to catastrophic outcomes – including death.[70, 76, 77]
Vila and colleagues [78] demonstrated the potential negative impact of implementing a hospital-wide pain
management protocol that treats pain based upon patient self-reports. After implementation of a numeric
pain treatment algorithm, the number of adverse drug reactions secondary to opioid oversedation more
than doubled when compared to pre-implementation values (24.5 vs. 11 adverse events per 100,000
inpatient hospital days; P<0.001). A decreased level of consciousness preceded 94% of events,
emphasizing the importance of careful clinical assessment and ongoing patient monitoring while
managing pain.[78] Overmedication in preparation for an imaging study,[70] overmedication after
discharge from the ICU ,[70] and the first 24 hours after surgery [77] appear to be the clinical scenarios or
time periods in which patients are at greatest risk for respiratory depression and oversedation.
Finally, clinical pathways that incorporate regional anesthesia and peripheral nerve blockade may
increase the likelihood of residual motor blockade – which may impede early mobilization, increase the
risk of patient falls, and prolong hospital length-of-stay.[43, 79-82] Kandasami and colleagues [80]
recently reported a fall rate of 2% in patients undergoing total knee arthroplasty with the use of femoral
nerve blockade. Fall-related injuries included wound dehiscence (n=4) and periprosthetic fracture (n=1).
Hospital length-of-stays were extended 10 to 42 days secondary to complications from the fall. However,
it has been argued that residual motor blockade is a multifactorial phenomenon – and cannot be entirely
attributed to regional anesthesia. In addition to local anesthetic-induced quadriceps weakness, it is
believed that motor block can occur secondary to surgical pain, muscle spasm, joint stiffness, swelling,
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dysesthesias, or other surgical factors.[83] Regardless of the cause, anesthesia providers need to play
their role in minimizing the risk of residual motor blockade in patients undergoing total hip and total knee
arthroplasty. Clinical pathways that incorporate peripheral nerve blockade need to do so in such a way
that the benefits of regional anesthesia are achieved (i.e., identifying the optimal local anesthetic, dose,
and concentration); while the contemporary concerns of delayed rehabilitation, prolonged hospital length-
of-stay, and increased hospital costs are avoided.
Summary
Total hip and total knee arthroplasty are two of the most commonly performed surgical procedures in the
United States with increased volumes expected over the next several decades. Clinical pathways
represent a standardized, evidence-based approach to patient care designed to enhance the quality,
improve the safety, and reduce the cost associated with surgical procedures. Clinical pathways for total
joint arthroplasty have been shown to significantly improve the perioperative outcomes of patients
undergoing joint replacement surgery. Effective clinical pathways include preoperative patient education,
a multimodal analgesic regimen, peripheral nerve blockade, standardized pain assessment and medical
record documentation, pain management protocols, staff education, and early and accelerated
rehabilitation. Potential clinical benefits include superior postoperative analgesia, fewer opioid-related
side effects, earlier ambulation, improved joint range-of-motion, fewer postoperative complications, and
reduced hospital length-of-stays. The financial benefits of clinical pathways include a reduction in both
total hospital and direct medical costs. However, further study is needed to determine precisely which
component(s) of a comprehensive clinical pathway are most active in contributing to these clinical and
financial benefits.
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2005;101(2):474-480, table of contents.
79. Ilfeld BM, Le LT, Meyer RS, et al. Ambulatory continuous femoral nerve blocks decrease time to
discharge readiness after tricompartment total knee arthroplasty: a randomized, triple-masked,
placebo-controlled study. Anesthesiology 2008;108(4):703-713.
80. Kandasami M, Kinninmonth AW, Sarungi M, et al. Femoral nerve block for total knee
replacement - a word of caution. Knee 2009;16(2):98-100.
81. Klein SM, Nielsen KC, Greengrass RA, et al. Ambulatory discharge after long-acting peripheral
nerve blockade: 2382 blocks with ropivacaine. Anesth Analg 2002;94(1):65-70, table of contents.
82. Williams BA, Kentor ML, Bottegal MT. The incidence of falls at home in patients with
perineural femoral catheters: a retrospective summary of a randomized clinical trial. Anesth
Analg 2007;104(4):1002.
83. Barrington MJ, Olive D, Low K, et al. Continuous femoral nerve blockade or epidural analgesia
after total knee replacement: a prospective randomized controlled trial. Anesth Analg
2005;101(6):1824-1829.
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Appendix 1. Mayo Clinic Total Joint Regional Anesthesia Clinical Pathway *
Patient Waiting Area (Pre-op)

 Oxycodone controlled release (OxyContin®) 20 mg PO once on arrival to patient waiting area if patient 18-59 years old; or 10 mg PO if patient 60-74
years old.
 Acetaminophen (Tylenol®) 1000 mg PO once on arrival to patient waiting area.
 Celecoxib (Celebrex®) 400 mg PO once on arrival to patient waiting area.
 Gabapentin (Neurontin®) 600 mg PO once on arrival to patient waiting area if patient 18-59 years old; or 300 mg PO if patient 60-69 years old.
Peripheral Nerve Catheter Infusions
(1) Femoral Nerve or Adductor Canal Catheter (TKA): 20 mL (Adductor) or 30 mL (Femoral) bolus dose of Bupivacaine 0.5% + 1:200,000 epinephrine at time
of placement
 Bupivacaine 0.2% 10 mL bolus upon arrival in PACU; then initiate continuous infusion Bupivacaine 0.2% at 10 mL/hour.
 Continue Bupivacaine 0.2% continuous infusion at 10 mL/hour until 0600 the day after surgery. At 0600 the day after surgery, change to Bupivacaine
0.1% continuous infusion at 10 mL/hour. On the second day after surgery, stop infusion and discontinue femoral nerve catheter infusion before 0800.
(2) Posterior Lumbar Plexus Catheter (THA): 30 mL bolus dose of Bupivacaine 0.5% + 1:200,000 epinephrine at time of placement
 Bupivacaine 0.2% 10 mL bolus upon arrival in PACU; then initiate continuous infusion Bupivacaine 0.2% at 10 mL/hour
 Continue Bupivacaine 0.2% continuous infusion at 10 mL/hour until 0600 the day after surgery. At 0600 the day after surgery, change to Bupivacaine
0.1% continuous infusion at 10 mL/hour. On the second day after surgery, stop infusion and discontinue psoas nerve catheter infusion before 0800.
Intraoperative
 Spinal anesthesia preferred intraoperative primary anesthetic  Tranexamic acid 1 g I.V. prior to incision and 1 g I.V. during closure
 Fentanyl 50-150 mcg IV PRN
 Ketamine 10-20 mg IV (150-200 mcg/kg; Maximum 20 mg) NOTE: Tranexamic acid is not administered to high-risk ASA III or IV
 Dexamethasone 4-8 mg IV patients (High risk = Prior history of DVT, PE, MI, CVA
CABG, Stent placement, or other Pro-thrombotic conditions)
Post-Anesthesia Care Unit (PACU)
 Oxycodone 5-10 mg PO PRN once for pain rated 4 or greater. Give 5 mg if patient 70 years old or older; give 10 mg if patient 18-69 years old.
 Fentanyl 25 mcg IV PRN for pain rated 7 or greater; may repeat every 5 minutes (maximum 100 mcg)
 Ketorolac (Toradol®) 15 mg IV PRN once for pain rated 4 or greater
Postoperative Nursing Floor †
 Acetaminophen (Tylenol®) 1000 mg PO 3 times daily at 0800, 1200, and 1600 hours.
 Tramadol (Ultram®) 50–100 mg PO every 6 hours
 Celecoxib (Celebrex®) 200 mg PO BID x 10 days
 Ketorolac (Toradol®) 15 mg IV every 6 hours PRN for pain rated more than 4 (maximum of 4 doses)
 Oxycodone 5–10 mg PO every 4 hours PRN. Give 5 mg if patient reports pain and rates pain score less than 4; give10 mg if patient complains of pain
rated 4 or greater.
Monitoring
Refresher Course Lectures Anesthesiology 2016 © American Society of Anesthesiologists. All rights reserved. Note: This publication contains material copyrighted by others.
Individual refresher course lectures are reprinted by ASA with permission. Reprinting or using individual refresher course lectures contained herein is strictly prohibited without
permission from the authors/copyright holders.
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 Continuous pulse oximetry telemetry monitoring for 48 hours postoperatively
* Perioperative analgesic options are selected based upon each patient’s associated comorbidities.
† Selection of postoperative medications at surgeon’s discretion.
Refresher Course Lectures Anesthesiology 2016 © American Society of Anesthesiologists. All rights reserved. Note: This publication contains material copyrighted by others.
Individual refresher course lectures are reprinted by ASA with permission. Reprinting or using individual refresher course lectures contained herein is strictly prohibited without
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Epidemic of Opioid Prescriptions for Chronic Pain: An Update of the Literature
Asokumar Buvanendran Chicago, IL
The RCL is to provide appropriate opioid prescribing suggestions. It is the result of a review of
the expert review, evidence based research, and clinical practice experience. Nearly one third of
the United States population suffers with chronic pain. Pain severe enough to limit activity is
present in approximately 25 million Americans; the societal costs of chronic pain are
astronomical, estimated at over $600 billion alone in annual lost work productivity and medical
expenses.1 These costs (including direct medical costs and lost wages) are higher than those for
heart disease, cancer, and diabetes combined.
Physicians who care for patients with chronic, non-cancer pain must balance many
important considerations when commencing with pain management treatment and most
importantly opioid therapy. While opioids can be effective for well-selected patients, many may
not obtain sustained benefit from this class of medications and many may potentially have the
increased risk of inappropriate misuse or abuse due to opioid dependence and addiction.2 Opioid
prescriptions increased dramatically from the 1990’s to 2004 and have remained high in
subsequent years3 with nearly 220 million prescriptions written in 2011, compared to 76 million
in 1991.4 Simultaneously, a dramatic increase in opioid addiction, overdose and death is
occurring.5,6 It is important to recognize that predominate source of opioids misused by patients
is leftover or surplus prescription medication. To understand where these prescription opioids are
coming from, a 2013 national survey reported that 53% of those abusing prescription painkillers
received them from a friend or relative; and further, the source of the prescription was a single
doctor in 84% of these cases.7
Despite lowering the risk of subsequent overdose, discontinuation of opioid therapy after
the initial opioid overdose often does not consistently occur in the majority of cases.8 Clinicians
from all specialties have the responsibility to address this issue and also understand the
inadvertent role that they have contributed to the rise in opioid prescriptions. The greatest
number of opioid prescriptions are written by primary care physicians and advanced practice
providers, and the highest concentration on opioid prescribing is in pain management, physical
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medicine and rehabilitation, and anesthesiology.9 The dramatic increase in opioid prescribing has
contributed to the prevalence of prescription drug abuse in the United States. It is imperative that
opioid prescribers must carefully weigh risks versus benefits of opioids for chronic, benign pain
and contemplate important questions such as patient selection, initiation and titration of opioids,
establishing effectiveness, random drug testing, collaboration with specialists and other
caregivers, and cessation of opioids when indicated.
A systematic, multimodal, and comprehensive approach to opioid prescribing is
necessary to optimize outcomes for this patient population while minimizing the risk of opioid
related long-term disability, morbidity, mortality, abuse and diversion. Failure to recognize the
complexity of chronic pain and the need for comprehensive care may potentially lead to
significant risk and ineffective treatment.
Prior to Initiation of Opioid Therapy

Patient assessment begins with a comprehensive history and physical exam to: (1) determine the
diagnosis for the patient’s pain complaint which may involve a detailed assessment with various
diagnostic tests, (2) evaluate how the pain is affecting the patient’s quality of life and function
and ability to enjoy life, (3) characterize co-morbidities and psychosocial factors which could
affect the choice of therapies, (4) assess prior approaches to pain management and their
effectiveness, and (5) establish a basis for developing a treatment plan to help reduce the
patient’s pain and return them a desired level of functioning and quality of life and ability to
enjoy life as per CDC recommendations for pain assessment, including documentation of pain
intensity, aggravating and relieving factors, history of pain treatments and level of functioning.
Providers must bear in mind that patient’s pain and response to treatment will vary over time and
according to genetic, psychosocial and cultural factors.
As such, pain is a subjective and dynamic experience and at present, physicians lack
options to objectively quantify pain severity other than by patient reported measures such as pain
intensity and its impact through pain interference. It is critical to understand that clinicians need
to demonstrate empathy in accepting the patient’s report of pain and simultaneously determine if
the magnitude and characteristics of the pain complaint is commensurate with causative factors
and if these have been adequately evaluated and treated with non-opioid therapy. In addition to
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non-opioid medication therapy, many pain treatments can be employed before initiating opioids,
such as physical/occupational therapy, psychological approaches (e.g. cognitive behavioral
therapy, biofeedback and relaxation therapy), complementary treatments, alternative medicine
treatments, chiropractic manipulation, osteopathic treatment, and interventional pain treatments
such as epidural steroid injections, radiofrequency denervation and spinal cord stimulation
(SCS). Efficacy of SCS has been demonstrated in RCTs and can be of value in selected chronic
pain patients.
If opioid therapy is considered, patients at risk for abuse and opioid related complications
should be carefully and meticulously identified including those with a history of current or
former substance abuse, misuse, or under-treated mental health disorders (e.g. depression,
anxiety, post-traumatic stress disorder). Additionally, a comprehensive assessment should be
completed of all social factors that may impact pain management including: employment, job
satisfaction, marital history, social network, and history of legal problems. Patients with multiple
co-morbidities and concurrent use of medications likely to interact with opioids may also be poor
candidates. In particular, central nervous system depressants which include benzodiazepines can
act synergistically with opioids and place the patient at risk for adverse respiratory outcomes.
Additional assessment may be necessary to determine the appropriateness of opioid therapy
which may include testing for important co-morbidities such as respiratory conditions, liver
dysfunction, renal insufficiency, sleep apnea (both obstructive and central), cardiac disease, and
medication allergies. The geriatric population is a vulnerable group that needs special attention
if opioid therapy is considered. In general, lower starting dose and longer dosing intervals are
advised until patient response is assessed.
References
1. Reuben DB, Alvanzo AA, Ashikaga T, Bogat GA, Callahan CM, Ruffing V, Steffens
DC: National Institutes of Health Pathways to Prevention Workshop: the role of opioids in the
treatment of chronic pain. Annals of internal medicine 2015; 162: 295-300
2. Han B, Compton WM, Jones CM, Cai R: Nonmedical Prescription Opioid Use and Use
Disorders Among Adults Aged 18 Through 64 Years in the United States, 2003-2013. JAMA
2015; 314: 1468-78
3. Kantor ED, Rehm CD, Haas JS, Chan AT, Giovannucci EL: Trends in Prescription Drug
Use Among Adults in the United States From 1999-2012. JAMA 2015; 314: 1818-31
4. http://docs.house.gov/meetings/IF/IF02/20140429/102161/HHRG-113-IF02-Wstate-
VolkowN-20140429.pdf,
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5. Okie S: A flood of opioids, a rising tide of deaths. The New England journal of medicine
2010; 363: 1981-5
6. Case A, Deaton A: Rising morbidity and mortality in midlife among white non-Hispanic
Americans in the 21st century. Proc Natl Acad Sci U S A 2015; 112: 15078-83
7.
http://www.samhsa.gov/data/sites/default/files/NSDUHresultsPDFWHTML2013/Web/N
SDUHresults2013.pdf,
8. Larochelle MR, Liebschutz JM, Zhang F, Ross-Degnan D, Wharam JF: Opioid
Prescribing After Nonfatal Overdose and Association With Repeated Overdose: A Cohort Study.
Ann Intern Med 2016; 164: 1-9
9. Chen JH, Humphreys K, Shah NH, Lembke A: Distribution of Opioids by Different
Types of Medicare Prescribers. JAMA Intern Med 2016; 176: 259-61
10. Dowell D, Haegerich TM, Chou R: CDC Guideline for Prescribing Opioids for Chronic
Pain-United States, 2016. JAMA 2016
11. Chou R, Turner JA, Devine EB, Hansen RN, Sullivan SD, Blazina I, Dana T, Bougatsos
C, Deyo RA: The effectiveness and risks of long-term opioid therapy for chronic pain: a
systematic review for a National Institutes of Health Pathways to Prevention Workshop. Ann
Intern Med 2015; 162: 276-86
12. Furlan AD, Reardon R, Weppler C: Opioids for chronic noncancer pain: a new Canadian
practice guideline. CMAJ : Canadian Medical Association journal = journal de l'Association
medicale canadienne 2010; 182: 923-30
13. Nuckols TK, Anderson L, Popescu I, Diamant AL, Doyle B, Di Capua P, Chou R: Opioid
prescribing: a systematic review and critical appraisal of guidelines for chronic pain. Annals of
internal medicine 2014; 160: 38-47
14. http://www.agencymeddirectors.wa.gov/opioiddosing.asp,
15. http://americanpainsociety.org/uploads/education/guidelines/chronic-opioid-therapy-
cncp.pdf,
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Perioperative Glucose Control: Creating a Shared Mental Model

Stephen M. Rupp, MD Seattle, WA
Introduction: In this Refresher Course we will build the fundamental concepts and language needed by the
Perioperative Team to develop a shared mental model for glycemic monitoring and control throughout the
perioperative period. We will share key tools used by Virginia Mason Medical Center to embed good choices in
anesthesiologist flow. The mental model and tools are based upon National Guidelines developed by The American
Association of Clinical Endocrinologists1, The American Diabetes Association2 (ADA), and The Society of Critical
Care Medicine (SCCM)3 (for CCU-bound patients). Due to the scope of the literature, we will not be able to review
the scientific background for every recommendation by these societies. The reader is referred to these references for
the strength of the evidence behind each suggested action.
Scientific Background: Observational studies show that hyperglycemia adversely affects outcome rates including
death for many hospital diagnoses including sepsis, wound infection, heart attack and stroke. 4,5 The predicted
morbidity and mortality increases as mean blood glucose (BG) rises. Interestingly, the risk of negative outcome is
higher for a given mean BG in hyperglycemic patients without the diagnosis of diabetes (DM) than those that carry
the diagnosis of DM. The metabolic stress of surgery triggers counter-regulatory hormones such as glucagon,
norepinephrine, cortisol and growth hormone which can exacerbate hyperglycemia in the perioperative period. 6,7
Hyperglycemia affects the immune system by releasing inflammatory cytokines and reducing chemotactic and
phagocytic function of neutrophils and monocytes.7 Wound healing is impaired when mean BG is > 180 – 200
mg/dL. Poor longitudinal BG control (HbA1c > 6.7%) is associated with increased risk of wound complications. 8
Developing a Shared Mental Model: Perioperative care is intensive and segmented by multiple complex tasks
over time including the initial preparation in the surgeon’s office, the anesthesia preoperative assessment,
preoperative instructions for DM care prior to day-of-surgery, day-of-surgery, and arrival in Surgery Preparation,
intraoperative, PACU and then to home, ward or CCU. Key Concepts that need to be shared across the continuum
include the type of DM, baseline medical management including a standard insulin vocabulary, the measure of
overall baseline control (HbA1c), targets for Perioperative BG, intervals of BG testing and appropriate BG triggers
for action when BG is outside or headed outside the target range.
Type of Diabetes: Type 1 DM is characterized by lack of production of insulin.2 It is usually diagnosed in children
and young adults (though not all) and was previously known as “juvenile onset” DM. It is a form of DM that results
from autoimmune destruction of insulin-producing beta cells in the pancreas. It can be distinguished from Type 2
DM by autoantibody testing. It accounts for approximately 5 – 10% of DM incidence. Important characteristics of
Type 1 DM include the propensity toward insulin sensitivity and being subject to large swings in BG (“brittle”).
Type 2 DM is the most common type of DM (90%) and is characterized by insulin resistance and relative lack of
insulin. Cells do not respond adequately to normal levels of insulin. Type 2 diabetics on insulin at home are likely
to be very resistant when the total daily dose of insulin exceeds 0.6 units/kg/day. Type 2 DM management is
typically started by life style changes and diet management, followed by oral anti-diabetic agents in a step-wise
fashion over time. Finally, if the disease cannot be controlled, insulin is added. The language used in describing
diabetics is critical to appropriate management, decision-making and handoffs down the value stream. The use of
outdated terms including “juvenile onset,” “adult onset,” “insulin-dependent,” “insulin-requiring,” and “non-insulin
dependent” should be discouraged as they do not adequately separate the types of DM.
Insulin Vocabulary and Use: A normal person has a basal level of plasma insulin and a post-prandial peak which
returns to baseline in 2-3 hours. The modern medical management of DM is based upon trying to match the insulin
levels in normal patients both when fasting and after meals.1,2 Accordingly, subcutaneous insulin regimens try to
match this pattern with the “Basal – Bolus” insulin regimen. Basal insulin is the insulin that covers the sugars the
body makes all the time. Nutritional insulin (“Bolus”) covers sugars taken in. “Correctional” insulin refers to a
sliding scale that covers any left-over sugars. A key concept:
Basal + Nutritional + Correctional = Total Daily Dose (TDD) (0.4 – 0.6 units/kg/day)
Typically, basal insulin equals ½ of TDD and nutritional equals ½ of TDD. Thus, each meal one administers 1/3 x
½ TDD = 1/6 of TDD units. It is important to realize that when diabetic patients are NPO, they still need basal
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insulin. During NPO, one gives basal insulin and then a correctional dose if the BG is headed out of range. This is
called the “Basal – Plus” approach. Thus, searching the diabetic’s medication list to understand how much and
when they take their basal insulin and then insuring they receive their basal insulin on their normal schedule is a
critical portion of the shared mental model in Perioperative Services. Use of sliding scale alone is outdated in caring
for hospitalized patients.9,10 A vast array of insulins are available in the United States and Canada. Table 1 is a handy
list of available insulins. They are noted as “Nutritional/Correctional” or “Basal.” Glargine, NPH and detemir are
“basal” insulins and have a no peak or low peak (NPH) in plasma levels and are administered once or twice a day.
Aspart, lispro and glulisine are “nutritional/correctional” and have a rapid-onset, high peak of action which is then
gone in 2-3 hrs.
Calculation of Total Daily Dose of insulin can help you determine if the patient is sensitive, normal or resistant to
insulin. Again, the normal total daily dose ranges between 0.4 and 0.6 units of insulin/kg/day. Risk factors for
sensitivity to insulin and thus risk for hypoglycemia include age > 70, lean body mass (< 25 BMI), history of labile
BG, type 1 DM on < 0.4 u/kg/d and renal insufficiency. 1-2 Glargine is the most popular long-acting basal insulin. It
is given once or sometimes twice a day. NPH and detemir are typically given twice a day. The rapid-acting aspart,
lispro and glulisine are nutritional/correctional insulins and are typically dosed with meals. Importantly, the
propensity of an insulin to cause hypoglycemia is inversely proportional to the height of its peak plasma
concentration. For example, it is very difficult to acutely cause hypoglycemia by glargine as compared to lispro.
U-500 insulin is 5 times more concentrated than other insulin and is used by some endocrinologists for severe
insulin resistance to reduce the total volume of injected drug. Correspondingly, U-300 is 3 time more concentrated.
Since many patients don’t have access to the special syringes used for these insulins, complications can occur when
they are used with normal insulin syringes. For example, since U-500 is 5 times more concentrated, what appears to
be “10 units” of U-500 in a normal insulin or TB syringe actually contains 50 units of insulin. Due to this
complexity, we reserve the use of these concentrated insulins to specific instructions from endocrinologists only.
Preoperative Assessment and Instructions Given to the Patient Prior to Day-of-Surgery:

Patients are called by an RN preoperatively or seen in the PreAnesthesia Assessment Clinic. During the call/visit,
the patient’s medical history and problem list are assembled and updated. The patient’s type of DM is noted and the
patient’s medication list is reviewed and updated. TDD of insulin is noted in addition to whether the patient has a
propensity to hypoglycemia or wide swings in BG. HbA1c is recommended to be measured within 30 days or on
admission to the hospital.1,2 HbA1c is important in diagnosing DM and assessing overall control in the previous 3
months. Though no data supports an absolute cut-off for canceling elective surgery, the level of HbA1c is predictive
of likelihood of wound complications.8 It is used to guide recommendations on management intensification
including begining insulin treatment if HbA1c > 10%. NPO instructions are given following the ASA Guidelines
for Preoperative Fasting. All oral hypoglycemics and non-insulin injectable diabetic drugs are continued on the day-
prior-to-procedure and then stopped on day-of-procedure. The propensity of metformin to induce lactic acidosis has
recently been challenged.11 Accordingly, our inclination to cancel cases when patients inadvertently take metformin
on the day of surgery has waned. Important process items to manage include: day-prior-to-surgery diet and
medications; whether or not the patient will be taking a regular diet or on a bowel prep; the type of insulin regimen
they are on and any oral diabetic medications as well as instructions on what to do if they become hypoglycemic.
RN preoperative diabetic management instructions to the patient for day-before-surgery and day-of-surgery are
summarized in Table 2. Taking diabetic management instructions out of the hands of the surgeon is important to
reduce variability and standardize care. Also, note that we have chosen not to have patients administer insulin to
themselves on the day-of-surgery at home unless they take morning basal insulin and have an afternoon check-in. In
Table 2, you can see that patients take their normal insulin schedule on the morning-prior-to-surgery then take 80% -
100% of their PM glargine or 50% of PM NPH or detemir. 1 This is based upon the pharmacokinetics of these
insulins and their propensity to cause hypoglycemia. A few patients are on glargine alone. Here, their doctor is
covering both basal and some nutritional needs with basal insulin. Thus, the PM dose is reduced to 80% because
they will become NPO. If patients on glargine also take nutritional insulin, we give 100% of the glargine. Patients
who are NPO or on clear liquid diet take correctional insulin based on their BG the night before surgery. Surgery is
scheduled for as early in the day as possible to minimize DM regimen disruption.
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Management of Diabetic Patient Day-of-Surgery: The shared mental model of DM management1,2 includes:
 Target range for BG 100–180 mg/dL. Trigger BG treatments to keep in-range when BG > 140-150 mg/dL
 Recognize the type of DM and take key actions
 Use Basal-Bolus or Basal-Plus subcutaneous regimens for patients bound for the wards
 Match home basal insulin use (dosage and time) and return them to their home regimen asap
 Give weight-based glargine for T2DM patients on oral hypoglycemic treatment alone and are admitted
overnight9,10
 Use insulin infusions for CCU-bound patients.3
 All diabetic and all am-admit patients have the BG tested on admission to surgery prep.
 Test BG q 2 hrs throughout the periop period for diabetic patients and those with hyperglycemia but no DM
 Make clear handoffs down the line
Having a BG target is critical for management. The Endocrine Society1 and ADA2 suggest a 100 - 180 mg/dL range
while the Society of Critical Care Medicine3 targets 140 – 180 mg/dL. In 2001, the Van den Bergh trial12 promoted
the concept of tight glucose control in the CCU but this approach was subsequently shown to have a higher mortality
(due to hypoglycemia) by the NICE Sugar trial.13 Consequently, “tight control” has fallen out of favor. Both the
ADA2 and SCCM3 recommend triggering treatment to keep BG in range when BG hits 140 or 150 respectively.
Thus, the concept of a target range and a trigger to begin correctional insulin.
It is important to detect hyperglycemia in non-diabetic patients due to the increased risk associated.4,5 Thus, preop
BG testing on arrival of all patients being admitted is recommended. Sheehy et al. showed 56% of am-admit
patients will have a BG > 100mg/dL (abnormal fasting value) on arrival. 14 18% will have known DM, 24% will
have new DM or pre-diabetes and 14% will subsequently be shown to have normal fasting BG at follow-up.14 When
a fasting BG >100 is found in a patient without the diagnosis of DM, that patient goes into the q 2h point-of-care BG
testing group. This allows you to follow BG closely in these patients and begin treatment if necessary.
The key actions by the anesthesiologist on admission are based upon the type of DM, the regular daily medicines,
the meds taken in the last 24 hours, the overall control of BG and the point-of-care BG on admission.
Here separation into major categories based on type of DM and daily anti-diabetic meds allows guidance in
management. These separations and key actions are:
Diabetes Type Key Action Steps
Type 1 diabetics -Try to match home basal insulin + SSI if > 140
Type 2 diabetics managed with diet alone -Use sliding scale initially if over 140
Type 2 diabetics on oral hypoglycemic drugs -Use weight-based glargine SQ if admit, no oral meds9,10
Type 2 diabetics on oral meds and insulin -Match home basal insulin, no oral meds9,10 + SSI if > 140
Post-Pancreatectomy -Needs basal insulin: start 0.15 u/kg/d glargine + correctional
Hyperglycemia without a diagnosis of DM -Check HbA1c to diagnose DM, use sliding scale initially
Table 3 is embedded in the insulin order set in the electronic medical record to assist the anesthesiologist in
remembering and being confident in these key action steps. Table 3 Grid Assumptions include: the home regimen
is known, patient is NPO, nutritional insulin is stopped and the patient took 80% of their glargine dose or 50% of
their NPH dose last night.1-2 Use continuous insulin infusion for patients bound for CCU. 4 Instructions for use of
the embedded DM Management Grid (Table 3): Match your patient’s diabetic status (Diet Only, Oral meds only,
type 1 or type 2 DM on insulin with their home insulin regimen and admission BG. Then order that type and
amount of insulin. The admit RN will administer and document. Check BG q2 hr throughout periop period.
Correctional (SSI) insulin should not be administered more frequently than q 4 hr to prevent “stacking” of insulin
doses. The home insulin regimens in Table 3 reflect our most frequent patient presentations in descending order.
Note that in addition to the basal insulin, a sliding scale of correctional insulin is triggered when BG > 140 mg/dL.
Reminders: insulin is dosed on total body weight. Total Daily Dose (TDD) of insulin = sum of all insulins usually
taken at home. TDD usually ranges from 0.4 – 0.6 u/kg/day. Those over 0.6 u/kg/day are insulin resistant. Don’t
mix types of insulin in one syringe. They are incompatible. A hypoglycemia protocol is triggered when BG < 70
mg/dL1-3 The ADA recommends IV dextrose 15-20 grams IV push with recheck in 15 min and repeat dextrose as
necessary.1,2
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As previously noted, the use of oral hypoglycemic drugs is not recommended for hospitalized patients. 1,2,9,10 We use
weight-based glargine regimen only for type 2 DM patients on oral meds alone when patients are admitted to
hospital overnight (not outpatients).9,10 This management above is based upon the Rabbit 29 and Rabbit 2 General
Surgery10 trials where weight-based basal insulin for these patients was more effective than sliding scale insulin in
controlling BG. We use glargine 0.15 units/kg for this group as the dose of 0.25 units/kg used in the Rabbit 2
Surgery10 trial had a 23% hypoglycemia rate (BG < 70 mg/dL). This lower dose is very effective for us and has a
very low rate of hypoglycemia.
For patients that are resistant to insulin (TDD > 0.6 units/kg/d), a more aggressive sliding scale can be constructed
using “the rule of 1800.”15 Here, 1800 is divided by TDD to estimate the expected decrease in BG with 1 unit of
insulin. For example, if the TDD was 120 units, one unit would decrease BG by 1800/120 = 15 mg/dL/unit. If this
patient’s BG was 255 mg/dL and you wanted them back close to 150 mg/dL, you would be looking for a 105 mg/dL
drop in BG. Thus, 105/ 15 = 7 units of rapid-acting insulin would be a good estimate of need.
Since the grid frequently calls for both a dose of basal insulin and some correctional insulin (sliding scale) two
injections are required. We frequently give the basal insulin subcutaneously in the surgery prep area and then
administer the correctional after the patient has been anesthetized. Our pharmacy will draw up the exact dose and
label insulin syringes and deliver them to the OR once an order has been placed.
Handoffs: Continuing care of the diabetic after their surgery requires a good handoff to the surgical or hospitalist
service caring for the patient. This information includes the type of DM, the home regimen, what their BG course
and insulin regimen has been today and when their next point-of-care BG test and insulin admin should occur. For
example: “This is a type 2 diabetic on night-time glargine at home. She took her home glargine last night. We didn’t
give her any basal insulin today. Her BG on admission was 176, so we gave her lispro 2 units. Her last BG was
135. She’ll need her glargine again tonight.” This makes it clear when to resume her home regimen and who is
responsible. Additionally, discussion of the patient’s HbA1c and intensification of DM management may be
needed. Patients without the diagnosis of diabetes and demonstrating hyperglycemia will need a follow-up HbA1c
to diagnose or rule-out DM and perhaps a glucose tolerance test. Diabetic patients with an HbA1c > 10% should be
on insulin maintenance.1-2 Additionally, communication, handoffs, education and medical decision-making can be
enhanced in provider flow by glycemic tracking tools in the electronic medical record and resources like the insulin
dictionary (Table 1) on your intranet.
Education, implementation and measuring performance: Implementation of this treatment protocol has been
very effective in reducing our hyperglycemia rate (BG > 180) in patients coming through periop (see control graph
next page representing 11,947 inpatient days). We began 2012 with a broad educational effort for anesthesiology,
surgery, nursing and hospital medicine. In November 2012, we had an improvement event where we embedded the
tools noted in this refresher course in the workflow of the team. In January 2013, we implemented a real-time
monitoring and coaching effort to help the team apply the principles to patient care. The baseline hypoglycemia rate
did not increase subsequent to these interventions.
Controversies: Due to time, we will not be able to address the following controversies in detail. I will briefly note
our approach. However, the reader is referred to the reading for more information. 1-3,6,7,9,10,16
Fear of insulin-induced hypoglycemia: Attributed to be the biggest obstacle to ordering/giving insulin. 16 It needs to
be overcome by anesthesiologist to be equipped to keep BG in target range. BG < 70 mg/dL is generally considered
the hypoglycemic trigger for treatment.1,2 Still, symptoms of hypoglycemia may be masked by anesthesia.
Insulin infusion titration formulas: Take the initial BG and divide by 100. Give that amount of regular insulin as a
slow bolus via infusion pump, then set that amount as an hourly rate. Check BG in 1 hr and adjust. For example, if
the BG is 220, give 220/100 = 2.2 units reg slow bolus over 10 min via pharmacy mixed infusion (after 20 ml prime
of tubing and discard); then start infusion at 2.2 units/hr and recheck BG. Then adjust. Turn off if BG < 100 mg/dL
Use of Patient’s Insulin Pumps: Permissible as long as it is out of the surgical area and patient can show
anesthesiologist how to run it / turn it off.17 Keep basal rate, turn off boluses. Know bolus amount to reduce BG by
50 mg/dL. Check BG q 1-2h17
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Routine use of IV dextrose as background infusion. Not used in all cases. Poor evidence to support need. We start
D5/0.45NS as BG approaches 100 mg/dL. 5 grams/hour IVPB.
Mixing of antibiotics and vasoactive drugs with dextrose containing diluents: can contribute to hyperglycemia.
Work with pharmacy to try to limit when possible.
Intravenous bolus of regular insulin rather than SQ: IV bolus insulin is used in the treatment of hyperkalemia. A
slow bolus is used to start a continuous insulin infusion (see above). Otherwise, insulin is given subcutaneously.1-2
Dexamethasone for PONV and its effect on BG: Both steroids and surgery/anesthesia cause elevations in BG. It
can be difficult to separate their effects as both usually occur together. It appears that the time course of BG
elevation due to surgery/anesthesia hits a peak at two hours18 or the midpoint of surgery.19 As for dexamethasone, it
has a more pronounced effect on non-DM patients than patients with DM, though BG rises in both groups. 19
Abdelmalak et al.19 recommend not denying the PONV benefits of dexamethasone 8 mg in diabetic patients.
Canceling cases due to high BG or elevated HbA1c: no firm scientific evidence.1-2 We halt elective surgery if BG >
400 mg/dL and rule out diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome. Some institutional
protocols recommend delay of elective surgery if HbA1c is > 9%.20 Prudence would suggest halt of elective surgery
if DM out of control (especially if implant involved).
Three new SGLT-2 inhibitors are now available in the U.S. Their mechanism of action is to inhibit urinary glucose
reabsorption and cause glycosuria. Unfortunately, they also stimulate glucagon secretion which increases hepatic
glucose production and ketones. Euglycemic ketoacidosis has been reported.21 These patients require insulin for
treatment. Holding insulin in these patients in response to “normal” BG is a trap. Our approach to ensure patients
with DM receive their basal insulin on day-of-surgery should prevent or ameliorate this effect. Patients with severe
PONV and DM should have their urine or serum promptly checked for ketones to detect this problem. 21
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References:
1. Umpierrez GE, et al. Management of hyperglycemia in hospitalized patients in non-critical care setting: An
Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2012;97:16
2. Standards of Medical Care in Diabetes-2016. American Diabetes Association. Diabetes Care. 2016;39:S99-104
3. Jacobi J, et al. Guidelines for the use of an insulin infusion for the management of hyperglycemia in critically ill
patients. Crit Care Med. 2012;40:3251
4. Kwon S, et al. Importance of Perioperative Glycemic Control in general surgery. Ann Surg. 2013;257(1):8
5. Falciglia M, et al. Hyperglycemia-related mortality in critically ill patients varies with admission diagnosis. Crit
Care Med. 2009;37:3001
6. Lipshutz AKM and Gropper MA. Perioperative glycemic control. Anesthesiology. 2009;110(2):408
7. Akhtak S, et al. Scientific principles and clinical implications of perioperative glucose regulation and control.
Anesth Analg. 2010;110(2):478
8. Stryker LS, et al. Elevated postoperative blood glucose and preoperative hemoglobin A1c are associated with
increased wound complications following total joint arthroplasty. J Bone Joint Surg Am. 2013;95:808
9. Umpierrez GE, et al. Randomized study of basal-bolus insulin therapy in the inpatient management of patients
with type 2 diabetes (Rabbit 2 Trial). Diabetes Care. 2007;30(9):2181
10. Umpierrez GE, et al. Randomized study of basal-bolus insulin therapy in the inpatient management of patients
with type 2 diabetes undergoing general surgery (Rabbit 2 Surgery). Diabetes Care. 2011.34:256
11. Salpeter SR. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes. Cochrane Database
Syst Rev. 2010;(4)CD002967
12. Van den Bergh, et al. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001;345:1359
13. Finfer S, et al. Intensive versus conventional glucose control in critically ill patients. The NICE-SUGAR trial. N
Eng J Med. 2009;360:1283
14. Sheehy AM, et al. Preoperative “NPO” as an opportunity for diabetes screening. J Hosp Med. 2012;7:611
15. Joshi GP, et al. Society for Ambulatory Anesthesia Consensus Statement on Perioperative Blood Glucose
Management in diabetic patients undergoing ambulatory surgery. Anesth Analg. 2010;111:1378
16. Maynard G, et al. Perioperative care of the geriatric patient with diabetes or hyperglycemia. Clin Geriatr Med.
2008;24:649
17. Ahmed Z, et al. Advances in diabetic management: implications for anesthesia. Anesth Analg. 2005;100:666
18. Hans P, et al. Blood Glucose concentration profile after 10 mg dexamethasone in non-diabetic and type 2
diabetic patients undergoing abdominal surgery. Br J Anaesth. 2006;97:164
19. Abdelmalak BB, et al. The hyperglycemic response to major noncardiac surgery and the added effect of steroid
administration in patients with and without diabetes. Anesth Analg. 2013;116:1116
20. Miller JD and Richman DC. Preoperative evaluation of patients with diabetes mellitus. Anesth Clin 2016;34:155
21. Peters AL et al. Euglycemic diabetic ketoacidosis: a potential complication of treatment with sodium-glucose
cotransporter 2 inhibition. Diabetes Care 2015;38:1687
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Table 1: The “Dictionary” of available insulin preparations.
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Table 2
Table 3:
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Title: State of the Art Labor Analgesia

Kenneth E Nelson, M.D. Winston-Salem, NC
Learning Objectives
At the conclusion of this activity, participants should be able to:

- Utilize the latest technical advances for instrumenting the spinal and epidural spaces
- Employ non-neuraxial analgesic techniques
- Apply newer techniques and technologies for maintaining labor analgesia
- Select the most appropriate analgesic agents and adjuncts to use with spinal and epidural techniques
Introduction
The options for providing labor analgesia have undergone continuous change over the past few decades, culminating
in the current state of the art. Although the available number of topics, issues, and controversies in labor analgesia
are nearly unlimited, the current discussion will be limited to the following three main topics: Maintenance of Labor
Analgesia, Controversies, and Techniques.
Maintenance of Labor Analgesia
PCEA/PIEB
Once a catheter has been placed into the epidural space, several options are available to maintain analgesia. One of
the first methods to be employed was intermittent bolusing on patient request. Once the effect of the initial dose of
local anesthetic began to subside, contraction pain would return and the patient would request more medication, at
which time the anesthesiologist would provide analgesia using another bolus dose of local anesthetic. The obvious
disadvantage to this technique is the relatively large amount of manpower required. Other disadvantages include
non-continuous pain relief and an intermittent increase in side effects such as hypotension and motor blockade. The
natural progression in management was then to employ infusions to maintain analgesia, but early infusion pumps
were relatively primitive and sometimes unreliable, and data were lacking to guide infusion rates 1. A large volume
of research was eventually published to help rectify this problem, and it was during this time that the next step in the
evolution of maintenance of labor analgesia occurred: patient controlled epidural analgesia (PCEA) 2. By this time,
copious experience had accumulated with the use of intravenous PCA, and the same principles were then applied to
PCEA. However, it was soon discovered that there are some important differences between opioid-based IVPCA
for acute postoperative pain and local anesthetic-based PCEA for labor analgesia. Perhaps most importantly, a basal
infusion was found to be very effective with PCEA3. Studies continued, however, and further information has
emerged over the past 2 decades suggesting that even more effective methods can be employed, such as intermittent
bolusing at programmed intervals4. Epidural catheters with multiple holes are commonly used to maintain labor
analgesia, and “differential flow” occurs through epidural catheters containing multiple holes 5. During clinically
relevant continuous infusion rates, the vast majority of flow occurs through the proximal port (see figure 1). Only
when pressures become significantly higher will flow begin to occur at the middle and distal holes, which is what
occurs during a rapid bolus. As expected, analgesia can be improved by employing flow through all three holes.
The superiority of programmed intermittent epidural bolusing (PIEB) plus PCEA over continuous infusion (CI) plus
PCEA has already been demonstrated, and pumps are currently being developed in order to exploit this
advantage6,7,8. The concept of differential flow through multiple epidural catheter ports also implies the possibility
that different ports can reside in different places (epidural space, intravenous, subarachnoid) and can cause different
clinical characteristics depending on whether continuous infusion or intermittent bolusing is being employed. The
next step in the evolution of maintenance of epidural labor analgesia will be computerized pumps with a feedback
loop that can continuously adjust basal infusion rates based on average patient requirements, allowing for automatic
changes in infusion rates to match the changing analgesic needs during the course of labor. These so-called “smart
pumps” are currently under development, and future research will guide the best combination of their use with basal
infusions and programmed intermittent bolusing.
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Figure 1. “Differential Flow” occurs through a multihole catheter, where at low pressures encountered
during continuous infusion, the majority of flow occurs at the proximal port. Only at higher pressures
encountered during rapid bolusing will flow occur at the middle and distal holes.
Intravenous Opioids
There are several acceptable opioids that can be used to provide labor analgesia. Partial agonists such as
butorphanol have a ceiling effect for respiratory depression, thus making them an attractive choice in laboring
women due to a theoretically lower risk of maternal side effects and neonatal depression 9. However, the analgesic
effect is likewise limited, and analgesic efficacy has been reported to range from moderate to non-existent. A
commonly used dose of butorphanol is 1mg IV every hour as needed, held when delivery is imminent.
Other opioids without ceiling effect have also been used, and one of the most commonly studied is
meperidine. However, as with all intravenous opioids for labor analgesia, the reported efficacy is variable and often
disappointing. One report even concluded that intravenous opioids for labor analgesia are “unethical and medically
incorrect”10, but the vast majority of studies report at least a moderate effect11. Potential drug interactions with
meperidine have contributed to its decline in popularity, including serotonin syndrome in patients taking MAOIs or
SSRIs. Another potential problem with meperidine is accumulation of the metabolite normeperidine, which has
been reported to cause convulsions, yet should only be an issue with chronic administration.
Fentanyl is another commonly used intravenous opioid for labor analgesia, and it has been extensively
studied for this use. It rarely causes allergic reaction, and is relatively free of drug interactions, but has no ceiling
effect for respiratory depression, so must be used with caution on the labor ward. It can have a cumulative effect;
therefore neonatal respiratory depression is an important concern12. Dosage recommendations are found in figure 2.
Remifentanil is a newer opioid analgesic with a rapid onset and short duration of action, and its unique
pharmacodynamic profile created early enthusiasm for its use in labor analgesia. However, even with the rapid
onset, it is nearly impossible to deliver remifentanil in such a way that the analgesic effect mirrors the time course of
the contraction. Doing so would require remifentanil dosing to occur about 2 minutes prior to the onset of
contraction, which, of course, is difficult if not impossible to predict. One published study attempting to accomplish
the goal of providing the remifentanil dose 140 seconds prior to contraction failed to improve labor analgesia13. In
spite of this shortcoming, there are several reports of its successful use in labor analgesia, including a comparison
with fentanyl, which concluded that both drugs provide moderate analgesia, with remifentanil causing more
maternal oxygen desaturation, and fentanyl causing more neonatal depression8. Dosage recommendations for
remifentanil are found in figure 3.
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Figure 2. Dosage recommendations for fentanyl PCA for labor analgesia
Figure 3. Dosage recommendations for remifentanil PCA for labor analgesia.
Controversies
Air vs Saline for Loss of Resistance

Either air or saline can be safely used to test for loss of resistance when accessing the epidural space. Recent
debates on the subject have brought to light the list of reasons to avoid air, whereas no such list exists for the
argument against saline. The proponents of air correctly argue that the efficacy and overall incidence of clinically
significant morbidities have not been shown to differ between the two techniques, yet case reports and clinical
experience have amassed a list of reasons to avoid air. Incomplete analgesia due to air pockets in the epidural space
has been reported in pediatric patients20. For the same to occur in obstetrics, it would presumably require large
volumes of air, but this is still a potential risk that is avoided by using saline. Venous air embolism 21 and
pneumocephalus22 are more likely to occur with the use of air, and although a small amount of intravenous air is
rarely a problem, pneumocephalus is the presumed reason that using air for loss of resistance is more likely to cause
headache than when using saline. Finally, nerve root compression23 and subcutaneous emphysema24 have been
suggested as additional potential complications. One historical argument against saline that is now antiquated, but
deserves mention, is the theoretical possibility of confusing saline for CSF when performing a CSE. In a recent
study comparing air to saline for LOR during the CSE technique, no difference was seen in failure rates, and there
were no cases of saline being confused for CSF25. This scientific report concurs with what should be expected under
these circumstances, where saline injected into the epidural space distributes amongst the tissues such as fat and
blood vessels, and is then not available to subsequently be aspirated through a spinal needle.
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Accidental Dural Puncture: What Next?

The risk of accidental dural puncture (ADP) can be minimized, but not completely eliminated, and carries an overall
risk of approximately 1 in 200. Once an ADP occurs, there are two basic management choices that can be made: 1)
resite the epidural, or 2) insert a spinal catheter. When choosing a spinal catheter, potential complications to keep in
mind include infectious risk26, spinal cord trauma27, neurotoxicity28, and inappropriate injection through the
catheter29. When choosing to resite an epidural, potential complications to consider include inferior analgesia 30
(compared to a spinal catheter), increased headache risk31 (also compared to the spinal catheter), and the risk of
unexpected high block32. The SCORE (Serious Complications Obstetrics REpository) Project has demonstrated that
one of the highest risk scenarios for developing high spinal is when an epidural that is resited after a wet tap is being
dosed for surgery. Data are mixed on whether the use of a spinal catheter after wet tap can reduce the incidence of
PDPH, but no study has demonstrated an increase in headache risk. Whether choosing a spinal catheter or a resited
epidural, perhaps the most important consideration is conspicuous labeling of the catheter at the proximal connector
in order to minimize the risk of inappropriate injections.
Techniques
Combined Spinal Epidural (CSE)

Combining spinal analgesia with epidural analgesia was developed as a way of exploiting the attributes of both
techniques, i.e. the reliability and fast onset of the spinal combined with the duration and versatility of the epidural.
Although the CSE technique is well established, its role in labor analgesia is still in the process of being defined.
For instance, the use of CSE for patients at high risk for Cesarean delivery remains controversial to some, due to the
“untested” nature of the catheter immediately after placement. Once the spinal analgesic dose is administered and
an epidural catheter is placed, it is appropriate to test for spinal placement of the catheter using local anesthetic, but
ruling out intravenous placement is more problematic. Furthermore, even if the catheter is appropriately in the
epidural space and not intravenous, its functionality is for subsequent labor analgesia and/or unexpected Cesarean
delivery is unproven. The theoretical concern of higher failure rate and greater morbidity with these untested CSE
catheters has not been borne out in studies, but the thought of a STAT Cesarean delivery in an morbidly obese
preeclamptic parturient with an untested catheter is enough to dissuade many anesthesiologists from using a CSE
technique under these circumstances. Intrathecal opioids can also cause pruritus, which is often negligible but
sometimes distressing enough to cause patients to request treatment, and even to choose against a CSE with
subsequent pregnancies. Nevertheless, the CSE technique has many advantages over the epidural technique alone,
including rapid onset, reliability, and minimal motor block. Also, the rate of cervical dilatation has been shown to
be enhanced by the use of CSE compared to both epidural 33 and systemic analgesia34. Figure 4 shows a typical
recipe for the spinal portion of CSE labor analgesia.
Figure 4. A typical recipe for the spinal portion of CSE labor analgesia.
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Dural puncture epidural

A recent addition to the obstetric anesthesiologist’s toolbox is the “dural puncture epidural”35. This technique seeks
to improve the quality and reliability of epidural analgesia by making a small dural puncture during epidural
placement, but without the introduction of spinal medication. Then, the catheter can be fully tested for efficacy,
while small amounts of the epidural drug passes through the dural puncture to improve efficacy. While still not in
widespread use, this technique has been thoroughly investigated and appears to improve analgesia without
increasing side effects. Additionally, it addresses the theoretical disadvantage of the CSE technique described above
by “proving” the catheter to be fully functional in the event of an unexpected Cesarean delivery.
Unintended Catheter “Pullback”

Regardless of the epidural catheter technique used, the timing of securing the catheter to the skin can
significantly influence the amount of catheter that remains in the epidural space (see figure 5). When the patient is
in the sitting position and flexion of the lumbar spine is optimized, the distance from the skin to the ligamentum
flavum is minimized. When the patient returns to a relaxed sitting position this distance increases, and the skin and
soft tissues move caudad. Therefore, if the catheter were to be secured to the skin before the patient is allowed to
return to a relaxed position, the catheter will be pulled back out of the epidural space by the distance that the soft
tissues travel when returning to this position, even as the catheter mark at the skin stays constant. This effect can be
further exaggerated by obesity, and can lead to complete failure of the epidural catheter if not recognized. To avoid
this unintended catheter “pullback”, the patient should be allowed to return to a relaxed position before securing the
catheter to the skin. Additional consideration should be given to allowing the patient to lie in the lateral position
prior to securing the catheter, as this could allow the soft tissue to move even further, especially in the obese patient.
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Figure 5. Unintended catheter “pullback” can occur after securing the epidural catheter to the skin while the
patient is still in position for the procedure. A. With the patient in position for epidural placement, the soft
tissue is compressed against the spine. B. When the patient returns to a natural sitting or lateral position, the
soft tissue relaxes and the distance from the skin to the ligamentum flavum (LF) increases. If the catheter
was secured to the skin while the patient was in the procedural position, then its tip will be withdrawn from
the epidural space as the patient resumes a relaxed position. The solid blue/red line represents the epidural
catheter, and the dotted line represents the original catheter path.
Ultrasound guided neuraxial block

Advancing technology has made its way onto the labor ward in the form of ultrasound guided epidural
placement36,37. Popular for many years in the practice of peripheral nerve blocks, the use of ultrasound has recently
seen a flurry of activity in the obstetric anesthesia literature for use in neuraxial procedures. Traditional LOR
technique is “blind” in that the anesthesiologist relies on tactile cues to determine whether the epidural is midline,
which tissues the tip of the needle is passing, and when the tip of the needle enters the epidural space.
Ultrasonography adds a visual tool that can be used to determine the position of landmarks and to measure a depth
from the skin surface to the epidural space prior to initiating the procedure. Using ultrasound to guide a neuraxial
block in real time is more problematic, however, due to the narrow “window” between spinous processes being
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shared by both the ultrasound probe and the epidural needle. Proponents of the technique hope that safety will be
enhanced with the use of ultrasound. Epidural hematoma and infection are fortunately extremely rare, and so it will
be difficult to ever say conclusively whether the use of ultrasound reduces the incidence of these complications by
decreasing the number and duration of attempts required to access the epidural space. Similarly rare is the
complication of direct trauma to the spinal cord or conus medularis, but this grave complication can be theoretically
avoided by performing the technique below the terminis of the spinal cord. Previous studies have shown that even
experienced anesthesiologists are frequently incorrect when predicting interspace level using manual palpation of
anatomical landmarks, and when wrong, we are usually higher than predicted38,39,40. Ultrasound allows for precise
determination of spinal interspace levels, thus avoiding unnecessary neuraxial procedures above the cauda equina 40.
Ultrasound remains less ubiquitous on the labor and delivery ward than it is in the peripheral nerve block suite, most
likely due to the perception of a very high rate of success without its use, along with the limitations against its use in
real time. Also, the routine use of ultrasound would result in an increase in the amount of time from patient request
to first pain free contraction, causing some resistance to its use from both the anesthesiologist and the patient. In
spite of some limitations, ultrasound is gaining in popularity as a tool for lumbar epidural placement, and in the
future is likely to be widely considered an important tool for assisting in lumbar epidural placement in select cases.
Novel Approaches to Locating the Epidural Space

The use of ultrasound waves emanating from the tip of the needle has proven successful for identifying the epidural
space in animal models, and is expected to reach clinical trials in the future 41. Another similar technology uses
optical spectral absorption of the different tissue planes rather than sound waves 42. The hope is that some day, our
current “blind” approach to the epidural space through loss of resistance will be replaced with advanced technology
that will allow identification of the tissue planes and epidural space with real-time visualization.
Conclusion
What is “State of the Art Labor Analgesia”? The definition is constantly evolving as research and clinical
experience guides changes in analgesic agents, neuraxial adjuncts, pumps for maintaining epidural analgesia, and
techniques for obtaining access to the epidural and subarachnoid spaces. During this evolution, controversies will
inevitably arise, and the anesthesiologist needs to be aware of the pros and cons of choosing opposing techniques
such as air vs saline for loss of resistance, and whether to place a spinal catheter or resite an epidural following
accidental dural puncture. Technology also provides an evolving definition of state of the art as devices are
developed and perfected which allow an easier path to the epidural space while minimizing complications.
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syndrome after continuous spinal anesthesia. Anesth Analg. 1991 Mar;72(3):275-81.
29. Mappes A, Schaer HM. Accidental injection of ether into the epidural space Anaesthesia. 1991
Feb;46(2):124-5.
30. Arkoosh VA, Palmer CM, Yun EM, Sharma SK, Bates JN, Wissler RN, Buxbaum JL, Nogami WM,
Gracely EJ. A randomized, double-masked, multicenter comparison of the safety of continuous intrathecal
labor analgesia using a 28-gauge catheter versus continuous epidural labor analgesia Anesthesiology. 2008
Feb;108(2):286-98.
31. Ayad S, Demian Y, Narouze SN, Tetzlaff JE. Subarachnoid catheter placement after wet tap for analgesia
in labor: influence on the risk of headache in obstetric patients. Reg Anesth Pain Med. 2003 Nov-
Dec;28(6):512-5.
32. Leach A, Smith GB. Subarachnoid spread of epidural local anaesthetic following dural puncture.
Anaesthesia. 1988 Aug;43(8):671-4.
33. Tsen LC, Thue B, Datta S, Segal S. Is combined spinal-epidural analgesia associated with more rapid
cervical dilation in nulliparous patients when compared with conventional epidural analgesia?
Anesthesiology. 1999 Oct;91(4):920-5.
34. Wong CA, Scavone BM, Peaceman AM, McCarthy RJ, Sullivan JT, Diaz NT, Yaghmour E, Marcus RJ,
Sherwani SS, Sproviero MT, Yilmaz M, Patel R, Robles C, Grouper S. The risk of cesarean delivery with
neuraxial analgesia given early versus late in labor. N Engl J Med. 2005 Feb 17;352(7):655-65.
35. Cappiello E, O'Rourke N, Segal S, Tsen LC. A randomized trial of dural puncture epidural technique
compared with the standard epidural technique for labor analgesia. Anesth Analg. 2008 Nov;107(5):1646-
51.
36. Carvalho JC. Ultrasound-facilitated epidurals and spinals in obstetrics. Anesthesiol Clin. 2008
Mar;26(1):145-58.
37. Vallejo MC, Phelps AL, Singh S, Orebaugh SL, Sah N. Ultrasound decreases the failed labor epidural rate
in resident trainees. Int J Obstet Anesth. 2010 Oct;19(4):373-8.
38. Broadbent CR, Maxwell WB, Ferrie R, Wilson DJ, Gawne-Cain M, Russell R. Ability of anaesthetists to
identify a marked lumbar interspace. Anaesthesia. 2000 Nov;55(11):1122-6.
39. Van Gessel EF, Forster A, Gamulin Z. Continuous spinal anesthesia: where do spinal catheters go?
Anesth Analg. 1993 May;76(5):1004-7.
40. Margarido CB, Mikhael R, Arzola C, Balki M, Carvalho JC. The intercristal line determined by palpation
is not a reliable anatomical landmark for neuraxial anesthesia. Can J Anaesth. 2011 Mar;58(3):262-6.
41. Chiang HK, Zhou Q, Mandell MS, Tsou MY, Lin SP, Shung KK, Ting CK. Eyes in the needle: novel
epidural needle with embedded high-frequency ultrasound transducer--epidural access in porcine model.
Anesthesiology. 2011 Jun;114(6):1320-4.
42. Rathmell JP, Desjardins AE, van der Voort M, Hendriks BH, Nachabe R, Roggeveen S, Babic D,
Söderman M, Brynolf M, Holmström B. Identification of the epidural space with optical spectroscopy: an
in vivo swine study. Anesthesiology. 2010 Dec;113(6):1406-18.
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Legends for figures
Figure 1: “Differential Flow” occurs through a multihole catheter, where at low pressures encountered during
continuous infusion, the majority of flow occurs at the proximal port. Only at higher pressures encountered during
rapid bolusing will flow occur at the middle and distal holes.
Figure 2: Typical settings for a fentanyl IV PCA.
Figure 3: Typical settings for a remifentanil IV PCA.
Figure 4: Typical drugs used for spinal labor analgesia with a CSE.
Figure 5: Unintended catheter “pullback” can occur after securing the epidural catheter to the skin while the patient
is still in position for the procedure. A. With the patient in position for epidural placement, the soft tissue is
compressed against the spine. B. When the patient returns to a natural sitting or lateral position, the soft tissue
relaxes and the distance from the skin to the ligamentum flavum (LF) increases. If the catheter was secured to the
skin while the patient was in the procedural position, then its tip will be withdrawn from the epidural space as the
patient resumes a relaxed position. The solid blue/red line represents the epidural catheter, and the dotted line
represents the original catheter path.
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Current Concepts and Controversies in Acute Pain Management
Eugene Viscusi, M.D. Philadelphia, PA

Acute pain management continues to be challenging. Studies have demonstrated continued unmet needs with the
majority of patients experiencing significant pain at some point following surgery. 1 Analgesic gaps (periods of
breakthrough pain) continue to be a problem for most patients. The last year has brought an unprecedented focus on
opioid abuse even with the short term use of opioids for acute pain. There is increasing awareness to opioid related
side effects and the need to minimize opioids generally through the use of multimodal analgesic techniques. Opioid
related respiratory depression and sleep apnea are now major considerations in the postoperative period. The recent
Joint Commission Sentinel Event Alert of August 2012 highlights the need for greater caution when prescribing
opioids including patient risk stratification, heightened monitoring and les reliance on opioids. At the other end of
the opioid spectrum, we have the challenge of managing postoperative pain in the presence of opioid tolerance and
chronic opioid use. There is also an emerging theme of chronic pain following surgery. This year also saw the
publication of the combined societies Guidelines on Postoperative Pain. 2
The Perioperative Surgical Home (PSH) is a recent and important development in our specialty. Anesthesiologists
may be taking the lead in perioperative medicine but there remains controversy and competition among various
specialties as to whom will take the lead. Acute pain management and the resulting outcome benefits are an integral
part of the PSH.3-5 Acute pain management services have historically done a portion of this effort as well as the
creation of Enhanced Recovery After Surgical (ERAS) pathways6 The management of acute pain with an eye to
demonstrating outcome improvement will be an important part of the PSH and ERAS and a critical role for the
future of anesthesiology taking us well beyond the walls of the operating room. This Refresher Course Lecture will
present current and emerging concepts in acute pain management, many of which remain controversial. This lecture
will emphasize the impact of the operating room anesthesiologist on longer term outcome.
CDC and FDA Guidance on Opioids
Opioid associated risks are now major concerns even with acute pain and chronic non-cancer pain. CDC issued
specific guidance on the use of opioids for non-cancer pain.7). Previously in 2013, the FDA changed the labels for
extended release opioids clarifying that these potent agents are only for stable chronic pain when all other agents
fail. In March of 2016, the FDA issued guidance (which will lead to label changes) for immediate release opioids
which are commonly used for acute pain. Summarizing these changes, opioids are not first-line analgesics and are
only for moderate to severe pain when other agents have failed. Further, the lowest effective dose should always be
used. Finally, opioids are only for short term use. The prevailing theme is that the role of opioids needs to be
reevaluated. Certainly much acute pain can be managed without opioids or with opioids as adjunctive agents for
short periods.
Multimodal Analgesia
Historically, opioids have been heavily relied upon as single agents for postoperative pain. Opioids have been
accepted as potent and effective analgesics but at the price of opioid related side effects. Patients typically balance
side effects with pain relief – often requesting less pain relief rather than suffer opioid related nausea and vomiting. 8
These gastrointestinal side effects are distressing to patients and the most common reasons for refusing treatment.
Further, opioids have limited efficacy for some types of pain, particularly visceral and neuropathic pain. Acute
postoperative pain is often a mixed pain syndrome with multiple components and hence may not be relieved well
with opioids alone. With aggressive multimodal analgesia incorporating regional/local anesthesia techniques,
opioids may be minimized and in some cases eliminated.
The concept of multimodal analgesia entered the acute pain literature in the early 1990’s when Kehlet described the
benefits of “balanced” analgesia.9 Today, multimodal analgesia, the application of two or more analgesics acting at
different pain pathways and by different mechanisms, is considered standard practice to enhance analgesia and
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minimize reliance on opioids. The ASA Guidelines on Acute Pain Management support the use of nonopioids as
around the clock agents with opioids as supplemental agent. The most commonly employed agents are local
anesthetics, acetaminophen, NSAIDs, COX-2 selective inhibitors, gabapentin and pregabalin, and ketamine. While
these agents may be viewed as less potent than opioids, emerging information suggests they may be able to play a
more significant role than previously thought.10 Opioid reduction or “sparing” is at the heart of many of the
challenges and controversies in acute pain management. Opioid reduction alone is not sufficient! True opioid
sparing requires not only a reduction in total opioid but also some concomitant benefit usually observed as a
reduction in opioid related side effects. Future acute pain management strategies will likely rely much less on
opioids.
Opioid Related Respiratory Depression and Sleep Apnea
The effects of opioids on respiration are well known. Opioids are known to inhibit the ventilator response to both
hypoxia and hypercapnea. In recent years there has been increasing awareness to critical respiratory events. 11,12The
emphasis place on “pain the 5th vital sign” by the Joint Commission several years back may have increased the use
of opioids in the hospital setting in an attempt to improve pain assessments. The increasing incident of sleep apnea,
often blamed on increasing obesity in our society, is also considered a risk factor for opioid use.
Obstructive sleep apnea (OSA) is usually associated with obesity, snoring or other signs of airway obstruction. Yet,
the majority of patients with OSA are undiagnosed and many are not obese. 13 Further, OSA may coexist with
central sleep apnea (CSA).14 Further, it has been demonstrated that patients with OSA may develop respiratory
depression from opioids but that it is in fact on a central basis and not obstructive. 15 Up to 50% of long term opioid
dependent patients may exhibit CSA.16 The severity of central sleep apnea is proportional to the daily chronic
opioid dose with morphine doses greater than 200 mg/day being a significant 17-19 Chronic opioid use reduces the
proportion of time spent in REM sleep. CSA worsens during nonREM sleep further increasing the risk of a
respiratory event in the chronic opioid.20,21 Postoperative sleep-disordered breathing is now recognized as a risk
factor for postoperative respiratory events. Chung and colleagues identified that at least 18.3% of non-sleep apnea
patients develop moderate to severe sleep disordered breathing postoperatively.22
While respiratory depression (RD) is a serious problem, definitions of RD vary widely. Reported incidences range
from 1% to approximately 40%.23 However, these definitions include transient oxygen desaturation or transient
respiratory rates below 10 breaths per minute. While these events should not be taken lightly, it is difficult to
predict which or how many of these events will progress to critical situations requiring intervention. In one series of
over 2000 patients with standard patient controlled analgesia settings, the incident of critical respiratory depression
was 0.1-0.3%.24 The controversy here is determining if and what type of monitoring is appropriate for patients
receiving opioids and how to minimize opioid use.
An ASA task force provided guidance on managing patients with OSA. 25 There are no specific analgesic
recommendations but rather favor minimal opioid use and multimodal analgesia. Local / regional anesthetic
techniques are encouraged as is epidural analgesia without opioid.
There are various monitoring techniques recommended for the OSA patient but no definitive approach. Pulse
oximetry is generally recommended although capnometry may be a more sensitive indicator. Observational
monitoring in the PACU with an OSA prescreening tool may have a role in risk stratifying patients who would
benefit from the most aggressive monitoring.26 The STOP-Bang scoring system has also shown merit in identifying
at-risk patients.27
Using the STOP-Bang questionnaire, one team of investigators found 41.5% of a standard preoperative elective
population had OSA. These investigators also identified a ten-fold increase in pulmonary and cardiac complications
in patients with OSA.28 Clearly, patients with OSA may benefit from advance planning. Early identification is key.
This allows planning an anesthetic to minimize reliance on opioids both intra- and postoperatively as well as
designing an appropriate multimodal approach with appropriate monitoring.
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The role of postoperative CPAP has remained somewhat controversial. Liao and colleagues found that auto-titrated
CPAP in surgical patients with OSA reduced the apena-hypopnea index (AHI) but that only 26-48% of patients used
their CPAP device more than 4 hours each night.29 In a systematic review by Nagappa, there was no significant
difference between postoperative adverse events with or without CPAP although the AHI was reduced. 30
The recent closed claims analysis identified that the vast majority of incidents occur in the first 24 hours and were
deemed largely preventable.31 Opioids were a common theme along with other nonopioid sedative agents.
Continuous delivery of an opioid by infusion (intravenous or neuraxial) was a significant factor. This follows the
emerging signal with extended release / long acting oral opioid formulations leading to respiratory deaths. While
enhanced monitoring may reduce critical opioid events, clearly opioids are a major factor and it behooves us to
minimize their use when possible.
Emerging Views on Opioids
Mu-opioid receptors are ubiquitous within the CNS and at peripheral sites. The analgesic action of opioids within
the CNS is well known. Opioid adverse events are related to both central and peripheral receptors. Peripheral
opioid receptors have a role in ileus, constipation, hormonal regulation, tumor growth, angiogenesis and
immunological function. While long term opioid use has clear risks, there is emerging evidence that the short term
use of opioids may have significant consequences. Use of opioids for as little as one month may produce lasting
changes in the brain.32 Elderly patients given opioids for postoperative pain are at risk for long term opioid use. 33
Opioids may reduce survival after cancer surgery. 34 In retrospective studies, perioperative plans that reduce opioids
have been shown to increased cancer survival following surgery for breast cancer, prostate cancer and possibly
bowel cancer. These typically involve regional anesthetic techniques (paravertebral blocks, epidurals). Opioids are
known to enhance angiogenesis leading to tumor growth and to inhibit the immunological response which may alter
survival. Recent work in rodents with peripheral opioid antagonism demonstrated an inhibition of tumor growth. 35
Opioid Tolerance and Hyperalgesia
Long term use of opioids is known to produce tolerance or decreased efficacy requiring dose escalation. Some
patients on chronic opioids also exhibit hyperalgesia or altered pain sensitivity. 36 As a group, patients on chronic
opioid therapy for pain or methadone maintenance are well known to present significant postoperative pain
challenges.
For these patients in the postoperative period, increased opioid requirements are expected but often pain is
unrelieved with opioids alone.37 Opioid tolerant patients benefit from aggressive multimodal analgesia with regional
anesthetic techniques. Recently, ketamine has shown efficacy in this setting. In opioid tolerant spine surgery
patients, Loftus and colleagues demonstrated that pre- and intra-operative ketamine reduced pain and opioid
requirements in the immediate postoperative period and up to six weeks following surgery. 38-40 Low dose ketamine
is now commonly employed in opioid tolerant patients. There is some controversy as to when and where ketamine
should be administered. Loftus and colleagues demonstrated benefit from pre- and intra-operative administration.
Postoperative ketamine infusion is a useful adjunct in multimodal analgesia for these patients but further studies are
warranted to evaluate dosing and duration of treatment.
Chronic Pain Following Surgery
Chronic pain may be a consequence of surgery. Until recently, normal resolution of acute pain was expected to be a
routine occurrence. There is a significant burden of long-term pain following surgery. The incidence following
thoracotomy and radical mastectomy may exceed 50%. The incidence following inguinal hernia repair is 19-40%.
There is now an understanding that healing with neuronal plasticity may occur resulting in chronic postsurgical pain
(CPSP). CPSP has been linked to severity of acute pain.42 Following thoracotomy, patients who experience pain of
greater intensity and for a longer duration had a higher risk of persistent pain. Kehlet has identified not only intense
acute pain but also, nerve injury and intense inflammatory response as associated factors.42
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Surgery often results in an intense peripheral inflammatory response (peripheral sensitization) as a consequence of
the release of local inflammatory mediators. This “inflammatory soup” causes peripheral sensitization leading to
central sensitization (the release of central inflammatory mediators) which in turn results in further pain
sensitization.43 Even in the presence of total neuronal blockade (spinal anesthesia), there is still a central humoral
response to peripheral inflammation. Hence, local anesthetic techniques alone cannot inhibit this process of central
sensitization.
Total knee arthroplasty has a reported incidence of CPSP approaching 9%. A recent study utilizing a complex
multimodal regimen with pregabalin for total knee arthroplasty showed a marked reduction in chronic neuropathic
pain.44 While this is one study, it provides a basis for the potential use of multimodal analgesia as an approach to
reducing the prevalence of CPSP. Still, another study with chronic pain following total joint arthroplasty supports
that patients may have underlying vulnerabilities such as major depression or chronic pain elsewhere. 45 There is
some evidence correlating CPSP to individual pain response with experimental pain models.46
In a number of surgical models, perioperative pregabalin either alone or within a complex multimodal regimen has
been shown to reduce pain in the immediate postoperative period and in some studies in the months following
surgery.47-52 Recently, intraoperative lidocaine infusion was shown to reduce chronic pain following breast
surgery.53
Ultimately, chronic post-surgical pain is likely to be multifactorial in origin. Current best evidence suggests that a
multimodal analgesic approach may offer the best current approach for reducing long-term pain after surgery. If
specific at-risk individuals can be identified in the future, targeted approaches might be possible.
Anesthesia and Longer Term Outcome
In addition to the implications for cancer survival and chronic pain, our intraoperative anesthetic management may
also influence important aspects of quality of life. A recent study demonstrated that pre-incision dosing of ketamine
during on-pump cardiac surgery attenuated postoperative cognitive dysfunction. A concomitant reduction C-reactive
protein was also noted.54 Surprisingly, high-dose dexamethasone did not reduce cognitive dysfunction so this
ketamine effect is not from anti-inflammatory properties.55 Intraoperative lidocaine was shown to improve quality
of life and reduce pain at three months following complex spine surgery along with a slight reduction in 30 day
complications. Lidocaine, in addition to its local anesthetic properties, is known to have potent anti-inflammatory
properties.56
Expanding Role for Ketamine
There is increasing use of ketamine both intraoperatively and postoperatively. While the utility of ketamine is
gaining acceptance, concerns for potential side effects have limited use. Recent publications have reviewed large
databases where ketamine is routinely used on standard wards, demonstrating remarkable safety compared to opioid-
related side effects.57 Other authors applaud the use of postoperative ketamine as a means to reduce the known
complications of opioids in the postoperative period.58
Combined Society Guidelines
This year saw the publication of the consensus guidelines on postoperative pain from the American Pain Society,
The American Society of Regional Anesthesia and the American Society of Anesthesiologists.2 The document is
highly recommended reading for anyone managing surgical patients. These evidence-based guidelines support the
use of multimodal analgesia and in particular the use of intraoperative ketamine and lidocaine.
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Conclusions
Acute pain management continues to be challenging. While significant strides have been made in many areas,
specific patient populations and surgical pain models remain underserved. Opioid related adverse events,
particularly respiratory depression are now identified for their significant impact on poor outcome. Patient
satisfaction, largely driven by experience with pain and treatment side effects, is now an important component for
reimbursement within the Affordable Healthcare Act. Multimodal analgesia is now recognized as a standard of care
and is familiar to our surgical colleagues. The most current literature supports opioid reduction techniques and
multimodal analgesia from the preoperative period and through the recovery period. Integration of multimodal
analgesia into our anesthetic plan will promote early utilization both pre- and intra-operative to maximize the
benefits. The emerging information on opioids suggests that these agents will likely play a lesser role in our future
approaches both in our anesthetic management and for acute pain management. The role of the anesthesiologist has
potentially far reaching implications on the long-term welfare of the surgical patient but only if we as a specialty
embrace our role as perioperative physicians.
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opiate-dependent patients with chronic back pain undergoing back surgery. Anesthesiology 2010;113:639-46
39. Angst MS, Clark JD. Ketamine for managing perioperative pain in opioid-dependent patients with chronic
pain: a unique indication? Anesthesiology 2010,113:514-5
40. Domino EF. Taming the ketamine tiger. Anesthesiology 2010;113:678-86
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qualities, and postoperative determinants. Pain 2011;152:566-73
46. Werner MU, Mjobo HN, Nielsen PR, et al. Prediction of postoperative pain: a systemic review of predictive
experimental pain studies. Anesthesiology 2010:112:1494-502
47. Kim JC, Choi YS, Kim KN, et al. Effective dose of peri-operative oral pregabalin as an adjunct to multimodl
analgesic regimen in lumbar spinal fusion surgery. Spine 2011;36:428–33
48. Burke SM, Shorten GD. Perioperative pregabalin improves pain and functional outcomes 3 months after
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49. Gianesello L, Pavoni V, Barboni E, et al. Perioperative prebagalin for postoperative pain control and quality
of life after major spinal surgery. J NeurosurgAnesthesiol 2012;24(2):121-6
50. Trabulsi EJ, Patel J, Viscusi ER, et al. Preemptive multimodal pain regimen reduces opioid analgesia for
patients undergoing robotic-assisted laparoscopic radical prostatectomy. J Urology 2010;76(5):122-4
51. Balaban F, Yagar S, Ozgok A, et al. A randomized, placebo-controlled study of pregabalin for postoperative
pain intensity after laparoscopic cholecystectomy. J Clin Anesth 2012;24:175-8
52. Bornemann-Cimenti H, Lederer AJ, Wejbora M, et al. Preoperative prebagalin administration significantly
reduces postoperative opioid consumption and mechanical hyperalgesia after transperitoneal nephrectomy. Br
J Anaesth 2012;108:845-9
53. Grigoras A, Lee P, Sattar F. Perioperative intravenous lidocaine decreases the incidence of persistent pain
after breast surgery. Clin J Pain 2012;28(7):567-72
54. Hudetz JA, Iqbal Z, Gandhi SD, et al: Ketamine attenuates post-operative cognitive dysfunction after cardiac
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surgery. Anesthesiology 2014;121:492-500
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opioid consumption, and quality of life after complex spine surgery. Anesthesiology 2013:119(4):932-40
57. Schwenk ES, Goldberg SF, Patel RD, et al: Adverse drug effects and preoperative medication factors related
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The Centralization and Persistence of Postoperative Pain

David J. Clark, M.D./Ph.D. Palo Alto/California
Introduction
At this point the magnitude of the problem is becoming clear. Chronic pain affects nearly 25% of the US population,
and the prevalence is 50% or greater within certain populations such as military veterans. The costs in terms of
direct medical care and lost productivity total in the hundreds of billions of dollars per year [1]. An undefined but
likely large percentage of this unfortunate group developed chronic pain after some form of trauma. Traumatic
causes of chronic pain can be divided further according to their initial causes although the mechanisms supporting
chronic pain have significant overlap as will be discussed in the course of the presentation. On-the-job injuries,
motor vehicle accidents, sports-related injuries and surgery are all well-recognized causes of chronic pain. In each of
these cases pain continues well past the time at which tissue healing would be expected to be complete. Why then
does the pain problem persist and even spread to involve mood, cognition and other functions? The so-called
centralization of pain whereby changes within the CNS support an ongoing pain state provides an important part of
the answer to this vexing question.
Epidemiology of pain after surgery, costs
Chronic post-surgical pain (CPSP) is a common after surgery, and is in fact a common etiology of chronic pain in
the general population. Although we may not have absolute consensus on the definition of CPSP, many reviews
suggest that between 5 and 85% of patients experience pain that persists months after surgery. Most surgical
procedures have some identifiable rate of CPSP with some, especially those in which nerve damage is common,
having especially high rates. Limb amputation, thoracotomy, breast surgery and herniorrhaphy are amongst those
procedures with the highest rates of CPSP. Cross-sectional analyses have suggested that more than 20% of patients
with chronic pain could identify surgery as a causal factor [2]. Chronic pain such as chronic neuropathic pain from
traumatic and surgical causes is immensely expensive. Recently the direct and indirect annualized costs for caring
for these patients were estimated to be approximately $12, 000 and $30,000 respectively [3].
Is it just pain?
Chronic pain including but not limited to CPSP evolves to encompass problems separate from those related to
nociceptive signaling and the experience of pain itself. Abundant evidence from psychophysical evaluations and
imaging studies has demonstrated adverse effects of chronic pain on mood and cognition. To some extent these
changes have been traced to multi-functional areas of the brain. Thus “centralization” of pain is a set of maladaptive
changes with multiple dimensions. The suggestion has been made that the centralization of pain be defined as,
“pain-induced changes in brain circuits resulting in altered/pathological behaviors” in order to capture the multi-
faceted nature of centralization [4]. Nociceptive drive may initiate these changes, but it is not clear that ongoing high
levels of nociceptive input are required to maintain the maladaptations. Thus once established, therapies limited to
peripheral targets may no longer be effective.
Imaging studies have shown that noxious input not only activates areas of the brain commonly associated with
sensory function, e.g. the thalamus and somatosensory cortex, but also regions involved in emotions, e.g. the
cingulate cortex and insula, pain modulation, e.g. the anterior cingulate cortex (ACC) and cognition, e.g. the ACC
and prefrontal cortex. Similarly, imaging studies have shown a detrimental effect on hippocampal volume in patients
with chronic back and limb pain [5]. Together the data indicate that brain-level activation of centers and circuits
with pain, cognitive and emotional functions may explain the association of chronic pain with changes in executive
function, memory, depression and anxiety.
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Pain resolves at rates specific to individual patients
The rate of resolution of pain after surgery is highly specific to the individual. A high level of variability in recovery
rates is seen in major surgeries, e.g. joint replacement and minor procedures, e.g. carpal tunnel release, alike. For
almost no form of trauma, operation or procedure does the fraction of patients with no pain drop to zero. Thus we
might be best served in our efforts to understand persistent postoperative pain to examine processes governing the
rate of resolution of pain in addition to identifying the very persistent changes that might explain chronic
postoperative pain.
Within this framework we can identify processes that are clearly near-term and transient such as wound area
processes. Factors relevant to the fist moments to days after surgery include the release of algogens, production of
inflammatory mediators and infiltration of immune cells. Intermediate processes supporting pain may involve the
production of trophic molecules both supporting healing and pain sensitization and nerve regrowth into damaged
tissues. Physical forces applied to healing tissue while simple movements like breathing or more forceful ones as
involved in physical rehabilitation result in disruption and remodeling of the healing tissue. As the sometimes
months long healing process nears completion, however, we are forced to look at more central changes to explain
ongoing pain.
The need to separate persistent pain in the setting of adequate healing from ongoing pathology
Critical to the care of patients after injury who report ongoing pain is to rule out persistent or recurrent pathology. It
is worth careful consideration in addressing any patient with delayed resolution of pain or certainly when evaluating
worsening pain to consider the possibility that a complication arising from the surgery or trauma exists. Infection is
a clear example of a secondary process that can affect superficial or deep tissues and enhance pain levels. Infection
may not be obvious such as when a deep abscess or osteomyelitis is present. Appropriate physical examination,
laboratory studies and imaging may be required. Additional causes of pain reflecting a tissue-level problem rather
than a fundamental alteration in nociceptive signaling include fracture from intramedullary component placement,
physical compression of nerves from misplaced staples or sutures, and adhesions in joints or soft tissue arising from
immobilization. As each of these etiologies of pain has a distinct treatment approach, they need to be considered
without delay.
Risk factors
Many risk factors for the development of CPSP have been identified with varying degrees of certainly, and attempts
have been made to construct predictive tools [6, 7]. This area of investigation is being pursued actively as the
identification of specific risk factors may shed light on mechanisms of CPSP, provide the means to construct risk
stratification tools and suggest avenues for the prevention and treatment of this condition. The factors currently most
strongly associated with CPSP are listed below. Additional contributors including genetic factors, immune system
responsiveness and the efficacy of endogenous pain control systems are undergoing evaluation as well.
Perioperative pain – The existence of either preoperative or high levels of acute postoperative pain are relatively
well-reproduced risk factors for chronic postoperative pain. Very recent evidence connects chronic wide-spread pain
with CPSP via pathways involving the brain itself.
Psychological characteristics – Several psychological constructs have been associated with CPSP. Amongst the best
studied and validated are depression, anxiety and catastrophizing.
Opioids – Patients consuming opioids preoperatively have substantially higher rates of acute and chronic
postoperative pain. This association is not limited to a single type of surgery, but most studies have been performed
in orthopedic and spinal surgery populations in which the proportion of patients taking opioids is relatively high.
Demographics – Demographic characteristics are very easily assessed, but widely reproduced associations have not
been established. At least some evidence exists, however, for a protective effect of age and perhaps male sex on
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chronic pain after certain surgeries. A special set of considerations may apply to pregnant females as chronic pain
after cesarean section has been noted to be particularly low.
Genetics and epigenetics – Less well studied perioperatively than for other chronic pain conditions, but strongly felt
to impact acute and chronic pain.
Surgical technique – Performing surgeries in ways that speed recovery in general if not CPSP specifically has been a
focus for the surgical community for some time. To this end, laparoscopic and nerve-protecting surgeries have been
developed, and there is some evidence that for procedures such as herniorrhaphy, newer techniques might offer
better pain outcomes. Longer surgeries may lead to higher rates of CPSP as well.
The Centralization of Pain – Spinal: Secondary hyperalgesia, wind-up, synaptic efficiency, glia
The dorsal horn of the spinal cord is perhaps the best studied area of the CNS related to pain processing and
analgesic mechanisms. A large body of information suggests that this area of the spinal cord is critical to central
sensitization after noxious stimulation and injuries of many types [8]. Sensitization of the dorsal horn and
enhancement of nociceptive signal transmission has been observed in association with peripheral nerve damage,
inflammation, incision, tumor growth and other events. In association with spinally-mediated central sensitization
we often observe secondary hyperalgesia, enhanced temporal summation and, of course, increased pain. Under some
circumstances these changes are reversible, but sensitization outlasts the period of high intensity noxious stimulation
and can be maintained by low levels of c-fiber input. These observations are in fitting with the idea that spinal
sensitization might support persistent pain.
Key events driving central sensitization at the spinal level include 1) the enhancement of synaptic efficiency akin to
the process of long-term potentiation (LTP) well-studied in the field of memory research. This enhancement derives
from augmented neurotransmitter release from afferent neurons and increased excitability of second order neurons,
2) the activation of glial cells including astrocytes and microglia leading to the production of cytokines,
neurotrophins and other mediators supporting the excitability of nociceptive neurons, and 3) the ability of formerly
non-noxious input from low-threshold mechanoreceptors to activate nociceptive circuits thus providing a
neurophysiological basis for allodynia. Understanding these processes also provides a basis for the hypothesis that
the use of neural blockade, spinal anesthesia and NMDA receptor blockers might reduce spinal cord sensitization
and speed the resolution of pain after injury.
The Centralization of Pain – Brainstem: Conditioned pain modulation, descending inhibition and facilitation
Nociceptive signal transmission and ultimately the experience of pain are regulated by many mechanisms including
descending modulation. Descending modulation can be inhibitory or stimulatory. These systems are capable of
modulating acute and chronic pain, although it is chronic forms of pain that clinically seem to have the strongest
evidence for involvement of descending control. The principal modulatory systems include the noradrenergic system
involving the locus coeruleus (LC) and the serotonergic system involving the rostral ventromedial medulla (RVM)
[9]. The periaqueductal gray (PAG) is the primary control center for descending inhibition, and is a major site for
the analgesic actions of endogenous and exogenous opioids. At the level of the spinal cord, norepinephrine controls
nociceptive signal transmission through alpha-2 adrenergic receptors while serotonin acts through the 5-HT3
receptor and others to control the flow of nociceptive information. More recently the dopaminergic system has been
implicated in regulating pain via descending inhibition targeting D1, D2 and D5 receptors [10].
Acute postoperative pain is poorly correlated with preoperatively assessed conditioned pain modulation (CPM) [11,
12]. More persistent forms of pain after injury may be more strongly regulated by these centers, however. For
example, thoracotomy and abdominal surgery patients with more efficient CPM responses measured preoperatively
were less likely to develop persistent postoperative pain. Simple measures of nociceptive thresholds were not
predictive in the same way. Laboratory studies reflect and extend these observations. For example, Peters et al.
demonstrated that the rate of resolution of allodynia after nerve injury depended on descending noradrenergic input
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to the spinal cord. Intriguingly, preoperative conditioned pain modulation (CPM) correlated with the timecourse of
postoperative resolution of mechanical hypersensitivity after spinal nerve ligation [13]. Persistent opioid
administration is linked both to reduced net inhibitory control and enhanced levels of pain-related behaviors after
incision and other forms of injury. Imaging studies have begun to suggest that descending inhibition is disrupted in
various chronic pain states as well. These and other observations suggest that we may be able to predict delayed pain
resolution preoperatively by measuring CPM, and that treatments enhancing descending regulatory circuits might be
effective in controlling postoperative pain.
The Centralization of Pain – Cortical/Subcortical structures
The intense afferent barrage that accompanies surgical incision and manipulation is not limited to the activation of
spinal cord circuits alone. While sensory structures in the brain such as the thalamus and somatosensory cortex are
activated by noxious input, so are areas such as the cingulate cortex (emotion) and prefrontal cortex (cognition).
While brain imaging studies specific to chronic postoperative pain are limited in number, many relevant
investigations involving neuropathic, musculoskeletal and visceral pain have been completed shedding light on brain
changes underlying the acute to chronic transition. These alterations in the brains of patients with chronic pain can
be divided into changes in activation state, structure, connectivity and cortical organization [14]. Briefly, some of
those changes are:
Activation: In patients with chronic pain, the anterior cingulate and prefrontal cortices, areas involved in the
affective component of pain, are differentially regulated.
Structure: Reductions in grey matter have been noted in several imaging studies in involve changes in the anterior
cingulate, thalamus, insula and hippocampus.
Connectivity: This parameter reflects the communications between different regions of the brain. One of the more
reproducible patterns of change is in the so-called default mode network. This network reflects the coordination of
activity between brain centers when a person is not focused on a task.
Cortical organization: Changes in cortical representation and reorganization are especially common after amputation
and spinal cord injury, but can occur in other chronic pain syndromes. The degree of reorganization has been
correlated with post-injury pain. Likewise, normalization of cortical representation is associated with reduced pain.
Unknown is when and to what degree these changes are reversible and which of the changes explain the various
symptoms of pain centralization. Evidence from others investigating brain mechanisms for chronic pain suggest
therapies like cognitive behavioral therapy (CBT) [15], ketamine infusion [16], and antidepressants [17] may reverse
the pain-related brain changes and associated pain, cognitive and emotional symptoms. CBT has been shown to
reduce hyperalgesia in controlled experimental settings as well [18]. When and how specific imaging parameters can
be used as biomarkers of specific types of persistent pain remains undefined.
The vulnerable brain
Recognizing the important role for the brain in supporting chronic pain, the concept of individuals having a
“vulnerable brain” has emerged. This vulnerability is supported first by induced changes or “priming” of brain areas
by stressful environmental conditions and diseases (especially psychological ones). The second component is the
intrinsic vulnerability of the brain. Recent prospective work suggests that preexisting factors related to corticolimbic
neuroanatomical structure are highly associated with the probability of developing chronic low back pain after an
acute episode [19]. Similar studies could be performed in surgical patients aided by the very predictable time and
date of injury and ability to study patients preoperatively with the hypothesis that these same corticolimbic
neuroanatomical features will predict chronic postoperative pain.
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Strategies to prevent chronic pain – Medications
Attempts to reduce the rates of chronic postoperative pain build on earlier efforts to provide preemptive or
preventative analgesia in earlier postoperative time frames. There are various rationales for these efforts including,
1) because high levels of perioperative pain are predictive of persistent postoperative pain, measures that
aggressively reduce perioperative pain may reduce chronic postoperative pain, and 2) specific medications may
target receptors, structures or systems that support chronic pain.
The best studied medications for reducing chronic postoperative pain are gabapentinoid drugs and ketamine
(reviewed recently in [20]). Gabapentin and pregabalin bind to the alpha-2-delta subunit of certain calcium ion
channels. The overall effect is to reduce the activity of the associated neurons thus reducing some forms of pain,
especially neuropathic pain. Many studies are available studying the effects of these drugs on early-term
postoperative pain. Those results are somewhat mixed with effects possibly specific to particular types of surgery.
Likewise, several trials are available examining longer term pain outcomes using perioperative gabapentin and
pregabalin. Systematic review of those data did not provide a clear conclusion as to long-term efficacy. Our
knowledge base in this area suffers from lack of consistent dose and duration of treatment using the gabapentinoid
drugs.
Ketamine is a drug with multiple targets including the NMDA receptor. This receptor is key in establishing LTP, a
process intimately involved with memory and persistent pain after injury. Many studies using ketamine are
available, most of which involve protocols with a loading dose followed by infusions terminating at wound closure,
PACU discharge or after some time on the postoperative ward. The drug is generally very well tolerated at low
doses, and few neuropsychiatric side effects were seen when infusion rates were low. A recent Cochrane Database
review suggested that these protocols were in fact effective in reducing chronic postoperative pain. This drug may
have special value in the perioperative pain treatment of patients receiving opioids for pain [21].
Strategies to prevent chronic pain – Neural blockade
Strategies involving neural blockade leverage the concept that preventing or reducing the barrage of afferent input
might prevent neuroplastic changes in the spinal cord and brain linked to chronic postoperative pain. Techniques
included in this group are epidural anesthesia, paravertebral blocks and other more peripheral blocks with or without
catheter administration of local anesthetic. One recent Cochrane review found beneficial effects of epidural and
paravertebral blocks in thoracotomy and breast surgery patients for 6-12 months [22]. Other studies have shown
benefit for regional techniques in terms of reducing persistent pain for various periods for laparotomy, cardiac
surgery and others although sample sizes for all these analyses remain fairly small. The duration and density of the
blocks necessary to achieve prevention of chronic pain have not been defined and remain important research
priorities.
Strategies to prevent chronic pain – Rehabilitative
Complementing pharmacological and interventional strategies for pain management are ones based on behavioral
and rehabilitative approaches. “Prehabilitation” is being discussed more often these days as an approach to
optimizing physical condition prior to surgery to promote optimal outcomes. While some evidence suggests
prehabilitation can reduce acute postoperative pain, little information related to the effects of prehabilitation on
long-term pain is available. Recently a hybrid cognitive-behavioral-physical therapy (CBPT) postoperative program
was used to optimize the outcome of high risk patients after spine surgery [23]. Both pain and disability were
improved in the active program vs. an education only group when treatment was initiated 6 weeks postoperatively.
Studies like this demonstrate that even postoperatively it may be possible to target therapies on groups of patients
with higher than normal likelihoods of poor pain-related outcomes.
Conclusions
Chronic postoperative pain is remarkably common although it has received very little attention until recently.
Beyond pain, these patients tend to experience higher rates of depression, anxiety and cognitive changes. There are
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likely many etiologies for this type of pain, but pain due to intraoperative nerve injury is one clear cause. Among the
changes occurring within the nervous system that support chronic postoperative pain, spinal cord sensitization and
neuroplastic changes in the brain are strongly linked to ongoing pain as is deficient descending inhibition. The
prevention and treatment of this type of pain are at early stages. The perioperative use of ketamine and
gabapentinoid drugs has some support as does the use of regional anesthesia. Amongst the most important
unanswered questions for the prevention of centralization and chronification of pain after surgery are, 1) How do we
identify those at greatest risk?, 2) How do we help the patient understand this possible complication of surgery?, and
3) What are the best strategies for preventing and treating chronic postoperative pain?
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3. Parsons, B., et al., Economic and humanistic burden of post-trauma and post-surgical neuropathic pain
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D1/D5-mediated mechanism. J Neurosci, 2015. 35(16): p. 6307-17.
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endogenous pain inhibition and more postoperative hyperalgesia: a pilot study. J Pain Palliat Care Pharmacother,
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12. Yarnitsky, D., et al., Prediction of chronic post-operative pain: pre-operative DNIC testing identifies
patients at risk. Pain, 2008. 138(1): p. 22-8.
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resolution of postoperative pain in the rat. Anesthesiology, 2015. 122(4): p. 895-907.
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Anaesthesiol, 2011. 24(5): p. 515-23.
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with chronic pain. J Pain, 2013. 14(12): p. 1573-84.
16. Becerra, L., et al., CNS Measures of Pain Responses Pre- and Post-Anesthetic Ketamine in a Patient with
Complex Regional Pain Syndrome. Pain Med, 2015. 16(12): p. 2368-85.
17. Lopez-Sola, M., et al., Effects of duloxetine treatment on brain response to painful stimulation in major
depressive disorder. Neuropsychopharmacology, 2010. 35(11): p. 2305-17.
18. Salomons, T.V., et al., A brief cognitive-behavioural intervention for pain reduces secondary hyperalgesia.
Pain, 2014. 155(8): p. 1446-52.
19. Vachon-Presseau, E., et al., Corticolimbic anatomical characteristics predetermine risk for chronic pain.
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21. Loftus, R.W., et al., Intraoperative ketamine reduces perioperative opiate consumption in opiate-dependent
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Neurologic Complications of Neuraxial Anesthesia in Obstetrics
David J. Wlody Brooklyn, NY
The increasing use of neuraxial anesthesia in obstetrics has unquestionably led to decreases in maternal morbidity and
mortality associated with general anesthesia. However, this has been accompanied by a subsequent increase in the number
of complications of regional anesthesia. While some of these complications may be mild and self-limited, others may lead
to permanent neurologic injury or even death. In this presentation, the risk factors and underlying pathophysiology of the
neurologic complications of regional anesthesia in the parturient will be described, with the dual goals of permitting the
quantitation of the risk of neurologic injury in patients receiving neuraxial anesthesia, as well as describing techniques
designed to decrease the risk of those complications. The obstetric nerve palsies will be described, with the goal of
enabling the practitioner to distinguish those deficits from those due to regional anesthesia. Finally, a review of diagnostic
studies for evaluating neurologic deficits will enable the anesthesiologist to differentiate lesions requiring urgent
intervention from those in which intervention is not indicated, and to help determine their prognosis.
Incidence-Studies in the obstetric population have demonstrated a consistently low risk of significant neurologic injury
after neuraxial anesthesia. In a prospective study, 487 French anesthesiologists reported two peripheral neuropathies and no
serious sequelae in 5640 obstetric spinal anesthetics. In almost 30,000 epidural anesthetics, there were no neurologic
sequelae. (1) A retrospective postal survey and national registry search of complications of obstetric neuraxial anesthesia
in Sweden from 1990-1999 demonstrated that the risk of serious complications was 1:25,000 for both spinal and epidural
anesthesia. (2) The third National Audit of the Royal College of Anaesthetists estimated that the incidence of permanent
neurologic injury caused by obstetric neuraxial anesthesia ranged from 0.3 to 1.2 per 100,000 anesthetics. (3)
Infectious complications-overview-Infection after neuraxial anesthesia is much more common in elderly,

immunocompromised patients than in the obstetric population. Nevertheless, the ASA Closed Claims Project revealed that
46% of all obstetric anesthesia claims filed from 1980-1999 involved infectious complications. (4) It is clear that common
anesthetic practices and lapses in operator technique can have a significant impact on the development of these
complications.
Infectious complications-Risk factors and prevention-In a 2008 review of neurological infection after neuraxial
anesthesia, Reynolds illustrated the difficulty of identifying risk factors for infection in the obstetric population. The
incidence of meningitis after spinal anesthesia was 1:39,000, and that of epidural abscess after epidural anesthesia was 1:
303,000. It was impossible to identify risk factors for infection due to the small number of cases. (5) Duration of
catheterization, multiple insertion attempts, hyperhidrosis, and use of an occlusive dressing have been proposed as risk
factors for epidural abscess. (6) Diabetes has been shown to be a significant risk factor for infection in patients undergoing
continuous regional anesthesia with an indwelling catheter; with lumbar epidural anesthesia, the odds ratio for infection in
diabetic patients was 2.09. (7) Any condition or medication predisposing to immunosuppression increases the risk of
infection; in the Swedish study described above, 9/13 patients developing epidural abscess had such a condition. (2)
Chorioamnionitis has not been shown to be a risk for neuraxial infection. (8,9)
Hand hygiene is an integral part of infection control in the health care setting. Appropriate hand washing with an
antimicrobial soap containing alcohol will decrease the bacterial inoculum should a glove be punctured during the
procedure. Rings and wristwatches should be removed prior to hand washing.
Appropriate skin preparation is essential to the prevention of neuraxial infection. Numerous studies have shown the
superiority of chlorhexidine-alcohol to povidone-iodine in reducing growth of staphylococcus aureus, and in the
prevention of central line associated infections. (10-12) Chlorhexidine is not inactivated in the presence of blood, and its
penetration of the skin gives it a prolonged duration of action, effectively killing bacteria within hair follicles and
sebaceous glands. While the package insert for chlorhexidine-alcohol states that it is not to be used prior to lumbar
puncture (13), both the ASA (14) and ASRA (15) have recommended the routine use of chlorhexidine-alcohol solutions
prior to neuraxial anesthesia. Following the manufacturer’s instructions to allow the solution to dry for two to three
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minutes after application can further minimize any risk of toxicity of chlorhexidine. Use of chlorhexidine impregnated
dressings may reduce bacterial colonization of epidural catheters. (16)
Wearing a facemask results in a marked reduction in the bacterial contamination of a surface in close proximity to the
upper airway. ASA and ASRA recommend the routine use of a face mask during neuraxial anesthesia, and this is also a
requirement of the Centers for Disease Control (CDC). (17) Two separate outbreaks of meningitis in five obstetric patients
receiving neuraxial anesthesia have been described by the CDC. (18) Three women in New York who received CSEA
from the same anesthesiologist were found to have the identical strain of streptococcus salivarius, a common
nasopharyngeal organism. While the anesthesiologist reported wearing a mask during the procedures, the hospital allowed
unmasked visitors to freely enter labor rooms during epidural placement. In Ohio, two women received spinal anesthesia
from the same anesthesiologist, who routinely performed neuraxial procedures without a mask; one of these women died.
The causative organism in both cases was a strain of s. salivarius that was genetically identical to an organism cultured
from the anesthesiologist’s nasopharynx. The need for the operator to wear a mask during neuraxial procedures
cannot be overemphasized. Requiring any other personnel in the labor room during the neuraxial procedure to wear a
mask, including family members, should be considered as well.
The integrity of the epidural infusion system must be maintained at all times; this is of particular importance in patients
receiving postoperative analgesia on the postpartum ward, where the level of surveillance for breaks in sterility may not be
as great as in a labor and delivery unit. Disconnections and reconnections should be minimized, and catheter removal
should be seriously considered in the setting of an unwitnessed disconnection. Per recommendations of the United States
Pharmacopeia, multi-drug infusions such as the opioid-local anesthetic mixtures typically used for labor analgesia should
be prepared by a pharmacist under a laminar flow hood.
ASA suggests consideration of the use of in-line bacterial filters in the setting of long-term epidural catheterization,
although the ability of these filter to prevent catheter tip colonization and neuraxial infection is unproven. (19-22)
Clinical aspects of infectious complications-The two major infectious complications of neuraxial anesthesia are
meningitis and epidural abscess. While there may be some overlap in their clinical presentations, they differ significantly
in their incidence, risk factors, microbial etiology, pathophysiology, and treatment.
Meningitis-The frequent local clustering of cases of meningitis after neuraxial anesthesia, which suggests a unique
causation, (e.g. a practitioner using poor sterile technique), makes the task of estimating the incidence of infection a
difficult one. Older surveys and case reports may reflect obsolete practices; multi-institutional surveys may reflect a wide
range of clinical practices that influence the risk for infection. A review of large-scale nationwide surveys may be useful in
determining the risk of meningitis. In the Swedish survey referenced above, the incidence of meningitis after spinal block
was 1:53,000; a cluster of four cases in a single institution clearly skewed the results. (2). The Third National Audit
Project of the Royal College of Anesthetists identified three cases of meningitis in over 700,000 neuraxial anesthetics,
performed for obstetric, surgical, and chronic pain indications. (3)
Much of our knowledge of the clinical presentation of anesthesia-related meningitis is based on case reports. Reynolds
identified 38 cases of meningitis in obstetric patients that received neuraxial anesthesia; in all but two cases the anesthetic
was determined to be the causative factor. (5) The clinical presentation is not unlike that of meningitis seen in other
settings, with headache, nausea, fever, meningeal signs, and alterations in consciousness appearing hours to several days
after anesthesia. Notably, meningitis has been confused with PDPH, one of these patients having received two epidural
blood patches.
A practitioner confronted by a patient developing meningitis after neuraxial anesthesia would understandably consider the
possibility that this was unrelated to the anesthetic procedure, and that the development of meningitis was coincidental.
However, the organisms responsible for community-acquired meningitis are only rarely found in obstetric patients. Most
often, meningitis seen in the setting of neuraxial anesthesia is caused by alpha-hemolytic streptococcus, typically s.
salivarius, which as noted previously is a common nasopharyngeal organism; it is also found amongst vaginal flora.
Epidural abscess-The great majority of epidural abscesses are unrelated to neuraxial anesthesia, usually a result of
hematogenous seeding of the epidural space from a distant infection. The most common risk factors are diabetes, trauma,
intravenous drug abuse, and alcoholism, i.e. conditions that predispose to immune suppression. (23) Bacterial colonization
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of epidural catheters is surprisingly common; in one study, 5.8% of patients receiving postoperative epidural analgesia for
an average of five days had positive catheter tip cultures, 75% of which were staphylococcus epidermidis. None of these
patients developed an epidural abscess. (24) It is difficult to describe a true incidence of epidural abscess in the obstetric
population, but it appears to be extremely low; in Moen’s study, one case of epidural abscess was identified in 200,000
obstetric epidurals (2), and in the Royal College survey, one case of epidural abscess was identified in 161,000 obstetric
patients receiving epidurals. (3)
Kindler described the clinical presentation of 42 cases of epidural abscess after epidural anesthesia in both surgical and
obstetric patients. (25) Back pain and fever were seen in over 90% of patients. Leukocytosis was common, and the
erythrocyte sedimentation rate and C-reactive protein levels were elevated in all patients in whom those studies were
obtained. 36% of patients had a risk factor, including diabetes, corticosteroid therapy, and alcoholism. Staphylococcus
species were the causative organism in 70% of cases. Only 45% of patients had a full recovery; early surgical
decompression after symptom onset was a key factor in improved outcome. A consistent pattern in case reports of epidural
abscess is the poor outcome seen when definitive therapy is delayed. In the setting of fever, back pain, and
leukocytosis, prompt imaging of the spine is essential, especially when lower extremity neurologic changes are
present. MRI is the imaging technique of choice. (26)
Epidural hematoma-The presentation of epidural hematoma is similar to that of epidural abscess, that is, back pain,
sometimes severe, eventually followed by weakness and sensory alterations in the lower extremities. Unlike epidural
abscess, however, which may take days to manifest itself, the signs and symptoms of epidural hematoma may develop
within 12 hours of the initial neuraxial procedure. Thus, epidural hematoma may develop during the time period in which
motor and sensory blockade might be expected to persist after an uncomplicated neuraxial anesthetic. Recurrence of
motor block after partial recovery, or prolonged block in patients at risk for an epidural hematoma, should serve as
a red flag to initiate diagnostic studies to rule out possible spinal cord compression. As with epidural abscess, optimal
results of surgical intervention are seen when decompression occurs soon after the development of neurologic changes.
Epidural hematoma is exceedingly rare in the obstetric population. In the Royal College survey, there was not a single
incidence of epidural hematoma in 295,000 neuraxial anesthetics. (3) A retrospective study of 505,000 obstetric epidurals
administered over a five-year period revealed one epidural hematoma. (27) In Moen’s study, two patients with HELLP
syndrome developed an epidural hematoma, one after subarachnoid block and one after epidural block, yielding an
incidence of epidural hematoma after spinal and epidural anesthesia of 1:50,000 and 1:200,000, respectively. (2) In
contrast, the incidence of epidural hematoma in female patients undergoing knee arthroplasty was 1:3,600. This difference
is likely due to combination of the greater use of anticoagulants in this population, as well as a less compliant epidural
space secondary to anatomic changes in the osteoporotic spine. (28)
A common antecedent to most cases of epidural hematoma after neuraxial anesthesia is a disturbance of coagulation.
These disturbances can be divided into two groups: coagulopathy due to underlying disease, and iatrogenic disturbances
due to therapeutic anticoagulation.
Coagulopathy due to underlying disease-The most common disturbance of coagulation seen in pregnancy is
thrombocytopenia, which can be due to gestational thrombocytopenia, pre-eclampsia, or immune disorders. (29) For many
years a platelet count of 100x109/l was considered the minimum acceptable level for performing neuraxial anesthesia.
There is a large and growing experience in the administration of neuraxial anesthesia to obstetric patients with platelet
counts lower than the traditional threshold. Rasmus described 14 parturients who received epidural anesthesia with platelet
counts between 15-99 x109/l with no complications. (30) In a retrospective review of 119 deliveries in patients with
idiopathic thrombocytopenic purpura (ITP), 19 epidurals were placed with platelet counts of 76-100 x109/l, 6 with platelet
counts of 50-75 x109/l, and one with a platelet count of less than 50 x109/l; no complications were noted. (31)
Nevertheless, patients with thrombocytopenia should be approached with care. Pre-eclampsia is a dynamic process; the
pre-eclamptic parturient with a rapidly dropping platelet count is likely at higher risk than a patient with chronic, stable ITP
(with concomitant enhanced platelet function), and an identical platelet count. Clinical markers of coagulopathy such as
widespread petechiae suggest that regional anesthesia is contraindicated. Identification of additional risk factors, such as
an abnormality of platelet function, another disorder affecting coagulation (e.g. hepatic dysfunction), or concomitant
antiplatelet therapy should influence the decision to perform a regional anesthetic. Corticosteroid therapy should be
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considered in patients with ITP, as there is usually a significant response to such treatment. (32) There may also be a
benefit to corticosteroid therapy in the patient with HELLP syndrome. (33, 34) Ultimately, the decision to perform a
regional anesthetic in a patient with significant thrombocytopenia will be based on an assessment of the risks and benefits
in that patient; a morbidly obese patient with an anticipated difficult airway and a platelet count of 60 x10 9/l about to
undergo an urgent cesarean section may be a better candidate for regional anesthesia than a fully-dilated grand multipara
with a platelet count of 80 x109/l requesting epidural labor analgesia.
Coagulopathy due to drug therapy-Pregnant patients can receive a variety of medications that affect coagulation. ASRA
has published guidelines for the use of regional anesthesia in patients receiving antithrombotic or thrombolytic therapy.
(35) At the time of writing of this outline, the 4th edition of these guidelines is in preparation; an interim update is
available at www.asra.com/advisory-guidelines. The updated 4th edition will be presented as part of the Refresher Course
Lecture.
Non-steroidal anti-inflammatory agents (NSAIDs) are widely used during pregnancy, for example in the form of low-
dose aspirin administered for the prevention of severe pre-eclampsia in patients thought to be at high risk of developing the
disease. ASRA has concluded that the use of NSAIDs added no significant risk for the development of spinal hematoma. It
was recommended, however, that regional anesthesia be avoided if the patient was receiving any additional medications
affecting coagulation.
Subcutaneous unfractionated heparin is commonly administered to pregnant patients at high risk of developing DVT.
ASRA has concluded that a q12 hour 5000 unit dosing regimen is not a contraindication to regional anesthesia. The
guidelines, however, noted the increasingly widespread utilization of q8 hour 5000 unit dosing, and indicated that the risk
of hematoma in this setting could not be estimated; they recommended enhanced monitoring for the development of
neurologic deficits in patients on this treatment regimen.
Low molecular weight heparin (LMWH) is increasingly used for thromboprophylaxis during pregnancy. Unfortunately,
the anticoagulant effect of LMWH is not easily quantitated, making it difficult to determine when its effect has waned to a
level at which neuraxial anesthesia is safe; further, reversal of anticoagulant effect with protamine is unpredictable. ASRA
recommends that in patients receiving preoperative, once daily thromboprophylaxis with LMWH, needle placement should
be delayed at least 10-12 hours after a dose; that regional anesthesia be delayed at least 24 hours after LMWH
administration in patients receiving twice daily, therapeutic dosing; that an epidural catheter can be maintained during
once-daily postoperative dosing, but that catheter removal should not occur any sooner than 12 hours after a dose; and that
epidural catheters be removed at least two hours prior to the first postoperative dose when twice daily dosing is planned. It
should be noted that this last recommendation has been superseded by an FDA advisory stating that 4 hours should
elapse between catheter removal and the administration of the next dose. (36)
ASRA recommends that patients chronically anticoagulated with warfarin should not undergo neuraxial anesthesia until
the INR is within normal range; this can be expected to take 4-5 days after warfarin therapy is discontinued. If warfarin
therapy is restarted after delivery, epidural catheters should be removed when the INR is still less than 1.5, and enhanced
surveillance of neurologic function should occur for at least 24 hours after catheter removal.
Chemical injury-A wide variety of drugs have been accidentally injected into the epidural space, including neuromuscular
blockers, thiopental, and potassium chloride. Permanent neurologic injury is rare, but has been reported, as in the case of a
parturient who received an accidental injection of chlorhexidine through an epidural catheter and was rendered paraplegic.
(37). The causes for such errors are numerous, including “look-alike” drug ampoules, incorrect labeling of syringes, and
the accidental attachment of intravenous lines to epidural catheters. Drug administration errors can never be eliminated, but
appropriate vigilance should minimize their occurrence. Ampoules should be identified by their labeling, not by color;
syringes should be carefully labeled, preferably with pre-printed labels; hospital pharmacies should be notified if a
potentially neurotoxic agent has labeling similar to commonly used local anesthetics.
In vitro and animal studies demonstrate that commonly used local anesthetics, when administered in sufficiently high
doses, can be neurotoxic. Toxicity may be enhanced in the setting of pre-existing neurologic injury, such as diabetic
neuropathy. (38) Of the agents that are currently in common use in obstetric anesthesia, hyperbaric lidocaine for
subarachnoid block and 2-chloroprocaine have been most commonly associated with such injury.
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Hyperbaric lidocaine: Cauda equina syndrome and transient neurologic symptoms-In 1991 six cases of persistent
neurologic injury consistent with the cauda equina syndrome were reported in patients that received continuous spinal
anesthesia. (39, 40) In five of these cases hyperbaric lidocaine was administered via a 28 gauge spinal microcatheter. An
initial failure to achieve adequate levels of surgical anesthesia led to the administration of additional doses of local
anesthetic, one patient receiving lidocaine 285 mg over 30 minutes. Both publications suggested that the limited extent of
sensory blockade reflected a limited spread of local anesthetic within the subarachnoid space. It was hypothesized that the
limited spread of lidocaine within the subarachnoid space produced localized drug concentrations that exceeded the level
necessary to produce neurotoxicity. In 1992, spinal catheters were withdrawn from the United States market by the FDA.
However, cauda equina syndrome has been reported after a single-injection spinal anesthetic; should limited spread of
sensory block occur after attempted subarachnoid anesthesia, the risk of producing toxic drug levels in the CSF should be
considered before repeating the block.
In 1993 Schneider et al. described 4 patients who reported transient neurologic dysfunction after spinal anesthesia with 5%
lidocaine. (41) The patients received 50-75 mg of lidocaine, and all underwent procedures performed in the lithotomy
position. They all developed postoperative pain in the buttocks radiating to the thighs and calves. There were no motor or
sensory disturbances, and symptoms resolved within several days. Transient neurologic symptoms (TNS), as this
phenomenon has been named, is significantly more common with lidocaine than bupivacaine. (42) In patients receiving
lidocaine, procedures performed in the lithotomy position were more likely to be complicated by TNS than procedures
performed in other positions, and outpatients receiving lidocaine were more likely to develop TNS than inpatients. Age,
gender, and lidocaine dose and concentration did not influence risk. (42) Pregnancy, however, appears to have a protective
effect; the incidence of TNS after postpartum tubal ligation performed under lidocaine spinal anesthesia was 3% (43), and
the incidence after Cesarean section with lidocaine spinal anesthesia was 0%. (44) TNS appears to be unrelated to cauda
equine syndrome.
The range of neurologic complications that can follow the use of intrathecal lidocaine has called the continuing usefulness
of that agent into question. Unfortunately, there are few alternative agents that have a similar clinical profile and less
toxicity. Procaine and mepivacaine have a similarly short duration, and are less toxic, but are not readily available. There
is significant experience with the use of spinal chloroprocaine for brief surgical procedures. Removal of glucose from the
commercial preparation of lidocaine does not appear to offer any advantages with respect to neurotoxicity. (45) Drasner
made several recommendations regarding the use of lidocaine, including limiting the total dose of drug to 60 mg and
avoiding the use of epinephrine to prolong the duration of the block. (46)
Local anesthetic neurotoxicity: 2-chloroprocaine-2-chloroprocaine (2-CP) is unique due to its rapid onset, short
duration, and minimal systemic toxicity due to rapid hydrolysis by plasma cholinesterase. However, 2-CP can produce
significant, prolonged neurotoxicity when large volumes are accidentally injected into the subarachnoid space. An in vitro
study by Gissen et al. suggested that the cause of neural injury was a combination of low pH and the antioxidant sodium
metabisulfite, and not 2-CP itself.  (47) Subsequent to this study, 2-CP was reformulated in a less acidic solution without
sodium metabisulfite. Since that reformulation occurred, there have been no case reports of 2-CP neurotoxicity, although
other factors, such as the more widespread use of fractionated dosing, may be the reason for this. However, more recent
work suggests that the role of bisulfite in producing neuronal injury has been overstated, and that 2-CP in fact does have
intrinsic neurotoxicity (48), although this conclusion has been challenged. (49) To further complicate the issue, there is a
growing experience in the use of preservative-free 2-CP as a spinal anesthetic without any evidence of neurotoxicity. (50)
Nevertheless, we cannot assume that the accidental intrathecal injection of large volumes and large doses of drugs
meant for epidural anesthesia will be as benign as small doses of 2-CP intended for subarachnoid use. It thus
remains critically important that confirmation of placement of the catheter within the epidural space be demonstrated
before large doses of local anesthetics are injected, and that fractionated dosing be utilized unless there is an extremely
compelling argument to do otherwise.
Direct injury to the spinal cord- The ASA Closed Claims Project reported two cases in which spinal cord injury was felt
to be related to direct injury to the spinal cord. (4) Reynolds reported 6 patients who underwent spinal or combined-spinal
epidural anesthesia for cesarean section or vaginal delivery and were found to have deficits consistent with injury to the
conus medullaris. (51) In all cases, injection was reported to be no higher than the L2-3 interspace. Pain during needle
insertion occurred in all cases, but free flow of CSF was noted, and spinal anesthesia was adequate in most cases. All
patients were found to have residual unilateral sensory loss involving several dermatomes, most had residual foot drop, and
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three had urinary symptoms. MRI usually revealed a syrinx on the side corresponding to both the initial paresthesia, as
well as to the residual deficit. It was concluded that these injuries were in large part due to puncture at a level higher than
the actual termination of the spinal cord.
Reynolds noted a number of possible predisposing factors that may have led to these injuries. (51) An MRI study has
shown that the conus medullaris extends below the L1-2 interspace in over 21% of subjects (52), rendering lumbar
puncture at that interspace potentially hazardous. Tuffier’s line, connecting the posterior superior iliac spines, and which is
widely thought to indicate the L4-5 interspace, may indicate a level ranging up to one interspace higher. (53) Finally,
anesthesiologists are remarkably unsuccessful at identifying lumbar interspaces by external landmarks alone. One
radiologic study demonstrated that the level of lumbar puncture was misidentified in 59% of cases. (54) Given the
uncertainties in determining the site of injection, the L 3-4 interspace should remain the level of choice for spinal and
combined spinal-epidural anesthesia. It has been suggested that if an interspace is identified at the palpated Tuffier’s line,
needle insertion should take place one interspace below; if a spinous process is palpated, entry should occur two
interspaces below. (55) Pain upon injection of medication into the subarachnoid space should prompt cessation of injection
and repositioning of the needle.
Obstetric nerve palsies-Any postpartum neurologic deficit in a patient that received a neuraxial anesthetic is likely to be
attributed to that anesthetic. In reality, neurologic deficit after childbirth is most often secondary to compression or
stretching of a peripheral nerve as a consequence of pregnancy or delivery itself. Wong et al. asked over 6200 women on
the first postpartum day if they had leg weakness or numbness. Positive responses led to formal evaluation by a physiatrist.
0.92% of women were diagnosed with a peripheral nerve injury consistent with obstetric nerve palsy. (56) Familiarity with
and the ability to diagnose the common obstetric nerve palsies is important, both for medicolegal reasons, as well as to be
able to provide the patient with a more accurate prognosis for recovery. A summary of the most common obstetric nerve
palsies follows.
Lumbosacral trunk injury is caused by compression of this structure, consisting of fibers derived from the L4 and L5
roots, by the fetal head at the sacral ala. Patients present with weakness of ankle dorsiflexion and eversion (foot drop), and
decreased sensation along the lateral aspect of the lower leg and the dorsal surface of the foot. Risk factors include
prolonged labor, a large fetus, and a flattened, wide posterior pelvis with pronounced sacroiliac joints. (57) In Wong’s
study the incidence was less than 0.05%.
Common peroneal nerve palsy results secondary to compression of the nerve against the fibular head, usually due to
poorly positioned stirrups when patients are placed in the lithotomy position. It may be difficult to distinguish this lesion
from lumbosacral trunk injury, but normal ankle inversion and normal ankle jerk suggest this more peripheral lesion. (58)
Meralgia paresthetica is the most common of the obstetric nerve palsies, seen in 0.4% of patients studied by Wong. This
injury is secondary to compression of the lateral femoral cutaneous nerve under the inguinal ligament. There is a unique
pattern of decreased sensation in the superior portion of the anterolateral thigh; motor impairment is absent. The major risk
factor is prolonged hyperflexion of the hips, as in the lithotomy position or when a McRoberts maneuver is performed.
Femoral nerve palsy was the second most common injury seen in Wong’s study. It can result from compression of the
nerve within the pelvis by the fetal head, or by retraction during pelvic surgery. It can also be compressed more
peripherally under the inguinal ligament due to exaggerated hip flexion, but this mechanism is less common. This lesion
presents with quadriceps weakness, perhaps most noticeably during stair climbing. There is commonly a loss of sensation
on the medial calf and foot.
Pre-existing disease and the risk of neurologic injury-Pregnant patients may have any of a variety of pre-existing
disorders that may increase the risk of neurologic complications after neuraxial anesthesia. Hebl et al. reviewed the
experience with 937 patients at the Mayo Clinic who carried a diagnosis of spinal stenosis or lumbar disk disease and
received neuraxial anesthesia over a 15-year period. (59) New neurologic deficits or worsening of pre-existing deficits
were seen in 1.1% of patients, higher than the rate reported in previous studies of the general population. The presence of
preoperative compressive radiculopathy or multiple neurologic diagnoses were risk factors for postoperative injury;
previous spinal surgery, however, did not increase risk. It is not clear that this study is directly applicable to the obstetric
population, however, as 8 of 10 patients with new or worsened deficits were greater than 70 years of age.
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Parturients with multiple sclerosis clearly have an increased rate of relapse in the first three postpartum months (60, 61),
and there are some who would argue that a neuraxial anesthetic will be implicated should such a relapse occur, and should
therefore be avoided. However, Bader et al. demonstrated that the rate of relapse was no higher in women who received
epidural analgesia than in those who received local anesthetic infiltration alone. (62) Hebl et al. showed a similar lack of
effect of neuraxial anesthesia in patients with multiple sclerosis, as well as a wide variety of other chronic neurologic
diseases. (63)
Reynolds points out that patients with diabetes may be vulnerable to neurologic complications of neuraxial anesthesia on
several grounds: they are susceptible to infection, they may have vascular disease, and they may have a peripheral
neuropathy. (64) Hebl et al. retrospectively investigated 567 patients with pre-existing peripheral sensorimotor neuropathy
or diabetic polyneuropathy who underwent neuraxial anesthesia. Two patients suffered a new or worsening deficit in the
postoperative period. (65) While low, this still represented a higher level of postoperative neurologic deficit than that
reported in the general population.
Vascular abnormalities may predispose the parturient to neurologic injury in the postpartum period. An arteriovenous
malformation of the spinal cord can decrease cord perfusion through a steal effect, rupture and produce an epidural
hematoma, or compress the cord via mass effect. In patients with a so-called “high take-off” of the artery of Adamkiewicz,
perfusion of the lower spinal cord will be dependent upon lumbar branches arising from the iliac arteries. These vessels
can be compressed by the fetal head, resulting in spinal cord ischemia. (64)
Evaluation of neurologic deficit after regional anesthesia-The most important step in evaluating a post-anesthetic
neurologic deficit is to rule out a rapidly expanding mass lesion, such as an epidural hematoma or epidural abscess.
As cannot be overemphasized, the prognosis for recovery decreases dramatically if decompression is delayed. One review
suggests that recovery is most likely if decompression occurs within 12 hours of the onset of symptoms (66). However,
this time frame might be overly optimistic; patients with mild or slowly progressing deficits, which would be expected to
have a better outcome, may be more likely to undergo later intervention. As the authors state, “The question: ‘how soon
should a spinal epidural haematoma be evacuated’ is answered, obviously, ‘as soon as possible’…”. Therefore, urgent
radiologic investigation should not be delayed if there is any suggestion of spinal cord compression.
With a non-progressive deficit, investigation can occur at a more leisurely pace. History and physical examination alone
may be sufficient to make the diagnosis of an obstetric nerve palsy. Coexisting obstetric morbidities should be ruled out;
for example, bowel and bladder disturbances are not uncommon after childbirth. Pubic symphysis separation can lead to
difficult ambulation and subjective complaints of leg weakness. (58) The use of both routine lumbosacral films and more
advanced imaging techniques can be helpful in delineating the anatomic location of an injury. Electromyography (EMG)
can be helpful in defining both the anatomic and temporal location of a lesion, as denervation potentials do not develop
until two weeks after a nerve injury; the presence of such potentials soon after a regional anesthetic suggests that the injury
preceded the anesthetic.
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Developing a Clinical Pathway for the High-Risk Surgery

Patient
Maxime Cannesson Los Angeles/California
I. The Changing Healthcare Landscape and Perioperative Challenges
Over the past decade, attention has been placed on improving quality and safety in the
perioperative setting. In the US, 30 – day inpatient mortality has decreased from 1.68% to 1.32%
in 2006 with a continued improvement in this trend.
In a 1954 review of surgical procedures, 0.64% of patients died directly as a result of anesthesia.
This rate has constantly improved and in 1989, perioperative death directly attributable to
anesthesia was around 0.001% for healthy patients, with modern mortality rates now around 1.4
per 1,000,000 surgeries. Significant improvements in survival occurred in the 1980s, primarily
through the implementation of new practice guidelines, improvements in monitoring technology
and the introduction of new therapies.
In 2008, Weiser et al. estimated the global volume of surgery to be 240 million procedures a
year(1). According to Pearse et al., high-risk surgical procedures represent 12.5% of this volume
and account for 80% of overall patient mortality related to surgery(2). In addition, the incidence
of postoperative complications in high-risk surgery patients is about 35 %(1). These
complications increase LOS in the intensive care unit and in the hospital; increase readmission
rate and cost of surgery, and decrease patient satisfaction. As such, there is an urgent need to
develop and adopt interventions that are directed at improving the outcomes of high-risk surgical
procedures.
Healthcare delivery in the United States is currently plagued by variability in care, excessive
cost, and poor outcomes(3,4). In the perioperative setting, widely variable and fragmented
perioperative care exposes surgical patients to lapses in expected standards of care, increases
potential for mistakes and accidents in the operating room, results in unnecessary and potentially
detrimental tests, needlessly drives up costs, and adversely affects the patient healthcare
experience(5-9). Even for higher volume and thus relatively routine surgical procedures, like
total knee arthroplasty, substantial variations in surgery times, hospital lengths-of-stay (LOS),
discharge dispositions, and in-hospital complication rates exist across institutions(10).
A study analyzing complications and mortality in an older surgical population showed that 68%
of patients undergoing surgery had pre-existing co-morbidities with 20% suffering perioperative
complications and around 5% dying within 1 month after surgery. This seem to indicate that
further training leading to skills in risk reduction, patient optimization and knowledge in
perioperative medicine would reduce the disparity in outcomes. In parallel, an extended role of
the anesthesiologist as ‘the perioperative physician’ has emerged and is gaining momentum
internationally. Utilizing skills developed in clinical management, safety, and efficieny,
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anesthesiologists as perioperative physicians are now delivering clinical leadership to improve

outcomes for high-risk surgical patients from admission to discharge.
II. New Models of Perioperative Care: Enhanced Recovery and The Perioperative
Surgical Home
Recently, the American Society of Anesthesiologists (ASA) indicated that a paradigm of

standardized patient preoperative evaluation and preparation, along with meticulous team-based
and evidence-driven care during and after surgery, has the potential to accomplish Berwick’s
Triple Aim of improving the individual experience of care; improving the health of populations;
and reducing per capita costs of care1. To achieve this goal, the ASA has developed the concept
of the Perioperative Surgical Home (PSH) and has characterized it as “a patient-centered and
physician-led multidisciplinary and team-based system of coordinated care that guides the
patient throughout the entire surgical experience”2. The central tenet of the PSH is to treat the
entire perioperative episode as one continuum of care rather than discrete preoperative,
intraoperative, and postoperative episodes. This single perioperative experience lasts from the
moment the decision is made for the patient to have surgery until 30-days after discharge from
the hospital. Indeed, in parallel to the Triple Aim promoted by Berwick, the aim of the PSH is to
provide better quality and better service within the context of lower costs for our surgical
patients(11,12). While the PSH concept has recently been described and discussed by several
authors(13-15), the actual implementation of this new model of care and its “real life” evaluation
has only been reported in small, observational studies.
The concept of anesthesiologists working as perioperative physicians in a Pre-operative Clinic is

becoming more popular and is considered as a key component of patient optimization, risk
assessment and informed decision making. This approach gives the anesthesiologist an
opportunity to prepare patients’ fitness before surgery by offering advice on smoking cessation,
exercise and weight reduction and by optimizing treatment of chronic conditions such as diabetes
and anemia. This closer working relationship between anesthesiologists, primary care and
patients may lead to improved survival, as well as decreased perioperative morbidity and
duration of hospital stay.
The goal of a well conducted Pre-operative Clinic is to minimize risk for all patients scheduled
for surgery, identify high-risk patients for perioperative complications and death and establish
clear and optimal pathways to allow the allocation of individualized resources to patients’ needs.
It is well identified that patient failure to access the Pre-operative Clinic can lead to higher costs,
ICU utilization and mortality. Improved selection of patients to nurse and/or physician
assessment better allows the targeting of risk assessment and prediction tools to individualize
1 ASA Committee on Future Models of Anesthesia Practice Annual Report to the house of delegates. August 18, 2013.
2 American Society of Anesthesiologists: The perioperative or surgical home. Washington, DC: American Society of
Anesthesiologists; 2011(https://www.asahq.org/~/media/For%20Members/Advocacy/Legislative%20Conference/2011%20-%20One-
pager%20Perioperative%20Surgical%20Home%20Pilot%20Project.pdf).
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risk. Close relationship with secondary care groups such as endocrinology and cardiology can
prevent protracted hospital stays. Today, it should be standard of care that all patients presenting
for surgery should undergo adequate preoperative evaluation in one form or another.
III. The way toward protocolized perioperative care
The concept of Enhanced Recovery After Surgery (ERAS) is based on a proactive patient
management pathway, which adopts multi-modal ‘care bundles’ and in which the patient has an
active role. ERAS is recognized as an example of high quality care improvement. The evidence
base for ERAS is clear and continues to strengthen; the evolving philosophy is now extending
beyond surgical ERAS and is being readily adopted for a wide range of hospital services. In the
UK, surgical ERAS has been supported by the National Health Service drive to Quality,
Productivity and Prevention in Practice (QIPP), bringing demonstrated quality benefits for
patients and reducing the length of hospital stay with no increase in surgical re-admission rates.
The Perioperative Physician is well placed to readily adopt ERAS culture. By crossing both
functional and organizational boundaries, they are able to influence, orchestrate and monitor
quality care improvements for surgical patients. This begins in the aforementioned Preoperative
Clinica, which facilitates more appropriate use of investigations, and has closer links to primary
care services, allowing optimization of care and effective communication prior to determining a
date for surgery.
The operative care bundle is well understood and in gastrointestinal surgery includes core
elements such as avoidance of bowel preparation and nasogastric tubes, goal directed fluid
therapy, immediate postoperative feeding and early mobilization facilitated by short acting
aaesthetic agents and regional analgesia. The body of evidence supporting ERAS is constantly
changing and is expected to continue to evolve as evidence-based techniques and therapies
emerge. In the UK, ERAS represents a best-practice model of care for colorectal, urological,
gynecological and orthopedic procedures and has been endorsed by professional organisations
including the Royal Colleges of Surgeons and Anaesthetists. ERAS improves the planned care
pathway for patients, reduces both the length of hospital stay and postoperative complications.
The ERAS model defends equity in healthcare provision by broadly treating all patients in the
same way. Recent focus on increased weekend mortality rates and inferred disparities in care
compared to weekday activity have been highlighted and ERAS may be seen as a way of
maintaining optimal care regardless of this parameter.
Due to the benefits of ERAS, many UK health care trusts now receive payment to incentivize the
adoption of best practice. The Commissioning for Quality and Innovation (CQUIN) payment
framework enables health care commissioners to reward excellence by linking a proportion of
providers’ income to the achievement of local quality improvement goals. Since the first year of
the CQUIN framework (2009/10), many CQUIN schemes have been developed and more
recently published national goals for 2011/12 detail enhanced recovery payment schemes. In
London, the enhanced recovery CQUIN payment covers eight elective procedures across the four
specialities mentioned and covers four components, each reflecting best practice in perioperative
care:
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1. Recording of comprehensive information about enhanced recovery patients on the national

database to allow Trusts to better understand ER implementation.
2. To ensure that the majority of patients admitted for colorectal surgery receive goal-directed
fluid therapy, the Trusts qualify for full payment if ≥ 80% of patients undergoing planned
colorectal surgery performed receive goal directed fluid therapy.
3. Targeted day of surgery admission, the Trusts qualify for full payment only if ≥ 80% of
eligible patients were admitted on the day of surgery.
4. Targeted length of stay for patients undergoing the eight specified operations. The target for
each procedure was to equal the national median from the previous year
In the USA, a model of enhanced recovery is also favored with detailed information given to
patients before their surgery and anesthesia to diminish anxiety and enhance postoperative
recovery and hasten hospital discharge. Preoperative psychological intervention including
personal counseling, pamphlets and multimedia information is aimed at decreasing patient
anxiety and improving recovery from surgery.
As ERAS programs evolve, it is expected future trends will focus on improved preoperative
assessment, shared decision making and the ready adoption of novel techniques shown to
provide benefit.
References
1. Weiser TG, Regenbogen SE, Thompson KD, Haynes AB, Lipsitz SR, Berry WR,
Gawande AA. An estimation of the global volume of surgery: a modelling strategy based
on available data. Lancet 2008;372:139-44.
2. Pearse RM, Harrison DA, James P, Watson D, Hinds C, Rhodes A, Grounds RM,
Bennett ED. Identification and characterisation of the high-risk surgical population in the
United Kingdom. Crit Care 2006;10:R81.
3. Berwick DM, Hackbarth AD. Eliminating waste in US health care. JAMA : the journal of
the American Medical Association 2012;307:1513-6.
4. Rogers S. Healthcare spending around the world, country by country. The Guardian,
2012.
5. Thilen SR, Bryson CL, Reid RJ, Wijeysundera DN, Weaver EM, Treggiari MM. Patterns
of preoperative consultation and surgical specialty in an integrated healthcare system.
Anesthesiology 2013;118:1028-37.
6. Thilen SR, Treggiari MM, Lange JM, Lowy E, Weaver EM, Wijeysundera DN.
Preoperative Consultations for Medicare Patients Undergoing Cataract Surgery. JAMA
internal medicine 2013.
7. Encinosa WE, Hellinger FJ. The impact of medical errors on ninety-day costs and
outcomes: an examination of surgical patients. Health services research 2008;43:2067-85.
8. Fry DE, Pine M, Jones BL, Meimban RJ. The impact of ineffective and inefficient care
on the excess costs of elective surgical procedures. Journal of the American College of
Surgeons 2011;212:779-86.
9. McCulloch P, Nagendran M, Campbell WB, Price A, Jani A, Birkmeyer JD, Gray M.
Strategies to reduce variation in the use of surgery. Lancet 2013;382:1130-9.
10. Tomek IM, Sabel AL, Froimson MI, Muschler G, Jevsevar DS, Koenig KM, Lewallen
DG, Naessens JM, Savitz LA, Westrich JL, Weeks WB, Weinstein JN. A collaborative of
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leading health systems finds wide variations in total knee replacement delivery and takes
steps to improve value. Health affairs 2012;31:1329-38.
11. Kain ZN, Vakharia S, Garson L, Engwall S, Schwarzkopf R, Gupta R, Cannesson M. The
Perioperative Surgical Home as a Future Perioperative Practice Model. Anesth Analg
2014;118:1126-30.
12. Vetter TR, Boudreaux AM, Jones KA, Hunter JM, Pittet JF. The Perioperative Surgical
Home: How Anesthesiology Can Achieve and Leverage the Triple Aim in Healthcare.
Anesth Analg 2014;118:1131-6.
13. Vetter TR, Goeddel LA, Boudreaux AM, Hunt TR, Jones KA, Pittet JF. The
Perioperative Surgical Home: how can it make the case so everyone wins? BMC
anesthesiology 2013;13:6.
14. Vetter TR, Ivankova NV, Goeddel LA, McGwin G, Jr., Pittet JF. An Analysis of
Methodologies That Can Be Used to Validate if a Perioperative Surgical Home Improves
the Patient-centeredness, Evidence-based Practice, Quality, Safety, and Value of Patient
Care. Anesthesiology 2013;119:1261-74.
15. Warner MA. The Surgical Home. ASA Newsl 2012;76:30-2.
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Developing a Clinical Pathway for the High-Risk Surgery Patient

Timothy E. Miller, M.B., Ch. B. Durham/North Carolina
Preoperative Optimization and Prehabilitation
Introduction
It is estimated that worldwide more than 230 million major surgical procedures are performed each year. Surgical
interventions are cost-effective and thus this surgical volume is likely to continue to increase. As life expectancy
increases, an increasing proportion of these patients are likely to be high-risk elderly patients with multiple
comorbidities. The optimum perioperative management of such patients requires input from a multidisciplinary team
ideally incorporating a process of shared decision-making.
Despite advances in surgical technology, anesthesia and perioperative care, recent case series have shown that 16-
18% of all patients undergoing surgery have postoperative complications, which presents significant health care and
social burdens.1,2 When considering major abdominal surgery, almost 30% of patients have postoperative
complications, and, even in absence of morbid events, major surgery is associated with a 40% reduction in
functional capacity.3 Long periods of physical inactivity induce loss of muscle mass and deconditioning.
Postoperative fatigue and complications are correlated with preoperative health status, functional capacity, and
muscle strength.
Postoperative complications not only increase short-term costs by prolonging hospital length of hospital stay but
also have long-term implications for mortality.1 Furthermore, they may lead to repeated hospital admissions and
chronic ill health. From the patient perspective this is often associated with a decline in functional capacity and
quality of life. The avoidance of postoperative complications is consequently of great importance. 2
There is mounting evidence that many of the negative immediate effects of surgery such as pain, fatigue, and
weakness, are potentially amenable to intervention. If proper interventions are carried out, these symptoms may be
readily controlled, allowing for a faster recovery and early hospital discharge. However, the effects of surgery are
felt far beyond the immediate convalescent period and patients can feel fatigued for many weeks; fatigue delays
return to usual function, and reduces quality of life. Traditionally, efforts have been made to improve the recovery
process by intervening in the postoperative period. However, the preoperative period may be a more opportune time
to intervene in the factors that contribute to recovery.
The usual current model for pre-anesthesia testing (PAT) exists along the continuum of preparing a patient for
surgery once they are declared “surgical”. It serves an important role, however patients are often seen in the PAT
clinic a few days before surgery and there are therefore significant limitations that must be addressed particularly in
an outcomes accountable health care system.
Ideally a surgical care plan should begin when a patient is first identified to be a candidate for surgery. Optimum
preoperative management requires input from a multidisciplinary team incorporating preoperative evaluation, risk
stratification and shared decision-making. There are two processes that should be an integral part of this evaluation
to potentially improve outcomes:
1. Optimization of modifiable risk factors

2. Prehabilitation – the process of enhancing functional capacity of the individual to enable them to withstand
an incoming stressor
Optimization of modifiable risk factors
Perioperative care must include, beside clinical and pharmacologic preparation of the surgical patient, preoperative
physical, nutritional, and mental optimization.
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Modifiable risk factors include:
 Anemia management
 Nutrition
 Diabetes mellitus management
 Lifestyle modification (smoking and alcohol cessation)
 Management of depression and anxiety
Anemia is common in patients presenting for elective surgery and is associated with increased risk of perioperative
blood transfusion, and consequential morbidity and mortality. In addition to its direct contribution to morbidity,
blood transfusion also burdens the health system financially in terms of both direct (acquisition, inventory,
verification) and indirect (increased length of stay, transfusion related events) costs. When preoperative anemia is
treated, reduced cost of care with improved quality of outcomes has been demonstrated.4
The primary goal of nutrition therapy is to optimize nutrient stores preoperatively and provide adequate nutrition to
compensate for the catabolic response of surgery postoperatively. Optimal nutrition care involves a continuous timeline
from the preoperative through the postoperative period. Greater emphasis on preoperative metabolic preparation and
optimizing health status is most likely to improve outcome through surgery, by reducing infection, total complications, and
hospital length of stay. A nutrition screening should be performed as part of the physician’s preoperative assessment on
any patient for whom major surgery is anticipated and should include the following elements:5
 Serum albumin level (high risk defined as <3.0 g/dL)

 CRP as a surrogate marker for inflammation
 BMI (high risk defined as BMI <18.5 or >40)
 Actual body weight as percentage of ideal body weight (high risk defined as <90%)
 History of weight loss prior to assessment (high risk defined as >5% over 1 month, >7.5% over 3 months, or
>10% over 6 months)
Any patient anticipating major elective surgery, regardless of nutrition status, should receive an immunonutrition formula
containing arginine, fish oil, nucleotides, and antioxidants 500–1000 mL/d for 5–7 days before the scheduled procedure.
For high-risk patients, the same formula should be provided postoperatively as tolerated.
Preoperative smoking cessation has been shown to improve outcomes, but the optimal duration of preoperative abstinence
still remains unclear.6 It is acknowledged that the implementation of such an approach in clinical practice is not always
feasible because of limited hospital resources, lack of organization, and waiting time before the operation. Nevertheless,
perioperative caregivers should take the opportunity to emphasize the importance of smoking cessation and be more
proactive in helping patients to quit smoking. Preoperative alcohol cessation can improve organ dysfunction, but the effect
on postoperative outcomes remains unclear.
Several observational studies point to a strong association between hyperglycemia and poor clinical outcomes,
including prolonged hospital stay, infection, disability after discharge from the hospital, and death. Preoperative
measurement of HBA1c may identify patients at higher risk of postoperative complications and could be used as a
trigger for modification of the perioperative management of such patients. Whether intervention to control glycemic
variability, per se, improves outcomes is not known.7
The physical burden of surgery is closely linked to the emotional one. Increased levels of psychosocial distress seen
in patients undergoing surgery are related to the diagnosis, the treatment (chemotherapy), and the disability. Several
studies have identified that anxiety and depression can adversely affect postoperative outcome.
Whether preoperative interventions to reduce stress preoperative can improve outcomes is largely unknown, as
although there has been great effort in studying the impact of physical exercise on postoperative outcome, little has
been done to address patient and caregiver’s emotional burden of surgery. One recent study showed that
prehabilitation producing preoperative improvements in functional capacity was associated with improvements in
mental health and reduced anxiety.8 Stress management before surgery has also been shown to positively affect
immune function.9
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Prehabilitation
Patients with poor baseline exercise tolerance and physical conditioning are at increased risk for serious
perioperative complications and prolonged disability, and improving functional capacity by increasing physical
activity before surgery may be protective. The process of enhancing functional capacity of the individual to enable
them to withstand an incoming stressor has been termed prehabilitation
Physical fitness can be improved in the time that patients are waiting for scheduled surgery, as modest
improvements in aerobic capacity can be seen in older adults after training only 1 hour per day, 4 times a week, for 4
weeks. Current recommendations include a combination of moderate and vigorous exercise, if deemed appropriate
for the individual.
In general, individuals who have been the least fit and the most sedentary show the most improvements when they
commence an exercise program. Since the ratio of actual physiologic reserve to total physiologic reserve is small,
even small amounts of physical training are remarkable. Patients following simple walking and breathing exercise
guidelines have made marked improvements in walking capacity, as measured by the 6-minute walk test. Older
adults are particular susceptible to bed rest and physical inactivity, because of their already low functional capacity;
therefore this is a patient population who particularly benefit from targeted intervention.
Several small trials have suggested that prehabilitation is effective for improving physical fitness and is safe,
although evidence for improved clinical outcomes related to preoperative exercise is limited. Prehabilitation
programs that are multimodal (including physical, nutritional, and psychological components) seem to be more
effective than programs that are unimodal, and have been shown to reduce postoperative complications after major
abdominal surgery.10 For these reasons, a multimodal prehabilitation program, with the aim of improving physical
capacity before cancer surgery, seems to be an efficient and cost-effective method to ameliorate patient outcome
after surgery.10 However, more studies are needed before delaying surgery in patients undergoing oncologic surgery
is warranted.
Summary
Preoperative optimization and prehabilitation are emerging concepts that derive from the realization that
perioperative care must include clinical and pharmacologic preparation of the surgical patient, as well as
preoperative physical, nutritional, and mental optimization. As the population ages and mortality decreases,
additional concerns in patients who undergo surgery and other treatment include quality of life, community
reintegration, and physical and mental performance after surgery and cancer treatment. The integrated role
optimization and prehabilitation deserves to receive more attention by clinicians.
References
1. Khuri S, Henderson W, DePalma R, et al. Determinants of long-term survival after major surgery and the
adverse effect of postoperative complications. Ann Surg 2005; 242:326–41
2. Ghaferi AA, Birkmeyer JD, Dimick JB. Variation in hospital mortality associated with inpatient surgery. N
Engl J Med 2009; 361:1368–75.
3. Schilling PL, Dimick JB, Birkmeyer JD. Prioritizing quality improvement in general surgery. J Am Coll
Surg 2008; 207:698–704
4. Leahy MF, Roberts H, Mukhtar SA, et al. A pragmatic approach to embedding patient blood management
in a tertiary hospital. Transfusion. 2014; 54:1133-45.
5. McClave SA, Kozar R, Martindale RG, et al. Summary points and consensus recommendation from the
North American Surgical Nutrition Summit. JPEN J Parenter Enteral Nutr 2013;37(suppl):99S–105S
6. Mills E, Eyawo O, Lockhart I, et al. Smoking cessation reduces postoperative complications: a systematic
review and meta-analysis. Am J Med 2011;124(2): 144–54.e8.
7. Moghissi ES, Korytkowski MT, DiNardo M, et al. American Association of Clinical Endocrinologists and
American Diabetes Association consensus statement on inpatient glycemic control. Diabetes Care 2009;
32:1119–31.
8. Mayo NE, Feldman L, Scott S, et al. Impact of preoperative change in physical function on postoperative
recovery: arguments supporting prehabilitation for colorectal surgery. Surgery 2011; 150:504.
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9. Cohen L, Parker PA, Vence L, et al. Presurgical stress management improves postoperative immune
function in men with prostate cancer undergoing radical prostatectomy. Psychosom Med 2011; 73:18–25.
10. Carli F, Scheede-Bergdahl C.Prehabilitation to enhance perioperative care. Anesthesiology Clin 33 (2015)
17–33
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Developing a Clinical Pathway for the High-Risk Surgery Patient

Monty G Mythen London / United Kingdom
Identification of the High-Risk Surgery Patients and Their Outcome
Body-Times New Roman 10 point-Headers Times New Roman 10 point Bold

8 Pages Maximum
Introduction:
Identification of higher risk patients presents the opportunity for more effective risk mitigation
and management and facilitates comparative research and audit. To state the obvious, high risk
patients have a worse short term and long-term outcome than lower risk patients and thus may
consume far more resources. This risk is compounded by the risk of the surgical procedure. They
are also less likely to gain improvements in quality of life from complex surgery (1-3). Factors
that are associated with greater risk of surgery include, age, co-mordities, functional capacity,
nutritional status, mental wellbeing, lifestyle factors (e.g. smoking and alcohol) and socio-
economic class (1,2, 5-10) .
Stratifying Risk
Risk stratification techniques alongside routine history and physical examination include risk
prediction models, assessment of functional capacity and novel biochemical markers (1,2).
Risk prediction models

Systematic review of the discrimination and calibration of risk stratification tools available for
use in major non-cardiac surgery by Moonesinghe et al. identified 34 options. Only 2 scores, the
Portsmouth-Physiology and Operative Severity Score for the enUmeration of Mortality
(PPOSSUM) and the Surgical Risk Scale were demonstrated to be reasonably accurate tools that
had been validated in multiple studies. Both have limitations and the commonly used ASA score
ranked quite highly and may be the most practical as it is easy to remember and deploy.
Validation of the accuracy of ASA scoring outside of clinical trials has been disappointing (11).
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The scoring systems have many overlapping components. The greater availability of hospital and
system wide outcome data and multi-component risk factor analysis has enabled the
development of web or app-based on line tools that are calibrated from the patient’s population
(e.g. see www.sortsurgery.com).
Functional capacity
Pre-operative functional capacity is an effective predictor of post-operative outcome. A basic

assessment can be made using structured questionnaires and scores that assign METS (metabolic
equivalents) to daily activities (e.g. dressing oneself vs 2 sets of tennis). Functional capacity can
be measured more objectively using supervised timed walk tests. The most accurate is
cardiopulmonary exercise testing (CPET) (12). Commonly done using a cycle ergometer and
breath-by-breath gas analysis to more precisely determine aerobic capacity, lung function. Both
anaerobic threshold (AT) and peak oxygen uptake (𝑉̇ 𝑂2 𝑝𝑒𝑎𝑘) (objective measures of exercise
capacity) have consistently been associated with post-operative morbidity, mortality and
functional recovery after surgery. The CPET test also gives a measure of lung function and a
stress ecg. Exercise capacity can be used to estimate individualized perioperative risk early in the
pre-operative pathway and can be improved with physical training (12-14).
Physical and behavioral factors
Modifiable physical and behavioral factors that carry increase include: nutritional status (5,6),
hemoglobin (7), lack of physical activity (8), smoking and excessive alcohol intake (9). Physical
factors interact with psychological state that can affect outcome indirectly by affecting patients’
motivation to engage in pre-operative optimization and directly by impacting on recovery (4).
Biomarkers
There have been advances in the measurement and interpretation biochemical markers for risk
prediction (17) such as brain natriuretic peptide (BNP), Cardiac Troponins (17,18), C-reactive
protein (CRP) and high-sensitivity CRP (19) alongside traditional measures such as serum
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Creatinine (20). More experimental measures include lymphocyte counts and reactivity (21).
None have yet clearly demonstrated superiority over more commonly available options that
include modifiable factors.
Summary
Individualized perioperative risk stratification early in the pre-operative pathway informs

collaborative decision making, and truly informed consent (22). Many of the factors associated
with higher risk are modifiable. Risk stratification also informs the choice and application of
clinical pathways including resource allocation such as O.R. scheduling, deployment of staff,
monitoring, therapies and post-operative care environment. Although intuitively sensible, the
clinical effectiveness of risk-adapted care is not yet fully determined.
References
1. Moonesinghe SR, Mythen MG, Grocott MP. High-risk surgery: epidemiology and
outcomes. Anesth Analg. 2011 Apr;112(4):891-901.
2. Moonesinghe SR, Mythen MG, Grocott MP. Patient-related risk factors for postoperative
adverse events. Curr Opin Crit Care. 2009 Aug;15(4):320-7.
3. Moonesinghe SR, Harris S, Mythen MG, Rowan KM, Haddad FS, Emberton M, Grocott
MP. Survival after postoperative morbidity: a longitudinal observational cohort study. Br
J Anaesth. 2014 Dec;113(6):977-84.
4. Salmon P, Hall GM. A theory of postoperative fatigue: an interaction of biological,
psychological, and social processes. Pharmacology, biochemistry, and behavior.
1997;56(4):623-8.
5. Evans DC, Martindale RG, Kiraly LN, Jones CM. Nutrition optimization prior to surgery.
Nutr Clin Pract. 2014;29(1):10-21.
6. Gillis C, Carli F. Promoting Perioperative Metabolic and Nutritional Care.
Anesthesiology. 2015;123(6):1455-72.
7. Spahn DR. Anemia and patient blood management in hip and knee surgery: a systematic
review of the literature. Anesthesiology. 2010;113(2):482-95.
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8. Dronkers JJ, Chorus AM, van Meeteren NL, Hopman-Rock M. The association of pre-
operative physical fitness and physical activity with outcome after scheduled major
abdominal surgery. Anaesthesia. 2013;68(1):67-73.
9. Oppedal K, Moller AM, Pedersen B, Tonnesen H. Preoperative alcohol cessation prior to
elective surgery. Cochrane Database Syst Rev. 2012;7:CD008343.
10. Lee IM, Shiroma EJ, Lobelo F, Puska P, Blair SN, Katzmarzyk PT. Effect of physical
inactivity on major non-communicable diseases worldwide: an analysis of burden of
disease and life expectancy. Lancet. 2012;380(9838):219-29.
11. Moonesinghe SR, Mythen MG, Das P, Rowan KM, Grocott MP. Risk stratification tools
for predicting morbidity and mortality in adult patients undergoing major surgery:
qualitative systematic review. Anesthesiology. 2013 Oct;119(4):959-81.
12. Levett DZ, Grocott MP. Cardiopulmonary exercise testing for risk prediction in major
abdominal surgery. Anesthesiol Clin. 2015;33(1):1-16.
13. Lee IM, Shiroma EJ, Lobelo F, Puska P, Blair SN, Katzmarzyk PT. Effect of physical
inactivity on major non-communicable diseases worldwide: an analysis of burden of
disease and life expectancy. Lancet. 2012;380(9838):219-29.
14. Levett DZ, Edwards M, Grocott M, Mythen M. Preparing the patient for surgery to
improve outcomes. Best Pract Res Clin Anaesthesiol. 2016 Jun;30(2):145-57
15. Evans DC, Martindale RG, Kiraly LN, Jones CM. Nutrition optimization prior to surgery.
Nutr Clin Pract. 2014;29(1):10-21.
16. Gillis C, Carli F. Promoting Perioperative Metabolic and Nutritional Care.
Anesthesiology. 2015;123(6):1455-72.
17. Ackland GL, Mythen MG. Novel biomarkers in critical care: utility or futility? Crit Care.
2007;11(6):175.
18. Biccard BM, Naidoo P, de Vasconcellos K. What is the best pre-operative risk
stratification tool for major adverse cardiac events following elective vascular surgery? A
prospective observational cohort study evaluating pre-operative myocardial ischaemia
monitoring and biomarker analysis. Anaesthesia. 2012 Apr;67(4):389-95.
19. Ackland GL, Scollay JM, Parks RW, de Beaux I, Mythen MG. Pre-operative high
sensitivity C-reactive protein and postoperative outcome in patients undergoing elective
orthopaedic surgery. Anaesthesia. 2007 Sep;62(9):888-94.
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20. Ackland GL, Moran N, Cone S, Grocott MP, Mythen MG. Chronic kidney disease and
postoperative morbidity after elective orthopedic surgery. Anesth Analg. 2011
Jun;112(6):1375-81.
21. Edwards MR, Sultan P, del Arroyo AG, Whittle J, Karmali SN, Moonesinghe SR,
Haddad FS, Mythen MG, Singer M, Ackland GL. Metabolic dysfunction in lymphocytes
promotes postoperative morbidity. Clin Sci (Lond). 2015 Sep;129(5):423-37.
22. Glance LG, Osler TM, Neuman MD. Redesigning surgical decision making for high-risk
patients. N Engl J Med. 2014;370(15):1379-81.
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Measuring Physician Performance: Metrics, Money, and Myths

Robert S. Lagasse, M.D. New Haven, CT
Jonathan P. Wanderer, M.D. Nashville, TN
Elena N. Bukanova, M.D. New Haven, CT
Performance measurement is required by accrediting agencies (e.g., TJC, DNV), credentialing agencies (MOCA),
specialty society data registries (ACS NSQIP, AQI NACOR), Quality Improvement Organizations, insurance
carriers, consumer advocacy groups, and regulatory agencies (CMS). Most notable among these is the Centers for
Medicare and Medicaid Services (CMS) who introduced the Medicare Access and CHIP Reauthorization Act of
2015 (MACRA). MACRA replaces the Sustainable Growth Rate (SGR) formula and moves us away from a volume
based fee for service payment system. Payment will move to a value based payment system via Alternative Payment
Models (APMs) and Merit-Based Incentive Payment Systems (MIPS). Payment under these new programs will start
in 2019. Both programs focus on clinical quality and the contribution to cost savings. 1
Physician anesthesiologists, certified anesthesiologist assistants and nurse anesthetists who opt to participate in
MIPS will receive payments that will be subject to positive or negative performance adjustments. MIPS will
measure these eligible professionals (EPs) in four performance categories to derive a “MIPS score” (0 to 100),
which can significantly change an EP’s Medicare payment in each payment year. The performance categories are:
Physician Quality Reporting System (PQRS) measured quality (up to 30 points), Value-Based Modifier (VBM)
measured resource use (30 points), Meaningful Use (MU) (25 points) and a new category named “Clinical Practice
Improvement Activities” (CPIA) (15 points). The MIPS score’s maximum negative impact on payment increases
from -4 percent for the 2019 payment year to -9 percent for the 2022 and subsequent payment years. Additionally,
MIPS scores will be publically reported on Physician Compare with ranges and benchmarks.2
Eligible professionals receiving a substantial portion of their revenue from APMs will receive an annual lump-sum
payment equal to 5% of their Medicare physician fees from 2019 to 2024. Eligible APMs, such as a Medicare
Shared Savings Program Accountable Care Organizations or The Health Care Quality Demonstration Programs,
must require that participants use certified EHR technology, pay based on quality measures comparable to those
used in the MIPS quality category, and place material financial risk on EPs. 2
PQRS is a quality-reporting program that uses negative payment adjustments to promote reporting of quality
information by individual EPs and group practices. Reporters may choose from the following reporting mechanisms
to submit their quality data: 1) Reporting electronically using an electronic health record (EHR), 2) Qualified
Registry, 3) Qualified Clinical Data Registry (QCDR), 4) PQRS group practice via GPRO Web Interface, 5) CMS-
Certified Survey Vendor, 6) Claims. In 2015, measures are classified according to the 6 National Quality Strategy
(NQS) domains. PQRS reporting mechanisms typically require an EP or PQRS group practice to report 9 or more
measures covering at least 3 NQS domains, and crosscutting measures for EPs with billable face-to-face encounters
for satisfactory reporting or participation to avoid the 2017 negative payment adjustment. Anesthesia providers
reporting less than 9 measures will be subjected to the Measures Applicability Verification (MAV) process to
determine whether an eligible professional should have reported quality data codes for additional measures. For
example, the EP needs to make sure that if a measure belongs to a PQRS cluster, all other measures inside that
cluster are also reported. For example, before being retired in 2016, #193 Perioperative Temperature Management
was part of the Anesthesia Care Cluster, along with #76 Prevention of Catheter-related Bloodstream Infections that
remains currently active. Other measures relevant to anesthesia providers might include #44 Continued
Administration of Beta Blockers to Cardiac Surgery Patients, #130 Documentation of Current Medications in the
Medical Record, #226 Tobacco Use – Screening and Cessation Intervention, #342 Pain Under Control Within 48
Hours, #358 Preoperative Risk Assessment Using a Validated Tool. Of note, measures #130 and #226 are
considered crosscutting measures because they apply to face-to-face encounters with nearly all types of
eligible professionals. There may be others that apply to anesthesiology, or subsepecialty practice. Also, several
other measures have been retired in 2015. Measure #30 Timing of Antibiotic Prophylaxis-Administering Physician,
has been deleted from the list of measures available for either claims-based or registry reporting. Measures #148-
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151, the Back Pain Measures Group, and #142 Assessment for Use of Anti-Inflammatory or Analgesic Over-the-
Counter (OTC) Medications, were also removed from the list. 3,4,5
Anesthesia professionals who meet their PQRS requirements through a QCDR must report a minimum of nine
measures, covering at least three NQS domains, on at least 50 percent of all the EP’s patients, not just Medicare
beneficiaries. Of these measures, 2 out of 9 must be outcomes measures. QCDRs differ from a qualified registry in
that they are not limited to current measures within PQRS. In 2015, a QCDR may include a maximum of 30 “non-
PQRS” measures. Currently, there are 5 QCDRs for anesthesia providers, including 1) ABG Anesthesia Data Group,
LLC, 2) Anesthesia Quality Institute (AQI) National Anesthesia Clinical Outcomes Registry
(NACOR), 3) Anesthesiology Performance Improvement and Reporting Exchange (ASPIRE) Multicenter
Perioperative Outcomes Group (MPOG), 4) Mednax Inc. Quantum Clinical Navigation System, and 5) TeamHealth
Patient Safety Organization (THPSO). There is considerable variability across these five QCDRs with regard to the
non-PQRS measures.6 Each measure should be evaluated based on the criteria discussed at the end of this handout
when choosing applicable measures.
The Value-Based Modifier (VM) adjusts payments to EPs based on the quality and cost of care they furnish to
patients enrolled in the traditional Medicare Fee-for-Service program. EPs practicing high-quality, low-cost care will
earn a positive VM, while those practicing lower quality at higher cost may have a negative VM. The quality
composite score summarizes performance for as many as six equally weighted quality domains: (1) Clinical
Process/Effectiveness, (2) Patient and Family Engagement, (3) Population/Public Health, (4) Patient Safety, (5) Care
Coordination, and (6) Efficient Use of Healthcare Resources. Each domain score is based on performance scores for
PQRS measures reported, using its associated domain. The cost composite score summarizes resource use across
two equally weighted cost domains: Per Capita Costs for All Attributed Beneficiaries and Per Capita Costs for
Beneficiaries with Specific Conditions (e.g., diabetes, CAD, COPD, and heart failure).7
Under the CMS Electronic Health Record (EHR) Incentive Program, EPs receive payment adjustments to encourage
the adoption, implementation and ‘meaningful use’ of certified EHR technology. Under the program there are two
categories of professionals: “Hospital-based eligible professionals” and “Eligible Professionals” (EPs). Hospital-
based eligible professionals are exempt from current penalties. To be deemed a hospital-based eligible professional,
one needs to provide 90 percent or more of their covered services in a hospital inpatient or emergency room setting.
The majority of anesthesiologists are deemed EPs, but MU requirements make it difficult for anesthesiologists to
achieve success. They focus on primary care functions and are less relevant to anesthesia information management
systems, perioperative workflow, and the nature of the patient-anesthesiologist relationship. In 2012, CMS created
a hardship exemption to allow anesthesiologists to avoid payment penalties in 2015. Anesthesiologists may attempt
to become meaningful users if they want qualify for an incentive payment, rather than just avoid the penalty. 8
With regard to required Clinical Practice Improvement Activities (CPIA), as defined by MACRA, there are six
qualifying categories: 1) Expanded practice access, 2) Population management, 3) Care coordination, 4) Beneficiary
engagement, 5) Patient safety, and 6) Practice assessment. CMS has solicited stakeholders to identify practice
improvement activities in these categories. The ASA recommended participating in one or more of the clinical data
registries within the Anesthesia Quality Institute, such as the National Anesthesia Clinical Outcomes Registry
(NACOR), Anesthesia Incident Reporting System (AIRS) and MOCA® Practice Performance Assessment and
Improvement (PPAI) as a CPIA.9
One of the advantages of participating in a QCDR is that a menu of anesthesia-specific quality measures is available,
rather than the fixed set of potentially applicable PQRS measurements as described above. Each QCDR is able to
define their own set of measurements, each of which consists of a measure definition that includes criteria for
qualifying in both the numerator and denominator. The number and type of measures differs significantly between
QCDRs. In 2016, for instance, MPOG’s ASPIRE QCDR measures include multiple anesthesia-specific process
measurements, such as train-of-four documentation after last dose of non-depolarizing neuromuscular blockade,
neostigmine administration prior to extubation, glucose recheck or insulin administration for hyperglycemia,
dextrose administration for hypoglycemia, avoiding high tidal volume ventilation, and avoiding gaps in
intraoperative blood pressure documentation.10 In contrast, AQI NACOR’s 2016 QCDR measurements did not
include any measures similar in content to those, but did include procedure-specific measurements for CABG,
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carotid artery stenting, endovascular aneurysm repair and total knee replacement,11 which were not represented in
MPOG’s ASPIRE.
In order to participate in a QR or QCDR, anesthesia practices must determine both the technical and administrative
requirements for data submission. Submitting data to the AQI NACOR, for instance, requires execution of a
participation contract and providing a month of representative production data within 60 days of signing. 12
Additional subsequent deadlines need to be met on a rolling basis. Prior to being able to submit data, practices need
to identify a quality champion to serve as a point of contact for the AQI, and that individual should choose the
specific, reportable measures that are applicable for all practice EPs. After choosing measures, infrastructure must
be assessed to determine if it is feasible to provide these data within the scope of existing software and services.
Some billing and practice management vendors have been designated as QCDR-ready, meaning that they are able to
submit data on behalf of practices. These vendors include abeo and Anesthesia Business Consultants, as well as
vendors that offer assistance with specific measures, such as SurveyVitals for assessment of AQI NACOR’s
composite patient experience measure.13 Regardless of the vendor’s status on the AQI’s QCDR-ready list, each
practice must verify end-to-end connectivity from data entry to receipt by AQI. Dashboards are available through
AQI that allow practices to perform quality assurance on data submitted on their behalf.
If it is not feasible for a practice to submit data to AQI NACOR through a vendor, or if another QR or QCDR is
being utilized that is similarly not supported by practice infrastructure, it may be necessary for a practice or
institution to develop their own capability to transmit data to AQI. This functionality typically requires a periodic
extract of electronic health record data to be created, which must be formatted appropriately to facilitate electronic
transmission. AQI provides a comprehensive user guide14 that specifies the minimum data fields necessary for data
submission as well as specifications for formatting. Practices that are implementing such an extraction and upload
process should anticipate that significant technical resources are required. For MPOG participants, an extract is
available that is AQI specific and should obviate the need for a custom, local solution. Although this extract does not
currently meet the AQI file format, this functionality is anticipated to be ready in the near term (Sachin Kheterpal,
personal communication to JPW, May 27th, 2016).
In addition to technical and administrative hurdles that need to be cleared, another consideration when implementing
a quality metric reporting program is local practice culture and the likely response to implementing a given metric.
While this may be driven to large degree by leadership, a metric developed in one practice may not translate in a
useful manner to another due to the clinical context. For instance, one of the 2016 MPOG ASPIRE metrics was
aimed at measuring the prevention of uncontrolled pain in the PACU, defined as a pain score of eight or greater on a
numeric rating scale of 0 to 10.10 Pain is a subjective phenomenon, one that is known to be influenced by a variety
of patient factors, such as age, gender, race and pre-existing conditions, as well as procedural factors, such as the use
of less invasive surgical techniques such as laparoscopy. These influences are in addition to what the measure seeks
to assess, which is the degree to which those factors are successfully managed by practices. After implementation at
one of the authors’ (JPW) institutions, the validity of this metric was called into question, giving variability in
attending-specific practice patterns. A comprehensive assessment of this metric at this institution was undertaken,
which revealed that the most influential factor in the assessment of the initial PACU pain score was none of the
existing known factors, but rather the individual nurse who was performing the assessment. 15 The signal attributable
to the individual attending anesthesiologist was not statistically significant. The authors speculated that this nurse
effect was due to variability in how the numeric pain scale assessment was performed. Regardless, at least at this
institution, this particular measurement lacked face validity in its ability to measure the effect of the intended
variable.
Regardless of what measures are ultimately selected by participants, and the extent to which these measures have or
have not been validated at a local level, a key component of a successful quality metric reporting program is
periodic review of the data generated. While significant technical, administrative and cultural challenges may lie at
the outset of such a program, the clinical workflows and supporting technical infrastructure at a practice rarely
remain static. These changes, whether at the forefront of care or in the background, can have significant, negative
impact on apparent clinical performance. For instance, at one of the authors’ (JPW) institutions, automated reporting
was developed that monitored how frequently intraoperative glucose measurements were obtained for patients with
known diabetes and those who received perioperative insulin, as documented by the EHR. Using clinical decision
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support technology, significant attention was devoted to performance on this measurement until adequate
monitoring was achieved. Over a year after implementation, performance was noted to have significantly degraded
without any apparent change. Subsequent investigation revealed that a laboratory system upgrade had impacted the
name of the glucose lab value generated by one of the several point-of-care glucose measurement devices, resulting
in that lab value no longer being identified as a glucose measurement. However, it took significant time and effort to
identify the issue. By contrast, larger scale technical issues, such as gaps for data for a month resulting in no
apparently clinical activity, or conversely, duplicate uploads of data for a month resulting in case volume suddenly
doubling, are easier to detect, compared to insidious, small-scale changes. Nevertheless, periodic monitoring of data
and auditing is essential for such a program to be successful. Successful programs have the ability to significantly
shift local practice, which can impact outcomes at a practice level. These programs, when replicated at scale, have
the potential to have significant impact on clinical practice at a national level.
In 2009, the Executive Office of the President’s Council of Economic Advisers (CEA) provided an overview of the
economic impacts of healthcare in the United States.16 The CEA suggested that, if healthcare costs continued to
grow at historical rates, its share of GDP would reach 34% by 2040. For households with employer-sponsored health
insurance, this implies that a progressively smaller fraction of employee compensation would be in the form of take-
home pay, while a significantly larger fraction would be in the form of health insurance, because health insurance
premiums are growing more rapidly than employee compensation. Between 1996 and 2006, the average annual
premium for family coverage obtained through an employer grew from $6,462 to $11,941. 16 Rising healthcare costs
may also reduce the profitability and competitiveness of many US industries. To put this into perspective, General
Motors spent $5.2 billion on employee health benefits in 2004,17 which was more than their annual expenditure for
steel. Perhaps most compelling, the 2009 CEA report projected that the current trend in Medicare and Medicaid
spending would lead to an unsustainable rise in the federal deficit. This impact is even greater at the state level,
where rising Medicaid costs for low-income populations compete with legislative requirements to balance state
budgets.
Although the United States devotes a far larger share of GDP to healthcare than other developed countries, it does
not achieve better health outcomes.18 According to the Organization for Economic Co-operation and Development
(OECD), the United States spent 16.9% of its GDP on healthcare in 2013. The next highest country was France,
with 11.6%, while many high-income countries spent less than 10%.18 Despite this level of expenditure, life
expectancy in the United States is one of the lowest among developed countries. In 2010, life expectancy for all live
births in the United States was 78.6 years, which was lower than that of 22 other developed countries. In fact, 18
countries had life expectancies of more than 80 years.18 Infant mortality rate in the United States is also substantially
above that of other developed countries. In 2010, there were 6.1 deaths for every 1000 live births in the United
States, which was higher than the rates of 25 other developed countries. In the top-ranked countries, like Finland and
Japan, the infant mortality rate was less than half the rate in the United States, at 2.3 deaths per 1000 live births.19
Many factors other than healthcare costs affect life expectancy and infant mortality rates, but life expectancy has
risen less in the United States than in other countries since 1970, when US healthcare costs were closer to those of
other high-income countries.20 These data strongly suggest that there are inefficiencies in the current US healthcare
system.
In 1999, the Institute of Medicine (IOM), through its Quality of Healthcare in America Project, published a sentinel
report, To Err Is Human: Building a Safer Health System. It reported that 44,000 to 98,000 Americans die each year
as a result of medical errors. Even when using the lower estimate, deaths caused by medical errors exceeded the
number attributable to the eighth leading cause of death in the United States at that time. According to the IOM,
more people died in a given year as a result of medical errors than from motor vehicle accidents (43,458), breast
cancer (42,297), or AIDS (16,516). Medication errors alone, occurring either in or out of the hospital, accounted for
an estimated 7000 deaths annually. That is more than the estimated 6000 Americans who die each year as a result of
workplace injuries. Translating quality into cost, the IOM estimated that preventable adverse outcomes increased
healthcare spending by $17 billion to $20 billion annually. 21 This observation led the IOM, in a second report from
the Quality of Healthcare in America Project, entitled Crossing the Quality Chasm: A New Health System for the
21st Century, to recommend that the US healthcare system be redesigned. According to this report, the healthcare
system should focus on applying evidence to healthcare delivery, using information technology, aligning payment
policies with quality improvement, and preparing the healthcare workforce for the necessary changes. 22
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Interest in improving healthcare quality while decreasing cost has increased significantly in recent years, but this
concept has existed for decades. In 1983, for example, unit pricing based on diagnostically related groups (DRGs)
shifted Medicare hospital payments from a retrospective, cost-based system to a prospective, condition-based
system. With DRGs, Medicare paid hospitals a fixed amount to treat a patient with a specific condition, regardless of
how long the treatment took or the resources expended in doing so. This new prospective payment system removed
incentives for keeping patients hospitalized because longer stays did not result in additional reimbursements. DRGs
resulted in lasting reductions in length of stay and services used in hospitals across the United States.23
Unfortunately, however, overall healthcare spending was not significantly affected because the bulk of patient care
merely shifted from inpatient to outpatient settings. This early experiment in the reform of healthcare financing did,
however, demonstrate that payment incentives could modify the behavior of healthcare providers.
For individuals looking to develop performance measures to leverage a value-based proposition locally (e.g.,
application toward bundled payment incentives) or QCDR measure developers feeding the value-based payment
system, it is good to consider the following design principles for performance measurement. With regard to the
payment structure, it is important to consider accountability level, distribution of financial incentives, financial
incentive types, and frequency of assessments and incentive distribution. With regard to transparency, it is important
to consider the public disclosure and methodology for comparison and benchmarking. With regard to the metrics
themselves, consider the type of measure and the metric attributes that include: 1) High volume, 2) High gravity
(severity), 3) Strong evidence-basis, 4) Gap between current and ideal practice, 5) Good prospects for quality
improvement, 6) Measurement reliability, 7) Measurement validity, and 8) Measurement feasibility. When possible,
metrics should be selected from the following quality and outcomes domains: 1) Patient-centeredness, 2)
Effectiveness, 3) Safety, and 4) Efficiency. 24
The ‘Triple Aim’ is a framework developed by the Institute for Healthcare Improvement (IHI) that describes an
approach to optimizing health system performance. It is IHI’s belief that new designs must be developed to
simultaneously pursue the three dimensions of this triple aim, which include 1) Improving the patient experience of
care (including quality and satisfaction); 2) Improving the health of populations; and 3) Reducing the per capita cost
of health care.25 Metric attributes are likely to evolve to include all three dimensions. For example, evidenced-based
research evaluating process and outcomes will likely evolve to effectiveness research including cost and return on
investment. High gravity will likely refer to potential cost savings rather than outcome severity. Gap closure will
refer to return on investment, rather than practice patterns, and metrics will be retired when they no longer produce a
financial return. Similarly, prospects for improvement will refer to return on investment. Data collection will be
likely more feasible via mandatory electronic health record reporting and automated validity checking. Performance
metrics in a value-based payment system are likely to have a greater effect on clinical practice patterns than our
current practice guidelines. For that reason, the medical profession must develop standards for the development of
performance metrics.
Until recently, the authority on healthcare quality measure development has been the National Quality Forum
(NQF), a not-for-profit membership organization that has operated for more than a decade to evaluate and endorse
standards, performance measures, best practices, frameworks, and reporting guidelines by employing a rigorous
Consensus Development Process (CDP). Use of this formal CDP gives NQF recognition as a voluntary consensus
standards-setting organization as defined by the National Technology Transfer and Advancement Act of 1995 and
Office of Management and Budget Circular A-119. The CDP involves eight principal steps—call for nominations,
call for candidate standards, candidate consensus standard review, public and member comment, member voting,
Consensus Standards Approval Committee decision, board ratification and appeals. The NQF serves as the
consensus-based entity on performance measurement for The Department of Health and Human Services, and when
feasible, NQF-endorsed measures are used in CMS public reporting and value-based purchasing programs.
CMS utilizes the Measures Management System (MMS), a standardized process for developing, implementing, and
maintaining PQRS measures. MMS lists five measure evaluation criteria—importance, scientific acceptability of
measure properties, feasibility, usability and use, and related and competing measures (harmonization)—to identify
priority areas during development.26 CMS measures are submitted to NQF for evaluation and endorsement. The
NQF prefers two systems for grading the evidence during measure development: the U.S. Preventive Services Task
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Force (USPSTF) grading definitions/methods and the Grading of Recommendations, Assessment, Development and
Evaluation (GRADE) guidelines.27,28 There is currently no oversight that requires QCDRs to utilize similar systems
when developing non-PQRS measures, and grading of evidence for non-PQRS measures is often not reported by
QCDRs. With hundreds of measures to choose from, the complexity of reporting and compensation may further
increase cost if performance metrics are not subject to uniform, rigorous methodology to target meaningful
improvements in healthcare.
In summary, performance measurement is required, and the results of our performance measurements will have an
increasing impact on reimbursement for healthcare services. Merit-based Incentive Payment Systems and
Alternative Payment Models will require measurement of patient outcomes, resource use, meaningful use of
electronic health records, and practice improvement. Providers and healthcare organizations will bear the increasing
burdens of performance measurement. There are costs associated with both the technical and administrative
requirements of data collection and submission. Anesthesia practices must assess their local resources and readiness
for performance measurement, if they want to maximize their return on investment. Return on investment may vary
by institution and the specific performance measures selected. Even after selecting appropriate measures at the local
level, one must assess reliability, feasibility, and validity on an ongoing basis. Additionally, our specialty must
develop standardized methodology for the development of performance metrics with strict adherence to attribute
guidelines. Performance metrics in a value-based payment system are likely to have a greater effect on clinical
practice patterns than our current practice guidelines, and should be developed with the same amount of rigor.
References
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Effectively Compared According to Their Patients' Postanesthesia Care Unit Admission Pain Scores.
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16. Hirsh S. GM plant a sign of decline. The Baltimore Sun. May 9, 2005.
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Developing Anesthetic Platforms for Ablations in the EP Lab
Wendy L. Gross MD Boston, MA 02115
Introduction:
Electrophysiology is the fastest growing subspecialty of cardiology. The scope, number and complexity of EP
procedures has grown enormously on the past 10 years. What was once principally a diagnostic specialty has
become the harbor of highly intricate and technical therapeutic undertakings. Not surprisingly, the acuity of
patients undergoing electrophysiology procedures has escalated enormously in recent years. 1
Unfortunately however, although technology and treatment modalities have accelerated, publications relating to
the Interface of EP and anesthesiology have been remarkably slow to emerge. To some extent this is due to the
difficulties inherent in creating a robust collaborative platform between two highly specialized and unique
branches of medicine; each with its own distinctive vocabulary, equipment and work venue.
Cardiac rhythm disturbances constitute an increasing source of mortality and morbidity in the US and around the
world. Alone, they bear responsibility for a large number of hospital admissions and remain a common
complication of surgery and medical procedures 2. This is a function of aging populations, increased incidence of
cardiovascular disease and longer survival of patients with related comorbidities.
As Anesthesiologists we suppress and/or cardiovert patients out of hemodynamically unwelcome rhythms

commonly. However, during catheter ablations in the EP Lab, we are expected to support patients by keeping
them hemodynamically stable, comfortable and still without impacting the rhythms to be eliminated. If both
groups maintain blissful disinterest in the effect of their interventions on each other’s progress, we miss the
opportunity to synergistically facilitate procedural process.
Important areas of common interest and overlap should be discussed by all participants when EP procedures
involve Anesthesiologists and Electrophysiologists. This is the best way to optimize outcome as we begin to
understand our mutual territory. Because therapeutic treatment of arrhythmias in the EP Lab involves patients
who are not “optimized” ACC/AHA guidelines do not provide a useful framework for perioperative decision
making. This refresher attempts to highlight general, critical procedural points which Anesthesiologists should
appreciate in preparing anesthetic plans for patients undergoing catheter-based treatment of Atrial and
Ventricular Arrhythmias. Arrhythmias can develop at the cellular, tissue or organ level. Aberrancy of the cardiac
action potential, disruption of the normal cardiac syncytium or neurohumoral effects on the heart as a whole can
result in the development of abnormal rhythms.
An understanding of normal physiology and relevant pathology as well as a firm grasp of key procedural steps of
Ablation procedures are important in formulating an approach most likely to achieve the goals of treatment.
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The Normal Cardiac Action Potential

In cardiac tissue as in other electrically active tissues, electrical and ultimately mechanical function is driven by
ionic flux across cell membranes. Ions flow in the direction of their gradient modified by the permeability of the
cell membrane to the specific ion. Cardiac action potentials vary according to their position and function within the
heart. However they do possess common features. At rest, cardiac cells are inside negative relative to the
extracellular space i.e., they are polarized. When they fire they become depolarized and then through a series of
(variable) regulated steps they become repolarized. The membrane potential cycles from about -80 mv at rest to
about + 40 mv at the peak of depolarization with some variation depending on the exact location and type of cell.
Although these fields may seem tiny, the change in electrical voltage occurs over a very small distance and
therefore the fields created are significant.
Cells that serve as conductors have different action potentials than those that serve as pacemakers. (Fig
1)Conducting myocytes are found in the atrial and ventricular myocardium as well as the His-Purkinje system. In
general these cells have “fast” action potentials characterized by a rapid depolarization phase (Phase 0), early
repolarization (Phase 1), a plateau phase (Phase 2), a rapid repolarization phase (Phase 3) and a resting phase
(Phase 4). The rapid depolarization phase is modulated by rapid Na influx. During early repolarization, once the
rapid Na channels close, rapid outward K channels open and K begins to move out of the cell so the voltage drops
back towards zero. The Plateau phase is characterized by inward movement of Ca, continued slow movement of K
out via slow rectifier channels and continuing activity of the K-Na pump and K-Ca exchange current, At the
conclusion of the plateau phase rapid repolarization is driven by inactivation of inward Ca channels and activation
of inward K channels. The duration of the AP determines the effective refractory period of conducting cells.
Cells that serve as pacemakers in the SA and AV node are characterized by “slow” action potentials which are
dependent on Ca channels for phase 0. They are less inside negative (-50 to-60 mV) and their membranes do not
contain active Na channels. Ca current is slower and smaller than Na current and this confers the property of post-
repolarization refractoriness on SA and AV nodal tissue. Their action potentials are different than conducting cells.
The phase 0 rapid depolarization phase is slower and generated by Ca channels rather than NA. Early
repolarization (phase 1) and phase 2 are essentially absent. Phase 3 is also Ca dependent and takes longer in these
cells. Phase 4 is characterized by (automaticity) spontaneous depolarization which occurs as a result of activated
inward Na channels, Ca currents and inactivated K rectifier channels. Ca is also sensitive to autonomic
neurotransmitters so nodal tissue is impacted by autonomic tone. The SA node acts as a predominant pacemaker
with the AV node as backup.
An interesting feature of cardiac electrical anatomy is the regional specificity of electrical characteristics (fig
2).There are several different types of Action Potentials found throughout the heart. Ventricular cells have an AP of
longer duration with a higher phase 2 and a faster phase 3. Cells within the His-Purkinje system have a more
prominent phase 1, a longer phase 3 and a spontaneous phase 4 (automaticity).There are subtle but important
differences in the membranes of myocytes throughout the endo and epicardium which reflect local functional and
environmental differences.
Neurohumoral Impacts on Action Potentials and Mechanisms underlying the development of

Arrhythmias
Cardiac Action Potentials confer specific cellular characteristics which integrate electrical and mechanical
properties in specific zones of cardiac tissue. They include:
1. Excitability: the capacity of a cell or tissue to respond to a stimulus

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2. Automaticity: the capacity of a cell or tissue to initiate an impulse
3. Conductivity: the ability of a cell or tissue to transmit an impulse
4. Refractoriness: the ability of a cell or tissue to remain unresponsive to an impulse for a period of time.
5. Contractility: the ability of a cell or tissue to respond to an impulse mechanically
Parasympathetic stimulation can directly impact nodal cardiac action potentials via acetylcholine by slowing
depolarization and decreasing chronotropic, dromotropic and inotropic effects. Increased automaticity.
Sympathetic stimulation via norepinephrine through B1 receptors can increase chronotropy, dromotoropy and
inotropy. Any change in parasympathetic and/or sympathetic tone can precipitate important effects on cardiac
conduction. Similarly…other stimuli that trigger Neurohumoral release of these substances or metabolic stress that
results from hypoxemia, hypercarbia, hypokalemia, hypomagnesemia, increase in afterload, myocardial wall
tension or ischemia can also impact conduction or precipitate a change in rhythm. Aberrations in any of the above
or mechanical disruption of the normal myocardial syncytium can enhance conditions which support the
development of rhythm disturbances and/or mechanical compromise.
Arrhythmias commonly treated in the EP Lab

An arrhythmia is any rhythm characterized by a rate that is irregular, too fast or too slow. Any rhythm at an
inappropriate rate can cause cardiac dysfunction. Types of arrhythmias include:
1. Bradyarrythmias due to abnormal impulse generation or abnormal impulse propagation
2. Tachyarrythmias
a. Regular with a normal QRS (AVNRT, Aflutter, SVT)
b. Irregular, normal QRS (Afib, MAT)
c. Wide QRS (VT, SVT with BBB or aberrancy)
Bradyarrythmias are usually dealt with in the EP Lab with implantation of pacemakers. Tachyarrythmias are
managed with ICDs if they are of a lethal nature or with catheter ablation procedures when medications are
unsuccessful or not tolerated by patients. Management of Catheter based ablation procedures often involves
Anesthesiologists and we will focus on those here. Common mechanisms of Arrhythmias include re-entry,
enhanced automaticity and trigger activity.4
Re-entry
Re-entry circuits develop when circuit pathways are created between connected tissues with different conduction
velocities and refractory periods (fig 3). Usually re-entry occurs around a core of non-excitable tissue, it is the most
common cause of tachyarrhythmias. It accounts for many forms of SVT, WPW and AVNRT. Monomorphic VT can
occur as a result of re-entry due to scar or fibrosis.
Automaticity
Pacemaker cells demonstrate spontaneous diastolic depolarization. Although the SA node is the primary
pacemaker, other cells with this property are fond in the CS, crista terminalis, AVJ and His-Purkinje system.
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Enhanced Automaticity can occur as a result of increased sympathetic tone or other metabolic triggers.
Automaticity accounts for a relatively small (10%) number of tachyarrhythmias.
Triggered Activity
After the depolarization phase of the AP, oscillations in membrane potential can trigger tachyarrhythmias. If the
fluctuation occurs prior to repolarization it is called an EAD (Early Afterdepolarization, if it is after repolarization it
is called a DAD (Delayed Afterdepolarization). EADs occur with delayed repolarization and can result in
polymorphic VT. DADs can occur with calcium overload or digoxin toxicity. (Fig 4) 5
Understanding the etiology of arrhythmias allows anesthesiologists to be aware of the metabolic, neural and
neurohumoral factors which might predispose patients under anesthesia to factors which could precipitate
arrhythmogenic conditions.
Effects of Anesthetic Drugs on Arrythmogenesis

Many drugs are used by anesthesiologists during EP procedures and it is difficult to separate the primary cardiac
effects of these agents from their indirect effects on the heart. In addition, little research has been done in the EP
lab and studies undertaken to understand the arrhythmogenic effects of agents in the OR or ICU are often
muddied and complicated by the multiple comorbidities of patient populations.
Inhalational Agents
All inhalational agents alter cardiac conduction in multiple ways. Common inhalation agents can enhance
automaticity of secondary atrial pacemakers thus enhancing the likelihood of developing secondary atrial
pacemakers or MAT. Inhalational agents can also prolong QT intervals and reduce contractility. 6 Isoflurane can
increase heart rate but slow His Purkinje conduction, while AV nodal conduction is spared. However, there is
research demonstrating suppression of SVT re-entrant tachycardia by isoflurane so it’s use is not recommended in
this case.7 Sevoflurane seems to have little-no effect on the SA or AV node or on accessory pathways
conduction….but it does have secondary effects via autonomic nervous system suppression.
Propofol
Propofol is widely used in EP Labs. Because patients recover rapidly from Propofol, it is helpful in long cases and
short cases alike. Propofol has been associated with both bradycardia and tachycardia and of enhancing
epinephrine induced arrhythmias in dogs. The hypotension associated with propofol administration is postulated
to be related to inhibition of the sympathetic nervous system. 8 In the EP Lab propofol does not appear to trigger
SVT or VT, nor does it demonstrate a direct effect on accessory pathways or normal Av nodal pathways. In children
undergoing SVT ablation propofol does not appear to alter SA nodal conduction. 9
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Benzodiazepines
All benzodiazepines decrease both peripheral vascular resistance via vasodilation and cardiac contractility. Large
doses of benzodiazepines can produce reflex tachycardia. There is no documented effect of benzodiazepines on
cardiac conduction. Due to relatively slow onset, benzodiazepines do not produce immediate sedation and
increasing doses can predispose patients to the need for advanced airway support. Time to onset of most
benzodiazepines precludes their use for urgent cardioversion and autonomic suppression makes the use of these
drugs less than desirable during the induction of ventricular arrhythmias. 10
Opiates
Opioids generally produce bradycardia via a vagotonic effect. They can prolong the AP by reducing Ca current via
an effect on K channels in cell membranes. 11 Opiods have been shown to prolong QT interval but the site of
action is unclear. Remifentanil is quite useful in the EP Lab because of its short half-life and rapid onset time. It acts
synergistically with other sedatives which can be helpful. Remifentanil does induce bradycardia and has been
shown to reduce conduction time from the atrium to the His bundle. In dogs, remifentanil does not affect
inducibility of VT. In children undergoing SVT ablation this drug does seem to slow of SA and AVN conduction.
Hypotension associated with Remifentanil is thought to be related to vasodilation and bradycardia. High doses of
Sufentanil are thought to prolong the QT interval.12-13
Dexmedetomidine
Dexmedetomidine has been used in the EP Lab. It is associated with decreased SA and AV nodal function in
children 9-40% of the time. Depending on the patient and the particular case, this drug may be useful due to its
ability to preserve respiratory function while creating a deep level of sedation. However, the a-2 properties of
Dexmetomidine decrease NE release and enhance vagal tone giving it anti-arrhythmogenic properties. 14-15
Etomidate
Etomidate may be useful for induction in patients with low EF or other cardiac compromise. Purely
electrophysiological effects are not reported. It can cause myoclonus and nausea.
N-M Blockade
Neuromuscular blockers ca impact cardiac conduction in several ways. Indirectly, via sympathetic and/or
parasympathetic pathways or via vasodilation as a result of histamine release. Succinyl choline is useful in the EP
Lab because phrenic nerve assessment during an ablation may require a non-paralyzed patient. Rocuronium has
not been demonstrated to cause direct or indirect cardiac conduction effects and it is usually gone by the time the
patient has been accessed and the EPS begins.
Electrophysiology Studies and Catheter Ablations for Tachyarrhythmias

EP Studies and Percutaneous catheter based ablations are popular methods of diagnosing and treating
supraventricular and ventricular tachycardias. Diagnostic EP studies were first performed in the early 1970s. Once
it became clear that catheter based EP studies could identify arrhythmogenic foci and mechanisms of tachycardia
the concept of applying current to the aberrant areas soon followed. Although application of D/C current was the
first treatment modality, Radiofrequency current became the treatment of choice. Tachyarrhythmias commonly
treated curatively via catheter based ablation include:
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AVNRT, WPW
Typical and Atypical Aflutter
Afib
Ventricular Tachycardia
Atrial Tachycardia
Catheter ablation can be palliative (i.e. AVJ ablation for Afib) and it is not indicated for VF.
AVNRT, WPW, and SVT ablations are usually short and most patients can tolerated the procedure with sedation
administered by an anesthesiologists or a nurse. Ablations for Afib, ATach or Atypical flutter can often be long and
challenging. These cases usually involve anesthesiologists.
EPS and Ablation Strategies

The point of catheter based procedures is to identify and treat dysrhythmias. This requires detailed mapping of the
heart and also includes assessment of the SA node, AV node and the His-Purkinje system. EP data can be acquired
during programmed atrial and ventricular stimulation via recording of intracardiac electrograms (EGMs). EGMs
record only localized areas between catheters (or anode and cathode), they can be unipolar or bipolar. They yield
information about activation timing, wavefront propagation (unipolar) and the state of myocardial tissue.
Intracardiac electrograms define and measure conduction times between anatomic areas.
Pacing catheters are typically placed in the high Right atrium, the RV apex and next to the bundle of His near the
tricuspid annulus. There are different shaped catheters for specific areas of the heart. By stimulating and recording
from different areas within the heart and manipulating the catheters, pacing can be performed from any area. This
is called programmed stimulation. Programmed stimulation can measure SA and AV nodal function and refractory
periods.
Localized depolarization of the proximal bundle of His is recoded on the His and the earliest deflection identifies
the AV node. The time required for conduction from the RA to the His bundle estimates the AV delay. A pacing
catheter/electrode in the RV can stimulate a tachycardia, overdrive pace or provide backup pacing if needed.
Pacing can introduce premature impulses in order to assess conduction or refractory periods and to induce re-
entrant pathways. Triggering of abnormal pathways can permit the electrophysiologist to observe the sequence of
propagation thereby mapping the site of activation of an aberrant pathway.
During catheter ablation ablative energy is applied to regions of abnormal conduction. If the arrhythmia has a
known anatomical course, a line of RF is delivered to his area. Atrial Flutter often propagates as a wavefront
between the tricuspid valve and the IVC. In this case a line of RF is performed along the Cavo-Tricuspid Isthmus
called a CTI line. Treatment of Afib centers on ablation of foci around the ostia of the pulmonary veins and other
trigger points located within the atrium.
Mapping and ablation of VT involves more heterogeneous approaches and is dependent upon the type of VT, its
location and focus. Several common mapping strategies are useful in this context: activation and entrainment
mapping as well as pace mapping and substrate mapping. Activation mapping is done during VT. Entrainment
mapping involves pacing at a rate faster than the VT cycle length in order to define re-entrant circuits which may
contribute to the arrhythmia. When it is necessary to perform VT ablation during sinus rhythm (because the VT in
question is unstable or non-inducible) pace mapping and substrate mapping are used. This involves identifying a
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region of scar, pacing along the scar border and analyzing the QRS morphology and activation sequences
produced. If endocardial mapping is unyielding, epicardial mapping may be necessary.
RF catheters are steerable and often cooled with saline. Catheter irrigation can be significant and it is important to
keep track of the ablationist’s fluid totals as well as those of the anesthesiologist in order to avoid volume
overload. This is particularly problematic in patients with poor renal function or low cardiac output. RF current is
the preferred ablation mode although laser and microwave catheters do exist. Cryoablation balloons are often
used for ablations of the PV ostia. Ablating around the pulmonary veins for AF can also be done with a
Cryoballoon, a catheter fitted with a balloon filled with liquid refrigerant which is used to occlude the pulmonary
veins and freeze the ostial tissue. If necessary alcohol ablations can be performed via the coronary branches.
Catheter ablations are done in the context of 3D mapping systems. A specialized catheter with a sensor tip that
interfaces with a mapping program superimposed on a previously obtained CT or MRI of the patient’s heart
generates a color coded map of electrical activity or isochrones which indicate zones of scar, ectopic activity and
re-entrant foci. Once delineated, the regions are targeted and radio frequency lesions are delivered. Once the
lesions are delivered, programmed stimulation is delivered to ensure ablation of targets and absence of any new
arrhythmias.
Anesthetic Techniques and Management during Ablation Procedures

Electrophysiology procedures are most often elective but they are sometimes performed urgently. Complications
can occur with little notice and can be life threatening. For this reason vigilance on the part of the anesthesiologist
is critical. For Typical Aflutter, most SVTs, AVNRT, and WPW sedation is adequate. The procedures are relatively
short and not overly painful. Most of these pathways are easily identified and complex mapping is not necessary.
Ablations for Afib are often lengthy…sometimes as long as 6-8 hours. GETA is recommended in these cases, not
only for patient comfort but because any kind of airway obstruction makes mapping and ablation difficult since it
adds to the motion of the catheters. GETA has been shown to reduce procedure time and improve outcomes in
ablations for Afib. At one year patients randomized to undergo Afib ablations under sedation (versed and fentanyl)
demonstrated a 70% freedom from their arrhythmias, whereas 90% of patients undergoing the procedure with
GETA had no recurrence. 17 The improvement is ascribed to improved catheter stability and increased precision of
energy delivery. Recently jet ventilation has been used during Afib ablations to minimize catheter movement. A
retrospective study demonstrated an increased freedom from Afib at 1 year in patients undergoing Afib ablations
from 66 to 74%. 18 Fluoroscopy time was also reduced in these patients. Some institutions impose apneic periods
when RF energy is delivered. In both situations, TIVA is necessary. Infusions of Propofol and remifentanil or
sufentanil are commonly used.
For cases in which patients present with PVCs which seem to be catecholamine sensitive, it may be necessary to
begin the case with little or no sedation in order to identify and map the arrhythmic focus. Once the area of
interest is identified it is often more comfortable for the patient to proceed under GA. This is particularly the case
with RVOT PVCs. General anesthesia is warranted for the ablation of unstable VTs although the need for
hemodynamic support increases with GA for patients with poor contractile reserve or right heart failure. Although
electrophysiologists have traditionally been concerned that GA could negatively impact inducibility and
hemodynamic stability of VTs this does not appear to be the case. A recent publication indicates that GA did
increase the need for hemodynamic support with Phenylepherine but did not affect the inducibility of VT. In this
study under GA nonclinical VTs were more frequently induced in patients with a lower EF and non-ischemic
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cardiomyopathy. 19 Phenylepherine is often used as a first line choice but this may be inadequate alone. The use
of phenylephrine does not appear to affect inducibility of VT in th is population. Vasopressin, low dose epinephrine
and/or levophed may also be required. For patients with low EF and hemodynamically unstable VT, mechanical
support may be necessary.
Continued investigation of the effects of anesthetics on procedural aspects and outcomes of catheter ablations in
the EP Lab is ongoing. As EP procedures become technically more advanced and the comorbidities of target patient
populations more significant, the interface of our two disciplines is likely to grow. Collaborative databases and
research projects will become more necessary in order to optimize patient safety and improve outcomes.
Figure 1
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References
1. Is EP’s success its own problem? An update on EP physician recruitment. EP Lab Digest 2010; 10:1–11
2. 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing
Noncardiac Surgery2014; 64(22):e77-e137. doi:10.1016/j.jacc.2014.07.944
3. A practical Approach to Arrhythmology Mont L, Brugada J Mars Medica 2010 Ch1 pp15-25
4-5 Clinical Cardiac Electrophysiology Handbook Andrade J Ch 1 pp1-8 cardotextpublishing 2016
6. Volatile anesthetics and cardiac function Semin Cardiothorac Vasc Anesth. 2006 Mar;10(1):33-42. DeHert SC
7. Comparison of electrophysiologic effects of propofol and isoflurane-based anesthetics in children undergoing

radiofrequency catheter ablation for supraventricular tachycardia. Erb TO, Kanter RJ, Hall JM, Gan TJ, Kern FH,
Schulman SR. Anesthesiology. 2002 Jun; 96(6):1386-94.PMID: 12170051
8. Liu Q et al Propofol and Arrhythmias: two sides of the coin. Acta Pharmacol Sin2011:32(6):817-823
9. Pires LA et al Electrophysiological effects of Propofol on the Normal Cardiac Conduction System Cardiology 1996;
87(4):319-324
10. https://www.pharmgkb.org/pathway/PA165111375
11. North RA Williams JT Opiate activation of potassium conductance inhibits calcium action potentials in rat locus
coeruleus neurones.Br J Pharmacol. 1983 Oct; 80(2): 225–228.
12. Mandel JE, Hutchinson MD, Marchelinski FE Remifentanil-midazolam sedation provides hemodynamic stability
and comfort during epicardial ablation of ventricular tachycardia J Cardiovasc Electrophysiol. 2011 Apr; 22(4):464-
6. Doi: 10.1111/j.1540-8167.2010.01889.x. Epub 2010 Aug 31.
13. Tanner J et al Anesthesiology for Electrophysiology Procedures in Non-Operating room Anesthesia Elsevier
2015 Phila., PA
14 Hammer et al the effects of dexmedetomidine on cardiac electrophysiology in children. Anesth Analg.2008;

106(1); 79-83
15. Bhana N et al Dexmedetomidine Drugs 2000:59(20) 263-268
16. Chua J et al Anesthetic Management of Electrophysiology Procedures Curr opinion in Anesthesiology Vol 25(4)
August 2012 470-481
17. DiBiase L et al General Anesthesia educes the prevalence of pulmonary vein reconnection during repeat
ablation when compared with conscious sedation: results from a randomized study. Heart Rhythm 2011:8:368-372
18. Hutchinson MD et al Efforts to enhance catheter stability improve atrial fibrillation ablation outcome. Heart
Rhythym2013:10(3):347-353
19. Nof E et al Impact of general anesthesia on initiation and stability of VT during catheter ablation Heart Rhythm.
2015 Nov; 12(11):2213-20. Doi: 10.1016/j.hrthm.2015.06.018. Epub 2015 Jun 10. PMID: 26072026
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Anesthesia for Hybrid EP Interventional Procedures

G. Burkhard Mackensen, MD, PhD, FASE Seattle/WA
Hybrid and structural heart interventions performed by the electrophysiologist represent an exponentially growing
field, which has expanded beyond established procedures such as radio-frequency catheter ablation for atrial
fibrillation (AF) and ventricular tachycardia (VT) to technology-driven procedures such as the convergent procedure
for atrial fibrillation, combined cardiac interventional and surgical procedures, laser lead extractions or transcatheter
exclusion of the left atrial appendage (LAA). Many of these combined cardiac interventional and surgical
procedures are now being performed in custom-designed “hybrid” catheterization laboratories. These procedures,
along with their rapidly evolving technology present new challenges and opportunities for the cardiac
anesthesiologist, both as the anesthesiologist and as the interventional echocardiographer who provides procedural
image guidance and monitoring with transesophageal echocardiography (TEE).
The anesthetic requirements for these procedures are becoming ever more complex and require the presence of a
cardiac anesthesiologist who can uniquely address the needs of the cardiac surgeons and electrophysiologists while
taking care of these very sick cardiovascular patients with all their comorbities. Often, these procedures also require
the involvement of a cardiac perfusionist, at least in stand by mode, to provide cardiovascular support with a heart-
lung machine as needed. In light of the increasing use of minimally invasive ventricular assist devices, such as the
Impella (Abiomed, Danvers, MA) and TandemHeart devices (Cardiac Assist, Inc, Pittsburgh, PA), for the
management of acute or chronic heart failure, the anesthesia provider also must be experienced with the pathology
and technical considerations associated with patients requiring this type of ventricular support. In many of these
interventions, there are specific key steps that are essential to the success and safe conduct of these procedures. Any
error or misunderstanding among unprepared team members can lead to devastating consequences.
Intraoperative Management: What are the options for anesthetic management and how to determine the best
technique?
General anesthesia: Benefits include airway control, continued monitoring of ventilation, patient comfort during
lengthy procedure, control of patient movement and ventilation, and improved catheter stability and potentially
better procedural efficacy. Drawbacks include the potential effects of the general anesthetics on the conduction
system.
Monitored anesthesia care: Benefits include that the depth of patient sedation can be adjusted according to need,
that patient feedback can be used to recognize early esophageal, pulmonary or other injury, and that it provides
direct neurologic monitoring. Drawbacks include a lack of airway control and that incomplete respiratory
monitoring may lead to hypercarbia and pulmonary hypertension. (Inadequate oxygenation/ventilation remains as
the most common injury in the closed claims database for non–operating-room anesthesia). In addition, negative
thoracic pressures secondary to respiratory efforts against upper airway obstruction can lead to air entrainment or
shifting of intracardial structures. Also, sudden patient movements/irregular respiration may increase procedural risk
Patient access and monitoring
Patient access is limited during the case due to the EP/catheter laboratory equipment. Intravenous access should be
established via at least one free-flowing peripheral intravenous line. It should be kept in mind that the groin access
via the catheter introducers may serve as emergency access for rapid administration of volume. Beat-to-beat blood
pressure monitoring should be established via an intra-arterial line. This line also allows blood sampling for ACT
monitoring during the procedure. Urine output should be monitored through a urinary catheter placed under sterile
conditions at the beginning of the case. Esophageal temperature probe is often inserted to identify potentially
dangerous heating of the esophagus in cases of radiofrequency ablation. However, within the broad esophagus, the
temperature probe may not align with the ablation electrode, giving a false impression of safety.
Echocardiography during hybrid EP interventional procedures:

Before engaging in catheter ablation for AF or VT, the electrophysiologist routinely requests a TEE to rule out the
presence of a thrombus in the LAA or the left atrium. In many centers, the cardiac anesthesiologist performs this
TEE assessment after the induction of general anesthesia, thereby optimizing workflow and maximizing efficiency.
An increasing number of electrophysiologists also rely upon TEE guidance during the ablation, often in recognition
of the risks of radiation exposure from fluoroscopy imaging during these long procedures. Procedural image
guidance with two-dimensional (2D) and three-dimensional (3D) TEE performed by cardiac anesthesiologists may
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also assist in catheter navigation, trans-septal puncture, or identifying catheter contact with important cardiac
structures. Similar to the practice of cardiac surgery, a cardiac anesthesiologist performing TEE for interventional
procedures serves as a more efficient patient care model than depending on a cardiologist echocardiographer whose
presence at key moments of the procedure may be uncertain due to other clinical responsibilities.
Although the convergent procedure for the treatment of AF may not necessarily require continued monitoring with
echocardiography, emergent echocardiography should be available to diagnose potential complications.
During laser lead extraction, emergent echocardiography (transthoracic and/or transesophageal) may be required to
rapidly diagnose a complication. The echocardiographic evaluation of the heart and surrounding structures adds
critical information regarding the presence and volume pericardial fluid as well as intracardiac blood flow velocities.
The quantitative grading of forming pericardial effusion is accomplished by estimating the distance between the
parietal and visceral pericardium, with interpericardial distances of 0.5 cm, 0.5-2.0 cm and > 2.0 cm corresponding
to mild, moderate and large effusions, respectively. A physician capable of performing and interpreting the
echocardiography must be immediately available. This may be either be the cardiac anesthesiologist involved in the
case, the physician performing the actual procedure or a cardiologist trained in echocardiography. In centers where
there is not a physician skilled in echocardiography in attendance during the procedure, an additional physician must
be available to perform and interpret these studies.
Percutaneous left atrial appendage (LAA) exclusion is an evolving treatment to prevent embolic events in patients
with nonvalvular atrial fibrillation. Over the past decade multiple percutaneous devices have been developed to
exclude the LAA from the body of the left atrium and thus from the systemic circulation. Both 2D and 3D TEE is
used to assess the LAA anatomy and its suitability for percutaneous closure to select the type and size of the closure
device and to provide procedural image guidance during the device implantation procedure in conjunction with
fluoroscopy. Further, 2D and 3D TEE is also used to assess the immediate success of the procedure and to evaluate
the device position and function during subsequent follow-up examination. For the cardiac anesthesiologist serving
as echocardiographer, knowledge of the available implantation options together with specific procedural steps is key
for choosing the appropriate device for a given patient and for the success of the procedure.
References:
Fuster V, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of
the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the
European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001
Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European
Heart Rhythm Association and the Heart Rhythm Society. Circulation 2006;114(7):e257-e354.
Mahajan A, and Chua, J: Pro: A Cardiovascular Anesthesiologist Should Provide Services in the Catheterization and
Electrophysiology Laboratory. J Cardiothor Vasc Anesth, Vol 25, No 3, 2011: 553-556
Calkins H, et al. HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial
fibrillation: recommendations for personnel, policy, procedures and follow-up. A report of the Heart Rhythm
Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation developed in partnership with the
European Heart Rhythm Association (EHRA) and the European Cardiac Arrhythmia Society (ECAS); in
collaboration with the American College of Cardiology (ACC), American Heart Association (AHA), and the Society
of Thoracic Surgeons (STS). Endorsed and approved by the governing bodies of the American College of
Cardiology, the American Heart Association, the European Cardiac Arrhythmia Society, the European Heart
Rhythm Association, the Society of Thoracic Surgeons, and the Heart Rhythm Society. Europace 2007;9(6):335-79.
Aliot EM, et al. EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias: developed in a
partnership with the European Heart Rhythm Association (EHRA), a Registered Branch of the European Society of
Cardiology (ESC), and the Heart Rhythm Society (HRS); in collaboration with the American College of Cardiology
(ACC) and the American Heart Association (AHA). Heart Rhythm 2009;6(6):886-933.
Shook DC, Savage RM. Anesthesia in the cardiac catheterization laboratory and electrophysiology laboratory.
Anesthesiol Clin 2009;27(1):47-56.
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Gaitan BD, et al. Sedation and analgesia in the cardiac electrophysiology laboratory: a national survey of
electrophysiologists investigating the who, how, and why? J Cardiothorac Vasc Anesth 2011;25(4):647-59.
Trentman TL, et al. Airway interventions in the cardiac electrophysiology laboratory: a retrospective review. J
Cardiothorac Vasc Anesth 2009;23(6):841-5.
Blanc JJ, et al. Consensus document on antithrombotic therapy in the setting of electrophysiological procedures.
Europace 2008;10(5):513-27.
Wunderlich NC, Beigel R, Swaans MJ et al: Percutaneous Interventions for Left Atrial Appendage Exclusion
Options, Assessment, and Imaging Using 2D and 3D Echocardiography JACC: Cardiovasc Imaging, Vol 8, 4, 2015
Wilkoff BL et al: Transvenous Lead Extraction: Heart Rhythm Society Expert Consensus on Facilities, Training,
Indications, and Patient Management. Heart Rhythm, Vol 6, No 7, 2009
Kratz JM and Toole JM: Pacemaker and Internal Cardioverter Defibrillator Lead Extraction: A Safe and Effective
Surgical. Ann Thorac Surg 2010;90: 1411–7
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EP for the Practicing Anesthesiologist
Life in the EP lab: High Acuity Patients in an Offsite Location
Jacques Prince Neelankavil, MD Los Angeles/California
Introduction
Cardiac arrhythmias account for over 881 000 hospitalizations and 40 700 deaths per year in the USA, with
a total of roughly 14.4 million patients affected by such conditions [1]. Many of these patients require
diagnostic or therapeutic intervention in an electrophysiology laboratory with involvement of an
anesthesiologist. Implantation of an artificial permanent pacemaker for bradyarrhythmias, or an implantable
cardioverter/defibrillator (ICD) for lethal tachyarrhythmias has been shown to significantly reduce morbidity
and mortality [2]. Perhaps the most important advance in the field of electrophysiology over the past decade is
development of the therapeutic electrophysiology study, sparing many patients the need for potentially toxic
drugs or cardiac surgery. As electrophysiology intervention comprises cardiac optimization for these patients,
the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines do not apply for
these procedures. Therefore, sophisticated understanding of the mechanisms behind various arrhythmias,
specific procedures performed for diagnosis and treatment, and associated risks is essential if the
anesthesiologist is to safely care for this unique patient population
Catheter Ablations
Programmed electrical stimulation with simultaneous recording of intracardiac signals was first performed in
1971 [3], and is the basis of the modern, diagnostic electrophysiology study. Once it became evident that
transvenous electrophysiology study could identify mechanisms of tachycardia and localize arrhythmogenic
foci, catheter-based ablation techniques soon followed. Although high-voltage direct current was originally
used, radio frequency current is now preferred, and catheter ablation has become first-line therapy for
many tachyarrhythmias
Electrophysiology studies and catheter ablations are performed in dedicated electrophysiology laboratories.
Access is typically via the femoral vein, but subclavian, internal jugular, or brachial approaches are also
used to introduce electrode catheters. If the left heart is instrumented, it is approached by either a
transseptal or retrograde aortic approach, and systemic heparinization is used to prevent systemic
thromboembolism. Once the electrode catheters are placed, initial baseline recordings are followed by burst
pacing at various fixed cycle lengths, as well as programmed electrical stimulation (PES), with or without
catecholamine infusion. PES consists of multiple delivered stimuli at a fixed cycle length (e.g., eight beats
at a rate of 100 beats/min), followed by a beat that is moved earlier and earlier, until it falls within the
tissue's refractory period, which can induce arrhythmias, thus allowing definitive diagnosis of arrhythmia
mechanism
Cardiac mapping identifies the temporal–spatial distribution of electrical impulses generated by the
myocardium during both normal and abnormal rhythms. Various mapping techniques are available to
identify sites for which radio frequency ablation can be curatively applied
Regardless of mapping technique, once an arrhythmogenic focus is successfully localized, ablation is

performed using low-voltage, high-frequency radio frequency energy (100 kHz to 1.5 MHz). Temperatures
above 90°C produce a high-impedance barrier of denatured tissue protein at the catheter tip, which
increases the risk of thromboembolism. Catheters with saline-cooled tips can decrease formation of this
coagulum, thus allowing production of larger radio frequency lesions with lower risk of thromboembolism
[4,5]. Cryothermal energy may overcome other disadvantages of radio frequency, such as tissue disruption
at excessively high temperatures and nonuniform lesions [6,7]. Subxyphoid access for epicardial mapping
and ablation has shown success in certain arrhythmias refractory to endocardial ablation [8,9]. Wider
application of this technique may be possible, but is currently only performed at a small number of
specialized referral centers
Refresher Course Lectures Anesthesiology 2016 © American Society of Anesthesiologists. All rights reserved. Note:
This publication contains material copyrighted by others. Individual refresher course lectures are reprinted by ASA
with permission. Reprinting or using individual refresher course lectures contained herein is strictly prohibited without
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Complications
Electrophysiology studies and catheter ablations are generally safe, but do carry definite risk [10,11] Most
complications are related to the vascular access (3–4%), including bleeding, infection, hematoma, and
vascular injury. Intracardiac catheter placement and PES can lead to hemodynamically unstable rhythms
requiring direct current shock. Cardiac perforation with tamponade and complete heart block requiring
pacemaker placement occur in less than 1–2% of radio frequency ablation cases. Risks specific to
pulmonary vein isolation include pulmonary vein stenosis and atrioesophageal fistula (0.01–0.2%) [12,13].
Rarer complications for all intracardiac radio frequency procedures include valve damage, systemic
embolization, and stroke (<1% when the left heart is accessed), phrenic nerve injury, and radiation skin
burn. Death due to complications is exceedingly rare (0.1–0.3%). Predictors for complication include
structural heart disease and ablating more than one target [14]
Anesthetic Management
Electrophysiology studies and catheter ablations are most commonly performed on an elective basis, but
are sometimes carried out urgently, usually in cases of recurrent, unstable ventricular tachycardia. For most
types of arrhythmias, sedation via propofol infusion is usually adequate. However, ablation of complex
atrial fibrillation can be time-consuming (6–8 h), and carries the risk of atrioesophageal fistula. This may
be reduced by using oral contrast via an orogastric tube placed at the gastroesophageal junction [15].
General anesthesia with endotracheal intubation is indicated when oral contrast is used, but as inadvertent
phrenic nerve stimulation with pacing can lead to phrenic nerve damage, neuromuscular blockader should
be avoided. General anesthesia is also indicated for ablation of destabilizing monomorphic ventricular
tachycardia in patients with ischemic heart disease
Aside from standard monitors, the need for invasive arterial monitoring is dictated by patient comorbidity.
Temperature monitoring is indicated for longer procedures; monitoring esophageal temperature can reduce
the risk of atrioesophageal fistula while ablating atrial fibrillation [16]. Adhesive surface
defibrillator/pacing pads should be applied in all cases, and a functional defibrillator readily available.
Transesophageal echocardiography is performed to rule out intracardiac thrombus in patients with atrial
fibrillation and atrial flutter. Precautions against intravenous air should be taken to prevent paradoxical
embolism during trans-septal puncture. When indicated, systemic heparinization is monitored with a
targeted activated clotting time greater than 300 s. Catheter tip irrigation fluid should be accounted for
when calculating total fluid administration and the urinary bladder should be catheterized to monitor urine
output for prolonged procedures. The upper and lower extremities should be properly supported to avoid
injury due to positioning and from multiple electrical wires near the patient
While inducing arrhythmias and mapping, transient hemodynamic instability commonly occurs.
Inotropes/vasopressors may help maintain hemodynamic stability. In such cases, clear and open
communication with the cardiologist is essential for achieving safe and successful mapping. Cardiac
perforation leading to tamponade must be ruled out in the presence of significant hypotension. Emergency
airway access may be obstructed by fluoroscopy equipment. Radiation exposure should be minimized by
using pulsed fluoroscopy and protective barriers.
REFERENCES
1. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics
2011 update: a report from the American Heart Association. Circulation 2011;
123:e18–e209.
2. Kuck KH, Cappato R, Siebels J, et al. Randomized comparison of

antiarrhythmic drug therapy with implantable defibrillators in patients
resuscitated from cardiac arrest: the Cardiac Arrest Study Hamburg (CASH).
Circulation 2000; 102:748–754.
3. Wellens HJJ. Electrical stimulation of the heart in the study and treatment
of tachycardias. Leiden: Kroese; 1971.
4. Jais P, Shah DC, Haissaguerre M, et al. Prospective randomized

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comparison of irrigated-tip versus conventional-tip catheters for ablation

of common flutter. Circulation 2000; 101:772–776.
5. Calkins H, Epstein A, Packer D, et al. Catheter ablation of ventricular

tachycardia in patients with structural heart disease using cooled
radiofrequency energy: results of a prospective multicenter study.
Cooled RF Multi Center Investigators Group. J Am Coll Cardiol 2000;
35:1905–1914.
6. Kimman GP, Theuns DA, Szili-Torok T, et al. CRAVT: a prospective

randomized study comparing transvenous cryothermal and radiofrequency
ablation in atrioventricular nodal re-entrant tachycardia. Eur Heart J 2004;
25:2232–2237.
7. Linhart M, Bellmann B, Mittmann-Braun E, et al. Comparison of

cryoablation and radiofrequency ablation of pulmonary veins in 40 patients
with paroxysmal atrial fibrillation: a case–control study. J Cardiovasc
Electrophysiol 2009; 20:1343–1348.
8. Schweikert RA, Saliba WI, Tomassoni G, et al. Percutaneous

pericardial instrumentation for endo-epicardial mapping of previously
failed ablations. Circulation 2003; 108:1329–1335.
9. Sosa E, Scanavacca M. Epicardial mapping and ablation techniques

to control ventricular tachycardia. J Cardiovasc Electrophysiol 2005;
16:449–452.
10. Hoyt H, Bhonsale A, Chilukuri K, et al. Complications arising from

catheter ablation of atrial fibrillation: temporal trends and predictors.
Heart Rhythm 2011; 8:1869–1874.
11. Sorgente A, Chierchia GB, de Asmundis C, et al. Europace.

Complications of atrial fibrillation ablation: when prevention is better
than cure 2011; 13:1526–1532.
12. Robbins IM, Colvin EV, Doyle TP, et al. Pulmonary vein stenosis after
catheter ablation of atrial fibrillation. Circulation 1998; 98:1769–1775.
13. Siegel MO, Parenti DM, Simon GL. Atrial-esophageal fistula after atrial
radiofrequency catheter ablation. Clin Infect Dis 2010; 51:73–76.
14. Doppalapudi H, Yamada T, Kay GN. Complications during catheter ablation

of atrial fibrillation: identification and prevention. Heart Rhythm 2009; 6 (12 Suppl):S18–S25.
15. Martinek M, Bencsik G, Aichinger J, et al. Esophageal damage during

radiofrequency ablation of atrial fibrillation: impact of energy settings, lesion
sets, and esophageal visualization. J Cardiovasc Electrophysiol 2009; 20:726–733.
16. Perzanowski C, Teplitsky L, Hranitzky P, et al. Real-time monitoring of luminal

esophageal temperature during left atrial radiofrequency catheter ablation for atrial
fibrillation: observations about esophageal heating during ablation at the pulmonary
vein ostia and posterior left atrium. J Cardiovasc Electrophysiol 2006; 17:166–170.
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Perioperative Management of Traumatic Brain Injury

Adult Head Injury: Are Guidelines Improving Outcome?
Audrée A. Bendo, M.D. Brooklyn, New York
Traumatic brain injury (TBI) is one of the most serious, life-threatening conditions in trauma victims. Prompt
and appropriate therapy is necessary to obtain a favorable outcome. Perioperative management of head-injured
patients focuses on aggressive stabilization of the patient and avoidance of systemic and intracranial insults that cause
secondary neuronal injury. Secondary brain injury complicates the course of the majority of head-injured patients,
adversely influencing outcome. These secondary insults are potentially preventable and treatable.
I. Epidemiology
An estimated 1.7 million people sustain TBIs every year in the United States. 1 Of these, over 50,000 people
die, and another 80,000 people become impaired or disabled for life. TBI is a leading cause of disability in the United
States, affecting approximately 5.3 million people.1 Head injury occurs most frequently in adolescents, young adults,
and people older than 75 years of age. In all age groups, males are affected two times more often than females and
are more likely to sustain severe head injury. The leading causes of TBIs are falls, motor vehicle crashes, and assaults. 1
From 2001 to 2010, the rates of TBI-related emergency department visits increased by 70%, hospitalization rates only
increased by 11% and death rates decreased by 7%.1
II. Head Injury Guidelines

In 1995, the Brain Trauma Foundation approved guidelines for the initial resuscitation of the severe head injury
patient and treatment of intracranial hypertension recognizing the need to standardize care to improve outcome in
head-injured patients.2 A task force was formed in 1998 to review and update the scientific evidence for the guidelines.
Evidence-based guidelines for the management of severe TBI were published in 2000 3 and updated in 2007.4 More
recently, the NICE Head Injury guidelines were updated in January 2014 in the UK. 5 These guidelines represent a
comprehensive review of the literature and provide the best treatment recommendations for the acute care management
of the hospitalized severe TBI patient. However, most of these guidelines are based on Class II or III evidence, and
therefore, are consensus-based recommendations.
Evidence-based guidelines for prehospital management of TBI6, pediatric brain injury7, and surgical
management8 have also been published. The TBI contributing authors have developed a 'Center for Guidelines
Management' which is responsible for generating new guidelines as well as updating existing guidelines. Their
mission is to improve outcome of TBI through collaboration and the promotion of evidence-based medicine.4
Current guidelines recommend that all regions establish organized trauma systems and protocols for
resuscitation. Resuscitation protocols from prehospital to critical care management have been developed and
instituted based on available information. This lecture will discuss the various guidelines and new research initiatives
to address whether or not implementation is improving outcome. The guidelines and controversies in management
will be discussed as we take a patient through the resuscitation protocol as described in Table 1.
Table 1: Severe head Injury (GCS 8 or less) Resuscitation Protocol

Prehospital Management and ER ATLS Evaluation
- emergency diagnostic or therapeutic procedures as indicated
- prioritizes CABs (circulation, airway, breathing), assessment and treatment
Endotracheal Intubation: Ventilation (PaCO2 35 - 40 mmHg); Oxygenation (SaO2 ˃ 90%)

Fluid Resuscitation/Hemodynamics: Maintenance of SBP ˃ 90 mm Hg
Herniation? Deterioration? Rx: ± hyperventilation; Mannitol (0.25-1 g/kg IV)
CT Scan: Surgical lesion → O.R.

Neuro ICU:
- ICP and/or other multimodality monitors
- ICP/CPP management
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from the authors/copyright holders.
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- Individualized assessment/multi-targeted approach
III. Prehospital Management

The “prehospital guidelines” are accepted as the standard by prehospital and emergency department clinicians.6
even though; there was insufficient data to support any Level I recommendations for prehospital assessment, treatment,
transport, and destination. Therefore, after the guidelines and recommendations were published and implemented,
several studies were performed to determine whether or not outcome was improved by following these guidelines. 9,
10, 11, 12, 13
The studies support the direct transfer of patients with severe TBI to a Level I or II trauma center, but
controversy remains regarding whether patient outcome is improved by paramedic intubations in the field and mode
of transport.13, 14, 15, 16, 17, 18, 19, 20, 21
IV. Preanesthetic Assessment and Stabilization

Preanesthetic assessment of the head-injured patient includes: airway (cervical spine), breathing (ventilation
and oxygenation), circulatory status, associated injuries, neurological status (Glasgow Coma Scale), preexisting
chronic illness, and circumstances of the injury (time of injury, duration of unconsciousness, associated alcohol or
drug use).
Secondary insults complicate the course of more than 50% of head-injured patients. An outcome study using
data from the Traumatic Coma Data Bank revealed that hypotension after head injury is associated with greater than
70% of patients experiencing significant morbidity and mortality. 3, 22, 23 The combination of hypoxia and hypotension
is significantly more detrimental (> 90% of patients with severe outcome or death). We know that hyperglycemia and
hypoglycemia can be detrimental to neurosurgical patients. However, currently there is insufficient evidence to
support the routine use of tight glycemic control (target BG 80–110 mg/dL) in the operating room or the ICU. 24, 25
The optimal blood glucose level for patients with damaged or injured brain is unknown.
Emergency Therapy. The first step is to secure an open airway and ensure adequate ventilation to prevent
secondary injury from hypoxia and hypercarbia. 26 When a cervical spine fracture has not been excluded by
radiographic evaluation, cervical alignment with manual in-line stabilization (MILS) is recommended during
emergent intubations.27 (Please note that a cadaver study suggests that MILS does not limit movement across a
complete C4-5 fracture dislocation with ligamentous injury). If facial fractures and soft tissue edema prevent direct
visualization of the larynx, a fiberoptic intubation or intubation with other airway imaging devices may be attempted.
In the presence of severe facial and/or laryngeal injuries, a cricothyrotomy may be required. Nasal intubations are
avoided in the presence of a suspected basal skull fracture, severe facial fractures, and bleeding diathesis.
Following control of the airway in the head-injured patient, attention should focus on resuscitation of the
cardiovascular system. A major concern during fluid resuscitation is the development of cerebral edema. Based on
animal research, it appears that the best way to avoid cerebral edema after fluid resuscitation in the injured brain is to
maintain normal serum osmolality and colloid oncotic pressure. Therefore, circulating blood volume should be
restored to normovolemia with glucose-free isotonic crystalloids and colloid solutions. Glucose-containing solutions
are avoided to enhance perioperative glycemic control. Hypertonic saline (HTS) has been proposed as an alternative
to normal saline (NS) for fluid resuscitation in patients with hemorrhagic shock and TBI. Controversy continues
regarding the selection of the best resuscitation fluids for patients with severe TBI. 28, 29, 30, 31, 32, 33
A full ATLS trauma evaluation is on-going as therapeutic interventions to control intracranial hypertension are
instituted. The head is elevated to 150 and maintained in a neutral position. Mannitol (0.25 to 1 g/kg) is administered
to acutely lower ICP.34, 35 Although mannitol is considered the mainstay of hyperosmolar therapy, HTS has gained
acceptance as an alternative agent for controlling intracranial hypertension. Neither mannitol or HTS solutions have
been associated with improved outcomes.36, 37, 38, 39, 40, 41, 42 After tracheal intubation, the patient is given a muscle
relaxant and mechanically ventilated to a PaCO2 of 35-40 mmHg. Hyperventilation to a PaCO2 of less than 35 mm
Hg is avoided unless transtentorial herniation is suspected.43, 44, 45, 46
V. Intraoperative Management
Anesthetic Management. In some patients, severe intracranial hypertension precipitates reflex arterial
hypertension and bradycardia (Cushing’s triad). A reduction in systemic blood pressure in these patients can further
aggravate cerebral ischemia by reducing cerebral perfusion pressure (CPP = MAP - ICP). CPP should be maintained
between 50 and 70 mm Hg.47, 48, 49, 50, 51 CPP less than 50 mm Hg should be avoided. The choice of anesthetic agents
depends on the condition of the patient. In general, drugs and techniques that reduce intracranial pressure are selected
and the overall management goal is to maintain cerebral perfusion and homeostasis. 52, 53, 54, 55, 56 Intraoperative
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hypotension secondary to blood loss or precipitated by anesthetic drugs must be avoided by appropriate volume
expansion.51 Maintenance of ventilation (PaC02 > 35- 40 mm Hg) and oxygenation (Pa02 > 60 mm Hg) is extremely
important.
VI. Postoperative Care/Critical Care.

In the critical care unit (CCU), the main objectives are to enhance recovery from primary brain injury and
prevent secondary injury.57 This requires provision of optimal systemic support for cerebral energy metabolism and
adequate CPP, and normalizing of ICP for the injured brain. Prompt recognition and treatment of systemic
complications that contribute to secondary injury are essential to head injury management. To achieve this,
multimodality systemic and cerebral monitoring should be instituted. 58, 59, 60 Monitoring of ICP, CPP and CBF should
be standard practice. In addition, monitors of cerebral oxygenation e.g. jugular bulb oximetry, partial pressure of brain
tissue oxygen (Pbt02), and brain metabolism, have been shown to provide more specific information for managing
cerebral hypoxia and ischemia. However, technology has lagged behind in the development of safe, reliable, and
continuous cerebral monitors for detecting ischemia.
There is controversy concerning the best management protocol for optimal recovery in TBI patients. 4, 60, 61, 62, 63
A management protocol that uses individualized assessment and a multi-targeted approach to institute therapy and
reduce the risk of iatrogenic injuries has gained acceptance.
VII. Summary
The major goal of perioperative management of TBI patients is to prevent secondary damage. Therapeutic
measures based on established guidelines and recommendations must be instituted promptly throughout the
perioperative course.64, 65, 66, 67, 68 Recent investigations have shown that not all of the recommended guidelines
improve outcome, and more randomized, controlled trials are necessary to clearly address unresolved clinical
guidelines.69 Another challenge for improving metropolitan and regional care of these vulnerable patients is the
development of systems and protocols that provide consistent application of the guidelines. There is no doubt that an
aggressive approach to managing head-injured patients can reduce mortality, but we must also improve functional
status among survivors. Therefore, future studies must focus on all aspects of perioperative care including
rehabilitation to reduce disability in survivors.
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65. Gerber, LM, Chiu Y-L, Carney N, et al. Marked reduction in mortality in patients with severe traumatic brain
injury. J Neurosurg 2013; 119:1583-1590.
66. Shafi S, Barnes SA, Miller D. Suboptimal compliance with evidence-based guidelines in patients with traumatic
brain injuries. J Neurosurg 2014; 120(3): 773-777.
67. Lee JC, Rittenhouse K, Bupp K, et al. An analysis of Brain Trauma Foundation traumatic brain injury guideline
compliance and patient outcome. Injury 2014; 46:854-858.
68. Faul M, Wald MM, Rutland-Brown W, et al. Using a cost-benefit analysis to estimate outcomes of a clinical
treatment guideline: Testing the Brain Trauma Foundation guidelines for the treatment of severe traumatic brain
injury. J Trauma 2007; 63(6): 1271-1278.
69. Warner DS, James ML, Laskowitz DT, Wijdicks EF. Translational Research in Acute Central Nervous System
Injury Lessons Learned and the Future. JAMA Neurology 2014; 71(10): 1311-1318.
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ICU Management of CNS Trauma

Arthur M. Lam M.D. Seattle, WA
Introduction
Traumatic brain injury (TBI) is an acquired insult to the brain tissue due to an external blunt or penetrating
mechanical force which may evolve into transient or long term impairment of cognitive, physical, and psychosocial
functions. In addition, TBI is often accompanied by other extracranial injuries. This refresher course will focus on
the neurocritical care aspect of patients with severe TBI, including multimodality monitoring, fluid management,
hypothermia, surgical treatment, and pharmacotherapy. In recent years it has been shown that the best outcome is
obtained from dedicated units (NCCU) staffed by specialty-trained neurointensivists.
Incidence
Incidence of head injury is increasing. Centers for Disease Control and Prevention (CDC) estimated that
traumatic brain injury (TBI) accounted for approximately 2.5 million emergency department (ED) visits. From these
presentations, approximately 87% (2,213,826) patients were treated in and released from EDs, another 11%
(283,630) were hospitalized and discharged, and approximately 2% (52,844) died. 1,2
Falls are the leading causes of non-fatal TBI (35%), followed by motor vehicle-related injuries (17%), and
strikes or blows to the head from or against an object (including sports related) (17%). Overall, motor-vehicle traffic
incidents constitute the most common cause of TBI related deaths, followed by self-inflicted/suicide, and falls.3
TBI is the commonest cause of death and disability amongst people under the age of 40. Improved
understanding of the disease process and technological advancements has reduced the TBI mortality by 8.2% in the
last decade.
Primary Injury and Secondary Injury
Damage to neural tissue directly related to the initial impact of trauma is considered the primary
injury and includes cerebral contusion, diffuse axonal injury, hemorrhage into the epidural or subdural space,
and intraparenchymal hemorrhage. Secondary injury is any insult to the brain occurring after the initial TBI
that causes further neuronal damage. Although cerebral ischemia or hypoxia is the ultimate cause of
secondary brain injury after TBI,4 systemic or local insults often contribute to such injury. Among these the
most important ones are elevated intracranial pressure (ICP), systemic hypotension, and hypoxemia. Others
include pyrexia, coagulopathy, hyperglycemia, and systemic infection.
Neuronal death is likely mediated by complex biochemical processes involving the release of
excitatory amino acids (e.g., glutamate) and the cellular influx of calcium. Actual cell death may be necrotic or
apoptotic in nature. Preventing or reducing secondary brain injury is the focus of most medical management
of TBI in both the operating room (for some patients)5, and subsequently in the neurocritical care unit
(NCCU).
PRIMARY TRAUMATIC BRAIN INJURY
Severity of TBI is commonly assessed by the Glasgow Coma Scale (GCS) (Table 1). A score of 8 or less
indicates severe TBI. However, severe TBI is a heterogeneous disease, and patients with differrent pathophysiologic
mechanisms can manifest with the same GCS score.
Along with the GCS, a careful history and physcial examination should be conducted to rule out other
concomitant systemic injuries.
Computed Tomography Findings
Cranial computed tomography (CT) is standard initial radiologic investigation for severe TBI. The Marshall
classification is commonly used to grade severe TBI. (Table 2). In addition, CT findings consistent with a
significantly elevated ICP include the following:
 Mass lesion greater than 25 mL
 Midline shift of 5 mm or more
 Compression of the basal cisterns or lateral ventricles
 Medial displacement of the uncus
SECONDARY BRAIN INJURY
Secondary brain injury can be due to systemic or cerebral factors (Table 3). Among these, hypoxemia and
hypotension are most likely to have an adverse impact on TBI outcome. Guidelines have been issed by the Brain
Trauma Foundation to standardize and improve the treatment of patients with TBI. 6 Most of the Guidelines,
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however, lack robust scientific basis, and by their very nature, do not take into account the heterogeneity of the
disease. Ultimately, the goal to prevent secondary injury is to optimize the physiologic enviroment to allow
maximal recovery. Increasingly, multimodality monitoring is used in the NCCU with the attempt to individualize
therapy within the broad guidelines.7,8
Cerebral Perfusion and Oxygenation Monitors
Intracranial Pressure Monitor (ICP): Either a fiberoptic intraparenchymal probe, or an intraventricular catheter can
be used to monitor ICP, and is indicated in all patients in coma with an abnormal admission head CT scan. The
relationship between elevated ICP and mortality is well established, and elevated ICP refractory to treatment is
frequently associated with death. With continous intra-arterial pressure monitor, CPP (MAP-ICP) can be
continuously displayed, and allow optimal management of brain perfusion pressure. Although the most recent
clinical trial (BEST:TRIP) suggests vigilant clinical management based on imaging can achieve similar results as
ICP based management9, the trial is not a stuy of ICP monitoring or its efficacy in management of TBI. For now
ICP monitoring and management of elevated ICP remains the mainstay of treatment, allowing judicious clinical
decisions based on instant feedback.
Jugular venous oximetry: A jugular venous bulb oximetric catheter (JBC) continuously measures brain venous
oxygen saturation (SjvO2), and provides an estimate of the balance between oxygen supply and demand. Low
brain perfusion increases oxygen extraction, causing a drop in SjvO2, while nonfunctioning brain extracts little
oxygen resulting in high SjvO2 values. SjvO2 less than 55% or greater than 75% is associated with a poor
prognosis. JBC lactate concentrations may also reveal anaerobic brain metabolism. A limitation of JBC is that it
monitors only global CBF-CMR balance. Despite initial enthusiasm, this has been largely superseded by brain
tissue oxygen tension sensors.10
Brain tissue oxygen tension (PbrO2): PbrO2 provides a continuous measurement of brain parenchymal oxygen
tension.11 This reflects the balance between local brain supply and demand for oxygen. The normal P brO2 is in
the range of 23-35 mm Hg. A PbtO2 threshold of less than 20 mmHg represents compromised brain oxygen and is
the threshold at which to consider intervention. The BOOST II trial showed that the addition of PbrO2 to existing
ICP/CPP guided management had statistically significant decrease in duration and severity of brain hypoxia along
with a 10% reduction in mortality and a trend toward reduced mortality and improved neurologic outcome at 6
months.12 The final results have not been published. This is an invasive monitor, and for it to be optimally
effective, it should be placed in the brain tissue most at risk, i.e. the ischemic penumbra, a feat that is seldom
accomplished. Instead it is often placed in the frontal region, in combination with the ICP monitor.
Near-infrared spectroscopy (NIRS): NIRS is based on reflectance spectroscopy; it measures the light reflected from
chromophobes in the brain (hemoglobin) to derive the regional oxygen saturation. It provides an information on the
balance between flow and metabolism. It is generally accepted that normal range varies between 60% and 75%, with
a coefficient of variation of almost 10%. Extracranial contamination of light reflection is a potential source of
artefact. A newer type of sensor using both NIRS and ultrasound appears more promising, but more data is needed. 13
Transcranial Doppler ultrasonography (TCD): TCD allows estimation of cerebrovascular resistance, displaying
increased pulsatility with elevated ICP and can be a confirmatory test for intracranial circulatory arrest. Recent
studies suggest that continuous monitoring of flow velocity with TCD may allow optimal blood pressure
management by determining the BP where cerebral autoregulation is most robust. 14 Alternatively, the optimal
cerebral perfusion pressure can be determined by monitoring the pressure-reactivity index in patients with ICP
monitor.15
Microdialysis: Microdialysis catheters are placed in brain parenchyma, where they continuously perfuse the
brain with a perfusate and sample small volumes of fluid (the dialysate), which is tested for lactate and
pyruvate, glutamate, glucose, and glycerol concentration. Lactate to pyruvate ratios (LPR) greater than 40
suggest insufficient cerebral oxygen delivery, inadequate glucose supply or underlying neuronal mitochondrial
dysfunction. However, at least one hour long lag time is needed to analyze samples, which hinders real-time
clinical decision making. It remains essentially a research tool at the present time.
Risk Assessment and Management Strategies:
Hypoxemia and Hypercapnia: TBI patients are at increased risk for airway obstruction and hypoventilation. These
lead to hypoxemia and hypercapnia, which cause cerebral vasodilatation[AD1], and may aggravate ICP.
Elevated Intracranial Pressure: An acute mass lesion increases ICP and reduces CPP. In addition, increased ICP can
lead to brain herniation.
Systemic Hypotension and Hypovolemia: Adults usually do not become hypovolemic and hypotensive as a result of
blood loss from TBI alone. In contrast, small children can lose enough blood with TBI to become hypotensive.
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Other injuries (e.g., splenic rupture, large bone fractures) can make TBI patients hypotensive and further
compromise CPP in those with increased ICP.16 Compensatory hypertension and bradycardia (Cushing’s reflex)
with elevated ICP may further complicate the clinical picture. 17 Thus, in patients with TBI, normotension and
tachycardia can still be compatible with severe hypovolemia, with the latter “concealed” by increased systemic
vascular resistance (Cushing’s reflex). Thus, careful volume assessment of the patient with TBI is essential, and
echocardiographic assessment may be indicated, particularly in view of the rare occurrence of stress cardiomyopathy
in some patients.18 Of all the factors associated with secondary brain injury, systemic hypotension is likely the most
significant. With impaired cerebral autoregulation, this invariably leads to reduced CPP. Patients with intact
autoregulation but reduced intracranial compliance are also at risk for impaired CPP with hypotension. Reduced
MAP dilates cerebral vasculature to increase cerebral blood volume and ICP. This increase in ICP further
compromises CPP, leading to further compensatory cerebral vasodilatation.
Impaired Cerebral Autoregulation: Cerebral autoregulation is a homeostatic mechanism that maintains near-constant
perfusion of the brain over a wide range of MAPs. In normal adults, this range is 60 to 160 mm Hg. Autoregulation
may be impaired in patients with TBI, and although the frequency of impaired autoregulation is higher in patients
with severe TBI, it is clinically impossible to predict which patients will be affected. Even minor TBI may impair
autoregulation.19,20 If so, CBF becomes directly proportional to blood pressure. Loss of cerebral autoregulation is
associated with worse outcomes with TBI.
Coagulopathy: Severe TBI liberates enough thromboplastin from damaged neurons to cause coagulopathies, which
may be mild to severe. They can increase surgical morbidity and mortality, can preclude or delay extracranial
surgical procedures, and are associated with poorer outcomes.
Pyrexia: Fever raises the CMR, increasing the risk for ischemia and neural injury, especially when cerebral
perfusion is marginal. Cerebral blood volume increases with pyrexia owing to flow-metabolism coupling,
exacerbating any ICH. Although human studies do not conclusively link body temperature to outcome in TBI, both
animal and human studies have linked brain infarct size and fever in ischemic brain injury.
Hyperglycemia: Hyperglycemia in TBI and stroke is associated with a poor prognosis 21, although a cause-effect
relationship has not been clearly established. In experimental cerebral ischemia, detrimental effects of
hyperglycemia have consistently been shown. However tight glucose control may lead to inadvertent hypoglycemia.
In addition, some experimental studies have suggested some regions may develop hyperglycolysis after brain
trauma, thus it is prudent to maintain gluocse between 120 - 180 mg%.
Fluid and Electrolyte Abnormalities: Acute fluid and electrolyte disturbances occur in TBI patients, often due to
inappropriate fluid administration. They can also be caused by diabetes insipidus. As water movement is primarily
determined by the osmotic gradient, hyponatremia and excessive free water will worsen cerebral edema, thereby
increasing ICP.22 Isotonic fluid should be used for volume replacement23, and colloids including albumin should be
avoided.24 Blood transfusion threshold remains controversial, but based on a recent randomized controlled trial, a
restricted approach is generally preferred.25,26 Commonly used fluids are listed in Table 4.
Associated Extracranial Injuries: As many as 10% of patients with TBIs also have spine injuries.16 Spinal evaluation
is often delayed if the patient requires emergent neurosurgical intervention (e.g., evacuation of epidural or subdural
hematoma). For this reason, spine precautions should be taken when moving or positioning patients before the
completion of a spine injury workup. TBI patients may also have undiagnosed extremity injuries.
MANAGEMENT GUIDELINES
Ph 7.35-7.45 SBP 100 -180 mmHg Glucose 120-180 mg%

PaO2 100 - 300 ICP < 20 mmHg Hemoglobin > 7 g/dl
PaCO2 35-45 mmHg CPP 60-70 mmHg Platelets > 75 x 103/mm3
Temperature 36 – 38 oC SvO2 50 – 75 mmHg INR < 1.4
PbtO2 > 15 mmHg Sodium 135 -145 mmol/L
Maintain Adequate Cerebral Perfusion Pressure

The updated Brain Trauma Foundation guidelines (2007) advise keeping CPP between 50 and 60 mm Hg.
The goal should be to maintain normovolemia.6
Vasopressors and inotropes may be required along with fluid resuscitation to maintain CPP. However, they
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should be used with caution, because they may increase the risk for acute respiratory distress syndrome. With ICP
monitor, the systolic BP should not be < 90 mmHg. The choice of vasopressors on outcome has not been studied.
One recent study in immature swine suggests that phenylephrine may be preferable to norepinephrine. 27
As ischemia is likely the final pathway in secondary brain injury, it is common practice to keep
hematocrit at 30% to provide adequate oxygen delivery. However, recent studies, similar to other studies in
critically ill patients, suggest that a restrictive approach is prefererable to a more conservative approach. 25,26
Aggressive Treatment of Intracranial Pressure

Intracranial hypertension is defined as a sustained (>5 min) elevation of ICP above 20 mmHg (although
this threshold has been debated and remains unproven). To optimize CPP, one must try to maintain ICP< 20 mm Hg
while maintaining CPP in the 50 to 60 mm Hg range. ICP monitor is required in patients with severe TBI who are
comatose after resuscitation (GCS <9) and have either abnormalities on cranial CT scan or meet at least two of the
following three criteria: age >40 years; systolic blood pressure <90 mmHg; or abnormal posturing. Recent
international multidisciplinary consensus conference recommended that ICP and CPP should be monitored in
patients at risk for ICP elevation based on clinical and/or imaging features to guide medical and surgical
interventions.
Osmotic Therapy: Mannitol (0.25 to 1 g/kg) is useful for reducing brain bulk and may decrease the production of
cerebrospinal fluid. Mannitol is given after volume repletion. Hypertonic Saline (HTS) (2%, 3% or 7.5% by
infusion, or bolus of 23.4%) appears to result in less rebound edema, longer lasting effect, and fewer systemic side
effects,28 although it did not show to decrease mortality or improve ICP compared to other solutions in the recent
meta analysis.29 A central line is generally required for HTS concentrations in excess of 2%.
Hyperventilation: Cerebral blood volume can be reduced with acute hyperventilation, and CBF decreases by about
3% for each 1 mm Hg decline in arterial carbon dioxide tension. There is the potential for cerebral ischemia with
excessive hyperventilation.29 Arterial carbon dioxide tension should not be decreased to less than 30 mm Hg, except
for brief periods (e.g., impending herniation). Otherwise, normocapnia or slight hypocapnia (35 to 40 mm Hg) is
desirable. Other important techniques to reduce ICP are slight head-up and neutral neck positions to promote
venous drainage and prevent venous obstruction, an often overlooked cause of elevated ICP.
Metabolic Coma: Barbiturates or propofol given to suppress CMR can reduce ICP. Effects are maximal with
electroencephalogram burst suppression or an isoelectric electroencephalogram. Vasopressors may be
required to support blood pressure. Low-dose propofol is often used in TBI, because it allows effective ICP
control while permitting prompt neurologic evaluation. However, metabolic syndromes characterized by
myocardial dysfunction and lactic acidosis have been observed after prolonged propofol infusion, especially
in children, and prolonged administration must be monitored and/or avoided. 31
CSF drainage: External ventricular drainage of cerebrospinal fluid (EVD) can reduce ICP if the ventricles are
not too compressed to prevent insertion. Lumbar spinal drainage catheter has also been reported with
success but the inherent risk of brainstem herniation is ever present with this technique, and therefore not
advocated.
Hypothermia: Mild to moderate hypothermia (330 C) has been extensively investigated both as a
neuroprotective technique32 as well as treatment for elevated ICP. While positve results for the former
indication continue to elude us,33,34 its efficacy for the latter indication is well established. For this to be
effective, shivering must be treated vigorously, and ICP must be monitored closely during the rewarming
phase. Given the negative results from multiple clinical trials, hypothermia should only be used to control ICP
when all other methods have failed, and the patient is not considered a candidate for decompressive
craniectomy.
Decompressive craniectomy (DC): This should be considered in patients whose ICP elevation is refractory to
medical management. This can be primary (bone flap removal during evacuation of intracranial hematoma)
or secondary (subsequent removal because of sustained elevated ICP). DC remains controversial as improved
survival is attained at the expense of increased proportions of patients with severe disability and poor quality
of life.35,36 Both primary and secondary DC are subjects of ongoing clinical trials.37
Maintain Normoxia
While hyperbaric oxygen has been shown to be of some benefits in severe TBI, the use of normobaric
hyperoxia is controversial. There is no debate on the need to maintain adequate oxygenation, but in several
studies normobaric hyperoxia has been shown to have negative effects on outcome. 38 Many patients with TBI
may develop aspiration pneumonia, and some will develop acute respiratory distress syndrome from the
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excessive use of fluids and pressors, and oxgyen administration should be titrated to maintain normoxia.
Many intensivists advocate early intubation to protect airway and provide adequate gas exchange. Similarly,
early tracheostomy has been suggested by some to decrease mortality, but solid data is lacking. 40
Correct Coagulopathy
Acute coagulopathy of trauma and TBI associated coagulopathy are both well recognized phenomena and
result in significant coagulation dysfunction. Consumption coagulopathy and endogenious fibrinolysis apperars to
play role in the develoment of acute coagulopathy of trauma. In TBI large quantities of brain tissue thromboplastin
is released into the blood stream, causing disturbance in coagulation processes. In addition, damaged cerebral
endothelium activates platelets as well as clotting cascades to produce intravascular thrombosis and depletion of
coagulation factors. Coagulopathies increase the morbidity associated with any surgery in TBI patients. Coagulation
should be followed closely, and any deficient factors should be replaced aggressively. Recent meta-analysis based
on two tranexamic acid (TXA) trials demonstrataed statistically significant reduction in intracranial hemorrhage
progression secondary to TBI, but no statistically significant improvement in clinical outcomes. 41 International,
multi-center, phase III trial (CRASH-3) currently undergoing to evaluate the use of TXA on death and disability in
10,000 patients with TBI.
Transfuse to Threshold?
Anemia is common in the acute period after TBI, affecting up to 50% of patients. As ischemia is likely the
final pathway in secondary brain injury, it has been common practice to keep hematocrit at 30% to provide
adequate oxygen delivery. However, recent studies, similar to other studies in critically ill patients, suggest
that a restrictive approach is prefererable to a more conservative approach. Currently available evidence
supports a hemoglobin threshold level of 7 to 8 g/dL. Targeting Hb levels >10 g/dl after TBI is associated with an
increased risk of thromboembolic events and progressive hemorhagic injury, and without positive effects on
neurologic outcome. Furthermore, a clinical trial on erythropoietin fails to demonstrate any neuroprotective
value despite experimental evidence to the contrary.25
Treat Hyperglycemia
Dextrose-containing intravenous solutions are avoided during fluid resuscitation. They may cause
hyperglycemia and worsen cerebral ischemic injury. Current guidelines advise keeping blood glucose at 120 to 180
mg/dL.
Restore Normothermia
Clearly, hyperthermia is harmful to patients at risk for ischemic brain injury. Any beneficial effects of
hypothermia are less clear. Hypothermia also increases the risk of infection, and cooling patients to less than 35 oC
may lower PbrO2 owing to a leftward shift of the hemoglobin-oxygen dissociation curve. Given the inconclusive
evidence for hypothermia, we advise keeping temperature in a low-normal range (35ºC to 36ºC), unless indicated for
control of elevated ICP.
Treat Seizures
Seizure can occur in 20-40% of patients after TBI, and should be treated vigorously with antiepileptic drugs
(AED). The use of prophylactic AED is less clear, but it is common practice to treat patients for 7 days after TBI. In
addition, non-convulsive status epilepticus (NCSE) can occur, and patients without apparent cause of coma should
be monitored with continuous EEG for 48 hours. 42
Other Adjuncts:
Beta-Blockers
A recent review and meta-analysis suggests that beta blocker treatment following TBI is beneficial, 43 as
sympathetic overstimulation may have a nonspecific detrimental effect on organ functions. However, this needs to
be studied with a randomized controlled trial.
Steroids and progesterone
Despite positive results in experimental TBI, these drugs have proved to have no value in large multi-center
randomized clinical trials and should not be used.
Future Directions
The failure of multiple clinical trials of promising therapy may be disappointing, but the investigators have
learned from these studies, which help with directions of future studies as well organization of multicenter trials.
This has taken the form of different approaches: 1) Preclinical trials – A consortium of investigators have formed the
Operation Brain Trauma Therapy (OBTT) to systematically study different therapy in the most relevant animal
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model before moving to clinical trials.45 2) In the clinical arena, NIH has pioneered the introduction of Common
Data Elements, facilitating data collection and comparison46, and 3) The Europeans have formed the Collaborate
European NeuroTrauma Effective Research in Traumatic Brain Injury (CENTER_TBI) 47 to allow longitudinal
observational study in multiple center, essentially a running registry of all patients with TBI. These are exciting
steps that would help advance our knowledge of the pathophysiology of TBI, and in turns, its optimal treatment.
Summary:
There is no magic bullet for the treatment of severe TBI, as illustrated by the failures of multiple clinical trials of
promising therapy. It is important to recognize that TBI is a heterogenous disease with varying pathology, both
anatomically and physiologiclly. Within the frame work of published Guidelines, one must strive to optimize
individual therapy, which may require multi-modal monitoring with different physiologic targets.
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40. Baron DM, Hochrieser H, Metnitz, PGH, et al. Tracheostomy is associated with decreased hosptialmortality after
moderate or severe isolated traumatic brain injury. Wien Klin Wochenschr DOI 10.1007/s00508-016-1004-y, 2016.
41. Zehtabchi S, Abdel Baki SG, Falzon L, Nishijima DK. Tranexamic acid for traumatic brain injury: a systematic review
and meta-analysis. Am J Emerg Med 32:1503–9, 2014.
42. Ronne-Engstrom E, Winkler T. Continuous EEG monitoring in patients with traumatic brain injury reveals a high
incidence of epileptiform activity. Acta Neurol Scand 114: 47-52, 2006.
43. Alali AS, McCredie VA, Golan E, et al. Beta blockers for acute traumatic brain injury: a systematic review and meta-
analysis. Neurocrit Care 20: 514-523, 2014.
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44. Wright DW, Yeatts SD, Silbergleit R, et al. Very early administration of progesterone for acute traumatic brain injury.
E Engl J Med 371: 2457-66, 2014.
45. Kochanek PM, Bramlett HM, Shear Da, et al. Synthesis of findings, current investigations, and future directions:
Operation Brain Trauma Therapy. J Neurotrauma 33: 606-14, 2016.
46. Hicks R, Giacino J, Harrison-Felix, et al. Progress in developing common data elements for traumatic brain injury
research: Version two – the end of the beginning. J Neurotrauma 30: 1852-61, 2013.
47. Mass AIR, Menon DK, Steyerberg EW, et al. Collaborative European neurotrauma effective research in traumatic brain
injury (CENTER-TBI): a prospective longitudinal observational study. Neurosurgery 76: 67-80, 2015.
Table 1. Glasgow Coma Scale Score
Eye Opening Verbal Response Motor Response

Spontaneous 4 Oriented 5 Obeys commands 6
To speech 3 Confused 4 Localizes to pain 5
To pain 2 Inappropriate 3 Withdraws to pain 4
None 1 Incomprehensible 2 Flexes to pain 3
None 1 Extends to pain 2
None 1
Table 2. Marshall classification of CT abnormalities in brain trauma
Diffuse injury I (no visible No visible intracranial pathology seen on CT scan

pathology)
Diffuse injury II Cisterns are present with midline shift of 0-5 mm and/or lesions densities
present; no high or mixed density lesion >25 cm3 , may include bone
fragments and foreign bodies
Diffuse injury III (swelling) Cisterns compressed or absent with midline shift of 0-5 mm; no high or
mixed density lesion >25 cm3
Diffuse injury IV (shift) Midline shift >5 mm; no high or mixed density lesion >25 cm3
Evacuated mass lesion Any lesion surgically evacuated
Non-evacuated mass lesion High or mixed density lesion >25 cm3; not surgically evacuated
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Table 3. Risk Factors for Secondary Brain Injury
Cerebral Factors Systemic Factors

Increased ICP Hypotension
Expanding mass lesions Hypoxemia
Hypercapnia Anemia
Hypoxemia Hypovolemia
Venous obstruction (cervical collar, poor positioning) Hyperglycemia
Systemic hypotension (compensatory cerebral vasodilatation) Hyponatremia
Excessive hyperventilation Hypo-osmolar state
Post-traumatic vasospasm (patient with traumatic subarachnoid hemorrhage) Coagulopathy
Seizures Fever
Table 4. Intravenous Fluids

Fluids Osmolality Oncotic Na+ Cl- K+ Ca2+/Mg2+ Glucose
(mOsm/kg) Pressure (mEq/L) (mEq/L) (mEq/L) (mEq/L) (g/L)
(mm
Hg)
Plasma 289 21 141 103 4-5 5/2
Crystalloid
0.9% NS 308 0 154 154
0.45% S 154 0 77 77
3% HTS 1027 0 515 515
7.5% HTS 2400 0 1200 1200
23.4% HTS 8008
LR 273 0 130 109 4 3/0
D5LR 527 0 130 109 4 3/0 50
D5W* 252 0 50
D5 NS* 586 0 154 154 50
D50.45% S* 406 0 77 77 50
Normosol/Plasmalyte 295 0 140 98 5 0/3
Mannitol (20%) 1098 0
Colloid
Hetastarch (6%) 310 31 154 154
Albumin (5%) 290 19
Plasmanate 270-300 ? 145 100 0.25
*The osmolality of these dextrose solutions decreases as glucose enters the cells.
D5W, 5% dextrose in water; LR, lactated Ringer’s; NS, normal saline. S, saline, HTS, hypertonic saline
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Acute Spinal Cord Injury
Michael M. Todd MD Minneapolis, Minnesota
CNS Trauma: ER to OR to ICU

Note: The material here is largely a condensed and revised version of the paper by Rogers WK and Todd MM,
Acute Spinal Injury, Best Practice and Research Clinical Anesthesia (2016) 30: 27-39, with written permission of
the authors, the Editor-in-Chief of the Journal (Hugo van Aken MD) and the publisher (Ian Salusbury, Elsevier UK).
For additional detailed information and references, readers are referred to the original article.
Introduction
While the incidence of traumatic spinal cord injury (SCI) varies from country to country, a large fraction of
such patients require surgery in the acute phase of their injury, either to manage other injuries or to decompressor
stabilize the spine. As a result, anesthesiologists must have a general familiarity with the issues involved in their
care.
Injuries
Acute SCI is most commonly traumatic, and typically occurs in the young (50 years). On occasion other
disorders e.g. rheumatoid arthritis may play some role. Injuries may involve either fractures and/or ligamentous
injuries; the most common location for fracture in the cervical spine is the C1-C2 region (e.g. odontoid fractures)
while ligamentous injury with or without fracture is most common at C5-7. On occasion, extreme flexion-extension
may result in acute intervertebral disc rupture/herniation even without other injuries. Complete cord transection
may occur – but less complete injuries are much more common.
Treatment
While an SCI cannot be directly “treated”, therapeutic efforts are directed at stabilizing the spine,
decompressing the spinal cord, avoiding secondary insults to the cord (e.g. hypotension), minimizing injury
extension (e.g. due to edema) and providing general patient support.
Surgery
There is a general consensus (although not supported by rigorous randomized trials) that decompressive
surgery within 24hrs of injury may improve outcomes. In the face of instability, fusion can aid in restoring normal
spine alignment and can facilitate nursing care and mobilization.
Blood Pressure
Hypotension is common in acute SCI. It may result from concomitant injuries and blood loss, or may be
related to changes in venous and arterial tone associated with alterations in sympathetic nervous system function.
Cardiac output may be compromised due to venodilation (particularly in the splanchnic bed), while arterial
vasodilation (typically associated with relatively high injuries) can contribute to hypotension. Bradycardia
(typically with high cervical injuries) due to loss of cardiac accelerator fibers may also play a role.
There is substantial laboratory and good circumstantial clinical data suggesting that uncorrected hypotension
can worsen neurologic outcomes. Current guidelines recommend maintaining a mean arterial blood pressure
(MAP) >85-90 mmHg for at least the first week after an acute SCI, although the evidence for a specific MAP (80
vs 85 vs 90 or greater) is weak. The approach to correcting such hypotension is similar to that used in routine
clinical anesthesia. Initial intrascular volume expansion may, on occasion, be sufficient – but a very high fraction
of patients, particularly those with complete or high cervical injuries will require vasopressors or inotropes. At
present there is no evidence to support the use of any specific pressor; clinicians are advised to tailor their choice
based on experience and specific patient hemodynamics. For example, drugs such as norepinephrine, epinephrine
or dopamine may be preferable in bradycardic patients. It is important to realize that such agents may be required
for prolonged periods of times e.g. 5-7 days, since even delayed hypotension may be deleterious.
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Pharmacologic interventions (taken directly from Rogers & Todd)

Five different drugs - methylprednisolone, GM-1 ganglioside, naloxone, thyrotropin-releasing hormone, and
tirilazad (a steroid derivative with greater antioxidant properties than methylprednisolone) - have been studied in
randomized, controlled trials on humans for the medical treatment of acute SCI, and other agents have been
evaluated in preclinical experiments. Although the use of methylprednisolone continues to have some proponents,
none of these agents are broadly recommended for use. Since only methylprednisolone remains in (? sporadic)
clinical use, we will restrict out comments to this agent.
Methylprednisolone
Methylprednisolone is a familiar glucocorticoid that has been proposed, based on laboratory studies, to exert
an anti-inflammatory effect that might decrease the severity of secondary SCI. However, no prospective controlled
trial in humans have demonstrated a clinical benefit in primary analysis. Instead, the only clinical evidence
supporting the use of high-dose methylprednisolone comes mainly from small, retrospective subgroup analyses of
two large, well-publicized studies: the second and third National Acute Spinal Cord Injury Studies (NASCIS II-
III). The NASCIS trials were designed as large prospective studies, but the subgroup analyses of these trials
demonstrated improvements (albeit clinically irrelevant improvement) in neurologic outcomes for patients treated
with methylprednisolone within 3-8 h of injury. The positive results of these subgroup analyses were well
publicized, but include major statistical and methodological limitations. For example, they did not adjust for
anatomical level of injury and baseline severity of injury. The only study that did make such an adjustment failed
to demonstrate any benefit of methylprednisolone. As a definite risk of significant complications has been
demonstrated in a variety of studies when high-dose steroids are used to treat traumatic neurologic injury, major
society guidelines explicitly do NOT recommend the use of glucocorticoids in acute SCI, in any situation.
Surprisingly, a number of recent survey-based studies have shown a marked disconnect between how spine
surgeons use high-dose methylprednisolone and their articulated beliefs regarding its efficacy. For example, 10
years ago, almost 90% of the surveyed American spine surgeons said they would initiate methylprednisolone
within 8 h of injury, even though only 24% of respondents said they believed the steroids would improve
outcomes. Similar, more recent surveys from the last 2 years have shown that 55-70% of surgeons in a variety of
practice environments around the world still use high-dose steroids, but with even fewer believing that such use
has any meaningful benefit.
Hypothermia
While animal studies suggest that mild hypothermia initiated both before and shortly after SCI can improve
outcomes, no high quality clinical trials exist. Given the failure of hypothermia to provide benefit in multiple
other neurologic disorders (e.g. head injury, cardiac arrest, subarachnoid hemorrhage) – in spite of similarly strong
laboratory evidence – there is little reason to consider its use in SCI. One POSSIBLE exception is localized
intraoperative cooling of the cord but to date only uncontrolled case series data are available, and hence general use
cannot be recommended.
Deep venous thrombosis prophylaxis
Due to the often long periods of relative immobility, SCI patients are at high risk of developing venous
thromboembolic events (VTEs) such as deep venous thrombosis (DVT) or pulmonary emboli (PE). There is
reasonable evidence as to the value of anticoagulant therapy (e.g. low molecular weight heparin, subcutaneous
heparin), although initiation of such therapy may need to be delayed until hemorrhagic problems are resolved
and/or surgical decompression of the cord performed. The needed duration of such therapy is not clear and
depends on mobility. In some SCI patients, particularly those with other injuries that either increase the risk of
VTE or which prohibit anticoagulation (e.g. intracranial lesions), IVC filters may be indicated. The value of
routine prophylactic IVC filters, even in some subpopulations of SCI patients, is still debated, with inconsistent
guidelines.
Mechanical ventilation
70-100% of patients with cervical SCI require intubation and ventilation during their hospitalization, either
due to accessory muscle/diaphragmatic paralysis, or due to abdominal muscle weakness that limits forced
expiration (coughing). Emergent intubation may be required in some patients (even in the field), while in others,
the need may not arise immediately. In patients who are NOT intubated emergently, ventilatory failure most
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commonly occurs at about 5 days post-injury. It may also be prudent for anesthesiologists to consider leaving an
SCI patient intubated postoperatively if surgery occurs in this early window of time. This would be of particular
importance following cervical fusion procedures that would make emergent intubation difficult.
Conventional wisdom suggests that the majority of patients with complete injuries above C5 will require
prolonged mechanical ventilation (and tracheostomy) extending past primary hospital discharge. However, more
recent data suggests that successful extubation can be successful in many of these patients. For example,
noninvasive ventilation (e.g. BiPAP) may permit avoidance of intubation or facilitate extubation. One other option
is diaphragmatic pacing.
There are some interesting issues regarding pulmonary mechanics that influence management. In normal
patients, ventilation is often better in the upright position. By contrast, in quadriplegics, ventilation may actually
be better fully supine, since the upward movement of abdominal contents may serve to “splint” the diaphragm.
There is also some reason to believe that, contrary to usual practice large tidal volumes (up to 20ml/kg) may be
safe, largely because the increased compliance associated with paralysis minimizes peak airway pressures. CPAP
may NOT be efficacious in spontaneously breathing quadriplegics because it impairs exhalation.
Summary
While various guidelines exist regarding the care of SCI patients, most are dependent on relatively low quality
data; there is a clear paucity of high quality clinical trial-based evidence regarding the care of such patients. But
until such evidence is provided, clinicians are obligated to use the best information available.
For a detailed reference list, see Rogers WK and Todd MM, Acute Spinal Injury, Best Practice and Research
Clinical Anesthesia (2016) 30: 27-39,
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One-Stop Shop For Geriatric Anesthesia: Be An Expert In ONE Session

Ruben J. Azocar, M.D. Boston/Massachusetts
Alec G. Rooke, M.D. Ph.D. Seattle/Washington
Marek Brzezinski, M.D. Ph.D. San Francisco/California
I. Perioperative Care of the Elderly: Introduction to the Challenges We Face (Ruben J. Azocar, MD)
In the US, 10,000 people turn 65 years-old every day. Further, those age 85 years and older represent the fastest growing segment
of the population.1, 2 This accelerated growth of the geriatric population means that by 2030, the US population that will be older than
65 years of age is expected to be 19%, which will certainly have a tremendous impact on healthcare. Consider that in 1970,
individuals age 65 years and older only represented 10% of the population, accounted for 20% of hospital discharges, and only
accounted for 33% of hospital days of care. 1, 2 By 2007, the percentage of those age 65 years and older grew to 13% and their hospital
use increased drastically to 37% of hospital discharges and 43% of all hospital days used. 1, 3, 4 Additionally, in 2006, elderly patients
underwent 35.3% of inpatient procedures and 32.1% of outpatient procedures. 1, 5
Unfortunately, the perioperative outcomes of this patient population are significantly worse when compared to those younger than
65 years of age. In a prospective observational study of 1064 patients undergoing non-cardiac surgery, Monk et al reported that those
older than 65 years had a 1-year mortality rate of 10.3%, almost double that of the rest of the population at 5.5%. 6 This finding
suggested a relative risk of one-year postoperative mortality of 4.458, which was the highest risk factor after having three or more
comorbidities or having an ASA classification of 3 or 4. 6 These findings are similar to those of an epidemiological study looking at
surgical mortality in the US where mortality was found to increase dramatically in those over the age of 65. 7 A review of the National
Surgical Quality Improvement Program database from February 24, 2002 through June 30, 2005 which looked at 7,696 surgical cases
demonstrated an overall 28% morbidity rate and a 2.3% mortality rate; however, the alarming data was a morbidity rate of 51% and a
mortality of 7% in those older than 80 years of age. 8
Complications are also significantly associated with morbidity and mortality. Hamel et al published data that showed a 20% rate
of postoperative complications in those age 80 years and older. Those patients who suffered complications had higher 30-day
mortality rates than those who did not (26% vs. 4%, P<.001). 9 However, mortality should not be the only long-term outcome that we
investigate, as quality of life is also important for patients and families. Importantly, dependency upon others for activities of daily
living has been associated to perioperative complications in the elderly.10
Perioperative complications in the older adult and their relation with mortality have been well described. Complications involving
the central nervous system, cardiac system, pulmonary system and renal system seem to be common and have vast impacts on
outcomes.9, 11 The American College of Surgeons in collaboration with other professional societies published guidelines for the
optimal perioperative assessment of the older adult in 2012. 1 These guidelines are a good resource when evaluating and optimizing
the older adult presenting for surgery; however, in many cases, the recommendations do not vary from previously established
guidelines for the evaluation and management of patients of any age and specific comorbidities. Additionally, it seems that the
functional evaluation of the older adult might be just as important, if not more, than the patient’s comorbidities in predicting
outcomes. If we consider that aging, even when in good health, implies a loss of the capacity to respond to stress despite a relatively
stable basal functionality, it would not be difficult to understand the concept of frailty as a better method to assess the older adult in
the perioperative period.12
Multiple studies have revealed that evaluations of functional capacity and frailty might represent a better metric to use as a
predictor of outcomes in the older adult. Malaky et al created a scale that measures five frailty criteria: unintentional weight loss of
more 10 pounds in the last year, decreased grip strength (adjusted for gender and BMI), exhaustion (ascertained by questions about
effort and motivation), low physical activity, and low walking speed. 13 Those with a score of 2 or 3 were classified as intermediately
frail, and those with a score of 4 or 5 were classified as frail. Based on this classification, they reported that preoperative frailty was
associated with an increased risk for postoperative complications (intermediately frail: odds ratio [OR] 2.06, 95% CI 1.18-3.60; frail:
OR 2.54, 95% CI 1.12-5.77), prolonged length of stay (intermediately frail: incidence rate ratio 1.49, 95% CI 1.24-1.80; frail:
incidence rate ratio 1.69, 95% CI 1.28-2.23), and higher likelihood of discharge to a skilled nursing or assisted-living facility after
previously living at home (intermediately frail: OR 3.16, 95% CI 1.0-9.99; frail: OR 20.48, 95% CI 5.54-75.68).13 Similar findings
have been reported even when only considering a single marker of poor functional capacity such as mobility. 14, 15
Refresher Course Lectures Anesthesiology 2016 © American Society of Anesthesiologists. All rights reserved. Note: This publication contains
material copyrighted by others. Individual refresher course lectures are reprinted by ASA with permission. Reprinting or using individual refresher
course lectures contained herein is strictly prohibited without permission from the authors/copyright holders
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Firmly aligned with the concept that a poor preoperative functional status is associated with worse outcomes, the idea of pre-
habilitation is an emerging notion. Currently, there are studies which hypothesize that an exercise program aimed to improve the
functional status of patients before surgery might improve recovery and overall outcomes, including in the geriatric population.16, 17
Although the results do not yet clearly indicate improvement in outcomes, the data suggests that such programs are feasible and might
result in improvement of preoperative functional status. Pre-habilitation does not imply ignoring a complete perioperative evaluation
and optimization of the older adult presenting for surgery, but rather compliments that effort.
II. Intraoperative Care Of The Elderly Patient: What You Need To Know (Alec G. Rooke, MD, PhD)
When managing the various organ systems in the older patient, consideration should be given to the physiologic changes with
aging that will interact with anesthetic care.
In general, one can expect a given drug dose to have a greater effect on an older patient. Several effects contribute to this result.
Aging prolongs the rate of drug redistribution thereby maintaining higher blood levels over time and permitting more of the drug to
reach the brain. The older brain may be more sensitive to a drug, making the response greater at any given brain drug level. This is
particularly true for benzodiazepines and opioids. Ultimately, drugs must be metabolized. If the drug level after redistribution is high
enough to produce an effect, then that effect can only be eliminated by metabolism. With aging, any drug metabolized by the liver or
kidney will have a longer metabolic half-life.18 A rough rule of thumb is a 50% reduction in dosing of all drugs affecting the brain
(more in the very old). With volatile anesthetics, the increase in potency is approximately 6% per decade. There is evidence that
volatile anesthetic dosing is not adequately reduced in older patients. 19
The important cardiovascular changes of aging include a stiffening of the heart and blood vessels.20 Arterial stiffening leads to
systolic hypertension and increases the strain on the left ventricle at the end of ejection. These changes contribute to the development
of ventricular hypertrophy and ventricular stiffening. Vessel stiffening is also a marker for increased mortality in the general
population and after some surgeries.21 Ventricular stiffening often leads to an increase in atrial pressure (diastolic dysfunction) and
makes the range of acceptable filling pressures more limited at both the upper and lower bound. 22 Decreased responsiveness to beta-
receptor stimulation reduces the baroreflux control of blood pressure, and makes the ventricles more dependent on adequate filling
volume to maintain stroke volume. The lack of cardiovascular reserve, coupled with greater swings in sympathetic tone in response to
the normal waxing and waning of painful stimuli during surgery, likely accounts for the greater swings in blood pressure observed in
older patients undergoing anesthesia.20 The otherwise healthy, older heart should not have significant dysfunction from anesthetic
myocardial depression, but may become hypotension from relative bradycardia, hypovolemia and especially from a decrease in
vascular resistance from the anesthetic induced decrease in sympathetic tone. 20
Consequently, hypotension in the operating room should likely focus on maintenance of vascular tone with alpha-vasconstrictors
and possibly mixed alpha- and beta-agonist agents. Hypotension should be anticipated after the stress of intubation dissipates. All
agents may decrease pressure because when the brain becomes anesthetized, sympathetic nervous system activity decreases.
Escalated monitoring such as with an arterial line is rarely needed simply because of age, but simple measures such as cycling the
blood pressure cuff every minute at induction can be employed. Bradycardia should be diagnosed based on an assessment of the
patient, with recognition that an older patient may need a heart rate even higher than 60/minute. Volume administration may be
necessary, but it should be based on independent evidence of hypovolemia, not merely on the basis of hypotension alone. Fluid
overload in the operating room may not be clinically evident because the decrease in venous tone allows for peripheral pooling of
blood volume. But after surgery, when sympathetic tone returns or when third spaced fluid is mobilized, that volume may overload
the central circulation and lead to pulmonary congestion or even overt pulmonary edema. It is therefore important to avoid
inadvertent volume overload during surgery. It should also be recognized that vasoconstrictors have the added benefit of some degree
of venoconstriction, and the attendant shift in blood volume back to the central circulation. This increase in preload typically
increases the strength of the ventricular contraction. As such, cardiac output is often maintained or even increased despite the fact that
the left ventricle must pump against a higher blood pressure. Anesthesia caregivers should therefore not assume that crystalloid must
be administered in order to maintain cardiac output during surgery.
There is considerable controversy over intraoperative hypotension and/or low bispectral index values (BIS) and adverse
outcomes.23-25 It appears that the duration and not just the magnitude of the hypotension may play a role. It is difficult to interpret
such studies due to their retrospective nature. There are studies that suggest that these associations may not be true, including
editorials to that effect.26 The problem with such retrospective studies is that the association between outcomes and either hypotension
or low BIS is not proof of causation. It is entirely possible that frail patients who are likely at increased risk of complications or
mortality are also more likely to demonstrate significant hypotension or sensitivity to general anesthetics. In fact, intraoperative
hypotension or low BIS may simply be markers of risk and not the risk itself. Better studies will be needed to sort out reality. Until
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then, while it seems reasonable to avoid severe, prolonged hypotension or exceptionally low BIS values, it is unreasonable to expect
that such events can be completely prevented.
The pulmonary system changes with aging are multiple, but a key component is the decrease in lung elastin that leaves the
parenchyma less stiff and actually more compliant than lungs of younger patients. The consequences of increased lung compliance
are poorer ventilation/perfusion matching, and less tethering of the small airways.18 The latter causes an increase in the lung closing
volume that must be achieved in order to prevent atelectasis from developing in the dependent portions of the lung. There are two
strategies that can be employed to get the lung volume above closing volume at the peak of mechanical inspiration: employ a large
tidal volume, or use a more modest tidal volume coupled with positive end-expiratory pressure (PEEP). Recent studies suggest that
the modest tidal volume (6-8 ml/kg predicted body weight) strategy is associated with fewer postoperative pulmonary complications.27
Should oxygenation decline during surgery, the strategy would be to provide recruitment maneuvers to reverse the atelectasis and then
add/increase the PEEP, but keep the tidal volume modest.28
Other pulmonary changes of aging include a stiffened, barrel chest that not only worsens the mechanical advantage of the
diaphragm, but increases the overall work of breathing. Forced exhalation becomes less effective because the lung tissue tethering of
small airways fails to prevent airway collapse when the increased intrathoracic pressure compresses the lungs. A frail, sarcopenic
patient with a high ventilator requirement in the recovery room may be at risk for fatigue, and ineffective spontaneous ventilation
could lead to atelectasis with hypoxia as well as ventilatory failure. Coughing and sputum mobilization become less effective with
age. The elderly also appear to be at increased risk for silent aspiration. Postoperative sedation and muscle weakness will likely
increase this risk, and impair the patient’s ability to deep breath and expectorate secretions. The older patient is more sensitive to
anesthetic agents, particularly sedatives, opioids and volatile anesthetics. They are also more likely to experience postoperative
residual neuromuscular blockade.29 Recent research suggests that reversal of neuromuscular blockade is associated with increased
respiratory complications, unless performed in conjunction with neuromuscular blockade monitoring.30 Safe use of non-depolarizing
muscle relaxants involves a series of steps that include modest dosing that accounts for age and lean body mass, delaying reversal until
a train-of-four demonstrates four thumb twitches, selecting a reversal dose based on the degree of the residual blockade, and waiting at
least ten minutes (after neostigmine) to ensure maximal reversal effect.31
Aging results in decreases in heat production and impaired vasoconstriction. As such, the older patient is more prone to
hypothermia in the operating room than a younger patient.32 The usual methods for temperature regulation should be applied, only
perhaps with more meticulousness in the older patient.
III. Postoperative Complications and the Long-Term Outcome (Marek Brzezinski, MD PhD)
With growing geriatric population in the US, an increased emphasis has been placed on anesthesia care for the elderly in the
postoperative period.33-37 Geriatric care is quickly becoming a key area where Anesthesiologists can have a major positive impact in
the overall patient experience including their physiologic and emotional well being which will translate into better clinical outcomes
and increased satisfaction with the care team and institution. 35 To accomplish these goals, the Anesthesiologist needs to be familiar
with the potential and unique considerations in the elderly patient, as well as understand the key issues and main complications in this
medically complex patient population.35 The interested reader is referred to the best practices, entitled “Optimal Perioperative
Management of the Geriatric Patient”, providing guidance on managing the older adult in the perioperative period
(https://www.facs.org/quality-programs/acs-nsqip/geriatric-periop-guideline).33 The overall goal of the postoperative care can be
summarized as:
Keep the elderly patient mentally and physically active (i.e. multimodal pain control) to prevent complications (e.g. DVT,
infections, functional deconditioning, cognitive problems), normothermic and well-fed (i.e. prevent N/V, ileus) to facilitate their
recovery and wound healing, while being cognizant of reduced renal/hepatic function and the prevalent polypharmacy. –
Multidisciplinary approach is the way to do it! 33, 34, 37
1.0 Unique considerations relevant for postoperative care in the elderly patient33, 34, 37, 38
Aging affects baseline physiological functions, as well as the response to stressors and medications. Consequently, it is essential
for the clinician taking care of geriatric patients to be familiar with those changes:
 Pharmacokinetic and pharmacodynamic changes in the elderly.
o Aging is typically associated with an increase in adipose tissue mass accompanied by a loss of skeletal muscle mass, lean
body mass, and total body water; decrease in renal and hepatic function (see below), as well as malnutrition (low albumin).
Consequently, the geriatric patient has
 Increased reservoir, protracted clearance, and an increased duration/effect of lipid-soluble medications (e.g., opioids and
benzodiazepines)
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 Decreased reservoir for albumin-bound drugs, like diazepam or propofol, potentially leading to high plasma
concentration of the free drug.
 Decreased volume of distribution, and therefore higher plasma concentrations and greater clinical effects of water-
soluble drugs
o Consequently, the elderly patients frequently require a reduction in the dose of their medications.
 Polypharmacy is highly prevalent, with 40% taking ≥ 5 medications and 20% taking ≥ 10 medications per week.
 Kidney function decreases throughout life. In fact, the clinician should assume a 30-50% reduction in GFR in a geriatric patient.
The elderly surgical patient has a higher risk of electrolyte and fluid shifts as well as of acute renal failure after surgery.
 Liver function in the elderly is decreased, leading to an overall decrease in metabolism and clearance of medications commonly
used by the anesthesiologist.
 Aging brain can be associated with a decline in cognition as well as an increase in drug-sensitivity. Furthermore, the respiratory
drive is decreased, as is the autonomic response to hypoxia and hypercapnea (by 40-50%). Consequently, the elderly patient is
more sensitive to sedatives (e.g., 2x higher sensitivity/risk of respiratory depression).
 The GI tract undergoes significant changes as we age. For one, the gastric drug absorption is delayed, i.e., there is an inconsistent
dose-(time-)response relationship. The elderly patient has a higher risk of aspiration, as swallowing dysfunction and the loss of
the coughing reflex is commonly reported in this population; up to 30% carry the diagnosis of GERD. Gastric atrophy is also
prevalent, thus increasing the risk of GI bleed. Finally, up to 30% of the geriatric population takes laxatives preoperatively for
chronic constipation.
 Co-morbidities are prevalent in the elderly. They frequently have COPD, CAD, heart failure, diabetes, etc., placing them at higher
risk for perioperative morbidity and mortality.
 Spinal and epidural anesthesia, despite many advantages, may be associated with a higher risk of hypotension, dizziness, delayed
ambulance, and urinary retention postoperatively in the elderly.
2.0 Postoperative Pain management

Effective pain control is probably the key to prevent/reduce postoperative complications in the elderly, as pain can negatively
affect vital aspects of recovery, including ambulation, DVT, respiratory and GI function and cognition. Furthermore, exposure to
surgery has been also found to exacerbate chronic non-surgical pain, like back pain. Given the age-related changes mentioned above
(III.1), effective pain control can be challenging in the aged. The two principles of pain control in the elderly include 1)
individualization of the medications for the elderly patient to account for the less predictable onset, delayed effect, and protracted
clearance, as well as, 2) multimodal approach using different analgesics to minimize the side effects of opioids. While the full scope
of multimodal analgesia is obviously beyond the scope of this review, here are a few clinically relevant pearls:33, 34, 37, 38
 Acetaminophen (PO or IV) is one of the safest analgesics in the elderly, typically needing no dose adjustments.
 Peripheral nerve blocks using local anesthetics represent an excellent way to reduce post-operative pain and narcotic use. Adding
a glucocorticoid steroid, clonidine, or NSAIDs can increase the duration of the block.
 Glucocorticoids have been found to reduce surgical pain, and to augment the effects of local anesthesia (regional nerve block).
 NSAIDs, while effective, should be used with caution as they may increase the risk of GI-bleed or renal failure. In this context,
cyclooxygenase-2 (COX-II) inhibitors may represent a short-term alternative (long-term use is associated with cardiovascular
complications).
 In addition, there is a plethora of nontraditional drugs that have been found to reduce postoperative pain and deserve
consideration on individualized basis, including gabapentin, ketamine, clonidine, and dexmedetomidine.
 In patients with renal dysfunction: 39, 40
o Codeine and meperidine should not be used,
o Does adjustments are required when using morphine (active metabolites accumulate in renal failure), oxycodone (80%
metabolized in the liver, 20% excreted unchanged in the urine), or hydromorphone (metabolized in liver, but 3-glucuronide
metabolite can accumulate and produce neuroexcitatory effects)
o Fentanyl seems to be safe in renal impairment
 In patients with hepatic dysfunction:39, 41
o Codeine, methadone, and meperidine should not be used
o Morphine, hydromorphone, and oxycodone may not be readily converted to active metabolites
o Fentanyl seems to be safe
3.0 Postoperative Complications in the Elderly Patient

Given the page-limit, the RCL-synopsis here focuses on the most relevant postoperative complications:
 Postoperative cognitive decline is a common complication that can present as two separate entities:
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o Postoperative delirium (POD): an acute, early-onset, and transient disturbance of consciousness that is characterized by
inattentiveness and cognitive impairment which has a fluctuating course.42 POD is one of the most common complications in
the elderly surgical patient. Clinically, POD can present in three different subtypes: hyperactive delirium (i.e., the
“prototypical” combative and agitated delirious patient), hypoactive delirium (calm and quiet patient with decreased motor
activity), and mixed subtype.33 Typically, POD is diagnosed using the Confusion Assessment Method for the ICU (CAM-
ICU) [for ICU patients] or Confusion Assessment Method (CAM) [for ward patients].43 The POD diagnosis requires:33
 Acute onset or fluctuating course: Is the person different than at baseline; has the patient had any fluctuations in mental
status in the past 24 hours?
 Inattention. To test this you would say: “Please squeeze my hand whenever you hear the letter A“, and then say a series
of 10 letters that contain the letter A. For instance, “S-A-V-E-A-H-E-A-R-T” or “C-A-S-A-B-L-A-N-C-A”. More than 2
errors indicate inattention
 Altered level of consciousness (RASS ≠ 0) or/and presence of disorganized/incoherent thinking (e.g., ask the four CAM-
ICU questions: “Will a stone float on water?”, “Are there fish in the sea?” , “Can you use a hammer to pound a nail?”,
“ Does one pound weigh more than two pounds?” More than 1 error suggests disorganized thinking)
The reported incidence of postoperative delirium ranges from 5% to 15%, with rates as high as 16% to 62% in high-risk
groups, such as hip fracture patients.33, 44 Multiple risk factors for development of postoperative delirium have been
identified, with preexisting cognitive impairment and advanced age being the strongest predictors of postoperative
delirium.33, 45 Development of delirium is associated with increased mortality, 45 increased risk of institutionalization,46
development of dementia,46 increased length of stay,45 as well as with increased risk of major complications. 45 The
occurrence of delirium can predict long-term cognitive impairment.46
 Prevention: According to recent Cochrane reviews,47, 48 30-40% of cases of delirium are preventable using multi-
component interventions, including individualized care, pain management, cognitive reorientation, daily
mobilization/activity, attention to sensory deprivation, constipation prevention, facilitation of sleep, geriatric-focused
training of staff, etc.
 Treatment:33 It is recommended to start with the above mentioned multicomponent non-pharmacological interventions,
followed by antipsychotic agent like haloperidol starting at 0.5-1mg PO. However, the results for haloperidol have been
somewhat disappointing.49 When used as prophylaxis in a randomized, double-blind, placebo-controlled study of 430
elderly patients (≥70 years of age) undergoing elective hip-surgery, haloperidol failed to decrease the incidence of
postoperative delirium.50 Haloperidol prophylaxis did, however, significantly reduce the duration and severity of
postoperative delirium.50 In contrast to haloperidol, the atypical antipsychotic drug olanzapine significantly decreased the
incidence of the postoperative delirium, while significantly increasing the duration and severity of postoperative
delirium.51 Collectively, the data on the role of antipsychotic drugs in prevention of postoperative delirium are too
limited to draw any firm conclusion. Similarly, the cholinesterase inhibitors donepezil hydrochloride and rivastigmine
failed to reduce the incidence of postoperative delirium52, 53 or length of hospital stay.53 Finally, there is no clear
evidence that melatonin or melatonin agonists reduce delirium incidence compared to placebo.48
o Postoperative cognitive dysfunction (POCD): a longer-lasting decline in the level of cognitive performance after surgery as
compared to preoperative baseline.54 It includes acute (weeks), intermediate (months), and long-term (years) cognitive
decline. Up to 50% of surgical patients suffer from POCD in the early weeks following a major non-cardiac surgery.55, 56
Although the majority of patients gradually recover over time, permanent cognitive decline has been described. 57Advanced
age, history of cerebral vascular accident, lower educational level, and alcohol abuse have been shown to be independent risk
factors for POCD at 3 months.55, 58 POCD was found to be associated with poor short-term and long-term outcomes including
depression, decrease in daily functional ability, loss of independence, premature unemployment, and possible permanent
dementia.56, 59 Here are few clinically relevant pearls:60
 There is currently no strong evidence in humans that anesthetic agents or anesthetic techniques are a risk factor for
POCD.61-66 Two meta-analyses that compared GA vs. RA failed to demonstrate that GA is a risk factor for POCD. 62, 64 In
two recent clinical trials, the incidence of POCD in patients undergoing an intervention under RA or MAC was at least
as high as in the GA group.61, 65
 Furthermore, while volatile anesthetics have been found to promote and accelerate AD-neuropathology in animal
models, all human studies examining this subject have failed thus far to show such a relationship.67-69
 The mechanism underlying POCD is unknown.
 Prevention/treatment: Currently there no prophylactic/therapeutic interventions that consistently and predictably reduce
the incidence of POCD.
 Immobility, Fall Risk: 33, 34, 37, 38 Early ambulation, daily physical activity, and avoidance of falls are the key steps to prevent
functional decline as well as prevent respiratory, thromboembolic, and cognitive complications after surgery.33, 34, 37 Many elderly
patients have preexisting conditions that place them at higher risk of immobility or falls, including baseline functional
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deconditioning, malnutrition, sarcopenia, arthritis, poor sensory input (vision, hearing, etc), arthritis. In addition, surgery and
anesthesia may add surgical pain, sedatives, and analgesics that may make mobilization more challenging while increasing the
risk of falls. The latter is a real problem, with reported 1.5% of surgical inpatients suffering a fall after surgery. 33
o Fall Prevention/Early Ambulation: Multicomponent interventions are recommended, including early assessment, early
involvement of physical therapy, supervised and assisted exercises, maintaining call light within reach, placing handrails in
relevant areas, using nonslip footwear, and geriatric-focused training of staff, etc. Obviously, early ambulation with a low
risk of a fall is more likely in a patient with normal cognition who is not in pain – so effective pain control and prevention of
delirium are a must.
 Hydration in the Postoperative Period:33, 34, 37, 38 Loss of total body water, as well as decreases in the glomerular filtration rate
(GFR), urinary concentration ability, free water clearance, and thirst are common problems in the elderly, placing them at higher
risk for electrolyte and acid-base abnormalities as well as fluid disorders. Given an already impaired renal function, the elderly
patient is also at higher risk for acute postoperative renal impairment.
o Prevention: Early return to PO intake, balanced approach to fluid management, maintaining appropriate blood pressure, and
avoiding nephrotoxic drugs, especially in the context of the highly prevalent polypharmacy are essential. Consider
measuring electrolytes after surgery, remembering that even normal plasma level of creatinine in the elderly might be an
indicator of decreased GFR due to the decreased skeletal muscle mass.
 Nutrition in the Postoperative Period:33, 34, 37, 38 Postoperative problems with nutrition are notorious in the elderly. In fact, up to
40% of hospitalized patients are malnourished. Chronic constipation, poor appetite, or social isolation are additional factors in the
elderly that increases the risk for malnutrition. Surgery/anesthesia further compounds this problem with its attendant risk of ileus,
nausea/vomiting, and loss of appetite.
o Prevention/treatment: Early return to oral intake (daily evaluations of PO intake), enteral feeding if PO intake is not possible,
and nutritional supplementation in undernourished patients are key to reduce the risk of malnutrition. In addition, consider
early ambulation, opioid-sparing pain management, and normal fluid intake to prevent ileus.
 Wound healing and Pressure Ulcer: The prevalent co-morbid conditions, such as poor nutritional state, sarcopenia, diabetes,
circulatory and oxygenation problems, can impair wound healing in the elderly. Thus, it is imperative to avoid fluid overload,
hypotension, hypoxia, hypothermia, ileus, or hyperglycemia after surgery and provide appropriate antibiotics. Similarly, the
elderly are at higher risk to develop postoperative pressure ulcer.
o Prevention: Early involvement of physical therapy, turning patients regularly, oral/tube feeding, nutritional supplementation,
optimization of co-morbidities can be instrumental.
 Cardiovascular and Pulmonary Complications:33, 34, 37, 38 The burden of cardiovascular and pulmonary disease increases as the
body ages. In fact, cardiac pathology is the most common cause of death in the elderly surgical patient.
o Prophylaxis: Postoperative management should focus on maintaining stable hemodynamics, oxygenation, and electrolytes, as
well as restarting pre-operative medications early for pre-existing co-morbidities. The care should include vigilant
management of fluids (especially avoiding fluid overload), prevention of atelectasis and pneumonia (incentive spirometer,
upright position, pulmonary toilet, respiratory therapy), early mobilization, and oral intake of fluids and food.
4. Long-Term Outcome in The Elderly Patient:33, 37, 70

Long term postoperative outcomes in the elderly, while increasingly important, is still a developing field. A key difference in
assessing the long-term success between the non-geriatric and geriatric population is that in the former the outcome is typically
defined using standardized measures like morbidity (e.g., stroke, MI, creatinine, troponine, length of stay, etc) and mortality while in
the latter the emphasis is on the quality of life, cognitive function, the subjective perception of health, and the return to preoperative
baseline level of functioning allowing the patient to live an independent and fulfilling life. More research is required in this important
area to help us guide the postoperative care in the elderly surgical patient.
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Post Dural Puncture Headache and Epidural Blood Patch
Barbara M. Scavone, MD Chicago, IL
Introduction
Post dural puncture headache (PDPH) is one of the most common adverse events to occur after neuraxial anesthetic
procedures. Most of the data concerning both PDPH and epidural blood patch (EBP) comes from the obstetric
anesthesia literature, although a smaller amount derives from the pain and other anesthesia literature.
Incidence, clinical features, and etiology
Meta-analysis reveals that: The incidence of accidental dural puncture (ADP) with a large bore needle during
epidural anesthetic procedures is approximately 1-2%, although the range varies across different reports. In obstetric
patients, PDPH follows between 50-60% of ADPs. Of those patients with PDPH, 50-60% require EBP. PDPH
occurs in the absence of a recognized ADP in fewer than 1% of patients (1). A typical PDPH is positional, such that
headache worsens in the upright position, and abates (although perhaps not completely) when the patient assumes
the recumbent position. Headache may be accompanied by neck ache and back pain, visual symptoms such as
photophobia and blurred or double vision, auditory disturbances including decreased hearing acuity and tinnitus, and
even cranial and upper cervical nerve dysfunction. Onset is usually within 1-2 days, and duration, 7-10 days in the
obstetric population; onset may lag and duration may be shorter in general surgical patients (1). The differential
diagnosis of headache in postpartum patients includes states specific to pregnancy such as preeclampsia, venous
thrombosis, and intracerebral bleeds, as well as more generic causes of headache such as tension headache; migraine
may recur in the postpartum period also (2). Diagnostic neuro-imaging should be considered for postpartum patients
whose headache is accompanied by focal neurologic signs or lack of response to treatment, as these can be signs of
intracranial pathology (2).
Headache occurs due to leakage of cerebrospinal fluid (CSF); however correlation between headache symptoms and
degree of leak/intracranial hypotension is incomplete. Some patients with small lumbar leaks develop headache,
whereas some with large leaks do not report any symptoms (3). Similarly, a proportion of patients with severely
depleted intracranial CSF volume may remain asymptomatic, while some with only mild CSF decreases develop
severe headaches (4). When the brain loses its CSF cushion, downward displacement of the cranial contents may
occur, putting traction on pain-sensitive meningeal structures. Furthermore, reflex cerebral vasodilation occurs in
response to intracranial hypotension and pain-sensitive perivascular stretch receptors may contribute to headache
symptoms (5).
Risk factors for PDPH
Patient-related factors. Young age and female gender are risk factors for development of PDPH after dural puncture
(6). Whether pregnancy itself is an independent risk factor remains unclear. Obesity predisposes to ADP (7), but
obesity may decrease risk of headache once dural puncture occurs. Retrospective studies demonstrate lower PDPH
rates and better response to epidural blood patch (EBP) in obese versus non-obese patients (8,9). These studies are
not definitive, however, because they are confounded by the fact that obese patients are more likely to undergo
cesarean delivery and receive spinal opioids postoperatively, both of which lower PDPH rates (10, 11). One recent
group of investigators controlled for mode of delivery, and the protective effect of obesity on headache persisted
(12).
Technique-related factors. Headache rates increase after puncture with large-gauge versus small-gauge needles, and
beveled/cutting versus pencil point/non-cutting needles (6,13). One group of authors demonstrated that inserting an
epidural needle with the bevel parallel to, rather than perpendicular to, the longitudinal axis of the spinal canal,
decreased headache rate (14). They recommended holding the bevel parallel to the long axis to identify the epidural
space, and then rotating the needle within the space once it had been identified, to decrease the risk of the catheter
veering off to one side, resulting in unilateral blockade. Others questioned the utility of this practice, demonstrating
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that it was not necessary for satisfactory analgesia to rotate the needle before threading the catheter into the epidural
space (15). Rotation of the needle within the epidural space may increase ADP occurrence.
The effect of loss of resistance (LOR) medium used during epidural space identification on headache development
remains unclear. One author demonstrated higher headache rates in pain patients after LOR to air versus saline (16).
However, the air-related headaches had faster onset and shorter duration than the saline-related headaches, and
therefore may have been due to temporary pneumocephalus that resulted from injection of air into the intrathecal
space during LOR. Practitioners should aim to inject the smallest amount of air possible into the epidural space
during LOR in order to minimize the development of pneumocephalus should ADP take place.
Once ADP has occurred, one may elect to thread a catheter into the intrathecal space for continuous spinal
anesthesia, or to withdraw the epidural needle, and re-site it into the epidural space at a different intervertebral level.
Some have theorized that intrathecal catheter insertion causes inflammation near the dural tear, speeds healing, and
decreases headache risk. Retrospective and other uncontrolled studies addressing this possibility are confounded,
and therefore yield conflicting results, some demonstrating lower headache rates with intrathecal versus epidural
catheterization (17,18), and some showing no effect (19,20). Two randomized controlled trials investigating the
relationship of intrathecal catheterization and PDPH risk exist. Norris used a quazi-randomization technique to
assign parturients to receive intrathecal versus epidural anesthesia after ADP, and showed no difference in headache
rate or severity or in need for EBP (21). In the definitive study, Russel et al randomized obstetric patients to receive
intrathecal versus epidural catheterization after ADP (22). Intrathecal catheters were left in place for 24 hours post
delivery to maximize the pro-inflammatory effect. Headache occurred at equal rates in both groups, as did
performance of EBP. The weight of the evidence therefore does not support the notion that intrathecal
catheterization decreases headache risk after ADP. A meta-analysis that drew the opposite conclusion included both
randomized and non-randomized trials, and was therefore flawed (23).
Issues other than the effect on headache rate should be considered after ADP. In the Russell study, patients in the
epidural group suffered more complications than those in the continuous spinal group, such as repeat ADP and
failure to establish blockade (22). Therefore, the authors recommended intrathecal catheterization after ADP despite
its lack of efficacy regarding headache prevention. Some caution is warranted, however, because high spinal levels
may result if local anesthetic doses intended for the epidural space are accidentally administered intrathecally. High
spinal level can also result through an epidural catheter after a previous ADP because local anesthetics may
translocate across the large-diameter hole in the dura, particularly during bolus administration for cesarean delivery.
Similarly, epidural-administered hydrophilic opioids may traverse across the dural tear, so epidural morphine is
contraindicated after a prior ADP. (Lipophilic opioids such as fentanyl traverse the dura quite freely and so the
presence of the tear does not affect their dosing.)
Obstetric-related factors. Patients who have vaginal delivery are more likely to develop headache after ADP than
those who undergo cesarean delivery (10). Performance of Valsalva maneuvers during pushing may cause extrusion
of CSF, as headache rate is proportional to pushing time (24).
Prophylaxis and treatment
Conservative therapy. Bedrest after ADP does not prevent PDPH, and inactivity remains inadvisable for postpartum
patients due to their risk for deep venous thrombosis. One should maintain euvolemia as dehydration results in
decreased CSF production; excessive hydration, however, does not promote excess CSF production. Abdominal
binders may favorably affect pressure gradients across the dural tear and decrease PDPH after ADP; unfortunately,
they are not well-tolerated by most patients and are not popularly used. Practitioners commonly prescribe analgesics,
particularly those combination pills that include butalbital and caffeine. Caffeine, by way of its vasoconstriction
properties, may decrease headache symptoms (25), but its effect is modest and transient, and so while clinicians may
encourage patients to consume extra caffeine for mild or moderate headaches, severe headaches usually warrant
other treatments. Also, caffeine has a prolonged half-life in postpartum patients, and accumulation may occur after
repeated dosing or infusion (26). Furthermore, reports of seizure and arrhythmia during caffeine infusion exist
(27,28).
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Alternative therapies. One small trial investigating utility of sumatriptan in this clinical setting produced
disappointing results (29). ACTH analogs increase aldosterone levels, and some theorize that the resultant salt and
water retention may lead to increased CSF production, but studies investigating their usefulness have yielded
conflicting results. One investigation indicated ACTH analogs were appropriate for PDPH prophylaxis (30), but
another showed no effect of ACTH analogs on established PDPH (31). Further study is needed.
Epidural blood patch. EBP remains the treatment of choice for severe PDPH. Injection of blood into the epidural
space quickly produces a tamponade effect on the intrathecal sac, increasing epidural and intrathecal pressures in
both the lumbar and intracranial spaces, restoring intracranial pressure, and relieving adenosine-mediated
vasodilation (32,33,34,35). In addition, clot adheres to the dura after several hours, presumably decreasing leak and
promoting healing (34). MRI studies indicate that approximately 15-20 mL blood is sufficient for spread and
tamponade of the sac (32). A randomized controlled trial conducted by Paech et al compared 15 versus 20 versus 30
mL blood for EBP (36). All volumes of blood were similarly effective for treatment of headache symptoms;
however, the area under the time-pain curve over 48 hours was higher in patients given 15 mL of blood compared to
patients in the other groups, and the authors therefore recommended the use of 20 mL blood for EBP.
Retrospective audits reveal that 88-95% of obstetric patients with PDPH after ADP experience some degree of relief
after EBP; however, 33-44% of patients have only partial or temporary relief, and symptoms often return after a few
days (37,38). In the aforementioned Paech study, EBP efficacy was even lower (36). Only 67% of patients had any
headache alleviation at all, and just 22% had complete permanent resolution. Up to 31% of patients may require
repeat patching (36). Although EBP lacks perfect efficacy, complete lack of any effect at all should spur the
clinician to question the diagnosis of PDPH.
It remains unclear how timing effects EBP efficacy. Studies purporting to show decreased efficacy when patches are
administered within less than 24 to 48 hours of puncture are difficult to interpret because they include a mixture of
patients (male, female, obstetric, non-obstetric) and needle sizes and types used for puncture (39,9). It is just as
likely that patients at high risk (e.g., obstetric patients delivering vaginally, suffering large-bore dural punctures)
experience severe symptoms early after puncture, and are therefore patched earlier than others, and are also more
likely to need repeat patching (40). While it is certainly reasonable to offer a patient experiencing mild or moderate
symptoms a trial of conservative therapy, one should not hesitate to administer EBP to patients with severe
symptoms within a day of puncture. Such patients should be made aware of the possibility of repeat patch
requirement.
Prophylactic EBP can be performed through the epidural catheter before it is pulled out after delivery. Two
randomized controlled trials stand at odds regarding the efficacy of prophylactic EBP. One demonstrated no
difference in headache incidence, peak pain scores, or need for therapeutic EBP after prophylactic EBP compared to
a shame patch, although those who received the prophylactic patch had shorter duration of headache (10). A second
did show fewer headaches and therapeutic EBPs performed in those patients randomized to receive prophylactic
EBP versus nothing (41); however, this study has been criticized because the treating physician was not blinded to
patient group and treatment was not standardized, leading to possible bias (42). Considering these two studies
together, it is likely that prophylactic EBP provides some benefit in high risk patients, although probably not a
dramatic one.
Backache follows epidural blood patch in 85% of patients (36). Discomfort is usually mild, although occasionally
can be more severe or be associated with radicular pain. It may be advisable to limit injectate volume, particularly if
the patient feels pain or radicular symptoms during the procedure. Non-steroidal anti-inflammatory agents often
provide relief. Rarely, more severe complications follow EBP, including deterioration of mental status and seizures
when EBP is performed for headache other than PDPH (43), and arachnoiditis (44).
Scope of the problem
Postpartum PDPH increases length of hospital stay, increases hospital and emergency department visits after
discharge, and interferes with activities of daily living, including childcare (45). Rarely, subdural hematoma follows
PDPH, as bridging veins are stretched, and subjected to increased transmural pressures (46). The sixth cranial nerve
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may become stretched during downward brain displacement, causing nerve injury and subsequent double vision
(47). Often, PDPH responds to EBP treatment, but the diplopia persists for many months during myelin
regeneration, or in rare instances, is even permanent (47). Sixth cranial nerve palsy is a indication for immediate
emergency EBP to effect relief of nerve ischemia.
There may exist longer term consequences to ADP than has previously been thought. Investigators who compared
parturients who suffered ADP to a matched cohort who had not, revealed that patients in the ADP group had
increased rates of headache and backache approximately 12 to 24 months post-delivery (48,49). EBP appeared to
provide some protective effect against these long-term symptoms; however, the lower headache and backache rates
in patients who had received EBP versus those who had not, did not reach statistical significance, possibly because
the study was underpowered for this outcome (48).
Conclusions
ADP and PDPH continue to pose vexing problems for the anesthesiologist. EBP remains the mainstay of therapy for
severe headaches.
References
1. Choi PT, Galinski SE, Takeuchi L, et al: PDPH is a common complication of neuraxial blockade in
parturients: a meta-analysis of obstetrical studies. Can J Anesth 2003; 50:460-469
2. Stella CL, Jodicke CD, How HY, et al: Postpartum headache: is your work-up complete?
Am J Obstet Gynecol 2007;196:318.e1-318.e7
3. Iqbal J, Davis LE, Orrison WW: An MRI study of lumbar puncture headaches. Headache 1995;35:420-422
4. Grant R, Condon B, Hart I, et al: Changes in intracranial CSF volume after lumbar puncture and their
relationship to post-LP. J Neurol Neurosurg Psychiatry 1991;54:440-442
5. Benzon HT, Wong CA: Postdural puncture headache: mechanisms, treatment, and prevention. Reg Anesth
Pain Med 2001;26:293-295
6. Vandam LD, Dripps RD: Long-term follow-up of patients who received 10,098 spinal anesthetics. JAMA
1956;161:586-591
7. Hollister N, Todd C, Ball S, et al: Minimizing the risk of accidental dural puncture with epidural analgesia
for labour: a retrospective review of risk factors. Int J Obstet Anesth 2012;21:236-241
8. Faure E, Moreno R, Thisted R: Incidence of postdural puncture headache in morbidly obese parturients.
Reg Anesth 1994;19:361-363
9. Kokki M, Sjovall S, Keinanen M, et al: The influence of timing on the effectiveness of epidural blood
patches in parturients. Int J Obstet Anesth 2013;22:303-309
10. Scavone BM, Wong CA, Sullivan JT, et al: Efficacy of a prophylactic epidural blood patch in preventing
post dural puncture headache in parturients after inadvertent dural puncture. Anesthesiology
2004;101:1422-7
11. Al-metwalli RR: Epidural morphine injections for prevention of post dural puncture headache.
Anaesthesia 2008;63:847-850
12. Peralta F, Higgins N, Lange E, et al: The relationship of body mass index with the incidence of postdural
puncture headache in parturients. Anesth Analg 2015;121:451-456
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13. Vallejo MC, Mandell GL, Sabo DP, et al: Postdural puncture headache: a randomized comparison of five
spinal needles in obstetric patients. Anesth Analg 2009;91:916-920
14. Norris MC, Leighton BL, DeSimone CA: Needle bevel direction and headache after inadvertent dural
puncture. Anesthesiology 1989;70:729-731
15. Richardson MG, Wissler RN: The effects of needle bevel orientation during epidural catheter insertion in
laboring parturients. Anesth Analg 1999;88:352-356
16. Aida S, Taga K, Yamakura T, et al: Headache after attempted epidural block. Anesthesiology 1998;88:76-
81
17. Cohen S, Amar D, Pantuck Ej, et al: Decreased incidence of headache after accidental dural puncture in
caesarean delivery patients receiving continuous postoperative intrathecal analgesia. Acta Anaesthesiol
Scand 1994;38:716-718
18. Ayad S, Demian Y, Narouze S, et al: Subarachnoid catheter placement after wet tap for analgesia in labor:
influence on the risk of headache in obstetric patients. Reg Anesth Pain Med 2003;28:512-515
19. Rutter SV, Shields F, Broadbent CR, et al: Management of accidental dural puncture in laboour with
intrathecal catheters: an analysis of 10 years’ experience. Int J Obstet Anesth 2001;10:177-181
20. Van de Velde M, Schepers R, Berends N, et al: Ten years of experience with accidental dural puncture and
post-dural puncture headache in a tertiary obstetric anaesthesia department. Int J Obstet Anesth
2009;17:329-335
21. Norris MC, Leighton BL. Continuous spinal anesthesia after unintentional dural puncture in parturients.
Reg Anesth 1990;15:285-287
22. Russell IF. A prospective controlled study of continuous spinal analgesia versus repeat epidural analgesia
after accidental dural puncture in labour. Int J Obstet Anesth 2012;21:7-16
23. Heesen M, Klohr S, Rossaint R, et al. Insertion of an intrathecal catheter following accidental dural
puncture: a meta-analysis. Int J Obstet Anesth 2013;22:26-30
24. Angle P, Thompson D, Halpern S, et al: Second stage pushing correlates with headache after unintentional
dural puncture parturients. Can J Anesth 1999;46:861-866
25. Camman WR, Murray RS, Mushlin PS, et al. Effects of oral caffeine on postdural puncture headache – a
double-blind, placebo-controlled trial. Anesth Analg 1990;70:181-4
26. Aldridge A, Bailey J, Neims AH. The disposition of caffeine during and after pregnancy. Semin Perinatol
1981;5:310-4
27. Cohen SM, Laurito CE, Curran MJ. Grand mal seizure in a postpartum patient following intravenous
infusion of caffeine sodium benzoate to treat persistent headache. J Clin Anesth 1992;4:48-51
28. Cua WL, Campbell JAP, Stewart JT. A case of ventricular tachycardia related to caffeine pretreatment. J
ECT 2009;25:70-71
29. Connelly NR, Parker RK, Rahimi A, et al. Sumatriptan in patients with postdural puncture headache.
Headache 2000;40:316-319
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30. Hakim SM. Cosyntropin for prophylaxis against postdural puncture headache after accidental dural
puncture. Anesthesiology 2010;113:413-20
31. Rucklidge MWM. All patients with a postdural puncture headache should receive an epidural blood patch.
Int J Obstet Anesth 2014;23:171-174
32. Szeinfeld M, Ihmeidan IH, Moser MM, et al. Epidural blood patch evaluation of the volume and spread of
blood injected into the epidural space. Anesthesiology 1986;64:820-822
33. Griffiths AG, Beards SC, Jackson A, et al. Visualization of extradural blood patch for post lumbar
puncture headache by magnetic resonance imaging. Br J Anaesth 1993;70:223-225
34. Beards SC, Jackson A, Griffiths AG, et al. Magnetic resonance imaging of extradural blood patches:
appearances from 30 min to 18 H. Br J Anaesth 1993;71:182-188
35. Vakharia SB, Thomas PS, Rosenbaum AE, et al. Magnetic resonance imaging of cerebrospinal fluid leak
and tamponade effect of blood patch in postdural puncture headache. Anesth Analg 1997;84:585-90
36. Paech MJ, Doherty DA, Christmas T, et al. The volume of blood for epidural blood patch in obstetrics: a
randomized, blinded clinical trial. Anesth Analg 2011;113:126-133
37. Williams EJ, Beaulieu P, Fawcett WJ, et al. Efficacy of epidural blood patch in the obstetric population.
38. Banks S, Paech M, Gurrin L. An audit of epidural blood patch after accidental dural puncture with a Tuohy
needle in obstetric patients. Int J Obstet Anesth 2001;10:172-176
39. Loeser EA, Hill GE, Bennett GM, et al. Time vs success rate for epidural blood patch. Anesthesiology
1978;49:147-148
40. Safa-Tisseront V, Thormann F, Malassine P, et al. Effectiveness of epidural blood patch in the
management of post-dural puncture headache. Anesthesiology 2001;95:334-9
41. Stein MH, Cohen S, Mohiuddin MA, et al. Prophylactic vs therapeutic blood patch for obstetric patients
with accidental dural puncture-a randomized controlled trial. Anaesthesia 2014;69:320-326
42. Scavone BM. Timing of epidural blood patch: clearing up the confusion. Anaesthesia 2015;70:119-134
43. Kardash K, Morrow F, Beique F. Seizures after epidural blood patch with undiagnosed subdural
hematoma. Reg Anesth Pain Med 2002;27:433-436
44. Carlsward C, Darvish B, Tunelli J, et al. Chronic adhesive arachnoiditis after repeat epidural blood patch.
45. Angle P, Tang SLT, Thompson D, et al. Expectant management of postdural puncture headache increases
hospital length of stay and emergency room visits. Can J Anesth 2005;52:397-402
46. Zeidan A, Farhat O, Maaliki H, et al. Does postdural puncture headache left untreated lead to subdural
hematoma? Case report and review of the literature. Int J Obstet Anesth 2006;15:50-58
47. Hofer JE, Scavone BM. Cranial nerve vi palsy after dural-arachnoid puncture. Anesth Analg
2015;120:644-6
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48. Webb CAJ, Weyker PD, Zhang L, et al. Unintentional dural puncture with a Tuohy needle increases risk
of chronic headache. Anesth Analg 2012;115:124-132
49. Ranganathan P, Golfeiz C, Phelps AL, et al. Chronic headache and backache are long-term sequelae of
unintentional dural puncture in the obstetric population. J Clin Anesth 2015;27:201-206
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Pediatric Patient Selection for Ambulatory Surgery Centers
Raafat S. Hannallah, M.D. Washington, District of Columbia
Children are excellent candidates for ambulatory surgery. Most children are healthy, and most surgical procedures
performed on children are brief and associated with prompt recovery. It is not surprising, therefore, that up to 80%
of pediatric surgery in this country is performed on an ambulatory basis. In fact, in many cases ambulatory surgery
is now synonymous with elective surgery. As anesthetic and surgical techniques evolve many children with
previously unacceptable co-morbidities undergoing more complex surgical or diagnostic procedures are now
ambulatory candidates. The key to the success and safety of pediatric ambulatory surgery lies in careful selection,
screening and preparation of prospective patients. This lecture will focus on the appropriateness of performing
ambulatory surgery in a free-standing ambulatory surgery center (ASC) vs. a hospital outpatient department
where extended recovery and/or overnight admission can be more easily arranged.
A successful ASC program requires that well-defined patient selection criteria be established, and strictly
adhered to by all surgeons who have admitting privileges in the facility. The primary factors that must be considered
when selecting a child for an ASC are the physical status of the patient, and the type of surgical procedure to be
performed. These factors must be balanced with the capability of the surgical facility and the ability of its staff to deal
with any expected or unexpected complications.
Minimal Age: Premature and Full-term Infants
Studies published over the past 30 years have shown that very young infants undergoing ambulatory surgery are at an
increased risk for perioperative morbidity and mortality. Of particular concern is the risk of post-anesthesia apnea, which
if it happens after discharge, may result in death. Although the premature infant is particularly vulnerable (several
studies have confirmed a high incidence of perioperative complications including apnea in these infants)1, the young full-
term infant is not immune. The age at which a former premature infant (ex-preemie) attains physiologic maturity and no
longer presents an increased risk for postoperative apnea remains controversial. It is generally considered that infants
younger than 46-50 weeks post-conceptual age (PCA) and/or preoperative history of apnea are at greatest risk. Many
anesthesiologists admit to a hospital or to a 23 hr. recovery facility (which would exclude most ACSs) all ex-premature
infants who are younger than 60 weeks post-conceptual age so that they may be monitored postoperatively for apnea,
bradycardia, and oxygen desaturation. If the infant was extremely premature, has bronchopulmonary dysplasia (BPD),
anemia or other neonatal problems, this period may need to be extended. Infants who develop apnea in the recovery
room should also be admitted and monitored.
Recently the American Academy of Pediatrics (AAP) published a policy statement describing critical elements
for the pediatric perioperative anesthesia environment (Pediatrics 2015;136:1200-05; located on the World Wide Web at:
<content/early/2015/11/25/peds.2015-3595.full.html>).2 They recommend at least 12 hours of monitoring after
anesthesia and surgery for preterm infants younger than 50 to 60 weeks’ PCA (again effectively excluding most ASCs).
Moreover, for full term infants, if they are younger than 4 weeks of age they recommend 12 hours of monitoring. For
healthy full-term infants >4 weeks and <6 months old, they recommend monitoring for ≥2 hours after surgery and if
possible, scheduled early in the day. Although not stated in the policy statement, avoiding opioids and relying on
local or regional anesthesia for pain management would increase the margin of safety. It is not known, however, if
these recommendations are widely adopted at present.
Adenotonsillectomy (T&A) for Obstructive / Sleep-disordered Breathing (SDB)

T&A is one of the most commonly performed pediatric surgical procedures worldwide and one in eight American
children will undergo adenotonsillectomy. Chronic or recurrent tonsillitis and obstructive adenotonsillar hyperplasia
are the major indications for surgical removal. Recent experience indicates that ambulatory T&A for appropriately
selected children is safe and cost-effective and that there is little benefit in keeping these patients in the facility once they
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achieve predetermined discharge criteria which at minimum should include absence of bleeding, adequate hydration,
absence of PONV, and adequate pain relief.
In North America, the indication for adenotonsillectomy in 77% of children is obstructive sleep apnea
syndrome (OSAS) or sleep-disordered breathing (SDB). SDB describes a spectrum of abnormal breathing patterns
during sleep. These include snoring, paradoxical chest wall motion and increased respiratory effort, apneas,
hypopneas and arousals leading to recurrent episodes of hypoxia, hypercarbia, and sleep disruption. The obstructive
events that characterize OSAS occur most often during rapid eye movement (REM) sleep. The frequency and
severity of obstructive events worsen after midnight, a finding that may reflect the greater proportion of REM sleep
in the latter part of the night and fatigue of the upper airway musculature.
Accordingly, the single most important task during the preoperative evaluation of the child for
adenotonsillectomy is to distinguish the child with the OSAS from the child with benign snoring or obstructive
breathing, because the former is at greater risk for developing severe perioperative respiratory adverse events
(PRAEs), possibly including death, after adenotonsillectomy and are not appropriate candidates for ASC
scheduling3. Two recent studies have reported unexpected deaths following adenotonsillectomy from presumed
sleep apnea following discharge from a monitored setting; including at home. A meta-analysis of 3 retrospective
studies (n = 371 children) revealed that children with OSAS proven by polysomnography (PSG) criteria have a 5-
fold increase in the odds for PRAEs compared with children without OSAS. In contrast they were less likely to have
postoperative hemorrhage (odds ratio 0.4, 95% confidence interval 0.2 – 0.7).4
Patino et al identified three important factors that can be used to determine whether an individual child can
be an appropriate candidate for ambulatory T&A or scheduled for overnight monitored observation. These include
the severity of OSA, age under 3 years, and presence of co-morbidities (See graph below). The recognized co-
morbidities that will increase the risk of postoperative respiratory events, including life-threatening apnea, are (but
not limited to) craniofacial abnormalities, obesity, Down syndrome, neuromuscular diseases, history of prematurity,
failure to thrive, chronic lung disease, right ventricular hypertrophy, and sickle cell disease. .
Post T&A disposition of Children with OSA. From Patino M, et al. Br J Anaesth 2013;111 (S1):i83-95.
Determining the severity of obstructive symptoms remains a challenge. Polysomnography (PSG) is the
gold standard diagnostic test for evaluation of SDB. The polysomnogram simultaneously records the
electroencephalogram, electromyogram, electrocardiogram, pulse oximetry, airflow, and thoracic and abdominal
movement during sleep. Apneas are classified as central, obstructive, and mixed. A central apnea occurs when there
is no apparent respiratory effort. An obstructive apnea is associated with vigorous inspiratory efforts that are
ineffective because of lack of upper airway patency. A mixed obstructive apnea is diagnosed when both central and
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obstructive components are present. Hypopnea is defined as a reduction in airflow of more than 50%. The Apnea
Hypopnea Index (AHI) is the summation of the number of obstructive apnea and hypopnea events per hour and is
analogous to the respiratory disturbance index (RDI).
The diagnostic criteria for pediatric OSAS from the American Academy of Sleep Medicine are: mild
OSAS corresponds to an AHI > 1 < 5 event per hour; moderate OSAS corresponds to an AHI >5 <10 events per
hour and severe OSAS corresponds to an AHI ≥10 events per hour. However, less than 10% of patients scheduled
for T&A are evaluated with a sleep test prior to surgery. The challenge is to evaluate the severity of SDB / OSAS
based on clinical criteria alone in the majority of children. A high index of suspicion is required since clinical
criteria do not always distinguish primary snoring from OSAS in children. Parents should be asked if the child
snores loudly, if the snoring can be heard through a closed door, if there are gasps or pauses in respirations, if there
is daytime somnolence, night terrors, nocturnal enuresis, attention deficit disorder, or poor school performance.
However parental report of symptoms has a poor positive predictive value and clinical features obtained from
demography, parental report and physical findings do not robustly identify OSAS severity. There is a greater
incidence of OSAS in Asian and African American populations. African American children tend to desaturate more
profoundly during sleep-related obstructive airway events than do Caucasian and Hispanic children. Obese children
(BMI greater than the 95ile) are at higher risk for OSAS especially if other comorbidities are present.
The general health of the child and the indications for surgery must be reviewed. URIs are frequent in these
children and can interfere with the timing of adenotonsillectomy because the risk of respiratory compromise and
hemorrhage is increased. Obese children often have sleep disordered breathing. A history of bleeding tendencies
requires investigation. Medications that interfere with coagulation include aspirin, NSAIDs, and valproic acid.
Discontinuation of these drugs preoperatively is sometimes problematic, and preoperative consultation with
neurology, cardiology, and hematology specialists may be indicated.
A careful cardiorespiratory history and physical examination is essential. Children with chronic tonsillar
hypertrophy may have long-standing hypoxemia and hypercarbia, which can lead to cor pulmonale. In some centers,
a complete blood cell count is required before adenotonsillectomy. There is no evidence that routinely performed
preoperative coagulation studies are beneficial unless they are indicated by history. The indications for the
procedure should be clearly delineated in the surgical plan of care.
The anesthetic techniques for adenotonsillectomy are varied and include the choice of an inhalational or
TIVA technique, the choice of an ETT or LMA, and the choice of spontaneous or controlled ventilation. The use of
spontaneous ventilation allows titration of small opioid doses to effect while monitoring respiratory rate and end-
tidal CO2. Maintenance of anesthesia with desflurane (for those whose airway is secured with an ETT) provides a
rapid emergence and recovery. Over the last decade, there has been a shift from opioids as the mainstay of
perioperative analgesia to non-opioid regimens including dexmedetomidine, acetaminophen, NSAIDs,
dexamethasone and ketamine. In children with severe OSA , the severity of the nocturnal oxygen desaturation
correlates with the sensitivity to exogenously administered opioids The morphine (or morphine equivalent) dose
required to achieve a uniform analgesic endpoint in children with OSA who exhibited a low preoperative nSAT
(less than 85%) was less than in those whose preoperative nSAT ≥85%. Children with severe OSAS who exhibit
nocturnal hypoxemia require OSA-appropriate opioid regimens. Although for hospital-based surgery, an infusion of
dexmedetomidine 1-2 µg/kg iv may reduce postoperative opioid requirements After larger doses of
dexmedetomidine (2 and 4 µg/kg), the opioid-free interval increases and the postoperative opioid requirements
decrease. However, duration of stay in the PACU is prolonged, and it is not used in ASC patients. Many young
children (< 3 yr.) who are undergoing
Perioperative Overnight Oximetry in a Severe OSA T&A Patient
tonsillectomy for the relief of severe
airway obstruction, with or without sleep apnea
(OSAS), continue to suffer from the same
symptoms and exhibit worse apnea and
Preoperative Study
desaturation in the immediate
postoperative period and should,
therefore, be admitted to a hospital or a 23 hr.
recovery facility for close observation and
monitoring postoperatively.
First Post-op Night
Reprinting or using individual refresher course lectures contained
6 weeks herein is strictly prohibited without permission from the
after T&A
Nixon GM, et al. Pediatr Pulmonol 2005;39:332-8

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Despite removal of the hypertrophied tonsils and adenoids, children with severe OSAS continue to
demonstrate obstructive apnea and desaturation during sleep on the first night after adenotonsillectomy (Fig.). This
underscores the need to admit these children to a hospital for continuous overnight monitoring postoperatively.
Because the onset of respiratory complications in children with severe OSAS may be delayed, practice guidelines
from the AAONHS, the AAP and the ASA all recommend that discharge criteria from a monitored setting should
include observation with saturation monitoring during sleep. However, a recent survey of North American pediatric
tertiary centers showed that only 73% complied with this recommendation although 93% had a minimum time for
observation with a median of 2 hours.
The Obese Child
The worldwide prevalence of childhood obesity has increased greatly over the past 3 decades, and in many countries
is becoming the “new normal”. Extremely obese children have increased risk for perioperative complications
including hypertension, dyslipidemia, insulin resistance diabetes, fatty liver disease, and psychosocial
complications, and may require prolonged recovery and occasional overnight observation especially after airway
surgery (T&A). Obstructive sleep apnea (OSA) is reported in 13–59% of obese children, compared to 1–2% of
normal weight children. Although the implications of morbid obesity and ambulatory surgery have been extensively
studied in adult patients, little is known about its implications for the pediatric ambulatory surgical patient.
There are internationally agreed thresholds of body-mass index (BMI) for defining underweight,
normal weight, overweight, and obesity in adults, but in children, the marked effects of age, gender, pubertal status
and race/ethnicity on growth make classification difficult. Commonly used cut points for childhood overweight and
obesity include: 110% or 120% of ideal weight for height; weight-for-height Z-scores of >1 and >2, and BMI at the
85th, 90th, 95th, and 97th percentiles.11 One major problem in establishing guidelines for accepting “obese” children
for ambulatory surgery at an ASC is that BMI-for-age percentile does not directly measure body fat. Very athletic
adolescents (frequently presenting for orthopedic and joint procedures) can have a high BMI-for-age due to extra
muscle mass, but not necessarily excess body fat.
Establishing rigid guidelines for excluding obese children from ASC surgery can be challenging. At the
author’s institution, the scheduling procedure requires that the child’s weight and height are recorded on the surgical
plan of care. BMI-for-age percentile can be easily calculated using readily available CDC formula found at
https://nccd.cdc.gov/dnpabmi/calculator.aspx. For children who fall over the 97-98th percentile, the indication for
surgery and the presence of other co-morbidities are used to determine if surgery can proceed at the ASC. Most
airway cases (T&A) are not acceptable. Children presenting for peripheral surgery (plastic / orthopedic) may be
accepted on a case-by-case basis.
Although there is no need for longer fasting times simply based on the diagnosis of obesity, the obese child
may have increased risk of airway obstruction, intraoperative oxygen desaturation, difficult mask ventilation and
difficult IV access.
Obesity affects the pharmacokinetics of most anesthetics. In general (there are some exceptions), dosing of
lipophilic IV drugs can be based on total body weight (TBW) where as ideal body weight (IBW) is best used for
hydrophilic drugs. Of the inhalational anesthetics, sevoflurane provides hemodynamic stability and minimal airway
irritability and can be used for both induction and maintenance. Desflurane has a lower blood-lipid solubility,
provides a faster restoration of protective airway reflexes and a more rapid recovery profile than sevoflurane when
used in intubated obese children.
Asthma and Reactive Airway Disease
Asthma is the most common chronic disease of childhood, affecting 5-10% of children in the US, and the incidence
is on the rise. It is not therefore unusual for patients with asthma to present for what is often a minor surgical
procedure in an ambulatory setting. The decision to accept and proceed with such patients depends on the severity
and frequency of symptoms and the adequacy of pharmacological control. Children with mild asthma who have
infrequent symptoms and do not require continuous medications are excellent candidates for ambulatory surgery at
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an ASC. When children with moderate asthma (those who require daily medications to control their symptoms) are
scheduled for ambulatory surgery, they should be instructed to continue their medications until (and including) the
morning of surgery. A beta agonist can be administered in the holding area by a nebulizer to young children or by an
inhaler if the patient is older. If the patient is wheezing, has co-existing URI, persistent cough or tachypnea on the
day of surgery, it is best to reschedule the procedure. The choice of a specific anesthetic technique in an asthmatic
child is usually dictated by the nature of the surgical procedure. Most anesthetics available today have been used
successfully in asthmatics. The use of an LMA may decrease the incidence of intraoperative bronchospasm. If an
endotracheal tube must be used, sufficient depth of anesthesia should be established first. Intravenous lidocaine
and/or a beta agonist inhalant may be administered just before extubation. Deep extubation may be considered.
Patients may leave the facility when the usual discharge criteria are met. Children should not have any signs of
wheezing when discharged. Adequate hydration should be ensured.
Controversial Patient Selection issues
Malignant Hyperthermia (MH)
MH is just as likely to occur in a healthy ASC patient as in an inpatient; so one must be always prepared. The
Malignant Hyperthermia Association of the United States (MHAUS www.mhaus.org) recommends that an MH
“cart” be stocked with drugs (including an adequate supply of dantrolene) and equipment used to manage MH, and
that it be immediately available to any anesthetizing location where triggering anesthetics are used. Although it has
been frequently stated that there is no medically valid reason why known MH-susceptible patients cannot undergo
general anesthesia in a freestanding ASC, as long as the anesthesia machine is properly prepared and a non-
triggering anesthetic technique (i.e., total intravenous anesthesia) is used,13 accepting a child who survived a
previous MH crisis is a difficult decision to make. In MH-susceptible patients, surgery with non-triggering agents is
safe, prophylactic dantrolene premedication is not indicated, and postoperative discharge times do not need to be
prolonged for the sole reason of monitoring the patient for the occurrence of delayed MH. 13
Known difficult airway
Accepting a child with a known or strongly suspected difficult airway in a free-standing ASC is a difficult decision
that must be individualized. An important consideration is the availability of advanced intubation devices in the
facility which is frequently limited. Even if the proposed surgical procedure can be safely managed without tracheal
intubation (e.g., with an LMA), the need for intubation cannot be completely ruled out. Review of previous
anesthetic records can be helpful. If visualization of the larynx in a recent anesthetic was difficult but eventually
successful a procedure that can be managed with an LMA may be considered. A child who could only be intubated
fiber-optically in the recent past is best referred to a hospital facility. An additional consideration is the extra time
involved in securing a difficult airway, which would impact the efficiency of the ASC.
Sickle Cell Disease (SCD)
Patients with SCD are at risk for various perioperative complications, and it is imperative that the treating
hematologist must be consulted before any such patient is considered at an ASC. Although it is possible that select
patients with SCD who are well managed and do not require blood transfusion may undergo ambulatory surgery at
an ASC, anything other than minor superficial procedures are best referred to a hospital. This definitely includes
airway (T&A) surgery.
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FURTHER READING / REFERENCES
1. Coté CJ, Zaslavsky A, Downes JJ, et al. postoperative apnea in former preterm infants after inguinal
herniorrhaphy. Anesthesiology 1995; 82:809-822.
2. American Academy of Pediatrics Policy Statement: Critical Elements for the Pediatric Perioperative
Anesthesia Environment. Pediatrics 2015;135 (6):1200-5.
3. Hannallah RS, Brown KA, Verghese SV. Otorhinolaryngologic Procedures. In COTÉ, LERMAN, &
ANDERSON: A PRACTICE OF ANESTHESIA FOR INFANTS AND CHILDREN, Fifth Edition.
Elsevier Philadelphia, PA 2013. (An updated 6th edition is scheduled for early 2017)
4. De Luca Canto G, Pacheco-Pereira C, Aydinoz S, Bhattacharjee R, Tan HL, Kheirandish-Gozal L, et al.
Adenotonsillectomy Complications: A Meta-analysis. Pediatrics. 2015;136(4):702-18.
5. Patino M, et al. Br J Anaesth 2013;111 (S1):i83-95.
6. Schwengel DA, Sterni LM, Tunkel DE, Heitmiller ES: Perioperative management of children with
obstructive sleep apnea. Anesthesia and analgesia 2009; 109: 60-75.
7. Brown KA, Laferrière A, Lakheeram I, Moss IR: Recurrent hypoxemia in children is associated with
increased analgesic sensitivity to opiates. Anesthesiology 2006; 105: 665-9
8. Nixon GM, Kermack AS, McGregor CD, Davis GM, Manoukian JJ, Brown KA, Brouillette RT. Sleep and
breathing on the first night after adenotonsillectomy for obstructive sleep apnea. Pediatric
Pulmonology 2005; 39:332-8.
9. Coté CJ, Posner KL, Domino KB. Death or neurologic injury after tonsillectomy in children with a focus
on obstructive sleep apnea: Houston, we have a problem! Anesth Analg 2014; 118: 1276-83.
10. Welborn LG, Hannallah RS, Norden JM, et al. Comparison of emergence and recovery characteristics of
sevoflurane, desflurane and halothane in pediatric ambulatory patients. Anesth Analg 1996;83:917-20.
11. Mortensen A, et al. Anesthetizing the obese child. Paediatr Anaesth. 2011 Jun;21(6):623-9
12. Doherty GM, Chisakuta A, Crean P, Shields MD. Anesthesia and the child with asthma. Pediatric
Anesthesia 2005;15:446-54.
13. Litman RS and Joshi GP. Malignant Hyperthermia in the Ambulatory Surgery Center: How Should We
Prepare? Anesthesiology 2014;120:1306-8.
14. Marchant WA, Walker I: Anaesthetic management of the child with sickle cell disease. Paediatric
anaesthesia 2003; 13: 473-89.
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Building a Quality Management System
John Allyn, M.D. Portland, Maine
I. Introduction
This lecture will discuss how to build a Quality Management System (QMS) to demonstrate and improve the value
of anesthesia care provided to patients. Before beginning to build a QMS, the principles that should guide the design
and management of the QMS will be reviewed. Culture will be discussed in detail; without trust and universal
support of a vision, any design will fail to meet expectations, regardless of the management tools in place. Culture is
not fuzzy; its strength correlates closely with quality outcomes1. Finally, the structure of the QMS and methods of
data collection, analysis, and feedback will be discussed along with examples and present concerns.
II. Frame of Reference and Disclosure
Maine Medical Center (MMC) has approximately 40 anesthetizing locations on its main campus, 2 of which are
dedicated to obstetrics, 9-10 are located off-site or outside the operating room (ex. endoscopy suite), and there is a
separate outpatient surgery center with 10 operating rooms. On any given day, 24 anesthesiologists, at least 6
anesthesiology residents, and 46 CRNAs, staff these 50 anesthetizing locations. The anesthesiologists are employed
by Spectrum Medical Group (private practice), which markets FIDES, a quality improvement product. Additional
figures and the entire slide set for this RCL will be available from: allynj@spectrummg.com
III. Background and Resources Available
The history of quality assurance or quality improvement is beyond the scope of this RCL; however, the foundations
for this work, the principles guiding the structure and management of a QMS, were provided by individuals such as
Shewhart and Deming. They introduced control charts and the Plan-Do-Study/Check-Act cycle. For those interested,
links to more information about Shewhart and Deming and other topics (ex. Root Cause Analysis, RCA) are
provided at the end of this lecture. Directors of anesthesia services are constantly asked to provide provider-specific
quality outcome data to justify hospital privileges for the Center for Medicare and Medicaid Services (CMS) or an
entity with deemed authority for accreditation for CMS (ex. Joint Commission (JC) or Det Norske Veritas -
Germanischer Lloyd (DNV-GL)). Why this request should be denied and the focus maintained on a provider’s
participation in your QMS, which continues to learn about and improve patient outcomes will be discussed. Links to
more information about CMS’ Conditions of Participation (COPs), JC, DNV-GL, and ISO 9001, including
information about the JC’s Ongoing Professional Practice Evaluation (OPPE) are provided at the end of this lecture.
The ASA and AQI provide resources to help build and maintain a QMS; links to this information and more
information about work to ensure payment for services incentivizes performance improvement (Value-based
Purchasing (VBP); Qualified Clinical Data Registry (QCDR); Perioperative Surgical Home) are provided. Finally,
the safety culture of the QMS will be strengthened when providers understand the state and federal protection
afforded for this work. Links to information about Patient Safety Organizations (PSOs) are also provided.
IV. Why Have a QMS?
First, quality improvement work is required by CMS (COP 482.21) and is most likely also required by your state
regulations and hospital by-laws. For practices with anesthesiology residents, the Accreditation Council for
Graduate Medical Education (ACGME) Clinical Learning Environment Review (CLER) and Next Accreditation
System Milestones require residents to participate in a QMS.2 More importantly, for anesthesiology practices, there
is a growing need to demonstrate value within the health care system. For your practice this may require that you
demonstrate how your anesthetic care positively impacts the patient experience (ex. improved HCAHPS scores,
reduced expense, or LOS) especially when engaged in bundled payment discussions. This year 40% of the VBP
payment to hospitals is derived from outcome measures (ex. Central Line Associated Blood Stream Infections
(CLABSIs), payment is determined by performance in 2014 relative to a benchmark). To survive in this new health
care landscape, a QMS must exist to support data capture and analysis of the quality and cost of care provided to
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patients. Finally, many organizations are presently assessing physician and employee engagement (culture),
discovering challenges, and becoming frustrated in their attempts to develop a strategy to improve. Instead of hiring
engagement consultants, organizations might perform better by investing in their QMS and empowering the front
line to make decisions. Providing resources and restoring a degree of autonomy to physicians and other providers at
the front line might improve engagement scores while allowing the organization to hold these individuals
accountable for aligning with the goals of the organization’s QMS.
V. Guiding Principles
A. QMS and Provider Privileging are Separate Systems.
To achieve quality outcomes two separate systems are required, one assures quality providers, and the other assures
quality systems. Assuring that quality of the providers working within the system is the responsibility of the
provider-privileging process. The quality system is the responsibility of the QMS.
1. Why keep provider privileging (ex. OPPE) and the QMS separate?
Both JC and DNV-GL require provider-specific measures to justify granting hospital privileges to providers and
suggest possible measures for this purpose. However, any measure used to assess hospital privileges by its very
nature has potential negative consequences (i.e. an unsatisfactory measure could mean loss of hospital privileges).
Providers will not participate in a QMS by self-reporting data and openly discussing concerns if their reporting or
reviews might adversely affect their or their colleagues’ ability to practice. However, directors of anesthesia services
are required to perform both functions. Health care quality leaders and the airline industry have recognized this
conflict between provider privileging and a QMS. The Institute of Medicine concludes that “there is a role both for
mandatory, public reporting systems and voluntary, confidential reporting systems. However, because of their
distinct purposes, such systems should be operated and maintained separately.” 3 The Agency for Healthcare
Research and Quality also concludes, “The ability of health care organizations to replicate the successes of other
industries in their use of incident reporting systems will undoubtedly depend in large part on the uses to which they
put these data. Specifically, success or failure may depend on whether health care organizations use the data to fuel
institutional quality improvement rather than to generate individual performance evaluations.” 4 The airline industry
maintains two systems. For pilot “privileges,” the National Transportation Safety Board (NTSB) administers an
accident and event investigation process that might involve judgments regarding pilot competency and punitive
actions such as pilot sanctions and fines. At the same time, to enhance the system’s performance, the Federal
Aviation Administration (FAA) operates the Aviation Safety Reporting System (ASRS) through NASA, a
voluntary, confidential, non-punitive reporting system for the purpose of collecting, analyzing, and responding to
voluntarily submitted aviation safety incident reports in order to lessen the likelihood of aviation accidents
(aviation’s QMS).
2. How do we operate our privileging (OPPE for our hospitals) and QMS separately?
We developed a template for our OPPE measures that includes metrics in all six of the ACGME’s core
competencies.5 Data for each OPPE metric is gathered outside of our QMS. For the provider specific outcome data
that JC requires we report each provider’s participation rate in the QMS, which is neither self-reported nor subject to
patient or surgery related factors (i.e. no risk adjustment is needed). Additional OPPE measures include data from
reviews performed outside of the QMS, such as sentinel event reviews, malpractice cases, and feedback received
(praise or complaints). We rely greatly on the 360° reviews included in our OPPE process. We measure
anesthesiologists’ participation in evaluating their peers (% reviews complete). In addition, 360° reviews of each
anesthesiologist by CRNAs have been very valuable. The final determination of privileges is based on a subjective
assessment of these largely qualitative data by a committee separate from the QMS and is based on observed trends
in their professional performance. We find this to be a robust process that identifies deficiencies, resulting in
recommendations and actions for individual providers that lead to successful remediation of those deficiencies.
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B. Focus on Systems.
Focusing on the system’s performance should be the goal of any QMS. Deming estimated that 94% of performance
issues were the result of system issues and only 6% were due to a special cause (human error or machine failure).6
Therefore it should be expected that focusing on the performance of individual providers (peer review) will do little
to improve the system’s overall performance. Removal of a few “bad apples” (ex. subpar providers for a group of
process measures) does little to improve the overall average performance of the system. In contrast, education of all
providers in the system (ex. adopting a new protocol) may greatly enhance the system’s performance, improving
care provided to all patients. Hopefully, this improvement in patient care manifests as both an increase in the
system’s mean performance and a reduction in the variability around this mean. One exception: a system must not
tolerate individual behavior that is consistently toxic to the organization’s culture.
C. We are human.
As humans, we will make mistakes. Reason points out that our fallibility is predictable and rooted in the essential
and adaptive properties of our cognition. Human errors are the penalties, the debt side of the cognitive “balance
sheet,” for our remarkable ability to handle complex problems. 7 Human errors are not intentional, the individuals
involved should not be judged, but rather consoled, and the system assessed and modified to prevent future errors.
Other factors that may affect system performance are at-risk and reckless behaviors; individuals should be held
accountable for the latter behavior. At-risk behavior may not reflect the desired performance of a team member, but
rather a learned behavior in response to the existing environment. Our primary goal must be patient safety, but at
times efficiency, a secondary goal, may obscure this primary goal. An example would be rushing to set up a room to
decrease turnover time and neglecting a safety check. At risk behaviors should be addressed with coaching.8
D. “Culture eats strategy for lunch” or “Culture trumps tools”
Integrity and trust must define the foundation of the group’s culture and be demonstrated continuously in the
behaviors of the leaders of both the group and the QMS. Providers must feel safe when reporting concerns and feel
confident that their leaders are guarding the group’s safety culture. When providing information for the QMS,
providers should not feel they are reporting themselves, but rather are highlighting a safety concern for the entire
group. “Defects are treasures” and without a robust reporting culture, becoming a strong learning organization is not
possible.9,10 Consequently, without learning, resources would be wasted attempting to design an effective strategy
for improving patient care. In other words, a sophisticated reporting tool will be useless if the organization’s culture
does not support or trust how the data will be used.
Ongoing education about measurement is needed to support the group’s safety culture. When an audience hears that
there is a difference in outcome between individual anesthesia providers, the assumption is often that this difference
represents a disparity in the quality of care provided. We remind providers that because of a lack of clear data
definitions, robust risk adjustment, and chance, we do not have the ability to assign a variance in a provider-specific
outcome measure to a deficiency in the quality of anesthesia care provided by an individual. This last point cannot
be over-emphasized. To strengthen our culture, we are constantly protecting principle A above. Accrediting
organizations, such as the JC, will ask to see quality data that is provider-specific. We respond to this request by
providing our OPPE (or Focused Professional Practice Evaluation, FPPE) data that includes provider specific
participation rates in the QMS. This latter measure does not need risk stratification, is entirely under the control of
the provider, and can be assessed in a statistically meaningful manner. We then demonstrate the improvements in
patient outcomes that our QMS has produced over time with this high level of participation. We also re-state the
reasons outlined above that we keep our QI data separate from provider privileging data (OPPE). Finally, we point
out the existence of separate successful confidential reporting systems (QMS) and public reporting systems
(privileging) used by the airline industry as discussed in detail above. We believe this dialogue strengthens our
culture and thus improves our QMS.
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E. The goal may not be zero.
There are frequently unintended consequences of quality improvement work, not the least of which is resource
consumption. The consequence of aiming to reduce hospital readmission rates to zero may be added expense for a
long hospital stay. In addition, when provider-specific outcome measures are made public, high-risk patients may be
denied care.11,12 Certainly challenging your QMS to eliminate CLABSIs makes sense; however, labeling a pediatric
oncologist as “subpar” when his/her patients continue to have CLABSIs may not be fair. The patient factors
presented by this pediatric oncology patient population, including maintenance of the central line outside the
hospital, may be well outside the scope of the resources the pediatric oncologist is provided to influence this
outcome.
F. QMS takes resources.
Over a decade ago, the Institute of Medicine recognized the importance of resource allocation for a successful QMS.
The IOM states: “reporting systems without adequate resources for analysis and follow-up action are not useful.
Reporting without analysis or follow-up may even be counterproductive in that it weakens support for constructive
responses and is viewed as a waste of resources.”3 We have had experiences in our own practice that reinforce this
message. One of our greatest challenges is creating communication that provides effective education and serves as a
future reference for all members of the perioperative team. We can attempt to communicate at grand rounds or
morbidity and mortality conferences; however, not all anesthesia providers are present at these conferences
(vacations, working at different sites, conflicting meetings, on call etc.). We supplement this by sending emails with
educational content as well as posting new guidelines and protocols on our group’s resource web site
(theapms.com). Despite our efforts, we continue to make repeated errors. At one institution we were forced to repeat
a RCA surrounding a medication error, a medication error that had occurred in the same way, on the same unit, but
with different providers, two years earlier. In addition, when on-boarding new employees it is important to include
prior communication and education about patient safety concerns. How your department and hospital, or system,
manages these educational efforts can either help or hurt your QMS. The harm to your QMS occurs, in part, when
individuals spend valuable hours creating educational content that is not distributed effectively to produce a system
change and takes these same providers away from productive work for the QMS. As mentioned above, the ACGME
focuses heavily on residents participating in patient safety and quality improvement work. The CLER Program
assesses the sponsoring institution in six focus areas, two of which are patient safety and quality improvement. For
patient safety, the organization must demonstrate opportunities for residents to report errors, unsafe conditions, and
near misses, and to participate in multidisciplinary teams to promote and enhance safe care. 2 Within quality
improvement, how the sponsoring institution engages residents in the use of data to improve systems of care, reduce
health care disparities, and improve patient outcomes will be assessed. The milestones for anesthesiology residents
within the practice-based learning and improvement competency require a junior resident to select a topic for a
quality improvement project, a mid-level resident to develop an implementation plan, and a senior resident to
implement a plan for a quality improvement project. Certainly inclusion of learners in the QMS must happen for the
system to perform at its highest level; however, simply creating a program requirement for residents to create or
participate in a QI exercise during their training may put the department or institution’s QMS at risk. Each resident
designing a QI project will need resources, including mentorship and data, to be successful. In addition, these
resident QI projects must be collaborative and coordinated. If the end result for your institution is that you have both
a pediatric and an anesthesiology resident working independently on crisis checklists for managing the perioperative
care of neonates, individuals in both departments are likely to become frustrated, valuable resources will be lost, and
the performance of the QMS will suffer.
VI. Structure of QMS
The department or service line’s QMS should be structured to align with hospital or health system priorities.
Specifically, how a safety concern (ex. possible sentinel event) can be communicated reliably and efficiently to the
hospital’s patient safety officer should be defined; in turn the QMS may be asked to review concerns identified by
hospital leadership. Today we lack a robust inter-departmental quality and safety communication structure, but are
working to build this within a new service line structure. Originally our department’s Quality Improvement
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Committee (QIC) consisted only of anesthesiologists. Over time, we learned the value of including all members of
the perioperative team. Today, the committee includes all types of anesthesia providers, anesthesia techs,
perioperative nurses, and surgical techs. At one time we included a representative nurse from one of the busy
postoperative hospital floors; however, we struggled to create content that made monthly attendance valuable for
this individual. The wide representation on the committee enhances the QMS’ ability to capture and respond to
safety concerns while challenging the QIC to make valuable use of each member’s time. Our QIC meets monthly
and administrative support is provided to keep minutes; these minutes provide the foundation for the next meeting’s
agenda and assure that concerns are not “lost.” The QIC has one subcommittee, the Critical Incident Committee
(CIC), which reviews all critical events (ex. perioperative cardiac arrest). The CIC is made up of anesthesia
providers only. Members are assigned cases to review prior to meetings and a structured form is used to review each
case. Periodically the CIC provides reports to the QIC and may also provide education to the department if specific
concerns/trends are identified. New members of the department (anesthesiologists) are required to attend these
meetings for one year.
VII. Data Capture
The QMS needs reliable and sufficient data to function. To acquire this data, the QMS must have a protected and
efficient means for providers, recovery room nurses, and perhaps others to provide the desired information. Both
paper and electronic reporting forms can be used. These forms will need constant review, and education about data
field definitions needs to occur periodically. The intraoperative indicators for MMC’s QMS are shown in Appendix
1. The data entered by providers or recovery room nurses is linked to data already in our billing data base (ex.
procedure) to decrease the amount of data providers must enter, but also strengthen the scope of questions the QMS
is able to address. For certain sites of service, our QMS has specific forms to improve efficiency and performance:
specific patient type forms (ex. obstetrical patients) or procedure type forms (ex. ECT) allow for a focused
simplified data set in these areas.
VIII. Data Analysis and Feedback
Quality improvement is not achieved by collecting data or sending data to a registry. MMC’s program began in this
manner, but we now better understand the investment needed for data analysis and we are constantly learning how to
provide feedback in a manner that supports further dialogue and leads to improvements in patient care. Early reports
generated by our QMS were not always easy for individual providers to interpret and we implemented very few
quality improvement tests of change. Today we track “high frequency events” such as first temperature on arrival to
PACU or recovery room nausea or vomiting rates using trend graphs. Our QIC reviews these trends every 3-6
months. We have learned that it may take several years for us to demonstrate a sustained change or to recognize a
variance. For some of this data we have explored use of a statistical process control chart. For “low frequency
events,” such as desaturation in the operating room or recovery room, we group these data elements into categories
(ex. desaturation would be grouped with difficult intubation and reintubation). Each category of low frequency
events (equipment, hemodynamics, etc.) is then assigned to one anesthesiologist to review. Periodically, the
anesthesiologist assigned to review each category reports to the QIC and discusses any concerning trends in need of
further investigation.
The QMS also supports ad hoc analysis. As part of this analysis, even if the QMS is performing well on average for
all patients, we continue to learn. Two examples are provided below. Additional examples will be provided in the
lecture.
A. Crisis Management
Over a year ago our QI committee distributed crisis checklists to all anesthetizing locations. However, we are still
learning how best to educate the team about the existence and use of these checklists. When used, we have great
examples of success; however, their use has helped develop further questions. A long discussion about roles for the
peri-operative team during “codes” has led to developing a framework for a debriefing discussion for these events
and other crises (ex. massive transfusion).
B. Patient Satisfaction
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This example is now a few years old, but remains as the focus on the patient-rated outcomes continues to increase.
On average, our outpatients are very satisfied with their anesthesia care when asked as part of a postoperative phone
call (POD #1) by a preoperative nurse. However, our QIC chair tried to understand how we might be failing to meet
some patients’ expectations. A preliminary analysis demonstrated that two of our anesthesiologists were more likely
to have patients that were dissatisfied with their anesthesia care. We lack the ability today to risk adjust this
measure, but we discovered as part of this analysis that patients receiving care at one of our facilities were more
likely to be dissatisfied and in fact, they were more likely to be cared for by a particular group of surgeons that
practice at that facility. The two individual anesthesiologists identified in the initial analysis as having higher rates
of patient dissatisfaction practice more frequently at this facility and with these surgeons. Feedback to this individual
surgery practice has resulted in a decrease in the in the rate of patients’ dissatisfaction with their anesthesia care at
this facility and thus also for these two anesthesiologists.
IX. Feedback to Individual Providers for Self-Reflection
Our QMS lacks adequate risk adjustment tools and adequate numbers of cases to identify a statistically sound
difference in the quality of anesthesia care delivered by two providers. As stated previously, we believe utilizing QI
data for such purposes would also inevitably lead to under reporting and undermine our safety culture. We have thus
chosen not to use clinical outcome measures to judge our providers; however, we do provide feedback reports to
each individual provider in our practice for self-reflection; no one else reviews these individual reports. These
reports allow the individual provider to see their own outcome rates (ex. recovery room nausea and vomiting) as
well as the group average for the same data elements. We encourage providers to evaluate any variance in their rate
from the group average and consider possible hypotheses for the variance and implement tests of change in their
own practice. We believe dialogue about these variances also strengthens our culture. An example of self-reflection
leading to improvement would be a provider noting that his recovery room nausea and vomiting rates were higher
than the group average for patients cared for at an outpatient facility; a small subset of providers work at this facility
and the patients and procedures at the facility are relatively homogeneous. After comparing his practice with his
peers working at this facility, this provider implemented a change in his practice and reduced his rate of recovery
room nausea and vomiting to the group average for that facility.
The QMS also provides many types of reports. At times specific proceduralists will ask for data on their patients. In
addition, the QMS may respond to help confirm resident case numbers or compliance with SCIP measures (for
example). At times a query of our QMS will be the first step for the hospital when a process of care is being
evaluated. Finally, annual reports are provided to the group and the hospital.
X. Next steps
At present we are in the midst of several projects.

1. Our hospital has just adopted a QI tool that is designed to bring leadership daily to the frontline staff on
each patient care unit (ex. OR or PACU) to hear about the unit’s quality work and to help remove barriers.
As a department we are discussing how we best support this work and connect this process to our own
quality goals. For example, crisis management was mentioned above, and we are presently measuring
whether the team members’ names are on the white boards in each OR for every case.
2. Structured handoff tool (checklist) for transferring care to a recovery room nurse.
3. We continue to try to understand better what patients mean when they answer that they are satisfied or
dissatisfied with their anesthetic care.
4. We now have crisis checklists in each anesthetizing location, but need to continue to train the team in their
use.
5. We recently changed our peri-operative warming strategy for patients receiving total joint replacements and
are studying the impact of this change.
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References:
1. Leonard MW, Frankel A. The path to safe and reliable healthcare. Patient education and counseling. Sep
2010;80(3):288-292.
2. ACGME. Clinical Learning Environment Review (CLER) Program. 2013;
http://www.acgme.org/acgmeweb/tabid/436/ProgramandInstitutionalAccreditation/NextAccreditationSyste
m/ClinicalLearningEnvironmentReviewProgram.aspx. Accessed 4/25/13, 2013.
3. Kohn LT, Corrigan J, Donaldson MS. To err is human : building a safer health system. Washington, D.C.:
National Academy Press; 2000.
4. Barach P, Small SD. Reporting and preventing medical mishaps: lessons from non-medical near miss
reporting systems. BMJ. Mar 18 2000;320(7237):759-763.
5. ACGME. Program Requirements for Graduate Medical Education in Anesthesiology. 2016;
https://www.acgme.org/Portals/0/PFAssets/ProgramRequirements/040_anesthesiology_2016.pdf. Accessed
5/4/2016, 2016.
6. Deming WE. Out of the crisis. 1st MIT Press ed. Cambridge, Mass.: MIT Press; 2000.
7. Reason JT. Human error. Cambridge England ; New York: Cambridge University Press; 1990.
8. Marx D. Whack-a-mole : the price we pay for expecting perfection. Plano, TX: By Your Side Studios;
2009.
9. Just Culture and its Critical Link to Patient Safety (Part 1). 2012;
http://www.ismp.org/Newsletters/acutecare/showarticle.asp?id=22. Accessed 4/25/13, 2013.
10. Just Culture and its Critical Link to Patient Safety (Part 2). 2012;
http://www.ismp.org/Newsletters/acutecare/showarticle.asp?id=26. Accessed 4/25/2013, 2013.
11. Lee TH, Torchiana DF, Lock JE. Is zero the ideal death rate? The New England journal of medicine. Jul 12
2007;357(2):111-113.
12. Moscucci M, Eagle KA, Share D, et al. Public reporting and case selection for percutaneous coronary
interventions: an analysis from two large multicenter percutaneous coronary intervention databases.
Journal of the American College of Cardiology. Jun 7 2005;45(11):1759-1765.
Appendix 1: The intraoperative indicators collected for MMC’s QMS. The indicators collected by the AQI or the
ABG are noted in the left hand column.
ABG AQI Indicator
X X No Listed Observations/Interventions
Other Major Morbidity/Mortality
X Blue button/STAT page
Crisis Checklist Used
X Death
Airway/Respiratory
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X Unable to intubate
Expected Difficult Intubation
X X Unexpected Difficult Intubation
Difficult mask airway
Reintubation in OR
Unable to extubate in OR
Desaturation <90% for >3 min. or <80% for >1 min
Narcan/Flumanzenil given
X X Pulmonary edema requiring intervention
X X Bronchospasm requiring intervention
X X Laryngospasm requiring intervention
X Suspected aspiration
CardioVascular
Arrhythmia requiring treatment
X Myocardial infarction requiring intervention
X X Myocardial ischemia requiring intervention
X X Cardiac arrest
X X Hypotension (requiring vasopressor infusion)
Neurologic
X Seizure
X Central nervous system injury/Ischemia
New neurologic symptoms
Head/Neck Trauma
X Dental Trauma
Regional/Procedural
X X Failed regional (requiring GA or repeat for any reason)
X High spinal (requiring airway management)
X X Local anesthetic toxicity
X X Unintended dural puncture
X X Pneumothorax
X X Vascular access complication
Non-functioning catheter
Catheter not secured properly
Catheter disconnection
Catheter displaced
Remove catheter, technique change for side effects
Sedation or respiratory depression req. Naxolone
Neuro consult requested
Pharmacy/Blood Bank
X X Medication event
X Unexpected drug reaction
X X Malignant hyperthermia
Received blood transfusion
X X Anaphylaxis
X Transfusion Reaction
Patient Safety
X X Incorrect surgical site, side, patient, procedure, implant
X X Equipment malfunction
Near miss/Safety concern
X X Patient Burn/Fire
X X Patient Fall
Discharge/Planning
Case canceled in OR
X X Unplanned ICU admit
Miscellaneous
X Other
“Building a Quality Management System”

Dr. John W. Allyn, Spectrum Medical Group
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Resources:
1. Shewart: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2464836/
2. Deming: Deming Institute: https://deming.org/theman/overview
3. Donabedian: The quality of medical care. Science. May 26 1978;200(4344):856-864. (introduced structure,
process, and outcome measures)
4. Root Cause Analysis (RCA): http://psnet.ahrq.gov/primer.aspx?primerID=10
5. RCA2: Improving Root Cause Analyses and Actions to Prevent Harm:
https://psnet.ahrq.gov/resources/resource/29089/rca--improving-root-cause-analyses-and-actions-to-prevent-
harm
6. Failure Mode Effect Analysis: Description and example from Institute of Safe Medical Practices (ISMP):
http://www.ismp.org/tools/FMEA.asp
7. Lean Manufacturing discussion: Lean Manufacturing discussion:
http://www.lean.org/WhatsLean/
8. Centers for Medicare and Medicaid Services (CMS): CMS defines Conditions of Participation (COP) for
payment for anesthesia services. https://www.cms.gov/Regulations-and-
Guidance/Guidance/Transmittals/downloads/R74SOMA.pdf. These COP require QI work. In addition, “never
evens” – ex. Lack of payment for complications secondary to CLASBI or readmissions force hospitals to
improve their quality of care to avoid these complications.
9. Never Events: http://psnet.ahrq.gov/primer.aspx?primerID=3
10. Physician Quality Reporting System (PQRS):
a. http://www.cms.gov/Medicare/Quality-Initiatives-Patient-Assessment-
Instruments/PQRS/index.html?redirect=/pqri/
b. http://www.cms.gov/Medicare/Quality-Initiatives-Patient-Assessment-
Instruments/PQRS/Downloads/Physician_Quality_Reporting_Programs_Strategic_Vision_Docum
ent.pdf
c. More from the ASA on PQRS in the members only section: http://www.asahq.org/
11. The Joint Commission (JC). In 1910 Ernest Codman proposed that hospitals standardize and track patient
outcomes. When the American College of Surgeons (ACS) was founded in 1913, this principle was adopted and
the ACS began to inspect hospitals. In 1951, the American College of Physicians (ACP), the American Hospital
Association (AHA), the American Medical Association (AMA), and the Canadian Medical Association (CMA)
joined with the ACS as corporate members to create the an independent, not-for-profit organization, The Joint
Commission on Accreditation of Hospitals (JCAH), whose primary purpose is to provide voluntary
accreditation. (http://www.jointcommission.org/about_us/history.aspx) The JC publishes standards that
hospitals must meet to maintain accreditation. The JC has an entire chapter dedicated to Performance
Improvement. Most of the JC material must be purchased. More information is available at:
http://www.jointcommission.org/. In 2007, JC introduced two new privileging concepts, Ongoing Professional
Practice Evaluation (OPPE) and Focused Professional Practice Evaluation (FPPE) that require provider-specific
measurements as part of the hospital privileging process. (ex. Joint Commission Hospital Accreditation
Standards. MS.08.01.03)
12. Det Norske Veritas (DNV) was established in 1864, initially as a company that would inspect and evaluate
merchant vessels. They are relatively new to healthcare in the USA. DNV uses ISO 9001 for the design and
maintenance of a QMS. In 2013 DNV merged with Germanischer Lloyd (GL). More information about DNV-
GL is available at: http://dnvglhealthcare.com More information about ISO 9001 is available at
http://www.iso.org/iso/iso_9000
13. ASA’s MADOM – The American Society of Anesthesiologists’ Quality Management and Department
Administration Committee maintains a Manual for Anesthesia Department Organization and Management,
which provides guidance for building and managing a QMS. This is available (free to members) at:
https://ecommerce.asahq.org/p-154-madom-2010-manual-for-anesthesia-department-organization-and-
management.aspx
14. The Anesthesia Quality Institute (AQI) website offers guidance in building and maintaining a QMS. In addition,
the website provides definitions for the measures collected by AQI, how to join AQI and obtain assistance
moving data to AQI. Recently the ASA’s Closed Claims Database became part of AQI. Finally, the web site
provides more information about the importance of the AQI becoming a Qualified Clinical Data Registry
(QCDR). More information at: http://www.aqihq.org and at http://www.asahq.org/qcdr.
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15. Patient Safety Organization: Patient Safety and Quality Improvement Act, Public Law 109-41, §924 (2005).
More information at: https://pso.ahrq.gov/legislation/act
16. Patient Safety Culture:
a. http://www.ismp.org/Newsletters/acutecare/showarticle.asp?id=22
b. http://www.ismp.org/Newsletters/acutecare/showarticle.asp?id=26
17. Perioperative Surgical Home: http://www.asahq.org/psh
18. CMS Value-Based Purchasing:
a. http://www.cms.gov/Outreach-and-Education/Medicare-Learning-Network-
MLN/MLNProducts/downloads/Hospital_VBPurchasing_Fact_Sheet_ICN907664.pdf
b. https://www.cms.gov/Medicare/Quality-Initiatives-Patient-Assessment-Instruments/hospital-
value-based-purchasing/index.html
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Substance Abuse in Pregnancy

Lisa Leffert Boston, MA
Although the prevalence of substance abuse in pregnancy is less than in non-pregnant women of child-
bearing age, recent national statistics reveal that 5.4% of pregnant patients abused substances, with the highest
prevalence in the youngest age group represented (age 15-17 years;14.6%).1 This misuse continues throughout the
trimesters, although it is highest in the first trimester (9.0%) and lowest in the third (2.4%).
Depending on the substance used, there can be significant maternal, perinatal and anesthetic implications.
Opioids
Introduction
There has been explosive growth in opioid use and abuse in the United States in both the pregnant and non-
pregnant populations. Currently, the United States accounts for 80% of the opioids consumed worldwide.
Unfortunately, women are particularly prone to death due to abuse of and addiction to opioids. In a recent
population based review of over 56 million delivery admissions, the prevalence of opioid abuse or dependence was
shown to have increased 127% between the years 1998 and 2011, 2 with the highest increase in the 20-34 years old
age group. The suppliers of these opioids are often physicians: 14.4% of pregnant women with commercial
insurance3 and 21.6% of pregnant women with governmental insurance4 were recently found to have filled an opioid
prescription. The pregnant women with commercial insurance were most commonly prescribed opioids during their
third trimester (6.5%) 3 whereas those with governmental insurance typically received the opioids in their first
trimester (10.5%).4 Frequently treated conditions included back pain, headache, and abdominal pain.
Opioids were likely chosen because they have historically been thought to be the safe medications to use in
pregnancy. However, this notion is rapidly changing. The FDA has issued a back-box warning on immediate-release
opioids, highlighting the risk of “misuse, abuse, addiction, overdose and death”. Specific opioids of abuse include
non-medical use of oxycodone and diamorphine (heroin), both semi-synthetic opioids, and more recently, fentanyl.
Hydrocodone and oxycodone are commonly prescribed for post cesarean delivery pain management following
discharge. There are data to suggest that women often use substantially fewer tablets than the number prescribed,
likely resulting in unused tablets in households throughout the country. Although diamorphine is employed as an
analgesic agent in the United Kingdom, there is no clinical use in the United States. When used illicitly, heroin is
often combined with fentanyl, which increases the number of deaths from overdose. Other opioids of abuse include
other oral or IV morphine formulations (e.g. oxycontin) and substitution therapies (e.g. subutex). Crossover between
prescription opioid and heroin abuse has also been observed. Studies have shown that heroin users were almost four
times more likely to report nonmedical use of opioids in the previous year, and the nonmedical use of multiple
opioids has been associated with a transition to heroin.5-7
Fetal and Maternal Effects

Opioid abuse in the antepartum period has several potential negative effects on the pregnancy. A
retrospective study in women exposed to a variety of opioids in the first trimester of pregnancy suggested a higher
incidence of neural tube defects (aOR: 2.2, CI: 1.2-24.2).8 Though well designed and comparable with prior animal
studies, this study was subject to recall bias. In addition, pregnancies associated with opioid use/dependence during
pregnancy were found to have an increased risk of cesarean section (adjusted Odds Ratio (aOR): 1.2, Confidence
Interval (CI): 1.1-1.3), oligohydramnios (aOR: 1.7, CI: 1.6-1.9), preterm labor (aOR: 2.1, CI: 2.0-2.3), IUGR (aOR:
2.7, CI: 2.4-2.9). In the same study, these pregnancies were also associated with an increased risk of an extended
length of stay (aOR: 2.2, CI: 2.0-2.5) and in-hospital mortality (aOR: 4.6, CI: 1.8-12.1)!2 Women who abuse
opioids are more likely to engage in smoking and other polysubstance abuse, and are more likely to have
concomitant infectious disease (e.g. HIV or Hepatitis B or C). As with substance abuse in general, these women
often have untreated psychiatric disorders and sexual promiscuity, which leads to more frequent pregnancies. Their
subsequent lack of prenatal care is then associated with more frequent pregnancy complications.
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Acute detoxification is generally not recommended during pregnancy, in part due to the fear of
uncontrolled maternal and fetal withdrawal. The American College of Obstetricians and Gynecologists (ACOG)
recommends medically supervised substitution therapy with associated counseling and general prenatal care rather
than detoxification for these women.9 Common substitution therapies include methadone or buprenorphine (i.e.
subutex and suboxone). Although methadone was historically the substitution therapy of choice, the relative ease of
patient access to buprenorphine (i.e. the receipt of a multi-day supply rather than a daily visit to the clinic) and the
apparent decreased duration and severity of neonatal abstinence syndrome, have made buprenorphine an
increasingly popular choice during pregnancy.10 Breastfeeding is also endorsed in postpartum women who are on
stable substitution therapy program, are not abusing other illicit substances, and are not HIV positive.
The altered physiology of opioid abusing parturients and the pharmacology of their substitution therapy
contribute to challenges in their peripartum anesthetic care. Whenever feasible, a pre-delivery anesthetic consult can
help to establish trust between the patient and her providers, and an opportunity to discuss the multi-modal menu of
care options. These patients are typically tolerant to the analgesic effects of opioids, likely through a combination of
chronic changes in pain pathways, and, in those receiving buprenorphine, the very high µ receptor affinity of the
drug. It is the competition at the µ receptor between buprenorphine and other opioids that inhibits pain management,
not the small amount of naloxone (with low oral bioavailability) that’s incorporated into suboxone to discourage
intravenous injection. It is crucial that patients on substitution therapy NOT receive the mixed agonist/antagonist
medications so commonly used on labor floors (e.g. nalbuphine, butorphanol) as their use may precipitate maternal
and fetal withdrawal.
Neuraxial analgesia for labor, or anesthesia for cesarean delivery, is highly desirable if not otherwise
contraindicated. Studies show that the intrapartum pain scores for parturients on methadone and buprenorphine who
received neuraxial analgesia or anesthesia are reasonably similar to their respective controls. However, post-
cesarean delivery pain management needs between patient populations were dramatically different from controls not
on maintenance therapy. Specifically, obstetric patients on methadone therapy needed 70% more opiate analgesic
and those on buprenorphine needed 47% more opiate analgesic. However, these patients are not necessarily tolerant
to the sedative effects of additional opioids or adjunct medications, 11,12 likely increasing their risk of respiratory
compromise.
Substitution or chronic opioid therapy does not contribute significantly to acute pain management, but
should be maintained at a consistent level to satisfy chronic requirements. A patient’s methadone dose should be
confirmed with the primary prescriber and adjusted in collaboration with him or her, if needed. There are several
options for peripartum buprenorphine management, outlined in Table 1.
Pearls and Tips:

 Know the obstetric plan: likely vaginal delivery unless otherwise contraindicated
 Avoid other agonist-antagonist therapy
 e.g. Nalbuphine, butorphanol, pentazocine, naloxone
 Be creative (think multimodal therapy)
 For labor:
 Early epidural placement
 If persistent breakthrough pain, think non-functional catheter
 For post-cesarean delivery pain management:
 Include non-steroidal anti-inflammatory agents (NSAIDs) & Tylenol as standard care
 Tranversus abdominis plane blocks or catheters may be beneficial
 Consider neuraxial opioid (e.g. duramorph) +/- local anesthetic (e.g. PCEA) for first 12-
24 hours
 If adding adjunct medication with sedative effects (e.g. po gabapentin) or epidural
clonidine, must monitor patient closely for respiratory compromise.
 Intravenous opioids (via patient-controlled analgesia), as needed, without background
rate. Monitor patient closely for respiratory compromise.
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Alcohol
Introduction
Alcohol abuse occurs at a rate of 9.4% in the pregnant population, with about 0.4% reporting heavy use in
2012-3.1 Withdrawal from alcohol can produce the syndrome of tremor, confusion, electrolyte abnormalities, and
seizures (i.e. Delerium Tremens) which can be modulated by benzodiazepines (with or without dexmedetomidine),
haloperidol, or clonidine.
Maternal and Fetal Effects

Alcohol use acts as both a stimulant and a depressant to the maternal central nervous system through a
variety of neurotransmitters; endogenous opioids further reinforce alcohol use. Alcohol and metabolite
(acetaldehyde) are directly toxic to the brain. Heavy consumption can lead to cirrhosis with encephalopathy,
coagulopathy, and esophageal varices, each of which can complicate anesthetic management.
Alcohol use causes the single most preventable fetal birth defect (specifically fetal alcohol syndrome) which can
range in severity to characteristic facial features, failure to thrive and brain damage.
Anesthetic Implications
As is true in obstetrics in general, neuraxial anesthesia is preferred to general anesthesia if the patient is
otherwise an appropriate candidate.
Tips and Pearls:

 Airway
 Aspiration risk
▪ Decreased lower esophageal sphincter tone
 More colonization with pathologic bacteria
 Effect on minimum alveolar concentration (MAC)
 If acute intoxication, decreased MAC
 If chronic intoxication, increased MAC
▪ High risk of awareness
 Effect on P-450
 Short-term consumption- competes with P-450
 Long-term consumption- increases P-450 (associated with decreased levels of diazepam, labetolol)
 Causes decreased pseudocholinesterase levels, although not clinically significant
Cannabis
Introduction
Six to seven (6-7)% of pregnant women report recent cannabis use, but as it is often associated with
polysubstance abuse, it is difficult to separate out the cannabis-specific effects. Also, cannabis contains more than
400 compounds (>60 Cannabinoids) with THC responsible for most of psychotropic effects. Because cannabis is a
highly lipid-soluble drug that is sequestered in fatty tissues, it has a long elimination half-life (7 days or 1 month for
its metabolites).13-15

Cannabis interacts with peripheral and central cannabinoid receptors producing psychoactive effects
including primarily euphoria, anxiolysis, analgesia, and appetite suppression. 16 There is a biphasic effect on the
autonomic system with low doses producing a sympathetic effect and high doses, a parasympathetic effect. 17,18
Maternal effects center primarily around disruption of the airway due to smoking inhalation. A mild maternal
abstinence syndrome occurs with discontinuation of the drug. Although cannabis does pass through the placenta,
determination of the fetal effects is confounded by the frequent coincident use of other illicit substances.
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As is true in obstetrics in general, neuraxial anesthesia is preferred to general anesthesia if the patient is
otherwise an appropriate candidate
.
Tips and Pearls:
 Hemodynamic perturbations are minimal
 Atropine, ketamine may exacerbate tachycardia
 If general anesthesia, expect:
 Increased airway secretions
 Impaired mucociliary clearance
 Increased airway reactivity
 Produces an additive effect with other sedatives
 May have effect on pain perception19
 Low dose- no effect Medium dose- decrease pain High dose- increase pain
Stimulants
Introduction
Stimulants include cocaine, and the amphetamine analogues such as methamphetamine (i.e. “speed”;
methyl radical), Ecstasy (“MDMA”; methylenedioxy group confers hallucinogenic effects), ɣ hydroxybutyric acid
(GHB), 3, 4-methylenedioxypyrovalerone (MDPV or bath salts). These drugs of abuse are of particular interest to
anesthesia providers because of their intense activation of the sympathetic nervous system through release of and
block of reuptake of relevant neurotransmitters. The half life of amphetamines is approximately 12 times longer
than cocaine (12 vs. 1 hour). Cocaine is unique in its local anesthetic effects, although it is rarely, if ever, still used
for this purpose.17

Both Cocaine and Amphetamines can produce pathologic multi-organ sympathetic stimulation resulting in
myocardial ischemic, cardiac arrest, and stroke.17 Drug-induced hypertension can mimic severe preeclampsia.20
Fetal effects of antepartum use of these stimulants are associated with placental abruption, preterm delivery, and the
need for urgent cesarean delivery.21-23 Initial concern for congenital birth defects has not been corroborated in the
literature.
Neuraxial analgesia or anesthesia has several advantages in parturients who have consumed stimulants.
Advantages include decreasing circulating catecholamines, addressing pain management in a population where
changes in µ and κ opioid receptors and altered endorphin levels may increase pain, and providing an in situ epidural
catheter for conversion to surgical anesthesia in this high risk population. The thrombocytopenia initially associated
with cocaine use has not been confirmed in follow up studies.24 Challenges include potential for hemodynamic
instability. Although refractory hypotension in a long-time amphetamine user has been reported, use of IV fluids
and, if needed, direct-acting vasopressors is typically successful.18,24,25
Tips and Pearls:

 If hypotension, consider direct-acting rather than indirect acting vasopressor (e.g. phenylephrine).
 Avoid selective β-blockers leaving unopposed α blockade (i.e. choose labetalol rather than
propranolol)
 Cocaine could compete for available plasma cholinesterase
 For General Anesthesia:
▪ Induction:
 Airway
 Rotten teeth (“meth mouth”)
 Nasal septal defects
 Airway Burns
 Delayed Gastric Emptying
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 Avoid Ketamine
 Blunt hemodynamic response:
 If hypertension, consider nitrates
▪ Maintenance:
 Changes in µ and κ opioid receptors and altered endorphin levels may increase
pain
 Acute ingestion increases MAC according to animal studies
 Chronic ingestion decreases MAC
 Monitor for hyperthermia
Summary
In summary, the excessive use, abuse, and dependence on substance such as opioids, alcohol, and
stimulants during pregnancy can place both the parturient and the fetus at risk for adverse effects. The provision of
safe and effective maternal and fetal care is facilitated by a culture of trust, and an understanding of the physiologic
effects of the ingested substances. Whenever possible, an early anesthesia consult can facilitate planning. In most
instances, neuraxial anesthesia is the technique of choice for labor analgesia and cesarean delivery anesthesia if not
otherwise contraindicated or ill- advised. If the parturient has a history of opioid abuse, then she is not a candidate
for the mixed agonist-antagonist opioid medications frequently used for systemic labor pain management. If she
receives and is not comfortable with her labor epidural, then she should be assumed to have a dysfunctional catheter
unless proven otherwise. Opioid substitution therapy should be continued in the background to satisfy a parturient’s
chronic needs, with additional acute pain management tailored to the delivery plan. Working together as a
multidisciplinary team with the patient can maximize patient safety, pain management and satisfaction.
Table 1: Intrapartum Buprenorphine Management Options

Options Pro Con
Opioid Replacement ↑↑ μ receptor availability for Logistical challenge; Withdrawal
(prior to admission) analgesic opioids Risk
Stop Dose ↑ μ receptor availability for Risk of withdrawal; ↑opioid
(on admission) analgesic opioids requirements
Usual Dose Continuity ↑↑opioid requirements
Divided Doses ↑ analgesia May miss doses
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Toxicology and Maternal Self-Report. Pediatrics. 2001;107(2):309-317.
14. Arria AM, Derauf C, Lagasse LL, et al. Methamphetamine and other substance use during pregnancy:
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20. Towers CV, Pircon RA, Nageotte MP, Porto M, Garite TJ. Cocaine intoxication presenting as preeclampsia
and eclampsia. Obstet Gynecol. 1993;81(4):545-547.
21. Kain ZN, Rimar S, Barash PG. Cocaine abuse in the parturient and effects on the fetus and neonate. Anesth
Analg. 1993;77(4):835-845.
22. Gouin K, Murphy K, Shah PS. Effects of cocaine use during pregnancy on low birthweight and preterm
birth: systematic review and metaanalyses. Am J Obstet Gynecol. 2011;204(4):340 e341-312.
23. Little BB, Snell LM, Trimmer KJ, et al. Peripartum cocaine use and adverse pregnancy outcome. American
journal of human biology : the official journal of the Human Biology Council. 1999;11(5):598-602.
24. Kuczkowski KM. Peripartum care of the cocaine-abusing parturient: are we ready? Acta Obstet Gynecol
Scand. 2005;84(2):108-116.
25. Bloomstone JA. The drug-abusing parturient. Int Anesthesiol Clin. 2002;40(4):137-150.
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Patient Blood Management (PBM): A Pillar of Perioperative Surgical Home

Aryeh Shander, MD, FCCP, FCCM Englewood, NJ
Sajjad Naqvi, M.B;B,S Englewood, NJ
Tamara Friedman, PhD Englewood, NJ
Perioperative Surgical Home (PSH), is an innovative clinical care delivery model. The American Society of
Anesthesiologists proposed this model of care in response to the current costly and fragmented perioperative system
of care by introducing this concept based on a shared decision making model between health care providers and
patients by allowing a smooth transition between levels of care. (1)
The PSH is defined by the American Society of Anesthesiologists as a
“patient centered, innovative model of delivering health care during the entire patient surgical/procedural
experience; from the time of the decision for surgery until the patient has recovered and returned to the care of his or
her Patient Centered Medical Home or primary care provider. A comprehensive Perioperative Surgical Home
provides coordination of care throughout all of the clinical microsystems of care and embeds all of the above
strategic principles into its framework” (2)
Kash et al. and colleagues performed a comprehensive literature review and identified key elements of the PSH,
which are summarized in figure 1 (3)
PSH is a much broader and all-encompassing model that goes beyond concepts such as enhanced recovery after
surgery (ERAS) programs, bundled payment models, the patient-centered medical home (PCMH), and other care
coordination and patient engagement models cited in the literature. (3)
The PSH strives to enhance the patient experience and to improve the health of the surgical population at the same
or lower cost. Thus PSH is well positioned to achieve the Institute for Healthcare Improvement (IHI) Triple Aim
that includes (1) improving the individual experience of care, (2) improving the health of populations, and (3)
reducing per capita costs of care. (5) Achieving the Triple Aim can serve as a leverage point for anesthesiologists
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and other advocates to obtain the needed local political and fiscal support for developing and implementing a PSH
model. (5)
Better health is achieved via preoperative risk assessment and mitigation, including prehabilitation to increase
functional capacity (physiological reserve) in preparation for surgery. Unlike conventional preoperative evaluations,
PSH component is the use of standardized preoperative markers for frailty (Mini-Cog Test score), disability (Katz
score), and comorbidity (Charlson Index score), which have been shown to predict 6-month postoperative mortality
and post discharge institutionalization. A standardized clinical assessment and management plans (SCAMP)
evaluating preoperative frailty, using a consistent definition and assessment tool, strengthens risk assessment and
thus helps patients and physicians make better informed, shared decisions. Another prototypic SCAMP focuses on
perioperative patient blood management in a systematic manner with multidisciplinary teams. A preoperative
anemia management program can be incorporated into the comprehensive Preoperative Assessment, Consultation,
and Treatment Clinic within the PSH. (5)
Large studies have shown preoperative education and counseling can result in improve surgical outcomes. For
example, a study published by Jones S. et. al. in Ann R Coll Surg Engl on knee joint arthroplasty patients, showed
that a preoperative education program significantly reduced their length of stay (LOS) and readmission rates.
Similar results (reduced readmission rates) were observed in a Canadian study on an integrated multidisciplinary
approach to implementation of a fast-track program for laparoscopic colorectal surgery and the impact of a series of
coordinated patient education and nutrition programs. (3)
How does the anesthesiologist benefit from the PSH? Anesthesiology is uniquely placed to improve surgical
outcomes. Standardized, evidence-informed perioperative care plans, designed in a multidisciplinary and
cooperative team-based approach, will likely improve outcomes at reduced resource utilization. Anesthesiologists
could be the common denominator for achieving this enhanced care for several reasons. Anesthesiologists have
extensive training in preoperative evaluation, intraoperative management, postoperative and critical care, and pain
medicine. Anesthesiologists care for patients across the entire age range and spectrum of co-existing diseases.
Anesthesiologists also typically manage complex operating and procedural schedules and lead perioperative care
committees. (4)
The PSH model is valuable because it emphasizes the patient and coordination of care from the moment the patient
makes the decision to undergo surgery until 30 days after discharge. During that time, the PSH team implements
standardized evidence-based protocols that have been shown to be effective. Those in the US health care system
hope that the PSH model will provide positive outcomes and decrease costs and patients’ lengths of stay (1)
Anemia is a common, independent and modifiable risk factor for various unfavorable outcomes in a wide range of
patient populations including surgical patients. Recent studies continue to demonstrate the negative impacts of
anemia in various surgical populations. In addition, the presence of ‘unexplained’ anemia in the preoperative setting
should alert the clinicians to rule out the possibility of underlying conditions such as kidney disease or malignancy.
(13) Fowler A.J. et al. in a meta-analysis that included 24 studies and 949,445 patients showed that patients with
preoperative anemia had significantly higher mortality, acute kidney injury and infections. (40) Preoperative anemia
management has resulted in decreased cost.
Detection and Diagnosis of Anemia

What is anemia? Anemia is a condition in which the patient suffers from a paucity of healthy red blood cells; this
compromises the body’s ability to carry oxygen to the various organs. It could be a result of one specific factor or an
interplay of numerous variables, such as nutritional deficiencies, inflammatory processes, blood loss, or iron
deficiency (6).
How is anemia detected and diagnosed? Anemia is typically detected and diagnosed by measuring hemoglobin
levels. The World Health Organization published guidelines that define anemia as hemoglobin levels below 13.5
g/100 ml in men and below 12 g/100 ml in women, with sub-values to indicate whether the patient’s anemia is mild,
moderate, or severe (7). However, the use of these guidelines to diagnose and treat anemia is controversial. Some
argue that the method is inherently flawed because the cut-offs for anemia are artificial, based on epidemiological
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studies of normal hemoglobin distributions, an approach that might not be so appropriate for individual patients.
Another complicating factor is that hemoglobin levels are subject to considerable fluctuations, depending on
intravascular volume levels and may not reflect the red cell mass (8). Finally, the methods of measuring the
hemoglobin can be fallible, with a substantial margin of error (9). Although red cell mass does provide the most
accurate representation of anemia (10), hemoglobin is generally used because it is more easily measured.
How prevalent is anemia? The prevalence of anemia in the general population is quite high; possibly as many as
one out of every three to four people meets the WHO criteria for a diagnosis of anemia (7,11). This amounts to
greater than two billion people being affected globally. It is even higher in the surgical population (12). This is, in
part, due to the fact that many patients who have surgery suffer from chronic medical conditions, which increase the
risk of anemia. Additionally, certain surgeries are more commonly performed in the elderly, who are at a higher risk
of anemia. If the patient did not arrive at the hospital with anemia, s/he has an increased chance of suffering from it
from the surgery (and resulting blood loss) and hospital stay (13). Unfortunately, because of the ubiquity of anemia,
physicians often overlook it (14).
What are the negative outcomes associated with anemia? The detrimental outcomes associated with anemia have
been documented in numerous studies over the years, with more evidence continuing to emerge. A recent meta-
analysis summarized the effects of anemia on the surgical population, and concluded that it was associated with an
increase in mortality, acute kidney injuries (AKIs), strokes, and myocardial infarctions (15). These issues may be the
result of the anemia itself, i.e. the reduced capacity to deliver oxygen to the various organs. Alternatively, these
outcomes may be linked to the underlying cause of anemia. Notably, anemia may be a flag for another condition.
The connection may be a combination of both or may be part of a cycle (16).
PBM vs Transfusion Medicine

Anemia and transfusion An additional variable that might contribute to the poor outcomes associated with anemia is
the transfusion that can be part of the treatment. Anemia is a strong independent risk factor for allogeneic blood
transfusions, which are independently associated with a host of complications and worse medical outcomes (17)
(18), including higher rates of mortality (19) and morbidity (20). Blood transfusions are not without risks, including
the possibility of contracting an infectious blood-borne disease or developing an allergic reaction, among other
concerns (21).
Competing strategies to treating anemia: PBM With the exception of a small group of patients in emergency
situations who are hemorrhaging, an allogeneic blood transfusions is the result of factors that have coalesced over
time. Therefore, there are steps that can be taken to ensure that transfusions are only administered in the appropriate
and necessary settings.
Patient Blood Management is defined as “the timely application of evidence-based medical and surgical concepts
designed to maintain hemoglobin concentration, optimize hemostasis and minimize blood loss in an effort to
improve patient outcome [What is PBM? From the Society for the Advancement of Blood Management (SABM),
available at http://www.sabm.org/]. The focus of PBM is not on avoiding blood transfusions, but rather on
improving patient outcomes. Several strategies are used to attain that goal, including maintaining and optimal
hemoglobin level throughout the course of care, optimizing hemostasis, minimizing blood loss, and when absolutely
needed, using allogeneic blood components (22). The fundamental algorithm of PBM is depicted in Figure 1 below
(23).
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Figure 1. Patient Blood Management Algorithm
PBM is relevant very early on in the patient’s care. In fact, prevention holds a pivotal role in PBM. It is advised that
patients be screened for anemia as early as four weeks prior to surgery. This early screening provides physicians
with sufficient time to treat the anemia, so that the patient’s hemoglobin levels are restored to normal range before
surgery (24).
The treatment provided for anemia is generally dependent on its source. One approach is to utilize erythropoiesis-
stimulating agents (ESAs) or intravenous iron (IVI) for pre-existing anemia (25). It is also necessary for physicians
to continue to be keep a watchful eye on patients whose anemia could be exacerbated or who could develop anemia
as a result of their hospital stays (26). Other ways to manage anemia include increasing the patient’s oxygen supply.
Patients are also often discouraged from engaging in activities that demand oxygen, such as getting up from the bed.
Hemostasis is strategically optimized by assessing the patient’s coagulation and adjusting medications/treatments
accordingly.
Preventative measures are also taken in the perioperative period, including efforts towards blood conservation. One
method, cell salvage, involves salvaging the blood lost during the surgery and re-infusing it back into the patient.
This approach is recommended for patients who are at a high risk of surgical bleeding (27), since those patients have
a much greater risk of post-operative anemia (28). Physicians should also be mindful of minimizing the diagnostic
testing via phlebotomy or using smaller tubes (29), since diagnostic phlebotomy can contribute to anemia.
Lastly, a key aspect to PBM is the element of patient-centered decision-making. Patients are provided with all
treatment options available to them. The course of treatment is then tailored to their values or preferences.
Benefits of PBM Because PBM is an all-encompassing, multimodality approach that often spans the patient’s entire
treatment, it has proven challenging to conduct research on improved patient outcomes as a result of PBM.
Quantifying all the different measures that must come into play with PBM is a very formidable feat. However, a few
researchers did produce some convincing results. One especially informative retrospective study compared the rates
of mortality and complications between propensity-score matched cardiac patients who were either treated at a
hospital with a PBM program or one without. Those treated at the hospital with the PBM program demonstrated
lower rates of both endpoints. Further, although that hospital had a very low transfusion rate, it was ranked first in its
state for lowest risk-adjusted mortality (30).
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Gross et al. (2015) studied the effects of PBM in cardiac surgery on transfusion incidence and patient outcomes.
They compared patients in a hospital before a PBM program was in place and after it was implemented. While the
transfusion rate decreased substantially from 39.3% to 20.8%, the safety profile improved in several areas. Death
and stroke rates remained the same, but the incidence of post-operative kidney injuries and the length of patients’
hospital stays decreased (31).
Another recent study focused on demonstrating the safety of PBM via a non-inferiority multi-site study conducted in
Europe. As in the study above, the researchers compared patient outcomes in the hospitals’ pre-PBM phase (before a
PBM program was instituted) and post-PBM phase (several months after the program was in place). They studied
six components, including death, myocardial infarction, stroke, acute renal failure, pneumonia, and sepsis, to arrive
at a primary endpoint. There were no significant differences between the groups in any of the components, with the
exception of acute renal failure, which was lower in the post-PBM group (32).
In addition to better patient outcomes, the ultimate measure of success, PBM is also more cost-effective than
allogeneic blood transfusions. Transfusions can be very expensive, especially once the administrative costs are
included with the cost of the product itself. Further, the expenses of the complications associated with transfusions
run very high, as well. Therefore, it has been shown that PBM programs tend to be sound financial investments (33).
Impact of PBM and National and International Activities

PBM has impacted the medical community on both a national and international level. Domestically, there has been
a growth in the development of measures and guidelines from several government and private organizations, but the
execution of these initiatives has been slow to follow. Following the WHO’s passing of resolution WHA63.12,
which served as a global endorsement of PBM, the U.S. Department of Health and Human Services appointed the
Advisory Committee on Blood Safety and Availability to provide recommendations on implementing PBM;
unfortunately, they have yet to be put into effect(34). On another front, the Joint Commission has been working on
developing performance measures for PBM programs since 2005 and more recently updated them to relate to
electronic health records (30). The Society for the Advancement of Blood Medicine and the AABB have also
published clinical standards for PBM programs. However, efforts to integrate these standards need to be amplified
(36).
The effects of PBM on an international level vary significantly, depending on the region of focus. For example, in
Australia, it has made a considerable splash. This is most likely a result of government, clinician, and communal
motivation for an improvement in transfusion policies. The 2001’s government initiated Stephen Review, which
called for change in hospitals and the development of guidelines for the proper usage of blood, led to legislation that
supported PBM. Further, the implementation of safe and appropriate blood management was included among
government standards necessary for hospital accreditation (Standard 7). Finally, the Australian government funded a
National Patient Blood Management Collaborative, which promotes PBM as a standard of care. Australia also has a
multitude of resources available to physicians and hospitals to promote better blood management (36).
Europe’s adoption of PBM is a different story. While it is endorsed in the majority of European countries, its
implementation has been more restrained, for the most part, and variable throughout countries (37). In 2013, the
European Commission granted the Austrian Institute of Technology the contract to develop a project for “Good
Practices in the Field of Blood Transfusion.” As outlined on the website, their goals include developing an EU guide
for Member States and health professionals; implementing PBM programs in five teaching hospitals; and preparing
a PBM implementation strategy for all EU members (38. As demonstrated in the above non-inferiority European
study, they are conducting research to demonstrate PBM’s safety and effectiveness in order to garner more support
(32).
References:
1. Spruce L. Back to Basics: The Perioperative Surgical Home. AORN J. 2015 Sep;102(3):262-6
2. Perioperative Surgical Home vision, strategic principles, and definition 2013. American Society of
Anesthesiologists. https://www.asahq.org/resources/perioperative-surgical-home. Accessed June 4, 2015.
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3. Kash BA, Zhang Y, Cline KM, Menser T, Miller TR. The perioperative surgical home (PSH): a comprehensive
review of US and non-US studies shows predominantly positive quality and cost outcomes. Milbank Q. 2014
Dec;92(4):796-821.
4. Vetter TR, Goeddel LA, Boudreaux AM, Hunt TR, Jones KA, Pittet JF. The Perioperative Surgical Home: how
can it make the case so everyone wins? BMC Anesthesiol. 2013 Mar 14;13:6.
5. Vetter TR, Boudreaux AM, Jones KA, Hunter JM Jr, Pittet JF. The perioperative surgical home: how
anesthesiology can collaboratively achieve and leverage the triple aim in health care. Anesth Analg. 2014
May;118(5):1131-6.
6. Maccio, A., Madeddu, C., Gramignano, G., et al. The role of inflammation, iron, and nutritional status in cancer-
related anemia: results of a large, prospective, observational study. Haematologica ;100:124-132.
7. WHO. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Vitamin and Mineral
Nutrition Information System. Geneva, Switzerland: World Health Organization; 2011.
8. Shander A, Roy RC. Postoperative Anemia: A Sign of Treatment Failure. Anesth Analg 2016 Jun;122(6):1755-
1759.
9. Giraud B, Frasca D, Debaene B, Mimoz O. Comparison of haemoglobin measurement methods in the operating
theatre. Br J Anaesth 2013 Dec;111(6):946-954.
10. Jacob M, Annaheim S, Boutellier U, Hinske C, Rehm M, Breymann C, et al. Haematocrit is invalid for
estimating red cell volume: a prospective study in male volunteers. Blood Transfus 2012;10:471-479.
11. de Benoist, B., McLean, E., Egli, I., Cogwell, M. editor. Worldwide prevalence of anaemia 1993-2005: WHO
global database on anaemia. Geneva, Switzerland: World Health Organization; 2008.
12. Clevenger, B., Richards, T.,. Preoperative anaemia. Anaesthesia 2015;70(Suppl 1):20-28.
13. Shander A, Javidroozi M. The patient with anemia. Curr Opin Anaesthesiol 2016 Jun;29(3):438-445.
14. Shander A, Goodnough LT, Javidroozi M, Auerbach M, Carson J, Ershler WB, et al. Iron deficiency anemia--
bridging the knowledge and practice gap. Transfus Med Rev 2014 Jul;28(3):156-166.
15. Fowler AJ, Ahmad T, Phull MK, Allard S, Gillies MA, Pearse RM. Meta-analysis of the association between
preoperative anaemia and mortality after surgery. Br J Surg 2015 Oct;102(11):1314-1324.
16. Lobel GP, Javidroozi M, Shander A. Risks of Anemia in Cardiac Surgery Patients. Semin Cardiothorac Vasc
Anesth 2015 Dec;19(4):288-292.
17. Gombotz H, Rehak PH, Shander A, Hofmann A. The second Austrian benchmark study for blood use in elective
surgery: results and practice change. Transfusion 2014 Oct;54(10 Pt 2):2646-2657.
18. Prescott LS, Aloia TA, Brown AJ, Taylor JS, Munsell MF, Sun CC, et al. Perioperative blood transfusion in
gynecologic oncology surgery: analysis of the National Surgical Quality Improvement Program Database. Gynecol
Oncol 2015 Jan;136(1):65-70.
19. Hart A, Khalil JA, Carli A, Huk O, Zukor D, Antoniou J. Blood transfusion in primary total hip and knee
arthroplasty. Incidence, risk factors, and thirty-day complication rates. J Bone Joint Surg Am 2014 Dec
3;96(23):1945-1951.
20. McEvoy MT, Shander A. Anemia, bleeding, and blood transfusion in the intensive care unit: causes, risks, costs,
and new strategies. Am J Crit Care 2013 Nov;22(6 Suppl):eS1-13; quiz eS14.
21. Klein HG. Allogeneic transfusion risks in the surgical patient. Am J Surg 1995 Dec;170(6A Suppl):21S-26S.
22. Shander A, Hofmann A, Isbister J, Van Aken H. Patient blood management--the new frontier. Best Pract Res
Clin Anaesthesiol 2013 Mar;27(1):5-10.
23. Shander A, Javidroozi M. Blood conservation strategies and the management of perioperative anaemia. Curr
Opin Anaesthesiol 2015 Jun;28(3):356-363.
24. Goodnough LT, Maniatis A, Earnshaw P, Benoni G, Beris P, Bisbe E, et al. Detection, evaluation, and
management of preoperative anaemia in the elective orthopaedic surgical patient: NATA guidelines. Br J Anaesth
2011 Jan;106(1):13-22.
25.Enko D, Wallner F, von-Goedecke A, Hirschmugl C, Auersperg V, Halwachs-Baumann G. The impact of an
algorithm-guided management of preoperative anemia in perioperative hemoglobin level and transfusion of major
orthopedic surgery patients. Anemia 2013;2013:641876.
26. Koch CG, Li L, Sun Z, Hixson ED, Tang A, Phillips SC, et al. Hospital-acquired anemia: prevalence, outcomes,
and healthcare implications. J Hosp Med 2013 Sep;8(9):506-512.
28. Kozek-Langenecker SA. Coagulation and transfusion in the postoperative bleeding patient. Curr Opin Crit Care
2014 Aug;20(4):460-466.
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29. Spahn DR. Anemia and patient blood management in hip and knee surgery: a systematic review of the literature.
Anesthesiology 2010 Aug;113(2):482-495.
30. Dolman HS, Evans K, Zimmerman LH, Lavery T, Baylor AE, Wilson RF, et al. Impact of minimizing
diagnostic blood loss in the critically ill. Surgery 2015 Oct;158(4):1083-7; discussion 1087-8.
31. Moskowitz DM, McCullough JN, Shander A, Klein JJ, Bodian CA, Goldweit RS, et al. The impact of blood
conservation on outcomes in cardiac surgery: is it safe and effective? Ann Thorac Surg 2010 Aug;90(2):451-458.
32. Gross I, Seifert B, Hofmann A, Spahn DR. Patient blood management in cardiac surgery results in fewer
transfusions and better outcome. Transfusion 2015 May;55(5):1075-1081.
33. Meybohm P, Hermann E, Steinbicker A, et al. Patient blood management is associated with a substantial
reduction of red blood cell utilization and safe for patient’s outcome: a prospective, multicenter cohort study with a
noninferiority design. Annals of Surgery 2016.
34. Hofmann A, Ozawa S, Farrugia A, Farmer SL, Shander A. Economic considerations on transfusion medicine
and patient blood management. Best Pract Res Clin Anaesthesiol 2013 Mar;27(1):59-68.
35. Advisory Committee on Blood Safety and Availability (ACBSA) Update. Washington (DC): U.S. Department of
Health and Human Services. August 2011.
36. Electronic patient blood management performance measures [Internet]. Washington (DC): The Joint
Commission; Available at:
http://www.jointcommission.org/electronic_clinical_quality_measures_for_patient_blood_management/. Accessed
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37. Shander A, Isbister J, Gombotz H. Patient blood management: the global view. Transfusion 2016 Mar;56 Suppl
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38. Shander A, Van AH, Colomina MJ, Gombotz H, Hofmann A, Krauspe R, et al. Patient blood management in
Europe. Br J Anaesth 2012;109:55-68.
39. EU-PBM Patient Blood Management. Available at: http://www.europe-pbm.eu. Accessed June, 2016.
40. Fowler AJ, Ahmad T, Phull MK, Allard S, Gillies MA, Pearse RM. Meta-analysis of the association between
preoperative anaemia and mortality after surgery. Br J Surg. 2015 Oct;102(11):1314-24
41. Muñoz M, Gómez-Ramírez S, Kozek-Langeneker S, Shander A, Richards T, Pavía J, Kehlet H, Acheson AG,
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optimization in surgical patients. Br J Anaesth. 2015 Jul;115(1):15-24.
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Guidelines of the ASRA and other organizations on interventional pain procedures in

patients on anticoagulants
Honorio T. Benzon, MD Chicago, Illinois
Introduction
The American Society of Regional Anesthesia (ASRA) recently published their recommended guidelines
on interventional pain procedures in patients on anticoagulants. 1 The guidelines were endorsed by the European
Society of Regional Anesthesia, American Academy of Pain Medicine, International Neuromodulation Society, and
the World Institute of Pain. The guidelines were prompted by published case reports of spinal hematoma when pain
procedures were performed in patients in whom the ASRA guidelines on regional anesthesia were adhered to (Box
1).2-13 In some cases, the coagulation studies were normal.5,8,9,10,11
Box 1. Cases of Spinal Hematoma after Spinal Cord Stimulator Placements

Report Patient Profile Outcome Comment
Giberson et al2 2 cases: 53, male; 70 male Patient 1: Residual left leg Patient 1 took aspirin the
weakness day the leas were pulled;
Patient 2: Complete patient had not taken
recovery aspirin for 7 days before
trial
Buvanendran & Young3 73, female Complete recovery Took low-dose aspirin
daily
Takawira4 52, male Spontaneous recovery Symptoms on 3rd day of
trial
Smith5 2 cases: 44, male; 66, Patient 1: No recovery Coagulation studies
female Patient 2: Residual normal
numbness below T8
Kloss6 50, male Partial recovery No mention of
medications or recovery
Modified from Benzon HT, Huntoon M. Do we need new guidelines for interventional pain procedures in patients
on anticoagulants? Reg Anesth Pain Med 2014;39:1-3
The occurrence of spinal hematoma even when the ASRA guidelines were adhered to is due to several
reasons. Elderly patients with back pain have spinal stenosis, a known factor in the development of spinal
hematoma.14 Second, spinal cord stimulation involves the insertion of large bore needles and manipulations which
include several advancements and retractions of electrodes. Patients are on medications normally considered as not
causing clotting problems, such drugs include the anticonvulsants carbamazepine, oxcarbazepine, valproate, and
levetiracetam and the selective serotonin reuptake inhibitors (SSRIs).15-20 In addition to these medications, patients
with chronic pain may be on antiplatelets for cardiovascular or central nervous system (CNS) thrombotic/embolic
prophylaxis. It is known that the risk is increased in patients on multiple anticoagulants .21
Stratification of risks
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Cognizant of the fact that the risks of bleeding, progression of the hematoma from lack of compressibility,
sequelae, and other factors differ with the different procedures, the guidelines stratified pain procedures as to mild,
moderate and high bleeding risks and made recommendations accordingly (Box 2). Stratification makes sense since
the risks and consequences of the different pain procedures vary. There is also no reason to prolong the
discontinuation of the anticoagulant, when the risk and consequences are small, and expose the patient to stroke,
myocardial infarction, or venous thromboembolism (VTE).
Box 2. Pain Procedures According to the Potential Risks for Serious Bleeding
High Risk Procedures Intermediate Risk Procedures Low Risk Procedures
SCS trial and implant Interlaminar ESIs Peripheral nerve blocks
IT catheter and pump implant Facet MBB and RFA Peripheral joints and
musculoskeletal injections
Vertebroplasty, kyphoplasty Paravertebral blocks Trigger point and piriformis
injections
Epiduroscopy and epidural Intradiscal procedures Sacroiliac joint injections
decompression
Sympathetic blocks Sacral LBBs
Pocket revision and IPG/ITP
replacement
LBB: Lateral branch block; MBB: Medial branch block; RFA: Radiofrequency ablation; IPG/I TP: Intrathecal
pump
Patients who are at high risk for bleeding undergoing low- or intermediate-risk procedures should be treated as
intermediate or high-risk, respectively. Patients with high risk for bleeding include the elderly, concurrent use of
anticoagulants, low body weight, liver cirrhosis, or advanced liver disease, and advanced renal disease.
Aspirin and non-steroidal anti-inflammatory drugs (NSAIDs)

There have been several case reports of spinal hematoma after epidural steroid injection in patients on
aspirin or NSAIDs or with normal coagulation studies (Box 3).
Box 3. Reports of Spinal Hematoma after ESI in Patients on Aspirin or NSAIDs

Report Patient Profile Outcome Comment
Williams et al9 63, male, CESI Full recovery Indomethacin &
allopurinol
Ghaly10 57, male, CESI Full recovery Diclofenac, amitriptyline
Reitman & Watters11 62, female, CESI Partial recovery Normal coagulation
Similar to the ASRA guidelines on regional anesthesia, the patient can continue to take the aspirin when
low risk procedures are performed. However, the occurrence of these reports led ASRA to recommend stopping
aspirin before epidural steroid injections, medium- and high-risk procedures. The length of discontinuation depends
on the reason for the patient’s taking the aspirin: 6 days for primary prevention (aspirin in patients with no overt
cardiovascular disease) and 4 days for secondary prophylaxis. 22 The drug can be resumed 24 hours later.
A study showed the relative safety of doing ESIs in patients on NSAIDs. 23 Still, large scale studies on
interventional pain procedures in patients on NSAIDs made the ASRA Committee to use the drug’s half-life to
guide the duration of discontinuation of the drug before a pain procedure. Five half-lives have been decided to be
adequate as this represents 97% elimination of the drug.24 This range from 1-2 days for ibuprofen, diclofenac,
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ketorolac, indomethacin, 4 days for naproxen and meloxicam, and longer for namebutone and piroxicam. The drug
can be resumed a day after the procedure.25-28
P2Y12 inhibitors clopidogrel, prasugrel, ticagrelor, and cangrelor

The ASRA and European guidelines on regional anesthesia recommended a seven-day stoppage of
clopidogrel before regional anesthesia.29,30 The Scandinavian guidelines, on the other hand stated that 5 days is
adequate.31 This maybe reasonable as a study showed that most patients have no platelet inhibition after 5 days, the
rest had minimal inhibition.32 Since a spinal cord stimulator trial entails several days, most pain clinicians stop the
clopidogrel for 5 days. If this is the case then a test of platelet activity should be performed e.g. VerifyNow P2Y12
assay or the platelet mapping portion of the thrombelastography to document that platelet recovery is significant.
Unfortunately there are no studies which noted what values in the P2Y12 assay or the TEG signify minimal/no risk
when performing medium or high risk interventional pain procedures.
Similar to clopidogrel, prasugrel is an irreversible P2Y12 inhibitor. The drug is more potent, it causes 90
percent platelet inhibition compared to 60% inhibition by clopidogel. 33 For this reason, a 7-day stoppage is
recommended for medium and high risk procedures (Box 4).34 Ticagrelor is also a potent P2Y12 inhibitor, causing
90% inhibition of platelet aggregation. However, its effect is irreversible and studies showed that platelet function
recovery is adequate after 5 days of stopping the drug. 35 Prasugrel and ticagrelor can be resumed 24 hours after the
procedure as these drugs take effect within 2 to 4 hours. Clopidogrel, if given in its usual 75 mg dose, can be started
12 hours after the pain procedure. Since a 300-600 mg dose of clopidogrel takes effect after a few hours, this loading
dose should be started 24 hours later.
Cangrelor (KengrealR) is a new intravenous P2Y12 inhibitor that was approved by FDA in June 2015. It is
indicated for the reduction of periprocedural thrombotic events in patients who have not been preloaded with an oral
P2Y12 inhibitor and who will not receive a GP IIb/IIIa inhibitor. It is also used to bridge patients who require
P2Y12 inhibition and in high risk acute coronary syndromes treated with immediate coronary stenting. Cangrelor is
a direct-acting P2Y12 receptor inhibitor with a fast onset and is rapidly reversible. 36 Its ½ life is 3-7 minutes.37 Since
normal platelet function is attained within one hour,38 at least an hour should elapse before neuraxial procedure is
performed. Patients who are given cangrelor probably needs P2Y12 inhibitors and since pain procedures are mostly
elective, non-interventional measures, e.g. medications should be attempted first.
Box 4. Recommended Intervals between Stoppage and Resumption of the P2Y12 Inhibitors and Medium and High
Risk Pain Procedures
Drug Interval between Discontinuation Resumption of the Drug
and Pain Procedure
Clopidogrel 7 days, 5 days if platelet function 12 hours for loading dose, 24 hours
studies show adequate recovery for usual maintenance dose
Prasugrel 7 days 24 hours
Ticagrelor 5 days 24 hours
Cangrelor* 1-2 hours *
Patients who are given cangrelor most probably will be placed on P2Y12 inhibitors. Non-interventional pain
procedures, such as medications, should be attempted first. Cangrelor was not included in the ASRA published
guidelines nor in the ASRA coagulation pain app.
Older anticoagulants: Warfarin, heparin, low-molecular weight heparin, fibrinolytic agents

Similar to the ASRA guidelines on regional anesthesia, the pain guidelines recommended stoppage of
warfarin for 5 days and normalization of the INR (INR of 1.2 or less) before medium and high-risk procedures are
performed. It is interesting to note that the European and Scandinavian guidelines accept an INR of 1.4 or less as
long as the warfarin was stopped for 5 days.30,31 A LMWH “bridge” therapy may be considered in patients who are
at high risk for venous thromboembolism.
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The performance of pain procedures in patients on intravenous heparin should be avoided since
interventional pain procedures are usually elective procedures. Non-interventional procedures such as medications
(opioids, anticonvulsants, antidepressants) and adjunctive therapy can be performed to alleviate the patient’s pain. If
it is has to be done, pain procedures can be done 4 hours after the IV heparin is stopped.
While the ASRA guidelines on regional anesthesia allow the continued use of BID subcutaneous heparin,
the pain guidelines recommended that interventional procedures not be performed until at least 8 hours after the
subcutaneous heparin was given. The 8 hours correspond to dissipation of effect of the drug. The drug can be
restarted a minimum of 2 hours after the procedure. Interventional pain procedures are not recommended in patients
on TID subcutaneous heparin. Again, every effort should be done to alleviate the patient’s pain without resorting to
interventional procedures.
Similar to the ASRA guidelines on regional anesthesia, a 12-hour interval between stoppage of
prophylactic dose of enoxaparin and interventional pain procedures is recommended. For therapeutic dose of
enoxaparin and for dalteparin, a 24-hour interval is recommended. The drug can be resumed 4 hours after a low-risk
pain procedure, an interval similar to the 4-hour recommendation of a recent FDA Drug Safety Communication.39
In cases where the moderate or high-risk procedures are bloody, the resumption of warfarin, heparin, and
LMWH be delayed for 24 hours after the procedure (see Box 5). As in the regional anesthesia guidelines, drugs that
affect hemostasis (antiplatelet, NSAIDs, SSRIs, other anticoagulants) should preferably not be used in patients on
these anticoagulants.
The ASRA guidelines on regional anesthesia are a little vague with regards to fibrinolytic agents. This is
because of the dearth of studies on this subject. It is for this reason that interventional pain procedures, which in
most cases are elective, should be avoided in this situation.
Box5. Recommended Intervals between Stoppage and Resumption of the Old Anticoagulants Interventional Pain
Procedures
Drugs Drug Discontinuation and Pain Resumption of Drug
Procedure
Warfarin 5 days, INR back to normal 24 hours
IV heparin 4 hours 2-24 hours
BID subcutaneous heparin 8-24 hours 2-4 hours
TID subcutaneous heparin* -
LMWH, prophylactic dose 12 hours 4-24 hours
LMWH, therapeutic dose 24 hours 4-24 hours
LMWH, dalteparin 24 hours 4-24 hours
Fibrinolytic agents* -
* Interventional pain procedures not recommended
Clotting factor inhibitors: Fondaparinux and the novel anticoagulants

Fondaparinux is a synthetic anticoagulant that specifically blocks clotting factor Xa. The drug attains
maximum concentration within 2 h of administration and has a half-life of 17-21 hours Xa.40 In the EXPERT study,
2.5 mg fondaparinux was given 6-12 hours after surgery, the catheters were removed 36 hours after the last dose of
fondaparinux and redosing was 12 hours after catheter removal. 41 The 36-hour interval corresponds to two half-lives
of the drug which means that only 75% is eliminated. This is probably risky in patients with spinal stenosis and
other spine abnormalities. While a two half-life may be adequate in low risk procedures, a five half-life is
recommended (3-4 days) in medium and high risk pain procedures. The drug can be resumed 24 hours later.
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Dabigatran, rivaroxaban and apixaban are novel oral anticoagulants (NOACs). Dabigatran is a direct
thrombin inhibitor while rivaroxaban and apixaban are Factor Xa inhibitors. Several review articles appeared over
the last two years on the pharmacology, indications, pharmacokinetics, and reversal of the drugs. 42-52 There are no
published studies on the safety of NOACs and regional anesthesia. The pain guidelines recommended a five half-life
interval. The next edition of the ASRA guidelines on regional anesthesia will base their recommendations on five
half-lives of the drugs.
Dabigatran is a pro-drug, its onset is 1.5-3 hours, and has a half-life of 14-17 hours. It is 80% eliminated by
the kidneys and its half-life is doubled from 14 to 28 hours in patients with renal insufficiency. The drug is indicated
for the prevention of stroke in patients with non-valvular atrial fibrillation (AF) in the USA, Canada, and Europe. It
is indicated for the prevention of venous thromboembolism after knee or hip arthroplasty in Europe and Canada but
not in the United States. A five half-life, corresponding to four days, is the recommended interval between stoppage
of the drug and pain procedures (Box 5). A longer interval, 6 days, should be observed in patients with renal
problems. The drug can be resumed 24 hours after the procedure.
Rivaroxaban is a Factor Xa inhibitor. Peak concentrations are reached 2.5 to 4 hours after intake, half-life is
6 to 9 hours. One third of the drug is eliminated by the kidneys, one third by the fecal/biliary route, while a third is
changed to inactive metabolites. In the United States, Europe, and Canada, the drug is indicated for VTE
prophylaxis and stroke prevention in non-valvular AF, treatment of VTE, and prevention of VTE after orthopedic
surgery. A five half-life interval, or 3 days, is recommended between discontinuation of the drug and medium and
high risk procedures. The drug may be resumed 24 hours later.
Similar to rivaroxaban, apixaban is a Factor Xa inhibitor. Peak plasma concentrations are attained with one
to two hours, half-life is 13 +/- 9 hours. The drug is indicated for the prevention of stroke in patients with non-
valvular atrial fibrillation (USA, Europe, Canada) and for VTE prophylaxis after hip and knee arthroplasty (Europe
and Canada). There are very few pharmacokinetic studies on the drug and the studies that were done showed wide
standard deviation (13 +/- 9 hours). In patients who are not at high risk for bleeding, three days is recommended
between stoppage of the drug and pain interventional procedures. For patients who are at high-risk (elderly, low
body weight, liver and renal problems), a longer interval of 4-5 days should be considered. The drug can be resumed
24 hours later.
Edoxaban is a Factor Xa inhibitor not discussed in the published ASRA pain guidelines. It was approved by
the FDA on January 2015 for the prevention of stroke in patients with atrial fibrillation and for the treatment of deep
venous thrombosis and pulmonary embolism. Maximum concentration in attained in 1 to 2 hours, it is 60%
bioavailable, and 50% of the drug is excreted by kidneys. Half–life is 8.75-10.4 hours.53 Five half-lives is 55h or 2.5
days so a 3-day discontinuation in patients without renal problem, a longer interval (e.g. 6 days) should be
considered in patients with renal disease. The drug can be resumed 24 hours later. The ASRA Board of Directors
approved the Writing Committee’s recommendation and is now included in the ASRA app (see Box 6).
Box 6. Recommended Intervals between Stoppage and Resumption of the New Anticoagulants and Interventional
Pain Procedures, Laboratory Tests and Reversal
Drug Drug Resumption of Drug Laboratory Test Reversal
Discontinuation and
Pain Procedure
Fondaparinux 4d 24h Anti Xa assay?
Dabigatran 4d 24h Dilute TT Dialysis
(6d in renal patients) ECT Activated charcoal
within 2h
Idarucizumab
Rivaroxaban 3-5d 24h PT Activated charcoal
Anti Xa assay within 8h
Four-factor PCC
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Apixaban 3d 24h Anti Xa assay Activated charcoal

within 3h
Edoxaban* 3d 24h Anti Xa assay
(6d in renal
patients)
ECT – Ecarin clotting time (not readily available); PCC – Prothrombin complex concentrate;
PT – Prothrombin time; TT – Thrombin time
* Edoxaban was not discussed in the ASRA guidelines as it was approved by the FDA in January 2015, after the
guidelines were already formulated.
Note: Andexanet has been shown to be effective in reversing the effects of the factor Xa inhibitors; it is not yet
available in the U.S.
New reversal agents for the novel anticoagulants

Idarucizumab is a monoclonal antibody fragment that that binds with free and thrombin-bound dabigatran54
that has recently been approved by the FDA. Initial studies showed efficacy of the drug in reversing dabigatran in
healthy and elderly volunteers.55,56 A prospective cohort study of 90 patients showed idarucizumab to normalize the
elevated ecarin clotting time in 88% to 98% of patients and this effect was seen within minutes. 57 In the group with
serious bleeding, hemostasis was restored at a median of 11.4 hours. In the second group that required an urgent
procedure, normal intraoperative hemostasis was noted in 33 of 36 patients, while moderately or mildly abnormal
hemostasis were noted in one and two patients respectively. The dose of idarucizumab was 5 g intravenously,
administered as two 50-mL bolus infusions, 2.5 g each dose, given no more than 15 minutes apart.57
Andexanet is a recombinant modified human factor Xa decoy protein that binds and sequesters factor Xa
inhibitors within the vascular space, restoring the activity of the endogenous factor Xa. The activity of the
anticoagulant is reduced as noted by measurement of thrombin generation and factor Xa activity. 58 Studies in
healthy volunteers showed andexanet to reverse the anticoagulant activity of factor Xa inhibitors. 59,60 A two-part
randomized placebo controlled study was recently conducted in older healthy volunteers. 61 In the apixaban-treated
patients, anti-factor Xa activity was reduced by 94% after andexanet compared to 21% in the placebo group. Among
the rivaroxaban-treated patients, anti-factor Xa activity was reduced by 92% after andexanet compared to 18% in the
patients who received placebo. In the study, andexanet was administered as 400 mg intravenous bolus (30 mg per
minute) or as a 400 mg intravenous bolus followed by a continuous infusion of 4 mg per minute for 120 minutes
(total of 480 mg). This is not yet clinically available in the United States.
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DNR, EOL, and Palliation in the Elderly
Jason L. McKeown, M.D. Memphis, Tennessee
Rebecca A. Aslakson, M.D., PhD, FAAHPM Baltimore, Maryland
DNR, EOL, and Palliation in the Elderly
Introduction and demographics
The older adult population of the world is increasing at an unprecedented rate. Influential factors include lower birth
rates, improving quality and access to care, and improved longevity (1). Ten thousand Baby boomers register for
and begin collecting social security in the US every single day. This Medicare statistic reinforces that the US
population truly is aging. In 1960, 9% of the population was over the age of 65 and that proportion is projected to
reach 20% by 2050 (2,3). By 2060 that number is expected to more than double to over 90 million people. The
fastest growing segment in the so-called “Silver Tsunami” will be those 85 years and older and they will outpace the
growth of all younger age groups as well. With over two-thirds of these older adults having multiple chronic
conditions, the burden of serious and advanced illness is expected to proportionally increase within the population
(4). However, as the burden of serious illness among older adults grows and as these individuals reach the end of
their lives, the state of End of Life care in the United States is concernedly fractured. The seminal 2014 Institute of
Medicine Report Dying in America notes a widespread “[n]eed for public education and engagement about end-of-
life care…at the societal, community/family, and individual levels [and that] not only do most American lack
knowledge about end-of-life care choices, but the health community and other leaders also have not fully utilized
strategies to make that knowledge available, meaningful, and relevant across diverse populations” (pg2) (5).
In 2007, more than 4 million surgeries were performed on patients aged 65 or older (6); the same group in 2007
represented only 13% of the U.S. population yet 43% of all hospital days (7). Many surgical procedures will be
related to chronic illnesses common in old age: cancer, heart disease and degenerative joint disease. The prevalence
of chronic pain and age-related medical comorbidity is high in older adults. As the population ages,
anesthesiologists will be called upon more frequently to help care for older patients who have pain, other symptoms,
and end-of-life concerns within the perioperative period and beyond. While a recent, well-designed review (6)
summarizes both perioperative mortality for older adults as well as potentially modifiable domains to reduce
perioperative mortality and morbidity (Table 1), any decision to take an older adult to the operating room should
ideally integrate the risks and benefits of the planned procedure with the predicted prognosis of the patient’s
illness(es) and the patient’s own goals and hopes for the treatment and their medical care. The importance, and
potential nuance, of such conversations are further accentuated if the patient has a terminal illness, pre-existing
wishes for treatment limitations, and/or is pursuing the surgery for purely palliative reasons. This article summarizes
essential elements for these discussions.
Table 1: Perioperative optimization for older adults pursuing surgery - Adapted from (5)
Domain Potential optimization approaches
Cognition Easy access to assistive devices (e.g., glasses, hearing aids) and limitations of
perioperative sedatives
Function Perioperative physical therapy & ready access to assistive devices (e.g., walker,
braces)
Nutrition Preoperative referral to a dietician and/or nutritional supplementation
Frailty Preoperative strength training and/or nutritional supplementation
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Palliative Care - Definitions and the Current Evidence Base (8)
Although often conflated, the clinical entities of “hospice” and “palliative care” are distinctly separate in the United
States. This section will explicitly define these terms and concepts as well as summarize the current evidence base
for palliative care, particularly for older adults.
Definitions:
Hospice
Hospice is a regimented, government-regulated system of interdisciplinary care that specifically provides palliative
care for dying patients and their family members. The modern hospice movement was founded by Dame Cicely
Saunders in the mid-1900’s as she developed both locations (hospices) and care philosophies (hospice practice) with
a goal of optimizing quality of life, minimizing suffering, and providing emotional, spiritual, and psychological
support for dying patients and their families. To qualify for hospice, patients must have a legal “Determination of
Terminal Illness” in which two physicians attest to their medical estimation that the patient has less than six months
to live. For patients with a live-in caregiver, hospice care is usually provided at the patient’s home. For patients
without a live-in caregiver and/or whose symptoms are so severe as to be uncontrollable outside of a hospital setting,
hospice care is delivered at a skilled nursing facility, hospice house, or inpatient hospital hospice ward. By
definition, hospice care is multi-disciplinary care involving doctors, nurses, chaplains, social workers, aides, and
volunteers. Hospice philosophy and federal hospice regulations typically require hospice patients to forego life-
prolonging treatments and most care decisions are directed by the hospice team itself in partnership with the patient
and family.
Palliative care
Interdisciplinary care delivered by a team of doctors, nurses, pharmacists, chaplains, and social workers (if not also
interventional pain specialists, ethicists, and/or integrative medicine practitioners), palliative care has a goal of
improving quality of life and reducing physical, psychosocial, and spiritual suffering for patients with serious illness
and their families, regardless of prognosis or specific diagnosis! If a patient and/or family is suffering with a serious
illness for any reason, palliative care and palliative care practitioners seek to reduce that suffering. The National
Consensus Guidelines for Palliative care note eight domains for palliative care (Table 2) which can be summarized
into three general activities: (1) expert and aggressive symptom management, (2) psychosocial support of patients
and their families, and (3) expert and compassionate communication exploring patient goals and hopes in the setting
of their medical diagnosis and prognosis. Palliative care providers typically work with a patient’s other clinician
teams to provide an extra layer of support to ensure better patient experience and quality of life throughout serious
illness diagnosis and management. Many patients receive palliative care concurrent to life-prolonging and/or
curative-intent treatments and the palliative care team works with a patient’s other clinical teams, as well as with the
patient and family, to help support complex decision making throughout the full trajectory of illness.
Table 2: National Consensus Guidelines Domains for Quality Palliative Care and
Example Subdomains (9)
Structure/Process of care (e.g., continuity, communication)
Physical Aspects of Care (e.g., pain, dyspnea)
Psychological and Psychiatric Aspects of Care
Social Aspects of Care (e.g., caregiving)
Spiritual, Religious and Existential Aspects of Care
Cultural Aspects of Care (e.g., cultural competence)
Care of the Patient at the End of Life
Ethical and Legal Aspects of Care (e.g., care planning)
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Palliative care can be delivered by a specialist, specialty-trained, consultant palliative care team or by front-line,
non-specialist clinicians. Indeed, expert consensus notes a shortage of specialist palliative care providers and calls
for wider dissemination of “generalist” palliative care delivered by front-line providers (10).
Evidence Base for Palliative Care (8)

Multiple studies and evidence summaries support that proactive palliative care benefits patients, families, and
healthcare systems. Comprehensive symptom evaluation and treatment by palliative care teams not only reduces
pain but also addresses and reduces distress due to common symptoms such dyspnea, anorexia, anxiety,
constipation, nausea, depression, and fatigue. High quality randomized controlled trials comparing palliative care
management against routine care support that palliative care reduces symptoms while also improving quality of life
and family satisfaction and reducing healthcare utilization across a spectrum of populations including patients with
advanced cancer, neurologic disease, lung disease, frailty, and multiple coexisting conditions.
Common EOL symptoms in the elderly
Effective symptom treatment in the elderly patient with life-limiting illness is vitally important to maintaining
quality of life for the patient and family. The high prevalence of frailty, organ failure, cancer, and neurodegenerative
disease in elderly patients accounts for greater symptom burden than in younger counterparts. Because of the co-
existence of multiple severe illnesses in elderly patients the treatment of symptoms may be quite challenging and
treatment is rarely as straightforward as in younger counterparts. The clinician must be mindful of the unique
sensitivities of the older patient to various therapeutics. Analgesic pharmacokinetics change greatly with aging.
Adverse drug reactions are common as are drug-drug interactions with the older patient’s routine medications.
Anatomical considerations like obesity and frailty change approaches to regional anesthesia and other interventions.
Pharmaceutical approaches and interventional techniques must always be tailored to the elderly patient’s physiology
to avoid complications.
Pain
There is a high prevalence of chronic pain in older patients. Common complaints come from degenerative joint and
spine disease and over the last decade, similar to younger patients, there has been a rise in the number of patients
chronically treated with opioids. Opioid tolerance and dependence thus complicates treatment of pain. Cancer
related pain is well appreciated and readily treated, but pain may be less aggressively treated when it is associated
with congestive heart failure and COPD.
Delirium
Patients with serious and life-limiting illness, especially those with cognitive dysfunction and dementia, are at very
high risk for delirium during acute exacerbations, terminal decline and in the postoperative period.
Anxiety and Depression

Mood disorders are common in older patients. Depression can be confused with delirium and is commonly
associated with dementia. Treatment can be challenging because of the risk of polypharmacy with the drugs
commonly used for mood disorders.
Nausea and vomiting

Commonly associated with malignancy and with medications like opioids, treatment modalities are also limited (like
mood disorders) because of contraindications with many drug classes.
Dyspnea
Breathlessness like pain is multifactorial and a symptom that arises in many of the life-limiting illnesses which are
common among the elderly. Patients with cancer and COPD experience dyspnea frequently. Organ failure like CHF,
end-stage hepatic and renal disease leading to volume overload produce dyspnea also. It is also linked to anxiety and
neurodegenerative disease like ALS.
Palliation of symptoms
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In the case of life-limiting illness it is best to address the symptoms of the geriatric patient with a multidisciplinary
approach. The biopsychosocial theory explains the way in which pain has many sources all of which cannot be
treated pharmacologically. The other symptoms which cause suffering in life-threatening and terminal illness are
similar in this regard. A team of specialists such as physicians, nurses, psychologists and pastoral care experts is
often best suited to successfully palliate these complex symptoms.
Elderly patients experience pain in the same intensity as younger patients. Opioids are the mainstay of therapy for
moderate to severe pain as well as dyspnea. Opioids are potent, effective and can be administered by many different
routes. The adverse effects of opioids are well-known, and older patients are more sensitive to these; they are also
more sensitive to analgesic effects. Non-opioids are better as first-line for treatment of milder pain and are very
useful as adjuvant therapy to reduce the necessary dose of opioids and the likelihood of adverse effects. Similarly,
elderly patients are at increased risk for harm from non-opioids. Hepatic and renal toxicity can be seen with lower
doses of acetaminophen and NSAIDs respectively. The explanations underlying increased sensitivity and toxicity in
the aged include decreased neuronal function, and altered body composition, drug metabolism and clearance.
Elderly patients have many sensitivities to different drugs and are at increased risk for polypharmacy; consequently,
guidelines, like the Beers Criteria, are regularly updated to help clinicians avoid common adverse effects (11).
Because of these risks, pharmaceutical alternates can be sometimes limited. For instance, in the treatment of nausea
and vomiting, ondansetron has the lowest risk profile; yet, if zofran is ineffective, the option of promethazine can
still pose risk for delirium. When a higher risk alternate is required for symptom treatment, a low starting dose and
slow titration is always appropriate. Medications used in the treatment of nausea, mood disturbance, agitation, and
delirium all have greater potential for problematic polypharmacy and adverse effects and specialist palliative care
teams often have detailed protocols both to improve clinical care and to reduce the incidence of polypharmacy (12).
Ultimately regional anesthetic techniques like neuraxial analgesia and neurolytic injections can be valuable opioid
sparing interventions. Yet, they are invasive and consequenlty expose the patient to procedural and anesthetic risks.
Careful patient selection is key. Factors such as body habitus, malnutrition, cachexia, immune compromise, and
mood disorders must be considered especially in the case of percutaneous catheters or implantable therapies. Life
expectancy and caregiver support are other important considerations.
In the most severe cases of intractable pain or delirium, palliative sedation may be considered. Thorough exploration
of risks, benefits and the patient’s goals must precede this option. Palliative sedation is considered advanced practice
for palliative care and, if being considered, the care team is strongly encouraged to proactively engage a specialist
palliative care team and/or the hospital ethics team. Palliative sedation is effective to relieve symptoms and suffering
but may also shorten life. A full review of the Doctrine of Double Effect is beyond the scope of this lecture though
there are multiple literature reviews available on the topic (13).
DNR and perioperative concerns (14)
Cardiopulmonary resuscitation (CPR) is the only medical intervention in the United States for which no consent is
required and an explicit physician order is necessary for it to be withheld (12). From the rise of CPR in the 1980’s
until the early 1990’s, a patient’s DNR orders were routinely reversed on entering the operating room;
anesthesiologists and surgeons believed that routine anesthesia and surgical care such as operative room
resuscitation and vasoactive titration would otherwise constitute “resuscitation.” Yet, particularly when the Patient
Determination Act of 1990 cemented that a patient’s right to self-determination was the overriding standard in
medical ethics, opinions have evolved to clarify that typical operating rooms procedures do not constitute
“resuscitation” and that a patient’s DNR’s orders could be maintained throughout a surgical procedure. Indeed,
routine suspension of a DNR order in the perioperative period is now considered a direct violation of the patient’s
right to self-determination. Consequently, the American Society of Anesthesiologists’ practice guidelines (as well as
the guidelines forwarded by the American College of Surgeons) advocate for “required reconsideration” of a
patient’s DNR status prior to surgery as constituted by a discussion of the patient’s goals for the surgery and his or
her desire for DNR practices surrounding that surgery. Based on this discussion, the patient can have a portion, all,
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or none of the DNR wishes maintained in the operating room and for a designated perioperative period. Managing
patients with these treatment limitations and/or end-of-life issues can be psychologically and/or ethically challenging
for some providers. If an anesthesiologist feels ethically uncomfortable in these situations and as mandated by the
American Medical Association Code of Ethics, that clinician should not be compelled to provide care but, as in the
care of Jehovah’s Witnesses disallowing transfusion of blood products, the patient’s care should be promptly
transferred to another willing anesthesia provider.
Conclusion
In the coming decades as older adults continue to access healthcare for surgery in increasing numbers,
anesthesiologists must be prepared to meet the complex perioperative needs of these patients. Appropriate
perioperative care, such as resuscitation, must always be delivered in the context of the patient’s individual beliefs
and goals. Patient’s retain their autonomy in decision making, even when end of life care intersects with
perioperative care. Symptom treatment requires careful attention to the unique physiology of the older adult.
Because of their expertise in management of symptoms like pain, nausea and delirium, anesthesiologists may also
widen their scope of care for older patients with life-limiting disease outside of the perioperative arena.
Acknowledgments: The presenters thank Allen Gustin, MD for his aid in preparing this manuscript and his
guidance and expertise concerning these topics.
References:
1. Kinsella K, He W. An aging world: 2008. International Population Reports, P95/09-1. Washington, DC:
U.S. Government Printing Office; 2009:1-191.
2. He W, Sengupta M, Velkoff VA, et al. 651 in the United States. 2005. Available at:
http://www.census.gov/prod/2002pubs/censr-4.pdf. Accessed June 11, 2016.
3. Bureau of the Census. Projections of the population by age and sex for the United States: 2010 to 2050.
2008. Available at: http://www.census.gov/prod/2010pubs/p25-1138.pdf. Accessed June 11, 2016.
4. Centers for Disease Control and Prevention (CDC). The state of aging and health in America—2013.
2013.Available at:
http://www.cdc.gov/features/agingandhealth/state_of_aging_and_health_in_america_2013.pdf. Accessed
June 11, 2016.
5. Institute of Medicine. Dying in America: Improving Quality and Honoring Individual Preferences Near the
End of Life. Key Findings and Recommendations. Available at:
http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2014/EOL/Key%20Findings%20an
d%20Recommendations.pdf. Accessed June 11, 2016.
6. Elixhauser A, Andrews RM. Profile of inpatient operating room procedures in US hospitals in 2007. Arch
Surg 2010; 145(12):1201-1208.
7. Hall MJ, DeFrances CJ, Williams SN, Golosinskiy A, Schwartzman A. National Hospital Discharge
Survey: 2007 summary. National health statistics reports. 2010(29):1-20, 24.
8. Kelley AS, Morrison RS. Palliative care for the seriously ill. NEJM 2015;373:747-55.
9. Care National Consensus Project for Quality Palliative Care. Clinical Practice Guidelines for Quality
Palliative Care, Third Edition. 2015. http://www.nationalconsensusproject.org. Accessed on June 11, 2016.
10. Quill TE, Abernethy AP. Generalist plus specialist palliative care – creating a more sustainable model.
NEJM 2013; 368(13):1173-1175
11. American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older
adults. Journal of the American Geriatrics Society. 2012;60(4):616-631.
12. Gupta M, Davis M, LeGrand S, Walsh D, Lagman R. Nausea and vomiting in advanced cancer – “The
Cleveland Clinic Protocol”. J Support Oncol 2013; 11(1):8-13.
13. QuillTE, Lo B, Brock DW, Meisel A. Last-resort options for palliative sedation. Ann Intern Med 2009;
151(6):421-4.
14. Gustin AN, Aslakson RA. Palliative care for the geriatric anesthesiologist. Anes Clin 2015;33:592-605.
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Improving First-Case of the Day On-Time Starts

CAN Increase Operating Room Efficiency
Franklin Dexter, MD, PhD Iowa City, Iowa, United States of America
Principles in Calculating Allocated OR Time for Use in Reducing Over-Utilized Time
Before I consider how improving first case of the day on-time starts can increase the efficiency of use of
OR time, I need to cover: what exactly is meant by the OR efficiency? There are 3 simultaneous equations.
Suppose that the hours into which cases are scheduled in an OR have been calculated based on minimizing the
expected inefficiency of use of OR time. Then, fewer than these allocated hours would be under-utilized OR time
and greater than those allocated hours would be over-utilized OR time. For example, if the hours into which cases
are scheduled in an OR #1 are 7:15 AM to 3:30 PM, and the last case of the day ends at 1:30 PM, then there are
2 hours of under-utilized OR time from 1:30 PM to 3:30 PM.1 There is 0 hours of over-utilized OR time.
Conversely, suppose that the hours into which cases are scheduled in OR #2 are from 7:15 AM to 5:30 PM, and the
last case of the day ends at 6:30 PM. Then, there is 1 hour of over-utilized OR time from 5:30 PM to 6:30 PM.1
There is 0 hours of under-utilized OR time. These definitions for under-utilized and over-utilized OR time represent
2 of the 3 simultaneous equations.
The 3rd of the 3 equations is for the inefficiency of use of OR time itself. It equals the sum of two terms: (cost
per hour of under-utilized OR time multiplied by the number of hours of under-utilized OR time) plus (cost per hour
of over-utilized OR time multiplied by the number of hours of over-utilized OR time). Application of these
3 equations from operations research to OR management was figured out by Strum et al.2
These 3 equations have an implication. Suppose that the hours (above) into which cases were scheduled were
chosen by a committee decision (i.e., not by performing calculations to minimize the expected inefficiency of use
of OR time). Then, there are not 2 hours of under-utilized OR time in OR #1 and 1 hour of over-utilized OR time in
OR #2. There is not, as far as I know, a name for the hours until 3:30 PM and past 5:30 PM, respectively. Be careful
when you hear someone refer to “under-utilized” and “over-utilized” OR time. Hours are “under-utilized” and
“over-utilized” only if compared to allocated hours minimizing the inefficiency of use of OR time.
Continuing, OR workload for a service on a day of the week often follows a normal distribution.2
Consequently, in principle (but, in practice, it is more involved mathematically), the inverse of the normal
distribution function can be used to calculate the allocated OR time that maximizes OR efficiency.2
For example, suppose that, on Mondays, a hospital currently plans 3 ORs for orthopedics, each OR for
10 hours of cases (3 ORs x 10 hours = 30 hours). The total hours of orthopedic cases, including turnovers, follows
a normal distribution with a mean of 30 hours. The relative cost of 1 hour of over-utilized OR time equals 2.0
multiplied by that of 1 hour of under-utilized OR time.1,3 This is a typical value, being “time and a half” plus a bit
extra for an intangible cost. With it being twice as expensive for finishing late rather than early, one wants to
calculate the OR allocation that results in finishing early on 2/3 rd of Mondays. That is the 66th percentile.
To apply the 66th percentile, consider a standard deviation of orthopedics’ workload on Mondays, a typical
value of 5 hours. In Microsoft Excel, use the following formula: “= NORMINV( 2/3, 30, 5 )”. The answer that
appears in the spreadsheet is 32.0 hours. Thus, the 66th percentile of the inverse of the cumulative normal
distribution function with a mean of 30 hours and a standard deviation of 5 hours equals 32 hours. Using a mean
of 30 hours, what OR allocation minimizes the inefficiency of use of OR time? 4 ORs with 8 hours of allocated time
and 0 (zero) ORs with 10 hours of allocated time. The answer is not the mean of 30 hours.
{Note, this does not mean that the hospital “ought” to allocate 4 ORs for 8 hours. That depends on multiple
details such as the number of surgeons, whether there can be 4 ORs for 3 surgeons, etc.1,3-5 There are many papers
and review articles that examine what to do in these more complicated but realistic situations. However, for
understanding the principles of first case of the day starts, this simple approach is good enough.}
Suppose that the standard deviation of orthopedics’ workload on Mondays is 10 hours (a larger than typical
value). Since workload is assumed to follow a normal distribution, we again use the inverse of a normal distribution,
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and again use a ratio of 2.0:1.0 for the cost of over-utilized:under-utilized OR time. In Excel, this is the formula:
“= NORMINV( 2/3, 30, 10 )”. Notice that the formula only differs from the one above in that the last number is now
10 instead of 5. This formula gives an answer of 34 hours (i.e., the 66th percentile of the normal distribution function
with a mean of 30 hours and a standard deviation of 10 hours equaling 34 hours). Thus, for a mean of 30 hours, what
OR allocation minimizes the inefficiency of use of OR time? It would be 3 ORs with 8 hours of allocated time and
1 OR with 10 hours of allocated time, because that sums to 34 hours. Comparing this result to the preceding one
with 32 hours, because the variability in the workload among Mondays is greater (10 hours instead of 5 hours), the
anesthesia group, facility, etc. should allocate greater hours of OR time. Doing so reduces the expected hours
of over-utilized OR time, and that reduces the hours that anesthesiologists, nurses, etc., work late.6
Reducing Tardiness of First Case Starts Can Increase Efficiency of Use of OR Time
The remainder of the material depends principally on reducing the hours of over-utilized OR time. The reason
why the preceding principles matter is because, as already stated, the hours in an OR beyond the allocated hours
(i.e., hours into which cases are scheduled) is “over-utilized OR time” only if those allocated hours are that which
minimize the inefficiency of use of OR time.
At a facility, OR nurses, nurse anesthetists, and anesthesiologists are full-time employees. The allocated time
is from 7:00 AM to 3:00 PM. {I’m going to say this for the 3rd time, so that there is no misunderstanding; this means
that the hours of OR time that minimize the inefficiency of use of OR time is to 3 PM.} Today, there happens to be
9.0 hours of cases scheduled in one OR. The other 4 ORs are estimated to end earlier. The intravenous catheter and
regional nerve block are placed in the holding area from 6:25 AM to 6:55 AM, rather than in the OR as typical. The
OR finishes at 3:30 PM instead of at 4:00 PM. Has this resulted in an increase in the efficiency of use of OR time?
As we approach the day of surgery, the cost of an hour of under-utilized OR time becomes negligible, relative
to the cost of an hour of over-utilized OR time.7,8 The terms related to the cost per hour of under-utilized OR time
are no longer relevant. The remaining terms are only those related to over-utilized OR time. Continuing, the cost per
hour of over-utilized OR time will differ among anesthesiologists, OR nurses, nurse anesthetists, surgeons, surgical
technologists, etc. However, for each, it is a constant. The consequence is that for all the stakeholders, OR efficiency
is maximized on the day of surgery by minimizing the hours of over-utilized OR time.7,8
Returning to the scenario, the allocated time was from 7:00 AM to 3:00 PM. Having the existing personnel
target the OR with the largest hours of cases resulted in the cases finishing in 8.5 hours instead of the expected
9.0 hours. What was sustained was 0.5 hours of over-utilized time instead of 1.0 hours of over-utilized time. Thus,
reducing the time to incision of the first case of the day increased OR efficiency. Working faster early in the day
definitely can increase OR efficiency.
Suppose, on the other hand, that the allocated OR time was from 7:00 AM to 4:30 PM. Then, even if the cases
finished at 4:00 PM, there would not be over-utilized OR time. The same clinical intervention has not resulted in an
increase in OR efficiency.
What this shows is that working quickly is not synonymous with being efficient. Rather, working quickly can
increase efficiency, and whether efficiency is increased depends on the longer-term management decisions (i.e.,
those of the preceding section). That is why the preceding section matters. Good OR management operational
decision-making on the working day before (and on) the day of surgery is highly sensitive to the OR allocations,
which is why those values need to be calculated appropriately.5,6
Before investing financially in a lean initiative to improve on-time starts, I strongly recommend performing the
full analyses.1 That is what we published in our 2006 review article. 1 However, there is a simpler approach that
is suitable for screening for cost saving opportunities from improving on time starts. Suppose that the briefest period
of staff scheduling is for 8.5 hours (i.e., a typical US value). Then, for ORs with less than or equal to 8 hours of
cases, there would generally be no savings from reducing tardiness of first case starts. 9,10 The reason is that there
will not be any over-utilized OR time, because the briefest allocated OR time would be 8 hours. {This is part of the
real-world complexity I mentioned in the first section}. For ORs with greater than 8 hours of cases, each 1.0-minute
reduction in tardiness reliably results in a savings of greater than 1 minute of regularly scheduled time.9,10 One
simulation method (study) showed 1.1 minutes while another simulation method showed 1.2 minutes. 9,10 This
is principally achieved by reducing the allocated OR time.9 That is a very important finding and principle. Often
managers, clinicians, etc., think short term in relation to cost savings rather than to consider how staff scheduling
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can be adjusted long term. Reducing the tardiness of first case starts CAN increase OR efficiency and very often
does so not by making a difference “today,” but by progressive changes on a long-term basis in the staff schedules.
The full analysis of the cost savings from reducing tardiness of first cases of the day is the same as the analysis
of turnover times.1 Suppose that an OR has 3 cases and the first case of the day enters the OR 8 minutes late. Then,
that is the same as increasing the mean turnover time by 4 minutes.1,9 The analysis is performed for each
combination of service and day of the week. The review article shows that for multiple services and days of the
week, at the Australian hospital studied, reducing tardiness of the first case of the day had a large cost savings. 1
Perceptions, biases, and physicians’ roles
The preceding information essentially says to target ORs with expected over-utilized time for reduction in
tardiness of the first case of the starts. But, what about the other ORs? Behaviorally, do nurses, anesthesiologists,
etc., in ORs with substantial under-utilized OR time slow down (e.g., to prevent add-on cases). No: such behavior
is not what is observed in practice.4 There is a very slight but significant effect in the opposite direction (P = 0.008).
The reason is that, on days with substantial under-utilized time, there are more providers available to help in other
ORs.4 Furthermore, only 1% of the variance in tardiness among first cases are attributable to anesthesiologists; there
are generally not significant differences in tardiness among anesthesiologists when controlling for specialty.9
The most common cause of late first case of the day starts is tardiness of the surgeons.11-15 Time series models
of progressive changes over months in tardiness of first case starts show that anesthesiologists respond to greater on-
time readiness of nurses and equipment, with a lag of 1 month (P = 0.005).12 Surgeons respond to greater on-time
readiness of anesthesiologists, nurses, and equipment, with a lag of 2 months (P < 0.0001).12 This is, in my opinion,
one of the classic studies in the application of operations research and management science to OR management.
Quoting the authors: “These results contradict the Pareto principle: surgeons are the main cause of delay for first
surgeries but one should not focus on them. It is the first source of the chain that needs to be closely controlled
rather than the one which appears to cause the most delays.” 12 The lesson is not just for handling first case starts,12
but essentially all operational type problems in OR management.16 Unless your facility has research-level accurate
data and analysts who are going to perform the analyses as in the scientific papers, rely principally not on internal
data and analysis, but the results of those papers.16 There is no additional effort to do the literature search to find
those papers because you cannot know if your facility has accurate data or has performed the appropriate analyses
without having read the papers. Reference (16) reviews how to find OR management articles.
Why are these behavioral results counter-intuitive? Most anesthesiologists, OR nurses, surgeons, etc., lack
scientific knowledge of over-utilized OR time (P < 0.0001).17 When we studied why, the material in the first section
was not learned through experience of working in ORs.17 Also, most survey respondents falsely believe that 10-
minute tardiness of the first case causes subsequent cases in the OR to start at least 10 minutes late (P < 0.001).17
Although partly since most do not know that most cases take less time than scheduled (P = 0.008),17 not a single
respondent who knew that most cases take less time than scheduled applied that knowledge to infer that 10 minutes
of tardiness of the first case start time does not cause subsequent cases to start at least 10 minutes late (P = 0.0002).17
That is what is referred to as a cognitive bias. The importance is that institutions’ fixation on first cases of the day
will be immutable to education.17 Such cognitive biases are amplified by small groups (i.e., a surgical committee
is less likely to make evidence-based decisions than a scientifically knowledgeable manager).18,19 The route to
achieving rational goals is to rely on the autocratic manager.19 Knowledgeable physician leadership matters. 20
How managers can improve on-time starts and thus increase OR efficiency is in part by providing electronic
displays with evidence-based recommendations for use on the working day before surgery and the day of surgery.21
As described in the 1st section, by definition, such displays need to incorporate OR allocations calculated based on
maximizing efficiency of use of OR time.21 The manager can assure that staff can take courses (i.e., receive
education), which increases trust in the manager’s recommendations.21,22 When monitoring a manager’s
performance, a good criteria to use to evaluate the manager’s facility is whether the displays effectively provide
recommendations and the information and checklists for how to use the information.23 The anesthesia group-facility
agreement can be used to codify the performance criteria.20,24
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Achieving the reductions in time for use to increase OR efficiency: Notifications on the day of surgery
When each patient’s information was reviewed repeatedly, and an escalating notification system used to
contact each team member to attend to pending tasks, first case start delays were reduced significantly (P < 0.001).14
Similarly, patient care assistants were notified 45 minutes before OR start time to go to the selected ICU bed for
preparation for transport.25 The anesthesia provider was notified 15 to 20 minutes ahead of surgery for patient
communication handoff with the ICU RN.25 These notifications significantly reduced mean tardiness (P < 0.0001).25
Achieving the reductions in time for use to increase OR efficiency: Planning the working day before surgery
At facilities where anesthesiologists medically direct multiple ORs, they must effectively use staggered starts
( 20 minutes to incision) during first cases of the day, since otherwise they cannot be present at all critical portions
of the cases.26 With 1:3 MD:CRNA, and medical direction, lapses would occur on greater than 96% of the days.26
Therefore, as feasible, let surgeons know ahead which ORs will be the 3rd to start, so that those with later starts are
not waiting in the ORs.27 This can be done, because anesthesiologists are good at forecasting time from OR entrance
until start of positioning.28 Times differ depending primarily from anesthetic technique (e.g., general), American
Society of Anesthesiologists’ Physical Status of patient, and procedures to be done (e.g., arterial line placement). 29
Teaching of anesthesiology residents increases OR time before the start of surgery by a mean of 4 minutes. 30,31
Anesthesiologists are faster when not supervising multiple ORs.32 Therefore, as appropriate and feasible, assign
anesthesiologists practicing alone to the ORs with over-utilized time, and 1st and 2nd year anesthesiology residents
to ORs with substantial under-utilized OR time.33
Assigning sufficient numbers of anesthesiologists and support personnel to perform peripheral nerve blocks
before OR entrance can facilitate reduced tardiness of first case starts.34,35 As feasible, sequence cases within
surgeons’ lists so that more of the cases with peripheral nerve blocks are performed later in workday. Such
sequencing does not increase the incidence of days with delayed PACU entrance.36
Work with surgical residents of specific specialties to have systems in place to assure no or small tardiness
of starts, as relevant.37 An example is having a mid-level resident leave team rounds early when rounds are taking
sufficiently long as to influence first case start.37
For an OR to be used for patients who are inpatient preoperatively, identify the case most likely to start on
time.38 Schedule that case to be the first case start, changing it only if a new, emergency case arises. 38 This reduced
the mean tardiness of first case starts of the trauma list by 26 minutes (P < 0.001). 38
Disclosure
No financial relationships with commercial interest.
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References
1. McIntosh C, Dexter F, Epstein RH. Impact of service-specific staffing, case scheduling, turnovers, and first-case
starts on anesthesia group and operating room productivity: a tutorial using data from an Australian hospital.
Anesth Analg 2006;103(6):1499-516
2. Strum DP, Vargas LG, May JH, Bashein G. Surgical suite utilization and capacity planning: a minimal cost
analysis model. J Med Syst 1997;21(5):309-22
3. Pandit JJ, Dexter F. Lack of sensitivity of staffing for 8-hour sessions to standard deviation in daily actual hours
of operating room time used for surgeons with long queues. Anesth Analg 108(6):1910-5
4. Wang J, Dexter F, Yang K. A behavioral study of daily mean turnover times and first case of the day start
tardiness. Anesth Analg 2013;116(6):1333-41
5. Shi P, Dexter F, Epstein RH. Comparing policies for case scheduling within one day of surgery by Markov chain
models. Anesth Analg 2016;122(2):526-38
6. Dexter F, Wachtel RE, Epstein RH. Decreasing the hours that anesthesiologists and nurse anesthetists work late
by making decisions to reduce the hours of over-utilized operating room time. Anesth Analg 2016;122(3):831-42
7. Dexter F, Traub RD. How to schedule elective surgical cases into specific operating rooms to maximize the
efficiency of use of operating room time. Anesth Analg 2002;94(4):933-942
8. Dexter F, Epstein RD, Traub RD, Xiao Y. Making management decisions on the day of surgery based
on operating room efficiency and patient waiting times. Anesthesiology 2004;101(6):1444-53
9. Dexter F, Epstein RH. Typical savings from each minute reduction in tardy first case of the day starts. Analg
2009;108(4):1262-7
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recovery protocols to decrease the time for emergence or increase the phase I post anesthesia care unit bypass
rate affect staffing of an ambulatory surgery center. Anesth Analg 1999;88(5):1053-63
11. Truong A, Tessler MJ, Kleiman SJ, Bensimon M. Late operating room starts: experience with an education trial.
Can J Anaesth 1996;43(12):1233-6
12. Lapierre SD, Batson C, McCaskey S. Improving on-time performance in health care organizations: a case study.
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13. Shelver SR, Winston L. Improving surgical on-time starts through common goals. AORN Journal
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14. Panni MK, Shah SJ, Chavarro C, Rawl M, Wojnarwsky PK, Panni JK. Improving operating room first start
efficiency – value of both checklist and a pre-operative facilitator. Acta Anaesthesiol Scand 2013;57(9):1118-23
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20. Dexter F, Epstein RH. Associated roles of perioperative medical directors and anesthesia: hospital agreements
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25. Brown MJ, Kor DJ, Curry TB, Marmor Y, Rohleder TR. A coordinated patient transport system for ICU patients
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26. Epstein RH, Dexter F. Implications of resolved hypoxemia on the utility of desaturation alerts sent from an
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27. Koenig T, Neumann C, Ocker T, Kramer S, Spies C, Schuster M. Estimating the time needed for induction of
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29. Escobar A, Davis EA, Ehrenwerth J, Watrous GA, Fisch GS, Kain ZN, Barash PG. Task analysis of the
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Anesth Analg 2006;103(4):919-21
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37. Warner CJ, Walsh DB, Horvath AJ, Walsh TR, Herrick DP, Prentiss SJ, Powell RJ. Lean principles optimize on-
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Kaizen! Employing Lean Principles in the Ambulatory Setting
Douglas G. Merrill, MD MBA Orange, CA
I. INTRODUCTION
Why would we care about “Lean Principles” in the setting of a hospital outpatient department or
ambulatory surgery center? In the setting of modern healthcare policy, the advantage will generally be
to those providers who can prove their value to the payer. Value, typically defined as Quality/Cost, can
also be considered as a net equation that might be described simply as “Positive Outcomes, total -
Negative Outcomes, total = Net Benefit.” Providers who reliably produce a positive net benefit in
excess of the expected or average results among their competitors will be attractive to payers, patients,
and other providers, as well as regulators and accreditation agencies. The use of Lean principles -- the
culture of teamwork, relatively flat hierarchy and the pride in efficiency and cost reduction present in
the workforce at most ambulatory surgery centers – can be leveraged and channeled by leadership via
well-organized multiple team-based events.
II. HISTORY OF LEAN

Lean management is a technique of process improvement that grew out of the manufacturing
environment. “In short, Lean seeks to reconfigure organizational processes to reduce waste and
enhance productivity based upon the application of specialist analytical tools and techniques coupled
with creating a culture of continuous improvement” (Radnor, Holweg, & Waring, 2012). Lean
provides a methodology of process improvement that is inherently participatory, allowing front line
staff to define hurdles and create and trial solutions, helping to assure that outcomes are reality-based
and that employee acceptance of change is enhanced (Perez Toralla, Falzon , & Morais, 2012). The
Toyota Production System may be considered the penultimate application of Lean principles. Its
underpinning doctrines were applied in the 1880s by Sakichi Toyoda to reduce waste and inefficiency
in the loom industry before being developed fully and implemented in the automotive industry by
Taiichi Ohno, thereby leveraging the juxtaposition of automation and just-in-time production
methodology (Ohno, 1988). Ohno’s concept centered on asking “why?” five times or more in order to
distill the causative factors in a process, thereby eliminating those that were unnecessary and leaving
the process without waste. It is a continuous technique and its focus on the front line worker’s
participation can lead to a cultural change in which the employees are re-trained as experts in the field
of process improvement observation, now able to detect and uncover opportunities for improvement.
This is also congruent with the principles of High Reliable Organizations (HRO), where all
participants are expected and trained to observe for “the next error” to reduce the potential for system-
enabled error. Inherent in the theory and practice of HRO methodology is that there must be a concern
for the cost of error (Wiedlea, 2011). This fundamental concern translates into “waste” in Lean:
management and employees must be motivated to eliminate waste in order for Lean to be an effective
methodology.
The use of Lean is congruent with “management by measurement,” the review of outcome and process
metrics to direct process improvement (in as short a cycle as possible between measurement and
revision). It has been widely applied in healthcare, as reflected in Donabedian’s work on quality
improvement (Donabedian, 1966) (Schiff & Rucker, 2001). Indeed, outcome measurement is critical
to quality improvement. However, collection of data and sharing with providers so that they can assess
the need for change and its best iteration is not widespread in perioperative practice. In order for
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efficiency to be directed by the providers of care, measurement must be dependable and its findings
distributed to those who are being measured.
III. LEAN IN HEALTHCARE

The entry of Lean management principles into healthcare has resulted in some notable successes,
particularly on small scale projects, but also a few – such as the Virginia Mason Clinic – that have
occurred as full cultural change across an entire enterprise. Its introduction has been part of what has
been termed the “managerialization” of healthcare, in the application of private, business principles to
the organization and delivery of healthcare in an effort – at its most basic - to reduce its cost
(Pettigrew, Ferlie, & McKee, 1992). Virginia Mason was the first healthcare institution to introduce
what is now the Virginia Mason Production System™ as modeled after the Toyota Production System
(TPS™) in 2002 (Kenney, 2011).
Ohno construed Lean as the repeated effort to eliminate wasteful steps in a process. This has been
adapted to healthcare in the identification of seven types of waste and five lean principles, reproduced
here (Radnor, Holweg, & Waring, 2012):
The Seven Wastes and healthcare examples of each:

1. Transportation
• Staff walking to the other end of a ward to pick up notes
• Central equipment stores for commonly used items instead of locating items where they are used
2. Inventory
• Excess stock in storerooms that is not being used
• Patients waiting to be discharged
3. Motion
• Unnecessary staff movement looking for paperwork
• Not having basic equipment in every examination room
4. Waiting (Delay)
• Patients, theatre, staff results, prescriptions and medicines
• Doctors to discharge patients
5. Overproduction
• Requesting unnecessary tests from pathology
• Keeping investigation slots ‘just in case’
6. Over- Processing
• Duplication of information
• Asking for patients’ details several times
7. Defects and Correction:

• Readmission because of failed discharge
• Repeating tests because correct information was not provided
The Five Principles of Lean

1. Specify the value desired by the customer.
2. Identify the value stream for each product/service providing that value and challenge all of the
wasted steps.
3. Make the product flow continuously. Standardize processes around best practice, allowing them to
run more smoothly, and freeing up time for creativity and innovation.
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4. Introduce ‘pull’ between all steps where continuous flow is impossible. Focus upon the demand
from the customer and trigger events backwards through the value chain.
5. Manage towards perfection so that non-value-adding activity will be removed from the value chain
and the number of steps, amount of time, and information needed to serve the customer continually
falls.
A review of the literature reveals that Lean principles are most often used in healthcare in small
subunits (Radnor, Holweg, & Waring, 2012) such as a single department, rather than across an
organization, as was true of Virginia Mason. This is because it is most easily implemented within point
of care locations when designs do not require as much cross-unit coordination. The successful
implementation of Lean requires scrupulous measurement of a process and “biting off a big chunk”
often deters managers from looking at processes that cross outside their areas of hegemony. This very
nature of it can make it particularly valuable in an ASC or HOPD, however, as we shall explore below.
Nonetheless it has been implemented widely in healthcare in the attempt to replicate the decrease in
waste, inefficiency and cost that it has achieved in various business arenas (RDS, 2015).
IV. PREQUISITES TO MAKING LEAN WORK IN AN ASC

There are many aspects to Lean management but one concept that will be very congruent with the
culture of the ASC or HOPD is “Kaizen.” This is the practice of continuous improvement, such that
“big results come from many small changes accumulated over time.” (What is Kaizen?) Thus, a kaizen
“event,” which can be very effective, is not intended to ‘set and forget’ a process, but to get to a better
process, which will itself form a launching pad for further improvement for serial kaizen episodes.
Kaizen events have also been known as Rapid Process Improvement Workshops or RPIWs. Ideally
they would be led by an expert. A good approach is to hire a Blackbelt in Lean RPIW (not all
Blackbelts are equally versed in Kaizen, so it is important to determine that they are before engaging
one in this work). A Blackbelt will have received training and be experienced in Lean principles and
practice. He or she can help you by showing you how to define your problem, measure it, analyze the
data and then lead the team in brainstorming and implementing changes in their workflow (“improve”)
and then set you up to measure the outcomes to try to sustain improvement and continue to look for
other ways to improve the process (“Control”). Taken together, these steps are DMAIC – Define,
Measure, Analyze, Improve, and Control, which form the basis of quality improvement (Borror, 2009,
pp. 333-354). Inherent in this consultation is that he or she must be engaged to teach you and your
teams how to both look for opportunities and do the work after he or she is gone. It is important to
understand that this is an iterative process: one cannot expect results of this work if it is done once or
even once or twice a year. The ideal situation is a weekly or – at minimum – monthly exercise. You
would want to train at least two members of your staff in the measurement and facilitation process.
Ideally you would obtain for them some off-site training that would eventuate in their obtaining
certifications in Lean, which would increase their ability to implement it in your center and would be
valuable to their careers.
V. EXAMPLES OF LEAN PROJECTS IN AN ASC

In order to explain how a Kaizen might work for your center, I will present a couple of short examples
of events I have led in surgery centers and HOPDs in the past few years.
A. The Cataract Suite
In one ambulatory surgery center, the nursing and technical team noted that they were each having
to wait for the other with nothing to do during sometimes long periods of a cataract OR day. Often
patients would not be ready to come back to the pre-op area from registration when the RN went
to retrieve them, and then would be in process when the OR was ready and waiting. On other
occasions, the pre-op area was “backed up” with patients in all their beds because the OR was not
ready to receive the next patient, preventing the intake of ready patients from the reception area.
We convened a group consisting of one OR RN, one OR Tech, one Pre-/Post-Recovery RN, a
receptionist, a cataract surgeon and – as the champions – the ASC Medical Director and ASC
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Nursing Director. In this setting, the “Champion” sits in on the process and – if out – is called in
whenever a process that the team does not control (e.g., here, sterilization of instruments) has been
found to have a potential or actual significant contribution to either the current wasteful process or
be an area in which a solution might be found, or both. In that case, the champion can either pull
in an expert from that area or – if expected to be a small part of the issue – simply convey needed
change to that area. If resources are needed, such as money or equipment, the champion is
typically located high enough in the organizational structure to allow for expedited infusion of
those resources.
In this case, it was determined, for instance, that two more cataract sets would avoid the delays
seen in the afternoon due to turnover of sets, so I was able to approve that purchase for the team.
All the other changes were of the nature of process and did not require resource allocation. The
leader measured the process for a full day, using a stopwatch and following every other patient
through his or her complete “cycle” while on site. On a Friday that had been set aside for this
purpose, the team met and reviewed the data. A spaghetti diagram was created to show how each
employee and the patient traversed the physical space to accomplish the steps required. Times
used for each step were attached to a timeline and the several employees’ processes were shown in
parallel on a long sheet of paper that took up a whole wall of the room. Each of the representative
employees were asked to comment on the steps and explain the “5 whys” of why each step was
performed and to suggest alterations that might eliminate the steps. Other team members would
then weigh in with suggestions and unexplored congruencies of labor were discerned and
reviewed among them. It took a full day (and an order of pizza for lunch) but the team, working in
various subgroups and as a whole, reduced the steps of each process and altered key steps to
reduce the required time for registration, for pre-op assessment, for OR preparation, for transport
to and from the OR, and for time in the recovery area. Various steps were removed as they were
determined to be redundant of others, or unnecessary. Timing for some steps to allow simultaneity
was implemented.
The outcome at the end of this very busy day was that the anticipated time for a cataract patient to
transit the center from admission to discharge was reduced by 20 minutes. The following Monday,
the new process was in place (expedited by the changes in paperwork having been made during
the Kaizen event) and, over the course of the following week, a reduction of 28 minutes was the
actual outcome. By measuring the process repeatedly (either the ASC Nurse Manager or Medical
Director would follow a patient intermittently when time permitted, about once a month), the
gains were sustained. The surgeons were excited and determined that their average daily OR
schedule could now accommodate two more patients.
B. The Pink Bucket

A good exercise of Lean talent is the very easy process of the “pink bucket” exercise. If several
surgeons are performing similar procedures, as is usual in an ASC or HOPD, but there is a wide
variety and large volume of instrumentation among them, this process can help streamline. For
two weeks, each time one of the surgeons performs one of the identified procedures, there should
be a pink bucket on the back table. The surgical technicians are to put in the pink bucket only
those instruments which were used in the case. When the table is moved to decontamination, that
tech takes inventory of the pink bucket contents. At the end of two weeks, the Center should host a
breakfast for the surgeons and lay out the instruments that were used greater than 50% of the time,
between 10 and 50% of the time, and less than 10% of the time, on different tables, for each
procedure. They would be asked to trial a system in which the first group of instruments would be
up on the back table, the second group would be in the room but wrapped, and the third group
would remain sterile and wrapped in the central supply area. There will usually be some swapping
and cajoling to move instruments from one group to another, but often the surgeons will become
competitive to see who “needs” the least instrumentation.
You will, via this project, accomplish standardization and reduce wear and tear on the instruments.
As well, when a new surgeon comes, he or she is provided a list and told that “this is what our
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surgeons all chose for the hernia (or cholecystectomy, or hysteroscopy) kit,” with the certainty that
he or she will want to fit in. Three warnings:
1. Your technicians may slip instruments into the pink bucket that weren’t actually used
“because I don’t want to get yelled at” if they aren’t on the table.
2. Your surgeons may quietly ask for instruments to be opened onto the back table “every time”
even though they don’t use them often.
3. You have to repeat the process every year, at least, in order to undo these “backslides.”
Having said that, this kind of work, done for each specialty’s top five procedures, can greatly
reduce the cost of care and improve its safety as the technicians have a standard practice
among their surgeons and will thereby reduce errors.
Another form of this can be accomplished with the choices of local anesthetic. At one ASC, we
reduced the plastic surgeons’ choices of local anesthetic mixtures to three (lidocaine plain,
lidocaine with epinephrine, and a tumescent solution) from over ten, following a near miss with
epinephrine mixing that frightened all providers with its possible negative outcome.
VI. THE VALUE OF LEAN IN THE AMBULATORY SURGERY CENTER

The use of Lean principles in managing an ASC or HOPD has great potential for increased value due
to cost reduction and more efficient use of patient and provider time, increasing the satisfaction of
both. However, note must be made of some of the limits of Lean in the healthcare setting. At its core,
Lean is a change-introduction methodology. Healthcare providers are notoriously attached to anecdotal
non-standard practice and resistant to change. As such, Lean will require repeated and cheerful
implementation before the majority of physicians and staff will be won over. The ophthalmologists
were very happy with the outcomes of the Kaizen event that reduced turnover time and increased their
caseload capacity, but remained resistant to changing instrumentation and local anesthetic choices,
even when presented as a natural extension of streamlining the turnover process and enhancing patient
safety. Concerns for patient safety will also be raised by some staff, who are concerned that “this is all
so we can go faster and make more money.” Showing these staff that it is helpful to patients that they
not have to wait another week for surgery can be helpful. “Patient-centered care” is a salutatory goal
but is sometimes held up to resist change. On occasion, bringing such providers into the room and
showing them the waste incurred by the patient, in time and money, because the “patient-centered
care” is actually “Dr. Jones-centered care” has been successful, but it can take many such exposures
before the minds are changed.
Another limitation to the value of Lean is that an ambulatory surgery center tends to be capacity-
oriented, in that there are so many operating rooms and so many hours of operation. If a Kaizen leads
to increased capacity that cannot be filled with additional work (e.g., if additional operations aren’t in
the offing, as they were for our cataract physicians) then finishing earlier in the day will be the primary
outcome, which may or may not (depending upon the structure of your labor arrangements) provide
additional value to you or your payers. It will still provide additional value to your patients (Radnor,
Holweg, & Waring, 2012).
Finally, a fundamental difference between healthcare and most industry is that the customers are split.
Whereas the payer and customer are one in the same in most industries, in healthcare the majority of
our customers (e.g., patients, surgeons) are not the payers. They may not, and likely do not, value the
same outcomes. For instance, some surgeons see little import of the cost of labor at the surgery center,
but the Center does if there is no pass-through possible to the insurance company. The insurance
company might be concerned if there is a pass-through and it has no other option than to use your ASC
or HOPD (a vanishing condition). A patient will potentially want to stay until his or her spouse is done
with work at 5 or 6PM, whereas the Center (and its employees) sees value in rapid discharge.
Therefore, for these reasons, Lean management may not obtain great gratification even as waste is
removed. Recognizing who the customer is for any process is part of the original “Define” step in
DMAIC and may alleviate this issue, but it may not be avoidable until healthcare payment policy
unifies the goals of the payers and the customers.
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VII. GOOD READING
Borror, C. M. (2009). The Certified Quality Engineer. Milwaukee: ASQ Quality Press.
Donabedian, A. (1966). Evaluating the quality of medical care. Milbank Memorial Fund Quarterly, 44, 166-206.
Kenney, C. (2011). Transforming Healthcare: Virginia Mason Medical Center's Pursuit of the Perfect Patient
Experience. NY NY: Taylor and Francis Group.
Ohno, T. (1988). Toyota Production System: Beyond Large-Scale Production. Portland OR: Productivity press.
Perez Toralla, M. S., Falzon , P., & Morais, A. (2012). Participatory design in lean production: which contribution
from employees? For what end? Work, 41(Suppl 1), 2706-12.
Pettigrew, A., Ferlie, E., & McKee, L. (1992, September). Shaping strateci change - the case of the NHS in the
1980s. Public Money and Management, 27-31.
Radnor, Z. J., Holweg, M., & Waring, J. (2012). Lean in healthcare: the unfilled promise? Social Science and
Medicine, 74, 364-371.
RDS. (2015, August). Getting comfortable with lean: contract research, development, and manufacturing
organizations are embracing lean manufacturing, while Big Pharma is applying it, not so much for
inventory management, but to improve supply chain visibility and control. Pharmaceutical Technology
Europe, 37.
Schiff , G. D., & Rucker, T. D. (2001). Beyond Structure-Process-Outcome: Donabedian's seven pillars and eleven
buttresses of quality. Jt. Comm J Qual Imp, 27(3), 169-174.
What is Kaizen? (n.d.). Retrieved May 22, 2016, from Kaizen Institute USA: http://us.kaizen.com/know
Wiedlea, A. (2011). Highly Reliable Organizations. In S. B. Johnson, & et al, System health management with
aerospace applications (pp. 49-63). Chichester, UK: John Wiley & Sons, Ltd.
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Perioperative Management of Patients With Left Ventricular Assist Devices

Undergoing Noncardiac Surgery
Michael F. O’Connor MD FCCM Chicago, IL
As Left Ventricular Assist Devices are implanted in ever more patients, the chances that a patient with one might
come to your operating rooms or procedures suites is increasing; to the point where you may be asked to provide
anesthesia for emergency and even elective procedures in these patients. Copyright law precludes the inclusion of
the tables, figures, and photographs used in this lecture in this handout. With a few exceptions, these can be found
in the references at the end of this handout.
What you need to know:

• Anatomy of these devices?
• Indications for these devices?
• How do these devices change a patient’s physiology?
• Complications of implanting these devices?
• Clinical Implications of all of this?
• When is it time to stop?
What is the anatomy of these devices?

A subset of these devices represent the vast majority of their current use, with the Heartmate 2 and Heartware being
the most commonly implanted devices. A complete list is not easy to assemble or keep current.
Non-pulsatile = Continuous Flow

• Heartmate 2 (>10,000 Apr2012)
• Heartware
• Heartmate 3
• Heart Assist 5
• Duraheart
• Incor
• VentrAssist
• MiTiHeart
• Others……
•
Pulsatile
• Thoratec PVAD IVAD (>3000)
• Syncardia Total Artificial heart
Who gets these Devices?

Ischemic DCM
Non-Ischemic DCM
• Often ischemic
• Peri-partum CM
• EtOH (admitted or not)
• Auto-immune
• Not yet for muscular dystrophy, Marfan’s or ED
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Purpose?
This technology is now so commonly available that patients in crisis are often started on “short term devices”, and
then assessed for eligibility for longer-term devices or transplantation. In some instances, patients can recover
sufficiently that they may no longer require any mechanical support. Some of the devices employed for short-term
support (e.g. centrimag) may not be regarded as appropriate for longer term use. In many instances, the path to these
devices now begins with a cardiac arrest that ends with the placement of a patient on ECMO.
Short-term/Bridge to transplant
• Recipient is believed to be a good candidate for heart transplant
• Once upon a time, most patients listed for heart failure died awaiting an organ.
• ~70 % survive to transplant
• drive line infections and bleeding during transplant have increased interest in alternatives
•
Long-term support/Destination therapy
• Recipient is ineligible for heart transplant
• Dramatic improvement in functional status among those who do not suffer major complications
• 1 year survival
– 80% Low Risk
– 60% Medium Risk
– 30% High Risk
– 10 % Very High Risk
How do these devices change physiology?

• Pulse -> minimal pulse or pulseless
• Anticoagulation heparin -> warfarin - exact protocols and targets in evolution
• Acquired vWF disease
Pulsatility Index (PI)

• Occurs with all continuous flow devices (but not pulsatile), but is not reported by all manufacturers.
• Index of augmentation of forward flow from cyclical increased inflow by LV contraction
• Higher Pump flows -> Lower PI
• Increased Circulatory volume -> increased PI
• Decreased Circulatory volume -> decreased PI
PI = [(flow max – flow min)/ flow average] x10
Circulatory Physiology
• MAP is both created by the LVAD and the pressure against which it pumps
• Goal MAP = 70-80 mmHg (Watts = Heat)
• Aortic valve continuously subjected to high pressures (80- (-20)) and unfavorable geometry ->AI
• Fontan Flow is possible in patients with a normal PVR
• High Pump speeds suck septum into inflow tract (likely better than ) = Suction Event
• Venous return matters -> intravascular volume matters
• RV outflow is LVAD inflow
• MAP perfuses the RV (PA HTN)
• PVR still matters
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Complications – why YOU will see them:

• Bleeding 44%
• Infection 46%
• Respiratory Failure 20%
• Renal Failure 10%
• Stroke 6.5%
• Liver Failure 6.5%
• Hemolysis 3%
• Venous Thromboembolism 6.5%
• RV Failure 15%
• Depression 8%
• Acquired AI
• LVAD thrombosis (8.5% incidence with 48% mortality)
• Device Failure
Why do these patients come to the ICU/OR?

• EGD/colonoscopy/DBE for GI bleeding
• Drain pus – drive line, chest wall, pleural
• Drainage of hematoma – intracranial, other
• Cancer operations – esp abdominal operations/obstructions
• Thoracic procedures
• Aortic valve operations
• LVAD replacement
Clinical Considerations
• Is the stomach full? Blood?
• Hold or reverse anticoagulation as required (Acquired vWF) FFP preferable to rFVII or PPC
• Previous trach -> may require smaller tube
• Vasculopath?
• Sildenafil, milrinone, midodrine -> tenuous RV
• Patients with limited RV function kept very dry
• Wall Power > Battery Power (console calculates flow)
• Goal MAP = 70-80mm Hg (RV perfusion)
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• Spontaneous ventilation > Mechanical ventilation

• Least positive pressure ventilation is better (Small TV, low rate)
• AICD/pacemaker still requires evaluation and a plan for management
Monitoring
• Mission Impossible = Assessment of volume status. Pulsatility Index (PI) is most reliable. Low threshold
for TEE to assess LV volumes
• Patients with limited RV function may be very dry
• Bleeding can be insidious -> frequent ABGs (GI bleed)
• Central Line if vasoactives might be required (?PICC?)
• Meticulous Sterile Technique
• Echo?
Crisis Management
• BEWARE the RV! RV outflow is LVAD inflow
– Maintain the circulating volume (replace blood, bodily fluids, insensible loss)
– Maintain Perfusion – Neo, Vaso, Norepi (almost never lower flow)
– Maintain Contractility – Dobut
– Worst case scenario - iNO
• Remember – MAP perfuses the RV
• Rhythm matters – for the RV
• ACLS is for the RV – Do It!!!
References:
Stone M, et al: Trends in the Management of Patients With Left Ventricular Assist Devices Presenting for
Noncardiac Surgery:  A 10-Year Institutional Experience
Seminars in Cardiothoracic and Vascular Anesthesia  1-8, 2015
Kirkpatrick JN, et al: Ventricular assist devices for treatment of acute heart failure and chronic heart failure
Heart 2015;0:1–6. doi:10.1136/heartjnl-2014-306789
Sheu R, et al: Perioperative Management of Patients With Left Ventricular Assist Devices Undergoing Noncardiac
Procedures: A Survey of Current Practices.
Journal of Cardiothoracic and Vascular Anesthesia, Vol 29, 2015: pp 17–26
Partyka C, Taylor B: Review article: Ventricular assist devices in the emergency department
Emergency Medicine Australasia (2014) 26, 104–112
Barbara DW, et al: The Perioperative Management of Patients With Left Ventricular Assist Devices Undergoing
Noncardiac Surgery Mayo Clin Proc. 2013;88(7):674-682
Nguyen DQ: Third-Generation Continuous Flow Left Ventricular Assist Devices

Continuous Flow Left Ventricular Assist Devices Innovations 2010;5:250–258
Birks EJ: Left Ventricular Assist Devices

Heart 2010;96:63–71
Slaughter MS et al: Clinical Management of continuous-flow left ventricular assist devices in advanced heart failure
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Journal of Heart and Lung Transplantation 29:S1-S39, 2010
Starling RC: Results of the Post-U.S. Food and Drug Administration- Approval Study With a Continuous Flow Left
Ventricular Assist Device as a Bridge to Heart Transplantation
JACC 2011;57:1890–8
Park SJ et al: Outcomes in Advanced Heart Failure Patients With Left Ventricular Assist Devices for Destination
Therapy
Circ Heart Fail. 2012;5:241-248.
Starling RC, et al: Unexpected Abrupt Increase in Left Ventricular Assist Device Thrombosis
N Engl J Med 2014;370:33-40
Uriel N, et al Development of a Novel Echocardiography Ramp Test....

J Am Coll Cardiol. 2012;60(18):1764-1775
Chiu W. et al: Thromboresistance Comparison of the HeartMate II Ventricular Assist Device With the Device
Thrombogenicity Emulation-Optimized HeartAssist 5 VAD
J Biomech Eng 136(2), 021014 (Feb 05, 2014)
Topilsky Y, et al: Focused Review on Transthoracic Echocardiographic Assessment of Patients with Continuous
Axial Left Ventricular Assist Devices
Cardiology Research and Practice Volume 2011, Article ID 187434
Malhesa D: Acquired von Willebrand syndrome after exchange of the HeartMate XVE to the HeartMate II
ventricular assist device
European Journal of Cardio-thoracic Surgery 35 (2009) 1091—1093
Nir U: Acquired von Willebrand Syndrome After Continuous-Flow Mechanical Device Support
Contributes to a High Prevalence of Bleeding During Long-Term Support and at the Time of Transplantation
J Am Coll Cardiol 2010;56
Crow S: Gastrointestinal bleeding rates in recipients of nonpulsatile and pulsatile left ventricular assist devices
J Thorac Cardiovasc Surg 2009;137:208-15
Stern DR: Increased Incidence of Gastrointestinal Bleeding Following Implantation of the HeartMate II LVAD
J Card Surg 2010;25:352-356
Islam S, et al: Left Ventricular Assist Devices and Gastrointestinal Bleeding: A Narrative Review of Case Reports
and Case Series Clin. Cardiol. 36, 4, 190–200 (2013) 
Stone ME:Current Status of Mechanical Circulatory Assistance

Semin Cardiothorac Vasc Anesth 2007; 11; 185
Draper KV, et al: GI bleeding in patients with continuous-flow left ventricular assist devices: a systematic review
and meta-analysis Gastrointestinal Endoscopy 2015; 81: 776-777
Uriel N, et al: Device thrombosis in HeartMate II continuous-flow left ventricular assist devices: A multifactorial
phenomenon J Heart Lung Transplant 2014;33:51–59
Baumann Kreuziger LM, Kim B, Wieselthaler GM. Antithrombotic therapy for left ventricular assist devices in
adults: a systematic review. J Thromb Haemost 2015; 13: 946–55.
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Toeg H, et al: Anticoagulation strategies for left ventricular assist devices Curr Opin Cardiol 2015, 30:192–196
Abshire M, et al: Functional Status in Left Ventricular Assist Device-Supported Patients: A Literature Review
J Cardiac Fail 2014;20:973-983
Shinar Z, et al: Chest compressions may be safe in arresting patients with left ventricular assist devices (LVADs)
Resuscitation 85 (2014) 702–704
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Perioperative Delirium: Making Sense of all the Confusion
Christopher G. Hughes, MD Nashville, Tennessee
Introduction
Delirium occurs when a patient experiences fluctuations in mental status caused by acute cerebral
dysfunction. All hospitalized patients are at risk for the development of delirium, and patients in the perioperative
setting are no exception. The risk of developing delirium appears dependent on age, preexisting comorbid
conditions, severity of concurrent illness, and the severity of the surgical process. 1,2 Postoperative delirium has been
reported to occur in up to 50% of patients after both cardiac and non-cardiac surgery, typically developing on the
first or second day of admission.3 Studies in surgical patients focusing on delirium in the first few postoperative days
have found significant associations with increased length of stay, higher cost of care, readmission to the hospital,
higher rates of institutionalization after discharge, prolonged cognitive impairment, and increased mortality.4-7
Because delirium occurs commonly and is associated with worse outcomes, an understanding of its disease process,
risk factors, and management is essential for an anesthesiologist.
Definition and Diagnosis
According to The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5),8 delirium
is a disturbance in the ability to direct, focus, sustain, and shift attention. This is coupled with a change in cognition,
either in the form of memory deficit, disorientation, or perceptual disturbances, which is not accounted for by a
neurocognitive disorder or a severely reduced level of arousal. These mental status changes are acute in onset,
fluctuate throughout the day, and may be characterized by both hypoactive and hyperactive psychomotor activity.
While no consensus definitions exist, emergence delirium typically refers to agitation after discontinuation of an
inhaled anesthetic, post-anesthesia care unit (PACU) delirium refers to delirium occurring after emergence but
during initial recovery phase, and postoperative delirium refers to delirium that occurs after the patient meets PACU
discharge criteria or has been discharged from the PACU.
The perioperative setting poses some challenges in the diagnosis of delirium, including sedative medication
administration and emergence from general anesthesia. While there are no validated delirium assessment tools for
the PACU specifically, there are validated instruments that allow clinicians to assess for delirium even when a
patient is mechanically ventilated. The first step is to assess level of arousal, for assessment of delirium cannot occur
if a patient is unresponsive. The most commonly utilized arousal scales include the Richmond Agitation Sedation
Scale (RASS)9 and the Sedation Agitation Scale (SAS).10 If the patient can respond to verbal stimuli when assessing
their arousal, they can be assessed for delirium using tools such as the Confusion Assessment Method (CAM), 11 the
4AT,12 the Nursing Delirium Symptom Checklist (NuDESC),13 the Confusion Assessment Method for Intensive
Care Unit (CAM-ICU),14 or the Intensive Care Delirium Screening Checklist (ICDSC). 15 The CAM assessment
includes an evaluation of the patient for four key features of delirium: fluctuating mental status, inattention, altered
level of consciousness, and disorganized thinking. The 4AT is a brief tool that assesses alertness, orientation,
attention, and change in mental status. The NuDESC is a screening tool looking for disorientation, inappropriate
behavior and communication, hallucinations, and psychomotor retardation. If the patient is critically ill or
mechanically ventilated, the CAM-ICU and ICDSC scales are the most validated. The CAM-ICU assesses the same
four features as the CAM examination in a more abbreviated manner to fit the needs of ICU patients. The ICDSC
uses eight diagnostic features evaluated over a nursing shift to make the diagnosis of delirium, for which the patient
needs only four of those features.
Etiology and Risk Factors
There are many proposed mechanisms for the development of delirium, including systemic and central
nervous system inflammation, endothelial and blood brain barrier dysfunction, cholinergic deficiency, and
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disturbances in neurotransmitters such as serotonin and norepinephrine. 16 Studies have shown that there are
neuroanatomical changes associated with delirium, including brain atrophy and white matter changes. 17,18 Overall,
however, the pathophysiology of delirium remains poorly understand and likely variable depending on the patient
and clinical situation.
It is important for clinicians to understand the baseline risk factors and acute precipitants for delirium in
order to minimize its occurrence. The most common risk factors and precipitants are outlined in Table 1.
TABLE 1. DELIRIUM RISK FACTORS AND PRECIPITANTS

Risk Factors Precipitants
Increasing age Infection
Pre-existing cognitive impairment Dehydration
Hypertension Electrolyte abnormalities
Congestive heart failure Acute kidney failure
Acute myocardial infarction Acute liver failure
Mechanical ventilation Ethanol/drug withdrawal
Poly-trauma Fragmented sleep
Metabolic acidosis Central nervous system insults
Existing coma/delirium Benzodiazepines
In addition, risk factors of postoperative delirium reported in the literature appear to be influenced by the
severity of the surgical insult, comorbidities, and sedative and/or analgesic drug exposure (Table 2). 2 Administration
of benzodiazepines, in particular, have been associated with increased risk of emergence and postoperative
delirium.19,20 Opioid administration has been associated with delirium in the postoperative and ICU settings,21-23 but
data on this association is inconsistent as others have shown opioids to be protective (or have no effect) with regards
to delirium when used to appropriately control pain.24-26
TABLE 2. PERIOPERATIVE RISK FACTORS FOR DELIRIUM

Surgery Anesthesia
Major abdominal ASA >3 Classification
Cardiac Benzodiazepine premedication
Emergency vs. elective General anesthesia?
Open vs. endovascular Deeper sedation?
Increased duration Opioid administration?
Delirium Prevention
The evidence is inconclusive regarding the effects of anesthesia type or depth of anesthesia on the
development of postoperative delirium. Spinal anesthesia with lighter sedation vs. deeper sedation for hip surgery
has been studied in elderly patients and did show a decrease in the incidence of postoperative delirium in patients
receiving lighter sedation.27 Furthermore, monitoring depth of anesthesia was associated with less oversedation and
also with less postoperative delirium.28 No difference in delirium was found between a total intravenous propofol
general anesthetic compared to desflurane.29 There have been two low-quality randomized clinical trials that found a
lower incidence of delirium in patients who received regional anesthesia for lower extremity surgeries, 30 and a
Cochrane review suggested that regional anesthesia may decrease postoperative confusion in hip surgery patients
compared to general anesthesia.31 A large prospective study of elderly hip surgery patients, however, did not find an
increased risk of postoperative delirium with general anesthesia vs. regional anesthesia, and a neither did a more
recent meta-analysis.32 Current clinical guidelines30 for postoperative delirium prevention in the elderly state that
regional anesthesia can improve pain control and help prevent delirium, as studies have shown an association
between poor pain control and higher rates of delirium. 33A study of femoral nerve blockade in addition to patient
controlled analgesia demonstrated a lower incidence of postoperative delirium after total knee replacement. 34 A
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small randomized controlled trial in patients having spine surgery compared prophylactic gabapentin to placebo and
found that gabapentin reduced delirium.35 A fast-track surgery model for knee and hip arthroplasty found minimal
delirium when the non-opioid medications gabapentin, acetaminophen, and celecoxib were primarily used for pain
management.36 Finally, low rates of delirium have been reported after an enhanced recovery fast-track model for
colonic surgery that minimized opioid exposure.37
Studies investigating whether prophylactic antipsychotic administration reduces the incidence or duration
of delirium have had mixed results. Perioperative haloperidol prophylaxis in elderly hip surgery patients did not
affect the incidence of delirium but did decrease the duration. 38 A low dose haloperidol bolus followed by an
infusion in elderly patients admitted to the ICU after noncardiac surgery decreased the incidence of delirium only
after intra-abdominal surgeries.39 A before-after study of haloperidol as prophylaxis in ICU patients deemed high
risk for delirium showed significantly less incidence and duration of delirium,40 but a more recent randomized
controlled trial showed no difference in delirium duration in patients receiving intravenous haloperidol prophylaxis
or placebo.41
Numerous studies have examined agents to prevent delirium after cardiac surgery. A single dose of
sublingual risperidone upon regaining consciousness reduced incidence of delirium compared to placebo.42
Administration of dexamethasone upon induction of anesthesia did not reduce the incidence or duration of delirium
after cardiac surgery compared to placebo.43 To test the hypothesis that increased cholinergic activity would
decrease delirium after cardiac surgery (since low cholinergic activity and anticholinergic medications have been
associated with delirium), a randomized controlled trial of rivastigmine vs. placebo was performed but found no
difference in the incidence of postoperative delirium.44
In the ICU, sedative regimens can impact the occurrence of delirium. With regards to choice of sedation,
use of dexmedetomidine has been associated with improved delirium outcomes in randomized controlled trials when
compared to benzodiazepines, propofol, and morphine. 45-48 Bundles involving assessment and control of pain,
awakening and breathing trial coordination, light sedation, minimization of benzodiazepines, delirium monitoring
and management, and early mobility, often referred to as the “ABCDE” bundle, has been advocated to improve
outcomes associated with sedative administration, including delirium. 49 A before-after trial of the implementation of
this bundle found less delirium with a significant independent effect of the bundle on decreasing delirium.50
Statin medications have provided interest with regards to delirium due to their pleiotropic anti-
inflammatory effects. Ongoing statin therapy while in the ICU has been shown in two studies to be associated with
lower overall risk of delirium,51,52 and increasing duration of statin discontinuation in chronic statin users increases
the odds of developing delirium. Interest in the role of sleep disturbances in delirium has led to studies investigating
melatonin as an agent for delirium prevention. A double-blind randomized controlled trial of melatonin vs. placebo
in patients with hip fracture, however, did not demonstrate a difference in incidence of delirium.53
Delirium Treatment
Specific pharmacological agents for delirium are not supported by definitive guidelines or large clinical
trials. In general, pharmacologic treatment should only be considered once non-pharmacologic prevention strategies
have failed and the patient is a risk to self or others. Popular pharmacologic treatments used by clinicians are not
FDA approved for treatment of delirium but include antipsychotic medications (e.g., haloperidol, olanzapine,
quetiapine) and dexmedetomidine. In a pilot study of ICU patients, placebo vs. haloperidol vs. ziprasidone showed
no difference in delirium-free days among all three groups.54 An evaluation of haloperidol vs. olanzapine showed no
difference in length of delirium in ICU patients, although the patients receiving haloperidol did have more
extrapyramidal side effects.55 In a small study of ICU patients with delirium requiring intravenous haloperidol,
patients randomized to scheduled quetiapine in addition to haloperidol had a faster resolution of the first episode of
delirium vs. placebo.56 Based on evidence that impaired cholinergic neurotransmission may lead to the development
of delirium, rivastigmine was studied as an adjunct to haloperidol vs. a combination of placebo and haloperidol. 57
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This study found no decrease in delirium duration, and there was a trend toward increased mortality in the
rivastigmine group.57
A recently published trial randomized patients whose critical illness had otherwise resolved, but for whom
weaning from mechanical ventilation was prevented by hyperactive delirium, to receive dexmedetomidine or
placebo.58 Patients treated with dexmedetomidine had increased ventilator-free hours and had faster resolution of
their delirium symptoms. A recently published non-randomized study examined the effectiveness of
dexmedetomidine as a rescue therapy for non-intubated ICU patients with hyperactive delirium. 59 Patients whose
agitated delirium failed to be controlled with intravenous haloperidol received dexmedetomidine. Patients whose
agitated delirium improved after haloperidol received a haloperidol infusion. Patients receiving dexmedetomidine
had a higher percentage of time at target sedation, less over-sedation , and a shorter ICU length of stay without
increased incidence of hemodynamic side effects.59 Additionally, the overall failure rate for haloperidol in this study
was 43%, demonstrating the limited efficacy of antipsychotic agents in the treatment of delirium in these patients.
Overall, the treatment strategies for delirium are minimal, and the evidence does not support a single pharmacologic
approach to treatment of delirium. More studies are needed on dexmedetomidine as a first-line therapy for the
treatment of delirium.
Conclusions
Delirium is a common problem in the perioperative setting associated with important clinical outcomes. An
understanding of delirium risk factors, precipitating factors, and management is essential for an anesthesiologist in
the perioperative care of patients. Importantly, screening and assessment tools are readily available for delirium
diagnosis by non-psychiatry trained personnel to identify patients with delirium, including hypoactive and
hyperactive subtypes. Prevention of delirium is of utmost importance because the number of evidence-based
pharmacological options for delirium treatment is minimal, and those that exist have significant limitations.
Potential strategies to reduce delirium in the perioperative setting are listed in Table 3.
TABLE 3. PERIOPERATIVE CARE STRATEGIES TO REDUCE DELIRIUM

Avoid or minimize precipitating medications (e.g., benzodiazepines, meperidine, anticholinergics)
Insure adequate pain control through regional techniques and non-opioid adjuncts
Light sedation for monitored anesthetic care when able
Avoidance of oversedation with general anesthesia
Restore hearing aids and eye glasses, prompt removal of catheters and restraints
Attention to hydration and electrolytes
Dexmedetomidine use for postoperative sedation
Consultation services for elderly high-risk patients
Restart home statin therapy
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Deppen SA, Stiles RA, Dittus RS, Bernard GR, Ely EW: Effect of sedation with dexmedetomidine vs lorazepam on
acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA 2007;
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Ely EW, Rocha MG: Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial.
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48. Shehabi Y, Grant P, Wolfenden H, Hammond N, Bass F, Campbell M, Chen J: Prevalence of delirium with
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Sepsis: Current Concepts and Perioperative Management

Mark E. Nunnally, M.D., FCCM New York/New York
Introduction
Sepsis is a high mortality syndrome and substantial health burden. In the U.S., about 250,000 people die of sepsis
annually, killing more people than breast cancer, prostate cancer and AIDS combined (1). It is a comorbidity
complicating many major surgeries, and is often responsible for an “emergency” designation. The increased
morbidity and mortality of emergency status patients can be partially attributed to sepsis physiology.
Sepsis also entails a re-tuning of the body’s metabolic, inflammatory, neurologic and endocrine systems to
coordinate a systemic response in every organ system. A new consensus definition of sepsis defines it as a
dysregulated response to infection.” (2) A maladaptive response causes changes in physiology whose purpose is not
completely understood. Some adaptations, such as a loss of systemic tone, can be detrimental. Conversion to a
more stable but maladaptive chronic critical illness state is more ominous, and is a risk when control of sepsis is
delayed.
In an era of powerful antibiotics and a better understanding of how to use them, the primacy of sepsis should
confuse us as clinicians. Our patients are dying of the same illness (infection) that other patients did 100 years ago.
The details are different, but sepsis still persists and perseveres. In recognition of this intractable problem, basic
science research, translational clinical trials and guidelines production continue at a fast pace.
Mastering the care of sepsis involves understanding several important concepts. Sepsis is a spectrum of disease
requiring aggressive and timely management. Effective management is based on controlling the source of infection
and managing the body’s common responses to severe illness. It entails taking corrective actions before the
patient’s physiology transitions from an acute to a chronic critical illness state. Finally, sepsis is ideal for examining
the way clinical care is delivered and directed at institutional, societal and governmental levels.
The sepsis syndrome: common themes
Sepsis has been defined by a loose set of criteria (3), among which are signs of inflammation linked to infection.
Another system for describing the syndrome is the PIRO model (predisposition, infection, response, and organ
dysfunction) (4). The criteria for defining and characterizing sepsis are nonspecific. For example, urosepsis is
clinically different from sepsis with influenza, even though many factors are common to both.
The traditional definition of sepsis combined the systemic inflammatory response syndrome criteria with a suspected
or known infection (5). Severe sepsis was defined as sepsis plus evidence of organ dysfunction. Septic shock was
sepsis with hypotension unresponsive to fluid loading. These definitions, although helpful in describing the disease
state for research and discussion, lack accuracy (6). The definitions of sepsis have now been changed to reflect a
dysrregulated response to infection, manifest by organ dysfunction measured as a 2 point or greater increase in the
Sequential [sepsis-related] Organ Failure Assessment (SOFA) score (Table) (2). Efforts to distinguish types of
sepsis (e.g., by anatomic site or organism) in ways that impact prognosis and therapies are ongoing.
Table: Broad diagnostic criteria for sepsis (Modified from references 2 and 3):
Infection: documented or suspected
General variables: T > 38.3 or < 36°C, HR > 90/min,  RR, encephalopathy, edema or
positive fluid balance, hyperglycemia
Inflammatory variables: WBC > 12,000 or < 4000/mcL, > 10% immature forms,  C-reactive
protein, procalcitonin
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Hemodynamic variables: SBP < 90, MAP < 70 mmHg or a decrease > 40 mmHg, SvO2 > 70%,
Cardiac Index > 3.5 L/min
Organ dysfunction variables: hypoxemia, oliguria,  creatinine, coagulopathy, ileus,  platelet

count,  bilirubin
Tissue perfusion variables:  lactate,  capillary refill, mottling
[Sepsis-related] SOFA (qSOFA) Respiratory rate ≥22/min, altered mentation, systolic blood pressure
≤100 mmHg
Central to sepsis is inflammation. Systemic responses to infection range from elevated white blood cell counts to
fever, hyperglycemia, and changes in intercellular mediators. Inflammation has been the main focus of sepsis
research for over 40 years. Patients don’t usually die from inflammation, however; they die from organ dysfunction.
Organ dysfunction in sepsis takes many forms and affects every organ system. Renal (e.g., acute kidney injury),
vascular (vasoplegic shock) and respiratory failure (acute lung injury/acute respiratory distress syndrome) are well
recognized sequelae of severe sepsis, but endocrine (hyperglycemia), neurologic (encephalopathy), and
gastrointestinal (ileus) dysfunctions often presage severe sepsis and are signals to intervene before the syndrome
worsens.
The cardiovascular effects of sepsis most directly affect anesthetic management, but clinicians should be aware of
other risks, including electrolyte abnormalities, elevated aspiration risks, gas exchange abnormalities, and increased
sensitivity to anesthetic agents. Cardiovascular changes include a loss of arterial tone (vasoplegia), capillary leak
syndrome, venous pooling of blood, and ventricular dysfunction. Typically, a patient presenting with sepsis and
hypotension will respond favorably to fluid resuscitation, and guidelines commonly recommend volume challenges
on the order of 30 mL/kg crystalloid (7). However, the detrimental effects of tissue edema, especially on
oxygenation, may limit resuscitation. A subset of septic patients demonstrates right heart dysfunction, and
aggressive volume resuscitation in these patients might worsen their shock rather than improve it. For these reasons,
a rational approach to volume resuscitation combines a pragmatic early intervention of volume resuscitation with
boluses of crystalloid with enhanced monitoring to define endpoints of volume administration. Ultimately, many
patients in septic shock will require pressors. Data such as lactate clearance, pulse pressure variation while on
positive pressure ventilation and central or serial mixed venous oxygen saturation measurement can help determine
response to volume and define clinical criteria for vasoconstrictor or dobutamine administration to improve a still
insufficient circulation. The latter is only recommended in situations where impaired contractility is a suspected
contributor to shock. Recommended pressors include norepinephrine (first line), epinephrine (secondary) and
vasopressin (adjunct). In special circumstances (e.g., high suspicion of right ventricular failure), additional
monitoring, such as a pulmonary artery catheter or echocardiogram may be helpful. Finally, in the setting of shock
refractory to even pressors, empiric steroid administration (e.g., hydrocortisone, 50 mg IV every 6 hours) is
indicated. In this circumstance, clinicians may elect to sample plasma for cortisol levels.
Another characteristic of the pathogenesis of sepsis is energy failure. Defects at the level of the mitochondria alter
cells’ ability to generate energy. These failures can predict mortality (8). Patients with ineffective aerobic
respiration tend to be the ones who die. Conversely, the early sepsis response is associated with hypermetabolism.
Mixed venous or central venous oxygen saturation monitoring may help determine patients for whom metabolism
outstrips oxygen supply, with the caveat that energy failure may raise central venous oxygen saturations through
decreased consumption. Historically, evidence supported an “oxygen debt” of early sepsis, corrected with red cells
and inotropes (9). A curve of supply-dependent oxygen consumption suggested many patients required enhanced
oxygen delivery. This finding has not been replicated, and many now believe it to be an artifact of invasive
hemodynamic measurements. Repeat studies using calorimetry do not replicate the supply dependency (10).
Histologically, a characteristic of the septic response is apoptosis, or programmed cell death. Most commonly, this
is expressed in populations of lymphocytes (11). Why immune cells would selectively die off in the throes of
systemic infection is a mystery. Immune dysfunction is a classic finding in sepsis, and many septic patients suffer
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secondary infections. Organisms like vancomycin-resistant enterococcus species, acinetobacter baumannii, and
cytomegalovirus (12, 13) afflict septic patients more than healthy ones, likely because of immune dysfunction. This
combined with coagulation abnormalities (inflammation and coagulation are linked) and elevated risk of
thromboembolic disease, mean that septic patients are at heightened risk of complications.
Over time, and with worsening injury, patient physiology changes. Endocrine exhaustion manifests by a loss of
hormonal pulsatility and decreased levels of secretagogues and end hormones. Vital signs and physiologic rhythms
stabilize (an unhealthy response), the results of defective autonomic signaling. Delirium may transition to functional
cognitive deficits. Survivors of this syndrome have poor functional outcomes, but many do not survive.
Why do patients become septic?
Infection drives the septic response, yet many systemic changes during the sepsis syndrome are common to
noninfectious causes of inflammatory responses. Components of SIRS are conserved across animal species, and in
multiple animal models these components protect an organism from ongoing damage and allow it to heal. A
complicated network of signals and activities that correct derangements and repair damage results in an overlap of
inflammation, coagulation, metabolism, immunologic function, neurologic function, and tissue growth systems. The
syndrome is fundamentally adaptive. In a case of sepsis, these responses are appropriate, but are dysregulated, and
may be detrimental. Historically, many patients would not survive the initial insults of the sepsis syndrome. With
intensive care, patients survive these previously fatal insults, but survive to suffer the natural history of prolonged
sepsis physiology. Modern critically ill patients are unique and their illness has progressed to physiology that would
never be seen in “the wild.” In later phases (i.e., chronic critical illness) dysfunction becomes prominent. It is in
these later phases when many patients die.
Sepsis management: key interventions
The Surviving Sepsis Campaign, first launched in 2002, details the evidence in support of sepsis therapy, translating
the large body of sepsis literature into guidelines (7). Timely diagnosis, antibiotic therapy and goal-directed fluid
resuscitation are key components of sepsis management. Several of the suggestions and recommendations directly
influence management in the operating room. The anesthesia care team contributes to care by managing shock
resuscitation. This is facilitated with physiologic goals such as mixed-venous oxygen saturation and lactate
clearance. They confirm diagnoses by drawing blood, urine and sputum cultures. Finally, by facilitating the timely
administration of antibiotics (ideally after cultures are drawn, but as quickly as possible), the team can have a
positive impact on patient mortality. Anesthesiology-based expertise in monitoring and procedures can facilitate
timely and effective care. Central venous and arterial access helps with resuscitation and management. Support of
failing organs is ideally suited to anesthesiologists and should be viewed as akin to management in the intensive care
unit. With surgical sepsis, the locale of the intervention (intensive care unit versus operating room) should make no
difference in the goals of resuscitation and antibiotic therapy. Facilitating source control through timely surgical
intervention, however, can make a major difference in outcomes.
What sort of a difference can these interventions have? Absolute mortality from sepsis decreased more than 6% as
compliance with Surviving Sepsis Campaign recommendation bundles increased (14). Curiously, compliance in this
study increased from 18.4 to 36.1%, suggesting that the recommendations are neither easily nor frequently adopted.
Both evidence and rationale support timely intervention. Anesthesiologists can and should strive to facilitate
cultures, antibiotics and resuscitation for septic and suspected septic patients in their care.
An evolving understanding
Any improvements have to be viewed in light of limited progress and continuing mortality. What has been
accomplished in sepsis research in the last 40 years? Goal-directed resuscitation and antibiotics reduce morbidity
and mortality. Indirect evidence suggests that exposure to a septic source over time increases the collateral
physiologic damage and overall organ dysfunction burden. However, the “goals” of resuscitation and timing of
antibiotic therapy remain controversial. Adequate resuscitation underlies early sepsis care, but clinicians have crude
and uncertain tools to guarantee that resuscitation is adequate. A fixed goal such as a mixed venous saturation
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greater than 60% may not be as important as attention to other clinical signs in an unstable patient. Recent, well-
designed randomized-controlled trials (15, 16, 17) suggest that goal-directed resuscitation algorithms may not be as
critical to sepsis care as previously thought. Aggressive early antibiotic administration can lead to improper use of
antibiotics when a diagnosis of sepsis is unclear, as during an exacerbation of congestive heart failure.
Previous investigations document multiple failed therapies. Many of the studies were of inflammatory mediators
because of the theory that the inflammatory response to infection leads to organ dysfunction in sepsis. A long list of
failed therapies, including anti-TNF alpha, ibuprofen, anti-IL-2, branch-chain amino acids and, most famously,
drotrecogin alfa (activated protein C), suggests that not only is a single magic bullet for sepsis unlikely, but that the
model for therapeutic intervention may be wrong. Although inflammation is a key component of sepsis syndromes,
immune suppression, altered endocrine activity and decreased autonomic signaling appear to influence disease
progression. Since the septic patient who dies does so in a state of chronic critical illness with multiorgan failure, a
new model of disease and therapy is necessary. Sepsis patients manifest neuroendocrine exhaustion, immune
dysfunction and energy failure. These findings may provide an opportunity for intervention. In the future, therapies
targeting the central nervous system, hormones, or inflammatory cell apoptosis may improve outcomes more than
therapies targeting inflammation.
An administrative issue
Given the substantial impact that sepsis has on morbidity and mortality, the case has been made for aggressive
management and research investment. The successes of the Surviving Sepsis Campaign argue that recommendation
bundles directed at evidence-based and standardized care make a substantial difference. There is, however, a caveat.
The failures in sepsis management, best documented by the long list of failed anti-inflammatory therapies, suggest
that simple, single solutions will not be enough to change the course of disease for many patients. Controversy
continues around resuscitation and antibiotic therapy. Many adjunctive therapies, such as glucocorticoids, tight
glycemic control and pulmonary artery catheter-directed resuscitation have not fulfilled the promise they had 10
years ago. Are we too easily tempted to throw ineffective therapies at a largely insoluble problem? Clinicians may
be willing to embrace an uncertain therapy just to be able to do something. They want to be optimistic.
At an administrative level, problems like sepsis are an opportunity for regulation, standardization and general
control. Pundits argue eloquently that care variability is the problem and that standardization lets more patients get
better care. Guidelines that are useful tools to help clinicians manage complex problems also restrict their ability to
respond uniquely to unique circumstances. The more recent studies of protocol-driven sepsis care cast doubt on the
effectiveness of this approach (15, 16, 17). In the case of sepsis, standardized care can improve outcomes, but should
not be taken for granted. The failures in sepsis tell a story about a quest for an easy solution that sometimes misses
the important elements altogether. Re-thinking the problem might reveal elusive opportunities.
Conclusions
Sepsis is a syndrome with multiple etiologies and manifestations. Although commonly characterized for its
inflammatory characteristics, effects of sepsis are broad reaching, involving immune, neurologic, endocrine and
metabolic changes. Moreover, sepsis is a critical moment in a patient’s overall hospital trajectory. Unchecked
sepsis, inadequate source control and severe secondary injuries put a patient at risk for transition to a chronic critical
illness state and a worsening of morbidity and mortality. As anesthesia providers, we must be prepared to deliver
the best care to patients with sepsis, participate in the discussions about its causes and treatments, investigate new
ideas, and generate and promote measures that can improve outcomes. Our unique skills in critical care and
resuscitation make us ideally suited to these tasks. At the same time, we understand as well as any physician the
complex nature of medical therapies, the assets and liabilities of guidelines, and the need to think critically about
them during care and consultation. We can continue to care for septic patients with fluids, vasopressors, inotropes,
cultures, advanced monitoring and antibiotic therapy while supporting organ function. But as clinical experts in
neurosciences, anesthesiologists have an opportunity to investigate new means of treating sepsis. Finally, as experts
in safety and guidelines management, anesthesiologists should offer valuable expertise to future guidelines efforts.
References:
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1. NIH Sepsis Fact Sheet. Available from: http://www.nigms.nih.gov/Publications/factsheet_sepsis.htm. Accessed

April 9, 2014
2. Singer M, Deutschman CS, Seymour CS, et al. The Third International Consensus Definitions for Sepsis and
Septic Shock (Sepsis-3). JAMA 2016;315(8):801-10
3. Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definition
Conference. Crit Care Med 2003;31(4):1250-6
4. Rubulotta F, Marshall JC, Ramsay G, et al. Predisposition, insult/infection, response, and organ dysfunction: A
new model for staging severe sepsis. Crit Care Med 2009; 37(4):1329-35
5. Bone RC, Balk RA, Carra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of
innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of
Chest Physicians/Society of Critical Care Medicine. Chest 1992;101(6):1644-55
6. Kaukonen KM, Bailey M, Pilcher D, et al. Systemic inflammatory response syndrome criteria in defining severe
sepsis. N Engl J Med 2015;372(17):1629-38
7. Dellinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis Campaign: international guidelines for management
of severe sepsis and septic shock, 2012. Crit Care Med 2013; 41(2):580-637
8. Langley RJ, Tsalik EL, van Velkinburgh JC, et al. An integrated clinic-metabolomic model improves prediction
of death in sepsis. Sci Transl Med 2013; 5(195):195ra95. Doi: 10.1126/scitranslmed.3005893
9. Shoemaker WC, Appel PL, Kram HB. Role of oxygen debt in the development of organ failure sepsis, and death
in high-risk surgical patients. Chest 1992;102(1):208-15
10. Wood LDH, Hall JB. A mechanistic approach to providing adequate oxygenation in acute hypoxemic respiratory
failure. Respiratory Care 1993;38(7):784-99
11. Hotchkiss RS, Tisley KW, Swanson PE, et al. Sepsis-induced apoptosis causes progressive profound depletion
of B and CD4+T lymphocytes in humans. J Immunol 2001;166(11):6952-63
12. Limaye AP, Kirby KA, Rubenfeld GD, et al. Cytomegalovirus reactivation in critically ill immunocompetent
patients. JAMA 2008;300(4):413-22
13. Luyt CE, Combes A, Deback C, et al. Herpes simplex virus lung infection in patients undergoing prolonged
mechanical ventilation. Am J Respir Crit Care Med 2007;175(9):935-42
14. Levy MM, Dellinger RP, Townsend SR, et al. The Surviving Sepsis Campaign: results of an international
guideline-based performance improvement program targeting severe sepsis. Crit Care Med 2010;38(2):367-74
15. ARISE Investigators. Goal-directed resuscitation for patients with early septic shock. N Engl J Med
2014;371(16):1496-506
16. ProCESS Investigators. A randomized trial of protocol-based care for early septic shock. N Engl J Med
2014;370(18):1683-93
17. ProMISE Trial Investigators. Trial of eary, goal-directed resuscitation for septic shock. N Engl J Med
2015;372(14):1301-11
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Update on Cardiac Anesthesia
Martin J. London, M.D. San Francisco/CA
Cardiac Anesthesia: What is it, Who is it for, and Who provides it?
The classical definition of cardiac anesthesia and who provides it has changed dramatically over the past 25 years
when nearly all major cardiac interventions were performed exclusively in the operating room by a cardiac surgeon
via sternotomy on bypass (usually with moderate to deep degrees of hypothermia) monitored with a pulmonary
artery catheter with occasional use of TEE depending on the particular center. With the intervening development of
“fast tracking”, OPCAB, minimally invasive access approaches, and most recently TAVI and mitral clip procedures,
advances in cardiac protection strategies, 3D TEE, introduction of new anesthetic agents, increasing standardization
of practice by guidelines, performance measures and patient safety initiatives, how we anesthetize such patients,
where and with what monitors has changed radically. The cardiac anesthesiologist of today has to be nimble,
adaptable, and knowledgeable in a wider range of surgical interventions than ever before. Unfortunately, we also
have to realize that with newer “minimalist” approaches to a wider range of non-surgical cardiac interventions, less
specialized anesthesia providers or even ancillary nursing personnel are likely to be more cost effective. That being
said, most contemporary fellowship trained cardiac anesthesiologists are finding that they are keeping quite busy
and that increasing sophistication of medical/surgical interventions is opening up new economic and clinical
opportunities (and requiring concerted efforts at continuing education). This lecture will focus on selected
management issues for “bread and butter” adult cardiac surgical interventions likely to be seen at the (larger)
community hospital level driven in large part by our rapidly aging population, focusing on some the latest influential
publications including those in high impact multispecialty journals. Procedures encountered by most adult cardiac
anesthesiologists include CABG (on or off pump), SAVR or SMVR (“s” for surgical), TAVI/TAVR/TVT
procedures (via transfemoral, tranaortic, transapical or even transcaval approaches), mitral valve repair (open or
robotic), and most recently, mitral clips. Time limitations preclude covering all of these but common themes related
to anesthetic management will be emphasized.
Are there guidelines for how it should be performed?
Although there are a variety of evidence based guidelines for surgeons and cardiologists dealing a variety of cardiac
surgical procedures (primarily by the AHA/ACC1-3, STS or ESC with or without involvement of the SCA or ASA),
there is less standardization for how best to manage patients perioperatively. This is to be expected given the “art”
factor in clinical practice, uncontrolled introduction of new technology, and the general perception by referring
physicians that “process measures” are less likely to impact on long-term outcome than the actual surgical
intervention. With rare exception, there are few well documented Grade I, level of evidence A perioperative
processes that are well agreed upon and have stood the test of the time. That being said, a variety of process
measures have been evaluated in AHA/ACC and STS guidelines, some European countries have attempted to codify
perioperative management4 and subspecialty groups (SCA, EACTA) are attempting to develop more evidence based
recommendations either through ongoing literature review5 or registry type data collection6 of process variables
(STS-SCA database). However, guideline development methodology continues to evolve becoming more complex
and costly to develop and maintain. Thus, clinicians should remain appropriately vigilant about blanket
recommendations.
What is new in perioperative medication management of patients undergoing cardiac surgery?
Evaluation of the benefits and risks of preoperative continuation of existing medication or institution of new
potentially beneficial medications to naïve patients in this high risk setting has been an expanding focus of research
given the availability of forms of “big data” as well as the development of robust clinical trials networks (primarily
outside of the U.S.). There is an interesting degree of tension between major organizations such as AHA/ACC and
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periop based organizations given the desire of the former organizations to ensure that their patients either continue
or start “goal directed medical therapy” (GDMT) with agents such as statins, antiplatelet agents, ACE/ARB’s, and
beta blockers when some of these agents may have relative contraindications in the perioperative period. 1 7 In
contrast, some agents may potentially be of greater value in the perioperative period (eg. beta blockers for AF
prophylaxis) than they are in the longterm (for patients without prior MI or CHF). Fairly convincing observational
data have been recently published suggesting that the preoperative administration of beta blockers is not associated
with any benefit over early postoperative administration. 8,9 In fact, the impetus for these studies was economic push
back regarding the STS/NQF bundling of preoperative administration of beta blockers in a composite performance
measure which at least one influential practice group felt was unreasonable and penalized them financially.
However, the more recent analysis from this group demonstrated a substantial increase in the percent of patients
admitted on beta blockers and thus this is less of an issue than before.
The impact of periop statin use has been examined in 2 high profile RCT’s (NEJM & JAMA) this year and are
welcomed given purported benefits of statins in reducing postop atrial fibrillation, myocardial injury and acute
kidney from multiple observational analyses and small RCT’s. 10 The larger study (NEJM) evaluated as primary
outcomes AF & MI (with AKI as a secondary). 11 1922 patients undergoing primarily CABG (on/off pump roughly
equal) at a single center in China were randomized to rosuvastatin 20 mg qd (roughly two thirds were statin naïve
while one third were withdrawn) within 8 days of surgery and therapy was continued for 5 days postop. No
differences in the rates of AF (approx. 20%) were noted nor in the release of troponin I. Of a variety of secondary
outcomes no differences were noted with the exception of an increase in AKI (primarily stage 1) in the statin group.
The smaller JAMA RCT (from Vanderbilt University) 12, focused exclusively on the potential impact of high dose
statin rx (atorvastatin 80 mg) on AKI (0.3 mg/dl increase creatinine within 48 hrs), enrolling 615 patients (with
approximately 1/3rd statin naïve) undergoing valve or CABG surgery. No difference in the primary outcome was
noted in either group (approx. 20% in either naïve or continuing). Although these studies are not likely to have a
substantial impact on clinical practice given the increasing use of statins for primary and secondary prevention, they
do point to the hazards of relying on conclusions of observational analyses or small underpowered studies with large
effect sizes purporting amazing benefits of a particular class of drugs perioperatively.
Although it has been recognized that perioperative aspirin is of value in not only reducing postoperative graft
occlusion but also in reducing myocardial and possibly other organ damage, its antiplatelet actions have been well
appreciated to potentially increase bleeding if administered preoperatively. Despite guidelines for its postop use,
there has been little consensus on whether it should be administered up to and including the day of surgery.
Publication of the POISE-2 study 13, demonstrating increased bleeding without benefit in noncardiac surgery (in a
relatively low risk cohort), added further impetus to clarify this issue. Myles et. al. 14 recently reported aspirin results
of the placebo controlled ATACAS trial, evaluating use of either preoperative aspirin (100 mg po within 1 – 2 hrs
preop in patients in whom it was otherwise stopped 5 days prior to surgery) and/or tranexamic acid in 2100 patients
(1047 aspirin vs. 1053 placebo) undergoing primarily CABG surgery (all procedures on pump) considered “at
increased risk for major complications” on a primary composite outcome of death and thrombotic complications
within 30 days of surgery. The outcome occurred in approximately 20% of patients in either group and from a safety
perspective, there were no differences in the rates of surgical take-back (approximately 2%) or cardiac tamponade.
Based on these findings, the authors updated a recently published meta-analysis 15 now reporting a significant
reduction in periop MI with aspirin administration the day of surgery (O.R. 0.79 p = 0.04) with no increase in
bleeding, transfusion, or all cause mortality.
What monitors should be used?
How aggressively one monitors patients in this setting is influenced by a variety of factors including institutional
and surgical preferences that are not always evidence based, cost considerations (particularly in private settings),
cyclical changes in popularity of monitors based on recent publication in periop journals (as with PAC),
advancement of technology (as with 3D TEE and cerebral oximetry), etc. Clinical surveys in different countries
document wide variation in such practices. 16 Anyone living outside of a cave for the past 25 years has been privy to
the “great PAC debate” and most sides have long drawn their lines in the sand regarding use or non-use. Yet the
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PAC remains quite popular and in a recent unpublished analysis of the SCA-STS database (with approximately
10,000 patients as of May 2016) it was used in 68.5% of patients. In some systems it is used routinely (albeit
hopefully with common sense clinical judgment to avoid use in very low risk procedures) while in others it is
shunned like the plague. 1 17 Although most published studies suggest no benefit overall (with decidedly little
evidence of harm), 18 these are nearly impossible to interpret given how care is delivered between different types of
health care systems and the myriad of processes involved in determining patient outcome.
TEE use continues to increase in routine practice given the predominance of fellowship trained certified
anesthesiologists and younger surgeons who in contrast to the older guard welcome the information obtained that
increasingly influences various parts of the actual surgical procedure. The introduction and growing maturation of
3D TEE has provided additional impetus to use of TEE, although its value outside of mitral valve repair is unclear.
19,20
It does however hold great promise to quantitate many of the qualitative aspects of hemodynamic management
routinely assessed by 2D TEE (ventricular function and cardiac output), but most hard core users will admit that
inadequate resolution and software limitations of the current platforms remain substantial. 21,22 Other advances in
image processing and software such as tissue Doppler and speckle tracking assessment of myocardial strain hold
promise clinically, but convincing evidence of their value in the periop setting (especially given potential effects of
positive pressure ventilation and anesthesia) is in its infancy and even basic knowledge regarding effects of loading
conditions on these parameters complicate their interpretation. 23-25
In contrast to skepticism regarding the clinical value of processed EEG technologies to influence outcome (although
the heart room is one of its major remaining strongholds), cerebral oximetry has found a more welcome and
surprisingly rapid reception among a wide variety of stakeholders (perfusionists and surgeons) despite a distinct lack
of high quality evidence and substantial expense. It was rapidly adopted by the STS into their data collection.
However, most clinicians do not fully appreciate precisely what is being measuring (and the fundamental differences
between saturation and actual levels of perfusion) and differences between vendors. Despite an early single center
study suggesting strong efficacy, 26 literature evidence supporting claims of enhanced outcome is scant as
documented in a recent meta-analysis. 27 Recently, independent consortiums of Canadian and U.S. centers (8 in
each) have published “feasibility” studies evaluating whether following adoption of a standardized treatment
algorithm, adequate number of patients could be enrolled and processed to test control versus intervention arms. 28,29
Both studies report enrolling similar numbers of patients (201 – 235) and that their respective algorithms were
successful in reversing most of the observed desaturations. The studies were both underpowered to test outcome
(particularly but not exclusively cerebral) but both imply that they will proceed with larger scale definitive studies.
What is new and useful in perioperative cardioprotection? Does my anesthetic choice really matter?
Ever since the seminal studies in the late 1990’s demonstrating laboratory evidence of volatile anesthetic
preconditioning, 30 followed by a wave of small single center studies suggesting both biochemical and clinical
advantages over propofol-opioid TIVA techniques, 31 most clinicians have generously incorporated them into their
clinical routine (albeit driven primarily by the concurrent trend for early extubation). However, cracks have steadily
appeared in the wall with a later wave of neutral studies (in both cardiac and noncardiac surgery) including a
multicenter study organized the by most prolific clinical researcher in this arena32, to the point where in the current
noncardiac surgery AHA/ACC guidelines, 33 the prior recommendation for their preferential use has been nullified
(a less detailed analysis presented in the most recent AHA/ACC CABG guidelines suggested possible benefits with
a IIa recommendation, noting many inconsistencies in the literature) 1. Yet biochemical evidence for pharmacologic
cardioprotection remains strong, and animal studies continue to refine the mechanisms involved. Although the
prevailing opinion as to why clinical superiority with volatiles has not been demonstrated in cardiac surgery is that
advances in surgical cardioprotection (eg. cardioplegia type, timing and route along with other factors) likely
overshadow any advantages of a particular anesthetic agent, the topic remains “volatile” and contentious. As well,
the influence of factors demonstrated to interfere with preconditioning in the laboratory (including beta-blockade,
propofol and advanced age), remain murky from the clinical perspective. Critical studies will be reviewed along
with evolving mechanisms.
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An area that has gotten considerably more attention in the prior year is that of remote ischemic preconditioning
(RIPC) 34. This simple to perform, low budget procedure (all you need is a BP cuff) has been the subject of a
number of mostly positive, but small-scale clinical trials purporting not only cardio (primarily by reduction in
troponin levels), but also renal and other organ protection. Three recent larger multicenter publications in high
impact journals (JAMA & NEJM) have shaken up this community. The most influential (and contentious) are two
published simultaneously in the NEJM on cardioprotection (ERICCA and RIPHeart).
Hausenloy et. al. 35 (who previously published salutary data in the Lancet in 2007) (ERRICA) compared RIPC with
sham in 1612 patients undergoing on-pump CABG (with 50% undergoing concurrent valve surgery, EURO score >
5) at 30 UK centers. They were unable to demonstrate any improvement in the primary outcome of MACE at 12
mos. Neither were there any differences in a variety of secondary outcomes including periop myocardial injury.
Meybohm et. al. 36 (RIPHeart) reported on 1385 lower risk patients at 14 German centers (72% CABG with/without
valve on pump), reporting no differences between groups in a composite clinical outcome by the time of hospital
discharge. Anesthesia was not controlled in the former, but was in the latter. Propofol, a suspected inhibitor of
RIPC37 (and a potential preconditioning agent in its absence) was used in 90% of ERICCA (roughly 50% TIVA) and
100% of RIPHeart (which enforced a TIVA protocol).
In an accompanying editorial, 38 Michael Zaugg, a leading expert in anesthetic cardioprotection39 who previously
conducted a small (N = 55) but detailed RCT of RIPC (eg. multiple biomarkers with detailed gene expression
analyses) 40 in which no difference in the primary outcome of troponin release was noted, but a composite outcome
of arrhythmia and MI was higher in the RIPC group, emphasized the potentially dangerous effects of RIPC
(including a trend towards higher cardiovascular mortality in the ERRICA study), perhaps mediated by induction of
plaque instability with RIPC which has been shown to activate proinflammatory pathways as well. Readers are
referred to a particularly contentious online discussion forum for the NEJM in which Haunseloy and Zaugg battle
over the safety of RIPC and a more recent analysis of the future of RIPC based on these studies. 41
Zarbock et. al. 42 studied 240 patients at 4 German centers evaluating effects on acute kidney injury at 72 hrs. along
with a variety of secondary outcomes (including use of renal replacement therapy). A unique feature of this study
was collection of a number of biomarkers and avoidance of use of propofol, an agent which has implicated in
interfering with RIPC (although the mechanism and dose required remain controversial) and which was not
proscribed in the NEJM trial (although the number of patients in each group was equal). The patients studied were at
quite elevated renal risk (using a score developed at the Cleveland Clinic) and underwent CABG, Valve only or
combined procedures. They reported an absolute risk reduction of 15% in dx of AKI along with a 10% absolute
reduction in need for RRT and a slightly shorter ICU stay (no other differences in key secondary outcomes). Of the
biomarkers, early release of urinary insulin-like growth factor-binding protein 7 and tissue inhibitor of
metalloproteinases 2, components of a complex mechanism of G1 cell cycle arrest implicated in cytoprotection for
tubular epithelial cells, were significantly attenuated after surgery. Unfortunately for clinicians, as of yet, no one has
compared the results of this with the ERRICA or RIPHeart studies which present somewhat opposing results (heart
versus kidney).
There has been increasing interest in the potential cardioprotective effects of metformin in non-diabetic patients,
which has been shown to activate several prosurvival protein kinase pathways and increase intracellular adenosine in
animal models and enhance cardiovascular outcomes in type II diabetics relative to other agents. A carefully
performed small single center RCT (Netherlands) evaluating changes in perioperative troponin I along with ex-vivo
measures of contractile function and protein kinases (via right atrial tissue) in non-diabetic patients undergoing on-
pump CABG, reported no significant differences in either primary or secondary outcomes. 43 However, this small
study reported no mortality at 30 days and troponin levels were significantly lower than projected based on earlier
pilot data. Data such as this seem to support the growing opinion that attempts at additional cardioprotection in this
setting are likely to yield little benefit over todays surgical outcomes.
Is there any role for steroids in this setting?

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Pharmacologic manipulation of inflammatory response to cardiac surgery (particularly initiation of CPB), has been a
topic of great interest for several decades based on laboratory and clinical work done primarily by cardiac surgeons.
44
The adverse effects of certain cytokines on a variety of organ systems has driven this quest. 45,46 Although a
variety of potential inhibitors have been investigated, corticosteroids have been a primary focus given their
availability and low cost. In the more recent past, particularly with the advent of fast tracking, cardiac
anesthesiologists have spearheaded this line of investigation employing proper EBM approaches. Recognition that
steroids may have analgesic properties has provided additional impetus. 47 Two major large-scale trials have been
reported in high profile journals (Lancet SIRS & JAMA DECS). The DECS study48 was the first mega-study in this
arena, randomizing 4494 patients at 8 centers in the Netherlands to receive dexamethasone 1 mg/kg after induction
of anesthesia prior to CPB. The primary composite outcome of death, MI, CVA, renal or resp failure by 30 days was
no different between groups. Secondary outcomes including less postop infection (primary pulmonary), shorter
duration of ventilation, and lengths of stay were improved in the treated group although glucose levels as expected
were higher. The SIRS study, 49 ostensibly organized based on their interpretation that the DECS study showed a
beneficial effect on higher risk patients (which is not apparent in the DECS manuscript!), randomized 7507 “high
risk” patients (defined as Euroscore > 6) at 80 hospitals in 18 countries, evaluating the use of methylprednisolone
(250 mg at induction and 250 mg with CPB) with the same primary outcome as DECS. Once again, no difference
was noted. However, they report an increase in myocardial injury (defined by CK-MB using a complex formula) in
treated patients. Notably, the study hadIn a very high percentage of valve procedures (just over 70%) and thus
standards for such an outcome are vague. No notable effects on secondary outcome (aside from less mediastinal
drainage) were noted. Also, neither study measured inflammatory mediator levels, thus dosing issues could have
confounded results.
Several sub-studies have recently been published from DECS & SIRS. In 291 DECS patients, there were no
differences in the incidence of postoperative cognitive decline at 1 month. 50 In 1,125 DECS patients, there was no
difference in the incidence of posttraumatic stress disorder (9.3 vs. 12.3%) or depression (11.7 vs. 13.8%) at 1.5 yrs.
51
In 1,110 SIRS study patients the incidence of pain at 30 days or persistent incisional pain at 6 mos (15.7 vs.
17.8%) was not different. 52 Although DECS & SIRS are ostensibly neutral to negative trials, questions remain.
Although future large-scale trials of steroids are unlikely, we have not likely seen the end of interest in them.
A fertile line of research is the use of hemoabsorbtion on the CPB circuit to remove cytokines as they are released as
opposed to prophylactic or blocking drug strategies. At this stage, clinical data are quite limited although at least one
detailed clinical trial is ongoing.
Should Dexmedetomidine be used routinely in cardiac surgery?
There has been substantial interest in clinical applications of dexmedetomidine since the early-1990’s, however, few
large-scale, non-industry sponsored trials have been conducted to guide clinicians with regards to specific use in
cardiac surgery. A detailed (measuring catechols and dexmed plasma levels) but small (n=80), placebo controlled
RCT of intraop dexmed supplementation to a fentanyl-enflurane-pancuronium anesthetic for CABG (1992-3 time
frame), reported major reductions in sympathetic tone with an analgesic sparing effect, less tachycardia, a higher
incidence of hypotension, increased fluid requirements and less shivering in the treated group. 53 Interest in the drug
increased substantially with initial reports of lower rates of delirium post-surgery (and in medical patients in the
ICU) and use has further increased as the drug came off patent recently. Notably, much research has recently
appeared from non-U.S, non U.K. centers (particularly China) some of which purport preconditioning, 54 anti-
inflammatory55 and analgesic properties56 in animal and human models. A controversial observational analysis was
published in Circulation in 201357 reporting on 1134 patients undergoing cardiac surgery of which approximately
half received low dose dexmed for postop sedation (only in the range of 0.24 – 0.6 mcg/kg/hr) while weaning and
half received “routine care” of benzodiazepine-propofol infusions. A wide variety of outcomes were tracked
perioperative including mortality up to 1 year. Amazingly, despite no difference in major periop complications,
mortality was dramatically lower in-hospital, at 30 days and 1 year (with extensive statistical adjustment). It is not
clear from what institution this cohort was studied at (it mentions 2 centers, one in China the other, UC Davis but
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only one center was studied) and the fact that protocol-based care excluded anyone from receiving dexmed for more
than 24 hrs (per initial FDA guidelines) would strongly bias towards lower risk patients (despite their purported risk
adjustment) making this analysis suspect and likely to follow the growing trend of high effect size observational data
that are later disproven. 58 Nonetheless, the results are intriguing.
More recently, this group has more recently published a meta-analysis in PLOS One evaluating 14 RCT’s (or what
they term quasi-RCT’s) of 1702 patients. 59 They report significant risk reductions for ventricular tachycardia and
postoperative delirium and an increase in bradycardia but not hypotension. No differences in atrial fibrillation or
duration of intubation were noted (except for a subgroup of CABG patients in which it was reduced) were observed.
This analysis did not address any other outcomes (given the lack of literature and small sample sizes). The effect
size reduction for ventricular tachycardia was driven primarily by 24 hour Holter monitoring in one study. For
delirium, the largest effect was obtained from a controversial, open label, industry sponsored study (with heavy
promotion of its abstract results and claims it was to be published in the NEJM but ended several years later in a
very low impact journal) of 118 patients undergoing valve surgery at Stanford randomized to either dexmed,
propofol or midazolam at sternal closure. 60 Of the 90 patients completing the protocol, an absolute risk reduction of
47% was noted in the dexmed group relative to the others. Data on safety were not presented. A large study from
Australia (306 pts undergoing CABG and or valves) compared in a double blind manner dexmed to morphine/open
label propofol started within 1 hour postop. 61 Although no difference in the incidence of delirium was noted, there
was a significant reduction in its duration. Most recently, a single blind trial from Canada62 of 183 patients over the
age of 60, comparing dexmed versus propofol (started on arrival in the ICU) reported reduced incidence (17.5% vs.
31.5%), delayed onset (median onset postop day 2 vs postop day 1) and shorter duration (2 vs. 3 days) with dexmed.
No differences were noted in other outcomes (including inotrope/vasoconstrictor use) although hemodynamic data
were not presented. Although each of these studies have limitations, they do seem to have consistent results
regarding a protective effect which is also supported by much of the most recent ICU literature. As well, many
clinicians are starting dexmed earlier intraop (to avoid a precipitous wake up or for intraop sedation) which hasn’t
been studied. There are clearly patients in whom hypotension or bradycardia do appear more prevalent with dexmed
and they are most likely the older sicker patients, but most clinicians are able to deal with these issues. Dexmed is
not a wonder drug but clearly has some unique properties. Large scale studies will be helpful to attempt to better
delineate its benefits and cost-effectiveness.
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32. De Hert S, et al. A comparison of volatile and non volatile agents for cardioprotection during on-pump coronary
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40. Lucchinetti E, et al. Remote ischemic preconditioning applied during isoflurane inhalation provides no benefit to the
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Lessons Learned From ERICCA and RIPHeart. Circ Res. 2016;118(7):1052-1054.
42. Zarbock A, et al. Effect of remote ischemic preconditioning on kidney injury among high-risk patients undergoing
cardiac surgery: a randomized clinical trial. JAMA. 2015;313(21):2133-2141.
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46. Hall R. Identification of inflammatory mediators and their modulation by strategies for the management of the systemic
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Complications Associated with Interventional Pain Treatment
James P. Rathmell, M.D. Boston, Massachusetts
Overview
Complications arise in the course of any type of medical treatment and the common interventions used to treat acute
and chronic pain are no exception. The best approach to preventing adverse outcomes during the majority of these
treatments is to have detailed knowledge of the anatomy of the adjacent structures that lie near the target site for
each intended treatment and a clear understanding of how the technique has been devised to minimize the risk of
harm to those structures. Needle placement for many pain procedures is now best carried out with the use of image
guidance and the widespread availability of fluoroscopy and ultrasonography has increased both the precision and
the safety of many techniques. When complications do arise, prompt recognition and treatment can often prevent
serious sequelae.
Complications associated with epidural, facet joint, and sacroiliac injection

There are few reports of serious complications associated with epidural, facet joint, and sacroiliac joint injections.
The American Society of Anesthesiologists (ASA) maintains an ongoing surveillance of malpractice claims through
the ASA Closed Claims Study, and a report published in 2004 detailed 114 complications associated with chronic
pain treatment: nerve injury (28); infection (24); death/brain damage (9); headache (20); and increased pain/no relief
(10).1 In more recent report published in 2011, the ASA Closed Claims group found an alarming increase in the
number of claims associated with pain interventions carried out at the level of the cervical spine. 2 Injuries were often
severe and related to direct needle trauma to the spinal cord, most often resulting in permanent disabling spinal cord
injuries. Traumatic spinal cord injury was more common in patients who received sedation or general anesthesia and
in those who were unresponsive during the procedure. Pain medicine claims have increased over time and have
increased in severity.3 In addition, there are significant concerns about the neurotoxic potential of the corticosteroid
preparations.4 Neurotoxicity, neurologic injury, and the pharmacological effects of corticosteroids have all been
reported as complications following epidural, facet joint and sacroiliac corticosteroid injections.
Neurotoxicity
The intrathecal injection of neurotoxic substances can result in inflammation of the meninges with or without direct
neural injury in the form of arachnoiditis or cauda equina syndrome. Arachnoiditis is an inflammatory condition of
the meninges that can extend to the underlying neural structures. Cauda equina syndrome is a descriptive term that
refers to neurologic signs and symptoms that arise from dysfunction of the cauda equina. This is characterized by
bilateral leg pain, saddle hypesthesia, lower extremity weakness, and bowel, bladder, and sexual dysfunction. While
cauda equina syndrome is most often seen in association with compressive lesions (e.g. a large central disc
herniation), similar symptoms can occur with severe arachnoiditis.
Concern regarding the potential for neurotoxicity associated with epidural steroid injections stems from reports of
arachnoiditis that arose during the course of repeated intrathecal injections administered for the treatment of multiple
sclerosis.5,6,7 Only one case of documented arachnoiditis has been reported following epidural steroid injection for
sciatica complicated by a traumatic tap; the symptoms resolved following subsequent discectomy. 8 There is limited
evidence that any of the components of the available corticosteroid preparations are neurotoxic. There was much
controversy around the risk of arachnoiditis following epidural methylprednisolone acetate in Australia during the
1990s. This led some practitioners to use Celestone Chronodose (betamethasone 5.7 mg, as betamethasone sodium
phosphate 3.9 mg (in solution) and betamethasone acetate 3 mg (in suspension) per mL in an aqueous vehicle;
Schering-Plough, Kenilworth, NJ, USA) for epidural injection. This product contains sodium phosphate monobasic,
disodium edetate, benzalkonium chloride, and water. However, study in sheep demonstrated arachnoiditis in
animals receiving 2 mL or more of this preparation intrathecally. 9 More recently, practitioners have moved to the
use of the potent, soluble steroid dexamethasone for epidural use; a recent study in rodents found no evidence of
arachnoiditis or neural injury following intrathecal administration of this agent. 10
It is not clear that intrathecal injection of any of the available corticosteroid preparations will cause harm. However,
it is important to realize that, despite their widespread use for epidural injection, neither the United States Food and
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Drug Administration nor any other regulatory agency labels these steroid preparations for epidural use. Prompted by
increasing reports of harm, in 2014 the FDA issued a Drug Safety Communication describing a label change to warn
of rare but serious neurologic problems after epidural corticosteroid injections for pain.11 The most prudent approach
is to use all means available to avoid intrathecal injection. A local anesthetic test-dose prior to steroid injection can
rule out intrathecal placement. Use of radiographic guidance and injection of radiographic contrast can also be used
to confirm epidural localization of the injectate. In those patients where a dural puncture occurs during needle
placement, it is prudent to consider abandoning the procedure.
Neurologic injury
Direct injury to the spinal nerves or the spinal cord can occur during epidural injection. 2 The most common form of
nerve injury is persistent paresthesia. Injury to the spinal cord can occur when the needle enters the substance of the
spinal cord (Figure 1). Surprisingly, needle penetration in to the cord is not always catastrophic and may even
occur without the patient reporting symptoms. 12 More significant injury occurs if there is bleeding in to the spinal
cord or if injectate is placed in to the substance of the spinal cord.13,14 Neural injury occurred in 14 patients
following epidural steroid injection in the 2004 Closed Claims Study.1 Six resulted in paraplegia, 1 in quadriplegia.
In the 2011 Closed Claims report, of the 64 claims related to cervical procedures, 59% experienced permanent,
disabling spinal cord injuries, with direct needle trauma as the predominant cause (31%). 2
FIGURE 1. T2-weighted magnetic resonance

image of the cervical spine immediately
following cervical interlaminar epidural steroid
injection. Increase signal within the substance
of the cord and new onset of bilateral upper and
lower extremity neurologic deficits suggested
direct injection within the substance of the
spinal cord.
The risk of direct injury to the spinal cord is

greatest when epidural injection is carried out at
the high lumbar, thoracic, or cervical levels,
where the spinal cord lies directly anterior to
the path of the advancing needle. Two cases of
spinal cord injury following cervical epidural
steroid injections conducted with fluoroscopic
guidance were reported.15 The details of use of
fluoroscopy were not given. In both cases, the
patients received sedation. The authors
postulate that these patients failed to report any
symptoms due to the level of sedation. A more recent report details 3 cases of transient neurologic injury that
followed cervical epidural steroid injections in awake patients.16 All 3 patients had large disc herniations that
caused effacement of the epidural fat and spinal fluid surrounding the spinal cord at the level of injection. The
authors hypothesized that direct injury to the spinal cord could occur even without dural puncture when narrowing
or obliteration of the epidural space is present.
Fluoroscopy offers some protection against neural injury. The position of the needle in the AP view can be kept
midline as it is advanced, eliminating the risk of lateral deviation and injury to the nerve roots or the spinal nerve.
The primary means of detecting penetration of the epidural space remains the loss-of-resistance to injection as the
needle is advanced, but a lateral view on fluoroscopy can be used to assure that the needle tip is at the level of the
posterior border of the bony spinal canal. Once the tip of the needle appears to be in good position in both AP and
lateral views, injection of a small volume of radiographic contrast can be used to assure that the injectate is within
the epidural space. Most reports describe the immediate onset of severe pain in one or both lower extremities
reported by awake patients receiving epidural injections who went on to develop spinal cord injuries.13,14,16 Thus,
minimizing sedation is an important measure -- the patient should be alert enough to respond to paresthesias induced
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by needle contact with neural structures. In the majority of cases, there is probably little more than supportive care
that can be offered to those patients who do suffer neural injury in the course of epidural injection.
Pharmacologic effects of corticosteroids

The administration of exogenous corticosteroids can lead to hypercortisolism and suppression of the adrenal cortex’s
normal production of endogenous glucocorticoids. Cushing’s syndrome occurs as the result of excessive
endogenous cortisol production by the adrenal cortex and results in a characteristic pattern of obesity associated with
hypertension. Prolonged administration of exogenous glucocorticoids can result in similar manifestations, and is
termed cushingoid syndrome. The long-acting corticosteroid preparations used for epidural steroid injection slowly
release the active steroid over 1 to 3 weeks. Fluid retention and weight gain, increased blood pressure, and
congestive heart failure have been reported after epidural steroid injections, 17,18 and may be more likely in those with
a history of previous congestive heart failure or chronic diuretic use. Cushingoid side effects have been reported
even after a single epidural administration of corticosteroid. 19
Epidural administration of long-acting corticosteroid preparations leads to prompt, marked, and prolonged
suppression of serum cortisol levels. In 12 patients who received 80 mg of epidural methylprednisolone acetate,
ACTH and plasma cortisol levels were depressed from 1 to 21 days after treatment, and the ability of exogenous
ACTH to raise plasma cortisol levels was reduced over the same interval. 20 Three epidural injections of 80 mg of
triamcinolone acetate given at weekly intervals also reduced ACTH and serum cortisol levels starting within 45
minutes of the first injection; levels were nearly normal 30 days following the last injection. 21 There is no specific
treatment for the adrenal suppression that follows epidural injection of corticosteroid, however, it seems prudent to
consider coverage with an additional dose of exogenous steroid in those undergoing major surgery in the weeks
following epidural steroid injection.
Glucocorticoid administration reduces the effect of insulin and results in increased blood glucose levels and insulin
requirements in diabetics for 48 to 72 hours. A single caudal epidural injection of triamcinolone acetonide resulted
in an increase in serum insulin levels and a suppression of serum glucose response to insulin within 24 hours and
returning to normal after 1 week.22 Glucose levels in diabetic patients should be monitored closely during the week
following any type of long-acting steroid. Patients need to be informed that adjustment of insulin dose may be
required.
Bleeding complications
Similar to single-shot epidural placement for surgical anesthesia, epidural injection for pain treatment carries the risk
of intraspinal bleeding. Significant bleeding within the epidural space can cause compression of neural elements
potentially resulting in paraplegia or quadriplegia. Both epidural23 and subdural24 hematomas have been reported
following epidural steroid injections in patients without any apparent coagulopathy. A case of quadriplegia
following cervical epidural steroid injection in a patient receiving clopidogrel and diclofenac has also been reported;
this patient regained upper extremity function after surgical decompression. 25 In the Closed Claims Study,1 two
epidural hematomas occurred following epidural steroid injections; both patients had been receiving anticoagulants.
The risks and considerations regarding neuraxial blockade in patients receiving anticoagulation are similar in those
receiving the injections for treatment of pain to those who are receiving epidural anesthesia or perioperative epidural
analgesia;26 recently, recommendations regarding anticoagulants that are specific to interventional pain treatment
have been published.27 Epidural injection of steroids should be avoided in patients receiving systemic
anticoagulants (e.g. coumadin or heparin) or potent antiplatelet agents (e.g. clopidogrel or ticlopidine). However,
non-steroid anti-inflammatory drugs (NSAIDS), including aspirin, do not appear to increase the risk of epidural
hematoma formation associated with epidural injection.
Infectious complications
Injection therapy for pain treatment carries a small risk of both superficial and deep infection, including neuraxial
infection such as epidural abscess.28 Both superficial and deep infections have been reported after injection therapies
for pain including: epidural steroid injections, 29,30,31 facet injections,32 and trigger point injections.33 The most
worrisome and potentially devastating infectious complication is epidural abscess. Abscess formation within the
epidural space can occur without injection or instrumentation of the spinal canal. In a series of 46 cases of
spontaneous epidural abscess 46% occurred in diabetic patients. 34 Common presenting symptoms included paralysis
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(80%), localized spinal pain (89%), radicular pain (57%), and chills and fever (67%). The erythrocyte sedimentation
rate (ESR) was always elevated. Staphylococcus aureus was the most common organism isolated. A recent review
detailed 14 cases of epidural abscess following epidural steroid injection that have been reported in the literature.( 35)
Infection was listed in the Closed Claims Study1 as a cause for litigation in 24 cases involving epidural steroid
injections. There were 12 cases of meningitis and 3 cases of osteomyelitis. There were 7 cases of epidural abscess, 6
requiring surgical decompression and 1 resulting in permanent lower extremity motor dysfunction. In 1 claim there
was both meningitis and epidural abscess and in 1 a combination of meningitis, abscess, and osteomyelitis.
Similar to epidural infections, the majority of cases of septic arthritis of the facet and sacroiliac joints occur in the
absence of injection or instrumentation. Systematic reviews have reported 27 cases of facet joint infection36 and 166
cases of bacterial sacroiliitis.37 Following intraarticular facet injection, septic arthritis in the facet joints can extend
to involve the paraspinous muscles38 and the epidural space.39
Considerations regarding sterile technique and use of disinfectant solutions are similar to those recommended for
single-shot regional anesthetic techniques performed in the perioperative period.40,41 Most experts recommend the
use of an iodine-based skin preparation solution, routine use of sterile drapes and gloves, and strong consideration of
routine use of face masks and hats. Routine use of pre-procedure antibiotics does not appear to be warranted in the
majority of single-shot spinal and peri-spinal injections.28 Pain practitioners should establish written post-procedural
guidelines for their patients that include a clear description of the signs and symptoms of evolving infection and a
clear process for contacting pain clinic personnel.28
Complications associated with transforaminal injections

There have now been numerous reports of complications associated with both cervical and lumbar transforaminal
injection of steroids. The most concerning risk of transforaminal injection involves unintentional intravascular
injection of the steroid solution. The incidence of intravascular injection was 19% in a series of 504 cervical
transforaminal injections.42 Although the authors did not discern between intra-arterial and intravenous injection, the
observed vascular injections seem to have been intravenous and no adverse outcomes occurred. Intravenous
injection is an innocuous event during transforaminal injection; particulate steroid injected intravenously will be
carried away from the site inflammation, thus reducing any local anti-inflammatory effect. In contrast, intra-arterial
injection is far less common, but the effects may lead to catastrophic neurologic injury.43
In the cervical spine, the vertebral artery, the ascending cervical artery, and the deep cervical artery each furnish
spinal branches that enter the intervertebral foramina. These spinal branches supply the vertebral column but also
give rise to radicular arteries that accompany the dorsal and ventral roots of the spinal nerves. Not infrequently,
anterior radicular arteries are of significant caliber and reinforce the anterior spinal artery. Such reinforcing arteries
can occur at any cervical level, but appear to be more common at lower cervical levels. 44 If particulate steroid is
injected within a reinforcing radicular artery during transforaminal injection, infarction of the cervical spinal cord
could ensue. The vertebral artery lies anterior to the cervical intervertebral foramina, and should not be encountered
in a carefully executed transforaminal injection. However, radicular arterial branches arising from the vertebral
artery can also join the arterial supply that reaches the anterior spinal artery; it is feasible that injectate placed within
a radicular artery during transforaminal injection could reach the vertebral artery via retrograde flow through an
arterial anastamosis.44 If particulate steroid reaches the vertebral artery during transforaminal injection, infarction of
the posterior circulation of the brain including the cerebellum could ensue.
The first report of a complication attributed to cervical transforaminal injection of steroid described a patient who
died from a spinal cord infarction.45 The location of the infarction implied that a radicular artery that reinforced the
anterior spinal artery had been compromised. A subsequent case report described a possible mechanism by which
the spinal cord could be compromised.46 During a C5-6 transforaminal injection, the operator injected a test dose of
contrast medium. At this time filling of a transversely running vessel that satisfied the features of a radicular artery
was seen. The procedure was terminated and the patient suffered no ill effects. The authors postulated that
unintentional injection of an anterior radicular artery could occur during transforaminal injection. If particulate
steroids were to be injected into a reinforcing artery, they could act as an embolus to infarct the spinal cord. This
view was reiterated in a later review article,43 which described another case of radicular artery filling during cervical
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transforaminal injection and a subsequent case report.47 These cases indicate that injection was made into a radicular
artery, which reinforced the anterior spinal artery.
Several reports have now appeared implicating vertebral artery injection as the mechanism of injury during cervical
transforaminal injection. After attempted C5-6 and C4-5 transforaminal injections, a patient developed bilateral
blindness and MRI revealed bilateral parenchymal enhancement of the occipital lobes. 48 The clinical features and the
imaging results implicated unintentional injection into the vertebral artery. The offending agent was not apparent as
only contrast medium and air were used during the procedure. The authors argued that either the contrast medium or
air embolism could have caused the cerebral injury. In a second report implicating vertebral artery injection, a
patient developed respiratory and cardiovascular collapse shortly after a C6-7 transforaminal injection of steroids
and died in a coma 1 day later.49 A CT scan revealed a large hemorrhage around the brainstem. A postmortem
examination revealed cerebral edema, extensive hemorrhage in the brainstem and left cerebellum, and a thrombus in
the left vertebral artery. A third patient developed quadraparesis after a right C5-6 transforaminal injection and
expired the following day.50 No imaging or postmortem findings were provided.
Minor complications occurred in about 9% of a series of 322 lumbar transforaminal injections. 51 Transient
headaches (3%), increased back pain (2%), facial flushing (1%), increased leg pain (0.6%), and vaso-vagal reaction
(0.3%) were the most frequently reported. These complications are similar to those associated with lumbar
interlaminar and caudal injections. The major complications associated with lumbar transforaminal injections
involve the reinforcing radicular artery, known as the artery of Adamkiewicz. Although this artery typically arises at
thoracic levels, in 1% of individuals this artery arises as low as L2, and more rarely as low as the sacral levels.( 52) In
those with a low-lying radicular artery, the artery can be entered during lumbar transforaminal injections. There
have been two reports of complications that likely resulted from direct injection in to this vessel.
In one report, three patients developed paraplegia after lumbar transforaminal injections. In two cases the injections
were performed at L3-4 and in the third, the injection was at S1.53 In all cases, MRI demonstrated increased signal
intensity of the low thoracic spinal cord. A second report described one patient who developed paraplegia after an
injection at L2-3.54 MRI showed increased signal intensity in the lower thoracic spinal cord and conus medullaris.
The injection had been performed under CT guidance without a test dose of contrast medium.
The exact mechanism of spinal cord injury following transforaminal injections has not been determined. The pattern
of injury seen on subsequent MRI strongly suggests occlusion of a reinforcing radicular artery. Both spasm of the
artery or embolism of particulate steroids could account for these outcomes, but spasm seems less likely in light of
the permanent and catastrophic outcomes. However, direct evidence is still lacking.
Published guidelines for the conduct of transforaminal injections 43,55,56 are designed to guard against these
complications. The needle must be accurately and correctly placed using radiographic guidance. Once the needle
has been placed, a test-dose of contrast medium should be injected and its flow carefully monitored during injection,
using “live” or “real-time” fluoroscopy with or without digital subtraction. Under normal circumstances the injectate
should flow around the target nerve and into the lateral epidural space. Simultaneously, but more critically, this test-
dose of contrast shows if intravascular injection occurs. Close attention is required to notice if the injection is intra-
arterial. The rapid flow through arteries means that intra-arterial contrast medium will appear only fleetingly. This
event is unlikely to be captured by post-injection spot films. The flow of contrast medium must be monitored using
continuous fluoroscopy throughout the injection.
Neurologic complications of transforaminal injections are often

catastrophic. They are immediately obvious with the onset of spinal
weakness and numbness. Their recognition requires no special
investigations. Magnetic resonance imaging (MRI) of the spinal cord
and hindbrain serves only to identify the location and extent
of the neurologic damage (Figure 2). Immediate treatment is with
ventilatory and cardiovascular support as needed and subsequent
management and rehabilitation follow standard protocols for spinal
cord injury or stroke.
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FIGURE 2. Cerebrovascular accident following intra-arterial injection of particulate steroid within the vertebral
artery. Axial MRI (T1 FLAIR sequence) of the brain demonstrating massive bilateral stroke in the distribution of
the posterior cerebral circulation.
Complications associated with implantable devices

Spinal cord and peripheral nerve stimulation (SCS) and intrathecal drug delivery systems (IDDS) using implantable
devices is now commonly used in the treatment of chronic pain, with the pain physician typically assuming the role
of the surgeon. A recent report from the ASA Closed Claims group highlights the range of complications that can
occur with these implantable devices, some related to the technical aspects of surgical placement and others related
to the management of patient after implantation. 57 Device-related care consisted of surgical device procedures (n =
107) and IDDS maintenance (n = 41). Severity of injury was greater in IDDS maintenance claims (56% death or
severe permanent injury) than in surgical device procedures (26%). Death and brain damage in IDDS maintenance
claims resulted from medication administration errors (n = 13; 32%); spinal cord injury resulted from delayed
recognition of granuloma formation (n = 9; 22%). The most common damaging events for surgical device
procedures were infections, inadequate pain relief, cord trauma, retained catheter fragments, and subcutaneous
hygroma. Care was more commonly assessed as less than appropriate (78%) and payments more common (63%) in
IDDS maintenance than in surgical device procedure claims (P < 0.001). In an independent analysis of malpractice
claims,58 damaging events included IDDS refill errors (e.g., subcutaneous administration of medication,
reprogramming errors), intra-operative nerve damage, and post-operative infection (e.g., epidural abscess,
meningitis). High severity outcomes included nerve damage (e.g., paraplegia) and death. Medium severity
outcomes included drug reactions (e.g., respiratory arrest from opioid overdose) and the need for re-operation. For
both IDDS and SCS, reviewers noted that deficits in technical skill were the most common contributing factor to
injury, followed by deficits in clinical judgment, communication, and documentation. Implanted devices used for
pain management involve a significant risk of morbidity and mortality. Proper education of providers and patients is
essential. Providers must acquire the technical skills required for implantation and refilling of these devices and the
clinical skills required for the identification and management of complications, such as intrathecal granuloma.
Proper patient selection and clear communication between the provider and the patient about these possible
complications are of paramount importance.
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Complications Associated With Medical Management of

Chronic Pain
Richard W. Rosenquist, M.D. Cleveland, OH
Objectives
1) Describe the range of complications associated with pain treatment;
2) Discuss the causes of common and uncommon complications associated with pain treatment;
3) Outline an approach to minimizing the complications associated with pain treatment.
Introduction
The presence and incidence of chronic pain in the general population and its impact on healthcare cost and
utilization as well as its impact on productivity in the workplace has been widely published. In the last two
decades, treatment of chronic pain has grown exponentially with an emphasis on multimodal treatment including
medical management alone or in conjunction with interventional therapies. In the late 1980’s the IASP declared that
we needed to destigmatize the use of opioids and begin to promote their use to treat the epidemic of chronic,
untreated pain. In the ensuing years, the use of opioids exploded in concert with efforts on the part of the
pharmaceutical industry to promote their use and minimize the apparent risks. The USA now represents
approximately 5% of the world’s population and is using almost 80% of the world’s prescription opioids. This has
been accompanied by a meteoric rise in the number of patients dying from prescription opioid overdose and those
that are addicted to prescription or other opioids. In addition, evidence regarding the lack of long-term efficacy for
opioids and its detrimental effects on the nervous system has developed and there is a significant effort underway
nationally to reduce the use of opioids and their devastating outcomes. In parallel with this, there has been a
dramatic increase in the use of non-opioid agents to treat pain and the psychological consequences of chronic pain.
While these agents can have significant benefits for some, they are also associated with the potential for significant
and sometimes devastating consequences. The use of all medical management approaches should be undertaken
with consideration of the condition being treated, the co-morbid medical conditions, other medications currently in
use, the goals of therapy and the potential for adverse effects. They should be monitored for efficacy and adverse
effects and if there is either no appreciable benefit or definable adverse consequences, the medication should be
discontinued and a suitable alternative considered if appropriate.
Range of complications
The potential range of complications associated with medical management is broad and includes those that occur
quickly as well as those that occur over time. Short-term complications may include things like allergic reactions,
nausea and vomiting, sedation, blurry vision or loss of vision. Medium-term complications may include
constipation, memory loss, dry mouth, dry eyes, kidney stones, ulcers, endocrine abnormalities, elevated liver
enzymes, blood clotting, blood pressure and kidney function. Long-term complications may include osteoporosis,
gingivitis and dental caries. Complications such as respiratory depression and death with opioids can occur at any
time and are affected by other drugs and co-morbid health conditions. This refresher course will address common
drug related complications by class and will offer recommendations regarding monitoring and minimizing adverse
consequences of drug therapy.
Drug Classes
Opioids
The search for a safe, rapid, reliable means of reducing pain has been part of all recorded human history. Initially,
opium served this purpose, but in 1805, Friedrich W. Serturner isolated and described the principal alkaloid and
active ingredient in opium, which he named “morphium”. This was followed by the discovery of other opioid
alkaloids and in the 20th century, the development of numerous synthetic opioid compounds and a wide variety of
opioid delivery systems to provide sustained levels of opioids in the blood stream to treat chronic or cancer pain.
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Common opioid related adverse effects include constipation, urinary retention, sedation, delirium, dry mouth,
respiratory depression, hyperhidrosis, pruritus, muscular spasm, tremor, nausea and vomiting. In some cases,
tolerance develops and side effects diminish. In others, side effects persist for the duration of therapy. Constipation
should be anticipated and treatment should be initiated as soon as opioids are prescribed. This may be as simple as
changing diet, however, in other cases, it requires stool softeners, promotility compounds such as senna, osmotic
agents and bulk agents. Other alternatives include opioid antagonists such as alvimopan and methylnaltrexone that
block opioid receptors in the gut. Sedation is commonly observed with initiation of therapy or with significant dose
increases. In most cases this will resolve after a few days. However, persistent sedation or delirium may develop
and may be the result of other comorbidities or concomitant use of other sedating medications. The most dangerous
side effect is respiratory depression, which may occur at any time during therapy. The relative risk is highly
dependent on the total dose of medication and the presence of other drugs or comorbidities. In doses of 50mg
morphine equivalent, the risk of fatal respiratory depression is increased at least two fold. Concomitant use with
benzodiazepines increases the risk from 4-10 fold. Myoclonus and tremor may occur. This is more common with
high doses of opioids and when patients are drowsy or entering light sleep. Endocrine side effects often occur with
opioid therapy. They include hypogonadism, adrenocortical deficiency and growth hormone deficiency. Opioids
are also associated with immunosuppression through neuroendocrine effects or via a direct effect on the immune
system. Although opioids are prescribed to treat pain, there is a growing body of evidence that their use is
associated with the development of abnormal sensitivity to pain. The use of opioids also has a dark side, which
consists of addiction, physical dependence, tolerance, abuse, diversion, withdrawal and death. The exact incidence
in association with prescription use is not known, but the non-medical use of prescription drugs has grown to
epidemic proportion and it is estimated to be associated with 44 deaths per day. Addiction is not a predictable drug
effect, but certain risk factors should be taken into consideration prior to prescribign opioids for chronic use and the
use of urine drug screening, opioid risk tools, opioid agreements and prescription drug monitoring programs, while
imperfect may offer earlier detection. If a diagnosis of drug abuse or addiction is made, treatment or counseling
should be initiated as soon as possible. In some cases, a reiteration of the importance of taking the drug as
prescribed may be sufficient. Other cases may require cessation of drug therapy or referral to a substance abuse
program.
NSAIDs
Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in the treatment of a wide variety of pain
conditions and are available as mixed agents inhibiting both cyclooxygenase (COX) 1 and 2 and pure COX 2 agents.
They have both analgesic and anti-inflammatory effects. They are commonly prescribed for patients with
musculoskeletal pain, arthritis and bone pain. The most common side effects are gastrointestinal upset and GI
bleeding. This is the result of inhibition of prostaglandin synthesis that results in increased gastric acid secretion
and decreased bicarbonate and mucus secretion and diminished trophic effects on gastric mucosa. They should also
be used with caution in those with inflammatory bowel disease. This is increased in the elderly and in patients with
co-administration of other medications such as steroids and antidepressants. They also have an impact on renal
function and hypertension and may be associated with decreased GFR, renal dysfunction, fluid retention and
hypertension. They typically have an inhibitory effect on platelet function and may be associated with an increased
risk of bleeding complications during surgery or various percutaneous procedures. They have also been associated
with an increased risk of myocardial infarction and stroke and should be used with caution or avoided altogether in
those with a history of previous heart attack. There is evidence that naproxen is the least harmful of the NSAIDs
with regard to cardiac risk. NSAIDs have been associated with photosensitivity. NSAIDs are not recommended
during pregnancy, particularly during the third trimester due to their potential to cause premature closure of the
ductus arteriosus, premature birth and miscarriage. The use of NSAIDs following fractures, orthopedic surgery and
spine surgery is controversial due to delayed bone healing and potential for fusion failure.
Proton Pump Inhibitors and H2 Antagonists

Proton pump inhibitors (PPIs) are used to produce a long-lasting reduction of gastric acid production and may be
prescribed in conjunction with NSAIDs to reduce the risk of gastric ulcers. The most common adverse effects are
headache, nausea, diarrhea, abdominal pain, fatigue and dizziness. Infrequently, they can be associated with the
occurrence of myopathies and/or rhabdomyolysis. Consistent use may result in alterations of digestion and
absorption of micronutrients including vitamins and minerals. H2 Antagonists block the action of histamine at in the
parietal cells of the stomach and decrease the production of stomach acid. They are generally well-tolerated with the
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exception of cimetidine, which has the most significant interactions. Cimetidine inhibits cytochrome P450 enzymes
and may produce toxic serum levels of drugs such as warfarin, propranolol, methadone, tricyclic antidepressants and
some benzodiazepines.
Anticonvulsants
Anticonvulsant medications are commonly used to treat a wide variety of neuropathic pain conditions such as
diabetic neuropathy, post-herpetic neuralgia and other central and peripheral neuropathic pain conditions. They are
also commonly used in the treatment of headaches and depression. This class of medications has a diverse set of
complications. Common side effects include sedation, short-term memory loss and word finding difficulties.
Patients often report visual changes such as blurry vision. Topiramate is associated with acute effects on closed
angle glaucoma and can lead to loss of vision. Topiramate is also associated with an increased risk of kidney stone
development (reference). These drugs commonly produce xerostomia and are associated with dry eyes, dry mouth
and the subsequent development of dental caries. These drugs have also been associated with changes in personality
and in some cases the development of suicidal ideation. They are associated with changes in appetite and may be
associated with significant weight gain in the case of medications such as pre-gabalin or gabapentin and weight loss
in the case of topiramate. They may also be associated with significant water retention and peripheral edema.
Antidepressants
Antidepressant medications are widely used to treat both the psychological consequences of chronic pain as well as
a number of neuropathic and chronic widespread pain syndromes. This class includes “old school” antidepressants
such as the tricyclic antidepressants (TCAs) as well as new agents such as the selective serotonin reuptake inhibitors
(SSRIs) and the serotonin-norepinephrine reuptake inhibitors (SNRIs). As with the anticonvulsant medications,
they can be associated with personality changes and in some cases development of suicidal ideation. The tricyclic
antidepressants consist of a group of 12 agents with variable effects on serotonin, norepinephrine, 5-
hydroxytryptamine (5-HT), histamine and muscarinic acetylcholine receptors. These agents are associated with
sedation that may resolved with continued use. They are also associated with significant weight gain. The
anticholinergic effects often produce dry mouth and may cause postural hypotension, blurry vision, sexual
dysfunction, constipation and urinary retention. TCAs are metabolized by cytochrome P450 hepatic enzymes and
drugs that inhibit cytochrome P450 may produce a decrease in TCA metabolism and increase the risk of toxicity. If
they are given in combination with drugs that prolong the QT interval, there is an increased risk of ventricular
dysrhythmias. SNRIs inhibit the reuptake of serotonin, norepinephrine and a small amount of dopamine. Due to
the increased norepinephrine levels and higher noradrenergic activity, it should be used with caution in patients with
pre-existing hypertension and patients with coronary artery disease should avoid this class of medications.
Duloxetine has been associated with hepatic failure and should not be prescribed to patients with chronic alcohol use
or known liver disease. Both Duloxetine and milnacipran should be avoided in patients with uncontrolled narrow-
angle glaucoma as they increase the incidence of mydriasis. SNRIs have been associated with the development of
potentially fatal serotonin syndrome, which consists of a clinical triad of abnormalities involving cognitive,
autonomic and somatic effects. SSRIs are most commonly used to treat depression and anxiety. They are thought
to increase the extracellular level of serotonin by limiting its reabsorption. There is an increased risk of bone
fractures, akathisia, suicidal ideation and photosensitivity. They are commonly associated with sexual problems
such as anorgasmia, erectile dysfunction, diminished libido and sexual anhedonia. There is the potential for
arrhythmia in those with QT prolongation. SSRIs interact with anticoagulants like warfarin, NSAIDs and aspirin
and are associated with an increased risk of GI bleeding and post-operative bleeding. SSRIs may also be associated
with the development of serotonin syndrome.
Antispasmodics
Antispasmodics are central nervous system depressants commonly used as skeletal muscle relaxants and to treat
spasticity. They include drugs such as baclofen, tizanidine and dantrolene. Baclofen is a derivative of γ-
aminobutyric acid and may be administered orally, transdermally or intrathecally via an implanted pump. The most
common adverse effects include vomiting, weakness, sedation, respiratory depression and dizziness. The most
dangerous adverse effects are associated with sudden withdrawal, especially in those receiving intrathecal baclofen
for whom it is a potentially fatal problem that represents a true medical emergency. In all cases, baclofen should be
tapered and not simply discontinued. Withdrawal symptoms may include hallucinations, confusion, agitation,
delirium, altered consciousness, nausea, tachycardia, seizures, tremors, autonomic dysfunction, hyperpyrexia,
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extreme muscle rigidity resembling neuroleptic malignant syndrome and rebound spasticity. Tizanidne is a
centrally acting α2 adrenergic agonist. It may be very strong, even at low doses. It may cause hypotension and
should be used with caution in patients with a history of orthostatic hypotension. It has also been associated with
hepatocellular liver damage and up to 5% of patients treated with this medication developed elevated liver function
test values. Concomitant use of tizanidine with moderate or potent CYP1A2 inhibitors is contraindicated as it may
result in a dramatic increase in plasma drug concentrations. In addition, fluoroquinolone antibiotics will also
increase serum concentration. The most common side effects include dizziness, sedation, weakness, nervousness,
depression, dry mouth, constipation, increased muscle spasms and a tingling sensation in the extremities.
Benzodiazepines
Benzodiazepines enhance the effect of gamma-aminobutyric acid at the GABAA receptor and result in sedative,
hypnotic, anxiolytic, and anticonvulsant and muscle relaxant properties. They may also produce anterograde
amnesia and dissociation. Their use is controversial due to decreasing effectiveness over time as well as physical
dependence and withdrawal. They may cause respiratory depression in susceptible individuals and in association
with opioids, they may increase the risk of respiratory depression from 4-10 fold. In the elderly, they are
associated with memory problems, daytime sedation, impaired motor coordination and increased falls. The most
common adverse effects are related to their sedating and muscle relaxing action. The may also produce a lack of
coordination with an associated increase in the number of falls and injuries as well as impaired driving skills and an
increased risk of driving accidents. Decreased libido and erectile problems are common side effects as are issues
related to memory. Paradoxical effects may occur, but are rare and are more likely to occur in recreational users.
Acute withdrawal often produces insomnia, GI problems, tremors, agitation, fearfulness and muscle spasms. Most
benzodiazepines are metabolized by cytochrome P450 and drugs that impact its actions can either increase or
decrease their levels. The other group is metabolized through glucuronidation and have few drug interactions.
Muscle relaxants
Muscle relaxants affect skeletal muscle function and decrease muscle tone. They are commonly used to reduce
symptoms of muscle spasm, pain and hyperreflexia. The neuromuscular blockers are not used in the management of
pain. The other common class is known as spasmolytics or “centrally acting” muscle relaxants. They are
commonly prescribed for low back or neck pain, tension headaches or myofascial pain syndromes. They are not
recommended as first line agents and there is little evidence to support their use. They are not approved for long-
term use. The most common adverse effect is sedation and patients should be advised not to drive or operate heavy
machinery while using them. They have anticholinergic effects and commonly produce dry mouth, constipation
and blurred vision. Rarely, they may produce mental or mood changes, confusion or hallucinations. Carisoprodol
use is frequently associated with dependence, withdrawal and abuse as it produces all of the effects associated with
barbiturate receptor ligands. The most common adverse effect is somnolence and it may impair the patient’s ability
to drive or operate heavy machinery. This compound potentiates the effects of opioids and has been associated with
death in those carelessly combining overdoses of carisoprodol and opioids. Withdrawal of the drug may require
hospitalization in medically compromised patients. In severe cases, withdrawal mimics alcohol withdrawal with
the potential to develop lethal status epilepticus.
Minimizing Complications Associated with Pain Treatment

Complications associated with medical management of chronic pain can be severe. In order to minimize the risk of
complications, a number of fundamental principles should be followed:
1. The potential risk and benefit of the drug should be considered prior to starting the medication, including
an evaluation of all co-morbid conditions.
2. A clear understanding of the goals of drug therapy should be outlined with the patient.
3. With rare exception, drugs should be started slowly and increased gradually.
4. The total number of drugs should be minimized in order to reduce the risk of adverse drug-drug interactions
5. Appropriate laboratory monitoring of drugs and adverse effects should be utilized
6. The lowest effective dose of the medication should be used.
7. If the patient experiences adverse effects or reports no beneficial effect, the drug should be weaned and
discontinued before starting another medication.
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Conclusions
Effective treatment of chronic pain requires a multimodal, multidisciplinary approach that takes into consideration
all aspects of chronic pain including the physiologic, sensory, affective, cognitive, behavioral and sociocultural.
Medical management is an integral part of the multimodal approach to treating pain and involves a broad range of
drugs that are used to target pain of different etiologies. Despite our best intentions to develop effective treatment
approaches, inherent drug actions, variations in health, genetic predisposition, compliance and drug-drug
interactions may all contribute to the development of adverse effects that range from mild to life-threatening.
Vigilance on the part of the prescriber before and during the prescription of these medications as well as adherence
to a general set of good practices will increase the potential benefits to the patient and reduce the risks of adverse
effects.
References
1. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain – United
States, 2016. Recommendations and Reports 2016;65:1-49.
2. Ballantyne JC, and Mao J. Opioid Therapy for Chronic Pain. N Engl J Med 2003;349:1943–1953.
3. Dasgupta N, Funk MJ, Proescholdbell S, Hirsch A, Ribisl KM, Marshall S. Cohort Study of the Impact of
High-dose Opioid Analgesics on Overdose Mortality. Pain Med 2015;17:85-98.
4. Boulakh L, Gislason GH. Treatment with Non-Steroidal Anti-Inflammatory Drugs in Patients After
Myocardial Infarction – a Systematic Review. Expert Opin Pharmacother 2016;23:1-8
5. Yuan JQ, Tsoi KK, Yang M, Wang JY, Threapleton DE, Yang ZY, Zou B, Mao C, Tang JL, Chan FK.
Systematic Review with Network Meta-Analysis: Comparative Effectiveness and Safety of Strategies for
Preventing NSAID-Associated Gastrointestinal Toxicity. Aliment Pharmacol Ther 2016;43:1262-75.
6. Ungprasert P, Cheungpasitporn W, Crowson CS, Matteson EL. Individual Non-Steroidal Anti-
Inflammatory Drugs and Risk of Acute Kidney Injury: A Systematic Review and Meta-Analysis of
Observational Studies. Eur J Intern Med 2015;26:285-91.
7. Fox RK, Muniraj T. Pharmacologic Therapies in Gastrointestinal Diseases. Med Clin North Am
2016;100:827-50.
8. Gilron I, Baron R, Jensen T. Neuropathic Pain: Principles of Diagnosis and Treatment. Mayo Clin Proc
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9. Chiang MC, Tseng MT, Pan CL, Chao CC, Hsieh ST. Progress in the Treatment of Small Fiber Peripheral
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10. Moulin D, Boulanger A, Clark AJ, Clarke H, Dao T, Finley GA, Furlan A, Gilron I, Gordon A, Morley-
Forster PK, Sessle BJ, Squire P, Stinson J, Taenzer P, Velly A, Ware MA, Weinberg EL, Williamson OD,
Canadian Pain Society. Pharmacological Management of Chronic Neuropathic Pain: Revised Consensus
Statement from the Canadian Pain Society. Pain Res Manag. 2014;19:328-35.
11. Qin B, Zhang Y, Zhou X, Cheng P, Liu Y, Chen J, Fu Y, Luo Q, Xie P. Selective Serotonin Reuptake
Inhibitors versus Tricyclic Antidepressants in Young Patients: a Meta-Analysis of Efficacy and
Acceptability. Clin Ther. 2014;36:1087-1095
12. Jaracz J, Gattner K, Jaracz K, Gorna K. Unexplained Painful Physical Symptoms in Patients with Major
Depressive Disorder: Prevalence, Pathophysiology and Management. CNS Drugs 2016;30:293-304.
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15. Safaeian P, Mattie R, Hahn M, Plastaras CT, McCormick ZL. Novel Treatment of Radicular Pain With a
Multi-Mechanistic Combination Topical Agent: A Case Series and Literature Review. Anesth Pain Med
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16. Stetkarova I, Brabec K, Vasko P, Mencl L. Intrathecal Baclofen in Spinal Spasticity: Frequency and
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18. Park TW, Saitz R, Nelson KP, Xuan Z, Liebschutz JM, Lasser KE. The Association Between
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The Leading Articles in 2015-16 From Obstetrics and Obstetric Anesthesia That
Will Influence Your Practice
Robert Gaiser, M.D. Philadelphia, PA

Brenda A. Bucklin, M.D. Boulder, CO
For this lecture, we have gathered the most recent evidence-based information from various sources to
provide an overview of the leading articles from the obstetric and obstetric anesthesia literature.
Antepartum exposure of pregnant women to various medications during pregnancy continues to be of
concern. There has been no link to teratogenicity of the various anesthetic agents. A theoretical concern that
exposure to the various inhaled agents may cause learning difficulties if exposed during the third trimester
(the period of synaptogenesis) has been raised but not confirmed. 1 The FDA has established categories to
indicate the potential of a drug to cause birth defects if used during pregnancy:
 Category A – Studies have failed to demonstrate a risk to the fetus
 Category B – Animal studies have failed to demonstrate a risk to the fetus
 Category C – Animal studies have shown an adverse effect on the fetus but there are no human studies
 Category D – There is positive evidence of human fetal risk based on adverse reaction data but
potential benefits may warrant use of drug in pregnancy
 Category X – Studies in animals or humans have demonstrated fetal abnormalities and there is
evidence of human fetal risk based on adverse reaction data from investigations
Use of common prescription drugs was evaluated during pregnancy. The most common prescription
medications were antibiotics (nitrofurantoin, metronidazole, amoxicillin, and azithromycin) followed by
promethazine.2 The most common Class D medications prescribed were codeine (11.9%) and hydrocodone
(10.2%). In a study examining prescription-use during pregnancy in a large insurance database, 14.4% of
the 76,742 pregnant women were prescribed an opioid. 3 Of these women, 5.7% received an opioid during
the 1st trimester, 5.7% received an opioid during the 2nd trimester, and 6.5% received an opioid during the
3rd trimester. The most common opioid dispensed in pregnancy was hydrocodone (Class D), followed by
codeine, oxycodone, and propoxyphene. Backpain was the most frequent condition for which an opioid was
prescribed, followed by abdominal pain, migraine, joint pain, and fibromyalgia. When opioids are used for
extended courses during pregnancy, there is the risk of neonatal dependence and subsequent withdrawal
following birth. Examining the time period of 2008-2012, more than one fourth of privately insured and
more than one third of Medicaid-enrolled women of childbearing age filled a prescription for an opioid.4
Cardiac arrest during pregnancy is a rare event with data from the US Nationwide Inpatient Sample
suggesting an incidence of 1:12,000 admissions. Causes of cardiac arrest include high neuraxial block, local
anesthetic toxicity, hemorrhage, pulmonary embolus, and sepsis. In 2014, the Society for Obstetric
Anesthesia and Perinatology published a consensus statement for the management of cardiac arrest in
pregnancy.5 This statement presented an approach to the pregnant patient experiencing cardiac arrest. Two
points deserve highlighting from the statement. The first is early delivery of a fetus who is 24 weeks’
gestation or greater. The recommendation is for delivery to occur within 5 minutes if there has not been the
return of spontaneous circulation. Early delivery relieves aortocaval compression and allows for effective
cardiopulmonary resuscitation. It also improves the chance of optimal outcome for the infant. Early delivery
(within five minutes) is good for both the mother and the fetus. 6 The other point is use of left uterine
displacement (LUD) during chest compressions. The recommendation is that LUD could be performed
manually or by tilting the patient to a full 30°. The 2015 AHA guidelines now state that chest compressions
should be performed with the patient in the supine position with manual displacement. It is not possible to
perform adequate chest compressions with the patient tilted to the left. This is of interest especially given
the study by Higuchi, et al.7 Patients with term pregnancies had MRIs while in the supine, 15°, 30°, and 45°
position. Aorta was not compressed in the supine position. The vena cava was compressed; however, the
compression was not relieved until the patient was tilted 30°. According to this study, there is no value to
tilting the patient less than 30°. It is extremely difficult to perform chest compressions in a 30° tilt and also
difficult to operate. The consensus statement also addressed management of the arrest, stating that
medications do not require alteration in pregnancy and that no medication should be withheld because of
permission. Reprinting or using individual refresher course lectures contained herein is strictly prohibited without
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concerns about fetal teratogenicity. Finally, it is important to remember that fetal monitors should be
removed or detached as soon as possible during a cardiac arrest to facilitate CD without delay or hindrance.
Incidence of advanced maternal age continues to increase. According to the CDC, in 2014 the average
age of a woman having her first child was 26 years and 4 months, approximately, one year and 5 months
older than it was in 2000. Based upon ethnicity, Asian or Pacific Islanders had the oldest average age at 29
years and 6 months. The concern with the increasing age of pregnancy is that perinatal death, hypertensive
disorders, gestational diabetes mellitus, placenta previa, and placenta abruption are increased among
women 35 years of age or older than among younger women.8 Given these adverse outcomes, the question
arises whether early induction of labor and delivery would lower the complication rate. A study of 619
women randomized to induction of labor at 39 weeks gestation vs. expectant management revealed no
reduction in CD or in operative vaginal delivery. There was no difference in maternal or neonatal outcomes
between the two groups. There was no difference in postpartum hemorrhage (31%) in the two groups or in
the need for blood transfusion (3%).9 As such, anesthesiologists should be prepared to encounter older
parturients. These patients will not be induced just because of maternal age. However, advanced maternal
age is associated with increased epidural use during labor.10
Prolonged 2nd stage of labor for nulliparous parturients is currently defined as 3 h with epidural
anesthesia or 2 h without epidural anesthesia. This guideline is based upon expert opinion. Gimovsky et
al.11 randomized 78 nulliparous women with prolonged 2nd stage to either extending the labor by one
additional hour or CD. This simple maneuver decreased the CD rate from 43.2% to 19.5%. There was no
increase in neonatal or maternal morbidity with this simple maneuver. Given the results from this study, the
anesthesiologist may expect nulliparous women with prolonged 2nd stage to be pushing an additional hour,
assuming the FHR remains reassuring.
Zika virus has been extensively covered in the press and the medical literature. Zika is a mosquito-borne
favivirus with sporadic reports beginning in 2007. However, in 2015, an increase in the reporting of
infections with Zika virus occurred in Central and South America, with Brazil being the most affected
country. Zika virus is spread primarily through the bite of an infected Aedes species mosquito, although
there are documented cases of sexual transmission. The most common symptoms of Zika infection are
fever, rash, joint pain, and conjunctivitis. The illness is usually mild with symptoms lasting for several days
to a week after being infected. Zika virus infection during pregnancy may cause microcephaly as well as
other fetal brain defects. In one case of maternal infection in which the mother terminated the pregnancy,
the infant had micrenephaly, and multifocal dystrophic calcifications in the cortex and subcortical white
matter. The virus was found in the fetal brain.12 Laboratory diagnosis of Zika virus infection is possible by a
positive Zika virus real-time reverse transcription-polymerase chain reaction test or a positive Zika virus
immunoglobulin M neutralization test performed in conjunction with the IgM ELISA. In May 2016, there
were 279 reports of pregnant women with laboratory evidence of possible Zika virus infection, including
157 pregnant women residing in the US and the District of Columbia.13 Of these women, 73 reported
clinical symptoms consistent with Zika virus infection: 64 reported rash, 36 reported arthralgia, 37 reported
fever, and 17 reported conjunctivitis. For anesthesiologists, it is important to remember that Zika RNA has
been found in saliva, urine, and amniotic fluid. Currently, there have been no documented cases of
transmission from an infected patient to a health care provider. According to the CDC, anesthesiologists in
the labor and delivery setting “should adhere to Standard Precautions and wear sterile gloves and a surgical
mask when placing a catheter or administering intrathecal injections; additional equipment should be worn
based on anticipated exposure to body fluids. Double gloves might minimize the risk for percutaneous
injury when sharps are handled. Patient body fluids should not come into direct contact with health care
personnel clothing or footwear. Clothing, skin, and mucous membrane protections should be maintained for
procedures in the operating room.”14
Continuous fetal heart rate monitoring was developed to improve the detection of fetal hypoxia and to
intervene to prevent hypoxia-induced neonatal encephalopathy. In fact, the updated Practice Guidelines for
Obstetric Anesthesia states, “Fetal heart patterns should be monitored by a qualified individual before and
after administration of neuraxial analgesia for labor.” The good news is that the guidelines acknowledged
that it may not be required in every setting and may not be possible during placement of a neuraxial
catheter.15 Despite an increase in the incidence of CD due to nonreassuring FHR patterns, there has not been
a decline in hypoxia-related neonatal encephalopathy. It was hoped that the inclusion of fetal
electrocardiography would improve neonatal outcomes. The basis behind this recommendation is the
analysis of ST-segments and T-waves. Fetal academia is associated with fetal ST-Segment elevation and
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increased T-wave amplitude. In a study of 11,108 patients who had the monitor applied, 5532 of the cases
had the information available to the provider. The frequency of a 5-minute Apgar score of 3 or less differed
significantly between neonates and was 0.1% in the group where the information was provided as compared
to 0.3% in the groups that did not have the information. There was no difference in rates of CD or operative
vaginal deliveries. The study concluded that ST-segment analysis can be used as an adjunct to continuous
electronic fetal monitoring but neither improved neonatal outcomes nor reduced the rates of CD.16
The American College of Obstetricians and Gynecologists (ACOG) updated their committee opinion
on the use of magnesium sulfate in pregnancy. It is important to remember that the FDA advises against
the use of magnesium sulfate for more than 5-7 days to stop preterm labor, due to the concern for fetal and
neonatal bone demineralization. The uses of magnesium sulfate for obstetric practice include prevention
and treatment of seizures in women with preeclampsia or eclampsia and fetal neuroprotection before
anticipated early preterm delivery. While magnesium sulfate is not indicated for prolonged administration,
it is recommended for short-term prolongation of pregnancy (up to 48 hours) to allow for the administration
of antenatal corticosteroids in pregnant women who are at risk of preterm delivery within 7 days. As such,
this period would be between 34 weeks’ gestation and 24 weeks’ gestation.17 However, it is important to
realize that this recommendation may change as the indications for antenatal corticosteroids changes.
Antenatal steroids are administered to women between 24-34 weeks’ gestation who develop preterm labor
so that if the mother should deliver, there is improved lung maturity and decreased respiratory distress in
the preterm neonate. The lower limit of 24 weeks’ gestation was chosen as it is the limit of fetal viability.
However, the definition of fetal viability is being challenged as neonates born at 23 weeks’ and 22 weeks’
gestation have survived. The use of antenatal corticosteroids in infants born at 22-25 weeks’ gestation was
determined.18 Antenatal steroids were shown to decrease death and neurodevelopmental impairment at 18-
22 months in infants born at 23-, 24-, and 25-weeks’ gestation, with no improvement in infants born at 22
weeks’ gestation. There was a reduction in intraventricular hemorrhage and necrotizing enterocolitis for
infants born at 23-25 weeks’ gestation. The results of this study suggest that fetal viability may be pushed to
23 weeks’ gestation. If this is the case, then the indication for the use of magnesium sulfate for short term
prolongation of pregnancy may be extended to pregnancies at 23 weeks’ gestation.
There have been many major changes in the definition and management of preeclampsia. According
to the guidelines established by ACOG in 2013, the diagnosis of preeclampsia no longer requires
proteinuria. Renal and hepatic dysfunction may occur without proteinuria; furthermore, the amount of
proteinuria does not correlate with the severity of the disease.19 Preeclampsia may be diagnosed as new
onset hypertension with proteinuria or new-onset hypertension without proteinuria and any of the
following: 1) platelet count less than 100,000/µL, 2) serum creatinine level above 1.1 mg/dL or doubling of
serum creatinine in the absence of other renal disease, 3) liver transaminase levels at least twice the normal
concentrations, 4) pulmonary edema, and 5) cerebral or visual symptoms. These symptoms also make the
diagnosis as severe but includes SBP of 160 mmHg or higher or DBP of 110 mmHg or higher.
Preeclampsia has been shown to be associated with various changes in angiogenic proteins. There is an
increase in soluble fms-like tyrosine kinase 1 and endoglin (both antiangiogenic) and a decrease in placental
growth factor and vascular endothelial growth factor (both angiogenic). These changes may be measured in
the maternal serum or urine. As such, there are commercial tests that are being marketed for the prediction
of preeclampsia in the 1st trimester (before the onset of symptoms). ACOG has taken a stance against the
use of these tests as there are no studies documenting a benefit of reducing the incidence of preeclampsia
based upon these tests.20
Appropriate blood pressure management in women with hypertension during pregnancy not due to
preeclampsia has been debated. The question is what the appropriate blood pressure is for these individuals.
A large randomized study was conducted in 987 women with preexisting hypertension who were
randomized to tight control (DBP=85 mmHg) and to less-tight control (DBP=100 mgHg).21 Blood pressure
was primarily managed with labetalol. There was no difference in the risk of pregnancy loss, premature
birth, or maternal complications, although less-tight control was associated with a significantly higher
frequency of severe maternal hypertension. Given the results of this study, the anesthesiologist can expect
to encounter more women with poorly controlled blood pressure and have much more severe hypertension
during the labor process.
Neonatal resuscitation continues to be an important part of obstetric anesthesia practice. In an analysis of
closed malpractice claims for obstetric anesthesia, newborn death/brain damage was the leading cause for a
malpractice claim to be filed against an anesthesiologist.22 Most of the incidents were due to poor
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communication or anesthesia delay. Communication between the obstetrician and the anesthesiologist is
critical for an optimal outcome of the mother and neonate. According to the Guidelines for Neuraxial
Anesthesia in Obstetrics qualified personal, other than the anesthesiologist attending the mother, should be
immediately available to assume responsibility for resuscitation of the newborn as the primary
responsibility of the anesthesiologist is to provide care to the mother. However, there are times when the
anesthesiologist may be requested to provide assistance in the care of the newborn.
During the transition from intrauterine to extrauterine life, the neonate is required to make rapid and
profound physiologic changes as the neonate transfers from receiving oxygen from uterine blood flow and
nonfunctioning lungs to receiving oxygen completely from respiration. Approximately 10% of newborns
require some assistance to initiate respiration, while about 1% of newborns need extensive resuscitation.
Respirations are the first vital sign to be affected when a newborn is deprived of oxygen. After an initial
period of attempts to breathe, there is a period of primary apnea. During primary apnea, stimulation of the
infant will cause a resumption of breathing. If the oxygen deprivation continues, the baby gasps and enters a
period of secondary apnea. During secondary apnea, stimulation will not restart respirations. The only
therapy for secondary apnea is positive pressure ventilation.
There have been major changes in the provision of neonatal resuscitation.23 In infants not predicted to
require resuscitation, delayed clamping of the umbilical cord should be performed. Delayed clamping is
associated with less intraventricular hemorrhage, higher blood pressure, less need for transfusion, and
decreased risk of necrotizing enterocolitis. Another major change is thermal management of the neonate. It
is important to maintain thermal neutrality in the neonate, which means that delivery should occur in a
warm room. Admission temperature to the NICU is the strongest predictor of neonatal mortality.
Hypothermia is associated with an increased risk of intraventricular hemorrhage, respiratory difficulty,
hypoglycemia, and sepsis. Meconium should no longer be suctioned, even if the infant is depressed. It was
shown that more harm came from intubation and suctioning than benefit. In a comparison of stethoscope
versus EKG for determining the neonate’s heart rate, early application of EKG leads allowed for the
detection of a heart rate approximately 20-40 seconds faster. As such, use of an EKG for determining heart
rate is encouraged. If the neonate requires chest compressions, the two-thumb technique is recommended
as it generates higher blood pressure and coronary perfusion pressure. Following a successful resuscitation,
it is still recommended to have the neonate undergo mild hypothermia for 24-48 h.
Maternal mortality continues to be a worldwide concern. In 2006, the World Health Organization
concluded, “No issue is more central to global well-being than maternal and perinatal health. Every
individual every family and every community is at some point intimately involved in pregnancy and the
success of childbirth.”24 With the exception of the US, there have been worldwide decreases in maternal
mortality. Although maternal death is rare, reports from the Institute for Health Metrics and Evaluation in
2013 reported that the US experienced the largest increase in maternal death in the developed world since
1990.25 Increases in obesity, hypertension, diabetes, and abnormal placentation have “fueled” the recent rise
in maternal mortality, “near misses” and severe morbidity. Recently, data from the Pregnancy Mortality
Surveillance System was used to calculate pregnancy-related mortality ratios by year, age group, and race-
ethnicity during 2006-2010.26 Causes of pregnancy-related deaths were compared to causes since 1987.
Although pregnancy-related deaths due to hemorrhage, hypertensive disorders of pregnancy, embolism, and
anesthesia complications declined over the time period, pregnancy-related mortality ratios increased with
maternal age. Non-Hispanic black women were at highest risk of dying from pregnancy-related
complications. In addition, cardiovascular disease and infection were important contributors to maternal
mortality. This study suggests that chronic diseases are important contributors to pregnancy-related
mortality. Early detection, thorough assessment, disease stabilization, timely referrals, and counseling are
essential to improving outcomes.
Maternal comorbidities, disease and racial disparities contribute to risk during pregnancy. Increasing
numbers of pregnant women in the US have chronic medical conditions including hypertension, diabetes,
heart disease, and obesity.
Cardiovascular disease. The data from the Pregnancy Mortality Surveillance System indicate that
cardiovascular conditions including cardiomyopathy contributed to more than 26% of the
pregnancy-related deaths.26 A recent prospective review of 212 parturients with mechanical heart
valves revealed rates of maternal and fetal mortality of 1.4% and 18% respectively. Although
parturients had better outcomes with tissue values compared to mechanical valves, there were high
rates of thrombotic complications (5%) and hemorrhage (23%).27 The 1994-2011 Nationwide
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Inpatient Sample was used to evaluate trends and associations with hypertensive disorders of
pregnancy.28 In the study, patients with hypertensive disorders were at increased risk for stroke and
stroke-related complications. Patients with typical stroke-related risk factors (e.g., congenital heart
disease, atrial fibrillation, sickle cell anemia, congenital coagulation defects) have increased
independent risk for stroke when combined with a hypertensive disorder. This report and others
reinforce the importance of early identification and management of cardiovascular disease
including severe hypertensive disease.19
Infection and sepsis increase risk for morbidity and mortality. The Pregnancy Mortality
Surveillance System data revealed infection (13.6% of 8,645 pregnancy-related deaths) as a
leading cause of maternal mortality behind cardiovascular disease (14.6% of 8,645 pregnancy-
related deaths).26 The severe H1N1 influenza outbreak from 2009-2010 resulted in significant
morbidity and mortality among pregnant women.29 In the report, 75 women were confirmed to
have died from H1N1 with another 34 identified as probable cases. Flu vaccines are designed to
protect against the main flu viruses and are safe in pregnant women. A recent study of sepsis-
related deaths in the state of Michigan from 1999-2006 determined that death due to sepsis resulted
in 2.1 per 100,000 and 15% of all pregnancy-related maternal mortality.30 This study emphasizes
the importance of early diagnosis, appropriate antibiotic choice, and escalation of care.
Racial disparities have continued to be important contributors to maternal morbidity and mortality.
The Pregnancy Mortality Surveillance System data revealed that non-Hispanic black women were
at highest risk of dying from pregnancy-related complications.26 Besides a 3.2 times higher risk of
dying of pregnancy complications than non-Hispanic white women, these women were younger,
less educated, more likely to be unmarried, start prenatal care in the 2nd and 3rd trimesters of
pregnancy, and die of ectopic pregnancy complications than non-Hispanic white women. A
prospective study of the incidence of maternal morbidity (e.g., hemorrhage, infection, and perineal
laceration) also revealed stark racial and ethnic differences in the incidence maternal mortality. In
the study, non-Hispanic white women were least likely to experience hemorrhage (1.6% non-
Hispanic white compared with 3.0% non-Hispanic black compared with 3.1% Hispanic compared
with 2.2% Asian) and infection (4.1% non-Hispanic white compared with 4.9% non-Hispanic
black compared with 6.4% Hispanic compared with 6.2% Asian).31 The risk of perineal injury was
increased in Asian women. The authors suggest that the adverse outcomes could not be explained
by differences in patient characteristics or by delivery hospital and that racial and ethnic disparities
continue to persist in delivery of obstetric care. They emphasize the importance of determining the
cause of these racial and ethnic differences and prioritization of these important issues.
Thrombocytopenia (defined as a platelet count <100,000) develops in up to 1 in 20 healthy women by the
end of pregnancy. Although there is no consensus about the minimum platelet count that ensures safe
neuraxial techniques, most agree that a platelet count of 75,000-80,000 is adequate for safe administration
of neuraxial analgesia/anesthesia.32 However, more recent data were analyzed from a multisite retrospective
review of obstetric medical records from 1997-2007 and previous studies.33 Two hundred eighty patients of
~52,000 deliveries from two institutions and 254 of 499 patients from previous studies34-40 were analyzed.
The authors concluded that even with a large data set, the data may be insufficient to confidently offer
epidural analgesia to patients with platelet counts between 75,000-80,000. More recently, a database of
20,244 parturients was evaluated.41 Of those parturients, 368 met criteria and had platelet counts of <
100,000. These results were combined with results from the previous study33 for a final composite sample
size of 755. Results suggested that the upper limit of the 95% CI for the risk of neuraxial hematoma was
0.012 and of all cohorts together 0.004. The authors concluded that the risks of neuraxial anesthesia must be
weighed against the benefits and suggest that a national registry is needed to gather more robust data.
Important questions in assessment of thrombocytopenia include: 1) What is the etiology of the
thrombocytopenia?; 2) What is the absolute platelet count?; 3) What is the time interval since the platelet
count was measured?; 4) What is the trend in the platelet count?; 5) Are there clinical signs of bleeding?
Workforce surveys have been used since 1981 to measure trends in staffing and obstetric anesthesia
services every decade.42-45 The first survey revealed that more than 30% of epidural anesthetics were being
performed by obstetricians.42 In response, the availability of neuraxial labor analgesia not only increased
but was more often administered and managed by an anesthesiologist.43 However, in the smallest hospitals
neuraxial labor analgesia was unavailable in ~20% of cases. The 2001 survey reported further increases in
delivery of neuraxial labor analgesia, especially in the smallest hospitals, with 95% of all hospitals
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reporting availability of neuraxial labor analgesia.44 The most recent survey findings revealed the
following:45
 Neuraxial labor analgesia is now available 24 h per day, even in the smallest hospitals.
 Combined spinal epidural (CSE) is administered for labor in <20% of anesthetics, although it results in
improved maternal satisfaction and fewer top-ups during 1st stage labor.
 Use of PCEA was used at 82% of responding hospitals. It decreases workload and increases maternal
satisfaction.
 (TOLAC) was allowed in 65% of responding hospitals with 500-1499 births and <50% of hospitals
with <500 deliveries.
 Fewer hospitals are providing obstetric services, especially the smallest hospitals surveyed.
 Staffing for postpartum tubal ligation (PPTL) nights and weekends needs improvement, especially after
a 2010 study revealed that 47% of women who desired PPTL did not undergo the procedure while in
the hospital and had an unwanted pregnancy within 1 year of discharge from the hospital. 46
 Emergency cardiac life support training for nurses is an area of obstetric care needing improvement.
 Massive transfusion protocols are used in more than 76% of the largest responding hospitals and 42%
of respondents in the smallest hospitals. Implementing protocols is important to resolve maternal
hemorrhage, reduce blood product use and coagulopathy, and improve perception of patient safety.
 Independent CRNA practice is highest in hospitals with <500 deliveries per year.
American Society of Anesthesiologists Practice Guidelines for Obstetric Anesthesia have been updated
and recently published.15 Since the first guidelines published in 1999, these systematically developed
recommendations have been used to assist practitioners and patients in health care decision-making. The
new guidelines were developed to “incorporate an analysis of current scientific literature and expert
consultant survey results.”
 High-risk conditions and comorbidities may be associated with obstetric complications 47 48,49 28,50
 The oral intake of moderate amounts of clear liquids may be allowed. Solid foods should be avoided.
 A routine platelet count is not necessary in the healthy parturient.
 A routine blood cross-match is not necessary for healthy and uncomplicated parturients.
 FHR patterns should be monitored before and after administration of neuraxial analgesia for labor.
 Patients in early labor (i.e.< 5 cm dilation) should have the option of neuraxial analgesia when this
service is available. Offer neuraxial analgesia on an individualized basis regardless of cervical dilation.
 Neuraxial techniques should be offered to patients attempting TOLAC.
 IV fluid preloading or co-loading may be used to reduce the frequency of maternal hypotension after
spinal anesthesia for CD. Spinal anesthesia should not be delayed in order to administer IV fluid.
 For postoperative analgesia for CD, neuraxial opioids should be considered rather than intermittent
injections of parenteral opioids.
 IV ephedrine or phenylephrine may be used for treating hypotension during neuraxial anesthesia. In the
absence of maternal bradycardia, consider selecting phenylephrine because of improved fetal acid–base
status in uncomplicated pregnancies.
 Management of obstetric and anesthetic emergencies consists of (1) resources for management of
hemorrhagic emergencies, (2) equipment for management of airway emergencies,
and (3) cardiopulmonary resuscitation.
Failure of neuraxial blockade for CD is defined as a neuraxial block that is inadequate in density,
duration, or level. Failure may result from technical, anatomic, or obstetric factors. A multicenter
prospective observational study of more than 34,000 patients found that epidural anesthesia failed more
often than spinal or CSE techniques for CD.51 In the study, increased maternal size, rapid decision to
incision, and placement later in labor were all associated with risk of failed neuraxial anesthesia. A meta-
analysis of studies evaluating risk of failed extension of labor epidural anesthesia for CD determined that a
higher number of boluses administered during labor, patient characteristics (e.g., obesity), and time from
placement to CD increased the risk for epidural failure.30 More recently, a study examined unplanned
conversion to general anesthesia in 4300 parturients over a 6-year period.52 The study evaluated conversions
when there was adequate time to provide neuraxial anesthesia. Epidural anesthetics had the highest
conversion rate, followed by spinal, and CSE anesthetics. Conversion was most often associated with
hemorrhage and neonatal compromise.
Uterotonic agents are used prophylactically to prevent uterine atony. Oxytocin is the 1st-line drug for
prophylaxis and is used in conjunction with uterine massage during the active management of the 3 rd stage
of labor in order to decrease blood loss and reduce transfusion requirements. Several studies have evaluated
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the dose of oxytocin required to achieve uterine tone. The ED90 of bolus-dose oxytocin ranges from 0.35
international units (IU) in non-laboring women undergoing CD53 to ~3 IU in laboring women undergoing
CD for labor arrest after oxytocin augmentation during labor. 54 Because data demonstrate lower oxytocin
dose requirements than previously thought, there is now greater appreciation of serious side-effects55 when
higher doses are administered, especially in hypovolemic or hemodynamically compromised individuals. A
recent randomized, double-blinded trial of a “rule of threes” algorithm vs. continuous infusion of oxytocin
during CD determined that there were no differences in uterine tone, maternal hemodynamics, side effects
or blood loss between the two groups.56 However, the group randomized to the “rule of threes” using
oxytocin 3 IU, timed uterine tone evaluations, and a systematic approach to alternative uterotonic agents
received lower oxytocin doses when compared with a continuous infusion of oxytocin. When uterine atony
persists, 2nd-line uterotonic agents are utilized. A recent study of women receiving 2 nd-line agents
(carboprost or methylergonovine) revealed that women who received carboprost were more likely to
experience hemorrhage-related complications (hysterectomy, uterine artery ligation) compared with women
who received an ergot alkaloid.57 When women had received oxytocin during labor, the difference remained
but confidence intervals crossed. The authors suggest that methylergonovine may be more effective than
carboprost as a 2nd line uterotonic agent.
Maternal fever associated with epidural analgesia administration has been of great interest since it was
first observed in 1989.58 Although the mechanisms by which epidural analgesia are uncertain, several
explanations have been proposed: 1) thermoregulatory factors; 2) non-infectious inflammatory process; 3)
effects of systemic opioids in patients without epidural analgesia. Although there have been longstanding
concerns about whether epidural analgesia-related fever places the fetus at risk for neurologic injury, a
recent study of the Swedish Birth Registry including ~300,000 births over 10 years concluded that epidural-
related fever is a benign rise in temperature that is not associated with neonatal neurologic consequences. 59
Levels of maternal care and systems to facilitate rapid diagnosis and treatment are gathering increased
interest as the prevalence of severe illness and chronic comorbidities increase in obstetric patients. In 2015,
the ACOG and the Society of Maternal-Fetal Medicine proposed 4 Levels of Care [birth centers, basic care
(level I), specialty care (level II), subspecialty care (level III), and regional perinatal health care centers
(level IV)] with a goal of regionalizing maternal care for pregnant women who are at high risk in order for
them to receive specialized care.60 One specific example of a system approach is the recent postpartum
hemorrhage bundle developed by the National Partnership for Maternal Safety. 61 This document
recommends a system-wide approach to obstetric hemorrhage emphasizing a rapid response team and
anesthesiologist-led resuscitation. Such systems have been shown to improve outcomes.
Along with more system-specific approaches, there is increasing evidence that morbidity and costs are
increased in smaller-volume facilities.62 In addition to increased rates of hemorrhage and infection, one
recent report describes a 2-fold increased risk of major and minor anesthetic complications in hospitals that
perform <200 CDs per year.63 Costs are also increased at these facilities and likely result from prolonged
hospital stays, ineffective staffing models, billing exceptions, and increased morbidities.
Obstetric neuraxial drug administration errors can have serious consequences. A recent review of
published case reports and series were qualitatively analyzed for involvement of human factors in order to
propose modifications to practice.64 The analysis of 29 cases included identification of drugs, error setting,
source of error, observed complications, and therapeutic interventions. Although the most commonly
reported complication was the failure of an intended neuraxial anesthetic, 4 maternal deaths resulted from
the accidental intrathecal injection of tranexamic acid. The most common human factors were similar drug
appearances and drug storage problems. The authors suggest implementation of processes to reduce the risk
of such errors including: “(1) Careful reading of the label on any drug ampule or syringe before the drug is
drawn up or injected; (2) labeling all syringes; (3) checking labels with a second person or a device (such as
a barcode reader linked to a computer) before the drug is drawn up or administered; and (4) use of non-Luer
lock connectors on all epidural/spinal/combined spinal-epidural devices.”
Conclusion: The obstetric population is becoming older and pregnancies are often complicated by
comorbidities and illness. Levels of maternal care and systems will become increasingly important in order
to facilitate rapid diagnosis and treatment as the prevalence of severe illness and chronic comorbidities
increase in obstetric patients. Care of parturients and pregnant patients requires knowledge about obstetric
and anesthetic concerns. The great news is that it is rewarding and appreciated by patients and families.
1. Anesthesiology 2010;112:546-556
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2. Obstet Gynecol 2015;126:465-473

3. Anesthesiology 2014;120:1216-1224
4. MMWR Morb Mortal Wkly Rep 2015;64:37-41
5. Anesth Analg 2014;118:1003-1016
6. Am J Obstet Gynecol 2015;213:653-656, 653 e651
8. Obstet Gynecol 2004;104:727-733
9. N Engl J Med 2016;374:813-822
10. J Matern Fetal Neonatal Med 2008;21:517-521
11. Am J Obstet Gynecol 2016;214:361 e361-366
12. N Engl J Med 2016;374:951-958
16. N Engl J Med 2015;373:632-641
17. Obstet Gynecol 2016;127:e52-53
18. JAMA 2011;306:2348-2358
19. Obstet Gynecol 2013;122:1122-1131
20. Obstet Gynecol 2015;126:e25-27
21. N Engl J Med 2015;372:407-417
23. Circulation 2015;132:S543-560
24. WHO. Ensuring Skilled Care for Every Birth. 2006.
(http://www.who.int/maternal_child_adolescent/documents/MPS_factsheet_ensuring_skilled.pdf
25. The Lancet 2014;384:980-1004
26. Obstet Gynecol 2015;125:5-12
27. Circulation 2015;132:132-142
28. Obstet Gynecol 2015;125:124-131
29. Obstet Gynecol 2015;126:486-490
30. Obstet Gynecol 2015;126:747-752
31. Obstet Gynecol 2015;125:1460-1467
32. Br J Haematol 2010;148:15-25
33. Anesth Analg 2015;121:988-991
34. Blood 1996;88:349-352
35. Anesth Analg 1997;85:385-388
36. Obstet Gynecol 1989;73:943-946
37. Obstet Gynecol 1988;71:918-920
38. Rev Bras Anestesiol 2009;59:142-153
39. Blood 2003;102:4306-4311
40. Can J Anaesth 2005;52:114
41. Anesth Analg 2016 May 6. [Epub ahead of print]
45. Anesth Analg 2016;122:1939-1946
46. Obstet Gynecol 2010;116:1071-1077
47. BJOG 2014;121:1386-1394
49. Am J Obstet Gynecol 2005;192:1423-1426
51. Obstet Gynecol 2005;106:281-287
52. J Perinatol 2015;35:695-699
53. Obstet Gynecol 2004;104:1005-1010
54. Obstet Gynecol 2006;107:45-50
55. Br J Anaesth 2002;89:499-508
58. Lancet 1989;1:1250-1252
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59. Acta Anaesthesiol Scand 2015;59:486-495

60. Am J Obstet Gynecol 2015;212:259-271
61. Anesth Analg 2015;121:142-148
62. Anesth Analg 2010;110:1368-1373
63. Anesth Analg 2016;122:1947-1956
64. Anesth Analg 2015;121:1570-1577
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Nerve Injury after Peripheral Nerve Block: Evaluation, Management, Best Practices, and
Medicolegal Issues
H. David Hardman, MD, MBA Chapel Hill, North Carolina
Nerve Injury after Peripheral Nerve Block: Evaluation, Management, Best Practices, and
Medicolegal Issues
Introduction
Nerve injury after peripheral nerve blockade (PNB) for surgical procedures and post-operative pain relief
continues to be a source of attention and concern for patients, anesthesiologists, and surgeons, despite significant
advances in training and equipment technology for nerve localization. When a significant nerve injury is
recognized for the first time after surgery, a cascade of events can be set into motion leading to strained professional
relationships between anesthesiologists and surgeons, not to mention the potential for medicolegal action by
patients. Professional relationships can be preserved with focused communication and education to improve
understanding of the underlying risks and etiologies of nerve damage after surgery. Medicolegal action can be
allayed with attention to appropriate patient selection, informed consent, shared decision making, and enhanced
documentation made possible by the electronic medical record.
Incidence of nerve injury after peripheral nerve block and risk factors
The absence of a standard definition of nerve injury after surgery has hampered understanding of the incidence
and severity of the problem. The use of the term, post-operative neurologic symptoms (PONS), or peripheral nerve
injury (PNI), is an attempt to adopt a standard definition of incidence, without describing severity or causation.
Temporary sensory and motor injuries are common; permanent motor injuries are rare. Alarmingly, up to 16%-30%
of patients may report sensory or motor abnormalities during the first weeks after surgery, decreasing to 3% several
months later, with less than 1% persisting beyond 6 months.1-3 Among elective procedures, orthopedic arthroscopic
and open shoulder procedures report some of the highest overall injury rates, with diffuse brachial plexus injuries, as
well as single nerve injuries to the axillary, musculocutaneous, suprascapular and radial nerves.3 Fortunately, long
term severe injuries (motor loss or significant neuropathic pain) lasting longer than 6-12 months are exceeding rare,
with level III evidence consistently demonstrating an incidence of 2-4 severe nerve injuries per 10,000 PNBs, in
both the pre (nerve stimulation) and post-ultrasound introduction era.4-9
In clinical practice, it is not unusual for surgeons to assume that anesthesiologists and their regional anesthesia
techniques are the proximate cause of a newly discovered post-operative neurologic injury, and block-related nerve
injury rises to the top of their differential diagnosis list. This attitude reflects a lack of understanding of the current
literature, and perhaps a reliance on surgical studies that report neurologic injury where neurologic injury is not the
primary outcome variable. The differential diagnosis should always consider patient related and surgery related
causes, as well as anesthesia related causes.
Although causation may be difficult to determine at times, there are many high quality studies that can shed light
on this controversy. Three large single-institution clinical registries reporting the incidence of nerve injury after
elective orthopedic joint replacements for hip, knee and shoulder surgery, have demonstrated that PNB does not
increase the risk of PONS; on the contrary, in patients having shoulder replacement the odds of a PNI was reduced
by about 50%.10 Further evidence that PNB is not associated with increased risk of PONS comes from a large case
series of over 7,000 PNBs associated with a variety of surgical procedures, with a neurologist determining causation
of long term severe injuries, based on the results of electrodiagnostic studies. The authors of this study concluded
that non-anesthesia related causes of injury were 9 times more likely than anesthesia related causes. 7 Lastly, a large
single institution case series of over 380,000 surgical procedures during a 10 year time interval, was not able to
identify PNB as an independent risk factor for the development of PONS. On the other hand, patient related risk
factors such as diabetes mellitus, hypertension, and tobacco use, as well as surgery procedure types (neurosurgery,
cardiac surgery, orthopedic surgery, and general surgery), were all demonstrated to be independent risk factors for
the development of PONS.6
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What can we conclude from this information? A postoperative neurologic injury is most likely multifactorial in
nature, and although an anesthesia related cause should be part of the differential diagnosis, it should never comprise
the entire differential diagnosis, as other causes are more common, including surgery specific procedures. Patients
with underlying microvascular disease (tobacco use, hypertension, diabetes) and those with chemotherapy-induced
neuropathy (CIPN) (cisplatin, oxaliplatin, carboplatin, vincristine, paclitaxel, suramin), especially those with sub-
clinical injury, are at risk for post-operative double crush injuries, which may manifest as new clinical nerve deficits
post-operatively.6,11
A recent publication from the 2nd ASRA Practice Advisory on Prevention of Neurologic Complications after
regional anesthesia cites class II recommendations to conclude that PNB may increase the risk of new or progressive
deficits in patient with diabetic peripheral neuropathy (DPN), and also recommends decreasing the concentration of
local anesthetic, total volume, and eliminating or reducing the concentration of adjuvant vasoconstrictors
(epinephrine).1,11 Patients with central nervous system disorders such as multiple sclerosis, amyotrophic lateral
sclerosis, and post-polio syndrome may have subclinical injury, along with a natural waxing and waning of the
disease, which may be exacerbated after surgery. Although there is insufficient evidence to suggest that PNBs may
increase the risk of PONS in these patients, if it occurs, it may be incorrectly attributed to the PNB. The decision to
offer a PNB in these patients should be individualized after a risk-benefit discussion.11 Consideration may also be
given to performing blocks after surgery, in patients at higher risk for developing complications, after a
postoperative neurologic assessment has been completed.
Mechanisms of nerve injury and classification system

Each individual axon is surrounded by a connective tissue layer known as the endoneurium. Individual axons are
packed together to form fascicles (100-1000 µm diameter), surrounded by a circumferential impermeable connective
tissue layer (perineurium), containing non-fenestrated capillaries. Collections of fascicles are then further
surrounded by an outermost connective tissue layer, (epineurium), which is a thick, but permeable layer. Deep to
the epineurium, but between fascicles (interfascicular) lies a loose areolar connective tissue layer, composed of
adipose cells, fibroblasts, mast cells, arteries, arterioles, veins, capillaries, and lymphatics. This layer is also known
as the sub-epineurium.
Even though nerves are delicate structures, at the same time, their connective tissue architecture affords several
layers of protection to prevent direct axonal injury. However, a variety of mechanisms can injure the axonal and
connective tissue components of the nerve, resulting in demyelination and or axonal loss, with disruption of
electrical conduction. These injuries can include stretch and compressive forces; ischemia; blunt and penetrating
trauma; thermal injury; tissue edema; hematoma formation; toxic or metabolic injuries; and inflammatory or
infectious etiologies.12 Mechanisms of injury can be surgery related (positioning, tourniquets, retractors, scalpel,
hematoma, edema, thermal, inflammatory), patient related (ischemic, inflammatory), or anesthesia block related
(needle trauma, inflammation, hematoma, local anesthetic toxicity).12,13 Although nerves tend to pinwheel away
from a compressive force exerted by an advancing block needle in clinical settings, if a block needle penetrates the
epineurium, inflammatory changes will occur.14 However, the major danger appears to be associated with
intrafascicular penetration, and subsequent generation of high intrafascicular pressures causing ischemia, either with
or without fascicular disruption. These changes can occur experimentally even with injections of saline, although
local anesthetic injections are much more neurotoxic.12,13 Advancing short bevel block needles of sizes and
diameters commonly used clinically, directly into fascicles, is difficult to achieve experimentally, due to the
resistance encountered trying to penetrate the tough perineurium, as well as due to the large diameter of needles
relative to fascicle size. Nerve fascicles range in size from 100-1000 µm, while a 22 gauge block needle is 700 µm
in diameter.13 Unfortunately, block needles can also injure the nerve fascicles by disrupting small vascular structures
in the interfascicular space (sub-epineurium), creating intraneural hematomas, which can subsequently compress
nerve fascicles. Additionally, block needles coming in close proximity to the nerve may disrupt the external vasa
nervorum, leading to hematoma formation outside the epineurium, which may cause nerve compression and
ischemia.
Nerve injury can be graded based on anatomic levels of injury, which also provide a clinical prognosis.12,15,16
The Seddon classification divides injury into three grades; neurapraxia (myelin injury only), axonotmesis (axon
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injury only), neurotmesis (axon injury and connective tissue disruption involving the endoneurium, perineurium, and
epineurium). Neurapraxic injuries will resolve spontaneously with full recovery, axonotmetic injuries have a mixed
prognosis for spontaneous recovery and may require surgical intervention, while neurotmetic injuries require
surgical nerve reconstruction with mixed outcomes. Motor nerve injury on clinical exam is graded on the following
6 point British Medical Research Council (MRC) scale: 0=no visible twitch; 1=visible twitch; 2=movement
insufficient to overcome gravity; 3= movement sufficient to overcome gravity; 4= movement against gravity plus
additional resistance; 5=normal strength.16
The Sunderland classification system further refines the Seddon system, to clarify the level of connective tissue
disruption. Sunderland grade 1 and grade 2 correspond to neurapraxia and axonotmesis, grade 3 is considered
neurotmesis with disruption of endoneurium continuity, grade 4 is neurotmesis with disruption of endoneurium and
perineurium continuity, while grade 5 is complete nerve transection, including disruption of the epineurium. In
general, nerve reconstruction surgery tends to have a poor prognosis with Sunderland grade 4 or higher injury
level.16 The overwhelming majority of patients diagnosed with PONS see complete resolution of their symptoms
within 3 months; hence, most injuries are neurapraxic, or Sunderland grade 1 injuries.
The clinical challenge is to diagnose Sunderland grade 3 or higher injuries as soon as possible, in order to provide
counseling and surgical referral on a timely basis. In general, nerve reconstructive functional outcomes are
improved with earlier surgery, usually between 6 and 9 months, although recovery has been reported with repairs
initiated up to 18 months after injury.16 On the other hand, when spontaneous recovery occurs, outcomes are usually
better than with reconstructive surgery, with the full extent of possible recovery not being apparent for up to two
years.16 This may create tension between the anesthesiologist advocating watchful waiting, hoping for complete
neurologic recovery, and the surgeon pressing to go ahead in order to obtain the best reconstructive result with nerve
grafting or nerve transfers.
Evaluation of neurologic symptoms after surgery: Imaging (US, MRI, MRN) and electrodiagnostic testing
(NCS, EMG)
Early recognition and documentation of PONS is important for several reasons, including diagnostic and
therapeutic interventions for reversible lesions such as hematoma evacuation, as well as for medicolegal protection.
Barriers exist to early recognition of PONS secondary to patients’ residual sedation and misunderstanding of the
significance of extended duration of motor or sensory nerve loss after surgery. The presence of casts, splints,
stabilization devices and dressings may impair a patient’s perception of motor or sensory abnormalities and
contribute to a delay in diagnosis. An urgent neurology consult is warranted in any patient with significant motor or
sensory loss that persists beyond the expected duration of the block. A recent review article presents an algorithm
for the evaluation and management of a new postoperative neurologic deficit following regional anesthesia. 15
The goal of imaging or electrodiagnostic testing (EDX) is to help determine the location, severity, and prognosis
for recovery of the neurologic abnormality; unfortunately, EDX cannot always establish causation (surgery,
anesthesia, patient).17 EDX is also useful in demonstrating the presence of a pre-existing neurologic lesion that may
not have been clinically apparent prior to surgery. High resolution (12-20 MHz) ultrasound (US) is being increasing
utilized as part of the initial evaluation of PONS, in order to help localize and define the severity of the lesion.18 US
images of affected peripheral nerves can be traced along the course of the nerve and spot potential disruption in
nerve continuity, consistent with neurotmetic injury, which can be verified with magnetic resonance imaging (MRI)
or magnetic resonance neurography (MRN). However, the lateral and axial lateral resolution of US is superior to
that of MRI/MRN. Non-specific pathology visualized with US imaging includes increases in cross-sectional nerve
area (CSA), along with loss of fascicular detail, as compared to the asymptomatic side.18 MRN is a term used to
signify alterations in processing of the conventional MRI signal in order to enhance peripheral nerve imaging. A
two-dimensional T1 diffusion weighted signal with fat suppressed T2 weighted signal will display the outline of
nerve roots, plexus and peripheral nerves, and display a bright or hyperintense image, in areas with increased water
content associated with edema. However, the hyperintense signal is not able to distinguish between neural edema
associated with less severe injuries, such as neurapraxia, versus more serious axonotmetic or neurotmetic injuries. 16
MRI imaging is also able to detect denervation injuries (axonal) in muscle, before they become apparent during
EMG examination.16
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The utility of EDX studies lies in their ability to localize the site of injury in the peripheral nervous system (nerve
roots, plexus, proximal peripheral nerve, distal peripheral nerve) and to distinguish between demyelination and
axonal injury, and hence prognosis for recovery.19 EDX studies consist of nerve conduction studies (sensory and
motor), along with needle electromyography. Compound motor nerve potentials (CMAPs) are measured bilaterally
by stimulating peripheral nerves suppling normal and abnormal muscles. Nerves are stimulated proximally and
distally, with muscle depolarization associated with individual fibers summated together and measured with surface
electrodes on target muscles. A characteristic signal is obtained with measurement of latency, amplitude and
duration. Latency measures onset of depolarization of the fastest myelinated fibers, while amplitude reflects the
summation of individual muscle fiber depolarization potentials based on the number of axons recruited with
supramaximal stimulation current.19 Duration is a reflection of synchrony and efficient muscle contraction. Signals
are biphasic or triphasic in nature, with deflections above baseline described as negative by convention, and those
deflections below baseline being described as positive.19 Sensory nerve action potentials (SNAPs), as well as
CMAPs are commonly measured. SNAPs are low amplitude (µA), short duration (1-2mS) signals, as compared to
CMAP higher amplitude (mA), longer duration (5-6mS) signals. Temporal dispersion and phase cancellation have a
greater effect on SNAPs versus CMAPs, and in cases of severe neuropathic injury, SNAPs may be difficult or
impossible to detect.19
In general, demyelination injuries are characterized by slower conduction and increased latency (conduction time
<75% of lower limit of normal, latency > 130% of normal).19 As conduction velocity slows, temporal dispersion
will occur with increasing time separation of depolarization signals from faster and slower fibers, leading to an
increase in duration, and a decrease in measured peak amplitude, due to temporal dispersion and phase cancellation
of the biphasic electrical signals. When demyelination is focal and severe enough to prevent depolarization, the term
“conduction block” is used to describe this phenomenon. The site of injury can be determined by progressively
stimulating the peripheral nerve of interest from distal to proximal, until a jump in latency is detected, or in the case
of a conduction block, no CMAP is detected.
Axonal injuries are characterized primarily by a decrease in peak amplitude, with limited effect on conduction
time and latency. Conduction velocity is within 75% of the lower limit of normal conduction velocity, while latency
is within 130% of the upper limit of normal.19 Unlike demyelinating injury, once axonal injury occurs, within 3-5
days, Wallerian degeneration prevents depolarization distal to the site of injury, and CMAPs and SNAPs can no
longer be detected at distal muscle or sensory sites innervated by the affected nerve. However, within the first
several days after injury, the nerve is still electrophysiologically active distal to the site of injury, and can still be
stimulated, generating distal CMAP and SNAP potentials. This phenomenon is known as a pseudo-conduction
block since it mimics a demyelination conduction block.17,19
EMG studies confirm the results obtained by nerve conduction studies, and provide additional localization
information for proximal injury sites than cannot easily be measured with NCS. Denervation potentials measured
with needle EMG (fibrillation waves, positive sharp waves) are never associated with demyelination injuries; when
present they indicate more serious axonotmetic or neurotmetic injuries.17,19 The presence of denervation potentials
imply injury to the nerve at or proximal to the branch point of the most proximal muscles with denervation
potentials. 19 EMG studies also assess the number and type of motor unit action potentials (MUAP), and measure
recruitment and activation of motor units. MUAPs can sometimes be detected, when asking a patient to try and
contract a muscle, even when no visible motor activity is apparent on clinical exam. This is a positive sign, and
indicates that partial innervation is still present, without neurotmetic injury. However, this pattern cannot
distinguish between severe demyelinating injury versus axonal injury, as in either case, recruitment of additional
motor units will be impaired.19 After several weeks, the underlying etiology will become apparent, as a
demyelinating injury will rapidly recover and motor unit recruitment will increase or return to normal. Abnormal
recruitment of motor units appears as a “picket-fence” tracing pattern on EMG exam; normal recruitment appears as
a “complete interference” pattern on EMG exam, with no space between adjacent MUAP spikes. 19
The change in morphology of MUAPs is used to follow the presence of reinnervation after axonal injury. With
moderate injury, normal motor units adjacent to injured motor units will send out collateral branch point sprouts to
innervate adjacent muscle fibers innervated by damaged nerves. This will increase the size of the motor unit
(number of fibers innervated by a given axon), and increase the duration and number of phases of the MUAP. These
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collateral sprouts are initially unmyelinated, and appear as delayed low amplitude satellite potentials. 19 With
increasing severity of injury, no normal adjacent motor units exist, and collateral branching cannot occur. Axons
can only extend unmyelinated growth sprouts from the proximal uninjured axon stump. These low amplitude
potentials connote more severe injury and are termed nascent potentials.19
EDX studies are typically obtained initially 3-4 weeks after injury, when the most information is obtainable from
a single study.15 The exam can be uncomfortable, since small caliber 25 gauge unipolar recording needles are
inserted multiple times in a variety of different muscles, in a non-sedated patient. Pathologic denervation potentials
associated with axonal injury are first detected in muscle 3-4 weeks after injury, while CMAP and SNAP amplitude
loss due to Wallerian degeneration will be complete in NCS.15,17,19 Demyelinating injuries can be reliably
distinguished from axonal injuries at this time, and patients can be either reassured about the prospects of full
recovery, or counseled about the possibility of partial recovery and the potential need for future reconstructive
surgery. With evidence of moderate to severe axonal injury, EDX studies can be repeated at 3 months and 6 months
to assess the presence and magnitude of reinnervation, with referral to a reconstructive peripheral nerve surgeon for
injuries not demonstrating further improvement.
An alternative approach is to obtain EDX studies several days after the initial injury is manifested, which several
authors advocate.16,17 The advantage of an early exam is the ability to demonstrate a pre-existing injury with
reinnervation, characterized by polyphasic, long duration MUAPs with satellite or nascent potentials, along with the
presence of positive sharp waves and fibrillation potentials. These EMG changes are consistent with chronic injury,
and would not be detectable until at least 3-4 weeks after injury. Delaying initial EDX studies until one month after
injury would limit the ability to establish that an injury was present prior to the surgical and anesthetic procedure,
and not caused by it. Early EDX studies in the setting of axonal injury, prior to complete Wallerian degeneration,
also allow the ability to localize the site of the neuropathic lesion. Normal distal muscle CMAPs will still be
manifested, as the nerve stimulating site moves distal to proximal, until the stimulating needle is at the level of
injury. After Wallerian degeneration, abnormal distal CMAPs will be measured at any point along the nerve,
including proximal needle stimulating sites where the nerve is undamaged.
During the recovery process, a regular program of physical therapy should be prescribed in order to maintain
joint range of motion and prevent flexion contractures, utilizing splints if needed.15 Neuropathic pain can be
managed with a tiered approach, utilizing first line agents such as tricyclic antidepressant secondary amines
(nortriptyline, desipramine) or SSNRI’s (duloxetine), gabapentinoids (gabapentin, pregabalin), and topical 5%
lidocaine patches.15 Opioids may be considered as second-line agents.
Reconstructive surgical options and pain management for severe injuries

Peripheral nerve reconstruction surgery should be considered for any persistent serious motor nerve injury on
clinical exam (MRC grade 0-3) that affects shoulder or elbow function, with minimal evidence of reinnervation on
EDX studies at 6 months.16 Axon regeneration occurs at a rate of about 1 mm per day, or 1 inch per month, but until
distal reinnervation occurs, deterioration continues in the muscle fiber, neuromuscular junction, and endoneurial
tunnel basement membrane.16 Irreversible functional changes in target tissues will occur between 1-2 years after
denervation, leaving reinnervation moot, with muscle and tendon transfers from normally innervated tissue the only
option to partially restore function. When neuropathic injury is distal, there may be sufficient time for spontaneous
reinnervation; with proximal injury, surgical reconstruction is more likely to be required. Neurotmetic injuries with
complete nerve transection (Sunderland 5), should be repaired as soon as possible, as spontaneous recovery is
unlikely, and painful neuroma formation can occur.16 A sharp, clean transection (unlikely with a block needle)
should be repaired immediately before stump retraction occurs. There are multiple options to repair nerves and
restore function. In general, best results are obtained when the proximal and distal nerve stumps can be trimmed and
directly opposed with microsurgical techniques involving fascicular reattachment and restoring epineural continuity.
However, if the resulting neurorrhaphy has any residual tension, the repair is likely to scar with neuroma formation,
with a poor surgical outcome. In this setting, an autologous nerve interposition graft, harvesting a non-critical nerve
such as an intercostal, sural, superficial radial, or lateral antebrachial cutaneous nerve is used to bridge the gap. For
best results harvested sensory nerves are used to repair sensory nerve injuries, while mixed or motor nerves are used
to repair motor nerve injuries.16
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Since the late 1990’s, treatment has shifted from interposition grafts to nerve transfer techniques, where
improved results have been obtained (MRC 3-4), especially in the setting of proximal injuries, by mobilizing the
distal portion of a viable nerve branch, and connecting it to the distal portion of the denervated nerve, close to the
target muscle.16 For example, in the setting of an injury to the suprascapular nerve and axillary nerve, shoulder
abduction can be restored by mobilizing the distal portion of the spinal accessory nerve, thereby denervating the
lateral aspect of the trapezius, and connecting the mobilized segment of the spinal accessory nerve to the distal
portion of the suprascapular nerve (end to end or end to side), restoring function to the supraspinatus and
infraspinatus muscles. To further improve function and restore abduction, a terminal branch from the radial nerve
supplying either the long or medial heads of the triceps can be mobilized, without adversely affecting triceps
strength, and connected to the distal anterior branch of the axillary nerve to restore function to the deltoid and teres
minor muscles. Using the same concept, in the setting of a musculocutaneous nerve injury, elbow function can be
restored by mobilizing a proximal branch of the ulnar nerve, containing fascicles innervating the flexor carpi ulnaris
muscles (without compromising wrist flexion), and connecting them to a branch of the musculocutaneous nerve near
the biceps muscle. Clearly, this is demanding, extensive and meticulous surgery, requiring intraoperative nerve
stimulation and microsurgical suturing technique, along with an extended recovery period. Even the best outcomes
will not completely restore pre-injury strength and function.
Best practices to prevent nerve injury

The 2nd ASRA Practice Advisory on Neurologic Complications Associated with Regional Anesthesia updates the
previous 2008 version, and offers guidance on potential best practices to potentially reduce the risk of block related
nerve injury.1 This is not a standard of care, nor is it a guideline, due to the limited evidence basis underlying the
recommendations. Adherence to the advisory is intended to provide optimal care, but cannot guarantee the
avoidance of adverse outcomes. As in the previous advisory, the current advisory recommends against a routine
practice of deep sedation or general anesthesia when performing regional anesthetic procedures in adults, although
the practice in children does not appear to increase baseline risk. The advisory also affirms that there is no data to
demonstrate superiority of one nerve localization technique over another (ultrasound, nerve stimulation, paresthesia
technique) with respect to reducing the incidence of PNI. Other important points include the following: 1) the
presence of an evoked motor response at a current of <0.5 mA indicates needle-nerve contact, or intraneural needle
placement 20; 2) there are no human data that confirm or refute the effectiveness of injection pressure monitoring for
limiting PNI; 3) the practice of subjectively assessing injection pressure by hand feel is inaccurate 21 ; 4) ultrasound
can detect intraneural injection 22; 5) intraneural needle insertion does not invariably lead to functional nerve injury
23,24
; 6) intrafascicular needle insertion and injection should be avoided since it can cause histological and/or
functional nerve injury; 7) ultrasound does not have the resolution to distinguish between interfascicular and
intrafascicular injection; 8) adequate images of needle-nerve interface are not consistently obtained by all operators
in all patients.
Although not addressed in the recent advisory, all local anesthetics are neurotoxic, myotoxic, and cytotoxic in
animal experimental in vitro models. However, there is no clinical evidence to choose one local anesthetic in favor
of another in order to reduce the likelihood of PNI. Adjuncts such as clonidine, buprenorphine, dexamethasone, and
dexmedetomidine appear to be safe in commonly used perineural concentrations, and show less neurotoxicity than
ropivacaine in animal models. 25,26 Lastly, there is accumulating evidence to suggest that depositing local anesthetic
at a distance farther away from the target nerves, in muscle or fascial planes, may be equally effective in producing a
successful block compared to deposition of local anesthetic adjacent or circumferential to the nerve. 27 Although yet
to be proven, this practice could potentially decrease the likelihood of needle-induced nerve injury.
Medicolegal concerns and risk reduction

A review of the ASA closed claims data from 1990-2007 demonstrates that only 2% of all malpractice claims
were related to PNBs.28 Examining the data in more detail, most of these claims were for temporary injuries of all
types, while a majority of all claims involved nerve injury. Two-thirds of the nerve injury claims were felt to be
block-related by the reviewers. Hence, even though the overall risk is low, malpractice risk occurs with PNB
procedures, even when injuries are only temporary in nature. Given that the benefits of PNBs are short term
(enhanced quality of recovery), and catastrophic debilitating outcomes are possible, it is imperative to obtain
informed consent, and discuss and document the possible serious complications that can occur, including permanent
nerve injury.29 The results of a survey of academic anesthesiologists performing regional anesthesia indicates that
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there is room for improvement with respect to disclosure of serious complications related to regional anesthesia.30
The option to choose regional anesthesia should always be part of a shared decision making process between the
patient and the anesthesiologist, after a discussion of the material and patient specific risks, without coercion from
anesthesiologists or third parties, including surgeons, and documented on an anesthesia consent form separate from
the surgical consent form. Consideration may be given to offering PNB after a surgical procedure, after neurologic
status has been documented, for patients deemed to be at higher risk for developing PONS.
Should a patient suffer a serious nerve injury after a PNB, and decide to hire a plaintiff’s attorney to pursue
litigation, in order to prove malpractice, the attorney will need to introduce evidence to convince a jury that the
physician breached the standard of care, and that by breaching the standard of care, an otherwise preventable injury
occurred. Given the multifactorial nature of PNI after surgery, this is a high hurdle to overcome. Frequently, these
cases may hinge on a physician’s ability to demonstrate that deliberate intraneural injection did not occur, either via
documented nerve localization techniques or by lack of compromise of patient awareness and communication
abilities during the block procedure. Fortunately, the electronic medical record can be a powerful tool to capture
detailed information related to the block process, and defend your practice against negligence should a serious PNI
occur. Block specific templates can be created to document the detailed work flow associated with the block
processes long after the event originally occurred. Items to consider documenting could include a pre-procedure
neurologic exam, as many patients present with poorly documented pre-existing abnormalities, which could be
erroneously attributed to the block process postoperatively. Nerve localization documentation might include pre and
post-injection ultrasound images to exclude intraneural diameter expansion; opening injection pressure recording;
absence of expansion in nerve cross-sectional volume in response to low volume (1 mL) test injection; absence of
response to low current (0.2mA) neurostimulation; and documentation of a patient’s ability to maintain meaningful
verbal contact throughout the procedure. Taken collectively, this information will demonstrate a pattern of careful
and deliberate practice, and raise the bar for plaintiff’s attorneys’ to prove a breach in the standard of care.
References:
1. Neal JM, et al. The second ASRA practice advisory on neurologic complications associated with regional
anesthesia and pain medicine. Executive summary 2015. Reg Anesth Pain Med. 2015;40:401-430.
2. Neal JM. Ultrasound-guided regional anesthesia and patient safety. Update of an evidence-based analysis. Reg
Anesth Pain Med. 2016;41:195-204.
3. Dwyer T, Henry PDG, et al. Neurological complications related to elective orthopedic surgery. Part 1: common
shoulder and elbow procedures. Reg Anesth Pain Med. 2015;40:431-442.
4. Auroy Y, Benhamou d, Bargues L, et al. Major complications of regional anesthesia in France. The SOS regional
anesthesia hotline service. Anesthesiology. 2002;97:1274-1280.
5. Brull R, McCartney CJL, Chan VWS, El-Beheiry H. Neurological complications after regional anesthesia:
contemporary estimates of risk. Anesth Analg. 2007;104:965-974.
6. Welch MB, Brummett CM, Welch TD, et al. Perioperative peripheral nerve injuries. A retrospective study of
380,680 cases during a 10-year period at a single institution. Anesthesiology. 2009;111:490-497.
7. Barrington MJ, Watts et al. Preliminary results of the Australasian Regional Anaesthesia Collaboration: a
prospective audit of over 7000 peripheral nerve and plexus blocks for neurological and other complications. Reg
Anesth Pain Med. 2009;34:534-541.
8. Orebaugh SL, et al. Adverse outcomes associated with nerve stimulator-guided and ultrasound-guided peripheral
nerve blocks by supervised trainees: update of a single single-site database. Reg Anesth Pain Med. 2012;37:577-
582.
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9. Sites BD, Taenzer AH, Herrick MD, et al. Incidence of local anesthetic systemic toxicity and postoperative
neurologic symptoms associated with 12, 668 ultrasound-guided nerve blocks. An analysis from a prospective
clinical registry. Reg Anesth Pain Med. 2012;37:478-482.
10. Sviggum HP, et al. Perioperative nerve injury after total shoulder arthroplasty: assessment of risk after regional
anesthesia. Reg Anesth Pain Med. 2012;37:490-494.
11. Kopp SL, Jacob AK, Hebl, JR. Regional anesthesia in patients with preexisting neurologic disease. Reg Anesth
Pain Med. 2015;40:467-478.
12. Brull R, Hadzic A, Reina MA, Barrington MJ. Pathophysiology and etiology of nerve injury following
peripheral nerve blockade. Reg Anesth Pain Med. 2015;40:479-490.
13. Abdallah FW, Macfarlane AJR, Brull R. The requisites of needle to nerve proximity for ultrasound-guided
regional anesthesia. A scoping review of the evidence. Reg Anesth Pain Med. 2016;41:221-228.
14. Steinfeldt T, et al. Forced needle advancement during needle-nerve contact in a porcine model:histological
outcome. Anesth Analg. 2011;113:417-420
15. Watson JC, Huntoon MA. Neurologic evaluation and management of perioperative nerve injury. Reg Anesth
Pain Med. 2015;40:491-501.
16. Simon NG, et al. Advances in the neurological and neurosurgical management of peripheral nerve trauma. J
Neurol Neurosurg Psychiatry. 2015:0:1-11.
17. Aminoff MJ. Electrophysiologic testing for the diagnosis of peripheral nerve injuries. Anesthesiology 2004;
100:1298-303
18. Padua L, et al. Ultrasound as a useful tool in the diagnosis and management of traumatic nerve lesions. Clin
Neurophysiol. 2013;124:1237-1243.
19. Preston DC, Shapiro BE. Electromyography and neuromuscular disorders: Clinical-electrophysiologic
correlations (Expert Consult-Online): Elsevier Health Sciences; 2012.
20. Wiesmann T, et al. Minimal current intensity to elicit an evoked motor response cannot discern between needle-
nerve contact and intraneural needle insertion. Anesth Analg. 2014;118:681-686.
21. Gadsden JC, Choi JJ, Lin E, Robinson A. Opening injection pressure consistently detects needle-nerve contact
during ultrasound-guided interscalene brachial plexus block. Anesthesiology. 2014;120:1246-53.
22. Krediet AC, et al. Intraneural or extraneural. Diagnostic accuracy of ultrasound assessment for localizing low-
volume injection. Reg Anesth Pain Med. 2014:39:409-413.
23. Bigeleisen P. Nerve puncture and apparent intraneural injection during ultrasound guided axillary block does
not invariably result in neurologic injury. Anesthesiology. 2006;105:779-83.
24. Hara K, et al. Incidence and effects of unintentional intraneural injection during ultrasound-guided subgluteal
sciatic nerve block. Reg Anesth Pain Med. 2012;37:289-293.
25. Williams BA, Hough KA, Tsui BY, Ibinson JW, Gold MS, Gebhart, GF. Neurotoxicity of adjuvants used in
perineural anesthesia and analgesia in comparison with ropivacaine. Reg Anesth Pain Med. 2011;36:225-20.
26. Brummett CM, Williams BA. Additives to local anesthetics for peripheral nerve blockade. Int Anesth Clinics.
2011;49:104-116.
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27. Albrecht E, Kirkham KR, Taffe P, et al. The maximum effective needle-to-nerve distance for ultrasound-guided
interscalene block: an exploratory study. Reg Anesth Pain Med. 2014;39:56-60.
28. Lee LA, Posner KL, Kent CD, Domino KB. Complications associated with peripheral nerve blocks: lessons
from the ASA closed claims project. Int Anesth Clin. 2011;49:56-67.
29. Domino KB. Informed consent for regional anesthesia: What is necessary? Reg Anesth Pain Med. 2007;32:1-2.
30. Brull R, McCartney CJ. Disclosure of risks associated with regional anesthesia: A survey of academic regional
anesthesiologists. Reg Anesth Pain Med. 2007;32:7-11.
Disclosure: No financial relationships with commercial interest.
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Multimodal Analgesics for Pain Management
May L. Chin, M.D. Washington, D.C.
Introduction
Although opioids have traditionally been the analgesic of choice for postoperative pain control,
monotherapy using opioid analgesics alone is often inadequate and may be associated with significant
side effects1in addition to morbidity from opioid related respiratory depression2 and opioid abuse3.
Optimal patient care now emphasizes collaborative efforts to improve perioperative experience and
surgical outcomes, as in the Perioperative Surgical Home (PSH).4 Effective perioperative pain control
plays an important and essential role in achieving the desired outcomes in the PSH model. There are
significant efforts to optimize pain control with less opioid requirement and an increasing awareness of
the growing problem with opioid use. “Multimodal analgesia” coined 15 to 20 years ago, refers to the use
of a combination of pharmacologically different analgesics for additive or synergistic effects, in an effort
to optimize the control of postoperative pain.5
This lecture will review the evidence on 1) the current understanding of the pathophysiology of surgical
pain, 2) non opioid analgesics that can be used to optimize postoperative pain control and 3) examine the
impact of multimodal analgesia on patient outcomes.
Nociception, Sensitization and Neuronal Plasticity

Tissue injury and inflammation result in the release of chemical mediators which activate high threshold
nociceptors, A delta and C fibers. With peripheral sensitization the threshold for nociceptor firing is
diminished resulting in amplication of signaling from the periphery. Non noxious stimuli now elicit pain
(allodynia) and a painful stimulus produces an exaggerated pain response (hyperalgesia). The signals
from the periphery enter the central nervous system in dorsal horn of the spinal cord where complex
processing of the signals occur. The nociceptive signals from the periphery are modulated within the
spinal cord and by descending excitatory and inhibitory mechanisms. The result of this complex interplay
is ultimately transmitted to areas in the brain involved with sensory, motor, autonomic and emotional
processing, resulting in the perception of pain. With surgical trauma and continuous nociceptive input
from the periphery, the dorsal horn neurons become more excitable. The receptive field properties of
these neurons expand such that low threshold A beta mechanoreceptors which normally do not produce
painful sensations now do so. These changes ultimately result in a state of hypersensitivity called central
sensitization, in which the nervous system demonstrates an enhanced response to noxious stimulation.6
Tolerance and hyperalgesia

Repeated C fiber stimulation leads to central sensitization and hyperalgesia. The development of
hyperalgesia involves activation of excitatory amino acids which lead to intracellular events and nitric
oxide production. Activation of the mu receptor by opioids ironically also enhances NMDA receptor
activation through similar intracellular events, resulting in reduced potency of the opioid.5 These events
are thought to play a role in the development of tolerance to morphine suggesting that neural mechanisms
leading to hyperalgesia and tolerance both involve NMDA receptor activation.7,8
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Targets for adjuvant analgesics

The main contributors to sensitization and pain include the NMDA receptors, sodium channels, calcium
channels, descending modulation via serotonergic pathways, noradrenergic systems that activate alpha 2
adrenergic receptors, prostaglandins, cytokines and inflammatory mediators.
N-Methyl-D-aspartate (NMDA) receptor antagonists

NMDA receptors are activated by the excitatory neurotransmitter glutamate in the presence of tissue
injury. Consequently, the NMDA receptor plays a major role in pain processing in the spinal cord
whereby receptor activation results in a hyperexcitable state of the nervous system and increased pain.
NMDA antagonists may alleviate pain by the inhibition of central sensitization.9 The NMDA receptor is a
ligand gated ion channel permeable to calcium, potassium and sodium. At resting membrane potential,
the NMDA receptor is blocked by a magnesium ion which is removed on depolarization allowing
glutamate to activate the receptor.10 The NMDA receptor is composed of several subunits. Some of these
subunits are involved with CNS function; therefore an NMDA antagonist may produce undesirable
psychotomimetic effects, memory impairment, ataxia and uncoordinated motor function.9
Ketamine is an anesthetic agent that has been in clinical use for almost five decades. The risk of
unpleasant CNS side effects such as hallucinations has discouraged widespread use of ketamine in
anesthesia. However there is renewed interest in ketamine as an NMDA antagonist in the treatment of
pain, especially with the understanding of the role of the NMDA receptor in neuronal hyperexcitability.
Ketamine is a non-competitive antagonist that binds to the phencyclidine binding site of the NMDA
receptor. It is available in as racemic ketamine which contains equimolar amounts of S (+) and R (-) and
as the S (+) stereoisomer which is twice as potent. The S (+) ketamine has four times greater affinity for
the NMDA receptor than the R (-) ketamine (5Mao). Ketamine has an elimination half-life of 80 to 180
minutes. The metabolite nor-ketamine is one third as potent and has a longer half–life and may contribute
to the prolonged analgesic action of ketamine.10
Providing adequate analgesia for chronic pain patients who are opioid dependent has always been
challenging. The perioperative use of ketamine has been reported to be helpful in these circumstances
despite the lack of well conducted studies. There are several systematic qualitative and quantitative
reviews of randomized trials on the use of ketamine in perioperative pain management.8, 11, 12,13,14,15 The
reviews collectively reported on large numbers of patients worldwide but several criticisms were noted.
In particular, there were large variations in clinical settings, the trials were relatively small, and different
ketamine regimens and various routes of administration were utilized. Most of the studies reported
reduced pain and analgesic consumption immediately and beyond the duration of action of ketamine
when administered in the perioperative period. A small (sub anesthetic) dose of ketamine was noted to be
safe and afforded opioid sparing but the reviews differed on whether opioid related side effects were
decreased. The optimal timing for perioperative administration of ketamine is not clearly defined.
Various dosing regimens have reported effective analgesia with ketamine given in various combinations
of dosing such as preincision, intraoperative, at wound closure and continuing for 48 to 72 hours
postoperatively.16, 17,18,19,20
Recent efforts looking at the perioperative use of ketamine include prospective, randomized, double
blinded trials in patients undergoing total hip arthroplasty in one21 and major spine surgery in the other.22
Both demonstrated reduction in opioid use and decreased opioid consumption in opioid dependent
patients with chronic pain. Pain was decreased at six months in those who received ketamine undergoing
major spine surgery. The opioid dependent patients who underwent spine surgery received an initial dose
of ketamine 0.5 mg/kg at induction followed by 10 mcg/kg/min infusion prior to incision and terminated
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upon closure. The patients for hip arthroplasty did not have a history of high opioid use. They also
received ketamine 0.5 mg/kg at induction followed by an infusion for 24 hours at 2 mcg/kg/min.
An opioid administered by intravenous patient controlled analgesia (IV PCA) may be prescribed in the
postoperative period in addition to ketamine. Although reports on the effectiveness were conflicting 8,14 a
large prospective study of over one thousand patients found the combination of ketamine and morphine in
IV PCA to be safe on the general nursing floor.23 The same study also reported low pain scores and high
patient satisfaction. In a randomized double blinded study, the administration of a small dose of ketamine
at 250 mcg/kg (in addition to morphine), produced immediate and sustained analgesia in those patients
resistant to morphine in the post-anesthesia care unit (PACU).24 Patients who received ketamine reported
better pain scores, a better feeling of well being and wakefulness, higher oxygen saturation. They had
minimal nausea and vomiting or ketamine related side effects.
Memantine is a long acting oral NMDA antagonist which is FDA approved for use in patients with
Alzheimer’s disease. Case reports describe use for chronic pain as in phantom limb pain and opioid
tolerant cancer patients.25, 26, 27
Amantadine, another NMDA antagonist is available for both oral and parenteral delivery. It is primarily
prescribed for Parkinson’s disease, dementia and spasticity. Perioperative use has had mixed results; one
study showed parenteral amantadine to be ineffective in postoperative analgesia27 another reported
decreased postoperative opioid use.29
Dextromethorphan exhibits NMDA receptor antagonist property and a weak affinity for the mu opioid
receptor. It is commonly prescribed as an antitussive agent is associated with few side effects. Clinical
studies indicated that the administration of preoperative oral dextromethorphan resulted in an attenuated
response to tourniquet pain30 and that pre incisional dextromethorphan reduced postoperative morphine
requirements.31 However, a systematic review of the use of dextromethorphan in postoperative pain
control did not report consistent analgesic or opioid sparing effects of the drug.32 The authors were
unable to recommend a dosing regimen for the drug nor could they recommend routine clinical use of
dextromethorphan for postoperative pain control.
Voltage Gated Calcium Channel Blockers

In the postoperative patient, surgical trauma may lead to peripheral and central sensitization resulting in
hyperalgesia and allodynia seen as movement evoked pain. Several recent reviews on the use of
anticonvulsants in the postoperative period report opioid sparing effects, improvement in function and
anxiolysis.33,34,35,36,37,38 Gabapentin and Pregabalin are structural analogs of the inhibitory
neurotransmitter gamma-amino butyric acid (GABA), and both bind to alpha 2 delta subunits of voltage
dependent calcium ion channels to produce antihyperalgesic effects.39,40 A randomized placebo controlled
double blinded study in healthy volunteers showed that gabapentin enhanced the analgesic effect of
morphine.41 Gabapentinoids are known to be effective in reducing acute postoperative pain and opioid
consumption. One recommended dosing regimen would be gabapentin 1200 mg 2 hours before surgery
and 600 mg tid from 1-14 postoperative days and for pregabalin 300 mg preoperatively and 150 mg bid
postoperatively.42 A systematic review of perioperative pregabalin reported decreased pain scores at rest
and with movement and decreased opioid consumption. However pregabalin was associated with a
higher incidence of sedation, dizziness and visual disturbance.43 Further studies however are needed to
identify the anticonvulsant with the best therapeutic profile, the optimal dose and duration of use, the
prevention of persistent surgical pain, and the patient population that would benefit most from this
adjuvant analgesic.
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Serotonin and Norepinephrine

Descending inhibitory pathways in the central nervous system modulate the perception of pain through
actions of serotonin and norepinephrine. Serotonin (5-hydroxytryptamine) is a monoamine
neurotransmitter involved in pain processing. There are several different 5-HT receptor types such that
serotonin can inhibit or facilitate nociceptive transmission. Serotonin and norepinephrine reuptake
inhibitor drugs (SNRI) produce anti nociception and have been used in the treatment of certain chronic
pain states. A systematic review of 15 studies reported insufficient evidence at this time for use of
antidepressants for acute postoperative pain or for prevention of chronic postsurgical pain.44
Voltage Gated Sodium Channel Blockers

Local anesthetics disrupt nerve conduction by blocking voltage gated sodium channels. Several subtypes
of sodium channels (Nav1.7, Nav1.8, Nav1.9) are highly expressed in nociceptors. The TRPV1 (transient
receptor potential vanilloid 1) also found in nociceptors, and is activated by capsaicin followed by influx
of sodium and calcium ions. Lidocaine analogues acting on TRPV1 channels block sodium channels and
may be a future solution to a pain fiber specific block.45 Currently there is ongoing work to develop better
local anesthetics to produce selective prolonged analgesia.46
Lidocaine is a local anesthetic that may be given intravenously. A systematic review of perioperative
intravenous lidocaine reported benefits in abdominal surgery with reduced pain, opioid requirements and
opioid side effects, as well as decreased length of hospital stay.47 There were no beneficial effects were
seen with perioperative intravenous lidocaine in other types of surgery such as hip arthroplasty,
tonsillectomy or coronary bypass surgery.48,49
Continuous use of local anesthetics at the surgical site have shown efficacy in improving analgesia and
reducing opioid use and possibly reducing length of stay in a wide range of surgical procedures.,50,51 An
alternate approach with a single injection of a long acting local anesthetic negating the use of catheters
and pumps is appealing. Liposomal bupivacaine formulated for controlled release of bupivacaine is
currently approved for surgical site infiltration only but clinical efficacy is variable.52,53
Non-Steroidal Anti Inflammatory Drugs (NSAIDS)

Prostaglandins, produced in the periphery in the presence of inflammation and tissue injury, activate
peripheral nociceptors. Spinal neurons may also produce prostaglandins in response to peripheral injury.
COX inhibitors provide analgesia by inhibiting COX mediated production of inflammatory
prostaglandins. Centrally, COX inhibition prevents NMDA and AMPA (alpha amino 3 hydroxy 5 methyl
isoxazolpropionic acid) receptor activation and the development of central sensitization.54
NSAIDS are commonly prescribed in the perioperative period as part of a multimodal approach to
optimize pain control. Ketorolac, the most commonly prescribed parenteral NSAID in the US has shown
efficacy in the immediate postoperative period. A recent meta analysis55 reported better pain control and
less nausea and vomiting with a single dose of ketorolac as an adjunct analgesic. However there is no
uniform consensus on the optimal dose of ketorolac.55, 56,57
Non selective NSAID inhibition of prostaglandins can be associated with serious side effects which
include gastric ulceration, renal dysfunction, and bleeding diathesis. Selective COX 2 inhibitors have
been associated with fewer gastrointestinal side effects compared to the non-selective NSAIDS.
Although there appears to be little difference in analgesic efficacy between the two groups 58 others have
reported improved postoperative analgesia, decreased opioid use and opioid related side effects with
perioperative use of celecoxib.59
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Nonetheless concern for potential risks of surgical bleeding and impaired bone healing generate
controversy regarding the use of both selective and non-selective NSAIDS in the perioperative period.60 A
meta-analysis of several randomized controlled trials showed a higher risk for postoperative bleeding
after tonsillectomy with postoperative use of NSAIDS.61 However, others have disagreed with this
analysis, citing differences in the dosing of the drug, the duration of treatment, poor surgical technique,
and that in some patients, the bleeding occurred at a time when the drug had been eliminated from the
body.62 Spine surgeons are often reluctant to prescribe NSAIDS in the perioperative period because of
concern with impairment in bone healing. Animal and clinical studies suggest that NSAIDS can
potentially inhibit bone formation, healing, and fusion.60 It is thought that COX 2 inhibitors may have an
advantage since this effect has not been substantiated in humans even though evidence from animal
studies suggest impaired bone healing with COX 2 inhibitors.63
Acetaminophen
Acetaminophen, also known as paracetamol, has analgesic and antipyretic properties. Even though the
mechanism of action is largely unknown, it has a known safety profile and is used extensively in pediatric
population. As an adjunct analgesic, intravenous acetaminophen 1g given over 24 hours postoperatively
was effective for moderate to severe pain after orthopedic surgery.64 A meta-analysis of paracetamol,
non-steroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors show a morphine sparing effect
with each group. However, paracetamol may be less efficacious in decreasing morphine requirements but
nsaids are associated with an increased risk of bleeding.65
Alpha 2 agonists
Alpha 2 agonists produce sedation and analgesia with minimal respiratory depression. There are 3
subtypes of alpha 2 adrenoreceptors that mediate the physiologic functions which produce sedation,
analgesia, bradycardia and sympatholysis. The locus ceruleus is the predominant site for sedation and the
spinal cord the main site for analgesia although peripheral and supra spinal sites are described.66
Dexmedetomidine, Clonidine
Clonidine is a less selective alpha 2 agonist compared to dexmedetomidine. It has been prescribed for
analgesia and can be administered in several ways, namely: oral, parenteral, transdermal, neuraxial, by
intra-articular injection or injection around peripheral nerves. Dexmedetomidine, a highly selective alpha
2, has a significantly shorter half life and therefore easily titratable is administered for sedation and
analgesia. Dexmedetomidine infusions using small doses (0.2 or 0.6 mcg/kg/hr) has been shown to
produce easily reversible sedation and analgesia, associated with stable cardio-respiratory function and
therefore potentially useful in the intensive care unit and in the immediate postoperative period.67
A systematic review and meta-analysis looked at the effectiveness of perioperative use of alpha 2 agonists
in almost 1000 out of 1800 patients.68 Patients receiving clonidine or dexmedetomidine reported
decreased postoperative morphine requirement and pain intensity and had less nausea. However long
term effects, i.e. decrease in chronic postoperative pain is unknown.
Corticosteroids
Surgical trauma leads to inflammatory and stress responses and the production of cytokines which include
the interleukins, tumor necrosis factor (TNF) and chemokines all of which contribute to pain.
Corticosteroids inhibit phospholipase as well as cytokines, TNF and other inflammatory mediators and
may be useful in reducing postoperative pain. A meta-analysis reviewed 2500 patients receiving three
different dose range of dexamethasone with respect to opioid requirements and pain control.69
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Dexamethasone greater than 0.1 mg/kg IV decreased postoperative pain and opioid requirement.
However the resultant hyperglycemia from steroid administration and risk of wound infection were not
studied and the implications of these risks remain unclear.70
Outcomes
A Cochrane review on single dose analgesic studies show limitations in providing good pain relief 71and a
systematic review on the combination of two analgesics shows improved analgesic efficacy compared to
either drug alone.72 Using adjuvant analgesics in a multimodal approach has been shown to be beneficial
in the perioperative period by reducing opioid requirement, side effects of nausea and vomiting, early
recovery of bowel function and decrease in pain intensity.58 Some studies have shown pain relief and
facilitation of physical rehabilitation one month out from surgery21 and some show improved pain three
to six months beyond surgery.22,73 The role of ketamine in multimodal analgesia continues to be better
defined with higher quality studies. More information is needed from long-term outcome studies, on the
minimum effective dose, and the side effect profile of the drug. At the present time, there is data to
support that ketamine may be useful as an adjuvant analgesic in the opioid tolerant patient with a history
of chronic pain although this deserves further studies particularly in the long term benefits and reduction
of chronic postoperative pain.74
In a recent prospective study, the implementation of a quality management system (QMS) for the
treatment of postoperative pain demonstrated clear benefits. Multimodal analgesia was individualized
and the staff educated, resulting in better pain control, less analgesia related side effects and increased
patient satisfaction.75
Even so, despite knowledge of pain mechanisms and reported benefits of non-opioid analgesics, pain
control after surgery is often reported to be suboptimal.75 There may be several reasons for this
observation: (a) pain control not targeted to specific surgical procedures76 (b) the lack of consistent use of
multimodal analgesia techniques;78,79 and (c) inconsistent assessment of movement associated pain in
postoperative patients.80,81
Future directions toward improving postoperative pain control include (a) further investigation of the
effect of acute pain and the use of opioid analgesics on the immune system. Acute pain and surgical stress
may compromise immune function including suppression of natural killer (NK) cell activity.
Retrospective analyses by some have reported reduction in cancer recurrence using regional analgesia
82,83
but others found conflicting results suggesting age and tumor type may play a role 84,85 (b) further
investigation into role of preventive analgesia; 86 (c) identifying patients who may be at risk for
developing significant pain after surgery87,79, 88 and (d) the use of pharmacogenomics in tailoring effective
analgesic therapy.79
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11. Schmid et al. Pain 82 (1999) 111-125
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13. Subramaniam et al. Anesth Analg 2004;99:482-95
14. Elia et al. Pain 2005;113:61-70
15. Bell et al. Acta Anaesthesiol Scand 2005;49:1405-28
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17. Bilgin. J Clin Anesthesia 2005,17:592-97
18. Webb et al. Anesth Analg 2007,104(4):912-917
19. Suzuki et al. Anesthesiology 2006;105(1):111-9
20. Lavand'homme et al. Anesthesiology, 2005;103(4):813-820
21. Remerand. Anesth Analg 2009;109:1963-71
22. Loftus. Anesthesiology 2010;113:639-46
23. Svetick et al. Acta Anesthesiol Scand 2005;49:870-875
24. Weinbroum et al. Anesth Analg 2003; 96:789-95
25. Hackworth et al. Anesth Analg 2008;107:1377
26. Wiech et al. Anesth Analg 2004;98:408-13
27. Grande et al. Anesth Analg 2008;107:1380
28. Gottschalk et al. Anesth Analg 2001;93:192-6
29. Snijdelaar et al. Anesthesiology 2004;100:134-41
30. Yamashita et al. Anesth Analg 2004; 98:994-8
31. Helmy et al. Anesth Analg 2001; 92:739-44
32. Duedahl et al. Acta Anaesthsiol Scand 2006; 50:1-13
33. Kong et al. BJA 2007;99:775-86
34. Tippana et al. Anesth Analg 2007;104:1545-56
35. Gilron. Can J Anesth 2006;53:562-71
36. Hurley et al. Reg Anesth and Pain Med 2006; Vol. 31, No.3:237-47
37. Dahl et al. Acta Anaesthsiol Scand 2004;48:1130-36
38. Ho et al. Pain 2006; 126:91-101
39. Mao et al. Anesth Analg 2000;91:680-7
40. Gajraj et al. Anesth Analg 2007;105:1805-15
41. Eckhardt et al. Anesth Analg 2000; 91:185-91
42. Schmidt et al. Anesthesiology 2013;119:1215-1221
43. Mishriky et al. Br J Anaesth 2015;114:10-31
44. Wong et al. Anesthesiology 2014;121:591-608
45. Ilfield et al. RAPM 2009;34:85-87
46. Banerjee et al. Anesth Analg 2015;120:941-949
47. Vigneault et al. Can J Anesth 2011;58:22-37
48. Martin et al. Anesthesiology 2008;109:118-23
49. McCarthy et al. Drugs 2010;70:1149-63
50. Liu et al. J Am Coll Surg 2006;203:914-932
51. Beaussier et al. RAPM 2009;34:393-397
52. Berde. Anesth Analg 2015;120:718-720
53. Ilfeld et al.Anesth Aalg 2013;117:1248-1256
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Airway management for complex tracheal surgery

Paul Alfille MD Boston, Massachusetts
Introduction
Although airway management is central to the practice of anesthesia, the classical focus is above the vocal cords.
The diseased trachea presents a different set of problems. We will review many of the available management
strategies and interventions. There are a variety of techniques for managing the anesthetic, and choosing the best
approach involves understanding the patient’s airway and the planned intervention. These are cases that truly reward
good teamwork and communication.
Airway dynamics
The normal adult trachea is approximately 11cm in length and 2cm in diameter 1. The trachea is a dynamic structure
with the posterior membranous wall able to compress the gas flow in physiological (coughing) and pathological
conditions (tracheomalacia). Flow is normally laminar, and even in the healthy state the majority of airflow
resistance in in the upper generations of the airway, including the trachea.
Air flow resistance is proportional to the 4 th power of the airway diameter (Poiselle’s Law for laminar flow) and at
extreams becomes turbulent. Patients start to become symptomatic as the diameter is constricted below 6mm,
although this will vary with demand and the specific geometry of the pathology. In gradually worsening pathology,
patients learn to subconsciously compensate for their reduced flow. As seen classically in childhood croup, anxiety
and exertion can increase the flow demands, pushing flow into turbulent ranges (and thus higher resistance) as well
as increasing the transluminal pressure gradient causing airway occlusion. A general strategy is to mitigate anxiety
while maintaining respiratory drive.
Interventions
There are an increasing number of airway interventions coming both from the surgical as well as interventional
pulmonology2 disciplines. In general the techniques include ablative therapy to remove an obstruction, and dilation
or stenting to increase diameter.
Ablative therapies
There are a number of methods for removing intraluminal tumor, granulation, or foreign bodies. Laser or
eletrocautery can be used effectively. Clearly there are risks for airway fire, so low F IO2, and avoiding flammable
airway devices are required, as well as a clearly prepared algorithm for managing a fire. 3
Non heat-based techniques, such as forceps, snares, and even the edge of a rigid bronchoscope can be used, and
don’t carry the risk of fire but also can cause airway bleeding. Cryoprobes freeze tissue to the probe, allowing
contact-based removal without risk of fire. There is a technique of using sprayed liquid nitrogen, which is supposed
to destroy pathologic cells while leaving the extracellular scaffolding intact to allow healing. The risk in that case is
the 700-fold increase in volume from evaporation so this technique needs careful monitoring, a large diameter path
of egress, and should not be used distal to any obstruction.4
Dilation and stents
Although ablative therapies are well suited for intraluminal obstructions, there are many situations where the
primary approach of stretching the airway with dilators, or balloon makes more sense. The dilation can break scar
tissue and offer at least a temporarily improved airway caliber. The airway diameter can be maintained with coated
metal or silicone stents. Extrinsic compression is particularly suited to management with a stent.
Resection with reconstruction
Tracheal resection and reconstruction is a definitive solution to limited tracheal disease. The basic surgical technique
is an end-to-end anastomosis, with the limitation healthy tissue, exacting technique and no tension on the
anastomosis. The original anesthetic description was deep inhalation anesthesia with spontaneous ventilation and
cross field ventilation.5 A more modern approach has minor refinements to the surgical technique, initial
bronchoscopic assessment with a laryngeal mask airway total intravenous anesthesia with muscle relaxation if the
exam is encouraging.6 Other techniques have been employed including jet ventilation 7 and spontaneous ventilation
with local anesthesia8.
A similar shift in anesthetic approach has occurred for interventional pulmonology procedures, again with
intravenous anesthesia used for cases where awake techniques are not tolerated. 9
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Special ventilation techniques

Helium
Helium is biologically inert, and has 14% the density of air. Used in a mixture with oxygen of lowers the Reynold’s
number of tracheal flow and keeps flow laminar at lower airway diameter. 10 In clinical practice, Heliox (80%
Helium 20% Oxygen) is an excellent temporizing measure for acute decompensating airway obstruction, until
surgical therapy can be organized. There are even reports of using Heliox as the carrier gas with Sevoflurane for
general anesthesia in these cases.11
Jet ventilation
Jet ventilation finds special application in management of tracheal stenosis. Ventilation can be accomplished with
catheters as small as 2mm in diameter, or even with no catheter but just a well aimed jet above the stenosis.
Ventilation frequency can be varied from conventional rates, to high frequency. Modern automated jet ventilators
have many safety and convenience functions, like the ability to vary F IO2, humidify, and especially, monitor
pressures to ensure proper exhalation. Common modes of jetting include supraglottic (attached to the laryngoscope
for example), transglottic (with a Hunsaker of other catheter) transtracheal (via a catheter puncturing the
cricothyroid membrane) or via a port in the rigid bronchoscope. Because of the entrainment of gas, supraglottic
ventilation is the most effective for delivering a breath, but the least safe in the presence of tracheal stenosis with the
risk of air trapping and barotrauma. 12 Modern jet ventilators can measure the distal pressure when used in
transglottic mode and prevent stacking ventilation until end-expiratory pressure falls to safe levels.
Tracheostomy
If the airway disease is not too distal, and there is no large mass deviating or invading the trachea, a tracheostomy
may well be a safe initial approach to a severely compromised airway. There are challenges, including how well a
stridorous patient can cooperate, and mitigating the risk of airway fire. A tracheostomy can be a permanent device,
or placed to temporize until upper treatment is accomplished. Typically, the tracheostomy will not be coupled with
postoperative ventilator support, and means of allowing speech, like an uncuffed tube, or fenestration should be
considered.
References
1
Breatnach É, Abbot GC, Fraser RG. Dimensions of the Normal Human Trachea. AJR 1984; 141:903-6
2
Wahidi MM, Herth FJF, Ernst A. State of the Art: Interventional Pulmonology. Chest 2007; 131:261–74
3
Akhtar N, Ansar F, et al. Airway fires during surgery: Management and prevention. J Anaesthesiol Clin
Pharmacol. 2016; 32:109–11
4
Browning R, Turner FJ, Parrish S. Spray cryotherapy (SCT): institutional evolution of techniques and clinical
practice from early experience in the treatment of malignant airway disease. J Thorac Dis. 2015; 7: S405-14
5
Geffin B, Bland J, Grillo HC. Anesthetic Management of Tracheal Resection and Reconstruction. Anes Analg
1969; 48:884-94
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Hobai IA, Chhangani SV, Alfille PH. Anesthesia for Tracheal Resection and Reconstruction. Anesthesiol Clin
2012; 30:709-30
7
Adelsmayr E, Keller C, et al. The Laryngeal Mask and High-Frequency Jet Ventilation for Resection of High
Tracheal Stenosis. Anesth Analg 1998; 86:907-8
8
Loizzi, D, Sollitto F, et al. Tracheal Resection With Patient Under Local Anesthesia and Conscious Sedation. Anal
Thor Surg 2013; 95:e63-5
9
Powlowski J. Anesthetic considerations for interventional pulmonary procedures. Cur Op Anaesth 2013; 26:6-12
10
Skrinskas GJ, Hyland RH, Hutcheon MA. Using Helium-Oxygen Mixtures in the Management of Acute Upper
Airway Obstruction. Can Med Assoc J 1983; 128:555-8
11
Tobias JD. Helium Insufflation with Sevoflurane General Anesthesia and Spontaneous Ventilation During Airway
Surgery. Can J Anesth 2009; 56: 243-6
12
Ng A, Russell W, et al. Comparing Methods of Administering High-Frequency Jet Ventilation in a Model of
Tracheal Stenosis. Anesth Analg 2002; 95:764-9
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New Approaches for Cardiopulmonary Monitoring
Javier H Campos, MD Iowa City, Iowa
Introduction
Increased interest in a more proactive use of monitoring technologies has emerged1 and with the increased
number of thoracic surgical patients undergoing minimally invasive thoracic surgery, some of these
patients have multiple associated co-morbidities and low pulmonary function FEV1% and DLCO%
therefore it is important to use appropriate cardiopulmonary monitoring to optimize their intraoperative
anesthetic management while using the indicated technology and monitor to improve outcomes.2
The objective of this discussion will be focused on approaches for cardiopulmonary monitoring in the
thoracic surgical patient, with special attention to: 1) the use of transesophageal Doppler monitoring, 2)
transesophageal echocardiography and 3) monitors for fluid management.
Patients undergoing lung resection are prone to fluid overhydrations and the risk of developing acute lung
injuries. Recently a goal-directed fluid therapy using transesophageal Doppler monitoring has been
shown to improve postoperative clinical outcomes.3 The transesophageal Doppler monitoring allows non-
invasive beat-to-beat measurement of blood flow in the descending aorta, based on direct measurements
of red cell velocity and aortic diameter.4 This simple and reproducible technique has been validated for
cardiac output measurement against thermodilution, the Fick method and electromagnetic flow meters.
Optimization of fluid therapy has been shown to improve clinical outcome and to shorten the hospital
length of stay with the use of transesophageal Doppler monitoring in cardiac and non-cardiac surgery. In
the thoracic surgical patient the use of the Doppler flow profile and aortic measurements might be
difficult to obtain during surgical manipulations and the conversion from two-lung ventilation to one-lung
ventilation. However, some studies have shown a value with this technology.
In a study by Diaper, et al3, transesophageal Doppler monitoring was used to asses fluid and
hemodynamic variables during thoracic surgery. In their observational prospective study, they studied
127 high-risk patients undergoing lung resection. A restrictive fluid strategy was targeted to achieve a
stroke volume index (SVI) ≥ 30 ml/min/m2. SVI, corrected flow time (FTc) maximal acceleration (MA)
and velocity (PV) were recorded during two and one-lung ventilation. Prior to one-lung ventilation, 96
pts had SVI ≥ 30 ml/min/m2 whereas 21 pts had SVI < 30 ml/min/m2 associated with lower FTc values.
However after one-lung ventilation SVI transiently decreased in the group that had normal values (ie > 30
ml/min/m2) whereas in the group with low SVI, SVI increased until the end of surgery while other related
parameters remained unchanged (heart rate and mean arterial pressure). In their study they concluded
that transesophageal Doppler monitor can be used to detect and correct low flow conditions and perhaps
guide hemodynamic support in the intraoperative period. Some of the limitations of the use of
transesophageal Doppler monitor in the thoracic surgical patient includes: the accuracy of the
measurements are highly operator-dependant,5 failure rate is estimated at 10% and it can only be used
mainly in the intraoperative period.
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Another study, comparing measurements of cardiac output as assessed by transesophageal echo-Doppler

and transpulmonary thermodilution in patients undergoing thoracic surgery has been reported.6 In a
prospective, observational study, 16 patients scheduled for elective lung surgery were studied during two-
lung ventilation and one-lung ventilation. Absolute values of cardiac index as measured by both devices
were highly correlated.
Although this study has a very small sample of patients, transesophageal Doppler monitor appears to be
useful and fairly reliable in documenting absolute values and changes in cardiac output. Other derived
Doppler parameters may provide additional useful information regarding circulation volume (correlated
injection time) and ventricular contractility (flow acceleration and peak velocity). As a substitute for a
pulmonary artery catheter, it may help to guide hemodynamic control and fluid management in patients
undergoing lung resetion.6
Use of Transesophageal Echocardiography in Thoracic Surgery
In the last decade, transesophageal echocardiography (TEE) has become an essential component to assess
cardiac function in cardiac surgery. At the present time TEE has also expanded with a limited use in the
thoracic surgical patient.7 Thoracic surgery is naturally becoming an exciting field for the application of
this technology. In many institutions, cardiovascular anesthesiologists who are trained in TEE provide
expertise in thoracic surgery services.8
Right ventricular dysfunction is very common in patients with severe pulmonary disease. TEE allows
prompt diagnosis of right ventricular dysfunction. Right ventricular dysfunction is characterized by an
increase in right atrium pressure, venous stasis, low cardiac output, left ventricular diastolic dysfunction
and decreased left ventricular preload. It can be the result of right ventricular pressure or volume
overload and right ventricular ischemia. The assessment of the right ventricular function with the TEE
includes assessments of the right ventricle morphology and right ventricle systolic function.9
Use of Transesophageal Echocardiogram in Lung Resection Surgery and Pneumonectomy
The vast majority of thoracic surgery involves resection of cancer patients. In video-assisted thorascopic
surgery or lobectomy the TEE is rarely used unless there is an indication for i.e. pulmonary hypertension
or severe cardiac disease (i.e. low rejection fraction). However the use of TEE can be useful in patients
undergoing pneumonectomy in order to assess right ventricular function and hemodynamic management.
Pneumonectomy is a high risk procedure that carries a perioperative mortality rate of 5-15% and a high
morbidity. Fluid management in the pneumonectomy patient has been a topic of interesting discussion
for many years.10 The development of postoperative pulmonary edema greatly increases mortality. The
pulmonary edema can be multifactorial: cardiac overload, barotrauma, large volume of fluid
administration with an impaired right and left ventricle dysfunction. TEE views allow assessing right and
left ventricular function and making therapeutic intervention and progress through TEE assessment.
The use of TEE is very useful to assess right ventricular function during and after pneumonectomy. The
right ventricle can be assessed for wall motion abnormalities, however because of the thin muscular
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compartment, the amplitude of contraction on the right is less evident than on the left making subtle
abnormalities difficult to observe. Akinesia, diffuse hypokinesia or dyskinesia is required to make a clear
diagnosis, and the segments affected are usually described as occurring in the apex, base or free wall.
Moreover, the views of the right ventricular walls are often foreshortened in oblique planes rather than
being on the true axis, thus making the study more complicated.11, 12 This is especially true in the
presence of pathology that can displace the heart such as pulmonary hyperinflation or rotation after
pneumonectomy.
In case of right ventricular volume overload, both its size and shape change. In the long axis, the right
ventricle expands and appears round; whereas in the short axis it becomes oval all the classic crescent
shape is lost. The cardiac apex, normally formed by the left ventricle is now formed by the right
ventricle. The interventricular septum becomes flat and paradoxical motion occurs.12
Use of Transesophageal Echocardiography in Mediastinal Masses
TEE has been successfully used in the diagnosis and management of mediastinal masses: transthoracic
and transesophageal echocardiography is also useful in evaluating the patients with an anterior
mediastinal mass.13, 14 It can not only define the extent of cardiac involvement, if any, but also the
presence of pericardial effusion, impact of the mass on cardiac filling, and any other associated
abnormalities that might impact anesthetic or surgical management. Figure 1 shows transesophageal
echocardiography in mediastinal mass compressing right ventricular outflow tract.14 In addition, during
the anesthetic management as part of the intraoperative care, if an extension of the tumor invades the
great vessels or the heart, an evaluation with intraoperative transesophageal echocardiography is
necessary to rule out the presence of thrombus. Transesophageal echocardiography will also be helpful in
determining if there is any compression to right ventricular outflow tract.
Figure 1. Midesophageal modified right ventricular inflow/outflow view showing the right atrium (RA),
right ventricle (RV), and the right ventricular outflow tract (RVOT), including the pulmonary valve and
pulmonary artery (PA). Panel A illustrates the mediastinal mass (MM) compressing the RVOT and the
PA.
From: Redford DT, Anesth Analg 2006; 103: 578-579 ref (14)
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Fluid Management Monitoring
Fluid management in thoracic surgery is of particular importance because of the influence of one-lung
ventilation. There is some evidence that fluid restriction regimen may be beneficial in thoracic surgery.15
Unfortunately conventional intra-operative monitoring may not predict accurately fluid requirements
since mean arterial pressure is dependent on both cardiac output and systemic vascular resistance it is not
a good indicator of blood flow and thus oxygen delivery. 16 The emphasis for fluid administration should
be on individualized therapy and predicting responders to fluid and minimizing unnecessary fluid
overload. Stroke volume variation and pulse pressure variation have been shown to be such better
predictors of fluid responders then CVP or including PCWP. The limitation of stroke volume variations
or pulse pressure variations can only be utilized in mechanically ventilated patients with adequate tidal
volumes.17 In addition, the patient must be in sinus rhythm. In a fluid depleted patient the effect of an
increase in intrathoracic pressure will cause a greater variation in stroke volume with high stroke volume
variation due to the greater effect on venous return. However, as fluid boluses are administered and the
patient becomes fluid repleted, the stroke volume variation falls and by the time is around 5-10% the
patient is considered fluid optimized. Further administration at this stage is less likely to produce an
increase in stroke volume thus maintaining stroke volume variation at the 5-10% levels ensures
optimization of stroke volume whilst at the same time reducing the risk of fluid overload.
A new stroke volume variation (SVV) and cardiac output monitoring device, the Vigileo-FloTrac system
is based on arterial pulse contour and does not require external calibration, thermodilution or dye dilution;
therefore it offers the possibility of almost beat-to-beat measurements of cardiac output and SVV. Goal
directed fluid optimization based on SVV and cardiac index during one-lung ventilation in patients
undergoing thoracoscopic lobectomy surgery has been reported.18 Eighty patients undergoing thorascopic
surgery were randomized to a goal-directed group the SVV was controlled to a 10%±1% and cardiac
index at minimum of 2.5 L•mim-m2. In contrast in the control group, the mean arterial pressure was
maintained between 65mmHg and 90mmhg and a heart rate between 60-100 bpm. This study showed
that the PaO2/FiO2 ratio before the end of one-lung ventilation in the goal directed therapy group was
significantly higher when compared to the control group; extubation times were earlier. This study
demonstrated that an optimization protocol based on SVV and cardiac index obtained with the Flo
Trac/Vigileo device reduced fluid overload administration. Another study using SVV in thoracic surgical
patients undergoing one-lung ventilation also showed favorable results and did not result in pulmonary
fluid overload.19
Conclusion
With the increase number of patients requiring thoracic surgery, it is important to use the proper
minimally invasive monitors in patients with compromised lung and cardiac function particularly when
the surgical approach is by minimally invasive thoracic surgery particularly in the severely compromised
patient.
The SVV and cardiac index monitor devices although useful for the thoracic surgical patient will require
further studies to determine their specific uses because of the limited scientific evidence. It is also
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important to consider other factors that affect the outcomes in the thoracic surgical patients such as a
recent study that has shown that low tidal volume in the presence of low positive-end expiratory pressure
is associated with increased pulmonary complications.20
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References
1. García X, Pinsky MR: Clinical applicability of functional hemodynamic monitoring. Ann Intensive
Care 2011;1:35
2. Cerfolio RJ, Bryant AS: Does minimally invasive thoracic surgery warrant fast tracking of thoracic
surgical patients? Thorac Surg Clin 2008;18:301-304
3. Diaper J, Ellenberger C, Villiger Y, Robert J, et al: Transoesophageal Doppler monitoring for fluid
and hemodynamic treatment during lung surgery. J Clin Monit Comput 2008;22:367-374
4. Cholley BP, Singer M: Esophageal Doppler: noninvasive cardiac output monitor. Echocardiography.
2003;20:763-769
5. Hofer CK, Rex S, Ganter MT: Update on minimally invasive hemodynamic monitoring in thoracic
anesthesia. Curr Opin Anaesthesiol 2014;27:28-35
6. Diaper J, Ellenberger C, Villiger Y, Robert J: Comparison of cardiac output as assessed by
transesophageal echo-Doppler and transpulmonary thermodilution in patients undergoing thoracic
surgery. J Clin Anesth 2010;22:97-103
7. Sullivan B, Puskas F, Fernandez-Bustamante A: Transesophageal echocardiography in noncardiac
thoracic surgery. Anesthesiol Clin 2012;30:657-669
8. Meineri, M: Intraoperative transesophageal echocardiography in thoracic surgery. Chapter 20. PP.
Slinger (ed.), Principles and Practice of Anesthesia for Thoracic Surgery. 2011 pp 277-296
9. Haddad F, Doyle R, Murphy DJ, Hunt SA: Right ventricular function in cardiovascular disease, part
II: pathophysiology, clinical importance, and management of right ventricular failure. Circulation
2008;117:1717-1731
10. Slinger P: Update on anesthetic management for pneumonectomy. Curr Opin Anaesthesiol
2009;22:31-37
11. Smulders SA, Holverda S, Vonk-Noordegraaf A: Cardiac function and position more than 5 years
after pneumonectomy. Ann Thorac Surg 2007;83:1986-1992
12. Pedoto A, Amar D: Right heart function in thoracic surgery: role of echocardiography. Curr Opin
Anaesthesiol 2009;22:44-49
13. Campos JH, Managing the Patient with an Anterior Mediastinal Mass in Medically Challenging
Patients Undergoing Cardiothoracic Surgery. Ed. Neal H. Cohen. Society of Cardiovascular
Anesthesiologists Monograph 2009, Chapter 11: pp 285-302
14. Redford DT, Kim AS, Barber BJ, et al: Transesophageal echocardiography for the intraoperative
evaluation of a large anterior mediastinal mass. Anesth Analg 2006;103:578-579.
15. Brandstrup B, Tønnesen H, Beier-Holgersen R: Effects of intravenous fluid restriction on
postoperative complications: comparison of two perioperative fluid regimens: a randomized assessor-
blinded multicenter trial. Ann Surg 2003;238:641-648
16. Green D, Paklet L: Latest developments in peri-operative monitoring of the high-risk major surgery
patient. Int J Surg 2010;8:90-99
17. Renner J, Cavus E, Meybohm P: Stroke volume variation during hemorrhage and after fluid loading:
impact of different tidal volumes. Acta Anaesthesiol Scand 2007;51:538-544
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18. Zhang J, Chen CQ, Lei XZ: Goal-directed fluid optimization based on stroke volume variation and
cardiac index during one-lung ventilation in patients undergoing thoracoscopy lobectomy operations:
a pilot study. Clinics 2013;68:1065-1070
19. Haas S1, Eichhorn V, Hasbach T: Goal-directed fluid therapy using stroke volume variation does not
result in pulmonary fluid overload in thoracic surgery requiring one-lung ventilation. Crit Care Res
Pract 2012; 1-8
20. Blank RS, Colquhoun DA, Durieux ME: Management of One-lung Ventilation: Impact of Tidal
Volume on Complications after Thoracic Surgery. Anesthesiology 2016;124:1286-95
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The Patient with Cardiovascular Disease for Thoracic Surgery
Paul M. Heerdt, MD, PhD New Haven, CT
Evolution of the thoracic surgical population
The spectrum and severity of comorbidity in patients presenting for thoracic surgery has increased remarkably. Even
for major procedures such as esophagectomy, many patients considered relatively routine today would not have
been considered surgical candidates 20 years ago. This is particularly true for those with cardiovascular disease, in
large measure due to several factors:
a. An aging population: Over half of all newly diagnosed lung cancers are in patients > 65 years of age, and
the median age for patients undergoing lung resection is > 70 years (1). Cancer screening procedures have
been expanded to older age groups; survival has improved significantly with increasingly aggressive
treatment in the 75-84 age group, with benefits similar in females between 55-74 and 75-84 years old (2).
Some data indicate that although short-term surgical complication rates are higher, elderly patients may
have a better oncological outcome (3), justifying the risk.
b. Widespread use of percutaneous coronary interventions: Early and aggressive deployment of stents may
lessen risk of MI, but present the risks associated with antiplatelet therapy.
c. Improved monitoring and postoperative care: minimally and non-invasive technologies tend to make
clinicians feel more comfortable managing complex patients; true outcome benefit remains unclear. Access
to step-down or ICU care postoperatively often imparts a greater tolerance for operative risk.
d. Minimally invasive techniques: the widespread belief by many that VATS imparts less cardiovascular
stress.
Ultimately, while in the past cardiovascular disease in an elective thoracic surgical patient would generally have
meant rate-controlled atrial fibrillation, stable CAD, or modest and well-managed valve disease, today’s patients are
presenting with ischemic heart disease and recent stent placement, significant valve dysfunction (why have heart
surgery if I have lung cancer?), ischemic or dilated myopathy with an ICD or LVAD, and moderate to severe – and
sometimes occult - pulmonary hypertension.
Current considerations
Overall, the literature contains several reports regarding outcome for thoracic surgical patients with coronary stents
as well as approaches to management of anti-platelet therapy (4-6). In the past, patients have undergone
simultaneous lung resection and valve replacement without major complications (7). While still an option for severe
disease with co-existing heart failure, concerns have been raised about the potential for cardiopulmonary bypass to
increase the risk of cancer progression (8), a factor some patients take into account when considering the risk of lung
resection alone. Patients with reduced left ventricular ejection fraction and an ICD have become commonplace for
surgery in general, with suitability for ambulatory surgery discussed (9). Even those with severe cardiomyopathy
requiring LVAD have been deemed suitable candidates for lung resection (10,11).
Risk stratification indices for thoracic surgical patients have been devised and include consideration of renal
function, history of coronary artery disease or congestive heart failure, history/presence of cerebrovascular disease,
and extent of operation (12). While of some demonstrated value, aspects of the current thoracic surgical population
such as pulmonary hypertension but no history of heart failure are not accounted for.
Pulmonary hypertension
Pulmonary hypertension is actually a symptom of a disease spectrum that can result from pathology in both the
pulmonary arterial and venous circulations (see The World Health Organization (WHO) clinical classification of
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pulmonary hypertension (13)). Due to the ease of transthoracic echocardiography, it is commonly used to estimate
pulmonary arterial systolic pressure (PASP) as a screening tool for pulmonary hypertension. However, while
echocardiographic PASP > 45 mmHg is quite specific, it is relatively insensitive and cannot provide the accurate
mPAP measurement needed for definitive diagnosis (13). With right heart catheterization, severity of pulmonary
hypertension based upon measurements obtained at rest is characterized as mild (mPAP = 25-40 mmHg), moderate
(mPAP = 41-55 mmHg), or severe (mPAP >55 mmHg). Pulmonary hypertension can recreate some unique
physiological challenges intraoperatively, and when all etiologies are considered, prevalence in the surgical
population is probably substantial (13). Echocardiographic estimates of PASP indicated that 25% of the residents in
a Minnesota county had an PASP > 30 mmHg, with the magnitude age-dependent. Using an estimated PASP
threshold of 40 mmHg, 9.1% of over 10,000 residents in Western Australia were found to have pulmonary
hypertension, primarily related to left heart disease.
Occult pulmonary hypertension secondary to lung disease and/or hypoxia (WHO Group 3) may represent a
particular concern for thoracic surgical patients since it includes obesity-related disease. Roughly ~60% of the US
population is overweight or frankly obese, and it is estimated that pulmonary hypertension is present in 20% of those
with obesity-related obstructive sleep apnea and 50% with obesity hypoventilation syndrome (14).
It is important to consider that the specifics of many non-cardiac thoracic procedures may not be known to
physicians providing preoperative clearance. The ACC/AHA guidelines defining high-risk take on a somewhat
different connotation for patients with pulmonary hypertension. In the thoracic surgical population, “minimally
invasive” requires particular consideration; laparoscopic esophageal procedures produce elevations in venous and/or
airway pressure, and VATS procedures require single lung ventilation (hypoxic pulmonary vasoconstriction) with
eventual loss of pulmonary vascular volume. For patients with severe pulmonary hypertension requiring vasodilator
therapy, the potential influence on hypoxic pulmonary vasoconstriction during single lung ventilation is often not on
the radar.
Overall, published data demonstrate an increased perioperative risk for patients with pulmonary hypertension (13).
However, study results need to be interpreted in the context of disease etiology and diagnosis. In one study using
echocardiographic estimation of PASP, even with a mean preoperative value of 47 mmHg, the authors concluded
that lobectomy can be performed safely in selected patients, with complication rates comparable to those
experienced by patients without pulmonary hypertension (15).
References
1. Heerdt PM1, Park BJ. The emerging role of minimally invasive surgical techniques for the treatment of
lung malignancy in the elderly. Thorac Surg Clin. 2009;19(3):345-51.
2. Varlotto JM, Decamp MM, Flickinger JC, et al Would screening for lung cancer benefit 75- to 84-year-old
residents of the United States? Front Oncol. 2014;4:37.
3. Liu HC, Huang WC, Wu CL, Huang JT, Chen CH, Chen YJ Surgery for elderly lung cancer Ann Thorac
Cardiovasc Surg. 2013;19(6):416-22.
4. Cerfolio RJ, Minnich DJ, Bryant AS. General thoracic surgery is safe in patients taking clopidogrel
(Plavix). J Thorac Cardiovasc Surg. 2010;140(5):970-6
5. Brichon PY, Boitet P, Dujon A, Mouroux J, Peillon C, Riquet M, Velly JF, Ris HB.Perioperative in-stent
thrombosis after lung resection performed within 3 months of coronary stenting Eur J Cardiothorac Surg.
2006;30(5):793-6
6. Fernandez FG, Crabtree TD, Liu J, Meyers BF. Incremental risk of prior coronary arterial stents for
pulmonary resection. Ann Thorac Surg. 2013;95(4):1212-8
7. Danton MH, Anikin VA, McManus KG, McGuigan JA, Campalani G.Simultaneous cardiac surgery with
pulmonary resection: presentation of series and review of literature. Eur J Cardiothorac Surg.
1998;13(6):667-72.
8. Pinto CA, Marcella S, August DA, Holland B, Kostis JB, Demissie K. Cardiopulmonary bypass has a
modest association with cancer progression: a retrospective cohort study BMC Cancer 2013;13:519
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9. Joshi GP. Perioperative management of outpatients with implantable cardioverter defibrillators. Curr Opin
Anaesthesiol. 2009;22(6):701-4
10. Wei B, Takayama H, Bacchetta MD Pulmonary lobectomy in a patient with a left ventricular assist device.
Ann Thorac Surg. 2009;87(6):1934-6
11. Murakawa T, Murayama T, Nakajima J, Ono M. Lung lobectomy in a patient with an implantable left
ventricular assist device. Interact Cardiovasc Thorac Surg. 2011;13(6):676-8
12. Brunelli A, Ferguson MK, Salati M, Vigneswaran WT, Jimenez MF, Varela G Thoracic Revised Cardiac
Risk Index Is Associated With Prognosis After Resection for Stage I Lung Cancer Ann Thorac Surg.
2015;100(1):195-200.
13. McGlothlin D, Ivascu N, Heerdt PM Anesthesia and pulmonary hypertension Prog Cardiovasc Dis.
2012;55(2):199-217
14. Friedman SE, Andrus BW. Obesity and pulmonary hypertension: a review of pathophysiologic
mechanisms. J Obes. 2012;2012:505274.
15. Wei B, D'Amico T, Samad Z, Hasan R, Berry MF. The impact of pulmonary hypertension on morbidity
and mortality following major lung resection. Eur J Cardiothorac Surg. 2014;45(6):1028-33
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How Should I Manage My Patient's Pain During Thoracic Surgery?
Edward A. Ochroch, M.D.,MSCE. Merion Station, PA
Pain from thoracic surgery can be intense and prolonged in duration. After open posterolateral or
vertical muscle sparing incisions patients with epidural analgesia as well as NSAID therapy
reported pain of 5-6/10 while coughing and ~3/10 average pain over the last 24 hours (current
pain during the interview was 2.3/10 and underestimated the pain experience). 4 weeks after the
operation their pain experience was only marginally changed with 4/10 pain while coughing and
2.3/10 average pain. 26% of the patients reported ongoing pain from the incision at 48 weeks.1
Approximately 50% of pain reports indicate neuropathic type pain with burning and dysesthesia
probably originating from intercostal nerve damage. The rest of patients indicate somatic pain.
Video assisted thoracic surgery (VATS) and robotic assisted thoracic surgery hold the hope of
reducing pain, morbidity and mortality while producing at least as efficacious oncologic results.
A recent randomized study comparing open anterolateral thoracotomy to VATS, with all subjects
getting epidural analgesia, shows less short-term and long-term pain after VATS, but no
differences in morbidity and mortality. Quality of life (QOL) functional and performance
measures did not differ.2 However, only 103 subjects were in each arm and larger studies may
indicate whether QOL or other differences also occur. Recently introduced “wristed” robotic
instruments hold out hope for even less risk of intercostal nerve irritation due to decreased risk of
pressure against the rib. Currently there are no data examining this effect of the new robotic
instruments. Otherwise, robotic and VATS result in similar pain profiles.
Long term pain can cause suffering, decreased QOL, increased expense and inhibit return to
work. In-hospital pain can increase the risk of postoperative pulmonary and cardiac
complications. Patients recovering from thoracic surgery are at great risk of pulmonary
complications due to native lung disease, the inhibition of muco-cilliary clearance from
anesthesia/intubation/surgical resection, atelectasis, and pain. Thus analgesic regimens must be
optimized to allow aggressive pulmonary toilet without undue impact of pain and stress on the
cardiovascular system.
Epidural analgesia remains the gold standard for pain relief after thoracotomy. The typical
intrathoracic incision is in the 4th thoracic interspace to facilitate access to the hilum of the lung.
The chest tube typically exits through the 8th interspace. Thus an epidural place in one of
intervening interspaces can cover all of the somatic pain efferents. Most regimens focus on
bupivacaine with typical concentrations of 1 to 0.5 mg/ml (0.1% - 0.05%). No opioid has been
shown to be superior with excellent results obtained with fentanyl 2-5mcg/ml, hydromorphone
10-20 mcg/ml and sufentanil 0.2-1 mcg/ml. Recent work in obstetrical anesthesia suggests
intermittent bolus rather than continuous infusion may provide superior analgesia, but has yet to
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be studied. Adjunct epidural medications such as alpha-2 agonists, ketamine, and neostigmine
may be beneficial, but no conclusive data are available.
Paravertebral catheters placed with ultrasound guidance are at least equal in efficacy to epidural
and probably have less morbidity – less hypotension and urinary retention. There also seems to
be equal efficacy of surgeons placing the paravertebral catheter intra-thoracically and
externalizing the catheter, although randomized data for this approach do not exist. While some
studies placed catheters at T8 and T4, most studies place a multilumen catheter somewhere in
between. Paravertebral catheter infusions should only contain local anesthetics as there seems to
be no advantage when opioids are included, and this probably accounts for lower rates of urinary
retention. Due to greatly reduced risk of hypotension higher concentrations of bupivacaine are
typically used 1 to 2.5 mg/ml ( 0.1% – 0.25 %). Similar to epidurals, studies on intermittent
bolus vs constant infusion need to occur. Much of the published literature on clonidine as an
adjunct to paravertebral infusions comes from breast surgery and may not be applicable.
Exparel (liposomal bupivacaine) has been used for multilevel intercostal block. These are
typically done by the surgeon during open or VATS surgery. Exparel is not labeled for nerve
block. An analysis of the phase1-3 trials indicates that for femoral and ankle block the safety
profile is similar to plain bupivacaine with longer pain relief.3 Although potentially very
promising, no prospective data that compares multilevel intercostal blocks or paravertebral block
with Exparel have been published. There has been no accumulation of data on side effects or
blood levels of bupivacaine for paravertebral or intercostal blocks. The closest animal data
comes from dogs receiving brachial plexus blocks. Bupivacaine blood levels were less in Exparel
treated dogs than those receiving plain bupivacaine. The only Exparel-related effect seen was
“minimal to mild granulomatous inflammation of adipose tissue around nerve roots (8 of 24
rabbits and 7 of 24 dogs) in the brachial plexus sites.”4
Enhanced recovery after surgery regimens attempt to accelerate recovery by inhibiting the stress
response so that the duration of hospital stay and possibly the occurrence of postoperative
complications and mortality can be reduced, with the added benefit of reducing healthcare costs.
Currently there are no published thoracic surgery protocols. Preemptive gabapentin does not
decrease the rate of ipsilateral shoulder pain.5 Preemptive ketamine does not seem to affect post-
thoracotomy pain levels.6 NSAIDs are of significant benefit, particularly in treating ipsilateral
shoulder pain. Acetomenophen is a minor analgesic adjunct. Part of the goal in colon resection
ERAS protocols is to reduce opioid side effects. It is unclear if such side-effects are important
factors limiting recovery and discharge in thoracic surgery patients.
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References
1) Ochroch, E. Andrew, et al. "Long-term pain and activity during recovery from major
thoracotomy using thoracic epidural analgesia." The Journal of the American Society of
Anesthesiologists 97.5 (2002): 1234-1244.
2) Bendixen, M., Jørgensen, O. D., Kronborg, C., Andersen, C., & Licht, P. B. (2016).
Postoperative pain and quality of life after lobectomy via video-assisted thoracoscopic
surgery or anterolateral thoracotomy for early stage lung cancer: a randomised controlled
trial. The Lancet Oncology.
3) Ilfeld, Brian M., et al. "Safety and Side Effect Profile of Liposome Bupivacaine (Exparel)
in Peripheral Nerve Blocks." Regional anesthesia and pain medicine 40.5 (2015): 572-
582.
4) Richard, Brigitte M., et al. "The safety of EXPAREL®(bupivacaine liposome injectable
suspension) administered by peripheral nerve block in rabbits and dogs." Journal of drug
delivery 2012 (2012).
5) Huot, Marie-Pierre, et al. "Gabapentin does not reduce post-thoracotomy shoulder pain: a
randomized, double-blind placebo-controlled study."Canadian Journal of
Anesthesia 55.6 (2008): 337-343.
6) Dualé, Christian, et al. "Perioperative ketamine does not prevent chronic pain after
thoracotomy." European Journal of Pain 13.5 (2009): 497-505.
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New Approaches to Optimize Patient Outcomes in Thoracic Anesthesia – Prehabilitation

and Enhanced Recovery
Marcos F. Vidal Melo Boston,MA
Introduction
Surgical resection is an essential component of the treatment of patients with lung cancer.
Thoracic surgery and anesthesia are associated with a high incidence of cardiopulmonary and surgical
complications. This elevated complication rate derives from the complexity of surgical interventions and
the multiple comorbidities observed in patients with lung cancer. Consequently, it is essential to advance
approaches to optimize patient outcomes. Two of the ongoing advancements in the field are preoperative
rehabilitation and protocols for enhanced recovery.
Enhanced Recovery After Surgery (ERAS)

The concept of Enhanced Recovery After Surgery (ERAS) was introduced approximately twenty
years ago to expedite patient recovery and reduce hospital length of stay1,2. The approach uses a
combination of interventions aiming at minimizing the perioperative stress response, optimizing fluid
status, improving pain control, and encouraging early mobility. These interventions are expected to
reduce perioperative complications, improve patient outcomes, promote use of best practices, and
encourage the application of evidence-based innovations in care delivery. Ultimately, the approach aims
to focus surgical care on safely returning patients to their full functional status in the least amount of
time.
While to date most of the strategies were developed for abdominal and pelvic surgery, there is
increasing interest in implementing such strategies in thoracic anesthesia and surgery. Expectations are,
for instance, that patients undergoing a lobectomy would be able to return home the day after surgery.
Enhanced Recovery After Surgery in Thoracic Anesthesia and Surgery

Enhanced recovery protocols aimed at patients undergoing esophagectomy and lung resection
surgery have been developed and preliminarily show encouraging results measured as lower incidence
of postoperative pulmonary complications 3-5, and decreased morbidity, mortality and length of stay2, 6, 7.
Essential components of ERAS protocols include preoperative counseling, optimization of nutrition and
hydration, standardized analgesic and anesthetic regimens, and early mobilization. Specific focus on the
preoperative phase as a period of opportunity to optimize patients before the surgical insult has been
increasing, and interventions targeting that period are integral to ERAS protocols. Considering that most
patients have a diagnosis of cancer, they are especially prone to physical deconditioning, nutritional
deficiencies, anxiety and depression. Accordingly, patient education aimed at setting expectations and
providing counseling is an integral component of the preoperative procedures. Dietary interventions
have been varied and target avoidance of a catabolic state and optimization of immunological response
and healing in the perioperative period. Immediately preoperatively, this goal has been targeted with
carbohydrate loading and minimization of the time spent NPO. In the weeks preceding surgery,
Refresher Course Lectures Anesthesiology 2016 © American Society of Anesthesiologists. All rights reserved. Note: This publication
contains material copyrighted by others. Individual refresher course lectures are reprinted by ASA with permission. Reprinting or using
individual refresher course lectures contained herein is strictly prohibited without permission from the authors/copyright holders.
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interventions involving concepts such as immunonutrition have been implemented with beneficial
effects8.
Pain management is a critical component in the management of patients undergoing thoracic
surgery9. ERAS protocols have implemented various pain management strategies including patient
controlled epidural analgesia3, 4, paravertebral block with and without supplemental analgesia with a non-
steroidal anti-inflammatory drug10, multimodal approaches including preoperative preemptive analgesia,
intraoperative infiltration of local anesthetic agents at surgical sites, short acting intravenous analgesia
intraoperatively as well as in the immediate postoperative period, and scheduled non-narcotic analgesia
and PRN oral narcotic administration5.
Early ambulation is understood as one of the most critical elements of successful early
recovery11, sometimes cited as the only element to date to show a definite association with better
outcomes12. Following thoracic surgery, it has been successfully achieved in patients undergoing open
lobectomies3. Presumably, this is due to improvement in lung expansion and bronchopulmonary
hygiene. Optimal pain management will be key to achieving early ambulation. Accordingly, the
managing team should be invested in this goal, and patient preparation/education and management
should target it.
Robotic-assisted thoracic surgery has been advanced as a method to minimize surgical
complications and expedite patient recovery. Given current costs associated with this new technology
and the necessary period required for achieving expert performance, final conclusions have not yet been
reached. Besides the increased costs associated with the surgical procedure in itself, substantial
acquisition and maintenance costs are present13.When this is combined with the limited availability of
high-quality clinical evidence of its advantage as compared to traditional video-assisted thoracic surgery
for lobectomies and wedge resections, questions are raised about the cost-effectiveness of that
technology13. Finally, robotic surgery usually requires a specialized surgical team and additional
surgeon, generally not required for standard video-assisted thoracic surgery procedures. Such additional
costs should also be considered in final decision making on its implementation.
Information technology tools are increasingly used to implement and advance ERAS and
prehabilitation protocols14. An important consideration in any such clinical decision support system is to
deliver information with the “five rights”: the right information to the right person in the right format
through the right channel at the right time15. There is significant variability in the components of ERAS
protocols and in the compliance to them16. Information technology tools may play an essential role in
reducing variability of protocols and increase compliance of patients and health care providers,
ultimately optimizing outcomes. Whatever the system, its major priority should be to foster patient
safety and quality improvement14.
Preoperative Rehabilitation (Prehab)
Introduction
There is increasing interest in prehabilitation to improve outcomes in patients with cancer treated
clinically or surgically17-19. Broadly speaking, prehabilitation in this setting has been defined as “a
process on the continuum of care that occurs between the time of cancer diagnosis and the beginning of
acute treatment, includes physical and psychological assessments that establish a baseline functional
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level, identifies impairments, and provides targeted interventions that improve a patient’s health to
reduce the incidence and the severity of current and future impairments”17. The expectation is that
patient success in promptly achieving the highest level of function postoperatively is directly related to
their preoperative functional status.
Exercise modulates organ function, inflammation and immune response in normal and disease
conditions18. Specifically related to pulmonary function, basic science studies suggest a number of
beneficial effects related to exercise. Moderate exercise for several weeks has been found to improve the
cardiopulmonary, oxidative metabolism and inflammatory responses to sepsis and acute lung injury20-22.
Wistar rats performing two months of exercise and then subjected to intratracheal endotoxin showed
maintenance of energy metabolism in lung tissue (no decrease in succinate dehydrogenase and complex
II activities) and less formation of pulmonary edema as compared to non-exercising rats. Exercise also
partially prevented the increase in respiratory system resistance. Acute neutrophilic inflammation is a
hallmark of acute lung injury and the adult respiratory distress syndrome (ARDS). Indeed, this may
occur before signs of density changes are detectable23. Septic mice receiving regular and moderate
exercise for 8 weeks as compared to sedentary mice showed improved survival, higher static lung
compliance, less alveolar collapse, less collagen and elastic fiber content, lower number of neutrophils
in the bronchoalveolar and peritoneal lavage fluids, and plasma; less lung and distal organ cell
apoptosis; and increased anti-inflammatory biomarkers (IL-10) in the bronchoalveolar lavage fluid and
plasma, with reduced markers of inflammation (IL-6, KC, and IL-1) in the peritoneal lavage fluid20.
Interestingly, exercise of short duration and moderate intensity in the presence of acute lung injury (i.e.,
two days after instillation of endotoxin in mice lungs) also resulted in benefits: attenuation of muscle
ring finger 1 (MuRF1)–mediated atrophy of the limb and respiratory muscles and improvement of limb
muscle force generation. Importantly, exercise limited the influx of neutrophils into the alveolar space
through modulation of a coordinated systemic neutrophil chemokine response involving the granulocyte
colony-stimulating factor (G-CSF)22. All of these findings support a favorable effect of exercise in
optimizing pulmonary and systemic outcomes during and after surgery.
Preoperative Rehabilitation in Thoracic Anesthesia and Surgery

Lung cancer is one of the most frequent and most lethal types of cancer24, and is among the
conditions leading to the largest number of years of life lost due to premature mortality in the US25.
Complete surgical resection is the only curative treatment for lung cancer. Modern surgical treatment
includes both minimally invasive surgery, e.g. video-assisted and robotic-assisted thoracoscopic surgery,
and open surgery such as thoracotomy.
Postoperative cardiopulmonary complications are experienced by more than 25% of patients
undergoing lung resection even when modern less invasive and robotic techniques are used13, 26. The risk
of developing postoperative complications during the first two weeks after surgery is increased by poor
preoperative cardiorespiratory capacity, as measured by peak maximal oxygen consumption
(VO2peak)24, 27. The physiological consequences of aging and inactivity combined with the sequelae of
cancer and its treatment result in a marked reduction in VO2peak and functional capacity28-30. Other
factors such as smoking31, alcohol consumption32, nutritional status33 and comorbidities34 are also
predictors of postoperative complications.
Many patients with lung cancer are significantly deconditioned and present a number of co-
morbidities which increase their risk of postoperative complications, up to an extreme of being
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considered inoperable. After surgery for stage I-IIIa non-small cell lung cancer, a substantial fraction of
patients (15%) are admitted to a nursing home or die by 1 year after surgery. A large fraction of patients
have severe functional impairment following surgery, up to approximately 50% depending on age,
disease stage and comorbidities35. Poor preoperative fitness is associated with an increased risk of
postoperative morbidity and mortality after major anatomic pulmonary resection36, 37. A systematic
review indicates that exercise in patients with a variety of cancer diagnoses may have beneficial effects
on health related quality of life indicators38. Physiotherapy may mitigate systemic inflammation and
bolster immune function, improving immune clearance of residual tumor and increasing overall and
progression-free survival39, 40.
Accordingly, improvement in preoperative predominantly aerobic function has been sought as an
intervention to enhance patients’ perioperative performance. Intense physical therapy composed by chest
physiotherapy and walking exercise in a study with a small number of patients classified as eligible for
lung cancer surgery resulted in significantly reduced hospital stay and postoperative morbidity, and
improved preoperative spirometric parameters, PaO2, carbon monoxide diffusing capacity, and perfusion
distribution to the contralateral (non-affected) lung41. After lung resection surgery, preoperative
physiotherapy has been reported to improve exercise capacity and preserve pulmonary function42-45.
Pulmonary rehabilitation has been advanced as an intervention that improves exercise capacity,
reduces dyspnea45 and contributes as adjunctive preoperative therapy to decrease the risk of
postoperative pulmonary complications42. Patients receiving specific inspiratory muscle training and
incentive spirometry (1 hour/day, 6x/week, for 2 weeks before and 3 months after lung resection)
showed significant increases in inspiratory muscle strength both before and 3 months after surgery46.
These patients achieved a postoperative forced expired volume in 1 second (FEV1) substantialy higher
than their predicted FEV1 both after lobectomies and pneumonectomies.
The targeted populations differ between studies. For example, Benzo et al.44 focused on patients
with moderate-severe obstructive pulmonary disease (COPD) scheduled for lung resection. The authors
implemented ten preoperative customized prehabilitation sessions including exercise based on self
efficacy, inspiratory muscle training, and practice of slow breathing. In a small group of patients (n=10),
those interventions shortened length of hospital stay by 3 days, and reduced the fraction of prolonged
chest tubes (11% vs. 63%) and of days needing a chest tube (8.8 vs. 4.3 days) compared to controls.
These results reinforce the concept that short term preoperative pulmonary rehabilitation could be
achieved in patients with moderate-severe COPD undergoing curative lung resection. Another study also
addressing COPD patients supported such benefits. In this investigation, preoperative exercise, incentive
spirometry, breathing and coughing exercises with bronchodilators combined with postoperative
rehabilitation lead to reduced length of stay, and need for tracheostomy and prolonged oxygen inhalation
in patients receiving prehabilitation47.
An advanced application of prehabilitation principles has been pursued by Divisi et al48. These
authors used prehabilitation to convert COPD patients initially ineligible for lung cancer resection into
eligible patients48. This is particularly relevant considering that impaired cardiopulmonary reserve is a
major factor for inoperability in non-small-cell lung cancer. Patients in this study underwent an intense
program of prehabilitation including daily 50 min of respiratory physiotherapy and 40 min of aerobic
work under electrocardiographic control, 6 days a week for 4-6 weeks. Respiratory physiotherapy
included breathing exercises (20 min, intermittent positive pressure); inspiratory muscle training (20
min); and postural drainage (10 min). Aerobic training was implemented with a cycle ergometer (20
min) and walking (20 min). Medication and diet management, and smoking cessation support were also
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provided. Improved PaO2 (60 ± 10 to 82 ± 12 mmHg), VO2max (12.9 ± 1.8 vs 19.2 ± 2.1 ml/kg/min)
and FEV1 (1.14 ± 0.7 vs 1.65 ± 0.8 l, P = 0.02) were achieved suggesting the possibility of modifying
cardiopulmonary status before surgery in initially inoperable patients.
In summary, prehabilitation studies to date have been limited by small study populations and
interventions that vary in approach and duration. Nevertheless, they provide initial support to the
concept that prehabilitation can improve outcomes in patients undergoing lung resection surgery.
Furthermore, they advance the possibility that prehabilitation could also modify cancer treatment
options for patients with significant comorbid lung disease.
Acknowledgement: I would like to thank Dr. Elizabeth Cox Williams for comments on the manuscript.
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Regional Anesthesia and Acute Pain Medicine Education

Sandra L. Kopp M.D. Rochester, MN
Objectives:
• Recognize the impact education has on patient care and safety

• Understand learning styles and preferences of adult learners
• Analyze the current method and future directions of regional anesthesia
education
Education experts have suggested that many physicians know what to teach, but few know how to teach. Since
most physicians have received little formal instruction in education theory or methodology during their own
training, this assessment may be accurate. Traditionally, residents have been taught regional anesthesia in an
apprenticeship model; without a formal regional anesthesia rotation or curriculum. Limitations to this style of
teaching include: inconsistent learning experiences and limited case numbers. It is also dependent on the sheer
amount of exposure and not on a specifically designed curriculum. Standardized educational performance
objectives [Accreditation Council for Graduate Medical Education (ACGME) competencies] and minimum
block numbers for resident trainees have also been implemented and widely accepted during the past decade.
However, there are residents that fail to meet these requirements or develop proficiency in peripheral nerve
blockade. Formal regional anesthesia rotations consisting of a defined curriculum have recently been introduced
into several anesthesia residency programs. These programs are now trying to identify the most beneficial
teaching tools and many have started to utilize simulation and web-based education. The challenges of teaching
ultrasound-guided regional anesthesia (UGRA) are similar to those experienced by our surgical colleagues with
the introduction of minimally invasive surgery. The surgeons used theories of surgical skills training, simulation
and the concept of deliberate practice and feedback to shift the paradigm of learning from experience-based to
competency-based learning.
While web-based learning possesses several unique benefits and is increasingly used in university and graduate
medical education, it has not been developed or studied in regional anesthesia. Benefits of web-based education
include: the ability to standardize the quality and content of learning material, build appropriate learning
progressions, incorporate multi-media technology, and individualize delivery of course materials in terms of
time, pace, repetition, and location. Experts in adult learning have argued that traditional, didactic-style teaching
promotes passive learning; and higher order cognitive skills are only developed through interactive learning,
such as simulation or group discussion. Web-based education has been considered a form of interactive learning
and therefore many have hypothesized that web-based education should be superior to the more traditional
didactic approaches in terms of knowledge acquisition. Although web-based modules are considered effective
teaching tools, the existing literature does not consistently support that hypothesis. Many suggest that researchers
should concentrate on determining the optimal module design, usage pattern, assessment tools and integration of
web-based education, rather than focusing on whether it is superior to the more traditional methods of education.
Currently the main limitations to evaluating web-based education compared to more traditional approaches are
1) ensuring that each group of learners is exposed to the same content, and 2) developing an assessment tool that
measures the appropriate learning outcomes.
Simulation training is a popular method of medical education because knowledge does not equal competence.
It’s use is increasing in regional anesthesia with a wide variety of available simulators ranging from low fidelity
to higher fidelity models (tissue models, gel phantoms, cadaver training, partial task trainers). Simulation
practice decreases time to proficiency and is independent of the level of fidelity. It is essential to teach the
knowledge base first, and then use simulation training prior to or concurrent with patient care. Teaching and
testing the technical proficiency is essential. There are essentially three steps of technical skills acquisition;
cognition, integration, and automation. Checklists and global rating scales have been used to assess performance.
publication contains material copyrighted by others. Individual refresher course lectures are reprinted by ASA with
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Checklists need to be objective, observable and have clearly identified elements. Unfortunately, they likely test
throroughness more than they assess proficiency. Global rating scales are generally graded on a likert scale and
are more qualitative and less objective. They have been shown to be valid for interscalene block, epidural
placement and fiberoptic intubations. Unfortunately it is easier to identify unsatisfactory versus satisfactory
behaviors.
A recent study designed to determine whether residents trained using the simulation-based strategy of deliberte
practice show greater improvemnet of UGRA skills than residents trained using self-guided practice in
stimulation. Anestheisology residents new to UGRA were randomized to participate in either simulation-based
deliberate practice or self-guided practice (control). Participants were recorded and assessed while perfomring
simulated peripheral nerve blocks at baseline, immediately after the experiment and at 3 months. Both groups
showed a with-in group improvement from baseline immedately and at 3 months. The interesting part was that
the self-guided control group spent an average of 6.8 minutes vs the intervention group which spent 48.5
minutes. The authors concluded that both groups improved their skills from baseline, however, the group who
used self-guided practice required less time and faculty resources.
The use of visuospatial and psychomotor skill assessment to predict technical ability in regional anesthesia has
seen recent attention in the literature. Previous studies have suggested that a high degree of visuospatial aptitude
may predict the ease of mastery for learners of UGRA, but there is little evidence that the use of visuospatial
testing can identify who may benefit from early, focused training. Despite significant reliance on procedural
skills, anesthesiology lags behind other fields in assessing a learner’s technical aptitude. In addition to the
military and the manufacturing industry, surgical training programs have used visuospatial and psychomotor
testing to assess proficiency of trainees or workers. It is widely accepted that visuospatial ability correlates with
surgical skill, specifically the Perceptual Ability Test which tests a person’s ability to interpret 2-dimensional
shapes in a 30dimensional context. Dental schools have used this tool in their admissions process in hopes of
selecting applicants with an innate aptitude for technical skills.
Recently, the importance of multimodal acute pain management incorporating regional anesthetic techniques has
been recognized as a specialty within Anesthesiology. In addition to the knowledge of acute pain mechanisms
and nuances unique to the perioperative setting, regional anesthesia is now considered a specialized technical
skill set. In 2014, there are nearly 60 institutions that have listed themselves as having a nonaccredited
fellowship program focused on Regional Anesthesiology and Acute Pain Medicine. Therefore, it has become
apparent that accreditation of fellowship training in Regional Anesthesiology and Acute Pain Medicine is
essential. The Regional Anesthesiology and Acute Pain Medicine fellowship has recently been approved by the
ACGME Board of Directors to become the next accredited subspecialty fellowship training program within
anesthesiology and is currently in the process of developing program requirements.
The Ultrasound-guided Regional Anesthesia (UGRA) Education and Clinical Training Portfolio is a joint
initiative from ASA and ASRA designed for anesthesiologists who wish to distinquish themselves in the field
and provide evidence of training and experience to employers. The program guides participants through specific
criteria to demononstrate knowledge and achievement in UGRA procedures. Participants will build knowledge
through participation in CME activities and then validate experience with a case log. The portfolio does not
intend to restric the practice of UGRA, nor does participation ensure competency or certification in the
performance of UGRA.
The increased demand for productivity has resulted in less time for education and research, let alone research on
education. There are definitely questions that need to be answered within the field of anesthesia education and
more specifically regional anesthesia education. In addition to evaluating outcomes specific to a particular type
of education (web-based, simulation, etc.) - such as cost, structuring, and assessments - future studies should be
designed to assess the effect on patient care.
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REFERENCES
 Ahtsham NU, Philip, PW, et al. The future of regioanl anesthesia education: lesons learned from the
surgical specialty. Can J Anesth. Published online April 12, 2016
 Chuan A, Thillainathan S, Graham PL, et al. Reliability o fthe Direct Observation of Procedural Skills
Assessment Tool for Ultrasound-Guided Regional Anesthesia. Anaesth Intensive Care 2016: 44:2.
 Udani AD, Harrison TK, Mariano ER, et al. Comparative-Effectiveness of Simulation-Based Deliberate
Practice Versus Self-Guided Practice on Resident Anesthesiologists Acquisition of Ultrasound-Guided
Regional Anesthesia Skills.
 Chumley-Jones HS, Dobbie A, Alford CL. Web-based learning: sound educational method or hype? A
review of the evaluation literature. Acad Med 2002;77:S86-93.
 Cook DA. Learning and cognitive styles in web-based learning: theory, evidence, and application. Acad
Med 2005;80:266-78.
 Cook DA, Smith AJ. Validity of index of learning styles scores: multitrait-multimethod comparison
with three cognitive/learning style instruments. Medical education 2006;40:900-7.
 Cook DA, Thompson WG, Thomas KG, Thomas MR. Lack of interaction between sensing-intuitive
learning styles and problem-first versus information-first instruction: a randomized crossover trial. Adv
Health Sci Educ Theory Pract 2007.
 Friedman CP. The research we should be doing. Acad Med 1994;69:455-7.
 Kahn E, Lass SL, Hartley R, Kornreich HK. Affective learning in medical education. J Med Educ
1981;56:646-52.
 Kopacz DJ, Neal JM. Regional anesthesia and pain medicine: residency training--the year 2000. Reg
Anesth Pain Med 2002;27:9-14.
 Kopp SL, Smith HM. Developing effective web-based regional anesthesia education: A randomized
study evaluating case-based vs non-case-based module design. Reg Anesth Pain Med. 2011;36:336-
342.
 Richman JM, Stearns JD, Rowlingson AJ, Wu CL, McFarland EG. The introduction of a regional
anesthesia rotation: effect on resident education and operating room efficiency. J Clin Anesth
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 Smith HM, Kopp SL, et al. Designing and Implementing a Comprehensive Learner-Centered Regional
Anesthesia Curriculum. Reg Anesth Pain Med 2009;34:88-94.
 Smith MP, Sprung J, Zura A, Mascha E, Tetzlaff JE. A survey of exposure to regional anesthesia
techniques in American anesthesia residency training programs. Reg Anesth Pain Med 1999;24:11-16.
 Chin, Ki Jinn MBBS, FANZCA, MMed, FRCPC; Tse, Cyrus BSc; Chan, Vincent FRCPC, et al. Hand
Motion Analysis Using the Imperial College Surgical Assessment Device: Validation of a Novel and
Objective Performance Measure in Ultrasound-Guided Peripheral Nerve Blockade. Regional
Anesthesia & Pain Medicine. May/June 2011 - Volume 36 - Issue 3 - pp 213-219
 Taekman JM, Hobbs G, Barber L, Phillips-Bute BG, Wright MC, Newman MF, Stafford-Smith M.
Preliminary report on the use of high-fidelity simulation in the training of study coordinators
conducting a clinical research protocol. Anesth Analg 2004;99:521-7, table of contents.
 Cope, Daron H, Fenton-Lee, Douglas. Assessment of laparoscopic psychomotor skills in interns using
the MIST Virtual Reality Simulator: a prerequisite for those considering surgical training? ANZ J Surg.
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 Westman, Bo, Ritter, E Matt, Kjellin, Ann, Torkvist, Leif, et al. Visuospatial abilities correlate with
performance of senior endoscopy specialist in simulated colonoscopy. J Gastrointest Surg. 2006
Apr;10(4):593-9.
 Suozzi, Brent A, O'Sullivan, David M, Finnegan, Kyle T, Steinberg, Adam C. Can visuospatial ability
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Surg. 2013 Jul-Aug;19(4):214-8.
 Neal JM, Liguori GA, Hargett MJ. The training and careers of regional anesthesiology and acute pain
medicine fellows, 2013. Reg Anesth Pain Med. 2015 May-Jun;40(3):218-22.
 Neal JM. Education in regional anesthesia: caseloads, simulation, journals, and politics: 2011 Carl
Koller Lecture.Reg Anesth Pain Med. 2012 Nov-Dec;37(6):647-51.
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 Sites BD, Chan
VW, Neal JM, Weller R, Grau T, Koscielniak-Nielsen ZJ, Ivani G. The American Society of Regional
Anesthesia and Pain Medicine and the European Society of Regional Anaesthesia and Pain Therapy
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Reg Anesth Pain Med. 2010 Mar-Apr;35(2 Suppl):S74-80.
 Ultrasound-Guided Regional Anesthesia (UGRA) Education and Clinical Training Portfolio. Website:
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Fellowship Training in Regional Anesthesiology and Acute Pain Medicine: Third Edition, 2014.
Regional Anesthesia & Pain Medicine. 40(3):213-217, May/June 2015.
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Game Changers: The 20 Most Important Cardiac Anesthesia Articles Ever Published
Paul G. Barash, MD New Haven, Connecticut
Only a privileged few of the innumerable published articles related to the specialty of cardiac anesthesiology can be
considered seminal, landmark or, for the purposes of this article, a clinical “game changer.” A clinical game changer
is a publication that results in a revolutionary transformation that has been maintained in clinical practice since the
article first appeared. They follow Louis Pasteur’s dictum “In the fields of observation, chance favors only the well-
prepared mind.” The authors of these unique articles possess the unique ability of the creative mind to perceive
connections where others see none. The contemporary version of this statement is “connecting the dots.” Seven
recent publications are recommended to the reader for a further in-depth historical analysis. (1-7). In our original
game changers publication, which covers a range of publication dates from 1846 through 1987, 7/20 articles had a
direct impact on cardiac anesthesia. (8) (Table 1) The challenge for this review, albeit subjective, is to decide which
articles had the most profound effect on the practice of cardiac anesthesiology and medicine. Using specified
criteria, we chose the top 20 publications that, in our opinion, are the clinical "game changers" for the specialty of
cardiac anesthesiology
Table 1. Cardiac Anesthesia related articles from the original game changers’ article (8)
See article for citations.
RANK # SENIOR AUTHOR EVENT
4 SAKLAD, M ASA PHYSICAL STATUS GRADING SYSTEM
8 HICKEY, P NEONATAL PAIN PERCEPTION
10 EICHHORN, JH STANDARDS FOR PATIENT MONITORING
15 ENGSTROM, CG MODERN VENTILATOR
16 SEVERINGHAUS, JW pO2 and pCO2 BLOOD GAS ELECTRODES
17 SAFAR, P ABC’s of CPR
18 LOWENSTEIN, E HIGH DOSE NARCOTIC ANESTHESIA
Initially, based on the authors’ experience, a large group of articles were selected (~400). Additional bibliographic
research and personal communication with physician expert in cardiovascular anesthesia were also undertaken and
additional publications were identified. Our selection criteria included: 1) lasting impact of article on clinical
practice; 2) articles published in the medical literature regardless of age; 3) the articles appeared in English, or a
publication where an English translation is available and 4) three types of publications were considered: original
scientific publications, case reports and review articles. Exclusion criteria are: 1) reports involving animal studies
and 2) a copy of the scientific publication was unavailable or in a foreign language that was not translated into
English. Using the resources of the Wood Library-Museum of Anesthesiology, and the Cushing/Whitney Medical
Library at Yale University, publications were gathered, read and evaluated. Based on these factors and the authors’
judgment, this methodology resulted in a final list of the 20 most important cardiac anesthesia publications.
Below in Table format (Table 2) are the selected publications. Each article is ranked on the list in order of its
importance. At the Refresher Course Lecture, more detail will be discussed regarding rationale employed for
individual ranking as well as contender articles for a selection. The choices were difficult to create since
comparing/ranking two papers in highly different subject areas of cardiac anesthesiology (e.g. narcotic anesthesia
and echocardiography) is a subjective choice on the part of the authors. We also realize that many excellent and
important papers were omitted due to the limitations set by the inclusion/exclusion criteria.
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Table 2. Cardiac anesthesia game changer articles

SENIOR CIT*
AUTHOR SUBJECT #
1 LOWENSTEIN, E HIGH DOSE NARCOTIC ANESTHESIA 9
2 CAHALAN, M TEE DIAGNOSIS OF MYOCARDIAL ISCHEMIA 10
3 SWAN, HJC PULMONARY ARTERY CATHETER 11
4 SELDINGER, S VASCULAR CATHETERIZATION 12
5 KAPLAN, JA ECG LEAD V5 13
6 WAHR, J SAFETY IN THE CARDIAC OPERATING ROOM AHA GUIDELINE 14
7A McLEAN, J DISCOVERY OF HEPARIN 15
7B JORPES, E NEUTRALIZATION OF HEPARIN BY PROTAMINE 16
7C BULL, B ACTIVATED CLOTTING TIME (ACT) 17
8 MOFFETT, E CARDIO-PULMONARY BYPASS (ANESTHETIC MANAGEMENT) 18
9 MANGANO, D PERI-OPERATIVE BETA BLOCKER AND OUTCOME 19
10 PAYNE, J INTRA-OPERATIVE BETA BLOCKADE 20
11 EAGLE, K AHA GUIDELINES NON-CARDIAC SURGERY (NCS) 21
12 SLOGOFF, S MYOCARDIAL ISCHEMIA LEADING TO MYOCARDIAL INFARCTION 22
13 MANGANO, D USE OF PERIOPERATIVE MULTI CENTER STUDIES (MCSPI) 23
14A CHENG, D FAST TRACK EXTUBATION 24
14B BARASH, P FAST TRACK EXTUBATION 25
16 WYNANDS, E ANESTHESIA MANAGEMENT OF CORONARY REVASC. 26
17 HARMEL, M FIRST MODERN CARDIAC ANESTHESIA ARTICLE 27
18 TARHAN, S MYOCARDIAL RE-INFARCTION AFTER NCS 28
19A SLOGOFF, S ANESTHETIC AGENT AND OUTCOME 29
19B TUMAN, K ANESTHETIC AGENT AND OUTCOME 30
20 ZAPOL, W INHALED NITRIC OXIDE 31
* CIT# = Reference citation number
Certainly the articles chosen here represent cardiac anesthesiology’s major contributions to improvement of medical
care. The results demonstrate the wide contributions of the specialty of cardiac anesthesiology to the field of
medicine. The chosen publications reflect major themes: 1) innovation and creativity, 2) evidence-based medicine;
3) patient safety and 4) reduction of medical costs. In many cases, these articles were published in premier, high-
impact journals (both United States and international) and in both medical or surgical, as well anesthesia, journals.
with those having the greatest impact listed first, by its original citation and a short paragraph concerning its
uniqueness. The contributions cited in this review have a publication date range of 1946-2013, which is shorter than
the original game changers’ article (1846-1987) and most like reflects the relatively recent history of the
establishment of cardiac anesthesia.
Limitations exist to the selection process. First, is the use of the authors’ subjective judgment, which is based on
their perception of the relative contribution of a given publication. Secondly, to keep this purely clinical, we have
chosen not to include seminal articles involving animal subjects. Thirdly, by limiting our choices to articles
available in English (or translation available), we may have not included noteworthy seminal publications in other
languages. Whether in medicine or other disciplines, these limitations (subjectivity, citation index, etc) are also
present in other “top 10 lists.” (31-33) Finally, we realize a number of excellent articles have been published that are
not on this list. Similar to ranking of United States presidents, a certain amount of historical perspective is required
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to fully appreciate the importance of an article’s contribution.
In summary, the “Game Changers” list represents proof of the statement: Major achievements of modern surgery
could not have occurred without the accompanying vision of pioneers in anesthesiology. (34)
Denise Hersey and Karen Bieterman provided assistance in preparing this review in their personal capacity. The
opinions expressed in this article are their own and do not reflect the view of the Wood Library-Museum of
Anesthesiology, the American Society of Anesthesiologists and Yale University, respectively.
References
1. Jacob AK et al. History of anesthesia. In: Barash PG, Cullen B, Stoelting RK, Cahalan M, Stock C, Ortega
R. eds. Clinical Anesthesia. 7th ed. Philadelphia, PA: Wolters Kluwer/Lippincott Williams & Wilkins,
2013:3-27
2. Webster NR, Galley HF. Landmark Papers in Anaesthesia. Oxford, UK: Oxford University Press, 2013
3. Eger II EI et al. The Wondrous Story of Anesthesia. New York, NY: Springer, 2014
4. Lowenstein E et al. A history of cardiac anesthesia. In: Eger II EI, Saidman LJ, Westhorpe RN. eds. The
Wondrous Story of Anesthesia. New York, NY: Springer, 2014:829-846
5. Stanley TH. The history of opioid use in anesthetic delivery. In: Eger II EI, Saidman LJ, Westhorpe RN.
eds. The Wondrous Story of Anesthesia. New York, NY: Springer, 2014:641-660
6. Eger II EI. A history of research in anesthesia. In: Eger II EI, Saidman LJ, Westhorpe RN. eds. The
Wondrous Story of Anesthesia. New York, NY: Springer, 2014: 515-24
7. Hessel II EA. History of cardiac surgery and anesthesia. In Estafanous FG, Barash PG, Reves JG: Cardiac
Anesthesia. Second Edition. Lippincott Williams-Wilkins, 2001:3-36
8. Barash PG et al. Game Changers: the 20 most important anesthesia articles ever published. Anes Analg
2015; 120:663-670
9. Lowenstein E et al. Cardiovascular response to large doses of intravenous morphine in man. N Engl J Med
1969; 281:1389–93
10. Smith JS et al. Intraoperative detection of myocardial ischemia in high-risk patients: electrocardiography
versus two-dimensional transesophageal echocardiography. Circulation 1985; 72:1015–21
11. Swan HJC et al. Catheterization of the heart in man with use of a flow-directed balloon-tipped catheter N
Engl J Med 1970; 283: 447- 451
12. Seldinger SI. Catheter replacement of the needle in percutaneous arteriography; a new technique. Acta
Radiol. 1953; 39:368-76
13. Kaplan JA et al. The precordial electrocardiographic lead (V5) in patients who have coronary-artery
disease. Anesthesiology. 1976; 45:570-4.
14. Wahr J et al. Patient safety in the cardiac operating room: Human Factors and Teamwork: A scientific
statement from the American Heart Association. Circulation 2013; 18:1139-1169
15. McLean J. The thromboplastic action of cephalin. Am J Physio 1916; 41:250-7.
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16. Jorpes E et al. Neutralization of action of heparin by protamine. Lancet 1939; 237:975-6
17. Bull BS et al. Heparin therapy during extracorporeal circulation. II. The use of a dose-response curve to
individualize heparin and protamine dosage. J Thorac Cardiovasc Surg 1975; 69:685-969
18. Moffitt EA et al. Studies in extracorporeal circulation. V. Anesthesia and supportive care during
intracardiac surgery with the Gibbon-type pump-oxygenator. Anesthesiology 1957; 18:673-85
19. Mangano DT et al. Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery.
Multicenter Study of Perioperative Ischemia Research Group. N Engl J Med. 1996; 335:1713-20
20. Payne JP et al. Pronethalol in treatment of ventricular arrhythmias during anaesthesia. Br Med J 1964
7;1(5383):603-4
21. Eagle KA et al. Guidelines for perioperative cardiovascular evaluation for noncardiac surgery. Report of
the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
Committee on Perioperative Cardiovascular Evaluation for Noncardiac Surgery. Circulation. 1996; 93:1278
–317.
22. Slogoff S et al. Does perioperative myocardial ischemia lead to postoperative myocardial infarction?
Anesthesiology. 1985 Feb;62:107-14
23. Wahr JA et al. Cardiovascular responses during sedation after coronary revascularization. Incidence of
myocardial ischemia and hemodynamic episodes with propofol versus midazolam. Anesthesiology. 1996;
84:1350-60
24. Cheng DC et al. Early tracheal extubation after coronary artery bypass graft surgery reduces costs and
improves resource use. A prospective, randomized, controlled trial. Anesthesiology 1996; 85:1300-1310
25. Barash PG et al. Early extubation following pediatric cardiothoracic operation: A viable alternative. Ann
Thorac Surg 29:228-233, 1980
26. Wynands JE et al. Coronary artery disease and anaesthesia (experience in 120 patients for revascularization
of the heart). Can Anaesth Soc J. 1967;14:382-98.
27. Harmel MH et al. Anesthesia in the surgical treatment of congenital pulmonic stenosis. Anesthesiology.
1946;7:477-98.
28. Tarhan S et al. Myocardial infarction after general anesthesia. JAMA 1972;220:1451-54
29. Slogoff S et al. Randomized trial of primary anesthetic agents on outcome of coronary artery bypass
operations. Anesthesiology. 1989 ;70:179-88.
30. Tuman KJ et al. Does choice of anesthetic agent significantly affect outcome after coronary artery surgery?
31. Zapol W. Inhaled nitric oxide in persistent pulmonary hypertension of the newborn. Lancet 1992;340:818-9
32. Baltussen A et al. Citation classics in anesthetic journals. Anesth Analg 2004; 98:443-51
33. Bakkalbasi N et al. Three options for citation tracking: Google Scholar, Scopus Web of Science. Biomed
Digit Libr 2006;3: 7
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34. Kulkarni AV et al. Comparisons of citations in Web of Science, Scopus and Google Scholar for articles
published in general medical journals. JAMA 2009;302:1092-6
35. Barash PG, et al. Preface. In: Barash PG, Cullen B, Stoelting RK, Cahalan M, Stock C, Ortega R. eds.
Clinical Anesthesia. 7th ed. Philadelphia, PA: Wolters Kluwer/Lippincott Williams & Wilkins, 2013:xvii
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Blood Pressure and the Brain: How Low Can You Go?
John C. Drummond, M.D., FRCPC Del Mar, CA
A physiology-based answer to the title question, with its unattractive suggestion of the deliberate brinksmanship that
we all seek to avoid, should begin with reference to the standard depictions of cerebral blood flow (CBF)
autoregulation. One would pay particular attention to the inflection point at which CBF becomes “pressure-
passive”, i.e., that mean arterial pressure (MAP) below which reduction results in a pari passu reduction in CBF.
We refer to that MAP as the “lower limit of CBF autoregulation” (LLA). While the MAP value attributed to that
inflection point has traditionally been an MAP below a clinician does not want his/her patient to fall, MAP can, in
fact, fall below the individual’s LLA without doing immediate harm. Resting normal CBF levels actually provide
luxury perfusion to the central nervous system (CNS). Mother Nature has built in a buffer (herein referred to as
“the CNS blood flow reserve”) that allows a considerable reduction in MAP below the LLA before CNS ischemia
occurs. CBF can fall approximately 40% from resting values before symptoms of ischemia occur in awake subjects.
The Lower Limit of CBF Autoregulation. Diagrams that appear in standard texts have frequently depicted the
lower limit of human cerebral blood flow autoregulation as being a mean arterial pressure of 50 mmHg. While this
number may in fact be a reasonable representation of the LLA in several animal species, it is unlikely to be an
accurate value in adult humans. The first rendering of a CBF autoregulation curve was probably that drawn by
Lassen.1 His diagram depicted an LLA that might be easily interpreted to be 50 mmHg. On close inspection,
however, the inflection point of that hand-drawn curve is probably not less than 60 mmHg. Lassen’s diagram, and
the misreading of it, are probably the origin of subsequent widely reproduced diagrams that appeared in textbooks of
Anesthesiology depicting the human LLA as 50 mmHg. Numerous subsequent investigations (see Drummond2 for
additional references) suggest that the average LLA in non-anesthetized adult humans is nothing less than 70
mmHg. It is noteworthy that the BP ranges or standard deviations for the LLAs in the subjects in the cited studies 2
and in more recent investigations4 were large indicating that the variation about that average LLA among individuals
is substantial.
While the data just cited argue that the average LLA in non-anesthetized adults is nothing less than a value in the
low 70’s mmHg, it should be acknowledged that the “rules” might be different during general anesthesia. There are
at least two reasons. The first is the frequent inclusion of vasodilating substances in anesthetic recipes. Vasodilators
might serve to shift the autoregulation curve in a leftward direction. The second resides in the observation that
sympathectomy in both experimental animals and humans during hypotension increases CBF.3 This suggests that
the normal autonomic response to hypotension includes some vasoconstriction of large extracranial and perhaps
intracranial vessels thereby producing effective right shifting of the autoregulation curve. If a general anesthetic
were to effectively prevent that autonomic response, it is possible that some left shifting of the curve might occur.
The reality, however, is that there has been exceptionally little systematic study of normal (non-injured) adult human
CBF autoregulation during anesthesia. The only context in which extensive study has occurred is during
cardiopulmonary bypass ( involving, hypothermia, non-pulsatile flow, relative anemia, volatile agent and high-dose
narcotic anesthesia). In those circumstances, which are arguably poorly representative of the physiology that
prevails during the majority of general anesthetic states, the average LLA was in fact about 66 mmHg, with a very
large confidence interval indicating considerable inter-individual heterogeneity.4 However, it seems inappropriate to
extrapolate that average value (obtained in the context of non-pulsatile flow, low hematocrit and well maintained
cardiac output) to all other anesthetic circumstances. In fact, it further seems likely that what pertains to any one
anesthetic circumstance, e.g., spontaneous ventilation during anesthesia with a volatile agent, might not be relevant
in another, e.g., a TIVA anesthetic with remifentanil and propofol. We know very little about the LLA during
general anesthesia in humans and it seems prudent that conservative assumptions should be made in the absence of
more detailed knowledge.
The Physiologic Central Nervous System Blood Flow Reserve. Many clinicians may well respond to the
preceding discussion of the LLA with their own observation that numerous patients in the span of their experience
have tolerated MAPs in the 40’s, 50’s and 60’s, i.e., well below the proposed LLA of 70 mmHg. That is inevitably
true. Patients tolerate blood pressure (BP) below their individual LLAs because there is a substantial CNS blood
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flow reserve. That knowledge dates from the study of Finnerty et al., 5 data from which were used by Lassen to
anchor the low MAP end of his “first-ever” autoregulation curve. The left hand end of that hand-drawn curve, i.e.,
the region depicting the lowest CBF, is anchored by CBF data that were derived in non-anesthetized adults in whom
BP was lowered using cerebral vasodilating drugs (which might have helped to sustain CBF as MAP fell). In that
study, BP reduction was stopped when the subjects developed symptoms suggestive of cerebral ischemia. That
occurred at an average MAP of 48 mmHg, at which point CBF had been reduced by about 40% of its baseline
value. Quantitatively similar data were obtained in an investigation by Njemanze, who used a tilt table and a
transcranial Doppler to study individuals with postural hypotension.6 His observations were that symptoms
suggestive of CNS ischemia occurred with a 35% reduction in CBFV (cf: 40% reduction in the study by Finnerty
above) and that syncope occurred with a reduction of CBFV by 50%. There are additional data to support this
concept, i.e., that CBF can be reduced by approximately 40% of baseline values before symptoms of ischemia begin
to occur.7-9
Impairment of the CNS blood flow reserve. This reserve is, in essence, a physiologic buffer that protects patients
in the event of hypotension, and that buffer means that MAPs (at head level) in the upper 40’s will be tolerated by
many, if not most, normotensive adults. However, it is important that clinicians recognize the situations in which
that buffer may not be present, often because it has been encroached upon by some pre-existing pathologic process.
Among the most common situations in which the buffer is likely to have been attenuated are circumstances in which
CNS tissue is under increased local pressure.
Increased local CNS tissue pressure. This may occur in the circumstances of increased intracranial pressure (ICP),
increased intra-orbital pressure or when CNS tissue is under extrinsic pressure, e.g., compressed under retractors or
by a bulging disc or a stenotic spinal canal. The significance of these situations is that the principal determinant of
flow to the tissue is “transmural pressure” rather than blood pressure. Transmural pressure (which is commonly but
probably inaccurately referred to as “perfusion pressure”) equals MAP minus local tissue pressure. Among the most
commonly overlooked situations in which tissue pressure is increased (and the effective perfusion pressure is
therefore less for a given value of MAP) is in the circumstances of spinal stenosis, in particular cervical spinal
stenosis. In that group of patients, the normally wide latitudes for intraoperative BP that anesthesiologists
commonly allow should be tightly restricted. It is our approach at UCSD to maintain MAPs during anesthesia in
these patients (at least until the decompression is complete) very close to normal waking levels. With cervical spinal
stenosis the prudent answer to the “How low can you go” question is . . . “Not very”.
The other common situations that reduce the blood flow reserve are central nervous system injury and chronic
hypertension. Variability in collateral blood supply may also be relevant.
Central nervous system injury. Autoregulation is physiologically fragile and can be assumed to be impaired in at
least some portions of the nervous system in the common injury states, i.e., traumatic brain injury (TBI),
subarachnoid hemorrhage (SAH) and probably spinal cord injury. Resting CBF is commonly at values
approximately half of normal after TBI and SAH10-12 and can probably be assumed to be so after spinal cord injury
as well. The combination of impaired autoregulation and low resting blood flow means that BPs that would be
below the LLA but would probably be well-tolerated in normal subjects will have the potential to reduce flow to
precariously low levels in the common injury states.
Chronic Hypertension. Chronic hypertension is associated with a thickening of the intima and media of cerebral
vessels. Teleologically speaking, this is Mother Nature’s way of preventing vessel rupture and intracerebral
hemorrhage in response to the increased pressure head. The "downside" is that cerebral vessels are less able to relax
in the face of decreasing pressure. This results in a functional “right shifting” of the autoregulatory curve, with the
potential consequence that BPs that would be tolerated in normotensive subjects might have to potential to result in
ischemia in those with chronic hypertension. This phenomenon has been well demonstrated in human investigations.
While it is often said that treating hypertension “resets” the autoregulatory curve resetting has not, in fact, being
demonstrated in humans. It has been demonstrated in spontaneously hypertensive rats and in baboons with
relatively brief reno-vascular hypertension. The only study that has looked at treated hypertensive human beings,
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revealed persistently elevated LLAs. Intuition, which should not substitute for science, might lead one to be
suspicious of the resetting phenomenon. Does it seem likely that collagen deposition in intima and media of vessels
that has occurred over many years would resolve over any reasonably short time course?
Variability in collateral supply. Lastly, and perhaps most insidiously, a phenomenon with the potential to
encroach upon the reserve is variation in collateral circulation. A significant part of the CNS’s tolerance
hypotension resides in the generous collateralization that is present in many vascular beds. An analogy may help.
In most circumstances, the human nervous system is, in essence, like a very well watered lawn with numerous pop-
up sprinkler heads with overlapping circles of distribution. Pressure in the system can fall substantially before
“brown spots” develop between the overlapping distributions. However, congenital variation and vascular disease
can result in individuals, some of whom will be impossible to anticipate, who have less generous collateralization in
some vascular beds. The congenital variations include variability of the circle of Willis (see Drummond 13 for
references), variability of vessel input to the anterior spinal artery14 and probably variability in the vascular supply to
the optic disc and the mid-portion of the optic nerve.15 It is in particular variations in circle of Willis anatomy that
have the potential to give rise to the seemingly idiosyncratic occurrence of cerebral ischemic injury after BP
management that an individual clinician may think of as routine. 13,16. It is very difficult to translate this concern into
a firm clinical recommendation. The incidence of harm attributable to unanticipated collateral variation is probably
relatively low. Nonetheless, it is one more reason for clinicians to avoid hypotension, which I will arbitrarily define
has an MAP less than 60 mmHg at the level of the Circle of Willis, that is not necessary for the conduct of the
surgical procedure. I must emphasize that that threshold, 60 mmHg, is entirely arbitrary and is not evidence based.
It allows for some encroachment on the CNS blood flow reserve while avoiding burdensome constraints upon
clinicians. That number should be adjusted upwards in patients in whom the clinician has reason to suspect that the
CNS blood flow reserve is already compromised.
The Effect of Hydrostatic Gradients on Cerebral Blood Pressure. This phenomenon represents another,
probably under appreciated, mechanism for the potential encroachment on the CNS blood flow of reserve. As any
fluid (including blood) is pumped vertically against gravity, the pressure in the fluid column decreases as it rises
above the pump. When there is a vertical height difference between the heart and the head, a pressure differential
between the two that is equivalent to the weight of a column of blood of that height can be expected to occur. That
gradient will be equal to approximately 2 mmHg for each one inch of height difference. Accordingly, in many
vertical adults the mean pressure at the level of the circle of Willis (for which the tragus or external auditory meatus
(EAM) are commonly used as landmarks) is probably about 25 mmHg less than the pressure that would be
simultaneously recorded by a BP cuff on the arm. For a normotensive adult with a BP of 125/80 and an MAP of 95,
MAP at the EAM is approximately 71 mmHg. (95 – [12 inches x 2 mmHg/inch = 24] = 71). The first implication
of this is that with a patient in a horizontal posture and MAP of 70 mmHg at the level of a BP cuff on the arm has an
MAP at the EAM that is at the baseline waking value. In horizontal patients (supine, prone, lateral), in essence, the
first 20% of MAP “reduction” is physiologically absolutely free with respect to the brain! But, not so when
positions are used that place the head above the level of the heart.
When there is a vertical height difference between the height of the heart and the head, a pressure differential
between the two that is equivalent to the weight of a column of blood of that height can be expected to occur. The
standard teaching in neuroanesthesia has long been that BP should be transduced at (or an arithmetic correction
imposed using the formula in the preceding paragraph to correct to) the level of the EAM. Clinicians who are
unfamiliar with the neurosurgical use of the sitting position have occasionally failed to make this correction in
transducer height, or have raised it only to the level of the heart with sometimes severe adverse consequences for the
perfusion of the brain and/or the cervical spinal cord. 17,18 This issue has been popularized recently in the context of
injuries occurring in the so called “beach chair position”. A minority have disputed this notion, arguing that siphon-
like mechanism maintains CBF in spite of reductions MAP at the EAM as calculated above. 19 Unless and until there
is wider proof of that concept, i.e., the siphon or closed loop model of the cerebral circulation, conventional
hydrostatic gradient concepts should apply, and arterial transducers should be raised to the level of the EAM or
arithmetic corrections should be applied to BP cuff pressures in order to “think” in terms of BP at the EAM. 20
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Summary and Conclusions. Once upon a time, it was considered acceptable to reduce MAP to 50 mmHg because
50 mmHg was perceived to be the lower limit of human CBF autoregulation. However, an objective review of the
literature confirms that the LLA is actually nothing less than a value in the low 70s mmHg. If we were to be
consistent with the original rationale, we would now deem 70 mmHg to be an acceptable minimal intraoperative
MAP. But that would be unnecessarily restrictive. I say “unnecessary” because the CNS blood flow reserve, as
described above, assures that the CNS will be adequately perfused at MAPs significantly below the LLA in most
individuals. Data cited above suggest that an MAP in the vicinity of 50 mmHg (at the level of the circle of Willis) is
the average threshold for the onset of early ischemic symptoms in normotensive adults (and even at that level
hypotension will not be immediately injurious). Accordingly, when hypotension is absolutely necessary for the
efficient conduct of a surgical procedure and the clinician has reason to anticipate that the CBF reserve is intact,
MAPs as low as 50 mmHg (at the level of the circle of Willis) can be justified. However, hypotension of that degree
should be undertaken with the knowledge that there will be little remaining margin for error and that there may be a
small subset of physiologic outliers (outliers in terms of LLA or collateralization) who will be intolerant of even that
pressure. Hypotension should therefore be as brief as is necessary. For other normotensive adult patients
undergoing procedures with no necessity for hypotension who are in reasonable vascular health, with the CNS flow
reserve likely to be intact (this excludes patients with increased local pressures on CNS tissue), a minimum MAP of
60 mmHg (at the level of the circle of Willis) is likely to be safe.
1. Lassen NA: Cerebral blood flow and oxygen consumption in man. Physiological Reviews 1959; 39: 183-238
2. Drummond JC: The lower limit of autoregulation: Time to revise our thinking? Anesthesiology 1997; 86:
1431-3
3. Fitch W, MacKenzie ET, Harper AM: Effects of decreasing arterial blood pressure on cerebral blood flow in
the baboon. Influence of the sympathetic nervous system. Circ Res 1975; 37: 550-7
4. Joshi B, Ono M, Brown C, Brady K, Easley RB, Yenokyan G, Gottesman RF, Hogue CW: Predicting the
limits of cerebral autoregulation during cardiopulmonary bypass. Anesth Analg 2012; 114: 503-10
5. Finnerty FA, Witkin L, Fazekas JF: Cerebral hemodynamics during cerebral ischemia induced by acute
hypotension. J Clin Invest 1954; 33: 1227-32
6. Njemanze PC: Critical limits of presure-flow relation in the human brain. Stroke 1992; 23: 1743-7
7. Astrup J, Symon L, Branston NM, Lassen NA: Cortical evoked potential and extracellular K + and H+ at
critical levels of brain ischemia. Stroke 1977; 8: 52-57
8. Branston NM, Symon L, Crockard HA, Pasztor E: Relationship between the cortical evoked potential and
local cortical blood flow following acute middle cerebral artery occlusion in the baboon. Exptl Neurol 1974;
45: 195-208
9. Jones TH, Morawetz RB, Crowell RM, Marcoux FW, FitzGibbon SJ, DeGirolami U, Ojemann RG:
Thresholds of focal cerebral ischemia in awake monkeys. J Neurosurg 1981; 54: 773-782
10. Bouma GJ, Muizelaar JP, Choi SC, Newlon PG, Young HF: Cerebral circulation and metabolism after severe
traumatic brain injury: the elusive role of ischemia. J Neurosurg 1991; 75: 685-693
11. Ishii R: Regional cerebral blood flow in patients with ruptured intracranial aneurysms. J Neurosurg 1979; 50:
587-594
12. Kim DH, Joseph M, Ziadi S, Nates J, Dannenbaum M, Malkoff M: Increases in cardiac output can reverse
flow deficits from vasospasm independent of blood pressure: A study using xenon computed tomographic
measurement of cerebral blood flow. Neurosurgery 2003; 53: 1044-52
13. Drummond JC, Englander RN, Gallo CJ: Cerebral ischemia as an apparent complication of anterior cervical
discectomy in a patient with an incomplete circle of Willis. Anesth Analg 2006; 102: 896-9
14. Dommisse GF: The blood supply of the spinal cord. A critical vascular zone in spinal surgery. J Bone Joint
Surg Br 1974; 56: 225-35
15. Baig MN, Lubow M, Immesoete P, Bergese SD, Hamdy EA, Mendel E: Vision loss after spine surgery:
review of the literature and recommendations. Neurosurg Focus 2007; 23: E15
16. Drummond JC, Lee RR, Howell JP, Jr.: Focal cerebral ischemia after surgery in the "beach chair" position:
the role of a congenital variation of circle of Willis anatomy. Anesth Analg 2012; 114: 1301-3
17. Cullen D, Kirby R: Beach chair position may decrease cerebral perfusion: Catastrophic outcomes have
occurred. Anesthesia Patient Safety Foundation Newsletter 2007; 22: 25-7
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18. Drummond JC: A beach chair, comfortably positioned atop an iceberg. Anesth Analg 2013; 116: 1204-6
19. Hicks JW, Munis JR: The siphon controversy counterpoint: the brain need not be "baffling". Am J Physiol
Regul Integr Comp Physiol 2005; 289: R629-32
20. Drummond JC, Hargens AR, Patel PM: Hydrostatic gradient is important - Blood pressure should be
corrected. Anesthesia Patient Safety Foundation Newsletter 2009; 24: 6
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Promoting Cognitive Health in Geriatric Surgical Patients

Gregory Crosby, M.D. Boston, MA
People over 65 years of age have the highest rate of surgery of any age group (per
10,000 population, its about 2.5X that of people 45-64) and account for 30-35% of
surgical procedures in the U.S. This age group is also more vulnerable to cognitive
complications while hospitalized, an issue that has garnered much attention in both
the medical literature and lay press. This document will provide an overview of the
current status of and controversies around whether surgery and general anesthesia
harm the older brain and what, if anything, can be done about it.
Brain Aging - A Vulnerability Factor

Some physical changes of age (e.g. wrinkles, baldness) are obvious whereas those in
the brain, though unseen, happen just the same. Brain size peaks in adolescence and
it’s downhill from there. Even a healthy brain shrinks with age and these volumetric
changes accelerate as we get older, with areas involved in memory, processing speed,
and executive function being severely affected.1 The older brain is also structurally and
functionally different. There is extensive loss of synapses and neurotransmitters2 and a
markedly diminished ability to make new neurons.3 This is important because
neurogenesis is implicated in learning and memory and appears to be an adaptive
mechanism whereby the brain re-wires its own circuitry.3 In addition, the older brain
has more glia and their function is altered, leading to an exaggerated and prolonged
response to an immune challenge such as surgery.4 Finally, the older brain is less able
to generate the rapid, high fidelity communication between and among brain regions
that is essential for normal brain function.5 This may be due in part to breakdown of
myelin and / or disruption of white matter tracts, a process that begins as early as age
20.6 Collectively, these changes have a profound impact on normal brain function.
Thirty - 50% of seniors report problems with short-term memory and structured
assessments show that among community dwelling seniors 71 or older about 20%
have cognitive impairment without dementia.7,8 Thus, even healthy seniors have limited
brain reserve and may depend on compensatory processes to maintain normal
cognitive function.
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Superimposed age-related brain disease makes matters worse. Cerebrovascular disease

and dementing illness are common.9,10 10–15% of persons older than 65 years have
Alzheimer’s-type dementia and by 85 about 50% are afflicted. Fortunately, except for
trauma or urgent procedures, few clinically demented patients have surgery but the
underlying pathology begins long before clinical symptoms are evident.11 Therefore, it
is likely that many older patients coming for surgery and anesthesia have underlying,
occult AD-type brain pathology at baseline. Whether this confers added risk for
postoperative cognitive complications or decline is unknown and there is as yet no
way to identify people at risk for AD before they are symptomatic.
Perioperative Clinical Implications of Brain Aging

1. The older brain, even if healthy, is fundamentally different from a younger one.
2. A cognitively intact person can have substantial underlying age-related CNS
pathology.
3. Age is just a number. Specifically, chronological age is a notoriously poor predictor
of cognitive age. As such, forecasting risk for perioperative cognitive complications
by age alone is unreliable.
4. Given lower cognitive reserve (fewer synapses, dysfunctional networks), the older
brain may be more sensitive to anesthetics and normal synaptic / network activity
may take longer to “reboot” postoperatively.
5. Due partly to glial changes, the older brain is a set up for excessive and prolonged
surgery-induced neuroinflammation. In theory, interventions that tame this
response, without undermining the necessary and beneficial effects of
inflammation, could promote perioperative cognitive health.
Delirium
Delirium is an acute confusional state defined by an acute and fluctuating course and
inattention, along with either disorganized thinking and/or altered level of
consciousness.12 It’s extremely common in older surgical patients and is associated with
serious morbidity. Depending upon the type of surgery, 15-55% of older surgical
patients develop delirium and if admission to an ICU is required the prevalence
approaches 100%.12 This makes delirium the most common perioperative complication
in this age group. It is also expensive and deadly. Delirium is associated with prolonged
hospital stay, greater likelihood of discharge to a nursing home or other post acute-
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care facility, subsequent development of dementia, and a higher 1-year mortality.12-14

Consequently, hospitals are paying attention and welcome efforts to prevent, identify,
and manage it.
The vulnerability and predisposing factors for delirium are reasonably well
characterized but the neuropathology is not. A host of physiological (e.g. hypoxia,
anemia, metabolic disturbances, hypoalbuminemia, infection) and emotional or mental
disturbances (e.g. depression, dementia) are implicated.15 Drugs and drug interactions
are a major factor, particularly those with anticholinergic activity—of which there are
many.16 The well-known association between infection and delirium, combined with
the fact that delirium is more common after ‘big’, invasive procedures than minor ones,
makes a case for surgery-induced inflammation as a potential trigger of postoperative
delirium. A common theme that emerges is that cognitive reserve and susceptibility to
delirium are inversely proportional such that a lesser insult is required to trigger acute
brain dysfunction in a person with limited cognitive reserve and/or underlying brain
pathology.17-19 Differences between the young adult and old brain being what they are,
this helps explain why perioperative delirium is common in older persons.
The role of anesthetics and sedatives is complex. Certain anesthetic agents (e.g.
ketamine, benzodiazepines, propofol) are associated with delirium, others may be
protective (e.g. dexmedetomidine) but, somewhat paradoxically, the type of anesthesia
(spinal, epidural, general) has little bearing.20-22 However, depth of sedation / anesthesia
is a confounder in most of these studies. This becomes important since procedural
“sedation” often ends up being general anesthesia23 and deeper sedation / anesthesia
is associated with greater risk of delirium.24,25 One place this is changing practice is the
ICU, where “lighter” sedation with dexmedetomidine rather than benzodiazepines is
gaining traction.20,26-28 Finally, as far as postoperative pain management goes, the
effectiveness of pain control appears to be more important than the specific agents or
route of analgesia used.29-31 Analgesics should not be withheld for fear of inducing
delirium, as pain is a preventable cause of delirium.
Perioperative Clinical Implications of Delirium

1. Prevention trumps treatment. To identify the patient at high-risk for delirium, look
especially for cognitive impairment or frailty at baseline. Consider obtaining a
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geriatric consultation; a simple geriatrician-directed perioperative re-orientation

program markedly reduces the incidence of delirium.32 If available, admit the high-
risk patient to a geriatrics-oriented care unit postoperatively.33
2. Look for it. Delirium is not always obvious. Hypoactive or quiet delirium is more
frequent than agitated delirium and is easily overlooked. The Confusion
Assessment Method (CAM) or CAM-ICU for the non-verbal (intubated) patient are
the gold standards for bedside delirium assessment by non-psychiatrists and take
only minutes to administer.
3. Become familiar with the Beers Criteria. Many drugs have anticholinergic effects
and should be avoided.
4. Multi-component interventions, typically involving education, individualized care,
reorientation, and early mobilization, reduce the incidence of delirium whereas
pharmacologic interventions (e.g. antipsychotics, melatonin) do not.
5. Delirium in the elderly is often an early sign of underlying disease. Identify and
correct factors that can be modified (e.g. hypoxemia, low albumin, infection /
sepsis, pain).
6. The relationship of depth of anesthesia and delirium is controversial. Several
studies report an association between deeper anesthesia as measured by
processed EEG and a higher prevalence of postoperative delirium but some find
the opposite (i.e. less delirium with deeper anesthesia). Prospective randomized
trials are underway to resolve this issue.
7. When all else fails, pharmacological symptom management may be warranted.
Avoid benzodiazepines, as they make matters worse. Haloperidol is the go-to
agent but its efficacy is unproven.34 Dexmedetomidine is useful for managing
agitated delirium in the ICU.
Postoperative Cognitive Dysfunction (POCD)

Many elderly patients complain of cognitive fogginess for days to weeks after surgery,
a phenomenon called POCD. The deficits are subtle and mainly affect memory and/or
executive function. Unlike delirium, POCD is not a clinical diagnosis but is identified
by performance on a battery of neuropsychological tests. POCD is detectable in 30-
40% of non-cardiac surgery patients in the 1st postoperative week regardless of age
but is 2-3 times more common in older (10-13%) than younger adult surgical controls
or age-matched non-hospitalized controls (4-6%) 3 months later.35-37 POCD appears to
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resolve with time, typically within 6-12 months, but is associated with subsequent non-
participation in the workforce and, if present both at hospital discharge and 3 months
postoperatively, higher mortality 1-year later.35,38
The cause is unknown but likely is multifactorial. Advanced age, in combination with
other factors such as comorbid diseases (e.g. cerebrovascular disease) and genetic
susceptibility,39,40 clearly plays a role but illness, anesthesia, and surgery may as well.
Surgery causes inflammation and inflammation impairs cognition. Consistent with the
inflammation hypothesis, the incidence of POCD is higher after major inpatient than
minor outpatient procedures41 and work in animals reveals transient neuroinflammation
and learning impairment after surgery.42,43 The latter can be prevented or reversed in
animals by agents that mitigate CNS inflammation,42,43 offering hope that it might
someday be possible to do something to prevent POCD in humans. Data on the role
of general anesthesia are inconsistent. Among all the things that happen in the
perioperative period, general anesthesia has the most obvious effect (i.e. coma) on
cognition. Animal studies report prolonged changes in gene and protein expression,
increases in proteins such as amyloid β (Aβ) and phosphorylated tau that are implicated
in the neuropathogenesis of Alzheimer’s disease, and persistent learning impairment
after general anesthesia without surgery.44-46 The clinical literature, nearly all of which
comes from retrospective studies, is conflicted. Many find no difference in the risk of
prolonged POCD between regional and general anesthesia47,48 or between general
anesthesia (and surgery) and the development or progression of MCI (mild cognitive
impairment) or Alzheimer’s disease.49-53 but others support an association.54 Therefore,
the field is divided: some contend POCD does not exist or has nothing to do with
surgery / anesthesia55 whereas, based partly on the fact that most clinical studies are
retrospective and under-powered but show large effect sizes in favor of POCD, others
contend such conclusions are unjustified.56 Against this background, it is interesting to
note there is clinical evidence that an inflammatory event accelerates cognitive decline,
that non-critical medical illness increases the risk of incident dementia, and that illness
requiring intensive care is associated with long-lasting cognitive decline.57-59 Finally,
given that chronological age is a poor predictor of cognitive age and, possibly,
vulnerability to postoperative cognitive morbidity, patient-specific factors must be
considered. A recent prospective longitudinal cohort study showed, for example, that
although surgery was associated with cognitive decline generally, it was worse in
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certain subgroups, including ApoE4 carriers.54 Likewise, up to 40% of patients having

an elective major joint replacement procedure (total hip or knee) have cognitive deficits
preoperatively and 20% meet criteria for MCI.60-62 Frailty and functional dependence
are also common in this age group.63 As such, geriatric screening for preoperative
cognition and function may help identify seniors at high risk for postoperative cognitive
complications and help better characterize cohorts in clinical trials of POCD.
Perioperative Clinical Implications of POCD

1. Cognitive impairment occurs after surgery and general anesthesia and persists
in some older patients. Whether surgery and anesthesia cause this POCD de
novo versus uncovers a pre-existing problem is hotly debated.
2. POCD is not a clinical diagnosis. It is also phenotypically distinct from delirium
(typically acute, with a time course of hours to days) and dementia (insidious,
chronic, and progressive), possibly suggesting a different mechanism.
3. POCD nomenclature is confusing (Is mental fogginess on postop day 3 or 30
the same?). Look for introduction of a new classification system, likely in late
2016 or early 2017.
4. There are currently no proven ways to prevent or treat POCD. However, better
preoperative screening of geriatric surgical patients, looking specifically for pre-
existing cognitive impairment, frailty, and functional dependence, may identify
the patient at greatest risk and help resolve the question of whether POCD was
there before surgery (preoperative cognitive dysfunction?) or occurs anew after.
In summary, older patients having surgery and anesthesia are at risk for cognitive
complications postoperatively. There is therefore good reason for anesthesiologists
and surgeons to be informed about the issues and to do what we can to promote
postoperative cognitive health. Our elderly patients and their families are interested
but there is still much to study and do to improve cognitive outcomes for these
patients.
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New guidelines for pediatric advanced life support (PALS) for anesthesiologists
and perioperative considerations
Jayant K. Deshpande, M.D., M.P.H. Little Rock, AR
This lecture will provide the anesthesiologist a) a summary of the new (2015) American Heart Association
guidelines for pediatric life support and b) a discussion on management of perioperative cardiac arrest
resulting from selected causes.
Pediatric Basic Life Support (highlights of 2015 AHA recommendations)

 Check for responsiveness. Check for breathing and pulses (no more than 10 seconds).
 Just open the airway - No need to “Look, Listen, and Feel for Breathing”.
 C-A-B: compressions-airway-breathing is still recommended for infants and children.
 Witnessed arrest: activate emergency response/call for help/AED and start CPR;
 Unwitnessed arrest: provide 2 min CPR and call for help/AED
 Use AED when available.
 Chest compression depth: Appropriate depth for chest compressions is at least 1/3 of the anterior-
posterior chest diameter, or approximately 1½ inches (4 cm) for infants; 2 inches (5 cm) for children.
 Compression:ventilation ratio: 1 rescuer 30:2; 2 rescuers 15:2
 Compression rate: 100-120 per minute; Ventilation rate: 10 breaths/minute
 Allow full chest recoil. Minimize interruptions in compressions to <10 seconds.
 Defibrillation and use of the AED in infants: For infants, use a manual defibrillator instead of an
AED. If manual defibrillator is not available, use AED with a pediatric dose attenuator. If neither is
available, use AED without the pediatric dose attenuator.
Pediatric Advanced Life Support (highlights of 2015 AHA recommendations)

 Monitor exhaled CO2: use clinical assessment and exhaled CO2 detection to confirm tracheal tube
position for patients with perfusing rhythm in all settings and during interhospital/intrahospital
transport. Continuous monitoring can be beneficial during CPR to gauge effectiveness of chest
compressions.
 Defibrillation energy doses: Initial dose is 2-4 J/kg. For refractory VF, dose may be increased
start with 4 J/kg (biphasic) up to but not to exceed 10 J/kg (maximum dose 360 J monophasic).
 Arrhythmia treatment: Amiodarone or lidocaine is equally acceptable for the treatment of
shock-refractory VF or pVT in children. Lidocaine has been added back to the algorithm.
 Use 100% FiO2 for resuscitation. After resuscitation, limit supplemental oxygen to achieve
SPO2 94-99%. Avoid hyperoxia as well as hypoxia after resuscitation.
 Resuscitation of infants and children with congenital heart disease: The guidelines include
resuscitation measures for cardiac arrest in infants and children with single-ventricle anatomy,
Fontan or hemi-Fontan / bidirectional Glenn physiology, and pulmonary hypertension.
 Targeted temperature management: Avoid hyperthermia. For comatose children resuscitated
from OHCA, reasonable to maintain 5 days of normothermia (36°C to 37.5°C) or 2 days of
initial continuous hypothermia (32°C to 34°C) followed by 3 days of normothermia.
 Rapid response team (RRT) or medical emergency team (MET) systems can be effective in
reducing the incidence of cardiac arrest, particularly in the general care wards. The use of early
warning sign systems (e.g., Pediatric Early Warning Signs or PEWS) may also reduce in-hospital
morbidity and mortality.
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Perioperative cardiac arrest progressively has become less of a concern as anesthetics and anesthesia practices have
improved. Therefore, pediatric anesthesiologists may not be facile in resuscitation and post-resuscitation care.
Knowledge of the epidemiology of pediatric cardiac arrest and of current resuscitation techniques may further
reduce the associated morbidity and mortality. Recent studies of pediatric cardiac arrest (Flick et al 2007;Bhananker
et al 2008) indicate that the principal causes of perioperative arrest have remained fairly consistent throughout the
years. In decreasing order these are cardiovascular, respiratory, medication, equipment, combination of events and
other miscellaneous causes. Intraoperative arrests often are related to the cardiovascular system while respiratory
events are more likely to cause postoperative arrests. Higher ASA physical status and emergency procedures have
the highest association with perioperative cardiac arrest in children.
Epidemiology
Cardiac arrest in infants and children who are in-hospital or in the perioperative setting may occur from various
causes. Causes include Respiratory failure, Sepsis, Drug toxicity or overdose, metabolic disturbances and
dysrhythmias. Perioperative cardiac arrest may occur because of cardiovascular reasons; respiratory obstruction or
failure; medication overdose or adverse reactions; equipment failure or malfunction; a combination of events.
The causes of cardiac arrest are different for the different phases of care. In the presurgical setting, cardiovascular,
respiratory and medication related events are equally likely as the underlying cause of cardiac arrest.
Intraoperatively, the precipitating cause most likely is a cardiovascular event. Post-operatively, respiratory causes
account of the majority of cases, followed by cardiovascular events. The anesthesiologist must be cognizant of the
common causes in the different phases of surgical experience in order to properly treat the patient in a timely
manner. (Bhananker et al 2007; Christensen et al 2013) A recent study by De Bruin and colleagues (2015) reiterated
the risk factors for perioperative mortality: young age (neonates and infants), ASA physical status III or higher, and
emergency and cardiothoracic surgery. However, anesthesia and/or surgical causes comprise only a small percent of
these cases. Similarly, Schleleein et al (2016) found that decreased age, increased preoperative comorbidities,
multiple (vs single) surgical services involved in the care, location (operating room vs. nonoperating) location, and
decreased staff experience were associated with increased risk of events, which were predominantly respiratory in
origin.
Cardiorespiratory arrest in infants and children is an infrequent phenomenon as compared to adults. In the majority
of cases the etiology is respiratory distress and failure which can lead to cardiac arrest if not treated and reversed in a
timely manner. Primary cardiac events leading to arrest are rare in infants and children, whereas in adults cardiac
arrest may be the primary event resulting from dysrhythmias, which can quickly deteriorate to a non-perfusing state.
Out-of-hospital arrests have a poor prognosis, with less than 9% survival to hospital discharge. For in-hospital
arrest, CPR is successful in restoring spontaneous circulation in over 60% of patients. However, the rate of survival
to discharge decreases rapidly to approximately 15% or less.
Respiratory Failure
Successful cardiorespiratory resuscitation of infants and children begins with early recognition and reversal of
respiratory distress or shock.
Respiratory distress may be characterized by tachypnea, increased respiratory effort, nasal flaring, intercostal,
subcostal or substernal retractions, and stridor or grunting. Lethargy in a child with respiratory distress is a bad sign
indicating impending respiratory failure and requires immediate treatment. Other signs include inadequate or low
respiratory rate, decreased unilateral or bilateral breath sounds and pallor or cyanosis. Untreated, the patient will
suffer respiratory failure – defined as inadequate ventilation and possibly respiratory arrest.
Shock
Shock is defined as blood flow and oxygen delivery that is inadequate to meet metabolic demands. During the early
stage of compensated shock, tachycardia and peripheral vasoconstriction may sustain systemic blood pressure and
vital organ perfusion at marginally adequate levels. When the body’s ability to compensate is exceeded,
decompensated shock leads to rapid deterioration reflected as systemic hypotension and weak central pulses.
Because the normal values for vital signs vary with age, signs of compensated or decompensated shock may be easy
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to miss. Bradycardic shock or arrest in infants and children is characterized by a heart rate significantly lower than
expected (usually under 100) in the presence of other signs of circulatory failure.
Airway
Airway problems are a leading cause of respiratory distress and failure in children. Young infants are obligate nose
breathers who may develop significant distress which may be relieved by suctioning of the nostrils. The infant
anatomy may contribute to airway obstruction because of the relatively large tongue, rostrally placed larynx (“more
anterior”) and large occiput. Proper positioning of the head and neck or placement of an oral airway may relieve an
apparent airway obstruction. Airway adjuncts including laryngeal mask airway and endotracheal intubation should
be used as appropriate.
Oxygen
Standard recommendations for resuscitation include the use of 100% oxygen. This recommendation is classified as
Indeterminate because of the possible adverse effects of 100% inspired oxygen. These effects include increased
cerebrovascular resistance, oxidative stress on lung, cardiac and other tissues, and atelectasis. Once the patient has
been resuscitated, the FiO2 should be decreased to a level sufficient to maintain adequate systemic oxygen levels.
Ventilation
Manual ventilation during resuscitation often results in significant overventilation. Overexpansion of infant lungs
may result in barotrauma and even pneumothorax, and impede proper venous return and affect cardiac output.
Hypocapnia may exacerbate brain hypoperfusion. Therefore, care should be used to provide ventilation that is
adequate to inflate the lungs while avoiding overdistention.
Cuffed Versus Uncuffed Tubes

Both cuffed and uncuffed tracheal tubes are acceptable for infants and children. If cuffed tracheal tubes are used,
avoid excessive cuff pressures. Appropriately sized endotracheal tubes should be used and care should be taken to
minimize glottic and subglottic trauma. Tube size can be approximated as (age in years/4) + 4 for uncuffed tubes
and (age in years/4) + 3 for cuffed tubes. Even in emergency situations, tube placement should be confirmed by
chest auscultation and by detection of exhaled CO2.
Vascular Access
PALS guidelines emphasize the need for timely vascular access. If peripheral access is not obtained within 90
seconds, intraosseous (I/O) needle placement is advised. All resuscitation carts and operating rooms should have
access to I/O needles. Experienced providers may be able to place a central line for more secure access, but the
procedure may impede the ability to perform adequate chest compressions during cardiac arrest. In the absence of
IV or I/O access, most emergency medications may be administered via the endotracheal route but will require
higher doses than with the IV or I/O route.
Cardiac Arrest
Pulseless arrest requires both ventilatory support and effective chest compressions. The likelihood of effective
resuscitation and return of spontaneous circulation improves with starting timely and adequate chest compressions.
The goal is to achieve longer periods of diastolic pressure sufficient to perfuse the coronaries. Therefore, the
pediatric recommendations are similar to those for adults. For single rescuer, 2 breaths are given after each 30
compressions. The two rescuer method involves a ratio of 15 compressions to 2 manual ventilations. Compressions
should be of sufficient depth (1/3 to 1/2 of the anterior-posterior chest diameter) and allow full recoil of the chest.
The compression rate for all ages is 100/minute. Chest compression often is inadequately performed (Niles et al
2012).
Fluids and Medications

Dosing of fluids and medications in children is based on the child’s weight. Patients in hospital should have a
recently measured weight and pre-calculated doses of emergency medications available at the bedside. If the child’s
weight is unknown, length-based tape measures with pre-calculated doses have been validated and are commercially
available.
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Isotonic crystalloid solutions should be used for resuscitation. Glucose containing solutions are not recommended
for routine use. Because infants are at high risk for developing hypoglycemia, blood glucose should be measured
early during the resuscitation.
Resuscitation medications for children are similar to those used in adults. When indicated in pulseless cardiac
arrest, the “standard dose” of epinephrine IV is 0.01 mg/Kg. The higher dose may in fact have significant adverse
effects including worse outcomes, such as hypertension, ventricular ectopy, myocardial necrosis and prolonged
myocardial dysfunction.
Defibrillators in Pediatric Resuscitation

Because most pediatric arrests are a result of respiratory events, the most common dysrhythmias in children are
asystole and bradycardia with a wider QRS complex. Sudden cardiac arrest in children may result from ventricular
fibrillation (VF) or pulseless electrical activity (PEA). For children with VF, defibrillation may be a life-saving
intervention with the chance of survival approaching 20%. Out-of-hospital pediatric arrests are associated with 5-
15% incidence of VF. For these children, especially those with witnessed sudden cardiac arrest, defibrillation has
resulted in rapid resuscitation and functional survival. Because of the significant benefit of automated external
defibrillators (AED’s), many communities have instituted Public Access Defibrillator (PAD) programs.
Supraventricular tachycardia (SVT) and ventricular tachycardia (VT) in children may be associated with a pulseless
state or pulses may be present. For the pulseless patient, treatment should be instituted according to the cardiac
arrest guidelines. If pulses are present, treatment should include oxygen and airway support and assessment of the
underlying cardiac rhythm. Narrow QRS complexes likely represent supraventricular tachycardia which may be
treated progressively with vagal stimulation, intravenous adenosine, and electrocardioversion. Amiodarone or
procainamide may be needed if the SVT is unresponsive to other treatments or the rhythm relapses. These
medications prolong the QT interval and therefore should be used with caution. Wide complex tachycardia may
represent SVT with aberrant conduction or VT. This rhythm may respond to electrocardioversion but often requires
amiodarone or procainamide as well.
Torsade de Pointes
This is a polymorphic form of VT in children which may be congenital in origin or occur because of toxicity of
certain antiarrhythmics, antidepressants, or drug interactions. Intravenous magnesium sulfate is the treatment of
choice for torsade of any etiology. The initial dose of magnesium is 25 - 50 mg/Kg IV.
Duration of CPR
In general, the longer a patient needs CPR the worse the expected outcome. However, the situation in the pediatric
perioperative setting may be different. Matos et al (2013) reported that CPR duration was inversely associated with
survival to hospital discharge and neurological outcome, even after adjustment for confounding factors. Surgical
cardiac patients had improved outcomes compared with patients in all other illness categories. Importantly, the study
suggests that some children who might die without CPR survive with a favorable neurological outcome even after
prolonged CPR.
Rapid response ECMO (ECPR)

In some centers extracorporeal membrane oxygenation (ECMO) is available and has been used for rescue after
cardiac arrest (ECPR). Turek et al reviewed 3 years’ experience from several center and found that pediatric RR-
ECMO program for venoarterial ECMO initiation was associated with reduced neurologic complications. But RR-
ECMO did not improve survival during the first 3 years of program implementation. The 2015 Guidelines state that
if available, the use of ECPR may be considered for selected patients in settings where a reversible cause of cardiac
arrest is suspected.
Miscellaneous
Cardiorespiratory arrest in children may occur as a result of toxic ingestion. A focused history and rapid diagnostic
tests may indicate the specific causative toxin or medication. Treatment of the systemic effects depends on the
ingested drug or toxin. Tricyclic antidepressants, -blockers, calcium channel blockers, methamphetamine and
cocaine pose additional challenges.
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Post-Resuscitation Neuroprotection
Preservation of brain function and prevention of secondary brain injury is an important goal of resuscitation.
Hyperventilation and hypocapnea should be avoided as there is no demonstrated benefit. Severe hypocapnea may
cause cerebral ischemia and myocardial dysfunction. Maintaining a normal body temperature is a foundational
practice in pediatric anesthesia. Hyperthermia can have deleterious effects on brain recovery. Rapid rewarming of a
child during and after resuscitation is not necessary as it may result in hyperthermia. In patients who remain
comatose, therapeutic hypothermia (32oC-34oC) may improve brain recovery.
CARDIAC ARREST IN THE PEDIATRIC PERIOPERATIVE SETTING

Causes of circulatory failure may be categorized as related to: a) intravascular volume (low preload, volume
redistribution, obstructed venous return), b) myocardial contractility (dysfunction; contractility), c) vascular
resistance, or d) heart rate/rhythm. Respiratory failure may result from: a) upper airway issues, b) lower airway
issues, c) parenchymal disease or d) disordered control, among others. Several special circumstances related to
anesthetic management and surgery warrant mention. These will be discussed in more detail during the Refresher
Course. Anesthetic agent related effects include overdose of Intravenous or Inhalation anesthetic. A high neuraxial
block may result in near-total sympathectomy. Unsuspected malignant hyperthermia or drug administration errors
may result in circulatory compromise. Hypoxemia, auto PEEP, or acute bronchospasm may go undetected or
untreated. Cardiovascular effects of interventions under anesthesia may result cardiac arrest or circulatory
compromise. Infants and young children with high parasympathetic tone may experience severe bradycardia
induced by Vasovagal reflex. Other conditions that can result in arrest include hypovolemic and/or hemorrhagic
shock, tension pneumothorax, anaphylactic reaction, transfusion reaction, acute electrolyte imbalance (high K) –
particularly after succinylcholine administration, severe pulmonary hypertension, increased intraabdominal pressure
(e.g., laparoscopy) and known or unrecognized prolonged QT syndrome, pulmonary embolism, gas embolism.
Anaphylaxis
Common causes include IV contrast agents, latex, beta lactam antibiotics, non-depolarizing neuromuscular blockers.
The management of the patient with anaphylaxis consists of measures to interrupt the reaction and support the
patient. Surgery should be interrupted when feasible and the patient should be immediately supported with IV fluid
and vasopressors. It is imperative to remember that the Epinephrine administered to patients with anaphylaxis is
intended to interrupt the reaction, and not support the circulation. Thus it should always be given and at the full
recommended dose (0.01 mg/kg, or approximately 1mg in most adults).
Complications of Central Venous Access

Pneumothorax is a well described and relatively rare complication of central line placement in perioperative
patients. Most practitioners astutely suspect this complication in patients who become unstable after undergoing
central venous cannulation. More recent analysis from the closed-claims database suggests that both hemo-
pneumothorax and tamponade may be important and sometimes unrecognized fatal complications of patients who
undergo attempts at central venous cannulation. In those instances where a patient deteriorates following central line
placement, echocardiography should be considered in addition to chest radiography.
Local Anesthetics
Risk of local anesthetic toxicity is difficult to predict. In general, local anesthetics depress the heart in a dose
dependent fashion. Of the local anesthetics in widespread clinical use, bupivacaine is the most potent myocardial
depressant and most often associated with cardiac arrest. Most children receive local anesthetic blocks while they
are under general anesthesia. Therefore, clinical symptoms that may presage cardiac arrest in this setting are usually
masked. Signs of local anesthetic toxicity include PVCs, wide QRS complex EKG which can subsequently
deteriorate into EMD/PEA or asystole (bupivicaine), bradycardia or atrioventricular block (lidocaine and
etidocaine). Treatment includes stopping the administration of local anesthetic, CPR as indicated (pulseless for >10
sec), Epinephrine 10 mcg/Kg, tracheal intubation and ventilation with 100% oxygen. Intralipid (20%) 1.5ml/Kg IV
load, then 0.25ml/Kg/hr IV may be lifesaving. Sodium Bicarbonate should be used to maintain a pH >7.25. Other
treatment may include H1 and H2 blockers, transcutaneous or intravenous pacemakers for all bradycardic rhythms.
Continue CPR for at least 60 minutes, as very good neurologic recovery has been reported in patients after very
prolonged cardiac arrests from local anesthetic overdoses.
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Summary
The 2015 updated guidelines for pediatric advanced life support emphasize early recognition and treatment. Key
factors to successful resuscitation include early recognition/intervention, quality of chest compressions with minimal
interruptions, effective team work, and good post-resuscitation care (e.g., targeted temperature management).
Perioperative cardiac arrest in children may occur from a variety of causes, needing different treatments. Aids like
the Pediatric Critical Events Checklist (Apple App Store) developed by Children’s Hospital of Philadelphia and
Society for Pediatric Anesthesia allow anesthesiologists to provide timely resuscitative efforts.
Summary of Selected Doses in Pediatric Resuscitation

Dosage Comment
Adenosine 0.1 – 0.2 mg/Kg SVT
Amiodarone 5 mg/Kg Refractory VF or pulseless VT
(up to 3 doses)
Epinephrine 0.01 mg/Kg Pulseless or Bradycardic

Arrest
Intralipid (20% 1.5 mL/Kg bolus over 1 May need repeat doses. Max
emulsion) min then infusion 0.25 total dose of 10 mL/kg of lipid
mL/Kg/min for 10 min emulsion over 30 min.
Lidocaine 1 mg/kg bolus Refractory VF or pulseless VT
Magnesium 25 – 50 mg/Kg Torsade de Pointes
Cardioversion 0.5 – 1 joule/Kg SVT
Defibrillation 2-4 joules/Kg Ventricular fibrillation
(max 4 joules/Kg)
AED (Automatic Adult dose > 8 yoa Sudden Collapse

External
Pediatric attenuator < 8 Pulseness
Defibrillation)
yoa
VT/VF
See de Caen (Circulation, 2015) and Shaffner (Anesth Analg 2013) for detailed guidelines and precautions.
Recommended Reading:
Atkins DL, Berger S, Duff JP, Gonzales JC, Hunt EA, Joyner BL, Meaney PA, Niles DE, Samson RA, Schexnayder
SM. Part 11: pediatric basic life support and cardiopulmonary resuscitation quality: 2015 American Heart
Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.
Circulation. 2015;132(suppl 2):S519–S525.
Aufderheide T, Lurie KG: Death by hyperventilation: a common and life-threatening problem during
cardiopulmonary resuscitation. Crit Care Med 2004; 32[Suppl]:S345-351.
Berg RA, Otto CW, Kern KB et al: A randomized, blinded trial of high-dose epinephrine versus standard-dose
epinephrine in a swine model of pediatric asphyxial cardiac arrest. Crit Care Med 1996, 24:1695-1700.
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Bhananker SM, Ramamoorthy C, Geiduschek JM, Posner et al: Anesthesia-related cardiac arrest in children: update
from the pediatric perioperative cardiac arrest registry. Anesth Analg 2007;105:344 –50.
Boudreaux ED, Francis JL, Loyacano T: Family presence during invasive procedures and resuscitations in the
emergency department: a critical review and suggestions for future research. Ann Em Med 2002; 40:193-205.
de Caen AR, Berg MD, Chameides L, Gooden CK, Hickey RW, Scott HF, Sutton RM, Tijssen JA, Topjian A, van
der Jagt E, Schexnayder SM, Samson RA. Part 12: pediatric advanced life support: 2015 American Heart
Circulation. 2015;132(suppl 2):S526–S542.
Christensen R, Voepel-Lewis T, Lewis I, et al: Pediatric cardiopulmonary arrest in the postanesthesia care unit:
analysis of data from the American Heart Association Get With The Guidelines(®) -Resuscitation registry. Paediatr
Anaesth. 2013 Jun;23(6):517-23. doi: 10.1111/pan.12154. Epub 2013 Apr 1.
Turek JW, Andersen ND, Lawson DS, et al: Outcomes Before and After Implementation of a Pediatric Rapid-
Response Extracorporeal Membrane Oxygenation Program. Ann Thorac Surg. 2013 Mar 15. pii: S0003-
4975(13)00222-1. doi: 10.1016/j.athoracsur.2013.01.050. [Epub ahead of print].
Davis PG, Tan A, O’Donnell CPF et al: Resuscitation of newborn infants with 100% oxygen or air: a systematic
review and meta-analysis. Lancet 2004; 364:1329-1333.
Flick RP, Sprung J, Harrison TE, et al: Perioperative cardiac arrests in children between 1988 and 2005 at a tertiary
referral center. Anesthesiology 2007; 106:226–37.
Gabrielli A, O’Connor MF, Macchioli GA. Anesthesia Advanced Circulatory Life Support. American Society of
Anesthesiology Committee on Critical Care Medicine and American Society of Critical Care Anesthesiology.
February 2008. Downloaded May 2010 from <http://asahq.org/clinical/Anesthesiology-CentricACLS.pdf>.
Perondi M, Reis A, Paiva E, et al: A comparison of high-dose and standard-dose epinephrine in children with
cardiac arrest. N Engl J Med 2004; 350:1722-1730.
Matos, R. I., R. S. Watson, et al. (2013). "Duration of Cardiopulmonary Resuscitation and Illness Category Impact
Survival and Neurologic Outcomes for In-hospital Pediatric Cardiac Arrests." Circulation 127(4): 442-451.
Niles DE, Nishisaki A, Sutton RM, et al: Comparison of relative and actual compression depths during cardiac arrest
in children, adolescents and young adults. Resuscitation 2012; 83:320-326.
Ramamoorthy C, Haberkern CM, Bhananker SM, Domino KB, Posner KL, Campos JS, Morray JP. Anesthesia-
Related Cardiac Arrest in Children with Heart Disease: Data from the Pediatric Perioperative Cardiac Arrest
(POCA) Registry. Anesth Analg 2010; 110:1376-1382.
Reis AG, Nadkarni V, Perondi MB, et al: A prospective investigation into the epidemiology of in-hospital pediatric
cardiopulmonary resuscitation using the internation Utstein reporting style. Pediatrics 2002, 109:200-209.
Schleelein, L. E., Vincent, A. M., Jawad, et al. Pediatric perioperative adverse events requiring rapid response: a
retrospective case–control study. Pediatric Anesthesia, 26: 734–741.
Shaffner DH, Heitmiller ES, Deshpande JK. Pediatric perioperative life support. Anesth Analg 2013; 117:960-979.
Spittler KL: Family presence during CPR and invasive procedures. Pulmonary Reviews.Com 2006; 11(3).
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Perioperative Management of Pulmonary Hypertension
Ronald G. Pearl, M.D., Ph.D. Stanford, California
When the World Health Organization organized the first international conference on pulmonary
hypertension (PH) in 1973, there were no effective therapies, and survival in patients with primary pulmonary
hypertension (now termed idiopathic pulmonary arterial hypertension) was less than three years. Today, there are
multiple disease-modifying therapies, and survival has more than doubled. As a result, more patients with PH
undergo anesthesia and surgery. Successful management of the perioperative patient with PH requires seven steps:
recognizing the disorder, diagnosing the etiology, assessing the severity of the disease, assessing the risks and
benefits of anesthesia and surgery, developing an anesthetic plan, choosing the right monitoring, and managing the
anticipated complications of systemic hypotension and right heart failure (Fox, Hosseinian, Pilkington, Pritts,
Schisler, Yang).
The pulmonary circulation is normally a low pressure, low resistance circulation, and the stroke volume of
the thin-walled right ventricle decreases in response to increased pulmonary artery pressure (PAP). PH is defined as
a mean PAP ≥ 25 mmHg at rest. In patients with PH, altered vascular endothelial and smooth muscle function lead
to vasoconstriction, localized thrombosis, and vascular growth and remodeling. These processes increase pulmonary
vascular resistance (PVR), resulting in RV failure, inadequate oxygenation and death (Ryan; Vonk Noordegraaf).
PH markedly increases morbidity and mortality among patients undergoing surgery (Kaw, Minai, Price,
Ramakrishna; Schisler). Understanding the pathophysiology of PH allows accurate risk assessment, optimization
prior to surgery, and goal-directed intraoperative and postoperative treatment.
An approach to understanding the pathophysiology of PH is derived from the equation for PVR:
PVR = (PAP - LAP) / CO
where PVR is in Wood units (1 unit = 80 dynes.sec.cm-5). Rearranging this equation for PAP demonstrates that:
PAP = LAP + (CO x PVR)
Thus, the three factors which increase PAP are increased LAP, increased cardiac output, and increased PVR.
Therapy of the perioperative patient with PH requires an assessment of the quantitative contribution of each
component. For example, patients with mitral stenosis who have increased PAP due solely to increased LAP have
uncomplicated perioperative courses, but patients with mitral stenosis who have increased PAP due to increased
PVR frequently develop severe RV failure after surgery. Pulmonary vasodilator therapy would be inappropriate in
one patient but life-saving in the other. In patients with PH, analyzing whether cardiac output remains normal or is
markedly decreased helps assess perioperative risk (see section on risk assessment).
The current classification of PH involves five major categories (pulmonary arterial hypertension, PH due to
left-heart disease, PH due to lung disease or hypoxia, chronic thromboembolic disease, and PH with unclear or
multifactorial etiologies (Simonneau). It is important to distinguish between pre-capillary etiologies which have
increased PVR and an increased transpulmonary gradient (PAP minus LAP) and post-capillary etiologies which
have increased LAP. The above equation for PAP can be used to characterize the common etiologies of PH.
Increased LAP includes LV failure and valvular heart disease (particularly mitral stenosis and/or regurgitation).
Increased cardiac output includes patients with congenital heart disease with cardiac shunts. The major categories of
chronically increased PVR are pulmonary disease (parenchymal or airway), hypoxia without pulmonary disease
(hypoventilation syndromes, high altitude), pulmonary arterial obstruction (thromboembolism), and idiopathic
(primary) pulmonary hypertension. In addition to these etiologies of chronic PH, acute increases in PVR may result
from hypoxia, hypercarbia, acidosis, increased sympathetic tone, and endogenous or exogenous pulmonary
vasoconstrictors such as catecholamines, serotonin, thromboxane, and endothelin. Most perioperative patients with
decompensated PH have an acute increase in PVR superimposed on chronic PH; in general, therapy is directed at
reversing this acute increase in PVR.
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Evaluation: The diagnosis of PH is usually suspected either from symptoms or from diseases associated with
increased risk. Evaluation of the patient with pulmonary hypertension should determine the underlying diagnosis
and the severity of the disease (Haddad R; Hambly). History and physical examination should focus on issues such
as underlying lung disease, congenital heart disease, myocardial or valvular heart disease, thromboembolic disease,
connective tissue disease, liver disease, HIV infection, prior intravenous drug use, prior use of appetite-suppressant
drugs, and family history of pulmonary hypertension. Patients should be considered for evaluation for sleep-
disordered breathing, either as the primary etiology or as a complicating factor. Laboratory tests should include
routine chemistries, hematology, thyroid function tests, HIV serology, and autoimmune screen (antinuclear
antibodies including anti-centromere antibody, anti-SCL70, and ribonucleoproteins). Ventilation-perfusion lung
scan should be performed to exclude chronic thromboembolic PH; patients with this disorder should be considered
for surgical thromboendarterectomy (Banks, Jenkins, Shenoy). Echocardiography with Doppler measurements can
determine right ventricular function and right ventricular systolic pressure (Grünig Haddad F, Vonk-Noordegraaf).
Pulmonary artery catheterization will quantify pulmonary hemodynamics and demonstrate whether patients with
pulmonary arterial hypertension are reactive to vasodilators (Galie, Sharma). Vasodilator responsiveness should be
assessed with a short-acting vasodilator such as inhaled nitric oxide, inhaled prostacyclin, or intravenous adenosine;
vasodilator-responsive patients should be considered for chronic therapy with calcium channel blockers.
Measurement of PAP, cardiac index, PVR, and right atrial pressure can be used to predict survival. Other major
prognostic factors include the etiology of PH, functional status, renal insufficiency, age, systolic blood pressure,
heart rate, BNP level, pericardial effusion, DLCO on pulmonary function testing, and PVR (Cogswell). The six
minute walk test can be used to evaluate functional impairment, prognosis, and response to therapy.
Perioperative risk assessment: In the face of increased impedance to RV ejection, the compensatory reserves of
the RV are limited. Reductions in RV stroke volume and cardiac output occur, eventually resulting in ventricular
interdependence with decreased LV filling (Vonk-Noordegraaf). In the patient with PH, anesthesia and surgery may
produce hemodynamic deterioration and death due to additional increases in PVR and decreases in RV function.
Patients with PH have markedly increased morbidity and mortality with anesthesia and surgery (Kaw,
Madden, Meyer, Minai, Price, Ramakrishna, Rex). For patients with Eisenmenger's syndrome undergoing cesarean
section, mortality is as high as 70% (Lane). However, recent data suggest much lower mortality rates in both non-
cardiac surgery and in obstetrics, particularly in experienced centers with multidisciplinary PH teams (Jais,
Maxwell, Meyer). Patients undergoing liver transplantation have increased mortality related to the severity of the
PH, with mortality rates as high as 100% when the mean PAP exceeds 50 mm Hg (Ayoub). The risks associated
with idiopathic (primary) PH appear to be even higher than those related to secondary PH. Reports of successful
outcomes of surgery in patients with severe PH include curative procedures such as lung or heart-lung
transplantation, cesarean section, and minor procedures such as lung biopsy, cholecystectomy, femoral artery repair,
and laparoscopic tubal ligation.
Survival in patients with PH correlates with the ability of the RV to compensate for the increased PVR as
assessed by cardiac output, right atrial pressure, and functional status. These factors also are major predictors of
perioperative risk in the surgical patient. Perioperative risk is also related to the surgical procedure (MInai,
Ramakrishna). Procedures with rapid blood loss may result in fatal hypotension since venous return is required to
compensate for increased RV afterload. Major procedures which result in a systemic inflammatory response
syndrome (SIRS) may exacerbate PH. Finally, some procedures may pose special risks for the patient with PH, such
as pulmonary embolization of air, bone marrow, and cement during joint replacement surgery, hypercarbia and
atelectasis during laparoscopy and resection of pulmonary vasculature during lung surgery. Risk assessment requires
balancing the patient reserves against the increased demands of the surgical procedure. For the patient at high risk, a
preoperative pulmonary vasodilator trial with inhaled nitric oxide or prostacyclin may provide additional prognostic
information and be used for subsequent perioperative therapy.
In patients who pose an unacceptably high risk following optimization of therapy, consideration should be
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given to lung or heart-lung transplantation or to chronic treatment to decrease PH to acceptable levels before
surgery. Several authors and societies have created guidelines for the management of pulmonary hypertension
(Galie, Hoeper). In general, oral calcium channel blockers are used for patients with vasoreactivity, and prostanoids
(epoprostenol, treprostinil, or iloprost), endothelin antagonists, and PDE5 inhibitors (sildenafil or tadalafil) are used
in patients who either do not have acute vasoreactivity or fail calcium channel blocker therapy (McLaughlin).
Riociguat, a direct stimulator of guanylate cyclase, was recently approved (Ghofrani). The choice of specific agents
is primarily based upon the patient’s functional status, and combination therapy is increasingly used (Galie,
Pullamsetti).
Preparation of the Patient for Anesthesia and Surgery: Prior to anesthesia and surgery, patients with PH should
have an electrocardiogram, chest X-ray, arterial blood gas, and echocardiogram. Evidence of significant RV
dysfunction should prompt re-evaluation of the need for surgery. All attempts to reduce PH prior to surgery should
be performed, such as the administration of oxygen, bronchodilators, antibiotics, and steroids to the patient with
obstructive lung disease, and vasodilators and inotropes to the patient with cardiac disease.
Patients receiving chronic therapy for PH should continue on such therapy throughout the perioperative
period. Patients on chronic prostacyclin (epoprostenol) or treprostinil infusions should have the infusion continued
throughout the perioperative period, and management of hypotension should be with vasopressor therapy rather than
with downward titration of the infusion. Our approach at Stanford has been that a nurse specializing in PH converts
the infusion to the hospital pump system prior to surgery. Although prostacyclin inhibits platelet aggregation,
surgical bleeding is rarely a problem. Patients on chronic inhaled iloprost should receive a treatment prior to surgery.
If they are unable to continue inhaled iloprost after surgery, consideration should be given to perioperative inhaled
nitric oxide or nebulized prostacyclin.
Anesthetic management: The anesthetic management of patients with PH undergoing noncardiac surgery remains
controversial (Fox, Galante, Gille, Hosseinian, Pilkington, Pritts, Ross, Strumpher, Thunberg). Most reports have
involved obstetrical anesthesia in adults and repair of congenital heart defects in pediatrics. Most authors agree that
the way a specific anesthetic technique is managed is as important as the choice of the technique. In the absence of
evidence-based recommendations, anesthesiologists need to focus on basic hemodynamic principles.
Physiologic Considerations and Goals: The anesthetic plan for the patient with PH must account for the
underlying pathophysiology. The major abnormality is the elevated PVR, which increases RV afterload, thereby
increasing RV work and decreasing RV (and thus LV) output. Based on the underlying pathophysiology, the major
anesthetic considerations include:
1) Preload: Maintenance of preload (intravascular volume) at normal or increased levels is essential to
maintain cardiac output in the face of increased RV afterload.
2) Systemic vascular resistance (SVR): In normal hemodynamic states, SVR is a major determinant of LV
afterload (and, therefore, cardiac output). In PH, cardiac output is limited by RV function and is therefore
independent of SVR. In order to avoid systemic hypotension, SVR must be maintained in the normal-to-high range.
3) Contractility: Maintenance of normal-to-high contractility is essential to maintain cardiac output in the
face of increased RV afterload.
4) Heart rate and rhythm: Sinus rhythm is important for adequate filling of a hypertrophied right ventricle.
Stroke volume is limited by ventricular afterload, so bradycardia should be avoided. Patients with PH commonly
have excess vagal activity.
5) Avoidance of myocardial ischemia: Right ventricular subendocardial ischemia due to myocardial oxygen
supply-demand imbalance is common in PH. Systemic hypotension and excessive increases in preload, contractility,
and heart rate must be avoided.
6) Pulmonary vascular resistance: In PH, PVR is the major factor governing RV afterload and cardiac
output. Therefore, increases in PVR must be avoided and therapy to decrease PVR may be required.
7) Avoidance of hypotension: Systemic hypotension precipitates RV failure by decreasing coronary
perfusion of the RV and by decreasing the contribution of the interventricular septum to RV ejection.
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Perioperative Monitoring: Monitoring during anesthesia must be adequate to detect the causes and complications
of increased PVR. Arterial catheterization allows continuous blood pressure monitoring and arterial blood gas
measurements. Monitoring of preload requires understanding the altered physiology of PH. In the absence of PH,
cardiac output is determined by LV function, and preload is estimated by pulmonary artery occlusion (wedge)
pressure (PAOP). However, in severe PH, cardiac output is limited by RV function, so the relevant measurement is
right atrial pressure or CVP. Therefore, in severe PH, volume administration should be governed by CVP rather than
PAOP. In fact, excess volume administration may exacerbate RV failure and produce further hemodynamic
deterioration. In moderate PH, cardiac output varies with both left and right ventricular performance. In this case,
monitoring both CVP and PAOP and observing the response to volume administration is the best method for
assessing preload. Intraoperative transesophageal echocardiography (TEE) allows continuous assessment of the
filling and function of both ventricles.
Pulmonary artery catheterization allows measurement of CVP, PAOP, PAP, cardiac output, PVR, and
SVR. These values can guide therapy of systemic hypotension (see below). Monitoring mixed venous oxygen
saturation by pulmonary artery oximetry (or central venous saturation by oximetry) allows continuous assessment of
the adequacy of cardiac output. However, the risk of pulmonary artery catheterization in patients with PH is
increased, due to the high mortality of associated arrhythmias, pulmonary artery rupture, and venous air embolism or
thromboembolism. Thermodilution cardiac output determinations may be misleading if PH is associated with
anatomic shunting or tricuspid regurgitation. The risks and benefits of pulmonary artery catheterization must be
individually assessed. Pulmonary artery catheterization is usually not indicated in patients with intracardiac shunting
due to the high risk of catheter misdirection and the limited additional information over measurement of CVP alone.
Choice of Anesthetic Technique: Many anesthetic techniques have been successfully used in patients with PH.
Since general anesthesia in patients with PH has significant risks, peripheral nerve blocks should be considered
when appropriate. The use of neuraxial techniques (spinal or epidural block) may decrease SVR, and thereby
produce systemic hypotension when cardiac output is fixed due to PH. Thus, spinal anesthesia is contraindicated in
many patients. Epidural anesthesia has been successful in selected patients (Martin), particularly when the
magnitude of the block is limited, e.g., management of labor. Epidural anesthesia allows a slow onset of block and
titration of the extent of block so that adverse hemodynamic effects may be recognized in early stages and corrected.
Thoracic epidural blockade by itself has only minor hemodynamic effects but must be titrated slowly to avoid
bradycardia and decreased RV contractility. Excess sedation with associated respiratory depression should be
avoided when regional anesthesia is used. Intrathecal and epidural narcotics provide excellent pain relief
postoperatively or during labor without producing sympathetic blockade.
General anesthesia remains the method of choice for major surgery in many patients with PH. Isoflurane,
sevoflurane, and desflurane may produce beneficial pulmonary vasodilation, but decreased contractility and
decreased SVR can result in systemic hypotension. In general, patients with PH with adequate functional reserve
will tolerate volatile agents. Narcotic-nitrous oxide techniques maintain SVR, but may produce hypoxia and
decreased contractility; in addition, nitrous oxide increases PVR in patients with PH. In patients undergoing short
procedures with intense stimulation such as bronchoscopy, a remifentanil infusion can provide short-acting
analgesia. In poorly compensated patients, a high-dose narcotic-oxygen technique maintains preload, SVR, and
contractility without increasing PVR; in fact, the use of 100% oxygen may produce pulmonary vasodilation.
Dexmedetomidine has no direct effect on PVR and can be useful as an adjunct for general or regional anesthesia.
Anesthetic induction is an unstable period during which patients with PH are prone to develop systemic
hypotension and cardiovascular collapse; continuous monitoring of blood pressure by an arterial catheter is therefore
usually indicated prior to induction. Etomidate (supplemented by fentanyl) maintains systemic hemodynamics
during induction without affecting PVR and is usually the agent of choice. In contrast, pentothal and propofol may
decrease SVR, venous return, and/or contractility. Ketamine maintains systemic hemodynamics with little or no
increase in PVR when adequate ventilation is maintained (Friesen, Williams).
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Ventilatory management may affect PVR. Alveolar hypoxia produces pulmonary vasoconstriction, and
high inspired oxygen concentrations may produce pulmonary vasodilation. Hypercarbia with acidosis is a potent
pulmonary vasoconstrictor, and hypocarbia is a pulmonary vasodilator. Hyperventilation decreases the pulmonary
hypertensive response to various stimuli. PVR is dependent upon functional residual capacity (FRC), and PVR is
increased whenever FRC is increased or decreased from its normal value. Ventilatory parameters may affect both
FRC and peak lung volume. FRC is decreased during general anesthesia. This decrease in FRC can be reversed with
PEEP, resulting in a decrease in PVR. However, excessive PEEP will increase FRC above optimal values and
increase PVR. The effect of tidal volume on PVR may similarly be bimodal. At low tidal volumes, alveolar hypoxia
and hypercarbia may occur and thereby increase PVR. At high tidal volumes, lung volume compresses intra-alveolar
vessels and increases PVR. Therefore, ventilation of the patient with PH should use high concentrations of oxygen,
moderate tidal volumes, rates sufficient to prevent hypercarbia, and low levels of PEEP (5-10 cm H2O).
Management of emergence from anesthesia requires maintaining hemodynamic stability and adequate
alveolar ventilation. The major factor responsible for hemodynamic stability is the ratio of pulmonary to systemic
vascular tone. Extubation in a deep plane of anesthesia to avoid pulmonary vasoconstriction may be complicated by
decreased SVR, decreased contractility, and inadequate ventilation (producing hypoxemia or hypercarbia and
increasing PVR). Extubation in a light plane of anesthesia can result in severe pulmonary vasoconstriction. The
addition of narcotics or dexmedetomidine to a primarily inhalational technique may allow extubation in a light plane
of anesthesia without increasing sympathetic tone. A narcotic-oxygen anesthetic technique followed by
postoperative mechanical ventilation is sometimes required for patients with severe PH undergoing major surgery.
Patients with PH have limited ability to tolerate any further increase in PVR. It is therefore important to
avoid introduction of air or particulate matter into the venous system. In patients with anatomic shunting (such as a
PFO), venous embolization may result in systemic embolization.
Treatment of Perioperative Hypotension: Hemodynamic management in PH should maintain blood pressure and
cardiac output and minimize PVR. When cardiac output is inadequate, inovasodilator agents such as dobutamine and
milrinone can increase cardiac output and decrease PVR. Systemic hypotension should be aggressively treated since
it decreases right ventricular myocardial perfusion (producing ischemia) and decreases the contribution of the
interventricular septum to right ventricular cardiac output (Fox, Hosseinian, Thunberg). The management of
systemic hypotension in the patient with PH can be challenging. As shown below, systemic hypotension may result
from four etiologies, each of which has a specific hemodynamic pattern:
Etiology CVP PAP PAOP CO

Decreased preload    
Decreased contractility    
Decreased SVR    or   or 
Increased PVR    
Pulmonary artery catheterization allows differentiation among these etiologies. Decreased preload is the only
etiology which decreases CVP; titrated volume therapy is indicated since excess volume administration with a
failing RV may result in further distention and dysfunction. Decreased contractility is the only condition that results
in an increase in CVP with a decrease in PAP; inotropic therapy is indicated. When decreased systemic blood
pressure occurs without a decrease in PAP, the ratio of PVR to SVR has increased. The initial approach should be to
reverse correctable causes of increased PVR such as hypoxia, hypercarbia, acidosis, increased sympathetic tone, and
endogenous or exogenous vasoconstrictors. In patients without correctable factors, cardiac output measurement will
differentiate between decreased SVR (cardiac output increased or unchanged) and increased PVR (cardiac output
decreased with unchanged or increased PAP). Decreased SVR may be treated by using relatively selective systemic
vasoconstrictors such as phenylephrine or vasopressin. Vasopressin produces less increase in PVR than either
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phenylephrine or norepinephrine (Jeon, Siehr). A combined inotropic-vasopressor agent such as epinephrine or

norepinephrine may also be useful.
When an increase in PVR decreases cardiac output and produces systemic hypotension, pulmonary
vasodilator therapy is required to interrupt the cycle of PH producing hypotension which decreases RV coronary
perfusion which further decreases cardiac output; similarly, low cardiac output produces desaturation of mixed
venous blood, resulting in increased pulmonary vasoconstriction. Right ventricular failure causes right ventricular
dilation which results in tricuspid regurgitation, further decreasing forward blood flow. The goals of pulmonary
vasodilator therapy are two-fold: first, to reduce PVR and thereby decrease PAP and/or increase cardiac output, and,
second, to reduce the PVR/SVR ratio. All systemic vasodilators can produce pulmonary vasodilation, but use of
these agents frequently results in systemic hypotension. In PH, cardiac output varies with RV function. For the
majority of drugs, systemic vasodilator effects occur at doses which do not produce pulmonary vasodilation. Thus,
with a decrease in SVR and no change in PVR, cardiac output cannot increase and systemic blood pressure must
decrease (BP = CO X SVR).
Pulmonary vasodilators include direct-acting nitrovasodilators such as nitroglycerin and nitroprusside;

alpha-adrenergic blockers; beta-adrenergic agonists; calcium channel blockers; and prostaglandins. In the
perioperative setting, short-acting titratable agents should be used, and the effects should be assessed at each dose
before increasing to a higher dose.
For severe perioperative PH resulting in RV failure, inhaled vasodilator therapy is the treatment of choice
(Grinstein, Hill, Zamanian). This approach was first described with inhaled nitric oxide (NO). Inhaled NO diffuses
from the alveoli to the adjacent pulmonary vascular smooth muscle cells to produce pulmonary vasodilation. Inhaled
NO does not produce systemic vasodilation because any NO which diffuses into the blood is inactivated by binding
to hemoglobin. Inhaled NO may improve ventilation-perfusion matching by increasing blood flow to ventilated
alveoli. Inhaled NO decreases perioperative PH in multiple settings, particularly following cardiopulmonary bypass.
Inhaled NO may be useful in patients with allograft dysfunction following lung transplantation since NO may
decrease PH, improve ventilation-perfusion mismatch, and decrease ischemia-reperfusion lung injury. Inhaled NO
improves outcome in neonatal PH with hypoxic respiratory failure as judged by a decreased frequency of death or
ECMO. Although inhaled NO improves oxygenation and decreases PH in the acute respiratory distress syndrome,
randomized studies have not demonstrated sustained improvement or improved outcome (Adhikari).
In general, inhaled NO in patients with PH demonstrates maximal responses at doses of 10 ppm or less. A
trial of 20 ppm inhaled NO is sufficient to determine if the patient will have a beneficial response. Discontinuation
of inhaled NO after several hours of administration may produce rebound PH. Rebound PH may represent
progression of underlying PH, decreased endogenous NO synthesis, downregulation of guanylyl cyclase, or
activation of endogenous vasoconstrictor pathways such as endothelin. Approximately one-third of patients with PH
have little or no response to inhaled NO. Inhibition of cyclic GMP phosphodiesterase with sildenafil can increase the
frequency, the magnitude, and the duration of response to inhaled NO and decrease rebound effects. Sildenafil alone
is commonly used to prevent perioperative exacerbation of PH or to allow weaning of inhaled NO in the
postoperative period.
Other inhaled vasodilators may also produce selective pulmonary vasodilation (Buckley, Fattouch, Hill,
Winterhalter, Wang). These include prostaglandin derivatives (prostacyclin, prostaglandin E1, and iloprost),
nitrovasodilators (nitroglycerin, nitroprusside), and milrinone. Multiple studies indicate that inhaled prostacyclin is
as effective as inhaled nitric oxide, and many centers routinely use inhaled prostacyclin due to cost considerations.
Combinations of agents which affect different mechanisms of vasodilation (e.g., NO which increases cGMP and
prostacyclin which increases cAMP) may produce additive pulmonary vasodilation.
Finally, patients undergoing cardiac surgery who develop intractable RV failure due to PH may be
candidates for a percutaneous or surgically implanted right ventricular assist device, either on a temporary basis until
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RV function recovers or as a bridge to transplantation (Machuca). Drugs with combined intropic and pulmonary
vasodilator effects such as dobutamine, the phosphodiesterase 3 inhibitor milrinone, or the calcium sensitizer
levosimendan (not approved in the United States) can increase cardiac output in patients with PH and are commonly
used in the ICU or in the setting of cardiac surgery. However, their systemic vasodilator effects frequently
contraindicate their use in patients with PH-induced systemic hypotension until of the hypotension has been
corrected.
Postoperative Management: Although the focus in the literature has been on intraoperative management of PH,
most patients who die in the perioperative period do so several days after surgery. Causes of death include
progressive increases in PVR, progressive decreases in cardiac function, and sudden death. Patients should be
monitored in a setting appropriate for these complications. The use of epidural narcotics and local anesthetics,
continuous regional anesthesia, and non-narcotic analgesic adjuvants should be considered. Dexmedetomidine has
been used for sedation and analgesia without producing respiratory depression (Toyama). PDE-5 inhibitors such as
sildenafil may be useful postoperatively in allowing weaning from inhaled pulmonary vasodilators.
Summary: Patients with PH have markedly increased morbidity and mortality during anesthesia and surgery.
However, management based on physiologic principles using the seven steps outlined above can allow the majority
of patients with PH to safely undergo anesthesia and surgery.
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Shenoy V, Anton JM, Collard CD, Youngblood SC. Pulmonary thromboendarterectomy for chronic
thromboembolic pulmonary hypertension. Anesthesiology 2014; 120:1255-1261.
Siehr SL, Feinstein JA, Yang W, et al. Hemodynamic effects of phenylephrine, vasopressin, and epinephrine in
children with pulmonary hypertension: A pilot study. Pediatr Crit Care Med. 2016; 17:428-37.
Simonneau G, Gatzoulis MA, Adatia I, et al. Updated clinical classification of pulmonary hypertension. J Am Coll
Cardiol 2013; 62(25 Suppl):D34-41
Strumpher J, Jacobsohn E. Pulmonary hypertension and right ventricular dysfunction: physiology and perioperative
management. J Cardiothorac Vasc Anesth 2011; 25:687-704.
Subramaniam K, Yared JP: Management of pulmonary hypertension in the operating room. Semin Cardiothorac
Vasc Anesth 2007; 11:119-36.
Thunberg CA, Gaitan BD, Grewal A, et al. Pulmonary hypertension in patients undergoing cardiac surgery:
pathophysiology, perioperative management, and outcomes. J Cardiothorac Vasc Anesth 2013; 27:551-72.
Toyama H, Wagatsuma T, Ejima Y, et al. Cesarean section and primary pulmonary hypertension: the role of
intravenous dexmedetomidine. Int J Obstet Anesth 2009; 18:262-7.
Vonk Noordegraaf A, Groeneveldt JA, Bogaard HJ. Pulmonary hypertension. Eur Respir Rev 2016; 25:4-11.
Vonk-Noordegraaf A, Haddad F, Chin KM, et al. Right heart adaptation to pulmonary arterial hypertension:
physiology and pathobiology. J Am Coll Cardiol 2013; 62(25 Suppl):D22-33.
Wang H, Gong M, Zhou B, Dai A. Comparison of inhaled and intravenous milrinone in patients with pulmonary
hypertension undergoing mitral valve surgery. Adv Ther 2009; 26:462-468.
Williams GD, Philip BM, Chu LF, et al. Ketamine does not increase pulmonary vascular resistance in children with
pulmonary hypertension undergoing sevoflurane anesthesia and spontaneous ventilation. Anesth Analg
2007; 105:1578-84.
Winterhalter M, Simon A, Fischer S, et al. Comparison of inhaled iloprost and nitric oxide in patients with
pulmonary hypertension during weaning from cardiopulmonary bypass in cardiac surgery: a prospective
randomized trial. J Cardiothorac Vasc Anesth 2008; 22:406-13.
Yang EI. Perioperative management of patients with pulmonary hypertension for non-cardiac surgery. Curr
Rheumatol Rep 2015; 17:15.
Zamanian RT, Haddad F, Doyle RL, et al. Management strategies for patients with pulmonary hypertension in the
intensive care unit. Crit Care Med 2007; 35:2037-50.
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Preoperative Evaluation in the 21st Century
Each year, over 200 million people undergo surgery worldwide and this population is becoming
increasingly medically complex.1 In the United States, 26% of all inpatient adverse events within the Medicare
population are attributable to surgery and procedures.2 Further, the number of ambulatory procedures performed
now exceeds those done on an inpatient basis. 3-4 In such a progressively challenging environment, with an estimate
that 44% of adverse perioperative events are preventable, it is essential that the risk of perioperative complications
be mitigated. Also, the financial solvency of operating rooms in a fragmented health care system may be
jeopardized by incomplete patient information that leads to delayed and cancelled surgeries.5 As a result, having a
sound preoperative process or preoperative clinic creates the ideal setting to optimize the patient’s medical
condition, ensure patient safety, selection, and maximize economic efficiency within the pre-procedural arena.
Appropriate Pre-Procedural Testing

David L. Hepner, M.D., M.P.H. Boston, MA
Preoperative Assessment Testing Clinics coordinate preoperative surgical, anesthesia, nursing and laboratory
care. Such clinics have been noted to lead to efficiencies in perioperative care by seeing most patients days before
the surgery. The prior history, medical records, previous tests and consultations are reviewed, and a medical history
and physical examination are conducted. Laboratory testing, electrocardiogram, and chest x-ray should be ordered
if necessary, and it is essential to determine which patients need further workup or consultations in order to assess
the patient’s readiness for surgery.
The perceived benefit of risk stratification based on results of preoperative testing may be considered to vary
with surgical risk. What is the potential that screening tests will assist in risk stratification and management? A
number of institutions vary preprocedure testing guidelines based on the risk of the procedure, on the assumption
that routine screening is unlikely to impact risk stratification for low risk procedures. Preoperative testing should be
based on patient’s comorbidities (physical status), on the type of surgery (operative risk) and on findings from the
history and physical examination. It is important to avoid repetition of prior testing if there is no change in the
patient’s condition, and to avoid testing in healthy patients having minimally invasive procedures. Routine testing
does not increase safety or the possibility of surgery cancellation, even in elderly patients with multiple
comorbidities, for minimally invasive procedures. In a study randomizing approximately 20,000 patients, Schein et
al demonstrated that routine screening testing had no impact on risk management and outcome in cataract surgery. 6
There is no value for ordering laboratory tests solely because of planned surgery. Common tests ordered
include urinalysis, hematocrit, white blood cell count, platelet count, general chemistry labs (serum sodium,
potassium, chloride, bicarbonate, glucose, and blood urea nitrogen), prothrombin time, partial thromboplastin time,
chest x-ray, and electrocardiogram. It has been demonstrated that in close to 50 percent of cases, these tests have
been ordered for patients without recognizable clinical indications. Despite twelve percent of these routine tests
being abnormal in one study, only 0.5% led to a change in management. 7
It has been estimated that the annual cost of preoperative medical testing for all types of surgery in the United
States was as much as $30 billion in the 1980s with unnecessary diagnostic testing being a substantial component. 8
The value of routine preoperative medical testing has also been questioned.6 In a study of nearly 20,000 patients
undergoing elective minor surgery, patients were randomized to no testing or a standard battery of tests, including
ECG, CBC, electrolytes, urea nitrogen, creatinine, and glucose. There were no differences between the two groups
in the overall rate of intraoperative complications. Therefore, routine preoperative medical testing does not increase
the safety of minor procedures.
Chest X-rays are ordered frequently as part of a routine admission or preoperative evaluation even though
available data does not support this practice. Chest X-ray is one of the most expensive tests ordered, it is not
predictive of inpatient or postoperative pulmonary complications and very rarely leads to a change in management
or cancellation of elective surgery. 9,10 For these reasons, the American College of Radiology recommends against
routine admission and preoperative Chest Radiography. 11
Many physicians express the fear of increased medicolegal risk if they do not routinely order screening or
preoperative tests. It could be argued from a medicolegal standpoint that it is better not to order an unnecessary test
if the next step to take in the event of an abnormal result is unclear. Should a clinically insignificant abnormal
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laboratory test finding be uncovered but nothing done, legal action may result at a later time. A complication
unrelated to the abnormal result may develop at some point in the future and be blamed on the lack of follow-up.
In a recent population-based study evaluating preoperative blood work prior to low risk surgeries including
ophthalmologic surgery, Kirkham and colleagues report that routine blood work was done prior to nearly a third of
low-risk, mainly ambulatory, surgeries.12 They demonstrate that comorbidities, age, and preoperative medical
consultation were associated with routine blood testing. More importantly, they also found that there was significant
variation between institutions. Geographic location of surgery was the strongest predictor for preoperative
laboratory testing.12 Similarly, Chen et al. recently demonstrated that preoperative testing before cataract surgery
was more likely to be associated with the practice patterns of the ophthalmologist and whether patients had a
preoperative visit rather than with patient comorbidities. 13 Over fifty percent of patients underwent a preoperative
test prior to cataract surgery,13 despite significant evidence and national guidelines against the utility of routine
preoperative testing.14,15 The authors suggest that providing institutions and individual providers feedback about
rates of testing has the potential to reduce low value care. 12
Recently, multiple primary care and specialty physician groups joined forces to create the ‘Choosing Wisely’
campaign, aimed directly at decreasing the burden of unnecessary testing. 16 Each of the participating professional
physician societies provided a list of five tests that should be performed less often, and the necessity of which should
be questioned by physicians and patients when suggested. The American Society of Anesthesiologists is a partner in
the Choosing Wisely Campaign, and is encouraging ongoing dialogue between patients and anesthesiologists to
eliminate unnecessary tests and procedures.17 Common low-value tests to question in anesthesiology include
baseline laboratory studies in healthy patients without significant systemic disease when blood loss is expected to be
minimal.18 Even though baseline laboratory studies are discouraged in low risk patients based on low impact on
quality, high cost of care, and weak evidence for their recommendation, they were still ordered in a third to half of
patients in recent studies.12-13
The problem is not only the unnecessary test, but the actions taken as a result of an abnormal test. A false
positive result, or an abnormal result that may not affect the anesthetic or surgical management, can lead to further
testing, consults, and procedures that incur additional costs and potential complications. In an era of value-based
medicine, the only justification of preoperative screening is that the health benefits outweigh the health risks and are
worth the dollar costs. Laboratory tests are not good screening devices. 19
Preoperative Evaluation
The most recent revision of the ACC/AHA perioperative guidelines provides an algorithm for evaluation
and testing.20 Current guidelines for cardiac risk stratification rely on urgency of procedure, stability of disease,
clinical risk predictors including relative risk of surgery and functional capacity. Perioperative testing should only
be conducted if it will impact decision making towards the surgery or perioperative care. 20 However, routine
clinical evaluation is neither completely sensitive nor specific for cardiac risk estimation due to the inability to
assess the functional capacity in some patients with orthopedic, vascular or thoracic disease.
Cardiac risk factors are generally utilized as clinical predictors for coronary artery disease and are elicited
based on the history and physical examination. The most recent perioperative guidelines continue to use the revised
cardiac risk index (RCRI) developed by Lee and colleagues for the prediction of heart disease for stable patients.21
The RCRI identified six independent risk correlates, including ischemic heart disease, congestive heart failure,
cerebral vascular disease, high risk surgery, diabetes mellitus (insulin dependent) and chronic renal failure
(creatinine>2.0 mg/dL), where increasing number of risk factors correlated with increased risk for major cardiac
complications. Not only is it essential to take into account the patient’s cardiac risk factors, but also the relative risk
of surgery in order to appropriately develop guidelines for preoperative testing. For this reason, the algorithm
combines medical conditions and surgical risk for perioperative major adverse cardiac events. The relative risk of
surgery is based on the risk of developing cardiac death and myocardial infarction during noncardiac surgery and is
now divided into low and high risk procedures (previously low, intermediate and high). The risk of cardiac events
ranges from <1% for low risk procedures to >1% for high-risk procedures. The most recent perioperative guidelines
only considers intraperitoneal, intrathoracic, or suprainguinal vascular as high risk procedures. 20 The presence of
two or more of the above named risk correlates place the patient at high risk for perioperative adverse cardiac
events. For high risk procedures, one or more risk factors place the patient at high risk for major adverse cardiac
events.
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The probability of silent cardiovascular disease could be elicited by the presence of obvious symptoms
during the history taking. The patient’s functional capacity is assessed by daily living activities and exercise
capacity, and is used to evaluate symptoms of potential cardiovascular disease such as shortness of breath and chest
pain.22 Functional capacity is also a predictor for perioperative cardiac events. It is necessary to determine the
patient’s functional capacity for those patients at elevated risk for major adverse cardiac events. Patients that can do
at least 4 METS can reasonably proceed to the operating room without further cardiac testing. Patients at elevated
risk with poor functional capacity may benefit from further cardiac testing (pharmacologic stress testing). However,
this should only be done if the results will change decision making or the perioperative care plan. If testing will not
impact decision making or management care, then it is reasonable to proceed to surgery according to guideline
directed medical therapy. Alternatively, consider alternative management strategies such as noninvasive treatment
or palliation.
ADDITIONAL CARDIAC TESTING

Perioperative assessment for prevention of cardiac complications is an important task of the
anesthesiologist. Cardiac preoperative evaluation of the noncardiac patient relies on information from multiple
sources: the medical record, history, and physical examination; and findings from medical tests, including
electrocardiogram (ECG). As outlined above, other factors to be considered include coexisting medical disease,
clinical risk factors, and the patient's functional capacity.
Since risk assessment relies on a medical history and physical examination, it is important to be more
selective in the ordering of cardiac tests. A test is likely to be indicated if it can identify abnormalities and change
the diagnosis and management plan, or the patient's outcome.23 Excessive cardiac testing is expensive, and it may
delay the operation and place the patient at risk for unnecessary interventions. It has been shown that an efficient
anesthesiologist-directed preoperative clinic can decrease non-invasive diagnostic testing.24
Electrocardiogram
Routine ECGs have been reported to be abnormal in 7.0-42.7% of cases in 12 different studies but led to
changes in management in only 10% of these cases. 25 The rate of ECG abnormalities and changes in management
increased when the ECG was ordered based on the history and physical examination. Important clinical
characteristics to consider when making a decision to order an ECG include cardiovascular or respiratory disease,
multiple cardiac risk factors, and the surgical risk. There is currently no consensus regarding a minimum age for
obtaining an ECG prior to a noncardiac surgery. 25 Patients at higher risk of having a significantly abnormal ECG
are those older than 65 years of age or who had a history of heart failure, high cholesterol, angina, myocardial
infarction, or severe valvular disease.26 The ACC/AHA 2014 guidelines on perioperative cardiovascular evaluation
and care for noncardiac surgery discourage preoperative ECGs in asymptomatic persons undergoing low-risk
surgical procedures regardless of age.20 Even though ECG abnormalities are more common in older patients, they
are not predictive of postoperative complications. 27 Therefore, a preoperative ECG ordered routinely in those older
than 50-60 years does not seem to add any value in predicting postoperative complications beyond cardiac risk
factors. The ACC/AHA 2014 perioperative guidelines state that preoperative resting 12-lead electrocardiogram
(ECG) is reasonable for patients with known coronary heart disease, significant arrhythmia, peripheral arterial
disease, cerebrovascular disease, or other significant structural heart disease. Furthermore, they state that a
preoperative resting 12-lead ECG may be considered for asymptomatic patients, except for low-risk surgery.
Echocardiogram
A preoperative echocardiogram is recommended in patients with clinically suspected moderate or greater
degree of stenosis or regurgitation if there is any progression of clinical status or worsening of the physical
examination. Even if there have been no changes in clinical status, an echocardiogram is recommended if it has
been at least a year since the last one.
The current guidelines consider assessment of left ventricular function reasonable for patients that have
dyspnea of unknown origin or worsening dyspnea with a history of heart failure. It is also reasonable to repeat
echocardiography in patients with heart failure that have not been reevaluated during the last year.
Pharmacologic stress test

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Patients at high cardiac risk with poor or unknown functional capacity may benefit from further cardiac
testing to assess for myocardial ischemia if the results may lead to a change in management. It is also reasonable to
perform a stress test in patients at high cardiac risk with unknown functional capacity to assess for functional
capacity if it will lead to a change in management. Routine screening with noninvasive stress testing is not useful
for patients at low risk for noncardiac surgery.
SUMMARY
The preoperative assessment provides an invaluable opportunity to stratify, manage and optimize risk.
Risk stratification, management, optimization, documentation, and communication to the care team will allow all
providers involved in preoperative care the opportunity to ensure the best possible patient outcomes. Additional
tests, evaluations and consultations should only be done if the information to be obtained will result in changes in
the perioperative management of the patient.
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Moving away from preoperative testing to the practice of preoperative

medicine
BobbieJean Sweitzer, MD, FACP Chicago, Illinois
Major surgery is associated with significant physiologic stress and adverse outcomes short- and long-
term.28 Approximately 15% of patients having in-patient non-cardiac surgery are at risk for serious complications
including disability or death. Worldwide, 200-250 million patients have surgery yearly; many are aged with severe
comorbidities and advanced disease. Up to 2.5 million patients will die (1% risk) and 12.5 million will have costly
adverse events (5% risk).29 A little over 12% of patients account for 80% of postoperative deaths. 30 Mortality rates
vary widely across hospitals and countries. Evidence suggests that high-risk patients are often not identified
preoperatively, and proven strategies to lower risk are not implemented. Risk assessment can lead to changes in
medical management, planned anesthesia and surgery, postoperative care, or recommendations to avoid surgery.
Advanced age is a strong predictor of postoperative mortality and morbidity from cardiovascular (CV), pulmonary,
and infectious causes.31 Elderly patients >75 years have twice the risk of serious morbidity and 3-7 times the risk of
dying compared to younger patients. The frail elderly and those undergoing cancer procedures are at particular risk.
Frailty independently predicts postoperative complications, length of stay (LOS), and discharge to an assisted-living
facility.31 Determination of a frailty score supplements other risk models. Impaired cognition, low albumin,
previous falls, low hematocrit, functional dependence, and multiple co-morbidities are associated with 6-month
mortality and inability for discharge home postoperatively.
Most patients with chronic dyspnea of unclear etiology have one of four diagnoses: asthma, COPD,
interstitial lung disease, or cardiac dysfunction . Miscellaneous conditions, including deconditioning, account for
the rest. The history and physical examination leads to diagnoses in two thirds of cases. Initial testing includes an
ECG, hematocrit, arterial blood gases, thyroid function tests, chest radiograph, spirometry, and oximetry (resting
and after walking several feet).
Postoperative pulmonary complications (PPO) incur the highest costs. PPO reduce median long-term (5-
10 years) survival by 90%. Established risk factors for PPO include a history of cigarette use (current or exceeding
40 pack-yrs); ASA-PS > 2; age > 70 years; COPD; neck, thoracic, upper abdominal, aortic, or neurologic surgery;
procedures > 2 hr, general anesthesia (especially with intubation); albumin concentration < 30 g/L; inability to walk
2 blocks or climb 1 flight of stairs; or a BMI > 30.32 Heart failure (HF) is one of the strongest predictors of PPO.
Asthma, arterial blood gas, chest radiograph or pulmonary function test (PFT) results are not predictive of PPO.
Risk is greater with recent exacerbations, prior PPO, recent hospitalizations, or intubations for asthma. Some risk
factors for PPO are modifiable. Exacerbations or infections must be improved whenever possible. Antibiotics,
bronchodilators and steroids, or delay of surgery are important in high-risk patients. Delaying surgery up to one
month before lung resection in high-risk, cancer patients with respiratory compromise for “prehabilitation” is
associated with short- and long- term survival. Changes in management, including altering the surgical procedure,
alternatives to general anesthesia, and epidural pain management are effective in decreasing PPO.
Exposure to tobacco, directly or second-hand, increases perioperative complications.28 Smoking is
associated with 40% increased odds of 30-day mortality and 30%-100% increased odds of morbidity, including
surgical site infection, unplanned intubation, pneumonia and sepsis. Smoking decreases macrophage function,
negatively impacts coronary flow reserve, and causes vascular endothelial dysfunction, hypertension and ischemia.
Smokers require longer hospital stays and need postoperative intensive care more than non-smokers. A recent
systematic review found no increased adverse events with quitting smoking soon before surgery (i.e., within 8
weeks).33 Benefits are evident with cessation 3-4 weeks before surgery. Patients should be encouraged to quit
smoking at any point preoperatively. Soon after quitting, toxic substances and carbon monoxide and cyanide levels
decrease, improving wound-healing and oxygen delivery and utilization. Lower nicotine levels improve
vasodilatation.
Renal disease increases perioperative risk, especially cardiovascular complications. Chronic kidney disease
(CKD) is included in several risk scores. A creatinine > 170 µmol/L is an RCRI risk factor equivalent to known
stable ischemic heart disease in predicting cardiac risk.20-21 Estimated glomerular filtration rate (eGFR) is a more
accurate measure of renal function, especially for less severe disease. The eGFR predicts short- (< 30 day) and
long-term mortality.34 Even mild disease (eGFR <60 mL/min/1.73 m2) is associated with a threefold risk of death
within 30 days and mortality and CV events long-term. Preoperative kidney disease is the strongest predictor of
postoperative renal failure. Risk factors for CKD include age >55 yrs, smoking, diabetes, hypertension,
dyslipidemia and HF.
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Severe liver disease increases perioperative risk, especially with major surgery. Predictors of increased risk
include Child-Pugh-Turcotte class C, MELD (Model for End-stage Liver Disease) score >15, acute liver failure,
acute alcoholic hepatitis and a serum bilirubin >188 µmol/L. Renal insufficiency in association with hepatic disease
causes a particularly poor prognosis. The highest risk surgeries are abdominal (including cholecystectomy), cardiac
and emergency procedures, and those with high blood loss. Complications in surgical patients with cirrhosis include
pneumonia, infections, and renal and respiratory failure. MELD scores can be calculated with creatinine and
bilirubin levels and the INR.35
Malnourished patients have significantly higher rates of morbidity or mortality especially poor wound
healing, increased LOS and infections. Low albumin levels predict mortality and morbidity. Adequate
perioperative nutritional support decreases postoperative complications. Even mild preoperative anemia is
associated with increased 30-day mortality.36 Hemoglobin <8 g/dL is associated with a 16-fold increase in mortality.
Morbidity is increased with mild-moderate anemia. In patients with CV disease, diabetes, or CKD and anemia, the
perioperative mortality is twice that with the underlying disease alone. Perioperative transfusions are associated
with increased morbidity and mortality. A restrictive transfusion strategy (maintaining hemoglobin 7-9 g/dL) is as
effective, if not superior, to a liberal approach (hemoglobin of 10-12 g/dL) in critically ill patients, with the possible
exception of those with unstable coronary syndromes. Efforts to diagnose and correct anemia preoperatively,
especially for elective surgeries, in the elderly, in patients with other diseases or for surgeries with significant blood
loss is necessary.
SUMMARY
Optimal preoperative patient preparation is essential if risks are to be lowered. Further research and
development of evidence-based protocols are needed. Optimal results require a multidisciplinary approach with care
providers with various clinical skills. A starting point is to use a combination of age, type of procedure, co-morbid
conditions and biomarkers to stratify patients. Low-risk patients can proceed to surgery without special preparation.
High-risk patients must be evaluated by a specialist in preoperative medicine and undergo advanced testing and
prehabilitation if needed before proceeding to surgery in specialized centers.
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Organizing and Managing the Preoperative Process

Angela F. Edwards, M.D Winston Salem, NC
The primary goal of a preoperative process is to provide safe, reliable, risk reduction and medical
optimization in a comprehensive manner. In order to do so, preoperative clinics have been developed to enhance
operating room efficiency, decrease day of surgery cancelations, reduce hospital costs and improve the overall
quality of patient care. Although preoperative programs differ in structure, staffing, financial support, and daily
operations, they share the common goal of preoperative risk reduction in order for patients to proceed safely through
the perioperative period. Effective preoperative evaluation occurs if processes are standardized to ensure clinical,
regulatory, and accreditation guidelines are met while keeping medical optimization and patient satisfaction at the
forefront. With careful triage based on comorbidities, functional status, and medications, certain low risk patients
can often avoid unnecessary clinic visits while higher risk patients receive the necessary evaluations, consultations,
and laboratory testing to ensure medical optimization. Well-resourced clinics in centralized locations have the
ability to seamlessly provide preoperative services, ancillary testing (e.g. ECG, echocardiogram, laboratory testing
and/or prehabilitation), and patient education in addition to maintaining effective communication across the surgical
continuum. Collaboration and teamwork in a multidisciplinary context is paramount to such a program’s success.
Several models of preoperative care have been previously described in the literature. 37 While, no current
universally accepted standard model exists, key components and leadership are necessary to establishing and
maintaining a successful preoperative process. The first of which is to determine which patients are recommended
to have in-person visits to a preoperative clinic. Triage systems have been developed to assist referring surgeons
and proceduralists to choose appropriate patients for in-person clinic visits. Such tools may be either paper or
electronic, depending on the resources of the health care system. Historically, triage has been proposed using
medical comorbidities and/or American Society of Anesthesiology classification to assess physical status and
optimization.38 With this, ASA class 1 and 2 patients could be triaged to phone screens, whereas ASA class 3 and 4
patients require in person consultation. Phone screening nurses may collect critical information on the ASA 1 and 2
type patients to confirm demographic information, medical optimization, as well as providing pre-procedural
education. Higher risk patients with complex medical and social issues can be identified and triaged to in person
visits with a trained physician or advanced practice provider. During this time, risk stratification and medical
optimization of comorbidities can be ensured such that postoperative risks are minimized. Preoperative
identification and management of high-risk patients with complex medical and social issues prior to their surgical
admission has been shown to increase patient safety and satisfaction,39-40 as well as improve efficient utilization of
operating room resources.41 Preoperative clinic visits have been shown to reduce unnecessary testing, subspecialty
consultations, and decrease hospital stay.42-43 Further, preoperative interventions that reduce risk of postoperative
complications have led to significant cost savings. It has been well documented that centralizing and standardizing
even part of the preoperative process through obtaining outside records, completing history and physical
examinations, finalizing surgical, anesthesia, and nursing assessments increases operating room efficiency and
decreases costs. The direct and indirect savings achieved by minimizing redundancy, avoiding day of surgery
delays and cancellations, and ensuring appropriate documentation and coding offset direct expense of establishing
and maintaining a preoperative assessment clinic. 44
Benefits to developing an effective preoperative clinic include the following:

o Decreased surgical delays and cancelations due to non-medical issues
o Decreased perioperative morbidity and mortality
o Reduction in excessive and unnecessary testing and subspecialty consults
o Increased patient and surgeon satisfaction
o Increased regulatory compliance and operating room efficiency
o Improving information transfers; clean charts (consents, history and physical exams, etc.)
o Ensuring patient readiness promotes efficient operating room turnover times
o Improved patient satisfaction and education; opportunity for shared decision making
o Improved compliance with preoperative instructions (surgical & anesthesia)
o Implementing care coordination in a multidisciplinary context
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Well-established preoperative clinics can coordinate services such that most, if not all, components of
perioperative care are brought to the patient and discharge planning can be initiated before the patient leaves the
clinic. Medical optimization, chart completion, shared decision making and postoperative care coordination can all
be addressed early in the preoperative process. Ideally, the preoperative clinic sets the standards for care and is the
model of delivery for all preoperative processes in a given healthcare system.
The operational plan is the specific action plan developed to meet goals and objectives of the preoperative
program. The goals noted in the following tables can be used as a springboard for determining which services will
be delivered by the preoperative program, keeping current and future scope in mind. Furthermore, the design and
development of the preoperative clinic must serve the goals and objectives of the program well.
Goals of the Preoperative Process

Direct Patient Care
o Provide comprehensive preoperative evaluation
o Identify, communicate, and minimize the patient-specific risks of surgery and anesthesia
o Consistently apply evidence-based, standardized, consistent, condition-specific protocols for
preoperative testing
o Use goal-directed patient medical optimization to reduce case delays and cancellations
• Develop and implement individualized perioperative care plans
o Perform detailed review of patient medications and give patient-friendly preoperative medication
instructions
• Include any new preoperative medications and maintenance of the patient’s chronic
medications
o Initiate transitional care planning

• Plan the appropriate postoperative level of care
• Provide case management services to plan for post-discharge needs
o Provide patient education and counseling
• To reduce anxiety, increase participation and enhance recovery after surgery
o Obtain and/or confirm consent
• Confirm the presence of anesthesia & surgical consent prior to surgery
Indirect Patient Care and Non-Clinical Goals

o Model Process Improvement
• Create standardized protocols to improve patient outcomes and decrease unnecessary testing
• Distribute protocols as the standard of care for all periprocedural patients
o Centralize medical information and coordinate perioperative care
• Provide leadership in the perioperative services across service lines and department
• Manage tasks associated with perioperative patient care
o Coordinate chart readiness, control information systems, other pertinent tasks
o Comply with regulatory standards
o Improve Perioperative Efficiency and Finance
o Perform Research and Provide Education
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Surgical Appropriateness
Angela M Bader MD, MPH Boston, MA
Most efforts to improve the quality of surgical care in the United States have been programs to either credential
and certify providers, or measure and reduce surgical complications. The greatest unmet challenge in surgical
quality is how to address appropriateness, i.e., to ensure that every decision to perform an operation fully reflects
the conditions, circumstances, and values of individual patients. Appropriateness in surgery requires: 1) the best
clinical evidence (right operation), 2) a qualified surgeon (right provider); 3) a healthcare facility that has the
necessary resources to perform the operation safely (right place), and 4) a patient who is well-informed and
meaningfully involved, and who is undergoing surgery that meets his or her individual preferences and values (right
patient). Institutions and programs exist to address the appropriateness of provider and place, including board
certifications, hospital privileging procedures, certification, and “center of excellence” designations. In contrast, the
need to ensure that decisions for surgery reflect individual patients' values and preferences (right patient) is not as
easily addressed with a programmatic or institutional approach, and has thus received inconsistent attention. While
surgery often offers symptom relief or improved health status (e.g. reducing chance of heart attack or stroke),
surgery is not without risk. Individual patients vary in how much they are bothered by their symptoms, how much
they desire to reduce the chance of future health problems, and how much risk of surgical complications they are
willing to accept. Given this variability, clinicians, healthcare consumers, and researchers have recognized that
surgical decision making must be "patient-centered" and shared between patients and providers to ensure that
decisions are of high quality, and procedures are selected appropriately. Health care organizations caring for patients
undergoing surgical procedures must develop effective systems to ensure that all information, both clinical and
nonclinical, is available throughout the episode to ensure high quality decision-making that integrates patient
preferences, values and goals.
To achieve patient-centered care, providers need to ensure that patients are well informed and that medically
appropriate treatments address patients' needs, wants and preferences. Decision quality is an important indicator of
patient-centered care and an outcome relevant for surgical decision making. Prior research suggests that the patient's
viewpoint is often absent when treatment decisions are made. In a study assessing the quality of decision making by
surveying orthopedic surgeons (and not patients), reported deficits were related to fostering the patient's
involvement in making the decision, and making attempts to ensure the patient's understanding. 45 Patients with
chronic multiple comorbidities are particularly at risk; in a study of outpatient discussions of primary care doctors
and surgeons regarding clinical decisions, only 9% overall met the criteria for complete informed decision making;
less than 0.5% of intermediate or complex patients met this criterion.46 Physicians rarely explored patient
preference or whether patients understood the discussion. In summary, improving surgical decision making so that
it is oriented toward the outcomes that patients value most should have a significant impact on decreasing
inappropriate surgical care.
The reported incidence of poor surgical decision-making ranges from 15-50%. Postoperative studies in general
and orthopedic surgery populations testing patients' knowledge of risks of surgery after signing informed consent
paperwork have generally found understanding to be poor. Approximately 50% and 42% respectively were unable to
name any potential complications. Analysis of data regarding medical decision making during office visits showed that
fewer than 10% fulfilled minimum standards for informed decision making.47 These studies are limited because they
address only a few specific procedures, have small sample sizes, and are of inadequate scope to elucidate the reasons for
low quality decision making. In the absence of available data, it is difficult for clinicians, consumers or payers to
determine the quality of decisions made about most common medical tests and treatments.
Preliminary studies by our research team

Our pilot data showed that about 13% of patients exhibited deficits in their informed consent process before
surgery, and over 33% exhibited other types of deficits.48 Informed consent deficits refer to not knowing the procedure
being performed or the risks and benefits of the procedure. Other deficits related to not having addressed patient values,
preferences and goals. For example, 11% of patients expressed doubts about whether in fact they wanted to undergo
surgery at all, 76% had not completed advanced directives, and 25% of patients reported that they would have
benefited from further discussion.48 Non-English language and lower educational level were suggestive of higher risk
for these deficits. Also, because those scheduled for the intensive care unit postoperatively seemed to be at higher risk of
deficits, we have undertaken additional projects to improve communication and concordance in medical decisions for
high-risk surgical patients. This includes a grant funded by FAER to develop a training program for communicating
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with patients who are having surgery and have a DNR order. The purpose is to elicit patient expectations, preferences,
goals and values around postoperative care and use of life-sustaining therapy to should they be required to make decisions
in the postoperative period.
A recent review outlined the historical approaches to ensuring appropriateness in surgery, and noted that the
absence of concordance with patient values and preferences may not be considered sufficiently.49 In addition, we have
reported that within our normal preoperative clinic structure, there are patients who are considered inappropriate for
surgery for nonmedical as well as medical reasons.50 Some of these patients were referred to palliative care.
SUMMARY
A consideration of patient indications for surgery must be assessed in the context of complete assessment of
comorbidities as well as concordance with patient values and preferences . Ongoing work is needed to develop
frameworks to ensure that these conversations occur.
References
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strategy based on available data. Lancet 2008;372:139–44.
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Levinson DR. Department of Health and Human Services, Office of the Inspector General. Adverse Events in
Hospitals: National Incidence Among Medicare Beneficiaries. November 2010. OEI-06-09-00090. Available at:
https://oig.hhs.gov/oei/reports/oei-06-09-00090.pdf. Accessed June 2, 2016.
3
Cullen KA, Hall MJ, Golosinskiy A. Ambulatory Surgery in the United States 2006. National Health Statistics
Reports. 2009. Available at: http://www.cdc.gov/nchs/data/nhsr/nhsr011.pdf. Accessed June 2, 2016.
4
DeFrances C, Lucas, CA, Buie, VC, Golosinskiy A. 2006 National Discharge Summary. National Health Statistics
Reports. 2008. Available at: http://www.cdc.gov/nchs/data/nhsr/nhsr005.pdf. Accessed June 2, 2016.
5
Hobson and Co. The Case for a Perioperative- Focused Anesthesia Solution: Multiple Benefits from a Single
Solution. An ROI White Paper. 2008. http://www.sisfirst.com/pdf/articles/100220.pdf. Accessed June 2, 2016.
6
Schein OD, Katz J, Bass EB, et al. The value of routine preoperative medical testing before cataract surgery. Study
of Medical Testing for Cataract Surgery. N Engl J Med 2000; 342:168–175.
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Hubbell FA, Frye EB, Akin BV, Rucker L. Routine admission laboratory testing for general medical patients.
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Marcello PW, Roberts PL. “Routine” preoperative studies. Which studies in which patients. Surg Clin North Am
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Hubbell FA, Greenfield S, Tyler JL, Chetty K, Wyle FA. The impact of routine admission chest x-ray films on
patient care. N Engl J Med 1985;312:209-13.
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Joo HS, Wong J, Naik VN, et al. The value of screening preoperative chest x-rays: a systematic review. Can J
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Kirkham KR, Wijeysundera DN, Pendrith C, Ng R, Tu JV, Laupacis A, Boozari AS, Tepper J, Schull MJ,
Levinson W, Bhatia RS. Preoperative Laboratory Investigations: Rates and Variability Prior to Low-risk Surgical
Procedures. Anesthesiology 2016;124:804-14.
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Chen CL, Lin GA, Bardach NS, Clay TH, Boscardin WJ, Gelb AW, Maze M, Gropper MA, Dudley RA.
Preoperative medical testing in Medicare patients undergoing cataract surgery. N Engl J Med 2015;372:1530-8.
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Keay L, Lindsley K, Tielsch J, Katz J, Schein O. Routine preoperative medical testing for cataract surgery.
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2016.
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Cassel CK, Guest JA. Choosing wisely: helping physicians and patients make smart decisions about their care.
JAMA 2012; 307:1801-2.
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18
Onuoha OC, Arkoosh VA, Fleisher LA. Choosing Wisely in Anesthesiology: The gap between evidence and
practice. JAMA Intern Med 2014;174:1391-1395
19
Hepner DL, Bader AM. If I Had a Hammer: Building Alignment and Accountability. Anesthesiology
2016;124:755-7.
20
Fleisher LA, Fleischmann KE, Auerbach AD, Barnason SA, Beckman JA, Bozkurt B, Davila-Roman VG,
Gerhard-Herman MD, Holly TA, Kane GC, Marine JE, Nelson MT, Spencer CC, Thompson A, Ting HH, Uretsky
BF, Wijeysundera DN. 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of
patients undergoing noncardiac surgery: executive summary: a report of the American College of
Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;64:2373-2405.
21
Lee TH, Marcantonio ER, Mangione CM, et al. Derivation and prospective validation of a simple index for
prediction of cardiac risk of major noncardiac surgery. Circulation 1999;100:1043-9.
22
Reilly DF, McNeely MJ, Doerner D, et al. Self-reported exercise tolerance and the risk of serious perioperative
complications. Arch Intern Med 1999;159:2185-92.
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24
Cantlay KL, Baker S, Parry A, Danjoux G. The impact of a consultant anaesthetist led pre-operative assessment
clinic on patients undergoing major vascular surgery. Anaesthesia 2006;61:234-9.
25
Pasternak LR, Arens JF, Caplan RA, et al. Practice advisory for preanesthesia evaluation. An updated report by
the American Society of Anesthesiologists task force on preanesthesia evaluation. Anesthesiology 2012;116:522-
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26
Correll DJ, Hepner DL, Tsen LC, Chang C, Bader AM. Preoperative electrocardiograms: patient factors
predictive of abnormalities. Anesthesiology 2009;110:1217-22.
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Liu LL, Dzankic S, Leung JM. Preoperative electrocardiogram abnormalities do not predict postoperative cardiac
complications in geriatric surgical patients. J Am Geriatr Soc 2002; 50: 1186-1191.
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Banz VM, Jakob SM, Inderbitzin D. Improving outcome after major surgery: pathophysiological considerations.
Anesth Analg 2011;112:1147-55.
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Surg. 2004;199:531–7
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Jhanji S, Thomas B, Ely A, Watson D, Hinds CJ, Pearse RM. Mortality and utilisation of critical care resources
amongst high-risk surgical patients in a large NHS trust. Anaesthesia. 2008;63:695–700.
31
Makary MA, Segev DL, Pronovost PJ, et al. Frailty as a predictor of surgical outcomes in older patients. J Am
Coll Surg. 2010;210:901–8.
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Mooney, JF, Ranasinghe I, Chow CK, Perkovic V, Barzi F, Zoungas S, Holzmann MJ, Welten GM, Biancari F,
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Using Emergency Manuals in the OR: What is the evidence and how to be most effective?
Sara Goldhaber-Fiebert, M.D. Stanford, CA
Defining the problem

During critical events in operating rooms (ORs), clinician actions can significantly impact patient outcomes.(1) For
many life-threatening events, such as cardiac arrests, malignant hyperthermia, or local anesthetic systemic toxicity,
there are stacks of published literature on management details. Yet even when optimal treatment actions are clear,
for rare crises expert clinicians often omit or delay key actions. In multiple simulation-based studies, performance of
key actions dramatically increased when emergency manuals, crisis checklists, or cognitive aids were used.(2-4)
There are significant steps between proving effective use in simulated settings to enabling implementation and use
in clinical settings.
Dissemination, adoption, implementation, and clinical use of emergency manuals are relatively recent, but spreading
rapidly in many settings around the country and the world.(5) The Emergency Manuals Implementation
Collaborative (EMIC) provides implementation and training resources, as well as links to cost-free downloadable
tools, and published literature on rationale from multiple industries.) This refresher course presents the known
evidence on EMs from simulation-based OR studies as well as pertinent use in other industries, a conceptual
framework for clinical implementation, data from early clinical implementations and use, and lessons learned.
Introduction to Emergency manuals – an additional tool

Emergency Manuals (EMs), context-relevant sets of cognitive aids such as crisis checklists, provide professionals
with key helpful information for managing rare critical events. EMs are intended as both an educational and clinical
tool. The term emergency manual will be used throughout this article, though others may reasonably use the
overlapping terms crisis checklists or cognitive aids referring to these tools. They are symbiotic with rather than
replacing good preparation, teamwork, and judgment. EMs should never precede immediate actions such as chest
compressions for a pulseless patient, but rather are helpful once resources allow – either sufficient help is available,
or the initial clinical actions are already underway.
Figure 1. Emergency Manual use by anesthesiologists during simulated critical events. Photos ©D. Gaba left, S
Goldhaber-Fiebert right, reprinted with permission
Learning from other industries

High-hazard industries, such as aviation and nuclear power, routinely integrate emergency manuals into their
training exercises, and professional teams are expected to use EMs during real critical events, after ‘immediate
actions’ are begun. Human factors literature repeatedly shows that memory retrieval is impaired for rarely used
information, particularly under stressful and time-sensitive conditions, which makes relying on memory alone a
risky strategy. Even if an expert professional in any high-hazard industry knows the correct management choice
under standardized testing conditions, the detailed management knowledge is often not deployable under stress. (6,
7) Common errors during management of simulated OR critical events include both diagnostic and therapeutic
cognitive errors,(8) and also include cognitively recalling but never completing the action. One of the reasons for the
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latter is prospective memory error – forgetting to do something you intended to do – common because prospective
memory is vulnerable to interruptions which are frequent during crises.(9, 10) In early clinical uses, like in other
high-hazard industries, EM use – combined with good training, teamwork, and judgment - seems to be helping to
bridge this gap, via multiple mechanisms, to help teams deliver optimal care during critical events.(11-13) However,
high-quality prospective quantitative and qualitative research is needed on many aspects of EM clinical
implementation and use.
Four-element Framework
Prior work provided a conceptual framework for clinical
implementation of emergency manuals by analyzing emergency
manual implementation and use in high-hazard industries along
with early data in healthcare.(14) The framework is relevant for
EMs and similar patient safety tools because having a tool to
implement is a necessary start, but alone is vastly insufficient
for enabling use.
The four elements, which overlap and interact non-linearly, are:
1) Create (or customize an available manual): EM content and
design of what to implement; 2) Familiarize: clinician EM
training including why, when and how to use 3) Use clinically:
includes accessibility in all needed locations and team-EM
interaction e.g., triggering EM use and ‘reader’ role; and 4)
Integrate: safety culture strongly influences clinician behavior
as described in the field of implementation science.(15)
Figure 2. Four vital elements for implementing

emergency manuals. ©S. Goldhaber-Fiebert & S.
Howard, 2012, reprinted with permission
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Why now?
History: Emergency manual use builds synergistically
upon prior patient safety and quality improvement
developments in healthcare over the past few decades
and even century. The EM concept is not itself new,
with the first known mention of such a concept being
nine decades ago. In 1924, Anesthesia & Analgesia
published a manuscript by Dr. Wayne Babcock (of the
Babcock forceps) entitled “Resuscitation during
Anesthesia.”(16) In it, he states and I categorize here
by concepts mentioned above “If a response is not
instantly obtained by simple measures” –immediate
actions, “a fixed emergency routine” – standardized
content based upon best known data, which he
clarifies later this is open to local customization and
judgment, “posted on the walls of every operating
room” – accessible where needed, “and drilled into
every member of the staff should be enforced” – prior
training along with culture of expected use, albeit he
emphasizes here a top-down requirement over other
important behavioral impacts.
While a full history of simulation, teamwork training,

cognitive aids, and checklists is beyond the scope of
this lecture, some further background on each is
provided in the Reference section.(9, 10, 17-21)
Figure 3 on Crisis Resource Management shows
visually how cognitive aid use exists within the
broader context of teamwork and dynamic decision- Figure 3. Crisis Resource Management (CRM) teamwork
making skills. In his ASA 2014 Pierce lecture entitled and dynamic decision-making interacting skills, including
“Competence and teamwork are not enough: The "Use cognitive aids." Reprinted with permission
value of cognitive aids”, Dr. David Gaba provided a
detailed description of how emergency manuals emerged in anesthesiology and healthcare from a rich broader
history of cognitive aids and checklists.(22)
Accessibility: For many years, Advanced Cardiac Life Support cards and Malignant Hyperthermia posters were the
only readily available cognitive aids for OR critical events. Development work by multiple groups in parallel has
provided in the past few years cost-free access to several OR emergency manuals which are designed for use during
crises.(23)
Clinician Receptivity: In parallel, Dr. Atul Gawande’s popular book The Checklist Manifesto,(20) along with
multiple healthcare implementations and studies regarding routine checklist use, all impacted the receptivity of
clinicians and healthcare institutions to the concept and potential benefit of emergency manuals.(24, 25)
When Dr. Babcock had initially proposed the concept, at least for cardiac arrest, more than ninety years ago, the
healthcare community had not yet been ready. In contrast, the message of potential EM utility is now spreading
quickly. The November 2013 issue in Anesthesia & Analgesia focused on the topic, with three articles and two
editorials on emergency manuals, cognitive aids, or crisis checklists. Multiple ASA and APSF newsletter articles as
well as conference presentations spread the word efficiently and peaked interest in a healthcare community now
ready to begin using and assessing these tools. In September 2015, APSF held an experts’ conference focusing on
emergency manual evidence, implementation, and use. In ~3 years, the combined downloads of emergency manual
resources from Stanford, Ariadne labs, and Society for Pediatric Anesthesia have reached more than thirty thousand
in English, spanning diverse geography and practice settings, with tens of thousands more for translated versions
globally (EMIC Steering Committee Meeting, personal communication, February 10 2016).
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Summary of simulation-based data

There is now a decade of studies examining whether the use of emergency manuals during realistic mannequin-
based simulation scenarios helps clinicians to efficiently perform more key actions during crises. The preponderance
of the data points to yes, though there are clearly important nuances involved in how to best use these tools. A subset
of studies that are relevant to OR critical events are described here.
In a 2006 observational study of anesthesia residents managing simulated malignant hyperthermia (MH) cases,
Harrison et al. found a positive correlation between the frequency of MH cognitive aid use and appropriate treatment
of MH.(3) Burden et al. found that the majority of anesthesia and obstetrics residents did not use accessible
cognitive aids, and omitted key treatment actions during management of MH and obstetric cardiac arrest simulated
scenarios. When a “reader” was sent in explicitly to read to the team from the cognitive aid, key actions were then
performed.(26) Bould et al. found no difference in management of neonatal resuscitation with and without a
cognitive aid poster, but subjects were not familiar with the poster before the scenario and most in the intervention
group did not use it frequently.(27) Neal et al. found that anesthesia residents performed significantly better in
managing local anesthetic systemic toxicity when randomized to have access to a previously introduced LAST
checklist versus not. Moreover, within the intervention group the residents who used the LAST checklist more
frequently performed even better.(4) Arriaga et al. studied interprofessional operating room teams managing 8
different OR critical events. Each team was randomly assigned to half of the events with, and half without, crisis
checklists (CCs). When CCs were available versus not, 6% versus 23% of key management steps were missed.(2)
Marshall reviewed cognitive aid literature from a variety of settings more completely and discusses the potential
impact of design factors.(28) Following this review, Marshall’s group then conducted multiple simulation studies to
delve into the impacts of cognitive aid designs and use on team functioning and non-technical teamwork skills.(29,
30) Watkins et al. studied paper versus electronic, finding the paper version favored by users, though pointing out
that use of electronic cognitive aids will be greatly impacted by the design, training, and integration of the specific
tool.(31) Goldhaber-Fiebert and Howard put the healthcare literature into context with findings from other high-
hazard industries and human factors studies, as well as decades of iterative simulation-based development and
testing, and proposed the four-element conceptual implementation framework described above.(14)
Early clinical implementations and trainings: data and further resources

Neily et al. surveyed Veteran Health Administration (VHA) anesthesia professionals six months after national VHA
implementation of a 14-event clinical cognitive aid for OR critical events, which was initiated at the Palo Alto VHA
and drew on prior work in the book Crisis Management in Anesthesia.(9, 32) Of the respondents, 87% knew it
existed, half had used it as a reference, and 7% had used it during a crisis. Among crisis users, they had all used it
also as a reference and all felt it was helpful. Training varied across VHA sites, and crisis users were more likely to
have received formal training.(32) While 7% may not sound like many, the number of applicable critical events in
six months since implementation is not known, and likely is small with only a subset of respondents even
encountering an applicable opportunity.
Following widespread cost-free dissemination in the past few years of the Stanford emergency manual (SEM) for
perioperative critical events,(33) Ariadne Lab’s crisis checklists (ACC),(34) and Society for Pediatric Anesthesia’s
(SPA) critical events checklists (35) there have been case reports(12, 13) as well as many personal emails with
stories told about effective clinical uses of EMs during clinical critical events. The common emerging themes
include the importance of EM accessibility and familiarity, helpfulness of reader role when resources allow, and the
potential for EMs to improve team communication. None of these individual stories represent formal quantitative or
qualitative data, there are no denominators, and many potential biases exist. However, the multiple early reports do
suggest these tools are being used clinically, found by at least some clinicians to be helpful for patient care, and
underscore the need for more research on EM clinical implementation and use.
Clinical implementation research for EMs is nascent, with our team reporting a pilot study of clinical use with
mixed-methods survey data from Stanford anesthesia residents pre and >1 year post implementation, in press at
Anesthesia and Analgesia. (11) OR safety culture supporting appropriate cognitive aid use improved since
implementation, and trainings impacting residents most were mannequin-based simulations of critical events and
self-review. At least a quarter of all residents had used an EM during a clinical critical event, most often cardiac
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arrest, the vast majority of whom felt the EM helped their teams deliver better care to their patient, and none of
whom felt it hurt or distracted
Our team recently assessed the impact of brief, widespread, in-situ OR staff training on EMs, utilizing mannequin-
based simulations, showing increased awareness of, familiarity with and intention to use EMs in future.(36) The
curriculum, instructor guides, and handouts were published at MedEd Portal.(37) Multiple groups have shared
video-based materials for training clinicians on how and when to effectively use EMs as well as rationale for their
use.(38, 39) A brief graphically-illustrated overview for local leaders on EM implementation and use is also
available.(40)
As more institutions are pursuing EM implementation, they are finding important: local leadership buy-in, inter-
professional implementation teams, and local modification at least for key phone numbers and conformity with local
policies.
Discussion and Next Steps: Perioperative medicine has reached a tipping point regarding enabling effective use of
emergency manuals to help teams deliver better patient care during critical events. The evidence base from other
industries and from simulation-based studies has shown both a need and that emergency manuals can fill this need
when used effectively. Now, several cost-free tools are widely available for clinical settings. As clinical
implementation research expands, among the next priorities are to: assess barriers and facilitators for EM clinical
implementation and use; describe most effective implementation, training, and use strategies; actively seek out and
mitigate any potential harms; and describe dissemination and adoption. These goals will require rigorous mixed
qualitative and quantitative methods. While quantitative measures of patient morbidity may never be possible given
the rarity of events, and despite much still to learn about EM use, the data described here suggest a useful role for
emergency manuals in helping teams deliver optimal care to patients during critical events.
Acknowledgments: Many individuals, teams, and institutions have contributed to the development, testing, clinical
implementation, use, and study of emergency manuals. In particular, I’d like to thank: SACAG’s Stanford
Emergency Manual team, Ariadne Lab’s Project Check, and SPA’s Quality and Safety Committee for sharing cost-
free the tools they developed; EMIC steering committee for gathering EM tools, implementation, and training
resources in one location and ongoing collaborative work to enable interested institutions to implement successfully
– links to the free tools above and much more are all available via www.emergencymanuals.org; the many clinicians
who have given feedback to improve design, training, and use of EMs as well as those who have shared their
experiences using EMs during critical events have been invaluable – you know who you are; the Stanford
implementation team supported by Stanford Hospital and the Department of Anesthesia, Critical Care and Pain
Medicine; Dr. Sylvia Bereknyei Merrell for her proofreading and input. Thank you to Foundation for Anesthesia
Education and Research (FAER) for a Research in Education Grant that provides funding for our ongoing EM
implementation research.
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Examples from cost-free downloadable emergency manuals
Figure 4. Table of contents and sample page from the Operating Room Crisis Checklists, from Ariadne Labs. For latest
version see: http://www.projectcheck.org/crisis.html.
Figure 5. Table of contents and sample page from the PediCrisis Critical Events Checklist, from the Society for Pediatric
Anesthesia's (SPA) Quality and Safety Committee. For latest version see: pedsanesthesia.org, Quality and Safety
Committee, Critical Events Checklists.
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HYPERTHERMIA
MALIGNANT
Figure 6. Table of contents and sample page from the Stanford Perioperative Emergency Manual from the Stanford
Anesthesia Cognitive Aid Group (SACAG), 2014 V2.4. For latest version see: http://emergencymanual.stanford.edu.
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best practices for patient care during acute events? Anesthesia and Analgesia. 2013;117(5):1149-61.
15. Damschroder LJ, Aron DC, Keith RE, Kirsh SR, Alexander JA, Lowery JC. Fostering implementation of
health services research findings into practice: a consolidated framework for advancing implementation science.
Implementation Science. 2009;4:50.
16. Babcock WW. Resuscitation during anesthesia. Anesth Analg. 1924:208-13.
17. Howard SK, Gaba DM, Fish KJ, Yang G, Sarnquist FH. Anesthesia crisis resource management training:
teaching anesthesiologists to handle critical incidents. Aviat Space Environ Med. 1992;63(9):763-70.
18. Clancy CM, Tornberg DN. TeamSTEPPS: assuring optimal teamwork in clinical settings. American
Journal of Medical Quality. 2007;22(3):214-7.
19. Gaba DM. The future vision of simulation in healthcare. Simul Healthc. 2007;2(2):126-35.
20. Gawande A. The checklist manifesto : how to get things right. 1st ed. New York: Metropolitan Books;
2010.
21. Schmidt E, Goldhaber-Fiebert SN, Ho LA, McDonald KM. Simulation exercises as a patient safety
strategy: a systematic review. Annals of internal medicine. 2013;158(5 Pt 2):426-32.
22. Gaba DM. Ellison C. Pierce, Jr., M.D. Patient Safety Memorial Lecture: Competence and Teamwork Are
Not Enough: The Value of Cognitive Aids. American Society of Anesthesiologists Annual Meeting; October 11,
2014; New Orleans, LA2014.
23. Emergency Manuals Implementation Collaborative (EMIC): Free Tools Available from:
http://www.emergencymanuals.org/free-tools.html.
24. Hales BM, Pronovost PJ. The checklist--a tool for error management and performance improvement.
Journal of Critical Care. 2006;21(3):231-5.
25. Haynes AB, Weiser TG, Berry WR, Lipsitz SR, Breizat AH, Dellinger EP, et al. A surgical safety checklist
to reduce morbidity and mortality in a global population. N Engl J Med. 2009;360(5):491-9.
26. Burden AR, Carr ZJ, Staman GW, Littman JJ, Torjman MC. Does every code need a "reader?"
improvement of rare event management with a cognitive aid "reader" during a simulated emergency: a pilot study.
Simul Healthc. 2012;7(1):1-9.
27. Bould MD, Hayter MA, Campbell DM, Chandra DB, Joo HS, Naik VN. Cognitive aid for neonatal
resuscitation: a prospective single-blinded randomized controlled trial. British Journal of Anaesthesia.
2009;103(4):570-5.
28. Marshall S. The use of cognitive aids during emergencies in anesthesia: a review of the literature. Anesth
Analg. 2013;117(5):1162-71.
29. Marshall SD, Mehra R. The effects of a displayed cognitive aid on non-technical skills in a simulated 'can't
intubate, can't oxygenate' crisis. Anaesthesia. 2014;69(7):669-77.
30. Marshall SD, Sanderson P, McIntosh CA, Kolawole H. The effect of two cognitive aid designs on team
functioning during intra-operative anaphylaxis emergencies: a multi-centre simulation study. Anaesthesia.
2016;71(4):389-404.
31. Watkins SC, Anders S, Clebone A, Hughes E, Zeigler L, Patel V, et al. Paper or plastic? Simulation based
evaluation of two versions of a cognitive aid for managing pediatric peri-operative critical events by anesthesia
trainees: evaluation of the society for pediatric anesthesia emergency checklist. Journal of clinical monitoring and
computing. 2016;30(3):275-83.
32. Neily J, DeRosier JM, Mills PD, Bishop MJ, Weeks WB, Bagian JP. Awareness and use of a cognitive aid
for anesthesiology. Joint Commission Journal on Quality and Patient Safety. 2007;33(8):502-11.
33. Stanford Anesthesia Cognitive Aid Group (SACAG). Stanford Perioperative Emergency Manual
Available from: http://emergencymanual.stanford.edu.
34. Ariadne Labs. OR Crisis Checklists Available from: http://www.projectcheck.org/crisis.html.
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35. Anesthesia SfP. PediCrisis Critical Events Checklists

Available from: http://www.pedsanesthesia.org/newnews/Critical_Event_Checklists.pdf?201405121023.
36. Goldhaber-Fiebert SN, Lei V, Nandagopal K, Bereknyei S. Emergency Manual Implementation: Can Brief
Simulation-Based OR Staff Trainings Increase Familiarity and Planned Clinical Use? Joint Commission Journal on
Quality and Patient Safety. 2015, In Press.
37. Goldhaber-Fiebert SN, Lei V, Jackson ML, McCowan K. Simulation-based Team Training: Crisis
Resource Management and the Use of Emergency Manuals in the OR. . MedEDPORTAL Publications.
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38. Goldhaber-Fiebert SN, Lei V, Bereknyei Merrell S, Nandagopal K. Perioperative Emergency Manuals in
Clinical Clerkships: Curricula on “Why, How, and When to Use” for Teaching Medical Students. MedEdPORTAL
Publications. 2015.
39. Ariadne Labs V. OR Crisis Checklists Available from: https://youtu.be/iaHiSYR11u0.
40. Goldhaber-Fiebert SN. Why and How to Implement Emergency Manuals 2013 Available from:
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Perioperative Goal-Directed Therapy
Karsten Bartels Denver, CO
1) Traditional volume monitors, metabolic labs, and evolution to dynamic indices;

Dr. Andrew Leibowitz
2) Goal-Directed Therapy in sepsis; Dr. Jeffrey Katz
3) Goal-Directed Therapy in the operating room; Dr. Andrea Kurz
4) Cardiac output technologies; Dr. Karsten Bartels
History of clinical cardiac output monitoring
As a prerequisite to the widespread use of thermodilution pulmonary artery (PAC)-

based cardiac output monitoring in the 1970s, right heart catheterization had to
become feasible. In 1929, the physician Werner Forssmann was the first to perform
human right heart catheterization using a Foley catheter placed via his antecubital vein. 1
His German chiefs did not approve of his free spirit, so he ended up dismissed from his
position. Eventually however, this tremendous contribution to cardiovascular medicine
was recognized. Many years after leaving academics to pursue a successful career as a
private practice urologist Forssmann was called out of the operating room and received
notice that he had been awarded the Nobel prize in 1956.2
Inspired by sailboats flying large spinnaker sails on the Pacific, Jeremy Swan made
floating of a balloon-tipped catheter into the right heart and the pulmonary artery
clinically feasible.3 In collaboration with William Ganz, thermodilution-derived cardiac
output (CO) measurements became a reality at the bedside of critically ill patients in the
1970s.4
Methods for cardiac output monitoring
Thermodilution
Thermodilution, or for that matter any indicator dilution technique, are based on the
decrease of the indicator over time that is dependent on flow / cardiac output. The
Stewart-Hamilton equation is the basis for this technique:
m = Q 0∫∞ c(t)dt
m = mass of indicator, Q = flow, and c(t) = change in concentration over time.5
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Measuring CO using thermodilution is more complex and can be calculated as follows:
CO = VI (TB – TI) K1 * K2 / 0∫∞ ΔTB(t)dt [3]
VI = injectate volume, TB = temperature of blood, TI = temperature of injectate, K1 =

density factor, and K2 = a constant that characterizes dead space, heat exchange, and
speed of injection. The denominator in this equation is the change in blood temperature
over time (0∫∞ ΔTB(t)dt). 6
Swan-Ganz catheter CO measurements only measure right-sided CO and may not reflect
left-sided CO, e.g. in setting of shunt. Other limitations of thermodilution CO are
apparent from the assumptions made for this approach:
- Indicater and blood are perfectly mixed

- The difference in temperature over time is measured accurately
Hence, in situations such as severe tricuspid regurgitation,7 frequent repeated

measurements,8 low flow states9, or rapid temperature changes 10,11, thermodiultion CO
measurements may not be accurate.
Ultrasound
Austrian physicist Christian Doppler layed the foundation for ultrasoung-based cardiac
output measurements. Leveraging the relationship between the frequency difference of
sound wave that is reflected from a movig target, the speed of this target can be
calculated.
v = c/(20cos())
Δƒ = frequency difference between reflected and incidence ultrasound beam, c = speed

of sound in tissue, ƒ0 = frequency of the incident ultrasound beam, θ = angle of
incidence, v = velocity of a moving reflector.
See figure below for illustration.
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Fig 1. Principle of Doppler ultrasound measurements. Note that a significant

angle of incident θ will lead to velocity underestimation of the object of
interest (e.g. fire truck).
Doppler ultrasound measurements of cardiac output are non-invasive. Stroke volume is

measured over the entire hearbeat by capturing the velocity time integral and then
calculation stroke volume through multiplication of the relevant cross-sectional area.
For transesophageal echocardiography, this most commonly occurs in the left-
ventricular outflow tract (LVOT). Limitations of this technique lie in the assumption that
the velocity of blood flow is the same over the entire cross-sectional area (which it is not
as blood flow slows towards the vessel wall) and that the area does not change during
systole (which it does dependent on pressure change and vascular impedance).
Nonetheless, when compared to Swan-Ganz thermodilution, Doppler-based techniques
are slightly less precise, although these differences are unlikely relevant in clinical
practice.12
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Bioimpedance
Leveraging the relationship between the electrical resistance of the thorax and its
intrathoracic blood volume permit determination of cardiac output - a concept known
as thoracic electrical bioimpedance. Further, thoracic impedance is to be dependent
only on changes in intrathoracic blood volume. Maximum impedance changes within
the cardiac cyle are further related to peak aortic blood flow. Ventricular ejection time is
discerned from the EKG tracing. Based on the above assumptions, bioimpedance is
highly sensitive to electrode positioning, pulmonary edema, and electrical noise.
Pulse contour analysis
The Windkessel model assumes that blood flowing into a vessel of must be equal to the
blood volume exiting vessel during a cardiac cycle. The aorta behaves as a capacitor and
the arterioles act as a resistor.13 Blood pressure and heart rate are used to approximate
impedance.14 For clinical use, two broad categories exist: calibrated and uncalibrated
devices. Calibration is performed using indicate dilution technique (as described above),
e.g. using lithium. Cardiac output is more accurate when measured with calibrated
devices. A most usepful function of many devices that use pulse contour analysis is their
ability to report dynamic indices such as pulse pressure variation (PPV) and stroke
volume variation (SVV). These are more accurate when trying to predict volume
responsiveness than the CO measurement per se.
Summary
While thermodilution is still the clinical gold standard for cardiac output monitoring,
Doppler-based devices have comparable accuracy but are less invasive to place.
Calibrated pulse contour devices are more accurate than uncalibrated devices,
especially in hemodynamically unstable patients. Dynamic indices of fluid
responsivenessbetter guide fluid therapy than CO measurements. Most importantly CO
measuring devices should be scrutinized on their ability to inform decisions that
improve relevant clinical outcomes.15
References
1. [Munchener Medizinische Wochenschrift/20 March 1931 Contrast

representation of the cavities of the living right half of the heart by Werner
Forssmann, Eberswalde]. MMW Munch Med Wochenschr. 1978;120(14):489.
2. Heiss HW. Werner Forssmann: a German problem with the Nobel Prize. Clin
Cardiol. 1992;15(7):547-549.
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3. Swan HJ, Ganz W, Forrester J, Marcus H, Diamond G, Chonette D.

Catheterization of the heart in man with use of a flow-directed balloon-tipped
catheter. N Engl J Med. 1970;283(9):447-451.
4. Ganz W, Donoso R, Marcus HS, Forrester JS, Swan HJ. A new technique for
measurement of cardiac output by thermodilution in man. Am J Cardiol.
1971;27(4):392-396.
5. Profant M, Vyska K, Eckhardt U. The Stewart-Hamilton Equations and the
Indicator Dilution Method. SIAM Journal on Applied Mathematics.
1978;34(4):666-675.
6. Nishikawa T, Dohi S. Errors in the measurement of cardiac output by
thermodilution. Can J Anaesth. 1993;40(2):142-153.
7. Cigarroa RG, Lange RA, Williams RH, Bedotto JB, Hillis LD. Underestimation of
cardiac output by thermodilution in patients with tricuspid regurgitation. Am J
Med. 1989;86(4):417-420.
8. Maruschak GF, Potter AM, Schauble JF, Rogers MC. Overestimation of pediatric
cardiac output by thermal indicator loss. Circulation. 1982;65(2):380-383.
9. van Grondelle A, Ditchey RV, Groves BM, Wagner WW, Jr., Reeves JT.
Thermodilution method overestimates low cardiac output in humans. Am J
Physiol. 1983;245(4):H690-692.
10. Bazaral MG, Petre J, Novoa R. Errors in thermodilution cardiac output
measurements caused by rapid pulmonary artery temperature decreases after
cardiopulmonary bypass. Anesthesiology. 1992;77(1):31-37.
11. Latson TW, Whitten CW, O'Flaherty D. Ventilation, thermal noise, and errors in
cardiac output measurements after cardiopulmonary bypass. Anesthesiology.
1993;79(6):1233-1243.
12. Thiele RH, Bartels K, Gan TJ. Cardiac output monitoring: a contemporary
assessment and review. Crit Care Med. 2015;43(1):177-185.
13. Essler S, Schroeder MJ, Phaniraj V, Koenig SC, Latham RD, Ewert D. Fast
estimation of arterial vascular parameters for transient and steady beats with
application to hemodynamic state under variant gravitational conditions. Ann
Biomed Eng. 1999;27(4):486-497.
14. Wesseling KH, de Witt B, Weber AP, Smith T. A Simple Device for the Continuous
Measurement of Cardiac Output. Advances in Cardiovascular Physics.
1983;5(2):16-52.
15. Bartels K, Thiele R, Gan T. Rational fluid management in today's ICU practice.
Critical Care. 2013;17(Suppl 1):S6.
221
Page 1
Goal Directed Therapy in the Intensive Care Unit Goal

Directed Therapy in the Intensive Care Unit
Jeffrey A. Katz, MD Evanston/IL
Introduction
The physiologic changes in shock cause an imbalance between oxygen supply and demand. Sepsis
pathophysiology can present with a wide range of hemodynamic perturbations including hypovolemia, venous and
arterial vasodilation, hypoxemia, myocardial dysfunction, and microcirculatory and mitochondrial dysfunction.1
These changes can lead to lactic acidosis, increased oxygen extraction by tissue beds, organ dysfunction, and
eventually, if untreated, can lead to disruption of oxygen utilization and death. 2 Goal directed therapy (GDT) is a
resuscitation strategy that aims to improve oxygen supply to tissue beds by improving preload, contractility,
afterload, and oxygen carrying capacity.3 The Emanuel Rivers’ Early Goal Directed Therapy Trial3 published in
2001 investigated protocolized care in septic patients aimed at restoring tissue blood flow and oxygenation showed a
mortality reduction from 46.5% to 30.5% in the control versus study group, respectively. Prior to the Rivers Trial,
septic patients may have lacked aggressive medical intervention including timely assessment, diagnosis, treatment,
and re-assessment of their condition. GDT is a treatment protocol that involves intensive monitoring, aggressive
management with intravenous fluids, vasopressors, inotropes, and packed red blood cells to achieve pre-specified
hemodynamic and metabolic goals with continual reassessment to ensure that the goals are achieved.
Sepsis Definition
The classic diagnostic criteria of sepsis were outlined by guidelines from 1991 and upheld by a revision in the 2001
by the Society of Critical Care Medicine and American College of Chest Physicians. The clinical syndrome of
sepsis required the presence of the systemic inflammatory response syndrome (SIRS) with an associated or
suspected infection.4,5
Table 1: SIRS Criteria: Requires 2 of 44

Temperature >380C or <360C
Heart Rate >90 beats per minute
Respiratory Rate >20 per minute or PaCO2 < 32 mmHg
White blood cell count >12,000/mm3, <4000/mm3, or > 10% bands
The sepsis definition, however, has been updated in 2016 by the Society of Critical Care Medicine and the European
Society of Intensive Care. Sepsis is now defined as patients with an infection and a Sequential Organ Failure
Assessment (SOFA) greater than 2. The SOFA score can be simplified with the quick SOFA (qSOFA) which
includes altered mental status, respiratory rate greater than 22, and systolic hypotension less than 100mmHg 6. A
patient meeting 2 out of 3 of these criteria have a 10% mortality. 6 Septic shock is identified when patients without
hypovolemia require vasopressor support and a serum lactate concentration greater than 2 mmol/L. These patients
have approximately a 40% mortality rate.6
Timing
The concept of goal directed therapy and hemodynamic guided therapies in the intensive care unit (ICU) are not
novel to 2000’s. Supranormal oxygen delivery to tissue beds was tested in a randomized controlled trial published
in 1994 in septic patients admitted the ICU. Augmentation of cardiac index to 4.5 L/(M*BSA) and oxygen delivery
of 600mL per minute with volume expansion and dobutamine within 24 hours did not result in improve patient
outcomes and may have increased the likelihood of death.7 Another major GDT trial with 762 patients (GDT
parameters: CI and mixed venous oxygen saturation) was initiated in the ICU within 72 hours of admission
demonstrated the ineffectiveness of delayed care and no change in mortality.8 The clinical and cultural shift that
occurred with the Rivers trial was initiation of early goal directed therapy for septic patients within six hours and
221
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this prompt care subsequently became the focal points of the Surviving Sepsis Guidelines.9 If thought of in terms of
accumulated oxygen debt, the delay in care of these patients while awaiting ICU admission from the emergency
department resulted in continued tissue ischemia, risk for multi-system organ failure, and death.10 Restoration of
tissue oxygenation will not be effective if permanent organ damage has occurred. Timely initiation of care is
paramount if one is to expect a benefit from GDT.
Patient Selection
Patients at high risk for morbidity and mortality likely benefit far greater from GDT than do low risk patients. The
identification of sepsis and septic shock (Sepsis-3) are based on mortality risk characteristics. Patients with a
qSOFA score > 2 are at a 10% risk and patients with septic shock qSOFA > 2, lactate > 2mmol/L, and pressor
dependence may have a mortality as high as 40%.6 Lactate serves as an independent risk factor for mortality in
sepsis with a concentration dependent increase in mortality. Lactate ranges of 2.0-3.9mmol/L or >4.0mmol/L have
an odds ratio of 3.27 and 4.87 for mortality when compared to normal values.11 Additionally and unsurprisingly,
initial presentation of organ dysfunction in septic patients is also a risk factor for mortality. 12 Higher risk patients
are at a greater risk for hypoxic related injury and, therefore ,they maybe more likely to benefit from early GDT13. It
is often these patients who are protocolized to GDT. 14,15 Furthermore, there may even be a cost effectiveness of
GDT due avoidance of complications from organs system dysfunction. 16
Therapeutics
GDT is a treatment protocol that identifies hemodynamic or metabolic goals with associated interventions to meet
these goals. The hemodynamic parameters for GDT include both static (i.e., MAP, CVP, etc.) and dynamic
parameters (i.e., pulse pressure variation, systolic pressure variation). The dynamic parameters provide either a
direct or indirect measurement of stroke volume variation with changes in preload with mechanical ventilation or
passive leg raise and may be more reliable than static parameters.17 Metabolic goals most often include mixed or
central venous blood gases and lactate clearance. Conceptually protocols are targeted to improve cardiac output or
associated surrogates for cardiac output and thus improve tissue oxygen delivery. It is important to set appropriate
endpoints of resuscitations and have the ability to correctly interpret the associated data to improve outcomes.
Wrong interpretation due to lack of knowledge or a misunderstanding of the inherent limitations of a monitor
generated endpoint can lead to inappropriate therapy. An excellent example of this is CVP, used as a marker of
fluid responsiveness, but has not shown to be reliable in many clinical conditions18. A complete review of GDT
protocols is outside the scope of this outline. For a thorough review, several key references have been highlighted as
well as a GDT review article.19 (***).
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Controversies in Goal Directed Therapy in the ICU
The utility and feasibility of GDT has been questioned with the publication of several large randomized controlled
trials of GDT versus usual/standard care. The ProCESS20 and ARISE21 trials published in 2014 and the PROMISE22
trial published in 2015 did not show a survival benefit from the protocolized care groups versus the non-protocolized
“usual care” groups; however, a recent meta-analysis did show benefit from GDT when initiated within 6 hours of
initial presentation.23 This has led to questions regarding the clinical need for protocolization of care and if GDT
has become unnecessary.24,25 What appears to be evident, however, is that usual care has changed over the past two
decades and a cultural shift towards early aggressive fluid resuscitation is now “usual” care.
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Figure References: Rivers3, PROMISE22, PROCESS20, ARISE21
221
Page 5
1
H Bryant Nguyen et al., “Early Goal-Directed Therapy in Severe Sepsis and Septic Shock: Insights and
Comparisons to ProCESS, ProMISe, and ARISE,” Critical Care, May 23, 2016, 1–16, doi:10.1186/s13054-016-
1288-3.f
2
Paul Kasnitz, MD., "Mixed Venous Oxygen Tension and Hyperlactatemia: Survival in Severe Cardiopulmonary
Disease," JAMA Auguest 9, 1976;236(6):570-74.
3
***Emanuel Rivers et al. "Early Goal Directed Therapy in the Treatment of Severe Sepsis and Septic Shco. NEJM
October 26, 2001, 1–10.
4
Roger Bone et al., “Definitions for Sepsis and Organ Failure and Guidelines for the Use of Innovative Therapies in
Sepsis,” Chest 101 (1992): 1644–55.
5
Mitchell M Levy et al., “2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference,”
Critical Care Medicine 31, no. 4 (April 2003): 1250–56, doi:10.1097/01.CCM.0000050454.01978.3B.
6
Mervyn Singer et al., “The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3),”
Jama 315, no. 8 (February 23, 2016): 801–23, doi:10.1001/jama.2016.0287.
7
“Michelle Hayes FRCA, et al. "Elevation of Systemic Oxygen Delivery in the Treatment of Critically Ill Patients,"
NEJM1994 (1), October 8, 2008, 1–6.
8
Brazzi Luca Pelosi Paolo Latini Roberto Tognoni Gianni Pesenti Antonio Fumagalli Roberto Gattinoni Luciano,
“A Trial of Goal-Oriented Hemodynamic Therapy in Critically Ill Patients,” August 21, 2000, 1–8.
9
“Surviving Sepsis Campaign,” CCM, 2013(41), 580–637.
10
Robert Wayne Barbee, Penny S Reynolds, and Kevin R Ward, “Assessing Shock Resuscitation Strategies by
Oxygen Debt Repayment,” Shock 33, no. 2 (February 2010): 113–22, doi:10.1097/SHK.0b013e3181b8569d.
11
Mark E Mikkelsen et al., “Serum Lactate Is Associated with Mortality in Severe Sepsis Independent of Organ
Failure and Shock*,” Critical Care Medicine 37, no. 5 (May 2009): 1670–77, doi:10.1097/CCM.0b013e31819fcf68.
12
Nathan Shapiro et al., “The Association of Sepsis Syndrome and Organ Dysfunction with Mortality in Emergency
Department Patients with Suspected Infection,” Annals of Emergency Medicine 48, no. 5 (November 2006): 583–
590.e1, doi:10.1016/j.annemergmed.2006.07.007.
13
Rupert Pearse, et al. “Early Goal-Directed Therapy After Major Surgery Reduces Complications and Duration of
Hospital Stay. a Randomised, Controlled Trial [ISRCTN38797445],” Critical Care, October 20, 2005, 1–7,
doi:10.1186/cc3887).
14
*** Alan E Jones, “Lactate Clearance vs Central Venous Oxygen Saturation as Goals of Early Sepsis
Therapy<Subtitle>a Randomized Clinical Trial</Subtitle>,” Jama 303, no. 8 (February 24, 2010): 739–17,
doi:10.1001/jama.2010.158.
15
***C M Cannon et al., “The GENESIS Project (GENeralized Early Sepsis Intervention Strategies): a Multicenter
Quality Improvement Collaborative,” Journal of Intensive Care Medicine 28, no. 6 (November 11, 2013): 355–68,
doi:10.1177/0885066612453025.
16
Claudia Ebm et al., “A Cost-Effectiveness Analysis of Postoperative Goal-Directed Therapy for High-Risk
Surgical Patients*,” Critical Care Medicine 42, no. 5 (May 2014): 1194–1203,
doi:10.1097/CCM.0000000000000164.
17
***Paul E Marik, Xavier Monnet, and Jean-Louis Teboul, “Hemodynamic Parameters to Guide Fluid Therapy,”
Annals of Intensive Care 1, no. 1 (March 21, 2011): 1, doi:10.1186/2110-5820-1-1.
18
FCCP Paul E Marik MD, FCCP Michael Baram MD, and Bobbak Vahid MD, “Does Central Venous Pressure
Predict Fluid Responsiveness?*: a Systematic Review of the Literature and the Tale of Seven Mares,” Chest 134,
no. 1 (July 8, 2008): 172–78, doi:10.1378/chest.07-2331.
19
*** P Marik and R Bellomo, “A Rational Approach to Fluid Therapy in Sepsis,” ed. J G Hardman, British Journal
of Anaesthesia 116, no. 3 (February 10, 2016): 339–49, doi:10.1093/bja/aev349.
20
***The ProCESS Investigators, “A Randomized Trial of Protocol-Based Care for Early Septic Shock,” New
England Journal of Medicine 370, no. 18 (May 2014): 1683–93, doi:10.1056/NEJMoa1401602.
21
***The ARISE Investigators and the ANZICS Clinical Trials Group, “Goal-Directed Resuscitation for Patients
with Early Septic Shock,” New England Journal of Medicine 371, no. 16 (October 16, 2014): 1496–1506,
doi:10.1056/NEJMoa1404380.
22
***Paul R Mouncey et al., “Trial of Early, Goal-Directed Resuscitation for Septic Shock,” New England Journal
of Medicine 372, no. 14 (April 2, 2015): 1301–11, doi:10.1056/NEJMoa1500896. (PROMISE Trial)
23
*** Wan-Jie Gu et al., “The Effect of Goal-Directed Therapy on Mortality in Patients with Sepsis - Earlier Is
Better: a Meta-Analysis of Randomized Controlled Trials,” November 11, 2014, 1–10, doi:10.1186/s13054-014-
0570-5.
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24
Mitchell M Levy, “Early Goal-Directed Therapy: What Do We Do Now?,” December 11, 2014, 1–2,
doi:10.1186/s13054-014-0705-8.
25
Maurizio Cecconi and Andrew Rhodes, “Goal-Directed Therapy,” Anesthesia & Analgesia 119, no. 3 (September
2014): 516–18, doi:10.1213/ANE.0000000000000367.
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Perioperative Goal-Directed Fluid Management
Andrea Kurz, M.D. Cleveland, OH
Perioperative fluid management is a major determinant of morbidity and mortality. Thus,

maintenance of normal intravascular volume is highly desirable, especially during major
abdominal surgery. (1-4) The main purpose of avoiding hypovolemia or fluid overload is
to guarantee sufficient perfusion and oxygenation of tissues and organs. Inadequate
tissue oxygenation results in cellular changes leading to tissue acidosis, which if
prolonged, has detrimental effects on most vital organs. One of the determinants of
oxygen delivery to tissues is cardiac output, which is the result of adequate stroke
volume and heart rate. Stroke volume is dependent on cardiac preload conditions, thus
maintenance of a normal intravascular volume is needed to optimize oxygen delivery. In
the operative period, the tissue extraction of oxygen is impaired, and thus optimization of
oxygen delivery is essential. It is therefore not surprising that optimization of tissue
perfusion and oxygenation is associated with improved outcomes in patients undergoing
major vascular, general or urologic surgery. (5)
Optimization of tissue perfusion and maintenance of normovolemia in the perioperative
period has been a topic of research for the past 30 years. Traditional either restrictive or
liberal fluid management were studied. As a consequence perioperative IV fluid
regimens in abdominal surgery can lead to patients receiving 3 to 7 L of fluid on the day
of surgery and more than 3 L/day for the following 3 to 4 days, leading to a 3- to 6-kg
weight gain.
Several small trials have compared restrictive and liberal fluid regimens and showed that
restrictive volume administration most likely is beneficial and associated with fewer
postoperative complications. (6,7,8) Nisenavich et al (9) showed that restrictive fluid
management had faster return of bowel function, fewer complications, and shorter
hospital stay (P=0.01).
However, other studies found no difference in the rates of wound infection with restrictive
or liberal fluid management. (10) or found more complications with restrictive
management. A meta-analysis of the fluid trials up to 2007 (3) found restrictive regimens
reduced overall complications; but the authors noted the heterogeneity of fluid regimens
and definitions of outcomes. Another two recent small trials found either no benefit or
harm. A recent meta-analysis of relevant trials (12 trials, 1160 patients) by Paul Myles
and his group evaluated the overall effect of fluid restriction on morbidity/mortality and
found benefits of fluid restriction in regards to pneumonia, pulmonary edema, hospital
length of stay as well as hospital mortality.
One could argue that neither a strict restrictive nor a strict liberal fluid management
protocol serve patients physiological needs in the perioperative period. Instead fluids
should be administered guided by a specific physiological and dynamic goal.
Perioperative fluid administration for the longest time was mainly guided by static
hemodynamic parameters such as heart rate, blood pressure, and central venous
pressure, which are known to be poor predictors of mild hypovolemia. (11,12) To avoid
major complications associated with hypovolemia or fluid overload and to optimize
perioperative fluid management, many investigators have proposed the infusion of fluids
based on a targeted physiological outcome. Under normal circumstances mixed venous
Refresher Course Lectures Anesthesiology 2016 © American Society of Anesthesiologists. All rights
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reprinted by ASA with permission. Reprinting or using individual refresher course lectures contained herein is strictly
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saturation, shock index, tissue oxygenation, and stroke volume have been used as the
targeted variables to conduct preclinical and clinical studies evaluating goal directed fluid
administration. (13-16)
The goal-directed therapy (GDT) is based on the hypothesis that fluid management
should maximize oxygen delivery through well-defined goals based on flow related
dynamic parameters. Furthermore, an individualized approach is based on
maximization of flow-related variables such as stroke volume by fluid challenges. The
most successful of these monitors evaluated whether patients are responders or non-
responders to fluid challenges. The expected hemodynamic benefit of volume expansion
is an increase in LV stroke volume, and hence in cardiac output. A patient is a
‘responder’ to volume expansion only if both ventricles operate on the ascending portion
of the Frank–Starling curve (biventricular preload dependence). In contrast, if one of the
ventricles or both ventricles operate on the flat portion of the curve, then the patient is a
‘nonresponder’ (i.e., his/her cardiac output will not increase significantly in response to a
volume challenge).
Esophageal Doppler ultrasonography is a minimally invasive method that permits
continuous estimation of cardiac output by measuring the blood flow velocity through the
aorta and estimating stroke volume and cardiac output.(17-19) Goal-directed
intraoperative fluid therapy monitored by esophageal Doppler identified volume-
responders following a fluid challenge strategy. It has been validated in general,
gynecological, urological, and cardiac surgery, and proven to improve outcome in many
patient populations and probably still remains the gold standard for perioperative volume
guidance. (20-22)
In older studies performed more than a decade ago Doppler-guided fluid management
improved outcome and decreased duration of hospitalization in patients undergoing
orthopedic, abdominal, vascular, and cardiac surgery. (23-25) Similarly, esophageal
Doppler-guided fluid optimization was associated with significantly faster recovered gut
function and significantly less faster gastrointestinal and overall morbidity in patients
undergoing colorectal surgery. The first study of that sort by Gan et al. demonstrated
that esophageal Doppler goal-directed intraoperative colloid administration during major
gynecologic, general, and urologic surgery resulted in earlier gastrointestinal function,
fewer postoperative complications, and a shorter hospital stay than non-targeted fluid
administration.(25) In patients undergoing cardiac surgery, goal-directed fluid therapy
reduced the incidence of intestinal mucosal hypoperfusion, the number of patients in
whom major complications developed, days in intensive care unit, and the overall
hospital stay.(24)
Numerous newer studies demonstrate that goal-directed fluid therapy reduces
complications, infections, and the duration of hospitalization. (26) Results are generally
similar, even though devices and protocols differ. (27,28) Many monitors for
measurement of cardiac output or stroke volume or dynamic parameters derived from
those are available, and are being evaluated in terms of validity but also outcomes
related performance. For example, Benes et al used colloid and dobutamine infusion to
optimize cardiac index and stroke volume variation in high-risk elective abdominal
surgery group and report a 56% reduction in 30-day postoperative complications along
with a 10% reduction in hospital LOS.(27) In a quality improvement study by NHS/NICE
(National Health Service/ National Institute for Health and Care Excellence, UK), there
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was a 27% decrease in hospital length of stay, equivalent to 3.5 days, across all
specialties.(29) Esophageal Doppler has been successfully used to measure cardiac
output and stroke volume.(30-32) In a randomized, single-blind trial evaluating patients
having major operations, Ramsingh et al report faster return of gastrointestinal function
(3 vs. 4 days), faster return to oral nutrition (4 vs. 5 days), and a 2.5-day (33%) decrease
in hospital length of stay. GDT has also been shown to be cost effective and clinically
helpful in postoperative patients. (33) A recent meta-analasys demonstrated decreased
mortality with goal directed fluid therapy.
In contrast, there are some studies, which showed no benefit of GDT. In a pragmatic,
multicenter, randomized, observer blind trial (OPTMISE Trial) involving 734 patients,
Pearse et al observed no significant reduction in postoperative complication (relative risk
0.84 [95% CI: 0.71- 1.01]) and no significant reduction in hospital LOS.14 (34)
Nonetheless, most studies do report some benefit from GDT. Thus GDT has become an
important part of most ERAS (Enhanced Recovery After Surgery) protocols.
Interestingly, most GDT studies so far used colloids for fluid optimization. Even the
enhanced recovery protocols suggest usage of colloids for fluid optimization. There are
many reasons to believe that colloids result in better postoperative outcome as suppose
to crystalloids. Colloids mainly remain intravascularly, increase plasma volume, increase
hemodynamic stability, and thus have a positive effect on organ perfusion. They also
have a better hemodynamic effect than Ringer’s lactate, specifically in regards to blood
pressure, tissue oxygenation and pH. Moreover, cerebral oxygenation, and oxygen
consumption is improved by HES 140/0.4 compared to Ringer’s lactate.(35)
In contrast balanced salt solutions (as the only other administered type of fluid during
major abdominal surgery in humans) decreased mean tissue oxygen tension in the
deltoid muscle for 24 hours postoperatively by 23%, whereas additional treatment with
hydroxyethyl starch led to a mean increase of 59%. Furthermore, in hypovolemic
patients, resuscitation with hetastarch resulted in increased colloid oncotic and
decreased incidence of pulmonary edema as compared to patients resuscitated with
ClNa 0.9%.
Crystalloids quickly move to the interstitial space and only one 5th of the administered
crystalloids remain in the intravascular space. Furthermore, large amounts of crystalloids
dilute plasma proteins, reduce colloid oncotic pressure, and ultimately further promote
extravasation of fluids to the interstitial space; resulting in interstitial edema and weight
gain. As excess interstitial fluid does not participate in cardiac output, patients with
significant fluid extravasation may still be hypovolemic due to fluid misdistribution.
Administering volume deliberately and unguided in this situation worsens fluid
accumulation in the interstice resulting in undesired effects like hemodynamic
deterioration, pulmonary edema, tissue edema, and decreased O2-delivery. It is not
surprising that the frequency of postoperative complications is related to intravenous
fluid administration and body weight increase on the day of surgery. (8)
Previous crystalloid studies, unfortunately, did not use dynamic parameters for fluid
guidance, but administered either fixed amounts or based crystalloid administration
purely on variables such as mean arterial pressure, heart rate, central venous pressure
and on urinary output, which are known to be poor predictors of intravascular volume. It
is therefore likely, that crystalloid patients in previous studies as well as in daily clinical
practice are either under- or over-infused. On the other hand, it has been shown that
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goal-directed colloid administration decreases postoperative complications and shortens

duration of hospitalization. However, it is unknown, whether goal-directed crystalloid
administration might have similar beneficial effects on postoperative outcome as
compared to goal-directed colloid administration.
Very few studies have directly compared goal-directed fluid administration with
crystalloids or colloids. A study from Hiltebrand et al. evaluated splanchnic blood flow in
pigs undergoing laparotomy. Animals were treated with either a restricted administration
of Ringer Lactate, (3 mL/kg/Hr), goal-directed Ringer Lactate solution (3 mL/kg/Hr plus
intermittent boluses of 250 mL), or a goal-directed colloid solution (3 mL/kg/Hr of Ringer
lactate plus boluses of 250 mL of 6% hydroxyethyl starch (130/0.4). Arterial blood
pressure, cardiac output, mesenteric artery flow, and mixed oxygen saturation were
significantly higher in both the goal-directed group than in the restrictive group. However,
microcirculatory flow and tissue oxygen tension in the intestinal mucosa increased only
in the goal-directed colloid group.(36) Similarly goal-directed colloid fluid therapy
significantly increased microcirculatory blood flow and tissue oxygen tension in healthy
and injured colons compared to goal-directed or restricted crystalloid fluid therapy.(37)
These results support the notion that perioperative goal-directed therapy with colloids
might be beneficial during major abdominal surgery.
In preliminary studies in humans using esophageal Doppler for fluid optimization, goal-
directed colloid and crystalloid administration resulted in comparable hemodynamic
parameters. However, fluid responsiveness was much faster after colloid administration.
Thus crystalloid patients received much larger fluid amounts to achieve the same
hemodynamic goals as compared to colloid patients.
Despite similar hemodynamic performance Doppler-guided colloid administration
improved subcutaneous tissue oxygenation in patients undergoing colorectal surgery as
compared to goal-directed crystalloid administration.(unpublished data) Furthermore,
Doppler-guided administration of HES resulted in a lesser amount of fluid translocated to
the interstitial lung space compared to crystalloids. This is reflected by the fact that goal-
directed colloid administration improved postoperative spirometric lung function
represented by FTC measurements (unpublished data).
These studies support the notion that large amounts of crystalloids are associated with
more fluid accumulation in the interstitial compartment compared to colloids. Whether
these intermediate results translate into different outcomes such as major complications,
length of stay, readmission rates or mortality in patients undergoing abdominal surgery is
currently evaluated in a large randomized trial enrolling approximately 1110 patients.
In summary, goal-directed fluid management improves outcomes in patients undergoing
abdominal, urological, gynecological and vascular surgery. Many devices are available
to monitor dynamic hemodynamic parameters. Esophageal Doppler is probably still the
most used device and gold standard. Whether goal directed fluid optimization with
crystalloids is as beneficial in regards to major postoperative morbidity and mortality as
compared to goal directed colloid administration remains unknown.
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References
1. Shoemaker WC, Montgomery ES, Kaplan E, Elwyn DH. Physiologic patterns in surviving
and nonsurviving shock patients. Use of sequential cardiorespiratory variables in defining
criteria for therapeutic goals and early warning of death. Arch Surg 1973;106:630-6.
2. Holte K, Sharrock NE, Kehlet H. Pathophysiology and clinical implications of
perioperative fluid excess. Br J Anaesth 2002;89:622-32.
3. Arieff AI. Fatal postoperative pulmonary edema: pathogenesis and literature review.
Chest 1999;115:1371-7.
4. Prien T, Backhaus N, Pelster F, Pircher W, Bunte H, Lawin P. Effect of intraoperative
fluid administration and colloid osmotic pressure on the formation of intestinal edema
during gastrointestinal surgery. J Clin Anesth 1990;2:317-23.
5. Wilson J, Woods I, Fawcett J, et al. Reducing the risk of major elective surgery:
randomised controlled trial of preoperative optimisation of oxygen delivery. Bmj
1999;318:1099-103.
6. Rahbari NN, Zimmermann JB, Schmidt T, Koch M, Weigand MA, Weitz J. Meta-analysis
of standard, restrictive and supplemental fluid administration in colorectal surgery. Br J
Surg. 2009 Apr;96(4):331-41.,
7. Corcoran TR, JEJ. Clarke, S. Myles, PS. Oh, KM. Perioperative fluid management
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8. Brandstrup B, Tonnesen H, Beier-Holgersen R, et al. Effects of intravenous fluid
restriction on postoperative complications: comparison of two perioperative fluid
regimens: a randomized assessor-blinded multicenter trial. Ann Surg 2003;238:641-8.
9. Nisanevich V, Felsenstein I, Almogy G, Weissman C, Einav S, Matot I. Effect of
intraoperative fluid management on outcome after intraabdominal surgery.
Anesthesiology. 2005 Jul;103(1):25-32.
10. Kabon B, Akca O, Taguchi A, Nagele A, Jebadurai R, Arkilic CF, et al. Supplemental
intravenous crystalloid administration does not reduce the risk of surgical wound
infection. Anesth Analg. 2005 Nov;101(5):1546-53
11. Shippy CR, Appel PL, Shoemaker WC. Reliability of clinical monitoring to assess blood
volume in critically ill patients. Crit Care Med 1984;12:107-12.
12. Suzuki A, Ishihara H, Okawa H, Tsubo T, Matsuki A. Can initial distribution volume of
glucose predict hypovolemic hypotension after radical surgery for esophageal cancer?
Anesth Analg 2001;92:1146-51
13. Rady MY, Rivers EP, Martin GB, Smithline H, Appelton T, Nowak RM. Continuous central
venous oximetry and shock index in the emergency department: use in the evaluation of
clinical shock. Am J Emerg Med 1992;10:538-41.
14. Polonen P, Ruokonen E, Hippelainen M, Poyhonen M, Takala J. A prospective,
randomized study of goal-oriented hemodynamic therapy in cardiac surgical patients.
Anesth Analg 2000;90:1052-9.
15. Madsen PL, Secher NH. Near-infrared oximetry of the brain. Prog Neurobiol
1999;58:541-60.
16. Bundgaard-Nielsen M, Ruhnau B, Secher NH, Kehlet H. Flow-related techniques for
preoperative goal-directed fluid optimization. Br J Anaesth 2007;98:38-44.
17. Singer M, Clarke J, Bennett ED. Continuous hemodynamic monitoring by esophageal
Doppler. Crit Care Med 1989;17:447-52.
18. Dark PM, Singer M. The validity of trans-esophageal Doppler ultrasonography as a
measure of cardiac output in critically ill adults. Intensive Care Med 2004;30:2060-6.
19. DiCorte CJ, Latham P, Greilich PE, Cooley MV, Grayburn PA, Jessen ME. Esophageal
Doppler monitor determinations of cardiac output and preload during cardiac operations.
Ann Thorac Surg 2000;69:1782-6.
20. Wakeling HG, McFall MR, Jenkins CS, et al. Intraoperative oesophageal Doppler guided
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21. McKendry M, McGloin H, Saberi D, Caudwell L, Brady AR, Singer M. Randomised

controlled trial assessing the impact of a nurse delivered, flow monitored protocol for
optimisation of circulatory status after cardiac surgery. BMJ 2004;329:258.
22. Noblett SE, Snowden CP, Shenton BK, Horgan AF. Randomized clinical trial assessing
the effect of Doppler-optimized fluid management on outcome after elective colorectal
resection. Br J Surg 2006;93:1069-76.
23. Bundgaard-Nielsen M, Holte K, Secher NH, Kehlet H. Monitoring of peri-operative fluid
administration by individualized goal-directed therapy. Acta Anaesthesiol Scand
2007;51:331-40.
24. Mythen MG, Webb AR. Perioperative plasma volume expansion reduces the incidence of
gut mucosal hypoperfusion during cardiac surgery. Arch Surg 1995;130:423-9.
25. Gan TJ, Soppitt A, Maroof M, et al. Goal-directed intraoperative fluid administration
reduces length of hospital stay after major surgery. Anesthesiology 2002;97:820-6.
26. Bennett-Guerrero E: Hemodynamic goal-directed therapy in high-risk surgical patients.
JAMA 2014; 311: 2177-8
27. Benes J, Chytra I, Altmann P, Hluchy M, Kasal E, Svitak R, Pradl R, Stepan M:
Intraoperative fluid optimization using stroke volume variation in high risk surgical
patients: results of prospective randomized study. Crit Care 2010; 14: R118
28. Cecconi M, Fasano N, Langiano N, Divella M, Costa MG, Rhodes A, Della Rocca G:
Goal-directed haemodynamic therapy during elective total hip arthroplasty under regional
anaesthesia. Crit Care 2011; 15: R132
29. Kuper M, Gold SJ, Callow C, Quraishi T, King S, Mulreany A, Bianchi M, Conway DH:
Intraoperative fluid management guided by oesophageal Doppler monitoring. BMJ 2011;
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30. Sinclair S, James S, Singer M: Intraoperative intravascular volume optimisation and
length of hospital stay after repair of proximal femoral fracture: randomised controlled
trial. Bmj 1997; 315: 909-12
31. Venn R, Steele A, Richardson P, Poloniecki J, Grounds M, Newman P: Randomized
controlled trial to investigate influence of the fluid challenge on duration of hospital stay
and perioperative morbidity in patients with hip fractures. Br J Anaesth 2002; 88: 65-71.
32. McKendry M, McGloin H, Saberi D, Caudwell L, Brady AR, Singer M: Randomised
controlled trial assessing the impact of a nurse delivered, flow monitored protocol for
optimisation of circulatory status after cardiac surgery. Bmj 2004; 329: 258
33. Ebm C, Cecconi M, Sutton L, Rhodes A: A cost-effectiveness analysis of postoperative
goal-directed therapy for high-risk surgical patients. Crit Care Med 2014; 42: 1194-203
34. Pearse RM, Harrison DA, MacDonald N, Gillies MA, Blunt M, Ackland G, Grocott MP,
Ahern A, Griggs K, Scott R, Hinds C, Rowan K, Group OS: Effect of a perioperative,
cardiac output-guided hemodynamic therapy algorithm on outcomes following major
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(130/0.4), on cerebral oxygen supply and consumption in resuscitation of rabbit with
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36. Hiltebrand LB, Kimberger O, Arnberger M, Brandt S, Kurz A, Sigurdsson GH. Crystalloids
versus colloids for goal-directed fluid therapy in major surgery. Crit Care 2009, 13:R40
37. Kimberger O, Arnberger M, Brandt S, et al. Goal-directed colloid administration improves
the microcirculation of healthy and perianastomotic colon. Anesthesiology 2009;110:496-
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Administration of fluid guidance: An overview and history from CVP to GDT in 2016
Andrew B. Leibowitz, M.D. New York, NY
Note: This is one of a 4 part presentations as follows:

Andrew B. Leibowitz, MD Administration of fluids guidance: An overview and history from CVP to
GDT
Karsten Bartels, MD Monitoring technology used in GDT
Jeffrey Katz, MD GDT in sepsis
Andrea Kurz, MD GDT in the perioperative period
Introduction:
Goal Directed Therapy (GDT) refers to the use of defined goals to guide fluid, blood and vasoactive agent
administration. GDT is promoted to reduce perioperative morbidity and mortality and has been incorporated into
many institutions’ Early Recovery after Surgery (ERAS) protocols. The most common goal currently targeted in
Anesthesiology is stroke volume and there are currently several commercially available devices that utilize different
technologies aimed at assisting Anesthesiologists in “optimizing” the stroke volume, usually by the administration
of fluid boluses, in real time and with little additional effort. Anesthesiologists need to understand how these
devices work and have command of the recent literature published in top tier journals investigating this approach in
order to decide if it should be incorporated into their practice. Building up to this present knowledge is a 60 year
history dating back to central venous catheterization and initial attempts at using the CVP, later pulmonary artery
catheters (PACs) and even more recently pulse pressure variation and systolic pressure change to “optimize” patient
care. The purpose of this short overview is to summarize this history so that current technology may be understood
in an historical context.
Background:
Central venous catheterization was first described by Aubaniac1 in 1952 and in 1953 Seldinger2 described his safer
technique to accessing large vessels. With modification and improved materials in the early 1960’s central venous
catheterization, and then CVP measurement became commonplace coinciding with the establishment of the first
critical care units in the United States and then the founding of the Society of Critical Care Medicine in 1970. 1970
was also the year that the PAC’s clinical applications were described and the “modern era” of critical care was thus
launched3-6. In retrospect it seems that despite the CVP and PAC, approach to fluid administration was guided more
by faith and dogma than principle and recently long held beliefs regarding the 3rd space have been questioned7, while
variability in the amount of fluid administered for standard procedures commonly varies several-fold8.
Intravenous fluid is likely the most commonly prescribed and most poorly understood inpatient therapy. A large
percentage of physicians do not appreciate the differences between the main fluid types and despite hyponatremia
being a very common and usually iatrogenic inpatient diagnosis, the administration of hyponatremic solutions is
rampant, and the distinction between normal saline and balanced salt solutions is usually absent.
While adults have a blood volume of approximately 60-70 ml / kg, and hypotension will not usually occur with an
acute loss of < 15% of the blood volume, the determination of how much fluid any individual patient “needs” at any
given point in time and recognition of hypovolemia prior to the onset of hypotension are clinical conundrums while
there is a lack of acknowledgment that a pathologic condition of fluid overload – hypervolemia actually exists and is
common.
Also, the relative risks of hypovolemia versus hypervolemia have historically been viewed as favoring erring on the
side of hypervolemia, although recent evidence suggest the two conditions entail similar morbidity and mortality.
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Hypovolemia versus Hypervolemia Overview

Hypovolemia Hypervolemia
Decreased cerebral perfusion – stroke Brain swelling - delirium
Tachycardia and hypotension - MI Cardiac edema – arrhythmia, decreased contractility
Decreased bowel perfusion – ischemic bowel, Lung edema – respiratory failure, need for mechanical
anastomotic leak, ileus ventilation, resultant nosocomial pneumonia
Acute kidney injury secondary to hypoperfusion Bowel edema – anastomotic leak, ileus
Poor distal perfusion – ischemic hands and feet Acute kidney injury secondary to interstitial edema
Orthostasis – prolonged bed rest, falls Hepatic congestion – coagulopathy, hyperbilirubinemia
Prolonged bed rest – prone to pressure ulcer and DVT Wound edema / prone to skin breakdown and infection
Difficulty mobilizing – prolonged bed rest, falls
Prolonged bed rest – prone to pressure ulcer and DVT
Hypovolemia Hypervolemia
Depending on the preoperative morbidities, the surgical procedure and the amount of blood loss the target optimal
fluid zone might be very large with a wide u shape curve (e.g., healthy young patient coming for laparoscopic
cholecystectomy) and morbidity and mortality are highly unlikely despite a wide variation in the amount of fluid
that might be administered; or the optimal zone may be nearly non-existent (e.g., elderly patient with severe aortic
stenosis, hypertension on an ACE and chronic kidney disease stage III coming for major hepatic resection involving
an EBL of at least 1 liter.) and morbidity and mortality are likely despite best attempts at staying in a miniscule
zone.
One recent investigation nearly reproduced this theoretical curve in a database interrogation study of more than
600,000 patients that showed dramatic outcome differences between patients undergoing the same operations whom
received fluid volumes in the lowest quartile and highest quartiles versus the two intermediate quartiles9.
CVP, PAC, and Arterial Waveform Analysis
Attempts to utilize CVP and PACs in an attempt to optimize fluid administration and vasopressor administration
have been a complete failure although many physicians still insist on incorporating these devices, especially the
CVP, into their routine practice algorithms.
Utilization of the CVP is physiologically and practically incapable of predicting whether a patient will respond to a
fluid bolus with a rise in their cardiac output or blood pressure10, 11 and the change in CVP over time has been
repeatedly demonstrated to have no relationship to the amount of fluid administered and has not consistently been
shown in any management algorithm to change outcome.
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In fact, one of the reasons PACs were developed was the realization that right sided heart pressure were inadequate
in determining preload, and PAC’s pulmonary capillary wedge pressure in combination with cardiac output
determination capabilities and waveform generation-examination were thought to have offered significant
advantages and initially. There was great acceptance and widespread use of PACs within just a few years of their
introduction and while there were a few studies suggesting risk versus benefit it was not until 2000-2010 that
several major randomized controlled trials and other retrospective case controlled investigations of PAC use were
completed utilizing various different optimization strategies, intraoperative settings, shock, sepsis and ARDs, the
sum total of all demonstrating no improvement in outcome utilizing PACs coupled with any strategy 12-18 and an
overall risk actually slightly > benefit. In retrospect we should appreciate that is took 35 years from device
introduction until the supposed improved outcomes related to device use were established as absent!
Stroke Volume Variation/Systolic Pressure Change/Pulse Pressure Variation and fluid responsiveness:
While these investigations debunked the link between invasive monitoring and improved outcome, recognition of
the importance of the arterial pressure waveform, especially in mechanically ventilated patients was reported and
investigated 19,20.
Analysis of the arterial line tracing real time allows detection of changes with positive pressure ventilation that
provides a breath by breath recreation of the Starling curve.
Three main physiologic premises underlie the use of this phenomena as a monitor: 1) arterial pulse pressure (systolic
- diastolic pressure) is directly proportional to stroke volume and inversely related to arterial compliance; 2) a
positive pressure breath compresses the pulmonary venous system that causes an increase in left ventricular preload
and then an increase in stroke volume and arterial pulse pressure for a few beats; 3) a positive pressure breath also
decreases venous return to the right heart via an increase in thoracic pressure, compression of the vena cava and
right atrium and causes decreased left ventricular filling and subsequent decrease in stroke volume and pulse
pressure.. Hypovolemia magnifies the difference in change of the pulse pressure as the heart is functioning on the
steep portion of the Starling curve where these physiologic changes are much larger than in a well filled circulation
where the heart is operating on the flat portion of the curve.
In cases where the change in stroke volume, systolic pressure or pulse pressure, all of which can basically be used
interchangeably for most clinical purposes, exceed about 13% over the course of a breathing cycle, there is near a
90% chance that a fluid bolus will result in a demonstrable change in the CO and blood pressure; and if the
difference is < 9% the opposite is the case – there is about a 90% chance the patient will not respond to a fluid
challenge20.
These variations may be appreciated by the unaided eye, especially if a cursor is used to track the peak and nadir
systolic pressures, but most of the devices available will report this variation on a beat to beat basis and allow the
seamless integration of this variable into the monitored milieu. Some newer standard bedside monitors will report
this variable routinely whenever an arterial line is attached and there is now even a cell phone based application for
that21. Measuring this variation is even possible from advanced pulse oximeters that are now entering the
commercial marketplace too. Other technology to be discussed in this refresher course will incorporate stroke
volume, cardiac output and may even include estimations of end diastolic volume, extra vascular lung water and
other variables.
Conclusions:
Monitoring of patients in an attempt to guide the administration of the correct amount of fluid at the optimal point in
time is the current holy grail of acute care medicine including perioperative management, treatment of sepsis, and
resuscitation of the traumatized and hemorrhaging patient. The past 60 years have demonstrated that technologies
once embraced as both “state of the art” and “standard of care” should not have been considered either and a
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healthy dose of skepticism of all monitoring technology is warranted. Indeed, a recent issue of Anesthesia and
Analgesia had 3 articles clearly revealing that there is no consensus that GDT (the subject of 2 of the other talks in
this session) is anywhere near a standard of care22-24. The acknowledgement that hypervolemia is as important to
avoid as hypovolemia is long overdue, especially in patients undergoing more minimally invasive surgical
approaches in shorter operative times with less blood loss, less tissue trauma and expected to have shorter length of
stays. It is quite possible that the major benefit of all of the research and monitoring until now is to simply
recognize less fluid (but not too little) in general has benefits > risks that were heretofore unrecognized! Basic
application of arterial pressure waveform interpretation should be common practice, at least in patients ill enough to
require an arterial line, while technologically advanced devices that incorporate this automated feature need to prove
themselves as having an outcome advantage before they too are incorrectly assumed to be “state of the art” and
“standard of care.”
References:
1) Aubaniac R. L’injection intraveneuse sousclaviculare advantage et technique. Presse Med 1952; 60:1456
2) Seldinger SI. Catheter replacement of the needle in percutaneous arteriograpy. Acta Radiolo/ 1953;
39:368
3) Swan HJC, Ganz W, Forrester J, Marcus H, Diamond G, Chonette D. Catheterization of the heart in man
with use of a flow-directed balloon tipped catheter. N Engl J Med 1970: 283:447-451
4) Forrester J, Diamond G, Chatterjee K Swan HJC. Medical therapy of myocardial infarction by application
of hemodynamic subsets. N Eng J Med 1976; 295:1356-62
5) Diamond G, Chonette D. Catheterization of the heart in man with use of a flow-directed balloon tipped
catheter. N Eng J Med 1970: 283:447-451
6) Civetta JM, Gabel JC. Flow directed pulmonary artery catheterization in surgical patients. Ann Surg 1972;
176:753-56
7) Chappell D, Jacob M, Hofman-Kiefer K, COnzen P, Rehm M. A rational approach to perioperative fluid
management. Anesthesiology 2008; 109:723-40
8) Lilot M, Ehrenfeld JM, Harrington B, Canneson M, Rinehart J. Variability in practice and factors
predictive of total crystalloid administration during abdominal surgery: retrospective two-centre analysis.
Br J Anesth 2015; 114:767-76
9) Thacker JKM, Mountford WK, Ernst FR, et al. Perioperative Fluid Utilization Variability and Association
with Outcomes: Consideration for Enhanced Recovery Efforts in Sample US Surgical Populations. Annals
of Surgery 2016; 263: 502-510
10) Gelman S. Venous Function and Central Venous Pressure: A physiologic story. Anesthesiology 2008;
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11) Marik P, Baram M, Vahid B. Does central venous pressure predict fluid responsiveness? A systemic
review of the literature and tale of seven mares. Chest 2008; 134:172-174
12) Sandham JD, Hull RD, Brant RF, et al. A randomized, controlled trial of the use of pulmonary-artery
catheters in high-risk surgical patients. N Engl J Med 2003; 348:5-14
13) Polanczyk CA, Rohde LE, Goldman L, et al. Right heart catheterization and cardiac complications in
patients undergoing noncardiac surgery: an observational study. JAMA 2001; 286:309-314
14) Harvey S, Harrison DA, Singer M, et al. Assessment of the clinical effectiveness of pulmonary artery
catheters in management of patients in intensive care (PAC-Man): a randomised controlled trial. Lancet
2005; 366:472-477
15) Rhodes A, Cusack RJ, Newman PJ, et al. A randomised, controlled trial of the pulmonary artery catheter in
critically ill patients. Intensive Care Med 2002; 28:256-264
16) Binanay C, Califf RM, Hasselblad V, et al. Evaluation study of congestive heart failure and pulmonary
artery catheterization effectiveness: the ESCAPE trial. JAMA 2005; 294:1625-1633
17) Richard C, Warszawski J, Anguel N, et al. Early use of the pulmonary artery catheter and outcomes in
patients with shock and acute respiratory distress syndrome: a randomized controlled trial. JAMA 2003;
290:2713-2720
18) Pulmonary Artery Catheter versus Central Venous Catheter to Guide Treatment of Acute Lung Injury. The
National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials
Network. N Engl J Med 2006; 354:2213-2216.
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19) Michard F. Changes in arterial pressure during mechanical ventilation. Anesthesiology 2005; 103: 419-
428
20) Cannesson M, Le Manch Y, Hofer CK, et al. Assessing the diagnostic accuracy of pulse pressure
variation for the prediction of fluid responsiveness: a “gray” zone approach. Anesthesiology 2011; 115:
231-241
21) Desebbe O, Joosten A, Suehiro K, et al. A novel mobile phone application for pulse pressure variation
monitoring based on feature extraction technology: A method comparison study in a simulated
environment. Anesth Analg 2016 May 3 [Epub ahead of print]
22) Lefrant JY, Muller Laurent. Assessing fluid responsiveness in clinical practice: SO many tools available,
so many questions to answer. Anesth Analg 2016; 122: 1256-1257
23) Cannesson M, Tong G. PRO: Perioperative goal-directed therapy is an essential element of an enhanced
recovery protocol. Anesth Analg 2016; 122: 1258-1260
24) Joshi G, Henrik K. CON: Perioperative goal-directed therapy is an essential element of an enhanced
recovery protocol Anesth Analg 2016; 122 1261-1263
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Clinical Hemodynamics: Assessment and Management
Jeffery S. Vender, M.D., MCCM, FCCP, MBA Chicago, Illinois
Anesthesiologists typically receive direct feedback when they deliver a fluid bolus to a surgical patient which,
results in an increase in blood pressure and/or urine output. This process is interpreted as “fluid responsiveness” or
an improved cardiac output (via a boost in preload/stroke volume). We ultimately hope this intervention leads to an
improvement in end organ perfusion and subsequent favorable clinical outcomes. Realistically, this often times takes
a leap of faith that in order to become a reality requires a far more advanced level of knowledge, applied science and
appropriate therapeutic intervention.
Fundamental knowledge of hemodynamics is required in order to appropriately interpret physiologic responses in

different clinical settings. Cardiac output (CO=SV x HR) is predicated on the heart’s function and venous return
function (i.e. preload). Well over 100 years ago, Frank and Starling demonstrated that an increase in end diastolic
volume typically resulted in a greater cardiac force that produced an increase in cardiac output. The now famous
Frank-Starling curve taught in basic physiology courses in medical school infers that afterload, heart rate and
contractility are all constant (CO=MAP-RAP/ SVR). When heart rate or contractility increase or afterload decreases,
cardiac output increases for any given preload (a leftward shift of the curve). However, after some point (plateau), a
further increase in preload (end diastolic volume) will not result in further improvement in cardiac output. This
maneuver will likely result in ventricular overdistension, overfilling and a reduction in end organ perfusion. The
elegance of the Frank-Starling theory is echoed by “what comes in must come out.”
The other vital component to cardiac output is the venous return (VR) function. Venous return is predicated on the
elastic recoil of venous capacitance vessels. The mean circulatory pressure (Pms) minus the right atrial pressure
divided by venous resistance equals venous return (VR=Pms-RAP/RVR). The heart controls its blood return by
lowering right atrial pressure. An increase in stressed volume (volume stretching veins), results in a shift of the
return function curve to the right. Venous resistance can also alter the return curve, where an increase in venous
resistance leads to a decrease in venous return for a given right atrial pressure. Lastly, venous capacitance (the total
venous volume for total pressure) is another component that restricts the circulatory system response. Veins have a
small potential for contraction and when this threshold is reached, the so called, “unstressed volume” can no longer
be utilized for improved cardiac output. This area is well discussed in a recent article by Gelman.
Plotting both the cardiac function and venous return function curves on the same graph allow for the clear depiction
of the working relationship between these two important components. Physiologic and pathophysiologic states
(shock) can be examined utilizing some of these premises. For instance, giving a fluid bolus to a hypovolemic shock
patient will likely improve the associated cardiac output. However, giving fluid bolus to a patient who is past the
plateau portion of the Frank-Starling curve could result in fluid overload and a worsened cardiopulmonary status.
We will discuss the definition and pathophyisiologic explanations of shock (hypovolemic, cardiogenic, distributive
and obstructive) in this talk.
Clinicians may use Goal-Directed Therapy (GDT) to address patients in shock like states (or with abnormalities in
the cardiac function/return function relationship). Too often we have relied on monitoring and measurements
(assessment) to alter outcome when it is actually the application of a therapeutic intervention (management) based
on the information that alters outcome. Practitioners, who use goal directed therapy should recognize the following
factors that most commonly will determine outcome: outcome: appropriateness of care (i.e interpreting data
correctly and formulating the appropriate treatments), timeliness of care, and responsiveness (appropriate population
targeted) to that care. These axioms are vital to any clinician’s success with goal directed therapy.
Most GDT studies demonstrate improved clinical outcomes when appropriate physiologic end points are coupled
with appropriate therapeutic measures, in a higher risk population, and before end organ damage occurs. The most
difficult conundrum to address is which physiologic end points to use and how to accurately derive them. Endpoints
of resuscitation can be divided into two categories; upstream and downstream. Upstream endpoints may include:
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hemodynamic (preload (CVP, PAOP, PPV)), contractility (SV), afterload (MAP, SVR)) and global oxygen delivery
parameters (arterial oxygen saturation and oxygen carrying capacity). Downstream metabolic endpoints may
include: lactate, SVO2, pH, base deficit, tissue oxygenation, inflammatory mediators, etc. The intermediary between
the two is of course the microcirculation. Unfortunately, no widely adopted clinical monitoring system is available
to investigate the microcirculation consistently.
Improved clinical outcomes are primarily achieved when these endpoints are appropriately monitored to derive an
effective, timely therapeutic intervention. In this talk we will address various static and dynamic methods for
hemodynamic monitoring. Unfortunately, monitors have not consistently been shown to improve clinical outcomes
e.g. mortality (Ospina-Tascon FA ). Shoemaker, Kern, Berlauk and Boyd all demonstrated that optimizing
hemodynamic parameters derived from the pulmonary artery catheter (PAC) resulted in improved clinical outcomes
for high risk patients if instituted before organ failure.. However, subsequent clinical studies using the invasive PAC
did not show specific patient benefits. These studies are often flawed and have been criticized for their lack of
adoption of the outcome axioms discussed above (Vender). However, the negative PAC studies promoted the
development of several other less invasive devices and techniques to derive similar parameters as the PAC (i.e.
esophageal doppler, pulse contour analysis, pulse pressure variation, bioimpedance, bioreactance, partial CO2
rebreathing, transthoracic echocardiography, etc). It is still unclear as to whether these less invasive devices provide
the accuracy needed to aid clinicians in the development of helpful therapies. Still, recent studies have demonstrated
a clinical benefit in perioperative patients when using some of these noninvasive techniques coupled with GDT.
Further discussion of the benefits and liabilities of these invasive and less invasive hemodynamic monitors will be
discussed in this lecture.
Suggested Readings:
1) Pinsky M. Hemodynamic Evaluation and Monitoring in the ICU. Chest 2007;132:2020-2029.
2) Lobo S, Mendes C, Rezende E, Dias F. Optimizing perioperative hemodynamics: what is new? Curr Opin
Crit Care 2013;19:346-352.
3) Rinehart J, Liu N, Alexander B, Cannesson M. Closed-Loop Systems in Anesthesia: Is There Potential for
Closed-Loop Fluid Management and Hemodynamic Optimization? Anesth Analg 2012;114:130-43.
4) Geisen M, Rhodes A, Cecconi M. Less- invasive approaches to perioperative haemodynamic optimization.
Curr Opin Crit Care 2012;18:377-384.
5) Majder S. Fluid status and fluid responsiveness. Curr Opin Crit Care 2010:16:289-296.
6) Pinsky M. Recent advances in the clinical application of heart-lung interactions. Curr Opin Crit Care
2002;8:26-31.
7) Pinsky M. Functional haemodynamic monitoring. Curr Opin Crit Care. 2014;20:288-293.
8) Pinsky M. My paper 20 years later: Effect of positive end-expiratory pressure on right ventricular function
in humans. Intensive Care Med 2014;40:935-941.
9) Cove M, Pinsky M. Perioperative hemodynamic monitoring. Best Practice and Research Clinical
Anaesthesiology 2012;26:453-462.
10) Maas J, Pinsky M, Aarts L, Jansen J. Bedside Assessment of Total Systemic Vascular Compliance,
Stressed Volume, and Cardiac Function Curves in Intensive Care Unit Patients. Anesth Analg
2012;115:880-887.
11) Gomez H, Mequida J, Hermus L, Polanco P, Kim H, Zenker S, Torres A, Namas R, Vodovotz Y, Clermont
G, Puyana J, Pinsky M. Physiologic responses to severe hemorrhagic shock and the genesis of
cardiovascular collapse: Can irreversibility be anticipated? Journal of Surgical Research 2012;178:358-
369.
12) Maas J, Wilde R, Aarts L, Pinsky M, Jansen J. Determination of Vascular Waterfall Phenomenon by
Bedside Measurement of Mean Systemic Filling Pressure and Critical Closing Pressure in the Intensive
Care Unit. Anesth Analg 2012;114:803-810.
13) Pinsky M, Brophy P, Padilla J, Paganini E, Pannu N. Fluid and volume monitoring. Int J Artif Organs
2008;31:111-126.
14) Gelman S. Venous function and central venous pressure: a physiologic story. Anesthesiology
2008;108:735-748.
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15) Ospina-Tascon FA, Cordioli RL, Vincent JL. What type of monitoring has been shown to improve
outcomes in acutely ill patients? Intensive Care Med 2008;34(5):800-820.
16) Marik P, Monnet X, Teboul JL. Hemodynamic parameters to guide fluid therapy. Ann Intensive Care
2011;1:1.
17) Marik P, Cavallazzi R, Vasu T, Hirani A. Dynamic changes in arterial waveform derived variables and
fluid responsiveness in mechanically ventilated patients: A systematic review of the literature. Crit Care
Med 2009;37:2642-2647.
18) Marik P, Baram M, Vahid B. Does central venous pressure predict fluid responsiveness? Chest
2008;134(1):172-177.
19) Jones AE, Shapiro NI, Trzeciak S, et al. Lactate clearance vs central venous oxygen saturation as goals of
early sepsis therapy: A randomized clinical trial. JAMA 2010;303(8):739-746.
20) Hamilton M, Cecconi M, Rhodes A. A systematic review and meta-analysis of preemptive hemodynamic
interventions to improve postoperative outcomes in moderate and high risk surgical patients. Anesth Analg
2011;112:1392-1402.
21) Vender J Pulmonary artery catheter utilization: the use, misuse abuse. J Cardiothorac Vasc Anesth 2006:20:
295-299
22) Pinsky, Michael R. Advances In Hemodynamic Monitoring. Critical Care Clinics 31:1:i
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Enhanced Recovery After Surgery in Infants and Children (ERAS): A Multimodal

Approach to Continued Success
Patrick K Birmingham MD FAAP Chicago, Illinois

Anesthesiologists have an expertise and experience with both analgesics and regional anesthesia that enable
us to optimize perioperative pain relief. This has always been of value to patients and their families. It is
particularly so in the modern era of the perioperative surgical home. What we do in the operating room and
beyond may enhance recovery, improve time to discharge and decrease unplanned returns to the hospital
[1, 2]. These goals may be best achieved by a multimodal approach, combining local infiltration, regional
analgesic techniques, non-opioid analgesics, and/or opioids. The additive or synergistic effects of
multimodal analgesia ideally offer superior pain relief while minimizing side effects.
The menu of available pain management options will be discussed in the context of a case-based approach
using common pediatric surgical procedures.
Bowel surgery in a former preterm infant:
Anesthetic goals for the infant with a history of prematurity undergoing abdominal surgery (e.g. inguinal
hernia repair, colostomy closure) include lessening the risk of postoperative apnea of prematurity (POAP);
optimizing a faster return of bowel function; and minimizing potential long term cognitive effects on the
developing brain from exposure to general anesthetics and sedatives.
Avoiding general anesthesia with a primary regional anesthetic such as a subarachnoid block might achieve
these goals, but even at experienced institutions with high initial success rates of spinal anesthetic
placement, 19% or more may require supplemental anesthesia at some time during surgery [3, 4]. In
addition, authors have demonstrated that POAP can occur regardless of the type of anesthesia used. [5, 6].
Whether the former preterm undergoes general or regional anesthesia, the same criteria should be
considered for postoperative monitoring for apnea of prematurity.
With regard to possible long term neurocognitive effects, recent prospective trials, notably the General
Anesthesia compared to Spinal anesthesia (GAS) study and the Pediatric Anesthesia and
NeuroDevelopment Assessment (PANDA) project, were designed to address animal data and some
retrospective human studies that indicated deleterious effects from early life exposure to commonly used
anesthetic and sedative medications. Results from the PANDA project offer some reassurance of safety.
Within the construct of the study, children less than 36 months of age exposed to a single general anesthetic
showed no deleterious effect on IQ scores later in life.[7]
An excellent resource for this issue is the SmartTots website (www.smarttots.org), a collaborative effort
of the International Anesthesia Research Society (IARS) and the United States Food and Drug
Administration (FDA).
General anesthesia with single injection caudal epidural analgesia can provide excellent perioperative pain
control while minimizing or eliminating the use of opioids (table 1). Recent analyses from large multicenter
data bases such as the Pediatric Regional Anesthesia Network (PRAN) demonstrate the overwhelming
safety of performing caudal epidural anesthesia after induction of general anesthesia in children [8] .
Alternatives include truncal blocks such as ilioinguinal/iliohypogstric or transversus abdominis plane
(TAP) blocks, which can be performed under ultrasound guidance to optimize local anesthetic placement.
As with single injection caudals, and epidural catheter placement in neonates [7, 9], TAP blocks performed
under general anesthesia have an excellent safety record [10]
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Table 1: Ann & Robert H. Lurie Children’s Hospital of Chicago

Single Injection Caudal Epidural Dosing Guidelines
Medication Volume/Dose Comments
Test dose LA with 1:200,000 0.1 ml/kg up to 3 ml Look for increase in
(60 seconds) epinephrine (=5mcg/ml) HR (10 bpm),
SBP (10%), or
Twave amplitude
(25%)
Caudal epidural 0.125% bupivacaine or 0.7-1 ml/kg Approximate T10
0.2% ropivacaine block level
Additives Clonidine or fentanyl 2 mcg/ml Avoid clonidine < 1-6
mos of age (apnea?)
Upper dosing limit Bupivacaine/ropivacaine 2.5-3 mg/kg Reduce dose 30-50%
in pts < 4-6 mos age
One must be aware of local anesthetic dosing recommendations in children to avoid local anesthetic
systemic toxicity (LAST). There should be prompt access to 20% lipid emulsion in the event of systemic
toxicity. Recent regional practice guidelines emphasize the importance of slow injection of local anesthetic
with frequent aspiration, regardless of whether a test dose is employed. [11]
Intra- or postoperative intravenous supplementation can include acetaminophen and other NSAID’s. The
pharmacokinetics of ketorolac have been studied in infants and newborns, leading us to safe dosing
recommendations in the younger patient [12-14]. Parenteral ibuprofen is also now available in the USA.
Outpatient tonsillectomy:
Often overlooked in the discussion of ERAS are commonly performed outpatient surgical procedures,
which can result in prolonged time to discharge, unplanned inpatient admission, and/or readmission
following discharge. Perioperative management of children undergoing tonsillectomy can be particularly
challenging. Over 500,000 patients undergo tonsillectomy annually. 3.9% of them will require readmission
to the hospital for pain, dehydration, fever and/or bleeding [15], with some of those returning to the
operating room for control of bleeding. These concerns limit although do not eliminate the use of intra- or
postoperative NSAID’s for pain management. Ketorolac and more recently available intravenous ibuprofen
are parenteral options in addition to oral NSAID’s. A meta-analysis and systematic review came to
conflicting conclusions about whether NSAID’s should be used in tonsillectomy patients [16, 17]. The
American Academy of Otolaryngology-Head & Neck Surgery sites higher rates of hemorrhage with
ketorolac (4.4 -18%) versus other NSAIDs (0.1- 3%) [15], but also notes that other oral NSAID’s can be
safely used for pain control after tonsillectomy.
Intravenous acetaminophen can be an excellent adjunct in the perioperative management of patients

undergoing tonsillectomy. If acetaminophen is given by any route, it should be factored into subsequent
postoperative dosing ordered by the surgeon (table 2).
Table 2: NSAID General Dosing Guidelines (> 2 yrs age)

NSAID Route Dose mg/kg Dose Max Dose Daily
Interval (mg) Maximum/Comments
Ketorolac IV 0.5 mg/kg 6 hrs 30 mg (15 for ≤ 5 days
mg if < 50
kg or 16
yrs)
Ibuprofen PO 5-10 mg/kg 6 hrs 400 40 mg/kg (1200 mg)
Naproxen PO 5-7.5 mg/kg 8-12 hrs 200 10-15 mg/kg (600 mg)
Acetaminophen PO 10-15 mg/kg 4-6 hrs 1000 75-90 mg/kg (3000-
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4000 mg)
Acetaminophen PR 40 mg/kg 6 hrs 1000
load; then 20
mg/kg
Acetaminophen IV 10-15 mg/kg 4-6 hrs 1000 75 mg/kg (4000)
Opioids are also frequently utilized intra- &/or postoperatively in tonsillectomy patients. It is worthwhile in
the evaluation of tonsillectomy patient opioid studies to note whether the surgical indication is recurrent
tonsillitis vs. obstructive sleep apnea (sleep disordered breathing). The patient with recurrent tonsillitis may
be less at risk for opioid-related side effects, as the child with sleep disordered breathing may have altered
sensitivity to opioids [18]. Dosing should be adjusted accordingly. Patients with more severe sleep
disordered breathing may need to be admitted postoperatively for monitoring, sometimes in an ICU setting.
Single dose dexamethasone in tonsillectomy patients has been shown to be safe and effective in decreasing
postoperative nausea and vomiting [15, 19-21]. It also has an analgesic benefit as indicated by earlier return
to oral intake and decreased postoperative analgesic requirements. Doses as low as 0.0625 mg/kg have been
shown to be as effective as 1 mg/kg in this regard [22].
Dexmedetomidine at doses up to 4 mcg/kg, with or without an infusion (0.7 mcg/kg/hr), has been studied in
tonsillectomy patients. While prolonging the opioid-free interval and/or decreasing emergence agitation
postoperatively, the higher doses studied also prolonged PACU stay. A single dose of 0.5 mcg/kg has been
shown to be safe and effective with minimal clinical hemodynamic effect. [23]. Use of NMDA receptor
antagonists such as ketamine, magnesium and dextromethorphan in tonsillectomy patients have been
studied with little benefit shown versus standard opioid administration [24, 25]. Additional studies may
better define a role for these alternatives in the tonsillectomy patient.
Local anesthetic infiltration of the tonsillar bed is reported by 51.4% of surgeons [26], but interestingly has
not been shown in a recent systematic review to be of benefit [27]. The importance of fluid therapy in
tonsillectomy and other outpatient procedures should not be overlooked. Administering 30 ml/kg versus 10
ml/kg of crystalloid to pediatric outpatients undergoing strabismus surgery resulted in less nausea/vomiting,
fever and thirst [28].
The anesthesiologist can also contribute to the postoperative or post-discharge safety of these patients by
directing pain management away from the use of codeine. Codeine’s conversion to its active metabolite,
morphine, can be influenced by genetic variation in the cytochrome P4502D6 (CYP2D6) metabolic
pathway. A “poor” metabolizer will have lower levels of morphine, “resistance” to a given dose and
inadequate pain relief. The “ultrarapid” metabolizer will have higher morphine levels. Postoperative
respiratory depression and arrest have been reported with standard doses of codeine in post-tonsillectomy
patients [29, 30]. Codeine is being removed from pediatric hospital formularies and its use discouraged in
the postoperative tonsillectomy patient for this reason. This risk may not be altogether eliminated by use of
alternative opioid analgesics, which may also carry some risk of relative overdosage due to genetic
variability in metabolism. Much is still to be learned about the role of genomics in drug pharmacology.[31]
Major orthopedic surgery in a child:
Although children are much less likely than adults to undergo joint replacement, there are still a number of
orthopedic procedures in children that benefit from a multimodal approach. The children with cerebral
palsy undergoing femoral osteotomy and the adolescent with idiopathic scoliosis under posterior spinal
fusion are two examples.
The analgesic plan can start prior to surgery with the administration of the voltage-gated calcium channel
blockers, pregabalin or gabapentin. These medications can be effective in the management of centrally
acting pain, which may be a component of postoperative pain in these patients. A systematic review of
randomized controlled trials demonstrated that a single preoperative dose lowered opioid use, pain scores
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and opioid side effects (albeit with more sedation) over the 1 st 24 hrs postoperatively [32] . Postoperative
dosing in adolescents undergoing posterior spinal fusion extended the reduction in pain scores and opioid
consumption in the early postoperative period [33].
In the spinal fusion patient, surgical access to the epidural space allows for placement of an epidural
catheter under direct visualization after completion of instrumentation and before wound closure. Upon
awakening and surgical confirmation of motor function, a local anesthetic bolus dose followed by a
continuous infusion is started. Additives such as clonidine or an opioid can be added to the local anesthetic
solution. A meta-analysis of epidural opioid studies revealed no difference in analgesia between morphine,
sufentanil and fentanyl, but did demonstrate more emesis with morphine [34]. If parenteral opioids are also
being administered, consideration should be given to limiting or eliminating concurrent epidural opioid
administration.
A demand option added to the epidural catheter infusion can improve pain relief (table 3), and sometimes
prevent the addition or substitution of another modality. Both patient-controlled epidural analgesia [35] and
epidural analgesia by nurse- or parent-proxy [36] have been safely used in children undergoing major
surgery.
Table 3: Epidural Dosing Guidelines

Ann & Robert H. Lurie Children’s Hospital of Chicago
Local Additives Continuous Bolus dose Lockout 1 Hr Limit
Anesthetic infusion (ml) (minutes) (cont + bolus)
(ml/kg/hr) (mg/kg/hr)
0.1% Clonidine (1 0.1- 0.2 0.5-2 15-30 0.4 (lumbar
bupivacaine mcg/ml) catheter)
or or 0.3(thoracic
ropivacaine Fentanyl (2 catheter)
mcg/ml) 0.2 (< 3-6 mos age)
Alternatively, a single dose of intrathecal morphine (2-15 mcg/kg) can be directly injected by the surgeon
or prior to incision by the anesthesiologist. This has been shown to result in lower pain scores and opioid
consumption in the first 24 hours following surgery [37, 38].
Intravenous patient-controlled analgesia (PCA) is widely utilized in children and a routine component of
postoperative pain management for spinal fusion and many other pediatric surgical procedures (table 4).
The opioid “loading dose” is frequently given intraoperatively, and parameters are adjusted postoperatively
as needed to optimize pain relief. Children as young as 5-6 years of age will self-activate their PCA button.
Although safety concerns have been raised about parent or caregiver “PCA by proxy” and continuous
opioid infusions, both are utilized and can be done so safely [39-41]. In major procedures, intravenous PCA
can be used in combination with epidural infusions of local anesthetic. The optimal interaction between
these two modalities remains to be defined.
Table 4: IV PCA Parameters

Ann & Robert H. Lurie Children’s Hospital of Chicago
Opioid Bolus Dose Lockout Continuous 1 Hr Limit Maximum
(minutes) Infusion 1 Hr Limit
(default 8 min)
Morphine 0.01 - 0.02 5-15 0.01-0.02 0.2 mg/kg 15 mg
mg/kg mg/kg/hr
Fentanyl 0.2 - 0.4 5-15 0.2-0.4 4 mcg/kg 300 mcg
mcg/kg mcg/kg/hr
Hydromorphone 2 - 3 mcg/kg 5-15 2 - 3 mcg/kg/hr 30 - 40 3000 mcg
mcg/kg
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The use of non-opioid analgesics such as ketorolac should include the input of the surgeon because of
theoretical concerns about bleeding in the early postoperative period and surgical non-union in the months
following surgery. The likely of non-union is lower in the pediatric versus the adult spinal fusion
population. Intravenous acetaminophen is a useful addition in this and other patient populations.
Table 5: Ann & Robert H. Lurie Children’s Hospital of Chicago

Clinical Pathway for Spinal Fusion Patients
Modality Comment
Pregabalin Single dose preop; 4-6 doses over 2-3 days postop
Epidural Infusion Catheter placed by surgeon; local anesthetic
infusion; remove on POD 2
Intravenous Patient Controlled Analgesia (PCA) Continuous infusion + demand dose; stop
continuous infusion on POD 2; transition off
PCA by POD 3
Diazepam Low dose; prn or ATC as needed
Ketorolac Start on POD 2 with surgeon approval
Oral Opioid (oxycodone or hydrocodone)* Start when continuous PCA infusion stopped
Acetaminophen* Use in combination with oral opioid; consider
starting ATC earlier if needed
Ibuprofen* Transition from IV ketorolac
*= discharge medications PCA = Patient Controlled Analgesia
POD = Postoperative Day ATC = Around the Clock
Tramadol (1-2 mg/kg), a serotonin and norepinephrine uptake inhibitor with weak mu-opioid receptor
activity can be a useful transition from stronger intravenous opioids toward oral analgesics, and an
alternative to the use of oxycodone or hydrocodone [42].
Pain measurement and side effect management:
The goal of optimal pain management is accomplished by a combination of efforts, including daily
rounding by an anesthesiologist-directed pain management service; use of validated age- and
developmentally-appropriate pain scales; standardization of order sets; and creation of clinical pathways
(table 5) with input from surgeons, nursing and pharmacists.
Pain measurement tools in infants and children rely on physiologic, behavioral and/or self-report measures.
Physiologic measures such as blood pressure or respiratory rate are nonspecific but may have to be relied
upon in sedated, mechanically ventilated patients. Behavioral measures such as facial expression, body
posture, activity and quality of cry can be used in infants and children [43]. Age-appropriate self-report
measures have been developed for children as young as 3 years of age [44]
An important component of postoperative pain management is prevention or treatment of related side

effects. Nausea or vomiting is the most common concern (Table 6). The commonly used combination
therapy of dexamethasone and ondanestron has been shown to be effective in children [45]. Low-dose
naloxone by intravenous infusion (0.25-1 mcg/kg/hr) [46, 47], or by mouth or nasogastric tube (10-20
mcg/kg) is effective in management of opioid-related side effects such as nausea/vomiting, pruritus or
ileus. Metanalyses of acupuncture and acustimulation demonstrate their effectiveness in reducing
postoperative vomiting in children [48, 49]. Leg weakness from continuous epidural infusion can be
avoided or minimized by using lower infusion rates, lower local anesthetic concentrations, or substitution
of ropivacaine for bupivacaine.
Table 6: Risk Factors for Postoperative Vomiting (POV)

in Children (adapted from ref 45)
History of POV in patient, parent or sibling
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Age ≥ 3 years
Surgical time ≥ 30 minutes
Strabismus surgery
Be aware also of the use of herbal medications in children and their potential impact on postoperative side
effects and pain medication [50].
Recent national guidelines promote the use of a multimodal model for postoperative pain relief [51].
Evidence has strengthened that ultrasound guidance in nerve blocks improves safety.[52] Additional studies
are needed to more precisely define the role of regional anesthesia and opioid and non-opioid analgesics.
[53] For example, bilateral TAP blocks were shown to be more opioid-sparing than single injection caudals
in children undergoing ureteral reimplantation [54]
As we move forward in an evolving healthcare environment, hospital length of stay, unplanned readmission
and patient/parental satisfaction measures of pain management will be important metrics and play a role in
hospital ratings and reimbursement. We as anesthesiologists are uniquely positioned to provide leadership
and value in optimizing such quality outcome measures.
References:
1. Shafer, S.L. and J.F. Donovan, Anesthesia & Analgesia's collection on the perioperative
surgical home. Anesth Analg, 2014. 118(5): p. 893-5.
2. Kain, Z.N., et al., The perioperative surgical home as a future perioperative practice
model. Anesth Analg, 2014. 118(5): p. 1126-30.
3. Kurth, C.D. and C.J. Cote, Postoperative Apnea in Former Preterm Infants: General
Anesthesia or Spinal Anesthesia--Do We Have an Answer? Anesthesiology, 2015.
123(1): p. 15-7.
4. Frumiento, C., J.C. Abajian, and D.W. Vane, Spinal anesthesia for preterm infants
undergoing inguinal hernia repair. Arch Surg, 2000. 135(4): p. 445-51.
5. Davidson, A.J., et al., Apnea after Awake Regional and General Anesthesia in Infants:
The General Anesthesia Compared to Spinal Anesthesia Study--Comparing Apnea and
Neurodevelopmental Outcomes, a Randomized Controlled Trial. Anesthesiology, 2015.
123(1): p. 38-54.
6. Krane, E.J., C.M. Haberkern, and L.E. Jacobson, Postoperative apnea, bradycardia, and
oxygen desaturation in formerly premature infants: prospective comparison of spinal and
general anesthesia. Anesth Analg, 1995. 80(1): p. 7-13.
7. Sun, L.S., et al., Association Between a Single General Anesthesia Exposure Before Age
36 Months and Neurocognitive Outcomes in Later Childhood. JAMA, 2016. 315(21): p.
2312-20.
8. Suresh, S., et al., Are caudal blocks for pain control safe in children? an analysis of
18,650 caudal blocks from the Pediatric Regional Anesthesia Network (PRAN) database.
Anesth Analg, 2015. 120(1): p. 151-6.
9. Long, J.B., et al., The Use of Neuraxial Catheters for Postoperative Analgesia in
Neonates: A Multicenter Safety Analysis from the Pediatric Regional Anesthesia
Network. Anesth Analg, 2016. 122(6): p. 1965-70.
10. Long, J.B., et al., Transversus abdominis plane block in children: a multicenter safety
analysis of 1994 cases from the PRAN (Pediatric Regional Anesthesia Network)
database. Anesth Analg, 2014. 119(2): p. 395-9.
11. Ivani, G., et al., The European Society of Regional Anaesthesia and Pain Therapy and the
American Society of Regional Anesthesia and Pain Medicine Joint Committee Practice
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Advisory on Controversial Topics in Pediatric Regional Anesthesia. Reg Anesth Pain

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Page 1
Less Jolts from your Volts: Electrical Safety in the Operating Room
Jeffrey Gross, MD West Simsbury, CT
Introduction
The electrical nature of matter has been known since antiquity. In fact, the term "electricity" itself derives
from the Greek word "elektron" which means "amber." Approximately 600 years B.C.E., the Greek philosopher
Thales found that when rubbed with fur or wool, amber would attract small objects or give off an eerie bluish glow
in the dark. In the 1780's, Luigi Galvani discovered that when a metal scalpel touched the sciatic nerve of a frog, its
legs would twitch. A few years later, his colleague Alessandro Volta found the reason: When bathed in a
conducting medium (like interstitial fluid), two dissimilar metals generate an electrical current. His voltaic "pile" is
the precursor of modern batteries. Throughout the nineteenth century, scientists such as Faraday, Henry, Ohm, and
Maxwell discovered the basic principles of electricity, magnetism, and their interactions. Practical application of
their findings culminated with the development of the electric light and power distribution system by Edison,
Westinghouse, Tesla, and Steinmetz.
The perioperative environment poses unique electrical risks to our patients. Electricity is everywhere;
operating room tables, lamps, blood warmers, monitors, and cautery devices all pose potential risks. Additionally,
an abundance of electrically conductive liquids (e.g., intravenous and irrigating solutions, interstitial fluids)
increases the likelihood of electrical shock. Finally, anesthetized patients are unable to report or withdraw from a
painful electrical current, further increasing the risk of burns or cardiac arrest.
In this session, we will first discuss some basic electrical principles. Building upon these, we will learn
how electricity is transmitted from the generating station to our homes or hospitals, and the safety measures which
have been developed to reduce the risk of electrical shock in routine applications. Since some of these measures
may actually increase the risk of injury in "wet locations" such as the operating room (or your kitchen), additional
precautions must be taken to insure safety in these circumstances. Finally, we will discuss the electrocautery--how it
works, why it doesn't cause electrocution, and what problems may result if it is used improperly.
Basic Principles
The atoms of which all matter is composed consist of a positively-charged nucleus surrounded by a "cloud"
of negatively-charged electrons. In some materials (typically metals) the outermost electrons are loosely bound to
the corresponding nucleus and thus can move freely. These materials are said to "conduct" electricity. Solutions of
ions such as salt water can also conduct electricity; here, the ions
themselves are free to move within the solution. In either case, however,
the number of available current carrying charged particles (be they
electrons or ions) in a given system is fixed. Thus, the situation is similar
to that seen in an ornamental fountain, where water is pumped from a
reservoir in the base to the top of the fountain, at which point it washes over
the statue before ultimately returning to the reservoir below. Just as
interrupting the flow of water at any point in the "circuit" around the
fountain will quickly cause the flow of water to cease throughout the
fountain, interrupting the flow of electricity at any point in an electrical
circuit will cause the electrical current to stop throughout the electrical Figure 1
circuit.
Figure 1 is an example of just such an ornamental fountain. The flow of water in the fountain "circuit" is
limited by the flow through the orifice at the bottom of the reservoir tank. As the orifice gets smaller, the resistance
to flow of water increases, and the flow decreases. Conversely, as the height of the water in the reservoir increases,
the amount of pressure pushing water through the orifice increases, and
the flow increases. In this hydraulic analog, the flow is measured in units
of Liters/sec, while the pressure corresponds to the energy imparted by
the pump to each liter of water (Joules/L). The relationship between
flow, pressure, and resistance is given by: Flow = Pressure / Resistance,
which is the mechanical analogue of Ohm's law.
Figure 2
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Now consider the diagram of figure 2. In this case, the electric battery serves the role of the pump, pushing
electrical charge around the circuit. Electrical charge is measured in Coulombs (1 Coul = 6.2x10 18 electrons), and
the flow of electrical charge (denoted by the symbol "I") is measured in Amperes (1 A = 1 Coul/sec). Electrical
pressure (the amount of energy imparted to each Coul of charge by the battery) is denoted by the symbol "E" and is
measured in Volts (1 V = 1 Joule/Coul). The amount of current which will flow at any given voltage depends on the
resistance "R" according to Ohm's law: I = E/R. The product of current (I) and voltage (E) is the power delivered by
the battery to the circuit: P = I x E (Joule/Coul x Coul/sec = Joule/sec = Watts). By algebraic substitution, we can
also show that P = I2 x R.
Interaction of Electricity with the Human Body

The effect of electricity on the body depends upon the magnitude of the current as well as the composition
of the tissues through which the current passes. Currents of less than 1 mA are below the threshold of sensation.
However, if such currents are brought into proximity of the cardiac conducting system (by an intracardiac catheter
or electrode) the cardiac rhythm may be disrupted, as a result
of "microshock." Because the currents involved are so small, Table 1
special precautions must be used when intracardiac electrodes
are in place (see below).
Currents in the 1-10 mA range cause a tingling Current Effect
sensation by activating sensory nerves. For example, a 9V
10-100 μA V-Fib if applied directly to
battery may be tested by placing its contacts on the tongue; the
cardiac conducting system
resulting current will cause a tingling sensation. Currents in
(microshock)
the 10-100 mA range cause muscular contractions.
1-10 mA Minimal sensation
Anesthesiologists use this phenomenon daily with our
10-100 mA Muscle contractions
neuromuscular "twitch" monitors. Currents between 100 mA
and 5 A are likely to cause ventricular fibrillation if they pass 100 mA-5A V-Fib if current passes through
through the chest. In contrast currents in excess of 5A passing chest
through the chest cause complete ventricular standstill, allowing the heart to resume aCardiac
>5A normalStandstill /
rhythm when the
Defibrillation
current is removed; this is the principle of cardiac defibrillation. Note that electrical current can cause damage
without flowing through the chest. Currents on the order of 100 mA passing through the brain cause seizures
(electroconvulsive therapy), while currents in the 1A range passing through extremities can cause severe burns.
Because electrical burns involve not only the skin but also the underlying tissue, they can be very difficult to treat
and slow to heal.
Early Electrical Power Systems

The skin is the body's primary barrier to electrical current. Dry skin has a resistance of 1,000 to 10,000
ohms. Thus, in designing his original electrical distribution system, Edison limited the voltage to 100 V, so that an
individual accidentally touching the wires would be subjected to a current of no more than 0.1 A (100V / 1000
ohms), just below the limit of cardiac arrhythmia production. Unfortunately, limiting the voltage to 100Vcaused
significant problems in power distribution. Remember that power lines,
themselves, have some resistance to the flow of electricity. (Edison attempted
to minimize this by using thick copper conduits buried under the sidewalks.)
Nonetheless, some of the power delivered to the system was dissipated in the
power line before getting to the customer. In the example of figure 3, with a
single customer using 100 W of power at 100 V, the current is 1 A. According
to the I2R law (see above), 1 Watt is lost in the 1 ohm power line, so the
system is 99% efficient. However, when a second customer signs on, using
an additional 100 W, the current increases to 2 A, and the power dissipated in
the power line increases to 4 W. When a third customer turns on their 100 W
Figure 3
lamp, the losses in the power line increase to 9 W. Under these conditions, the
losses in the power line increase in proportion to the square of the power delivered to the customers. Therefore,
with Edison's system, it was imperative that the power lines be kept as short as possible (minimizing their
resistance), and power stations were necessarily located at intervals of 1 mile or less! As customers found more and
more uses for electricity (fans, toasters, space heaters, etc.) engineers sought more efficient ways of generating
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electricity. Near Buffalo, there was an apparently limitless source of power--Niagara Falls. The only problem was
how to transmit the power from the falls to the cities where it was needed. It became apparent that higher voltages
could overcome the problem of energy losses in the power line. If, in the above example, the voltage were 1000 V
rather than 100 V, the current required by a 100 W light bulb would be 0.1 A, and the power line loss would be 0.01
W. Even with three customers (each using 100 W), the power line dissipation would be only 0.09 W--a 100 fold
saving. The problem was that 1000 V was too dangerous for household use, and there was no practical way of
changing the voltage of the one-way or "Direct Current" used by Edison's system.
The Rise of Alternating Current

Some 40 years earlier, Faraday demonstrated the
interrelationship between electricity and magnetism: When a
changing magnetic field passes through a coil of wire, an electrical
current is generated. Furthermore, when a changing electrical
current passes through a coil of wire, a changing magnetic field is
produced. Using these two observations in tandem led to the
invention of the electrical "transformer." This ubiquitous device
allows electrical voltage to be changed, since the ratio of Figure 4
input:output voltage is the same as the ratio of turns in the
primary:secondary coils (figure 4). The only proviso is that the
electrical current fed to the device must be constantly changing. By using current which flows in a sinusoidal pattern
(first one way, then the other) Tesla and Westinghouse devised a practical "Alternating Current" or "AC" power
delivery system, whereby power is transmitted over long distances at high voltages and then "stepped down" to a
safe voltage by a transformer near the consumer. Note that although
the primary and secondary coils are magnetically coupled, they are
electrically insulated from each other.
Early AC power delivery systems presented significant
hazards to their users. Power was transmitted from the power station
to the user at the relatively high (then) voltage of 2400 V, and
"stepped down" to 120 V by a 20:1 transformer on the power pole
near the customer (figure 5). To save money on copper, engineers
used the earth as one of the conductors. Since normally functioning
transformers do not provide an electrical connection between the
primary and secondary circuits, the 120 V delivered to the user was
perfectly safe. That is, unless moisture got into the power pole
transformer, and allowed some of the 2400 V power to "leak" into the
secondary side of the circuit. Then, although there would still be 120
V between the two wires leading to the house, 2400 V would exist
Figure 5
between these wires and ground, creating risk of a lethal electrical shock. After several unfortunate people were
killed in this manner, Edison (whose patents covered DC but not AC power) lobbied to have AC power banned,
since people were likely to be "Westinghoused" by this dangerous system. However, engineers soon discovered
how to make AC systems safe: One side of the 120V power line entering the house was directly connected to
ground. Even today, the fuse box where power enters your house is directly connected to a cold water pipe or
grounding rod--take a look! While this innovation prevented high voltages from entering the house, having one side
of the power line attached to ground created other hazards.
Consider great-grandma's refrigerator (or FrigidaireTM) in the 1920's. When manufactured, the electrical
wiring was completely insulated from the steel cabinet; however with time
the insulation on the internal wiring was likely to deteriorate. If the non-
grounded or "hot" power conductor came into contact with the case, a
dangerous situation would be created. An individual touching both the
refrigerator case and any grounded object in the kitchen (like the proverbial
kitchen sink) would complete a circuit, and be subject to electrocution.
What's more, the refrigerator would appear to be functioning normally,
since household fuses are designed to "blow" when current exceeds the
authors/copyright holders. Figure 6
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safe capacity of the wiring (15-30 A) rather than the 0.1 A of current needed to cause ventricular fibrillation. A
dangerous situation could exist even if the refrigerator wiring were not in direct contact with the case. Moisture (in
the form of spilled liquids or condensation) could easily conduct sufficient current to the case to create an electrical
hazard. The risk that the case of an appliance might be electrically "hot" led to the ubiquitous warnings about never
touching an electrical appliance while your hands or feet are wet (and potentially grounded).
Safety Ground--Three-Wire Receptacles

By the 1950's, this risk was recognized, and a solution was adopted: appliances whose cases were likely to
become electrically "live" were fitted with 3-wire electrical plugs (figure 6). The third prong, slightly longer than
those used to power the device, served to connect the case of the appliance directly to ground; in this manner any
stray voltage which found its way to the case would be diverted to ground rather than posing a risk to the user. If the
"hot" power conductor were shorted directly to the appliance case, a high current would flow, blowing the main
fuse; if the problem were "leakage" through moisture or an indirect connection, the fuse would not blow, but the
user would still be safe since current would be shunted safely to ground via the third wire.
While the three-wire system is still widely used "around the house" it is not safe enough for use in "wet
locations" such as the kitchen, bathroom, or operating room. The reason is twofold: First, if the ground wire breaks
or becomes disconnected, users are at immediate risk; although grounding continuity is checked on an annual basis
by most hospital biomedical departments, rolling an operating table or anesthesia machine over an electrical wire
could easily disrupt the connection. Second, if an individual should accidentally touch the "hot" conductor (e.g., by
letting the hair dryer fall into the sink) grounding the case offers no protection (in fact, it may actually increase the
risk, by increasing the likelihood of touching the "hot" conductor and grounded case simultaneously. Finally,
anesthetized patients are at additional risk because they cannot "feel" potentially hazardous leakage currents and pull
away appropriately. For these reasons, operating rooms (and other wet locations) are required to have additional
safety devices.
Isolated Electrical Power

The older (and still more common) system used in operating rooms is "isolated electrical power." In this
system, a second 1:1 transformer is interposed between the standard hospital
power (having "hot" and "neutral") conductors and the electrical receptacles in
the operating room (figure 7). In this system, neither of the power conductors is
grounded. Therefore you could safely touch either of the power conductors and
ground simultaneously without any risk. This alleviates both of the problems
alluded to above: Even if the ground wire is defective, a short circuit (or
leakage) between one of the power conductors and the case of the monitor
poses no risk, because the other power conductor is not connected to ground.
Thus, touching an electrically "live" case and ground simultaneously does not
complete a circuit. However, if one of the power conductors should touch the
case of the monitor, that conductor is now grounded, and all of the power in that
operating room is no longer electrically isolated. Because it is important to Figure 7
know that isolation is no longer effective, isolated electrical power systems are
equipped with "line isolation monitors" or LIMs. These continuously monitor the power system, to determine if
there is a potential leakage of current from either side of the power line to ground (note that leakage does not
actually occur unless there is an electrical “path” from the other side of the power line to ground.). Thus, the LIM
monitors the maximum current which could flow to ground through the defective equipment if the other side of the
power line were connected directly to ground. Thus, it is an indication of the risk to which a patient (or
anesthesiologist) would be exposed if there were a second defective device in which the other side of the power line
was connected directly to the case. The third "grounding" wire plays an important role in isolated power systems; it
is current flow through this conductor which causes the LIM to register. Note that if the LIM registers leakage
current only when the operator (or patient) touches the defective device, a much more serious condition exists: Not
only is there a connection between one of the power conductors and the case of the defective equipment, but the case
itself is not effectively grounded.
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LIMs are designed to audibly alarm if the potential leakage current from either side of the isolated power
system to ground exceeds 5 mA. Hazard currents below this level are readily achievable, yet currents in this range
do not pose a hazard when applied externally. Note that isolated power systems do not protect against microshock,
which occurs with currents two orders of magnitude smaller. If the LIM alarms it is incumbent upon the OR
personnel to locate and remove the offending equipment from the electrical circuits. This may be accomplished by
unplugging devices one at a time (starting with the most recently plugged in, or with any devices which may have
been accidentally exposed to liquids) until the offending device is located. Note that hazard currents are cumulative.
That is, the electrical leakage from several devices, each of which is individually below the 5 mA threshold, may
combine to cause a potentially hazardous situation. If, after all portable equipment has been unplugged the LIM
continues to indicate a potentially hazardous condition, the problem most likely lies in the room wiring or fixed
devices such as the overhead surgical lamps. Note that life-sustaining equipment which does not have battery
backup should not be unplugged during a procedure in an effort to determine the cause of an LIM alarm condition.
(Don't unplug the cardiopulmonary bypass machine!) Remember, while the LIM is telling you that the electrical
power is no longer isolated (i.e., you have the same situation which existed in laundry rooms, kitchens, and
bathrooms until the 1980's), it is still necessary to have a second electrical defect to put you or your patient at
immediate risk.
Ground Fault Circuit Interrupters

With the advent of microelectronics in the 1970's and 80's, a new option has become available for
preventing electric shock in wet locations: the ground fault circuit interrupter (GFCI). These devices (which cost
less the $10 each) work in a different way than the isolated power systems described above. They continuously
monitor the current flowing in the "hot" and "neutral" power conductors of an ordinary (one side grounded) power
system. If the device senses that the current in the "hot" and "neutral" conductors differs by more than 5 mA, it
immediately (<25 ms) disconnects the power from the receptacle. Under what conditions would the current differ
between the two power conductors? First, if there is a direct connection (or leakage) between the "hot" conductor
and the case of the device, some of the current flowing in the "hot" conductor would return to ground via the safety
ground connection rather than the "neutral" conductor. Thus, the current in the "hot" conductor would exceed that in
the "neutral" and the current would be interrupted. Note that if the safety ground connection is defective, the GFCI
will not trip, and the equipment will continue to operate, even though its case is electrically "hot." However, if the
user (or patient) completes a circuit between the case and ground, a current imbalance will occur. A portion of the
current will return to ground via an alternate route (the user) rather than via the neutral conductor, and the GFCI will
disconnect the circuit. This occurs so quickly that arrhythmias are unlikely.
If a GFCI "trips" in the operating room, the first step is to press the reset button to see if the tripping was
caused by a current surge: some motors may cause a transient current imbalance which does not indicate a
hazardous condition. If the GFCI trips again, it is necessary to unplug equipment sequentially, resetting the GFCI
after each until the defective equipment is located. A disadvantage of the GFCI is that it protects by turning the
power off. Hence, if the defect lies in a piece of life-sustaining equipment, there is no way to continue using that
equipment until it is repaired. Resist the temptation to use a "cheater" which ungrounds the case of the defective
equipment. While the GFCI will not trip if the case is not grounded, the case is
electrically live and poses a hazard to the operator or patient. Note that if the
GFCI only trips when the equipment is touched by the operator or attached to
the patient, a more hazardous situation exists: Not only is there electrical
leakage from the "hot" side of the power line to the case, but the safety ground
of the equipment is not functional.
Microshock
None of the safety measures discussed so far has any influence on the
risk of microshock, which results when currents on the order of 10 to 100 μA Figure 8
are applied directly to the conducting system of the heart via intracardiac
catheters or pacing wires. Because such wires bypass the skin resistance, relatively small voltages may suffice to
produce microshock. Isolated power systems, ground fault interrupters, and equipment safety grounding cannot
prevent microshock. Rather, special precautions must be taken when the possibility of microshock exists.
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All monitoring equipment attached to intracardiac catheters or electrodes must be electrically isolated. This
means that there is no direct electrical connection between the wiring attached to the patient (e.g., ECG, pressure
transducers) and the internal wiring of the monitoring equipment. How can this be accomplished? The monitoring
modules are typically powered via special isolation transformers which effectively isolate the power within the
modules from the power system of the remainder of the monitoring unit as well as from ground. The monitored
signals are transmitted from the module to the main chassis of the monitor through "opto-isolators." These devices
convert the electrical signals corresponding to the ECG or pressure trace to a beam of light whose intensity is related
to the strength of the corresponding signal; the light beam impinges upon a photodetector which converts the light
intensity back to an electrical signal which is ultimately displayed on the monitor screen. In this way, a maximum
current of 50 μA can flow through an intracardiac electrode, even if the patient is attached directly to the "hot"
side of a standard, grounded power system. Temporary external pacemakers are typically battery powered and
hence are intrinsically electrically isolated unless one of the pacing wires or an internal component comes into
contact with an external conductor. Therefore, these devices should not be powered by "battery eliminators."
An important consideration is that "grounding" an intracardiac catheter or electrode does not provide an
increased margin of safety; rather, it actually increases the risk of microshock. The reason for this is that other
devices with which the patient may be in contact may not be electrically grounded. For example, suppose that a
patient's skin is in electrical contact with the operating table via moisture in the sheets. If the operating table is not
properly grounded (frayed or loose grounding conductor) a leakage current of several mA could be present with no
indication on the LIM. However, passage of this current to ground via the intracardiac catheter could suffice to
cause ventricular fibrillation (figure 8). The same scenario may occur if cardiac pacing wires accidentally touch the
operating table, even though the table is, theoretically, grounded.
Electrocautery
The electrosurgical unit (ESU) is designed to create a localized, high temperature electrical discharge at the
site of surgical bleeding, causing coagulation of tissues and cessation of bleeding. This is accomplished by creating
a high-density electrical current: When a large amount of current is concentrated in a small area, heating is
inevitable. In addition, the voltages produced by the electrosurgical unit are sufficient to ionize the adjacent air,
with the resulting "sparks" contributing to the heating and coagulation process. There are two reasons that those
parts of the patient not directly under the cauterizing electrode are unaffected by the process. First, immediately
after entering the tissues, the current spreads out to be conducted over a much wider area of the patient's body. Thus
the current density (and heating) is minimized. Of course, the patient forms part of the electrical circuit of the
cautery system, and thus a path must be provided to complete the circuit from the patient back to the unit (figure 9).
This is accomplished through the return electrode or "grounding pad." This pad is designed to dissipate the current
over a wide enough area to prevent accidental heating or burning of the region under the pad. Note that in modern
electrosurgical units, the pad is not "grounded" per-se. This prevents it from serving as an inadvertent means of
conducting macro- or micro-shock currents into the patient. If the return pad is not attached to the patient, current
from the active electrode will seek an alternative route to return to the generator. Because the electrocautery
produces alternating current of high frequency (typically 100 KHz or more), the current can actually be conducted
between two adjacent conductors, even if they are not in electrical contact (capacitative coupling). Furthermore, the
electrical isolation of monitoring equipment, and power systems is ineffective at these frequencies. Thus, if the
return electrode is not attached to the patient, the current may return to the generator via ECG electrodes or other
metallic objects (e.g., operating table) which may be in contact with the patient. Since these provide a smaller
contact area with the patient, the current will be more concentrated, and the patient may be burned at the site of these
inadvertent return paths. Modern electrocautery machines are equipped with "split pads;" the unit will not function
unless both halves of the pad are in contact with the patient.
Since it delivers currents in excess of those required to cause ventricular arrhythmias, why do we not see
such arrhythmias when the cautery is used? As mentioned above, the cautery uses high frequency alternating
current. Tesla demonstrated over 100 years ago that such currents are carried on the surface of a conductor rather
than penetrating it; this is the "skin effect." Thus almost all of the electrosurgical current is carried by the skin and
subcutaneous tissues rather than penetrating to the cardiac conduction system. In fact, it is possible to use the
electrosurgical unit on the epicardial surface of the heart without affecting the internally-located conducting system.
References:
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Gross JB, Seifert HA: Electrical, Fire and Compressed Gas Safety for the Patient and Anaesthetist in Wylie and
Churchill-Davidson's A Practice of Anaesthesia, 6th Edition. Edited By Healy TEJ, Cohen PJ. London, Edward
Arnold, 1995.
Jonnes J: Empires of Light--Edison, Tesla, Westinghouse and the Race to Electrify the World. New York, Random
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OR Capacity-Block Allocation and Utilization
Shubjeet Kaur MD, M.Sc.HCM Worcester/MA
Introduction:
Approximately 30% of the annual health care expenditure in the United States is related to surgical/procedural care.
The Institute of Medicine Report “The Health Care Imperative: Lowering Cost and Improving Outcomes (2012)
highlighted that 30% of the total health care expenditure is “waste”. Inefficient delivery of services contributes to
this high cost of care. A significant proportion of cost of delivering surgical care is related to Operating Room
Capacity. Determination of appropriate OR Capacity for a specific practice setting and subsequent allocation and
utilization monitoring of this expensive resource is fundamental to delivering value (quality outcomes at the lowest
cost) while improving patient and provider satisfaction ( timely access to the operating room for patients and
Surgeons) . Planning appropriate staffing based on the OR Capacity commitment and minimizing over and
underutilization of this capacity can lead to predictability in OR scheduling and enhanced professional satisfaction
for the Anesthesiology team and the Operating Room staff.
Determination of OR Capacity:
From a leadership perspective (Hospital or a free standing Surgery Center), there are two major components to
determine ideal OR capacity – Strategy and Operations.
Strategy:
The viable plan to grow surgical services should be based on a clear strategy that is guided by past data on surgical
volume, case mix and duration, utilization by Surgeon (and department in an employed model) and contribution
margin. Utilization metrics should include “Turn-Over Time” (TOT- Patient out to next patient in), over utilization
and under utilization statistics.
In addition a proactive strategic plan is anchored in a solid understanding of the demographics of the community,
anticipated surgical needs as well the current and projected market share. This in turn needs to drive recruitment of
surgeons in key sub-specialties.
Operations
Operating room capacity has two dimensions- the physical space (# of licensed rooms) and staffing (# of staffed
rooms). For maximal return on investment (ROI) there should be a zero gap between these two components during
prime time (elective block allocation grid). The capacity commitment (Block allocation grid) impacts the staffing
plan (For the Anesthesiology Department as well as the OR staff). The number of concurrent Operating rooms
(horizontal) determines the number of FTEs ( full time equivalents ) needed and the length of the OR Blocks
(vertical) impacts the shift duration for the OR team. The total capacity calculation is based on the proportion of
scheduled and add-on (urgent/emergent) surgical procedures as well as distribution during peak/prime time and non-
peak hours (evenings, nights and weekends). The ripple impact on upstream and downstream areas: preoperative
evaluation clinic, Post Anesthesia Care Unit (PACU), In-patient and ICU bed need as well as equipment (e.g. C-
Arms) should be factored into OR capacity commitment planning.
Block Allocation:
Definitions
• Block Time: Staffed OR Time Allocated to a specific Surgeon, Division or Department
• Over Utilization: Cases Running Past the end of the Allocated Block Time
• Under Utilization: Cases Finishing earlier than the Scheduled End Time
Models
 Fully Blocked: All Operating room time allocated as blocks to surgeons or/and Departments
 Fully Open: All Operating room time is open time- “ first come first served model)
 Hybrid: Mix of block allocation and open time.
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The fully blocked model can work well in an Ambulatory Surgery Center ( ASC) setting where there is a high
degree of predictability in the operating room schedule and where historical data supports optimal utilization ( 85-
90% or higher). In a non-ASC setting the risk of a fully blocked OR capacity plan include the following:
 Access for Add-on Cases (Safety/Quality/Satisfaction)
 Patient Leakage/Transfers
 Provider leakage- Employed vs. Private Surgeons
 Downstream Impact- LOS, In Patient Beds, ER Boarders, PACU Delays
A fully open OR scheduling system based on a “1st Come 1st Served” philosophy works well from the perspective
of surgeons with a predictable, elective and robust practice and comes with the following risks:
• Risk of Underutilization
• Patient Flow Variability
• Access -Risk of Patient and Provider Dissatisfaction
• Equipment & Support Services Availability e.g. C Arm
• Staffing Plan Challenge- Anesthesiology Perspective
A Hybrid model with a mix of allocated block time and open access time can work well in a practice setting with a
mix of elective and add-on ( urgent/emergent) volume ( e.g. a Level 1trauma Center). The optimal proportion of
open to blocked time can be calculated based on the historical and projected proportions of elective and emergent
case load (number of cases as well as average case length. Open time available for add-on cases can only be
optimally utilized if there is a surgeon available to use it. This is impacted by the proportion of employed and private
practice surgeons as well as the philosophical approach of the surgical practice (schedule flexibility and skill set that
promotes inter-changeability among surgeons). Some potential advantages of the Hybrid system include the
following:
• Decreases ‘bumping” of Elective Scheduled Patients
• Timely Care Delivery/Downstream Positive Impact on patient Flow
• Provider Morale- Less work during off-hours
The “one size fits all” approach cannot lead to success for all practices. Instead a well thought out plan based on the
principles outlined above, supported by a clear policy formulated with input from key stakeholders is key. The
foundation of the policy includes the following
• Blocks allocated based on time needed to meet budgeted volume and RVU targets.
• Allocation to individual Surgeons or Department Chairs (who allocates to individuals, small groups,
divisions
• Each block has an owner who surrenders and manages block time Block length varies by campus
• Blocks begin at same time OR begins
• Cases booked sequentially to minimize gaps
• Case lengths determined by Elective Scheduling policy
• Surgeons resigning or retiring have block time returned to the OR Governance Committee (or to
department to re-allocate )
It is important to Engage and Educate (all team members) and Execute (follow utilization metrics and re-
allocate based on agreed upon policy). This can lead to a “win win” endpoint for patients, providers and the
hospital. A governance structure that can implement the policy is critical for operational effectiveness. The
hallmark of success include
 Patients and Surgeons have timely and adequate elective access to OR schedule
 Surgeons have access that is consistent with needs and practice patterns
 Surgeon recruitment and retention is enhanced
 Anesthesiology and OR Staff satisfaction
 Overall OR utilization goals are achieved
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Utilization:
Definitions
Raw Utilization:
Total Hours (minutes) of Cases Performed ÷
Total Hours (minutes) of OR Time Allocated
Adjusted Utilization:
{Total hours of cases + “Credit Time”} ÷
Total Hours of time allocated
(Credit Time = Turn over Time + Surrender Time)
Auto Release of Block Time:

Block time automatically given back to OR based on service and campus parameters.
E.g. If a procedure is not scheduled into the allocated block time, the time is automatically released and is available
for another surgeon or service to us
• Allocated Block Time. Time allocated to the individual, service or department on block schedules
published monthly.
• Surrendered Block Time. Time given back to OR with four or more weeks’ notice; holidays
automatically surrendered.
Turnover Time:
Patient out to next patient in
Can use Average TOT or
Actual TOT between cases is calculated for each case. One possible method outlined below
One-third is allocated to first case; 2/3rds allocated to second case
If a case is first or last of day and there is no ability to calculate a turnover time, then the average for the service is
applied
The average for the service is also applied if the gap of time is greater than the turnover threshold
Block Utilization Calculation

= Total Patient In to Patient Out + Turnover Time during Allocated Block Hours ÷
Total Allocated Block Time-Surrendered Block Time
Establish Threshold Utilization

This can be determined based on practice location e.g.: 85% at an Ambulatory Surgery Center; 80% at Hospital
based practice. The OR policy governing utilization expectation, monitoring and criteria for re-allocation should be
clearly communicated to the Block owner.
Block use reviewed each month and acted on quarterly based on three-month trend.
Determining optimal OR Capacity, allocation of this valuable resource, monitoring utilization and actively
managing re-allocation requires a strong partnership between the hospital/ Surgical Center, the Surgeons and the
Anesthesiologists even though they may be approaching this challenge with different perspectives.
Anesthesiology Department Role

The goal of the Anesthesiology practice is to make themselves indispensable to the organization by providing
patient focused high quality care, supporting timely access to the operating room and promoting a culture of “yes”
when requested to provide anesthesia coverage. This in turn leads to stability, sustainability and growth
opportunities.
The Department of Anesthesiology can contribute in the following ways:

• Leadership- Clinical Director/Medical Director Perioperative Services
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• Proactive approach to building a staffing plan that supports the OR Capacity Commitment and Block
Allocation plan
• Innovation: bringing innovative approaches to achieve operational efficiency (e.g. Lean methodology) and new
patient focused health care delivery models (e.g. Perioperative Surgical Home) can place the Anesthesiology
group in a position of strength.
The overarching goal is to have the right capacity that helps meet patient needs by doing the right procedures at the
right time in the right location with the goal of achieving good outcomes at the lowest cost while achieving
operational effectiveness and financial viability for the organization (providers and the hospital.
References
1. Richard M.J. Bohmer, M.B, Ch.B. M.P.H., and Thomas H. Lee, M.D.: The Shifting Mission of Health
Care Delivery Organizations: N ENGL J MED 361; 6; 551-553, August 6, 2009.
2. Thomas H. Lee, M.D. Putting the Value Framework to Work. N ENGL J MED 362; 26: 2481-2483;
December 23, 2010.
3. Michael E. Porter, Ph.D. What is Value in Healthcare? N ENGL J MED 363;26: 2477-2481 ;
December 23, 2010
4. Institute of Medicine Report© September 2012: The Healthcare Imperative: Lowering Costs and
Improving Outcomes.
5. Dexter,F.et al: An Operating Room Scheduling Strategy to maximize the use of Operating Room
Block Time: Computer Simulation of Patient Scheduling and Survey of Patients’ Preferences of
Surgical waiting Time..Anesth Analg.1999;89:7-20
6. McIntosh C, Dexter F, Epstein RH. Impact of Service Specific Staffing, case Scheduling, Turnovers,
and First Case Starts on Anesthesia Group and Operating Room Productivity: Tutorial Using data from
an Australian Hospital. Anesth Analg. 2006;103:1499-1516
7. Siciliani, L.,Hurst,J. Tackling Excessive Waiting Times for Elective Surgery: A Comparative Analysis
of Policies in 12 OECD Countries. Health Policy 20015;72:201-205
8. Macario A, Dexter F, Traub RD. Hospital profitabilty per Hour of Operating Room Time can vary
Among Surgeons. Anesth Analg. 2001; 93(3):669-75.
9. Resnick AS, Corrigan D, Mullen JL, Kaiser LR. Surgeon Contribution to Hospital Bottom Line. Ann
Surg. 2005;242(4);530-539
10. Dexter F, Blake JT et al. Calculating a Potential Increase in Hospital margin for Elective Surgery by
Changing Operating Room Time Allocations or Increasing Nursing Staffing to Permit Completion of
More Cases: A Case Study. Anesth Analg 2002;94:138-42
11. Womack JP, PhD, Byrne AP,MBA, Flume JO,MS, Kaplan GS,MD, Toussaint J,MD: Going LEAN in
Health Care: Institute for Healthcare Improvement Innovation Series White Paper , 2005
12. Toussaint J and Gerard RA with Emily Adams: On the Mend- Revolutionizing Healthcare to Save
Lives and Transform the Industry ©2010 Lean Enterprise Institute Inc. ISBN 978-1-934109-27-4
13. Rother M, Shook J, Womack JP, Jones DT. Learning to See, Value- Stream Mapping to Create
Value and Eliminate Waste. Boston: Lean Enterprise Institute; Version 1.3, 2003
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Anesthesiologists As OR Managers: From the Surgical Suite

to the C-Suite.
Aaron J. West, MD, MBA Jacksonville, Florida
The operating room is perhaps the most dynamic – and volatile – location to manage within the confines of a
hospital. Consider that in any operating room in any hospital, at once there may be inbound trauma, complex
neurosurgery, routine cosmetic cases, all of which is subject to the immediate need of a patient in extremis. Perhaps
in no other single location is there the constant variety necessitating highly divergent and specialized skills that can
be required to change on a moments notice and to accommodate non-scheduled and non-anticipated cases What is
most unusual, is that every professional in the operating room has a singular task; only the anesthesiologist must be
able to literally do all things at any time with minimal notice. For example, a general surgeon will only perform
general surgery, and likewise a scrub nurse will only be responsible for scrubbing a case. The anesthesiologist has
the broad ability to vary from the induction of an elective case set up in one room, and then be called to handle a life
threatening trauma in another room with no time to set up. It is precisely this broad perspective and broad
functionality that makes the anesthesiologist the ONLY reasonable choice to manage an operating room
But what of typical operating room management today? Across the nation, operating rooms are generally managed
by nursing managers who assign teams to rooms and supervise scheduling, with the anesthesiologist routinely only
weighing in on the anesthesia provider deployment. In the current environment, the best option that exists is a
symbiotic relationship between the anesthesia provider managing anesthesia personnel and the nurse managers
scheduling and assigning cased from that perspective. In the worst case, however, the entire system depends on
which surgeon has the deepest bark or the most political clout to accommodate his or her whims with little thought
or regard o the remainder of the department.
If the climate of surgical medicine and perioperative medicine were stable, perhaps there would not be a need to
specialize anesthesiologists in management or leadership. However in the year 2016 there is nothing stable about
operating room efficiency or operating room forecasting. Anesthesia services are being required in remote places in
the hospital, often taking only an anesthesia team away from the familiar environs of the traditional operating room,
leaving a deficit in daily operation numbers among an ever tightening schedule. Consider that presently it is not
unheard of for anesthesia services to be required in: endoscopy suites, interventional cardiology suites,
interventional radiology suites, and critical care units. Additionally, with the concept and evolution of the
perioperative surgical home – the environment is created where the anesthesiologist must be in literally EVERY
floor and unit on the hospital. The question becomes, what is the future of our specialty, how are we resourced, and
is there an ability for anesthesiologists to create a unique niche in the overall management of the hospital that makes
our services indispensible? That answer is yes.
Anesthesiologists must be ready to deploy at minimum qualified anesthesia providers and care teams to the
operating rooms and labor and delivery unit in most hospitals. However, over the last several years,
anesthesiologists have become more active in critical care medicine and in many other procedural areas. With the
advent of TAVR, Watchman, Lariat and other highly specialized cardiac procedures, anesthesiologists and CRNA’s
with the cardiac skill set are being taken out of the operating room for these hybrid procedures in areas that
generally provide its own nursing support. Many groups also provide services to GI and endoscopy labs,
particularly where there are advanced procedures such as ERCP. Many institutions are also mitigating risk by
having anesthesiologists attend in endoscopy because nursing based sedation and analgesia is under the anesthesia
director according to CMS rules of participation.
One of the most impressive changes in the face of anesthesia now is the advent of the perioperative surgical home.
Although it exists in many formulations at this point, the unified and complete care of the surgical patient form the
admission process whether through the emergency department or through an elective venue, the anesthesiologist
may be required to see patients on the floor, in the operating room, in the intensive care unit, in the med-surg
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environment, and through the discharge process. The fact that one physician can take care of this entire process in
all clinical areas truly speaks to the versatility and breadth of knowledge of our specialty.
While the clinical side is well within our training, the deployment of the anesthesia care team is something that
requires additional skill development. There are a myriad of management theories that suggest proper deployment
to meet a diverse set of institutional needs. Recently several anesthesia-training programs have begun to
incorporate leadership development, crew resource management theory, lean and six-sigma theory into the
educational process. No longer is “pentothal – sux – tube” good enough to survive in an increasingly difficult
financial and political environment. Quality measures, efficiency standards, and patient satisfaction surveys are
now our bread and butter, and were not even on our radar scope merely four to five years ago.
Should management training be a standard (even examined?) portion of our anesthesia residencies? One of the
largest threats to anesthesiologists in general is the ever-increasing call for independent practice of non-physician
anesthesia providers. That is to say, how do we distinguish ourselves in a world where no matter how much we
discuss that physicians are the safest and most efficient anesthesia providers, we are in fact being replaced by non-
physician providers CRNA political lobby will only increase independent practice, not shrink it.
Anesthesiologists must become adapt that utilizing our unique set of clinical skills – after all being a doctor at
bedside is a very special and unique talent that belongs only to the physician and marrying it to standard operational
and process management. That is to say a non-clinical administrator has no idea what it means to be a bedside,
while a nurse, now matter how well trained as a CRNA, simply does not understand the complex physiology of the
surgical patient in the preoperative and postoperative period. It is this unique set of traits that foundationally is laid
on the clinical understanding of the surgical patient that makes the anesthesiologist the only physician in the hospital
that feels comfortable in a clinical areas and can operationalize and make efficient the interplay between
departments.
Anesthesiologists are the ONLY physicians in the hospital environment that can exist in every ward, at any time,
and be comfortable and functional. Data demonstrate that when the anesthesiologist is put in charge of the surgical
patient (and therefore the perioperative process) outcomes significantly improve, and markers of efficiency such as
length of stay and cost per case naturally decrease. It is this leveraging of clinical skills and process improvement
that make it a natural evolution for the anesthesiologist to lead the operating room and then move to the C-Suite
Anesthesiologists are increasingly becoming executives in the hospital industry. From Chief Medical Officer to
Chief Executive officer, anesthesiologists also procure invaluable operational experience in the operating room such
as supply chain, standardization of process, scheduling, and all other operational phases in a microcosm of the
overall health care industry.
Healing is an art, Medicine is Science, and Health Care is a business. These are the three legs upon which all
clinical practice currently sits, and in the future, it will only become more entwined. The call to action for the
physician anesthesiologist is to once again assert the natural leadership that is our birthright and it will not be
usurped, because it cannot be equaled. Anesthesiologists for over 3 decades have been looking for the unique niche
to define our specialty in such a way that no other clinical provider is able to duplicate. Through the emergence of
the perioperative surgical home and the divergence in location and evolution of many specialties becoming
proceduralists, who require anesthesia support, it is abundantly clear that anesthesiologists stand at the crossroads of
all avenues of medicine and administration. The only question that remains is: are we willing to accept this role, and
improve the lot of our patients and practices? Or will we abdicate our last – and best hope to create a role in
medicine that cannot be challenged.
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Common Pediatric Anesthesia Emergencies: Safety and Best Practice
R. Blaine Easley, MD Houston/Texas
Introduction:
Recent reports reviewing the status of pediatric emergency care have emphasized the fact that the majority of
pediatric patients around the world receive emergency anesthetic care by general anesthesiologists (1,2). In many
community hospitals and surgery centers, general anesthesiologist provide safe and effective care to children
undergoing routine surgery. However, in these same settings, clinically well children can acutely decompensate
from medical and surgical issues before, during and after an anesthetic. While a comprehensive review of this
subject is beyond the scope of this lecture, commonly encountered pediatric emergencies will be discussed along
with current literature and resources for management by the general anesthesiologist.
Common Pediatric Emergencies:
Infants and children often present after-hours to community hospital emergency rooms (ER). Often this makes the
“on-call” anesthesiologist one of the most valuable resources for airway management and vascular access in the
acutely decompensating child. Common medical conditions requiring emergent management are shock (from
dehydration or hypovolemia) and respiratory insufficiency (from pulmonary or central nervous system issues).
Common surgical conditions requiring emergent involvement of the anesthesiologist are: trauma (like a
supracondylar fracture), airway foreign body, appendicitis, post-tonsillectomy bleeding, sub-dural hematoma and
pyloric stenosis (see FIGURE 1). Many of the medical issues resulting in respiratory distress and hemodynamic
instability require similar management to those issues experienced in operating room (OR) or post-anesthetic care
unit (PACU) environments when caring for pediatric patients. Again making the anesthesiologist a valuable
resource.
FIGURE1: Common Pediatric Medical and Surgical Emergencies
Medical Surgical
Dehydration Trauma
Respiratory Disease Burns
CNS disease Airway Foreign Body
Sepsis Appendicitis
Cardiac Incarcerated Hernia
Metabolic disorder Intussception
Toxic ingestion Pylroic Stenosis
Testicular torsion
General Preoperative Preparation: Ideally an ER, OR or PACU environment will have pediatric specific equipment
and supplies available (i.e. intravensous/intraosseus catheters, central lines, endotracheal tubes, laryngoscope blades,
etc.) Since many children are previously healthy before the emergency, a history can focus on a few common
themes: 1) prior personal or family history of complications associated with anesthesia (like malignant
hyperthermia); 2) personal history of prior anesthetics (this may allude to other comorbid conditions); 3) any
problems that require visiting a doctor on a regular basis (including asthma, allergies, congenital heart disease, or
other conditions or congenital anomalies). While asking about preoperative fasting guidelines are important, the
majority will require an efficient assessment and anesthetic plan; making a rapid sequence intubation technique
(RSI) necessary. For the purposes of this discussion, RSI or modified RSI will be used for securing the airway in the
majority of clinical scenarios.
Based on the report from the Agency for Healthcare Research and Quality in 2012 the most common
surgical procedures performed on hospitalized children ages (0-17 years; excluding circumcision and cesarean
section) were appendectomy (103/100,000 population); bone fracture repair (20/100,000 population), and
tonsillectomy (20/100,000 population). Given the prevalence of these urgent/emergent procedures in the
community, a practicing anesthesiologist will most likely experience an emergent pediatric anesthetic case or
complication (2). The discussion will focus on six of the most common pediatric surgical emergencies in
community hospitals:
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1) Trauma/Fractured Long Bone (Opened reduction/fixation): Trauma is the leading cause of death in children
1-17 yo and accounts for almost 40% of deaths during childhood in developing countries.(3) While there is evidence
that outcomes after trauma in children are best at specialized pediatric trauma centers, acute injuries often
necessitate care at the nearest hospital.(4) There is widespread acceptance that uniform approaches to the injured
child such as emphasized by Pediatric Advanced Life Support (PALS) and Advanced Trauma Life Support (ATLS)
can improve communication and teamwork during pediatric emergencies.(5) Maintenance of certification in these
programs can help keep practitioners up to date on evolving changes in practice. Regardless, the approach to an
injured child is very comparable to an adult. Important differences are: a) Blood pressure is unreliable with regards
to intravascular status. Children may be normal or hypertensive regardless of the severity of injury and can maintain
perfusion with peripheral constriction with up to 75% of circulating blood volume absent, with minimal signs of
shock. If signs of shock are present, such as peripheral circulatory restriction, tachycardia and/or confusion, then
fluid resuscitation may be required before proceeding with any additional therapies. If there is evidence of delayed
capillary refill (> 3 seconds) this finding correlates with a higher likelihood of shock (5) b) Obtaining vascular
access is a priority and peripheral venous cannulation is preferable. Consider the saphenous vein at the ankle and/or
the external jugular vein – potential access sites that are often overlooked. Placement of an intra-osseous catheter
into the tibia is a very effective and reliable method of gaining vascular access and is advised before attempts at
central venous cannulation. In blunt trauma, hypovolemia should be treated with a bolus of 20 ml/kg of isotonic
fluid (i.e. normal saline or lactated ringers solution), followed by reassessment and further boluses as required. In
penetrating trauma with bleeding, 10 ml/kg should be given as the initial bolus, followed by another 10 ml/kg with
surgical consultation at time of the second bolus. As a rule, one should consider transitioning to blood product
administration after giving 40-60 ml/kg of crystalloid (sooner if blood loss is evident). c) Respiratory distress may
be multifactorial from shock, anxiety, pain and injuries. While rib fractures and flail chest are less common in
children compared to adults; hemothorax and/or pneumothorax may be present with minimal clinical or external
signs of injury. In addition, children will often swallow air when distress making their stomachs distended
increasing their risk of vomiting and further reducing their functional residual capacity. This net reduction in
functional residual capacity makes preoxygenation a crucial part of preparation for tracheal intubation. d)
Management of the pediatric airway may pose challenges for those unfamiliar with children. Infants and babies have
a larger head and higher, more anterior larynx compared with older children and adults. The higher metabolic rate in
young children combined with the decreased functional residual capacity that is often seen in trauma patients will
result in a rapid desaturation if airway management is not optimal. After circulation, airway, and breathing and have
been stabilized, an assessment of disability should be made using the AVPU scale (Alert, responsive to Voice,
responsive to Pain or Unresponsive). Formal Glasgow Coma Scale (GCS) assessment should take place as part of
the secondary survey. During the primary survey, careful attention should be paid to keeping the injured child warm.
The critical role of appropriate pain management has been recognized in pediatric trauma, and anesthesiologist
caring for injured children must have good working knowledge of appropriate drugs and techniques.
Fortunately most traumatic injuries in children are not severe and are often isolated to an extremity fracture
that requires urgent or emergent treatment. Supracondylar femur fractures represent 12% of femur fractures and
very common in children 1-4 yo, while distal arm fractures make up 20-30% of fractures requiring surgery. Boys
accounted for 61% of all fracture events, with a male:female ratio of 2:1 in childhood and 3:1 in adolescences. The
peak incidence of fractures occurs at 11-14yo with a seasonal peak in Summer months.(6) Mechanism of injury
include: trauma from automobile accidents, falls during play or sports and inflicted injuries. Most of these children
are healthy and have sustained an injury while in a playground or at school. Of note, they may have significant pain
and may require immediate surgery.
Preoperative preparation: While NPO time is important, it may be irrelevant as presence of the injury and pain
medications may reduce gastric emptying resulting in a high-risk for a full-stomach. Studies have shown that nearly
half of patients will have gastric aspirates greater than 40 ml/kg after 8 hours of NPO status following a traumatic
fracture.(7)
Induction and Maintenance of Anesthesia: Timing of the procedure depends on the vascular and neurologic status of
the limb. If no compromise, we still attempt to get these patients to the OR within 6 hours of presentation. While the
anesthetic is straight forward, if <8 hours an RSI technique is used to secure the airway secondary to concerns of a
“full stomach” while longer NPO times >8 hours may result in laryngeal mask airway placement; followed by a
combined general and regional technique. A combined general and regional anesthetic technique offers the
advantage of lower intraoperative general anesthetic requirements and the provision of postoperative analgesia, but
its use must be discussed with the surgeon before placement. For example, in the event of a fracture of the humerus,
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there is great risk of compartment syndrome and neurovascular compromise. Sensory testing postoperatively is
essential but may be difficult or impossible if a nerve block has been placed. In contrast, regional anesthesia may be
of great importance to the recovery after procedures in which the extremity will benefit from the vasodilatory
properties of the sympathectomy caused by the local anesthetic, or in an amputation in which preemptive analgesia
may diminish phantom pain. Ultimately, the use of a regional technique is full discussed with the surgeon and
deferred if they have concern.
Postoperative complications: If regional anesthesia would be of benefit, but the child is still at risk of compartment
syndrome, compartmental pressures should be measured frequently by the surgical team. Compartment syndrome,
even in the presence of a block, usually presents as breakthrough pain.(8) In all cases of regional block placement in
children, particular attention must be paid to adherence to dosing guidelines to avoid the risks of local anesthetic
toxicity. Conservative maximum allowable dosing is as follows: levobupivacaine of 2 to 2.5 mg/kg or ropivacaine
of 3 mg/kg. Test dosing with epinephrine (5 mcg/ml) in the local anesthetic solution may help the practitioner
recognize intravascular injection. While there is growing practice for doing regional techniques with emergent
fracture surgery in pediatric and adult patients, if an anesthesiologist does not perform pediatric regional techniques
often, then an emergent scenario should not be the time to attempt this approach. Typically post-operative opioids
and acetaminophen are adequate for pain control.
2) Airway foreign body: Airway foreign body (AFB) is a major source of morbidity and mortality in children under
5 yo, with a peak incidence at 2 yo. Though it was originally thought that death from AFB was rate if the child
reaches the hospital, recent studies suggest a hospital mortality rate of 3.4%.(9) Depending on the location of the
aspirated object removal can often be life-saving. A careful history may recall a remote history of choking that
appeared to resolve only to result in a later presentation with respiratory symptoms. There is usually a history of
cough or persistent wheezing, hoarseness and asymmetric lung exam. Very rarely there is stridor or significant
desaturation. Stable symptoms may suggest an immobile AFB; while a history of fluctuating symptoms such as
intermittent stridor or wheezing may be an indicator of a mobile AFB, which can be life-threatening. Of all the
presenting symptoms and signs, a choking episode has the highest sensitivity and specificity for an AFB. Organic
Preoperative evaluation: A plain film of the chest may be obtained by the emergency department doctor before
consultation of the otolaryngology service. This could reveal a foreign body (if radio-opaque) or may demonstrate
collapse of the lung or hyperinflation. Generally organic material like peanuts may not be seen in a plain film.
Historic information including the ingestion of organic material can usually be obtained and could give a clue to the
foreign body. Often these children are toddlers, they are fussy and can be very difficulty to console. Premedication is
not usually warranted. We have taken parents to the OR to prevent the child from getting upset at the time of
induction of anesthesia.
Induction and maintenance of anesthesia: There are multiple methods reported in the literature regarding the
anesthetic management of foreign body retrieval in children. The three techniques include inhaled induction with
spontaneous ventilation; TIVA using propofol and remifentanil with spontaneous ventilation; and using controlled
or manual jet ventilation. If possible, IV access is usually obtained in the ER. A smooth mask induction with
spontaneous ventilation with sevoflurane and oxygen is then performed. After securing the airway, the most
common approach is to allow for spontaneous ventilation since there is a potential for dislodging the foreign body
during retrieval. Factors associated with hypoxemia include younger patient, plant seed (organic) AFB, long surgical
duration, pneumonia and in some instances spontaneous ventilation.(10) A variety of ventilatory modes, especially
jet ventilation may have potentially benefit children but must be coordinated and prepared for with the surgeon –
since control of the airway during the procedure will be shared. While TIVA has been associated with longer breath
holding there is the association with adverse issues of longer duration of emergence and potential for laryngospasm.
Ultimately, maintenance can be achieved using either inhaled anesthetics or IV infusions.
Foreign Body removal: The AFB can be removed using several techniques. The common technique is to use a rigid
ventilating bronchoscope with a forceps to retrieve the foreign body. This technique has been shown to be 95-98%
successful. More recently, fiberoptic bronchoscopes have been used to retrieve the foreign body. The main problem
is when the foreign body is lost while in the process of retrieval especially if lodged in the main trachea. The most
important and potentially life-saving technique would be to advance the foreign body to one of the bronchi and
ventilate the child through the other lung. Children tend to desaturate rather rapidly and the situation could become
dangerous. It is important to prevent coughing and bucking, some anesthesiologists and/or surgeons use 1%
lidocaine spray for the cords before airway instrumentation.
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Postoperative complications: These include creation of smaller AFB in distal airways, pneumonia, laryngeal edema,
bronchospasm, hypoxic cardiac arrest, pneumothorax, pneumo-mediastinum, tracheal and bronchial laceration. It is
imperative that there is communication with the surgeon before and during the procedure. Since these patients are at
risk for sub-glottic edema treatment with dexamethasone (0.5-1.5 mg/kg) begins in the OR with continued treatment
may be desired by the surgeon for up to 3 days. If symptoms of stridor or issues of desaturation, prolonged periods
of PACU observation and/or admission for continued monitoring may be warranted. The outcome of the child is
based on proper communication as well as the superb skills of the surgeon and the anesthesiologist.
3) Acute Abdomen/Appendectomy: Acute appendicitis is the most common surgical condition of the abdomen,
with a 7% lifetime risk. While complications and death from appendicitis is rate (<1%) the rate of perforation in
young children (<4 yo) is 80-100% compared to 10-20% in older children and adults. Perforation is associated with
higher morbidity and mortality. The differences in perforation rates are most likely related to the lack of focal
symptoms in younger children. Symptoms in younger children are often irritability, nausea, vomiting and diffuse
abdominal pain. False appendectomy rates are between 5-25% in younger children and current diagnostic and
management practice are utilizing additional imaging modalities (like CT and MRI) to better assess likelihood of the
appendicitis and perforation.
Preoperative preparation: This has resulted in earlier courses of antibiotics and re-hydration therapy with a period
of observation if the possibility of rupture seems low. This creates a scenario of an urgent procedure in a more
stable patient, rather than an emergent procedure in an unstable patient.
Induction and maintenance of anesthesia: Usually anesthesia for appendectomy is straight forward utilizing a RSI
and general anesthesia. Laparoscopic approaches are more prevalent, though classic open incisions are performed at
the discretion and experience of the surgeon. Recent studies have demonstrated transversus abdominal plane (TAP)
blocks to reduce acute opioid needs, but may not alter overall need opioid requirements.(11)
Postoperative care: If no perforation or rupture and a laparoscopic procedure, patients are typically extubated,
undergo routine recovery and have pain management with ketorolac, acetaminophen and oral opioids. The addition
of patient controlled analgesia is usually required in those undergoing open procedures or with perforation and
peritonitis. Of note, patients with perforated appendix typically require a more involved perioperative fluid
resuscitation that extends into the post-operative period.
4) Acute Abdomen/Pyloric Stenosis: This is a fairly common emergency that can occur at most institutions. There
is an incidence of 1:500 in all live births with a propensity to occur in firstborn males. They are often healthy infants
who otherwise have a recurrent history of vomiting and often present to the emergency department with significant
dehydration. They often present with hypochloremic, hypokalemic metabolic alkalosis. However, there are studies
that also observed a hyperkalemic state in some infants.
Preoperative preparation: It is crucial that the infant is well hydrated. These infants are generally significantly
dehydrated with absent skin turgor and with a sunken fontanel. In addition, due to significant vomiting, it is
important to ensure that the child is also not hypoglycemic at the time of presentation. Adequate rehydration should
occur prior to the induction of anesthesia, since the surgery should be thought of as, “urgent but never emergent.”
Induction and maintenance of anesthesia: A RSI is generally planned with adequate pre-oxygenation since these
infants have a tendency to desaturate rapidly. The use of a small dose of hypnotic followed by a muscle relaxant
will allow for adequate placement of the endotracheal tube. Studies comparing succinylcholine versus a non-
depolarizing drug like rocuronium have shown the time to recovery may be slightly prolonged with the non-
depolarizing drug.(12) Like with the prior section on appendectomy, the surgical approach will dictate post-
operative pain requirements. If a laparoscopic procedure, careful attention has to be paid to the insufflation pressures
for the abdomen with can significantly reduce functional reserve capacity and venous return by collapsing the
inferior vena cava in an infant. Comparison of an open sub-umbilical approach has been compared to a laparoscopic
approach, with the laparoscopic technique being associated with a faster recovery and a shorter operating time.(12)
The maintenance anesthetic can be achieved with either inhaled anesthesia or a Total IV anesthetic (TIVA)
anesthetic. Studies of TIVA versus inhaled anesthetics demonstrate a more rapid return to baseline with ultra-short-
acting opioids like remifentanil.(12) Most recently the addition of a regional TAPS blocks for managing pain in the
postoperative period has demonstrated the acute reduction and potential elimination of opioid need for the surgery,
with potential benefits of further reducing post-operative apnea risks and monitoring needs in this infant group.
Emergence and postoperative care: Again with a focus on reducing post-operative respiratory issues, emergence
from surgery and extubation is typically performed in a fully awake patient. Maintaining an IV access is important
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for the infant to ensure adequate hydration and glucose delivery in the immediate postoperative period. These
children do very well and often have a rapid recovery to their normal state within hours of surgery.
5) Post-tonsillectomy Bleeding: Tonsillectomy is one of the most common pediatric surgical procedures. Post-
tonsillectomy bleeding is a serious complication. There are many factors that may lead to bleeding including poor
hemostasis, bleeding diathesis (including von Willebrand disease), infection, and foreign body irritation. Tonsillar
bleeding occurs in 2 phases, an early phase (within the first 24hours) that is associated with poor hemostasis or
bleeding issues, and a secondary bleed that occurs in the first week (between postoperative days 4 and 7), which is
associated with secondary infection. In the majority (66%) of children, bleeding occurs within the tonsillar bed, 27%
in the nasopharynx and 7% from both locations. In a large retrospective study, the incidence of post-tonsillectomy
bleeding was 2.15%. Therefore, the patient with bleeding tonsils may present as an inpatient or via the ER as an
outpatient. Major post-tonsillectomy bleeding may be sudden resulting in high-risk patient with hypovolaemic
shock and airway obstruction.(13) Rapid deterioration is possible, and the urgency to proceed to the OR must be
balanced with appropriate access and stabilization of the patient if eminent respiratory and/or hemodynamic collapse
can be avoided through aggressive volume and/or blood product resuscitation.
Preoperative preparation: Calculating the volume of blood loss may be difficult, as the child may have swallowed
significant amounts. Intravenous access should be secured and intravenous fluid resuscitation commenced.
Hemoglobin and blood cross-match should be sent along with coagulation profiles. Preparation for a potential
difficult intubation with adequate airway equipment and immediate surgical availability is essential. Checking
arterial blood pressures and pulse pressures may be useful to determine if they are compromised. In addition,
looking for skin turgor as well as checking for orthostatic hypotension especially in the older child may point to an
acute hypovolemic state. Blood should be sent for type and cross-match and if it is an emergency, and if the child
looks quite hypovolemic, it may be necessary to have blood available in the OR before induction of anesthesia.
Intraoperative management: There is a paucity of published papers on the anesthetic management of post-
tonsillectomy bleeding. Both intravenous and inhalational induction techniques have been described, with a RSI
being the most common approach.(14) A retrospective study of post-tonsillectomy bleeding found a difficult re-
intubation rate of 2.7%.
Induction of anesthesia: The child is likely to be anxious. Again, emphasis should be on the adequate hydration and
availability of fluid and/or blood products to continue hemodynamic resuscitation. Since the child is likely to also
have a full stomach as they potentially could have swallowed a large amount of blood from the oropharynx.
Attempts to keep the child with its face turned to the side may be helpful in keeping blood from being aspirated. A
RSI is usually planned with either propofol or ketamine (if the child is unstable) and succinylcholine or high dose
rocuronium. Typically a stylet and smaller sized, cuffed endotracheal tube is utilized in anticipation of potential
airway edema and clot. After securing the airway, the surgeon should be ready to look for active bleeders. In the
event there is no active bleeder that is visualized, there should be further investigations including a follow-up
coagulation profile including platelet count and hemoglobin. This may reveal a potential for an acquired or inherited
disorder of coagulation. Given the nature of the procedure, antiemetic therapy with 2 or more agents is typically
provided before extubation since these patients have a propensity to vomit after surgery.
Postoperative period: Given the dynamic and life-threatening nature of a routine outpatient procedure can change
turning into a surgical emergency, it is important to observe the patient for at least 6 hours post-procedure with
consideration for overnight observation.
Pedi-Crisis Checklist:
The application of perioperative checklists has greatly enhanced safety and efficacy of care in adult patients.
Recently data has grown to demonstrate enhanced outcomes for pediatric-based checklists to improve perioperative
handoffs, deep vein thrombosis-risk and reduced blood stream infections. Intraoperative checklists before initiation
of surgery have resulted in reduction of wrong-side surgery and improved team work in the OR environment.
Recent studies in adults have demonstrated checklists to improve crisis management – like intraoperative arrest.(15)
To improve the quality and content of pediatric care, a pediatric crisis checklist has been developed to improve
access to current clinical guidelines and assist in more effective pediatric emergency management in the OR by the
anesthesiologist. While studies of the pediatric crisis checklist in simulation and clinical management are underway,
the utilization of these checklists are growing and currently available via this link to the most up-to-date version.
http://www.pedsanesthesia.org/wp-content/uploads/2015/12/CriticalEventsChecklists_12142015.pdf
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Common Post-Anesthetic Emergencies:

Perioperative breathing problems are common in children, and we recommend a standard way to examine airway
and breathing, and ways to evaluate and treat a child with breathing problem. We listed the order or problems, from
the most common intraoperative issues to most common post-anesthetic issues. Frequent examination of the patient
to determine the cause of hypoxemia and respiratory distress is necessary and often may be dynamic, the
anesthesiologist to make repeated evaluations of the patient in order to refine therapy. (see Figure 2).
FIGURE 2: Algorithm for management of perioperative respiratory insufficiency
Laryngospasm, the involuntary contraction of the glottic muscles (vocal cords) leading to tight closure of the glottis,
happens quite often in pediatric anesthesia and can be a bad problem resulting in blockage of the airway, admission
to the hospital, need for a long time in PACU, and sometimes intubation and mechanical ventilation. If
laryngospasm is very bad, it can cause negative pressure pulmonary edema---fast onset of rales, respiratory distress,
and hypoxia.(16) Laryngospasm can happen any time during or after an anesthetic, the risk of laryngospasm is
highest immediately after tracheal extubation and may be increased by stimulation of the patient during emergence,
such as suctioning the airway. Laryngospasm happens more often in younger patients. Laryngospasm can also
happen in the OR or PACU, especially when the endotracheal tube was removed “deep” and who then emerge from
anesthesia in the PACU. The first treatment is continuous positive airway pressure (CPAP) via facemask with 100%
oxygen, which often is all that is needed. Some patients will require deepening of the anesthetic (like a bolus of
propofol or other induction agent) in addition to CPAP. The treatment that almost always treats laryngospasm is
neuromuscular blockade with a small dose of succinylcholine IV (0.1 mg/kg) or IM (0.3 mg/kg) to relax the vocal
cords. When the laryngospasm breaks, the anesthesiologist can support breathing with bag and mask ventilation, or
sometimes the patient’s trachea needs to be intubated.
Post-extubation stridor is a changing inspiratory upper airway obstruction that can occur in any age group, but
happens more often in pediatric patients due to anatomic differences of the airway. Because the subglottic region
(below the vocal cords) is the narrowest portion of the pediatric airway, an endotracheal tube that has been inserted
easily through the true vocal cords may still cause pressure resulting in edema and/or necrosis of the subglottic
mucosa. Also because the pediatric airway is smaller than the adult, when there is mucosal edema, even if mild,
then the airway obstruction can be severe. This is made worse a relative floppy upper airway and by increased
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negative intra-thoracic pressure; this leads to respiratory distress with inspiratory stridor. In its severe form, the
anesthetist can hear expiratory sounds as well; in patients with little to no ventilation (moving almost no air), many
times there is no stridor. The first treatment is inhaled vasoconstrictor (e.g. nebulized racemic epinephrine) to
decrease tissue edema. Giving racemic epinephrine (2.25%) 0.25mL in 3cc normal saline via high-flow
nebulization, and repeating up to 3 times with humidified oxygen in between treatments, is the first treatment.
Corticosteroids may also be administered for a longer-acting, anti-inflammatory effect. Those patients that receive
multiple racemic treatments and/or corticosteroids are often admitted to the hospital for observation. Dexamethasone
at a dose 0.5 mg/kg/dose IV every 6 hours for four to six doses (24-36 hours) often works well. Prophylactic steroid
treatment in patients with a history of stridor, croup or subglottic narrowing may be helpful. Treatment of every
small child should not be done. Rarely, patients may require re-intubation for significant obstruction. If re-
intubation is needed, a smaller endotracheal tube than the one placed for surgery should be used, and dexamethasone
treatment for 24 hours should be given. If stridor happens again, evaluation by an ear, nose, and throat surgeon by
bronchoscopy may be needed to examine the glottis and trachea for other abnormalities (such as arytenoid
dislocation or other trauma, tracheitis, or airway granuloma).
Bronchospasm, (wheezing) or reversible bronchiolar smooth muscle constriction leading to air-trapping, respiratory
distress, and the clinical sign of expiratory wheezing, is the main sign of asthma exacerbations. Bronchospasm is
most commonly seen in known asthmatics, but it can be seen in any patient after endotracheal intubation and/or
extubation through direct irritation of the airway. The first treatment for wheezing is inhaled beta-agonist therapy
(e.g. albuterol). However, anesthetic gases work very well to relax airway smooth muscle, and may be used (if blood
pressure is not to low) to treat severe wheezing in the OR. If the wheezing is not severe, inhalational bronchodilators
may be sufficient. The patient with moderate to severe bronchospasm may require more treatment, with
administration of steroids (like methylprednisolone 0.5 to 1 mg/kg/dose IV every 6 hours, max dose 80 mg/day) and
possibly subcutaneous epinephrine (10 micrograms/kg/dose subcutaneously, max dose 0.5 mg). If all these
treatments do not work, continuous infusions of adrenergic agents (e.g. terbutaline, epinephrine) are often used and
work most of the time.
Delayed Emergence and Emergence Failure- at the end of surgery, anesthetics are stopped and the patient emerges
(wakes up) from anesthesia as described above. While most of the events that happen are respiratory in nature,
sometimes even with a very good anesthetic, patients might not wake up quickly.(17) In this event, the
anesthesiologist should follow an algorithm to decide on the potential causes and treatments (see Figure 3).
FIGURE 3: Algorithm for management of delayed emergence
First steps are to be sure oxygenation, ventilation, and circulation are all normal. Check the pupils next--,if they are
of equal size, small to medium size, and react quickly to light, a serious brain problem is less likely. Assess a core
temperature (rectal or oral) again to be sure there is not hypothermia or severe hyperthermia. Next, too large a drug
dose, or leftover anesthetic effect should be checked. Look carefully at total doses of both intravenous drugs and
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anesthetic gases. Examination of pupils (see above) may help to decide if the patient received too much opioid like
morphine or fentanyl. If the pupils are very small (“pinpoint”) then they may have gotten a large dose. Reversal of
muscle relaxation should be checked with a twitch monitor. If no improvement, begin a check for derangements of
glucose, electrolyte, or other metabolic issue. A blood sample should be sent for glucose (exclude hypo or
hyperglycemia), arterial blood gas (hyper- or hypo-carbia), and electrolyte measurements (i.e. sodium, low
potassium, low calcium, high magnesium). Once in a while, severe anemia that is not realized may be seen as coma,
and so hemoglobin should be checked as well. The anesthesiologist should be aware that rare genetic diseases might
cause in metabolic crisis with mental status change or weakness (like periodic hypokalemic paralysis). This might
happen for the first time in the pediatric patient during a stressful event such as an anesthetic. If all of these tests do
not give a cause for delay in awakening, the patient should have a more thorough neurologic assessment including a
pediatric neurologist or neurosurgeon, if available. Independent of consultant availability, radiographic imaging to
look for stroke (i.e. computed tomographic (CT) scan or magnetic resonance imaging (MRI)) followed by ICU
admission or transfer to a tertiary care center with pediatric resources for ongoing evaluation and management.
Conclusions:
With proper preparation and resources the general anesthesiologist should be comfortable in managing common
pediatric emergencies. Clinical resources are available and can be incorporated into routine and emergent care to
make managing pediatric emergencies in the perioperative period safe and effective.
Disclosures:
No financial relationships with commercial interests
REFERENCES:
1. Rollin AM. Anaesthesia. 2006 Dec;61(12):1135-7.
2. ACHRQ report. Overview of Hospital Stays for Children in the United States, 2012. http://www.hcup-
us.ahrq.gov/reports/statbriefs/sb187-Hospital-Stays-Children-2012.pdf
3. Global and National Burden of Diseases and Injuries Among Children and Adolescents Between 1990 and 2013:
Findings From the Global Burden of Disease 2013 Study. AMA Pediatr. 2016 Mar 1;170(3):267-87.
4. Densmore JC, et al. J Pediatr Surg. 2006 Jan;41(1):92-8; discussion 92-8.
5. de Caen AR, et al. Circulation. 2015 Nov 3;132(18 Suppl 2):S526-42.
6. Joeris A, et al. BMC Pediatr. 2014 Dec 20;14:314.
7. Bricker SRW, et al. Anaesthesia 2007; 44:721–4.
8. Johnson DJG, Chalkiadis GA: Paediatr Anesth 2009; 19:83–91.
9. Fidkowski CW, et al. Anesth Analg 2010; 111:1016–25.
10. Chen LH, et al. Anesth Analg 2009; 109:1079–84.
11. Galante D, et al. Anaesth Pain & Intensive Care 2012; 16(2): 201-204.
12. Kamata M, Cartabuke RS, Tobias JD. Paediatr Anaesth. 2015 Dec;25(12):1193-206.
13. Collison PJ, Mettler B. Ear Nose and Throat Journal 2000; 79: 640–2.
14. Cohen D, Dor M. Journal of Laryngology and Otology 2008; 122: 88–92.
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15. Joseph A, et al. Pediatrics Jul 2009, 124 (2) 500-508.
16. von Ungern-Sternberg BS, et al. Anaesthesia. 2015 Apr;70(4):440-4.
17. Tzabazis A, et al. J Clin Anesth. 2015 Jun;27(4):353-60.
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Lipid Resuscitation for Local Anesthetic and Other Drug Overdoses

Guy Weinberg, MD Northbrook, IL
Introduction
Rosenblatt et al1 first reported the infusion of a 20% lipid emulsion (ILE) in successful treatment of severe local
anesthetic cardiac toxicity in 2006. This re-purposing of a total parenteral nutrition solution has subsequently been
widely adopted by the anesthesia community as an effective treatment for a potentially fatal complication of
regional anesthesia – one that had traditionally been viewed as exceptionally difficult to treat. A number of
professional societies in the US and abroad now include infusion of lipid emulsion in their recommendations for
treating local anesthetic toxicity and such solutions are routinely stocked for rapid access at anesthetizing locations
in hospitals and outpatient facilities. In 2007, Dr. Archie Sirianni2, an anesthesiologist working at a community
hospital, used ILE to save a patient with cardiovascular collapse related to a severe bupropion+lamotrigine overdose.
This index case brought ILE to the attention of emergency medicine physicians and toxicologists, leading quickly to
its use for treatment of many types of non-local anesthetic drug overdose and chemical poisonings. Now, a decade
after the report by Rosenblatt et al, is a good time to take stock of what we have learned about ILE, its mechanisms,
clinical use, controversies and future directions.
Mechanism
The formulation most commonly used in ILE is an emulsion of soy bean oil comprising mostly long chain fatty acid
triglyerides as small oil droplets (average diameter, 400nm) with negatively charged (~1.2%) emulsifying egg
phospholipids on the surface (z = -40mV). Glycerin (~2%) is added to make the solution isotonic and the pH is
approximately 8.0. Given the size of these particles one can consider ILE a form of nano-medicine, although the
goal instead of drug delivery is quenching adverse effects at targets of drug toxicity. Weinberg et al in reporting the
results of an early animal model of ILE posited several possible mechanisms for the benefit observed in treating
bupivacaine overdose: a partitioning effect, or ‘lipid sink’, based on bupivacaine’s high lipid solubility; preferential
shunting or redistribution; increased production of nitric oxide; and improved cardiac metabolism. Despite evidence
in support of other mechanisms and perhaps because of its simplicity, the sink concept gained favor and is often
cited as the chief mechanism of ILE. While it is easy to consider that the bulk lipid phase in blood could sponge
offending lipid soluble drug from target tissues, the evidence is clear that other mechanisms contribute and the sink
per se must be reconsidered or revised. In vitro experiments and post facto measurements from a rat model confirm
that bupivacaine substantially partitions into a lipid phase, experiments reported by Litinious et al 3 in human
volunteers given small doses of bupivacaine showed that ILE shortens the context-sensitive half-life of bupivacaine
but doesn’t alter the non-lipid bound plasma concentration – that is, no sink effect was observed at the time points
measured. Moreover, Kuo and Akpa4 used computational modeling to show that effects of a sink alone might not
suffice to explain the observed clinical efficacy of ILE in rapidly reversing local anesthetic toxicity. Meantime,
alternative explanations have appeared. Partownavid et al5 showed that inhibiting mitochondrial fatty acid oxidation
inhibited ILE-reversal of bupivacaine toxicity, suggesting that fatty acid metabolism likely contributes to local
anesthetic toxicity and that reversing such a block could underlie in part the efficacy of ILE. Results of Li et al6 from
the same laboratory confirmed earlier observations that ILE potently attenuates myocardial stunning following
ischemia-reperfusion. This occurred with activation of the RISK cytoprotective pathway, suggesting that ILE
stimulates biochemical signaling pathways that could contribute to reversal of drug toxicity. Fettiplace et al 7 showed
that ILE itself exerts both inotropic and lusitropic effects on cardiac function resulting in improved cardiac output
and performance. The same group later found that lipid infusion activates the same intracellular kinase cascade as
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insulin, suggesting a common mechanism for insulin and ILE-induced inotropy. They also showed in a
physiological study and confirmed by in silico modeling that reversal of bupivacaine toxicity in a rat model was best
explained by the combination of improved contractility and a partitioning effect. Subsequently, Shi et al8 reported in
a pharmacodynamic-pharmacokinetic study of rats that ILE increased clearance of bupivacaine, resulting in
pharmacokinetic effects reminiscent of those reported by Litinious et al3. Their most important finding is that ILE
reduced concentrations of bupivacaine in both heart and brain while increasing it initially in the liver. Fettiplace et
al9 showed in more fine-grained PK analysis that bupivacaine quickly partitions (<5 min) into the infused lipid and
is rapidly distributed from the blood to liver and skeletal muscle. This effect was most pronounced at high
bupivacaine blood concentrations suggesting it would be most effective if given early. Moreover, since inotropy
occurred only after cardiac bupivacaine concentrations declined below a threshold, high quality CPR in full cardiac
arrest will aid in ILE-based resuscitation by improving the coronary perfusion needed to remove bupivacaine. In
sum, a variety of mechanisms are involved in the observed benefit of ILE, including intracellular (signaling,
inotropy, cytoprotection10,11) and intravascular (pharmacokinetic) effects. The later can be described as ILE reducing
toxicity by shuttling drug from target tissues to receiver organs (e.g. liver, muscle). Further refinement of our
understanding of these mechanisms will lead to optimized regimes for using ILE in treating a variety of drug
overdoses. This is important since it is likely that different types of toxic exposure (eg parenteral versus oral
ingestion) will require different ILE administration strategies.
LAST
Initial case reports of ILE treatment of severe cardiac local anesthetic toxicity seemed to recapitulate the laboratory
experience: combining good CPR with ILE leads to very rapid recovery of heart rate and blood pressure and
normalization of rhythm. Moreover, neurologic signs of local anesthetic toxicity are also reported to abate with ILE;
this appears to apply to prodromal symptoms and altered mental status as well as seizure activity. The ASRA,
AAGBI and AHA recommendations for treating local anesthetic systemic toxicity provide specific
recommendations for administering ILE which is typically given as a large bolus (~100mL for an adult) followed by
a continuous infusion (~0.25mL/kg/min lean body mass; max dose, 12mL/kg) usually given several minutes past a
full recovery. These will be revised in the future to improve both efficacy and safety of ILE. Potential recurrence of
toxicity requires us to monitor the patient for some time after and event and to keep materials for ILE at the ready.
Early comparisons of ILE with standard ACLS drugs in treating rat models of bupivacaine overdose showed that
ILE was superior to epinephrine alone or in combination with vasopressin. ILE-treated animals had better
hemodynamic and metabolic parameters (pH, lactate and pO2) than animals given the pressors. It is important to
note that rats challenged with bupivacaine and treated with vasopressin alone did very poorly from the standpoint of
both hemodynamic and metabolic recovery. It was also reported in the same model that epinephrine when given
above a threshold dose of 10mcg/kg epinephrine impaired the efficacy of ILE in treatment of bupivacaine overdose
while lower doses of epinephrine accelerated recovery. Given the normal human dose (1mg) is ~15mcg/kg, this
suggests that much lower-than-usual doses of epinephrine might be more effective than the usual 1mg in treating
cardiac arrest secondary to LAST. Li et al showed in a rat model that adding epinephrine to ILE improved coronary
perfusion pressure but unlike ILE alone did not reduce cardiac bupivacaine concentrations. Moreover, they
confirmed that adding epinephrine to ILE worsened pO2 and pH. These findings comport with mounting evidence
that the standard (~1mg) dose of epinephrine does not contribute to improved survival in non-local anesthetic
cardiac arrest and suggest that lower-than-usual doses of epinephrine might improve recovery in both local
anesthetic and other causes of cardiac arrest compared to the standard dose. These findings inform the current
recommendations for treating local anesthetic toxicity that vasopressin not be used and that epinephrine bolus doses
should be reduced (e.g. ~ 1mcg/kg) especially when given with ILE.
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The approach to deciding when to use ILE in treating local anesthetic toxicity has evolved over the past several
years. The earliest recommendations were to use ILE only as a last resort. However, observations suggesting that
ILE might slow or prevent progression to cardiac toxicity lead to earlier use following symptoms of toxicity. This
and the difficulty predicting progression to cardiovascular compromise provide the rationale for early administration
of lipid. It is worth noting that some patients appearing to have fully recovered from local anesthetic-induced
seizures go on minutes later to full cardiac arrest. It seems reasonable to call for the materials necessary for ILE as
soon as the diagnosis of local anesthetic toxicity is considered, then decide whether to treat based on the patient’s
clinical picture and physician judgement. This decision should also factor in the potential for adverse effects of ILE
which are discussed below. While there are no commonly encountered scenarios where ILE should be given before
regional anesthesia, it is interesting to consider an accidental Bier block with bupivacaine as one situation where
‘pre-treatment’ makes sense – that is, ILE could be given before (incrementally) deflating the cuff.
Non-LAST Overdose
Sirianni et al reported a very dramatic save using ILE after more than an hour of CPR using standard ACLS
guidelines had proven unsuccessful in treating an adolescent with combined bupropion+lamotrigine overdose.
Emergency physicians and toxicologists have subsequently adopted this approach to treat a variety of lipophilic drug
overdoses and chemical exposures including calcium channel blockers, beta blockers, tricyclic and atypical
antidepressants, anti-psychotics, an anti-helminth, anti-arrhythmics and herbicides. The key difference compared to
treating local anesthetic (parenteral) toxicity is that most drug overdoses are oral ingestions (enteral toxicity) so that
blood levels are therefore far less predictable and drugs linger in the GI tract so that toxic levels are likely to persist
over long (and sometimes very long) timeframes. Thus, optimizing the timing and dose of ILE treatment becomes
very challenging. Most emergency physicians use the standard treatment regimen for LAST while recognizing the
lipid dosing limits (~12mL/kg lean body mass) but some reports indicate much larger doses are being infused (>3L
over 2 hours; see below). This approach cannot be condoned since it runs a risk of the patient developing fat
overload syndrome if the infusion continues for long periods of time, as might be seen when the patient has a
positive response to lipid and physicians are reticent about stopping it. One possible approach was outlined by
Fettiplace et al12; they used computer simulation to establish a regimen that allowed rapid attainment of ~1%
triglyceride blood (1000mg/L) levels while infusing for a prolonged period of time (up to ~6 hours): 1.5mL/kg bolus
followed by infusion at 0.25mL/kg/min for 3 minutes then reducing the infusion to 0.025mL/kg/min. Moreover,
there is the theoretical concern that lipid infusion could increase absorption of drug residing in the gut and thereby
accelerate early toxicity. There is no clinical evidence for this phenomenon and a recent series of cases reported to a
registry suggest this is not a common problem. This study indicated improvement in blood pressure and Glasgow
coma scale after ILE use for a variety of intoxications and survival in 5 of 8 patients with cardiovascular collapse
secondary to non-local anesthetic xenobiotic overdose who were treated with ILE. Notably, there was no control
group; however, the results are better than expected for patients in cardiovascular collapse. Nevertheless, given that
accidental and intentional drug overdose result in tens of thousands of fatalities annually in the US (nb: the scope of
the problem worldwide, particularly suicide by organophosphate ingestion in the third world, is absolutely
staggering) it is clear that much work needs to be done in optimizing treatment for oral ingestion. The key issues are:
when and how fast to deliver ILE, for how long and what is an acceptable dosing limit.
Controversies and Caveats
The most commonly used formulation for ILE (20% Intralipid) has a very favorable safety record in its fifty years of
clinical use as TPN. While the rate of infusion as a rescue agent is more rapid than for TPN, there is little indication
of consistent, clinically problematic adverse drug reactions for ILE in overdose, when the total dose is less than the
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accepted limit of 12mL/kig. Furthermore, when the patient has received large doses of pressors (which also cause
pulmonary and metabolic dysfunction) and may have low output state and, by definition, toxicity from the offending
drug, there are generally too many confounders to confidently ascribe any particular complication specifically to
ILE.
The most common anticipated effect is lipemia, which can potentially interfere with laboratory studies; this effect
can be circumvented by spinning the blood samples before chemical analysis. Chemical pancreatitis has also been
reported following ILE but these cases lacked confirmatory imaging studies; moreover, these chemical
abnormalities are not specific given that lipase assays often measure release of glycerol which is expected to
increase with triglyceride infusion. Pulmonary fat overload has been reported in neonates receiving large doses of
TPN so it is clear that volume and fat mass delivery have upper limits. Nevertheless, the LD50 for 20% Intralipid
delivered to rats over 30 minutes is ~67mL/kg, which exceeds the typical volume used in treating local anesthetic
toxicity (~4mL/kg) even accounting for allometric scaling. However, as noted above, the volume delivered in
treating oral ingestion can be much larger given that the infusion is likely to continue for extended periods of time.
Given that potential complications of ILE are related to the total volume of lipid administered, it is important to be
mindful of the dosing limit (12mL/kg) and that if you start a lipid infusion, remember to turn it off!
Models for studying ILE are context sensitive insofar as parenteral and enteral toxicity differ clinically and their
models aren’t mutually applicable; one doesn’t apply to the other. There is further controversy over the best animal
for studying ILE. While porcine models are often used for studying CPR and ischemic arrest because of the
anatomic and metabolic similarities with human cardiovascular physiology, pigs are sensitive to liposome infusions
including lipid emulsion. Bedocs et al13 showed that standard ILE infusion induces the generalized cutaneous
mottling and discoloration previously reported by others and as well as significant pulmonary hypertension. This
systemic sensitivity should disqualify pigs as a useful model for ILE.
Future Challenge
The pharmacokinetic mechanism for ILE-based rapid reversal of LA-induced cardiovascular toxicity is now
reasonably well-established. This understanding will help inform optimized treatment of severe LAST – a
potentially catastrophic event. However, the same cannot be said yet for treatment of enteral intoxications, a public
health hazard of much greater proportions. Determining what specific drug intoxications are most susceptible to ILE
reversal and identifying the best treatment regimes in terms of timing, dose and duration are the greatest challenges
for the future clinical application of ILE in treating drug overdose.
References
1. Rosenblatt MA, Abel M, Fischer GW, Itzkovich CJ, Eisenkraft JB: Successful Use of a 20% Lipid
Emulsion to Resuscitate a Patient after a Presumed Bupivacaine-related Cardiac Arrest. Anesthesiology 2006; 105:
217-218
2. Sirianni AJ, Osterhoudt KC, Calello DP, Muller AA, Waterhouse MR, Goodkin MB, Weinberg GL,
Henretig FM: Use of lipid emulsion in the resuscitation of a patient with prolonged cardiovascular collapse after
overdose of bupropion and lamotrigine. Ann Emerg Med 2008; 51: 412-15
3. Litonius E, Tarkkila P, Neuvonen PJ, Rosenberg PH: Effect of intravenous lipid emulsion on bupivacaine
plasma concentration in humans. Anaesthesia 2012; 67: 600-5
4. Kuo I, Akpa BS: Validity of the lipid sink as a mechanism for the reversal of local anesthetic systemic
toxicity: a physiologically based pharmacokinetic model study. Anesthesiology 2013; 118: 1350-61
5. Partownavid P, Sharma S, Li J, Umar S, Rahman S, Eghbali M: Involvement of Opioid Receptors in the
Lipid Rescue of Bupivacaine-Induced Cardiotoxicity. Anesth Analg 2015; 121: 340-7
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6. Li J, Iorga A, Sharma S, Youn JY, Partow-Navid R, Umar S, Cai H, Rahman S, Eghbali M: Intralipid, a
clinically safe compound, protects the heart against ischemia-reperfusion injury more efficiently than cyclosporine-
A. Anesthesiology 2012; 117: 836-46
7. Fettiplace MR, Ripper R, Lis K, Lin B, Lang J, Zider B, Wang J, Rubinstein I, Weinberg G: Rapid
cardiotonic effects of lipid emulsion infusion*. Crit Care Med 2013; 41: e156-62
8. Shi K, Xia Y, Wang Q, Wu Y, Dong X, Chen C, Tang W, Zhang Y, Luo M, Wang X, Papadimos TJ, Xu
X: The effect of lipid emulsion on pharmacokinetics and tissue distribution of bupivacaine in rats. Anesth Analg
2013; 116: 804-9
9. Fettiplace MR, Lis K, Ripper R, Kowal K, Pichurko A, Vitello D, Rubinstein I, Schwartz D, Akpa BS,
Weinberg G: Multi-modal contributions to detoxification of acute pharmacotoxicity by a triglyceride micro-
emulsion. J Control Release 2015; 198: 62-70
10. Li J, Fettiplace M, Chen SJ, Steinhorn B, Shao Z, Zhu X, Li C, Harty S, Weinberg G, Vanden Hoek TL:
Lipid emulsion rapidly restores contractility in stunned mouse cardiomyocytes: a comparison with therapeutic
hypothermia. Crit Care Med 2014; 42: e734-40
11. Rahman S, Li J, Bopassa JC, Umar S, Iorga A, Partownavid P, Eghbali M: Phosphorylation of GSK-3beta
mediates intralipid-induced cardioprotection against ischemia/reperfusion injury. Anesthesiology 2011; 115: 242-53
12. Fettiplace MR, Akpa BS, Rubinstein I, Weinberg G: Confusion About Infusion: Rational Volume Limits
for Intravenous Lipid Emulsion During Treatment of Oral Overdoses. Ann Emerg Med 2015
13. Bedocs P, Capacchione J, Potts L, Chugani R, Weiszhar Z, Szebeni J, Buckenmaier CC: Hypersensitivity
reactions to intravenous lipid emulsion in swine: relevance for lipid resuscitation studies. Anesth Analg 2014; 119:
1094-101
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Pain Outcomes and Learning Health Systems: Delivery of

Best Pain Care at Lower Cost
Sean Mackey MD, PhD Palo Alto, CA
INTRODUCTION
Pain is a subjective experience; therefore, unlike many other chronic diseases, there is no single objective
measurement to best characterize the extent of the problem or to evaluate treatment outcomes. Measuring a patient’s
pain means putting together objective data with the patient’s subjective reports to create a comprehensive view of
the pain state. Complicating the measurement of pain is the fact that there is often a wide variability in how much
pain a given stimulus or injury will cause. This variability is influenced by genetics, mood, beliefs, early life
experiences with pain, gender, ethnicity, and other factors1.
Chronic pain is often associated with an overall reduction in the patient’s quality of life and may cause
depression, anxiety, impaired social and physical function, and sleep disturbance. Therefore, to best capture the pain
experience and its impact, it is necessary to also define and characterize these related domains.
Why is it important to measure pain in a standardized and accurate way? Evidence-based medicine relies on
testing treatments, and uses the outcomes of those tests to support clinical decision-making. The outcomes are also
used to convince colleagues, patients, and payers of the most efficacious treatments. Standardization of outcome
reporting will allow for comparison of treatments, and the systematic review of the studies that already exist to help
answer the most pressing questions in the field of pain.
CONSIDERATIONS IN SELECTING AN OUTCOME MEASURE

Any tool used to measure pain should be appropriate for the clinician and patient needs. It is of little use,
for example, to have a patient fill out multiple forms if the provider lacks the staff or infrastructure to utilize the
data. In defining a standard set of outcome measures, the Initiative on Methods, Measurement, and Pain Assessment
in Clinical Trials (IMMPACT) consortium granted most weight to the following criteria2:
A) Reliability—The instrument should demonstrate test-retest, inter-rater and internal reliability.

B) Validity—The scale should measure what it is intended to measure.
C) Responsiveness—The scale must display the ability to detect changes over time and to distinguish between
treatments.
D) Appropriateness—The scale’s content should be in keeping with the measured outcome and relevant to the
patient population being studied.
E) Burden—The scale should be easy to administer, complete, and score.
UNIVARIABLE MEASURES
Unidimensional scales measure pain as a single quality varying only in intensity. These methods are most
effectively used in clinics and acute settings. Examples include:
Verbal Rating Scale

The Verbal Rating Scale (VRS) consists of a series of categorical descriptors ordered in increasing intensity
(i.e., none, mild, moderate, severe). The advantages of the VRS are that it is easy to administer and report,
particularly for elderly patients3. Disadvantages are that it has fewer response choices and the categorical options
limit statistical analysis. It has demonstrated ability to distinguish treatment effect, test-retest reliability, and
convergent validity4.
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Visual Analog Scale

The Visual Analog Scale (VAS) is typically a 10-cm line anchored with “no pain” at one end and “worst
pain” at the other. The patient marks a point on the line, and the clinician measures the length of the line on a 101-
point scale5. The advantages of the VAS are that there is good evidence for responsiveness, validity, and test-retest
reliability, and scores can be treated as ratio data6. The limitations are that it can be time-consuming, and elderly
people may have difficulty using the scale 7.
Numerical Rating Scale

The Numerical Rating Scale (NRS) is the most frequently used univariable instrument. It consists of a
rating scale from 0 to 10 (or 0 to 100 in some versions). Patients may respond verbally or by circling the appropriate
number. It demonstrates sensitivity to change and test-retest reliability, and correlates well with other measures of
pain intensity8. The NRS is recommended by IMMPACT as a core domain measure for future chronic pain clinical
trials9.
Patient Global Impression of Change

The Patient Global Impression of Change (PGIC) represents an attempt to capture pain improvement more
broadly using a single item measure. The patient is asked to rate their current status compared to a prior time point
(e.g. very much improved). This scale is applicable to many conditions and treatments but lacks sensitivity 10. It is
recommended by IMMPACT as a core domain measure and can be particularly helpful in gauging the clinical
importance of changes11.
EMOTION MEASURES
Clearly, there is a relationship between pain and emotional distress; there is also evidence of relative
independence. Measurements of depression include the Patient-Reported Outcomes Measurement Information
System (PROMIS) Emotional Distress – Depression Item Bank12. Beck Depression Inventory (BDI) 13, Zung Self-
Rating Depression Scale14, and Hamilton Rating Scale for Depression15. Anxiety and fear measures include the
PROMIS Emotional Distress–Anxiety Item Bank16, Pain Anxiety Symptoms Scale17, State-Trait Anxiety
Inventory18, and Fear-Avoidance Beliefs Questionnaire (FABQ) 19.
MULTIDIMENSIONAL MEASURES
Chronic pain requires a more comprehensive assessment than a univariable or single-domain measure can
provide. Multidimensional measures often combine several dimensions of pain, disability, emotional affect, and
effect on quality of life into a single instrument. Commonly used scales include:
Brief Pain Inventory

The Brief Pain Inventory (BPI) was developed to measure both the intensity of pain and the interference it
has in the patient’s life20. The BPI consists of a 17-item scale that typically takes under 15 minutes to complete. The
BPI Interference Scale, in particular, has been validated as a measure of physical functioning in multiple domains
and is recommended by IMMPACT as a core health related quality of life measure21.
McGill Pain Questionnaire

The McGill Pain Questionnaire (MPQ) was developed to specify the qualities of pain22. Pain is scaled in
three dimensions (sensory, affective, and evaluative) with 20 sets of words for each dimension. A four-point scale
accompanies each word, and for each term, users chose where on that scale they fall. Multiple studies have
supported the reliability and validity of the MPQ for specific pain syndromes23. The Short-Form McGill Pain
Questionnaire (SF-MPQ) was developed for research purposes and consists of 15 words from the sensory and
affective categories, with a four-point rating scale for each. It results in a pain intensity VAS score and overall
assessment of pain VRS score24.
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West Haven-Yale Multidimensional Pain Inventory

The West Haven-Yale Multidimensional Pain Inventory (WHYMPI) best assesses adaptation to chronic
pain25. It can yield clinically useful information regarding pain coping styles. It is composed of 52 items with 12
subscales. Patients respond to the questions on a seven-point scale. The WHYMPI interference scale correlates with
physical functioning and is recommended by IMMPACT as an alternative to the BPI26.
Medical Outcome Study 36-Item Short-Form Health Survey and Treatment Outcomes of Pain Survey
The 36-Item Short-Form Health Survey (SF-36) is a frequently used measure of function and quality of
life27. It consists of eight subscales, and while widely used, it features only two questions related to pain and there
are concerns about insensitivity to change when measuring an individual patient.
The Treatment Outcomes of Pain Survey (TOPS) is an extension of the SF-36 specifically designed for
patients with chronic pain28, 29. It consists of 120 items with a 61-item follow-up. It has been found to be sensitive to
change and have good validity.
OBJECTIVE MEASURES
Several physiologic variables have been suggested as surrogates for pain, including autonomic activity30, 31
or biomarkers of pain intensity32. Caution with interpreting these peripheral measures is urged, as they can be
influenced by arousal other than pain and can be modulated by medications. Physical function tests, such as range of
motion and strength, have also been used as proxies for pain33, 34, 35; however, these only modestly predict self-
reported pain scores. More recently, attempts to objectively measure pain have focused on using neuroimaging.
Indeed, recent studies suggest that brain imaging can be used to objectively distinguish evoked painful stimuli36 and
the presence of chronic low back pain37. Despite these promising early reports, there is still much research to be
done to validate its use. Furthermore, given the expense and time involved, it is more likely that neuroimaging will
primarily be used to help guide further research and understanding of the brain mechanisms involved in pain. All of
these data reinforce the complexity of pain and as such, it is unlikely that an objective measure for pain will soon
emerge.
CLINICAL TRIALS AND OUTCOMES DATA

The need to document data that will guide and justify appropriate pain treatments has resulted in efforts to define
and standardize outcome measures for pain and similar, related disease states. IMMPACT defined six core outcome
domains that should be considered when designing clinical trials38. IMMPACT went on to define specific validated
measures for each of the core outcome domains in IMMPACT-II39.
LEARNING HEALTH SYSTEMS AND PRECISION PAIN MEDICINE

Despite an increase in the number of available pain therapies, more than 100 million people in the U.S. still live with
pain. Little is known about which treatments are best for which patient, or even about the efficacy and safety of
various treatments over time. In recognizing this problem, the IOM Pain Report called for “greater development and
use of patient outcome registries that can support point-of-care treatment decision making, as well as for aggregation
of large numbers of patients to enable assessment of the safety and effectiveness of therapies.” Coinciding with this
call for patient registries is the recognition that Learning Health Systems (LHSs) are an important aspect of the
future of medicine40. The core features of LHSs combine science, informatics, incentives and culture that are then
aligned for continuous improvement and innovation. The Institute of Medicine recently extolled the virtues of
LHSs41, and in 2013 the National Science Foundation convened a workshop where it was declared that LHSs can
rapidly inform decisions that have transformative effects on improving health 42.
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The Collaborative Health Outcomes

Information Registry (CHOIR; Open Source Public-Private Partnership
http://CHOIR.stanford.edu) is one LHS developed to Learning Health System Network using
collect information on pain patients and the Collaborative Health Outcomes Information
effectiveness of therapies. The military has also
developed a system to address this need, called Pain Registry (CHOIR)
Assessment Screening Tool and Outcomes Registry Networked Learning Health Systems
(PASTOR) 43. The rest of this discussion will use
CHOIR as a model platform. CHOIR is an open
source, open standard, free, secure, electronic, LHS
designed to capture detailed, longitudinal patient-
reported outcomes data on physical, psychological,
and social health. CHOIR was developed to: inform
Best Practices
point-of-care decision making, provide software- Population Health Knowledge Base
based decision making, and act as a platform for (1) Care Coordination
comparative effectiveness research, (2) longitudinal
outcomes research, and (3) practice-based evidence
trials. Population Patient Experience
CHOIR also integrates NIH Patient Reported Management Network
Outcomes Measurement Information System
(PROMIS) measures to efficiently and rapidly capture
15-20 domains of physical, psychological and social
functioning. The role that psychological and social Outcomes Tracking
Decision Support
factors play in the incidence, magnitude, and
persistence of pain, as well as the associated costs of
care, have increasing come to light. At the same time,
there has been a demand to measure and monitor Across Patients Encounter Across Encounters
psychological and social factors in order to better
manage these complex diseases. An additional strength of PROMIS measures is that they allow comparisons of
individual patients against national population norms44, 45.
CHOIR was developed to allow for low-cost, large, prospective, observational studies on thousands of
patients in a “real-world” clinic setting. In addition to the broad research utility of CHOIR, the system provides
computer-assisted documentation, which has proven indispensable and invaluable in delivering comprehensive,
targeted interdisciplinary pain treatment. The platform is designed to be customizable to different settings (inpatient
and ambulatory), providers, and disease conditions. CHOIR provides rapid real-time, longitudinal feedback to
clinicians regarding standardized quantitative outcomes to guide decision-making regarding various treatments.
Standardized data capture can be included as part of ongoing, routine management. CHOIR, and other LHSs, have
the potential to address many fundamental questions regarding pain treatment and efficacy, and will allow for
further characterization of optimal patients for specific therapies46, 47. Testing of CHOIR has shown that it reduces
patient response burden by as much as 75% as compared to using traditional measures. This reduced burden, in turn,
has been shown to facilitate continued patient participation.
While evidence-based medicine is the standard for supporting clinical-decision making, the paucity of
prospective, placebo-controlled randomized trials in pain medicine has generated an urgent need to accurately and
consistently measure relevant patient outcomes with the goal of defining the most safe and effective treatments.
There is also a need to standardize the assessment and reporting of outcomes to allow for comparison across studies
and different patient populations. In addition to prospective, placebo-controlled randomized trials, which can be
difficult to generalize due to participant homogeneity, and require a large amount of resources (due to sample size),
systematic practice-based evidence may provide more useful data in the form of prospective, observational, cohort
studies48.
President Obama has recently called for a Precision Medicine Initiative. Precision medicine is an emerging
approach for disease treatment and prevention that takes into account individual variability in genes, environment,
and lifestyle for each person. While President Obama has called for a near-term focus of precision medicine to be
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cancers, the long-term aim is to apply this knowledge to the whole range of health and disease – including pain
management49. This effort will require a further advances in molecular biology, ’omics (e.g. genomics,
metabolomics, proteomics), and bioinformatics. LHSs will play a significant role in integrating this systems-based
information in order to derive accurate prevention and treatment recommendations. These LHSs and precision pain
medicine are within our grasp. Successful implementation will ultimately realize the call by the IOM Relieving Pain
in America Report to provide everyone with the best pain assessment, prevention and treatment.
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Human Factors in the Cardiac Operating Room

James H. Abernathy, MD, MPH Charleston, SC
Communication and Teamwork in the Cardiac Operating Room

Nancy A. Nussmeier, MD, FAHA Boston, MA
Learning Objectives:
As a result of completing this activity, the participant will be able to
1) Describe the current state and limitations of safety science as it relates to communication, culture and the
environment;
2) Incorporate current safety principles into their practice;
3) Differentiate latent errors in a care delivery system from adverse patient events.
Author Disclosure Information:

Dr. Abernathy has disclosed that he receives research funding from Pharmedium.
INTRODUCTION - The cardiac operating room (OR) is a complex environment consisting of four teams of
providers—surgeons, nurses, perfusionists, and anesthesiologists—and where a myriad of technical equipment is
often crammed into a space that might not have been designed for this purpose. Despite the obstacles, mortality and
morbidity from cardiac surgery have steadily decreased over the past decade.1 Inevitably, however, humans continue
to make errors.
Gawande found that adverse events occurred in 12% of cardiac surgical operations, compared with only 3%
in a general surgery population. A recent estimate ranks human error as the third leading cause of death in the united
states.2 Some 28,000 of the 350,000 cardiac surgical patients in the United States each year will have an adverse,
preventable event.3,4
For an outstanding review of patient safety in cardiac surgery, please refer to the recently published Scientific
Statement on the subject from the American Heart Association.5 What follows is a simplified summary of the full
document.
ERROR MODELS - Preventable errors are not related to failure of technical skill, training, or knowledge, but
represent cognitive, system, or teamwork failures.6 Jim Reason, the renowned human factors engineer, was the first
to propose a simplified model of error, now referred to as the “Swiss cheese” model (Figure 1):
Figure 1. James Reason’s ‘‘Swiss cheese’’ model of error, representing the errors committed when a patient
suffered a venous air embolism. From Reason J, Human Error. New York, NY: Cambridge University Press; 1990
This model eloquently describes how hidden, or in human factors terminology - latent, errors can line up to create
actual errors or patient harm. In one example, originally outlined by Peter Pronovost,7 a patient suffered from a
venous air embolism not because a doctor was careless, but because there were many hidden failures that added up
to create a catastrophe. In this example, components of latent error included poor communication, lack of protocols
or lack of knowledge of protocols, inadequate training, and fear of retribution if a team member spoke up. Resilient
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systems are designed to reduce the number of latent errors. If there are fewer latent errors, the holes in the Swiss
cheese are harder to align to allow an error to “pas through”.
The Systems Engineering Initiative for Patient Safety (SEIPS) model,8 now in generation 2.0, describes the
healthcare delivery system and its complex interactions (Figure 2):
Figure 2. The Systems Engineering Initiative for Patient Safety (SEIPS) model. From Holden RJ, Carayon P, Gurses AP, et al.:
SEIPS 2.0: a human factors framework for studying and improving the work of healthcare professionals and patients.
Ergonomics 2013; 56:1669–86.6 Reprinted by permission of the publisher (Taylor & Francis Ltd, http://www.tandfonline.com).
The work system comprises the tools and technologies we use, the tasks we complete, the physical
environment in which we work, the organizational structure, and finally the people—patients and healthcare
workers. The interactions of these complex parts, both with each other and with themselves, define the work system,
which defines a care process. Finally, the care process defines and determines the outcomes.
Poor equipment, poor organizational structure, and ill-defined, poorly executed tasks will lead to poor
processes and adverse patient outcomes. Summarized nicely by Holden, “According to the work system model, a
person (who can be a caregiver or the patient) performs a range of tasks using various tools and technologies. The
performance of these tasks occurs within a certain physical environment and under specific organizational
conditions.”7 In other words, all systems are perfectly designed to achieve the results they get.
COMMUNICATION - Communication failures are common and have been implicated as a cause of error and
adverse outcomes in both general and cardiac surgery.9,10 These occur primarily between caregivers, accounting for
87% of the system failures that led to an out-of-court malpractice settlement. Communication failures Breakdowns
in teamwork result in surgical disruptions, and consequent technical failures and adverse patient outcomes.11,12 Even
minor events, those that are easy to recover from and are seemingly trivial, reduce the team’s ability to recover from
major events. In one study, the more minor events that happened, the longer the operation and the more the
providers’ performance suffered.13 In short, the little things matter a lot.
Another comprehensive observational study of the hazards in the cardiac operating room was the Locating
Errors through Networked Surveillance (LENS) group as part of the FOCUS project (Flawless Operative Cardiac
Unified Systems).14,15 FOCUS was a collaborative study involving the Society of Cardiovascular Anesthesiologists
(SCA) and the Johns Hopkins Armstrong Institute. The study included observations of 20 cardiac operations by a
team of trained observers, including human factors engineers, anesthesiologists, and organizational psychologists.15
The analysis identified multiple hazards in the cardiac operating room. Details regarding the complex interaction of
organizational structure (lack of policies), teamwork behaviors (poor communication), system shortcomings
(inadequate support requiring multiple work-arounds), equipment and technologies (poorly designed and integrated),
and individual failings (situational awareness) were documented.15-19 The complexity of interactions between
system, provider, and processes point to the fact that a simple solution to patient safety is not feasible. Experts from
a variety of disciplines will be required to examine every aspect of the perioperative cardiac surgical care and
integrate proposed solutions.20-22
Research in aviation and the military has demonstrated that team training can facilitate improved coordination
and enhanced performance. Tools that teach teams how to perform and communicate better show promise. A trial of
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an evidence-based, government-sponsored program called Team Strategies and Tools to Enhance Performance and
Patient Safety (Team STEPPS) has been conducted in the Veterans Administration system with success. 23 However,
the results of increased teamwork and a reduction in errors were difficult to sustain and were lost within 12 months.
The frequency of retraining required to sustain improvements in team performance is not known. It is vital to realize
that teams should be trained as teams, not as individuals; that use of simulated scenarios is effective; that both
executive leadership and nurse managers are critical to effective implementation; and that repetition, continued
coaching, or both are required to strengthen and maintain benefits. 5
Today, the integration of and improvements realized with the checklist is no secret to all of us practicing
medicine. The World Health Organization’s Surgical Safety Checklist combined with JACHO’s timeout process has
been shown to decrease surgical error and reduce mortality when used appropriately. 24 Experts argue that it is the
adaptive work of the team, rather than the technology of a checklist, that generates improvements in patient safety. 25
Nonetheless, in the Netherlands, where checklist compliance was mandated, overall mortality decreased from 3.13%
to 2.85%.26
Arguably the most important part of the checklist process that is underutilized but most important to
improving communication is the preoperative briefing and the postoperative debriefing. Used often and consistently,
they have been shown to reduce surgical error and reduce distractions. Thankfully, the simple act of conducting
briefings has been shown to increase teamwork behavior and team performance. 27,28 The debriefing allows members
of the medical team to assess what went well and what did not, to coalesce as a team, and to improve their
performance in their next case.29 Debriefings provide teams the opportunity to formulate future plans, develop and
implement system improvements, and address areas of communication weakness. 30,31
Structured communication between two or more teams of people is an effective method to reduce errors,
especially in stressful environments. Techniques such as using words for letters (Alpha, Bravo, Charlie) or saying
the individual digits of a number can reduce ambiguity, enhance clarity, and specify the intended recipient.
Structured communication between the perfusionist and surgeon was clearly shown to reduce the number of
miscommunications between the two roles at key times during a cardiac operation. 31 Models of structured
communication between teams at all points of an operation have not been designed or studied. Pilots recognize a
10,000 foot ceiling below which no extraneous conversation can occur. There is no time during an operation when a
‘sterile cockpit’ can be identified and adhered to (Figure 3). 31
Figure 3. National Aeronautics and Space Administration (NASA) Task Load Index for members of an operating room team over the time course
of a cardiac operation. CRNA¼certified registered nurse anesthetist; CST¼certified surgical technologist; Postop: postoperative; Prep: surgical
preparation; RN¼: registered nurse. Reprinted from Wadhera RK, Parker SH,Burkhart HM, et al.: Is the ‘‘sterile cockpit’’ concept applicable
tocardiovascular surgery critical intervals or critical events? The impact of protocol-driven communication during cardiopulmonary bypass. J
Thorac Cardiovasc Surg 2010; 139:312–9,42 with permission from Elsevier and The American Association for Thoracic Surgery.
This author is convinced that structured communication at key points in the operation is our answer to the sterile
cockpit. However, we are a long way from understanding when and how these conversations should happen.
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Structured communication protocols have been studied extensively in information transfer during handoffs of
a patient from one caregiver or team to another. Handoff failures represent a significant source of medical errors and
patient harm, both between and within teams.32-36 The complexity of the information to be transmitted and frequent
interruptions and disruptions virtually guarantee loss of critical information.36-38
One study identified the critical elements of a handover from OR to PACU, and then structured a protocol to
ensure that all elements were included.32 Use of this tool reduced critical omissions from 9 to 3 per handover, and
task errors from 2.8 to 0.8.39 Another study of handovers in pediatric cardiac surgery noted that use of a protocol
reduced critical information omissions from 6.33 to 2.38.40 In a third study, implementing a process based on a
Formula-1 pit-stop that specified pre-handoff preparation (Phase 1), tasks to be completed before information
transfer (Phase 2), and specific information to be transmitted (Phase 3) reduced the number of information omissions
and shortened the handover process.41
TEAMWORK - As noted above, preventable adverse events or human error in the cardiac operating room are often
related to cognitive, teamwork, or system failures, rather than a lack of technical skill or knowledge base9-11,42,43 As
Frankel et al state: “we can assure our patients that their care is always provided by a team of experts, but we cannot
assure our patients that their care is always provided by expert teams.” 44
The quality of teamwork behaviors has been linked to surgical duration, 13 number of technical errors,45-48 and
number of major events.49 Mishra and colleagues46 found 0-6 technical errors per operation (mean of 2.62) and
found an inverse correlation between errors and the surgeon’s situational awareness score. Poor teamwork has been
found to directly increase stress among surgeons,50,51 and stressful situations degrade teamwork behaviors.52 At a
systems level, Materko and colleagues53 found a significant and positive correlation between institutional teamwork
culture and patient satisfaction scores and a significant and negative correlation between bureaucratic culture and
satisfaction scores. In their analysis of data from 125 VA hospitals, there was a full standard deviation in patient
satisfaction scores between hospitals that ranked in the top third and those ranked in the bottom third for teamwork
culture.
SAFETY CULTURE - An organization’s safety culture refers to those collective behaviors and values that
influence its ability to identify and mitigate hazards and systemic conditions that contribute to error. Safety culture
has been stated to be “the product of individual and group values, attitudes, perceptions, competencies and patterns
of behavior that determine the commitment to, and the style and proficiency of, an organization’s health and safety
management.”54 Although senior leadership is critical in establishing a safety-oriented culture, it is the frontline
providers who must be fully engaged in creating a climate of quality and safety.
A culture that permits disruptive behavior among healthcare workers directly impacts patient safety.
Disruptive behavior is common, reported by three-quarters of physicians and nurses,55 and cuts across all
disciplines.56 Respondents to a survey reported witnessing disruptive behaviors in 75% of surgeons, 64% of
anesthesiologists, and 59% of nurses. More than 80% reported loss of concentration, communication failures, and
poor patient safety as a result of disruptive behavior. 56
There are few tested methods for improving an organization’s culture. Thankfully, simple interventions to
improve communication in the cardiac OR, such as checklists, briefings, and teamwork training, are typically
associated with improvements in safety attitudes of OR personnel, as well as patient safety. 23,24,57 The
Comprehensive Unit-based Safety Program (CUSP), created in the Armstrong Institute for Patient Safety and
Quality at Johns Hopkins University, is a safety culture program that has been successfully tested in intensive care
units (ICUs) and recently in the OR.58 CUSP is a five-step iterative process that includes: (1) educating staff on the
science of safety, (2) identifying defects, (3) involving senior executives to work with staff to prioritize safety
hazards and provide resources, (4) learning from studying 1 defect per month, and (5) implementing teamwork and
improvement tools with intermittent quantitative assessments of culture. CUSP is integrated into the organization’s
strategic plan but defers to frontline workers, giving them autonomy to identify and rectify safety hazards. Use of
the CUSP approach together with specific checklists resulted in virtual elimination of catheter infections, a
significant decrease in ventilator-associated pneumonia, and significant improvements in teamwork climates. 58-60
Healthcare organizations typically investigate significant adverse events, but they do so to identify someone
to blame rather than find out how the system failed. Once identified, the individual is shamed at best, or prosecuted
at worst.60-64 This culture of blame results in a staff that maintain silence in the face of performance problems, near
misses, and violations because they fear blame and retaliation.65
Although healthcare organizations typically voice support of a just culture, establishing a climate in which
employees feel safe when voicing concerns or identifying vulnerabilities within their own unit requires moving from
a control-based management style to a commitment-based one, in which employees can continually learn from
errors to eliminate system vulnerabilities.66 Commitment-based management is essential to create a just culture in
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which individuals are held accountable only when they knowingly and unnecessarily increase risk, 44,67 and where
organizations learn and improve by openly identifying vulnerabilities and correcting them.
PHYSICAL ENVIRONMENT - The physical environment in which cardiac surgery occurs includes not only the
tools and technologies that we use to do our work, but also the physical placement of these tools, their alarms and
displays, and the characteristics of lighting, noise, vibration, temperature, physical layout and available space, and
air quality. Arguably no place in the health care system incorporates more tools and technologies into one space, and
no place uses more at the same time. Little work has been done to identify the optimal configuration and interaction
of equipment in the OR. Rather, objects have been added and added to an already crowded room with little thought
to integration. As a result, we have simply built larger and larger ORs, crowded with wires, cords, and display
screens, creating what has been termed the “spaghetti syndrome.”68
Pennathur and colleagues,18 using data collected from the Flawless Operative Cardiovascular Unified
Systems (FOCUS) Locating Errors through Networked Surveillance (LENS) study, have investigated the role of
technology in creating hazards and offer a framework to explain and categorize these errors. Technology is
problematic with regard to design and function, how the organization interacts with the equipment through
purchasing or training, and how a device is incorporated into the physical environment. Poor design and function or
poor interaction between technologies impacts the providers’ cogitative task load; the more we struggle with our
equipment, the more our brains are distracted from the patient.
In a review of hazards in cardiac surgery, Martinez and colleagues 14 identified four ways machines cause
harm: (1) misuse (poor training or negligence), (2) the inherent risks of using the device, (3) poor maintenance and
upkeep, and (4) poor machine design. Table 1 demonstrates concrete examples of each type of possible machine
harm:
A human factors analysis of modern-day cardiopulmonary bypass pumps found that information displays
suffer from placement, legibility, and format problems; components are poorly integrated into the machine; and the
alarms are too loud or too quiet.69 Alarms, designed to alert the team to an abnormal condition, occur at an
“alarming” rate of 359 per case, or 1.2 per minute, 70 and 90% are false positive.71 This quickly leads to alarm
fatigue, as well as increasing the noise level, which has been implicated in disruptions and even surgical site
infections.72 A recent editorial in JAMA suggests that alarm systems should be redesigned to (1) create clear,
priority-based sounds and alerts; (2) provide clinical information at the time of care; and (3) incorporate the
Bayesian nature of clinical decision making to create an intelligent and integrated system that helps clinicians piece
together disparate pieces of information.73 Information systems (monitors, electronic medical record systems,
alarms) are not integrated, and do not provide the comprehensive physiological disease model that is optimal for
patient safety.74
From this review of the hazards associated with tools and technologies as well as the physical environment, it
is clear that interventions to mitigate these hazards must include the system as a whole. The science of human
factors engineering has begun investigating how these complicated technologies are incorporated into the OR, 75 but
this work is in its infancy.
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We have much to learn about the ideal space and ideal layout. The guiding principles for optimal OR design,
as summarized by Killen,76 are as follows: (1) standardize the location of the head of the table and the handedness of
the room; (2) provide adequate space for equipment and for the staff to move around; (3) maintain focus on the
patient; (4) ensure that all staff have a line of sight to the patient at all times; and (5) use technology to help
workflow. Solving such issues as the “spaghetti syndrome”68 of wires and cables and the increased microbial count
associated with frequent door openings77 will take a coordinated and concerted effort. Reduction of distraction,
noise, and door openings by controlling traffic patterns has been recommended by the Association of Perioperative
Registered Nurses.78
Data such as that provided by the Realizing Improved Patient Care through Human centered Operating Room
Design (RIPCHORD) study group79 provides a framework and methodology that could be used to help understand
traffic patterns in the OR and determine optimal positioning of booms and equipment. As each of these problems
(noise, alarms, equipment position, and personnel traffic) is studied, high-fidelity simulation offers an opportunity to
evaluate possible solutions.
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Who¹s Controlling Your Digital Footprint?

Why and How Doctors Should Leverage the Power of Social Media
Marjorie Podraza Stiegler, M.D. Chapel Hill, NC
Who’s Controlling Your Digital Footprint? Why and How

Doctors Should Leverage the Power of Social Media
Like it or not, the internet is a rapidly growing repository of indelible information about you. Patients,
professional colleagues, future employers, and many others are reading about you online. Ignore your digital
footprint, and you’re missing opportunities to learn from others, share your expertise, grow your practice, network
with colleagues, and influence your own online reputation.
Why create and manage an online presence? This RCL will address the following possibilities:
1. Find collaborators
2. Keep up to date with medical news – both from academic journals, and the news that patients are reading
3. Contribute to health literacy by posting educational content. Otherwise, most of what patients, journalists,
and policy-makers find online is low quality and often not written by medical professionals.
4. Recruit the best and brightest colleagues and trainees to your institution
5. Reach more people with the healthcare messages you feel are important
6. Make your work easy to find, which leads to opportunities for professional advancement
7. Learn from others
8. Network far and wide
9. Protect your reputation from misinformation, bad reviews, or auto-populated digital noise
10. Professional medical social media usage is increasing by several thousand percent each year. Get out in
front, or get left behind.
11. Curate your library by keeping online “favorites” of journal articles, news coverage, and opinion pieces
12. Help patients find your practice (particularly relevant for pain medicine docs, but perhaps applicable to us
all)
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13. Influence public policy by engaging in professional advocacy. “preaching to the choir” does not advance
your cause.
14. Create an entirely new set of performance metrics for promotional purposes. Being able to share statistics
about the reach of your work represents a new academic currency.
15. Make your bigger projects easier. Experiment with small ideas that will be the basis for your next research
project, quality improvement effort, article, book chapter, or presentation.
There are many more applications for social media, personal websites, and online activities. As well, there are many
options for platforms on which to participate. Understanding the differences and having a clear agenda will help
you select the right one for you. This need not be onerous.
If you aren’t already taking charge of your online presence, get started today with these tips:
1. Give yourself a checkup. Especially if you are not active on the web with a blog, website, or social
media, most content about you will not have written or posted by you. Routinely check your own internet
presence to ensure that information about you is accurate and appropriate. A search of your name is likely
to lead to pages of healthcare rating sites (there are more than 75 such websites, and counting), including
healthgrades.com, vitals.com, doximity.com, betterdoctor.com, and so on. While they could contain a
negative review, most often these sites are nothing more than a sparse profile of publically available
information. However, this kind of digital clutter obscures content you might prefer to showcase, such as
your departmental profile page, presentations, manuscripts, and press releases.
2. Share your expertise. Patients find an abundance of both information and misinformation online. If
patients are searching for answers, shouldn’t you be providing them? As a physician or other healthcare
provider, you have unique expertise. You also have the ability to translate sophisticated material and years
of experience into easy-to-understand language. You can help only one patient at a time in the hospital or
clinic, but you can help thousands by disseminating education online and improving health literacy. When
the Mayo Clinic tweets, for example, over one million followers listen. Social media outreach is a key
strategic initiative for many major medical centers.
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3. Be professional, always. Regardless of your intention for online content to be private, anything has the
potential to become public and permanent. This is true for private Facebook or Instagram accounts, just as
it is with email. Privacy policies are continually evolving, and a simple click of a button is all that is
needed to “forward” or “share” your content to a public domain. Select your words and photos carefully;
even in casual settings, there is a professional standard expected of healthcare professionals. Be aware of
family and friends who “tag” you in photos and posts on their own accounts, and how that information may
be more public than you wish. And of course…
4. Don’t post about patients. Never post any content about patients, and certainly do not post any identifying
information. HIPPA violations, whether egregious or unintentional, can have serious professional
consequences. As well, health care professionals sometimes use dark humor as a way of coping with
stress, and to some degree, may become desensitized to illness and injury. Cases that are “great” for
trainees and conferences are often linked to really bad news for patients. Consider seriously how you
present content online, including your tone, use of slang, use of humor, and controversial or private topics.
5. Influence your web presence. Just as inappropriate posts can portray you unfavorably, the right kind of
posts put your best image forward. Start with a short biosketch and professional photo on your
departmental website. Use videos to tell your personal and departmental story. Provide educational
content. Link to awards, press releases, faculty CVs, and current activities. Finally, consider maintaining a
professional account on LinkedIn. This kind of content, as well as any blog or social media activity, is
likely to outrank random healthcare ratings sites and push them to the distant pages of an online search.
Therefore, by creating and publishing your own content, you can effectively curate digital search results.
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Check out the table below for a few best practice hints:
Share great content Share press releases, research papers, timely headlines,
and announcements. Include your brief opinion, or
simply that the content is thought-provoking.
Add a link Share the full story or webpage related to the your
commentary.
Add an image Posts with images and links get up to 40% more
engagement than those without.
Tag other relevant Tagging (including a person’s “@” name) is similar to
users email, bringing your posts to the tagged person’s
attention. Don’t spam, but do use tags to communicate
and credit the work of others.
Use appropriate Hashtags organize conversations and topics, helping
hashtags others find keyword topics of interest. Popular hashtags
in medicine include #meded and #ptsafety. Conferences
often use a hashtag as well.
Getting started on Twitter – best practices:
1. Set up an account at www.twitter.com Choose a professional username that does not have numbers, symbols,
slang, or your employer’s name (unless you are officially managing the employer’s account). Post a professional
headshot or other nicely cropped image of your face. No one will take you seriously until you replace the “egg”
placeholder with an image of yourself, or (less ideally) a professional logo or image. Carefully describe yourself in
your profile with a mix of professional and basic personal information (e.g. “I’m a father, little league coach, three-
time marathoner, and physician anesthesiologist specializing in pain medicine.” ). Also list your professional or
academic interests (no need for hashtags here – “I’m interested in health policy and patient safety.”)
2. Select accounts to follow, including other people (@drmstiegler), institutions or departmetns
(@UNC_anesthesia), and organizations (@ASALifeline). You can also choose to follow major news organizations
and major academic journals.
3. Listen. Spend some time simply reading and observing interactions before you start chiming in.
4. Keep your own tweets to about 115 characters. This allows others to “retweet” your messages without
truncating them. Remember that tweets max out at 140 characters, and when someone retweets your tweet, your
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user name is added to the front of the message. Leave enough room for that, and for short comments from others
who agree or disagree with the content.
LinkedIn and Google+ are also growing platforms for professional interaction.
Be sure your practice has a website and possibly a blog. At the very least, set up a simple webpage with basic
information about your team, including photos, bios, and contact information.
Marjorie Podraza Stiegler, M.D. is an Associate Professor of Anesthesiology at UNC Chapel Hill. Connect with her
on twitter @drmstiegler.
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Anesthesia for Routine and Advanced GI Endoscopy
Sheila Ryan Barnett, MD Boston, MA
The number and type of gastrointestinal (GI) procedures has increased dramatically in the last few decades. This is
perhaps most notable for screening colonoscopy, which is now recommended in patients over age 50 years; but in
addition to colonoscopy there has also been an increase in advanced GI procedures such as ERCP, Endoscopic
Ultrasound, ablation treatments for Barrett’s esophagus and numerous other procedures. As the types of procedures
have become more complex and the population ages, there has been a parallel increase in demand for anesthesia as
opposed to local anesthesia or moderate sedation for many of these cases. 1 GI cases are associated with little
residual postoperative discomfort, but can still present significant challenges for the anesthesia provider. This
review will address common anesthetic challenges encountered during both routine and advanced endoscopy.
Non operating room anesthesia locations

Several years ago data from the closed claims project in anesthesia provided a wake up call to the anesthesia
community regarding anesthesia and sedation practices in non operating room settings. In the most recent analysis
including cases after 1990; 10% of all cases involved a MAC anesthetic and a significant number involved GI and
remote cases. 2 Respiratory events accounted for over 20% of the MAC cases and death occurred in 38% of MAC
claims. On deeper analysis the authors found that several of the events were probably preventable and involved
inadequate monitoring and lack of recognition of over sedation. Patient risk factors included advanced age, obesity
and an ASA classification of 3 or 4. Since the closed claims data was published there have been significant
improvements in awareness and standardization of remote non operating room locations, including GI suites.
The anesthetic requirements for GI procedures can range from a simple propofol infusion to general anesthesia with
an endotracheal tube (GET). Irrespective of the procedure or type of anticipated anesthesia there are several
standards that need to be met for any non operating room location.
Monitoring Per the ASA basic standards (REF) patients must be monitored using continuous ECG, NIBP at no less
than 5 minutes intervals, pulse oximetry for oxygenation (with variable audible tones) and end tidal carbon dioxide
(ETCO2) monitoring of ventilation. ETCO2 monitoring has been shown to provide early warning of respiratory
impairment – this appears to have particular benefit in patients receiving propofol infusions. ( 3-5) In these cases it is
not uncommon to have patients obstruct or slip into a deeper plane of anesthesia than anticipated and ETCO2 can
provide an early warning of impending hypoxemia.
Equipment The type of anesthesia equipment will depend on the type of facility or location. Simple GI procedures
may be done in an office based setting while more advanced procedure such as ERCP are often done in a hospital.
At a minimum supplemental oxygen, an ambubag and oral or nasal airways for rescue, dedicated anesthesia specific
suction and access to appropriate ACLS medications for resuscitation is recommended in all remote locations. For
many advanced suites and ambulatory centers the GI suite procedure room will include an anesthesia machine and
equipment needed to provide GET. For all non operating rom anesthesia it is important to confirm that the
anesthetizing location is properly licensed for the type of anesthesia anticipated e.g. operating room equivalent, an
ambulatory surgery center or office based procedure suite. The type of licensing will dictate the minimum
requirements for equipment – for example if a GET with anesthetic gases is anticipated there are strict requirements
for gas evacuation and disposal that need to be met.
Additional resources: During upper endoscopy procedures (EGD, EUS etc) the airway is essentially shared with the
GI provider, for these cases it can be particularly valuable to have a second oxygen source that can be hooked into
the corner of the mouth and supplement the oxygen supplied through standard nasal cannula. During ERCP patients
are frequently positioned in the prone ‘swimmers’ position, a bolster placed under the right side can help elevate the
head and shoulder allowing better access to the airway for suctioning and supplemental oxygen.
Practical issues with remote anesthesia Even in a hospital setting the GI suites are usually remote from the main
operating rooms and there are several principles to be adhered to in order to avoid significant adverse events.
1. Identify how and who to call for help in the event of significant cardiorespiratory event. Although these events
are rare, they can occur and lead to significant harm and even death. This is especially true for higher risk
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procedures in sick patients for example those undergoing ERCP with acute cholangitis. 2. Appropriate access to
remote locations during off hours. With increasing concern surrounding hospital security these suites may be
locked, making it difficult for additional personnel to enter in the event of an emergency. 3. Many procedures are
conducted in the dark; there should be a separate light source for anesthesia 4. If an electronic record is being used,
computers and internet access will be needed. 5. Following sedation and propofol, patients are generally transferred
to a recovery area (which may be the same as the holding or preparation areas) and monitored by nursing. If general
anesthesia is administered, recovery can be more prolonged and there may be specific licensing issues with respect
to nursing training and even facility design.
Patient characteristics
GI procedures are in general low risk procedures; and most estimates of complications include moderate sedation as
well as propofol administration. For moderate sedation serious adverse events occur in less than 1% of cases, this is
similar for propofol anesthesia; although some estimates suggests incidence of minor events such as need to hand
ventilate or interrupt a case is slightly higher. Certain patient characteristics increase the risk of a complication or
predict an increased likelihood of difficulty with sedation. This includes obesity, sleep apnea, a history of difficulty
with moderate (nursing) sedation; significant alcohol or drug addiction history, use of chronic pain medications. In
addition patients with significant comorbidities e.g. chronic pain, cardiac or pulmonary disease can carry a higher
risk from an adverse event.
Carbon dioxide insufflation

Recently insufflation with carbon dioxide as opposed to air has become more popular for GI procedures.
Advantages of carbon dioxide include less pain after colonoscopy and more rapid recovery. When carbon dioxide is
used there is the potential absorption of CO2, leading to high CO2 levels. In patients with significant cardiac
disease (especially right sided failure or pulmonary hypertension) or a predisposition to CO2 narcosis, air
insufflation is probably safer, however there are few reports in the literature describing adverse events related to
CO2 per se. 6
GI Procedures and Risks

GI procedures can be divided into routine and advanced procedures. Routine procedures include diagnostic EGD
and routine colonoscopy, potentially with polypectomy. Examples of advanced procedures include ERCP,
Endoscopic ultrasound with or without biopsies, small bowel enteroscopy, radiofrequency or cryoablation for
Barrett’s esophagus, and endomucosal resection of lesions or polyps. The field of advanced endoscopy is rapidly
expanding and this is just a selection of procedures now offered; in the future it is likely that non-invasive
endoscopic surgery will become more popular.
Basic procedures such as EGD and colonoscopy are frequently performed with MAC utilizing propofol infusion
alone and the risk of a significant adverse event is low in healthy patients. The most commonly reported adverse
events related to anesthesia are cardiopulmonary; usually temporary respiratory compromise or transient
hypotension or hypertension. Respiratory compromise is often secondary to airway obstruction, this is more
common with propofol than moderate sedation; and is frequently relieved by reducing the propofol dose and
adjusting the airway through chin lift, head tilt or even the insertion of an oral or nasal airway. Airway obstruction
is more common in obese patients and those patients with known sleep apnea. Aspiration is a less common cause of
hypoxemia, although studies in colonoscopy have suggested that microaspiration –recognized by patients coughing
during colonoscopy, may be more common but usually does not lead to significant adverse events. 7 During EGD
procedures the risk of aspiration is greater and it is important to have dedicated suction ready.
Many of the advanced GI procedures are also amenable to MAC anesthesia – for example EUS. EUS are frequently
done to evaluate patients for pancreatic cancer or lesions, these cases relatively non-stimulating and propofol
infusions are usually adequate. 8 9
ERCP is unique amongst the upper GI procedures in that in general the prone position or swimmers position is
preferred by the gastroenterologists. The prone poison can make the airway more challenging and careful
positioning is key. Elevating the head slightly by using a bolster under the right side can improve access to the
airway. Manipulation of the bile ducts during an ERCP can be painful and sometimes using low doses of ketamine
or fentanyl can be helpful. 10,11
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Small bowel enteroscopy (SBE) is not generally a painful procedure, and is usually done as part of a work up for an
occult GI bleed, searching for arteriovernous malformations or other bleeding sources. A major challenge of the
SBE is the length of the procedure – these can be long procedures. Depending on the circumstances MAC can be
administered but there are instances for which a GET may be recommended e.g. the obese or high risk or an
unstable patients, especially in association with inexperienced endoscopist. 12-14
Treatment options for Barrett’s esophagus have revolutionized the approach to screening and treatment of early
dysplasia. Radiofrequency or cryoablation techniques applied to the areas of dysplasia are associated with reduced
transformation not cancer and improved patient outcomes. These procedures can frequently be performed with
MAC anesthesia, however they do involved several insertions of the scope, so patients will need to be at a relatively
deep plane of anesthesia. Communication between the proceduralist and the anesthesia provider is key to ensure
optimal outcomes.
General Anesthesia in GI
In certain cases a general anesthesia with an endotracheal tube will be needed to ensure a successful and safe
procedures, although there are few absolute indications, and the decision to do a GET should ideally be made
following an assessment of the patient and a discussion between the endoscopist and the anesthesia provider. A
common undisputed reason for a GET is for patients who are obstructed and presenting for a stent – often for
palliation in patients with large duodenal obstructing masses. If a patient has a small bowel obstruction there is a
very high risk of aspiration once the scope passes the obstruction and having a protected airway is critical. These
patients should be intubated prior to the GI procedure.
Choosing a GET for patients undergoing an ERCP should take into account the patient’s current status,
comorbidities and expertise of the proceduralist. In a busy advanced endoscopy unit it is not unusual for an ERCP
to be done in 30-45 minutes, however in units that do fewer procedures an ERCP may take lover an hour. The
expected length of time may influence the decision to do a GET, especially in patients with other comorbidities.
Obesity, acute cholangitis, recent surgery, ASA classification of 3 or 4 are common reasons to consider a GET. 11
Production pressure
In general GI suites are high volume procedure areas, and the anesthesia provider can face significant pressure to cut
corners and participate in practices that may lead to harm or reduce patient safety. Communication and an
understanding of the risks of the procedures and education with the endoscopists about anesthesia risks can enhance
communication and improve patient safety.
Conclusions
In summary GI procedures are common and the number and complexity of cases are increasing. Anesthesia for
these procedures will depend on the patient, the endoscopist and the setting in which the procedure is performed. In
all non-operating room cases, patient safety must be prioritized to prevent adverse events.
References:
1. Inadomi JM, Gunnarsson CL, Rizzo JA, Fang H. Projected increased growth rate of anesthesia professional–
delivered sedation for colonoscopy and EGD in the United States: 2009 to 2015. Gastrointest Endosc
2010;72:580-6.
2. Julia Metzner, Karen L. Posner, Michelle S. Lam, Study Karen B. Domino, Best Practice & Research
Clinical Anaesthesiology. Best Practice & Research Clinical Anaesthesiology. 2011;25(2):263-276.
3. Jonathan B. Waugh,  Chad A. Epps, Yulia A. Khodneva Capnography enhances surveillance of respiratory
events during procedural sedation: a meta-analysis. Journal of Clinical Anesthesia. 2011;23(3):189-196.
4. Beitz A, Riphaus A, Meining A, et al. Capnographic Monitoring Reduces the Incidence of Arterial Oxygen
Desaturation and Hypoxemia During Propofol Sedation for Colonoscopy: A Randomized, Controlled Study
(ColoCap Study). The American Journal of Gastroenterology. 2012;107(8):1205-1212.
doi:10.1038/ajg.2012.136.
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5. Bhavani Shankar Kodali. Capnography Outside the Operating Rooms. Anesthesiology 2013; 118:192–201
6. Wu J, Hu B. The role of carbon dioxide insufflation in colonoscopy: a systematic review and meta-analysis.
Endoscopy. 2012;44(02):128-136. doi:10.1055/s-0031-1291487.
7. Cooper GS, Kou TD, Rex DK. Complications Following Colonoscopy With Anesthesia Assistance. JAMA
Intern Med. 2013;173(7):551-556. doi:10.1001/jamainternmed.2013.2908.
8. Berzin TM, Sanaka S, Barnett SR, et al. A prospective assessment of sedation-related adverse events and
patient and endoscopist satisfaction in ERCP with anesthesiologist- administered sedation. Gastrointest
Endosc. 2011;73(4):710-717. d
9. Cheriyan DG. Propofol use in endoscopic retrograde cholangiopancreatography and endoscopic ultrasound.
WJG. 2014;20(18):5171. doi:10.3748/wjg.v20.i18.5171.
10. Garewal D, Powell S, Milan SJ, Nordmeyer J, Waikar P. Sedative Techniques for Endoscopic Retrograde
Cholangiopancreatography. (Garewal D, ed.). Chichester, UK: John Wiley & Sons, Ltd; 1996.
11. Barnett SR, Berzin T, Sanaka S, Pleskow D, Sawhney M, Chuttani R. Deep Sedation Without Intubation for
ERCP Is Appropriate in Healthier, Non-obese Patients. Dig Dis Sci. 2013;58(11):3287-3292.
12. Sethi S, Thaker AM, Cohen J, et al. Monitored anesthesia care without endotracheal intubation is safe and
efficacious for single-balloon enteroscopy. Dig Dis Sci. 2014;59(9):2184-2190.
13. Rondonotti E, Sunada K, Yano T, Paggi S, Yamamoto H. Double-balloon endoscopy in clinical practice:
Where are we now? Digestive Endoscopy. 2012;24(4):209-219.
14. Yun DY, Han J, Oh JS, Park KW, Shin IH, Kim HG. Is Endoscopic Retrograde Cholangiopancreatography
Safe in Patients 90 Years of Age and Older? Gut Liver. 2014;8(5):552-556.
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Environmental Sustainability in the Perioperative Setting

Brian P. Barrick M.D., D.D.S. Chapel Hill, North Carolina
“As anesthesia care providers, we have worked tirelessly on behalf of patient safety, comfort, exceptional quality
care, and OR expediency. We need to add environmental stewardship to our list of exemplary contributions to
medicine.” Anesth Analg 114 (5): 921-3, May 2012
First, let’s focus on the scope of the problem. Science has shed much light on the contributions of human activity to
the condition of our environment. While we have only been using fossil fuel on a large scale (and, coincidentally,
providing general anesthesia) for approximately 170 years, we have drastically changed many things about our
environment to make it less conducive to life. Carbon dioxide levels have risen to over 400 parts per million for the
first time since before the existence of Homo sapiens. The human population has increased exponentially in the past
200 years to over 7 billion people, many of them in developing nations that will require health care services. The
overall declining health and increasing obesity rates of developed nations means that these countries will consume
more health care resources as well.
Hospital care is the primary area of electricity use, water consumption, contribution to landfills, emission of
greenhouses gases, and potential pollution of drinking water supply in medicine. Specifically, the health care
industry is second only to the fast food industry for waste production in the United States. Over two million tons of
waste is generated annually, with hospitals comprising the vast majority. To break it down further, the operative
setting is responsible for about 30% of this figure. When combined with labor and delivery suites, the figure jumps
to 50-70%.
Volatile agents and nitrous oxide are potent greenhouse gases. These agents are present in the atmosphere at levels
100,000 times lower than CO2, but responsible for 10-15% of anthropogenic radiative force of climate change since
beginning of industrial age. This is due to a combination of their inherent ability to trap heat (thousands of times
more powerful than CO2) and their length of duration in the atmosphere (over 100 years for nitrous oxide). A
geophysical survey showed that levels of sevoflurane and desflurane, which have 500 and 2500 times the global
warming potential of CO2 respectively, have risen substantially over the past decade, even in remote places such as
the poles. In addition, sevoflurane is unique in that its chemical structure resembles chloroflurocarbons (CFCs) that
were banned by international treaty in 1979. Sevoflurane may have the potential to degrade the protective ozone
layer in the stratosphere.
Medications and their byproducts contribute to the pollution of the drinking water supply. For any given chemical,
the potential for this depends on inherent toxicity, duration in the environment (breakdown by natural processes),
and bioavailability. While the science behind this is in its infancy, there is good reason to suspect that agents that are
commonly used during anesthesia may be contributors to water pollution and, at the very least, should not be
disposed of in sinks.
What can be done? Let’s first focus on what an individual anesthesia provider can do to lessen his/her environmental
impact. The use of low fresh gas flows during the maintenance portion of a case is one simple but very effective way
to lessen both the release of nitrous oxide and volatile agents into the atmosphere and overall cost to an anesthesia
department. The amount of fresh gas flow need only be enough to replace the oxygen a patient consumes, the
amount taken by the gas sampling monitor, and enough to account for minor leaks in the system. This amount will
vary among patients, but will clearly be less than 1 liter per minute.
Another way to lessen impact is to do a total intravenous anesthetic (TIVA). The speaker will introduce the concept
of a Cradle-To-Grave Analysis (CTGA) here. For a particular substance, this involves the energy involved in
producing the product, water consumed in the process, impact of transport, energy required to power delivery
devices (infusion pumps, vaporizers, etc.), and the environmental impact of the substance or metabolites after
elimination. CTGA has shown that TIVA has by far the least environmental impact of general anesthetic techniques,
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at least from a CO2 emissions standpoint. The disposal and excreted metabolites of propofol may play an unknown
role, so isoflurane at very low fresh gas flows (less than one liter per minute) may have merit.
Let’s next focus on systems issues that can be addressed. There has been debate as to whether the use of reusable
versus disposable items will lessen environmental impact. While disposable items take up space in a landfill and/or
release harmful chemicals when incinerated, reusable items required the use of either an autoclave or harsh
chemicals for disinfection. Several recent studies have used CTGA or similar analysis to show that reusable items
are better in almost every setting. Reusable LMAs win out over disposable ones on many fronts. Reusable gowns of
equal protective quality and comfort win out over disposable ones. One study showed that disposable central line
kits were better than reusable ones (separated into single use and reusable items). However, when one looks further,
the reusable kit contained extraneous items, and the power source of the hospital was not clean and renewable
(“brown coal”).
There has been discussion, and some institutions have implemented recycling programs in the operative setting.
Much of the wrapping, container material, drug vials, and various other items that are opened and discarded before
the patient even enters the operating room are potentially recyclable. Implementing a recycling takes the
commitment of the entire staff to sort out and properly dispose of recyclable material. Many institutions place
recyclable materials in a bin during OR set-up in a bin that is removed before the patient arrives, preventing possible
contamination. A survey from 2012 identified barriers to OR recycling, namely staff attitudes toward recycling,
administration attitudes toward recycling, inadequate recycling facilities, and inadequate info on how and what to
recycling.
Certain items that are designed for single use (SUDs) may be disinfected and repackaged for reuse. This applies to
pulse oximeter probes, disposable NIBP cuffs, SCDs, drills, and most laparoscopic equipment. The FDA has stated
that companies must declare in writing that reprocessed SUDs are “substantially equivalent” (safety, efficiency, and
intended use). In the interest of transparency, reprocessed items must be clearly labelled as such, and the
reprocessor must be clearly identified.
Lastly, changing operating room/suite design can decreased energy and water use, lessen the amount of chemicals
that escape into the atmosphere and water supply, and be very aesthetically pleasing. Several newer operating rooms
are designed to take advantage of natural light (sunlight), breaking the unwritten rule that if can see outside, the
room is not sterile. LED lights, in use for many years, use much less electricity and are far more durable than
incandescent or fluorescent lights. Sensors at OR sinks, and the use of hand sanitization that does not require the
traditional “scrub”, can save water. A proprietary scavenging system that only runs at full energy during prime use
can be attached a single OR or from several ORs at once, and is currently in use at many institutions. 80% of the air
in the OR environment can be recirculated. This allows for better temperature and humidity control (use of less
energy) without putting staff at risk from ambient anesthetic gases. All of these changes have a high start-up cost,
but can amount to cost savings in the long run.
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Fluid Management in Neurosurgical Patients: Is Keeping Them Dry All Wet?

Donald S. Prough, M.D. and Stefanie Fischer, M.D. Galveston/Texas
Introduction
As a therapeutic goal, keeping neurosurgical patients “dry” has persisted for at least 40 years. However, in the
context of neurosurgical fluid management, the meaning of “dry” has changed. For many years, dating to the often-
cited publication by Shenkin,1 “dry” meant strict restriction of intravenous fluids, even to the point of hypovolemia,
based on the assumption that more fluid inevitably meant more cerebral edema. Current management is based on the
concept that “dry” does not imply hypovolemia but rather avoidance of unnecessary administration of free water.
Unnecessary administration of free water may reduce serum osmolality, which in turn may increase cerebral edema.
In contrast, iso-osmolar normovolemia does not exert adverse effects on the brain. Changing concepts regarding
appropriate fluid management of neurosurgical patients have developed in parallel with rapidly changing concepts
regarding appropriate fluid management of non-neurosurgical patients. Unfortunately, to date, randomized,
controlled trials of perioperative fluid therapy have been conducted in non-neurosurgical patients. As a consequence,
data only suggest that either “too dry” and “too wet” may increase morbidity in neurosurgical patients, 2 while also
acknowledging that clinical assessment of volume status is inherently inaccurate.3
This review will focus on three key topics, including:

1. The influence of fluid composition and volume on intracranial volume;
2. The influence of fluid composition and volume on outcome in traumatic brain injury (TBI); and
3. The influence of fluid composition and volume in specific neurosurgical situations
Influence of Fluid Composition and Volume on Intracranial Volume
Management of intracranial volume is important in any patient who is at risk for intracranial hypertension
or who requires adequate brain relaxation during craniotomy.4 Intracranial volume is a function of brain tissue
volume, cerebrospinal fluid volume, and cerebral blood volume (CBV), which is the sum of intracranial arterial and
venous blood volume. Perioperative fluid management potentially can influence brain tissue volume and intracranial
venous blood volume. Although compensatory mechanisms can adjust for substantial increases in intracranial
volume, particularly if increases occur slowly, larger or more rapid increases will result in increased intracranial
pressure (ICP) if the skull is intact. Preservation of cerebral perfusion pressure (CPP = mean arterial pressure – ICP)
necessitates maintenance of systemic normovolemia without adversely influencing intracranial volume or ICP.
Several physiologic principles underlie the relationship between fluid management, intravascular volume status,
intracranial volume and ICP.
First, cerebral venous volume is a function of cerebral venous capacitance and cerebral venous pressure.
Cerebral venous pressure is equal to central venous pressure in the supine position, but is reduced as the head is
elevated above the chest. Although it is reasonable to assume that any amount of systemic hypervolemia would be
associated with greater central venous pressure, and, as a consequence, greater cerebral venous pressure and greater
intracranial volume, few clinical data support that assumption. It is likely that the magnitude of differences in central
venous pressure that are associated with moderate differences in fluid administration are too small to significantly
influence ICP. In addition, if ICP exceeds systemic venous pressure, compression of the intracranial venous system
may effectively isolate cerebral venous from systemic venous pressure.2 However, considerable clinical evidence
demonstrates that increases in head elevation (reverse Trendelenburg position) produce decreases in ICP and dural
tension, and variable changes in CPP.5-7
It is important to note that excessive fluid administration in neurosurgical patients may exert adverse effects
on organ systems other than the brain. Although relative fluid restriction has been associated with worse outcomes
in head-injured patients,8 more aggressive fluid therapy has been associated with greater severity of pulmonary
infiltrates.9
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Second, brain tissue volume is a function of the integrity of the blood-brain barrier (BBB). In non-brain tissues, the
distribution of fluid between plasma volume and extracellular volume (ECV) is determined by capillary membrane
permeability, transcapillary hydrostatic pressure gradients, transcapillary colloid osmotic (oncotic) pressure
gradients and the function of the endothelial glycocalyx.10 Systemic capillary membranes are highly permeable to
water, ions, and other low molecular weight (MW) compounds, but limit the movement of high MW substances,
including albumin. Oncotic pressure is generated by solutes larger than approximately 30,000 MW (albumin has an
average MW of 69,000). In contrast to systemic capillary membranes, the cerebral capillary membranes that
constitute the BBB are impermeable to most hydrophobic solutes, including sodium, but may become highly
permeable if the BBB is disrupted.
Third, the terms hypotonic, isotonic, and hypertonic refer to intravenous fluids in which the total osmolality
is, respectively, less than, roughly equal to, or greater than serum osmolality. The sodium concentration ([Na +]) in
intravenous fluids is the most important component of osmolality, and must be considered in relation to plasma
[Na+] and osmolality. Normal plasma osmolality averages 290 mOsm/kg, of which 280 mOsm/kg is attributable to
Na+ and its associated anions. The calculated osmolalities of lactated Ringer’s solution and 0.9% NaCl are 270
mOsm/kg and 308 mOsm/kg, respectively. The effective, or in vitro, osmolalities of the two fluids are somewhat
lower -- ~257 and 285 mOsm/kg, respectively. 11 However, the most important clinical implications of intravenous
fluids are their effects on plasma [Na+] and serum osmolality, especially when administered rapidly. Because each
Na+ ion is accompanied by an anion, an acute increase or decrease of plasma [Na +] of 1.0 mEq/L generates both an
acute increase or decrease in osmolality of 2.0 mOsm/kg and a corresponding increase or decrease in osmotic
pressure of 38.6 mmHg (19.3 mm Hg per mOsm/kg). Therefore, small acute differences in plasma [Na +] generate
substantial osmotic pressure gradients across the intact BBB and may alter brain water to a clinically important
extent.
As an example of changes in [Na+] produced by rapid fluid infusion, in gynecological patients receiving
rapid infusions (60 mL/kg over two hours) of lactated Ringer’s solution ([Na +] 130 mEq/L), plasma [Na +] decreased
approximately 2.0 mEq/L, while in patients receiving 0.9% saline ([Na +] 154 mEq/L), plasma [Na +] increased nearly
2.0 mEq/L.12 These changes are equivalent to decreases and increases in osmolality of ~ 4.0 mOsm/kg, and in
plasma osmotic pressure of ~ 75-80 mm Hg, with a total difference in osmolality and osmotic pressure between the
two acute infusions of ~ 8.0 mOsm/kg and 150-160 mm Hg, respectively. For comparison, total intravascular
osmotic pressure generated by proteins is only around 24 mm Hg.
Although not conducted in neurosurgical patients, the study by Sheingraber at al. 12 suggests that rapid
administration of lactated Ringer’s solution to patients at risk for intracranial hypertension (e.g., hypotensive
patients with TBI) could substantially increase brain water and worsen ICP; conversely, rapid administration of
0.9% saline could exert opposite effects. However, there are few clinical data to support that contention, and
considerable clinical data address adverse effects, including mortality, related to hyperchloremia and metabolic
acidosis associated with rapid administration of 0.9% saline. 13 In practice, there is no need to choose between
lactated Ringer’s solution and 0.9% saline because balanced salt solutions that are not hyponatremic are
commercially available.
Therapeutic induction of hyperosmolality is routine practice in neurosurgery. Acute induction of

hyperosmolality to reduce brain water and intracranial volume is conventionally accomplished with mannitol, but
hypertonic saline solutions are preferred by some clinicians.14;15 Hypertonic saline solutions and mannitol solutions
of similar osmolality have similar effects on brain water, intracranial volume and ICP. However, infusion of
hypertonic saline increases intravascular volume while diuresis secondary to mannitol decreases intravascular
volume.16 While few complications relate specifically to osmotic therapy, acute severe hyperosmolality could,
theoretically, precipitate BBB opening. Clinical use of hypertonic saline is associated, as is 0.9% saline, with
hyperchloremic acidosis, which usually requires no treatment, but must be differentiated from other causes of
metabolic acidosis.
In contrast to Na+ ions, colloids contribute minimally to osmolality and osmotic pressure, and therefore to
gradients for water movement across the intact BBB. While some clinicians infer that increasing colloid osmotic
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pressure will decrease cerebral edema in neurosurgical patients, most experimental evidence suggests that, if the
BBB is intact, the small portion of total osmotic pressure contributed by colloid exerts little effect.
Influence of Fluid Composition and Volume on Outcome in Traumatic Brain Injury
Patients who sustain TBI may suffer hemorrhagic hypovolemia due to associated injuries. In the absence of
myocardial injury or dysfunction, and after other treatable causes (e.g., tension pneumothorax, tamponade) have
been excluded, hypotension in TBI patients should raise the suspicion of inadequate volume resuscitation.
Physicians caring for these patients should target adequate volume resuscitation while avoiding increases in ICP.
Isotonic crystalloid solutions (excluding slightly hypotonic lactated Ringer’s solution) are often the first solutions to
be infused in hypotensive trauma patients because they are readily available and inexpensive. As an initial
resuscitation fluid, 0.9% saline is acceptable, perhaps even defensible on the basis of slight hyperosmolality, but
more prolonged use will inevitably produce hyperchloremia and metabolic acidosis and could potentially worsen
outcome. If the initial clinical evaluation suggests intracranial hypertension, empirical mannitol (0.5 g/kg) may also
be appropriate, although the ensuing osmotic diuresis can aggravate existing volume deficits. Infusion of packed red
blood cells resuspended in 0.9% saline is a suitable alternative if severe dilutional anemia is present or suspected.
Resuspension in thawed FFP is appropriate if dilutional coagulopathy is present or suspected.
The role of colloids in TBI patients continues to be debated. A secondary analysis 17 of a recent randomized
18
trial, which compared 4% albumin to 0.9% saline for fluid management of critically ill patients after admission to
Intensive Care Units, suggested that the subset of trauma patients with TBI who were randomized to 4% albumin
had substantially worse long-term outcomes. A subsequent secondary analysis suggested that patients receiving 4%
albumin had a higher incidence of refractory intracranial hypertension. 19 Van Aken et al. offered a plausible
explanation, in that the 4% albumin solution used in the SAFE trial was suspended in a hypo-osmolar carrier
solution, so that the adverse effects of the infusion could have been due to reduced osmolality, independent of the
colloid content.11
In contrast, in anesthetized rats subjected to fluid percussion TBI followed by hemorrhage of 20 mL/kg,
resuscitation with 90 mL/kg of isotonic lactated Ringer’s solution was associated with equivalent blood volume
expansion to 20 mL/kg of 5% albumin, but at the expense of higher brain water. Resuscitation with only 50 mL/kg
of isotonic lactated Ringer’s solution did not increase brain water, but also failed to restore blood volume. 20 One
possible explanation for the apparently conflicting experimental and clinical data is that the 5% albumin used in the
experimental study was suspended in a slightly hyperosmolar solution in contrast to the hypo-osmolar 4% solution
used in the SAFE clinical trial.
Hypertonic saline solutions, which tend to reduce ICP and increase blood volume, are used by some
clinicians for rapid volume resuscitation of hypovolemic trauma victims with TBI and intracranial hypertension.
However, Cooper et al.21 found no differences in mortality or neurologic outcome when they randomized 219
patients with TBI to pre-hospital resuscitation beginning with 250 mL of either 7.5% saline or lactated Ringer’s
solution.
Recent studies of experimental TBI in rats suggest that administration of fluids containing lactate in
relatively high concentrations (100 mM) may improve brain oxygen consumption, but clinical confirmation of these
observations is necessary.22
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The Influence of Fluid Composition and Volume in Specific Neurosurgical Situations
Craniotomy. As a general rule, isotonic crystalloid solutions should be used to replace preexisting deficits
and blood loss. Transfusion may be indicated at a hemoglobin concentration ([Hgb]) of < 8 g/dL, with a higher
threshold being appropriate if there is evidence of tissue hypoxia or ongoing uncontrolled hemorrhage. Fresh frozen
plasma may be infused if there is persistent hemorrhage despite adequate surgical hemostasis. There are few clear
indications for the administration of albumin or synthetic colloids; they do not prevent the formation of brain edema,
and hetastarch, in sufficient quantities, may be associated with coagulopathy. To reduce brain volume and improve
operating conditions, hypertonic mannitol is frequently given, with hypertonic saline representing an alternative. In
238 neurosurgical patients randomized to receive either 160 mL of 3% saline or 150 mL of 20% mannitol to induce
brain relaxation during neurosurgery, brain relaxation was superior in the group receiving 3% saline, although there
were no differences in major outcomes.23 Solutions containing dextrose are best avoided unless there is a specific
indication for use (e.g., hypoglycemia).
Are there implications for perioperative neurosurgical fluid management in the multiple clinical trials of
“liberal” versus “restrictive” fluid therapy that have been conducted in non-neurosurgical patient populations?
Restrictive fluid therapy appears to most strongly improve clinically important outcomes, such as cardiopulmonary
complications and tissue healing, in patients undergoing intra-abdominal surgery, especially colectomy.24 However,
after less complication-prone procedures, such as laparoscopic cholecystectomy and arthroscopic surgery, more
liberal fluid administration has been associated with fewer less severe complications, such as nausea and
vomiting.25;26 In the absence of definitive data, fluid management during craniotomy should be targeted in the range
between “too dry” and “too wet.”
Disorders of Antidiuretic Hormome. One relatively common complication of neurologic and neurosurgical
disease is pituitary dysfunction. In a subset of neurosurgical patients, a relative excess of antidiuretic hormone
(ADH) is associated with hyponatremia,27 although the syndrome of inappropriate antidiuretic hormone (SIADH)
must be distinguished from other, more common causes of mild hyponatremia.28 Recent publications have
demonstrated that conivaptan is useful in hyponatremic neurosurgical patients in which fluid restriction is not
sufficient to resolve hyponatremia.29
Less commonly, neurogenic diabetes insipidus (DI), characterized by the production of large volumes of
dilute urine in the face of a normal or elevated plasma osmolality, may occur in association with hypothalamic
lesions or after pituitary surgery or TBI. After TBI or pituitary surgery, polyuria may be present for only a few days
within the first week, may be permanent, or may demonstrate a triphasic sequence: early diabetes insipidus, return of
urinary concentrating ability, then recurrent diabetes insipidus. In severe cases, urinary output can exceed 1 L/hr.
The diagnosis of DI requires a high index of suspicion when dealing with patients at risk. Confirmatory evidence
consists of low urinary osmolality despite hyperosmolality and hypernatremia.
Left untreated or unrecognized in patients who cannot ingest sufficient water to balance urinary output, DI
can quickly result in severe hypernatremia, hypovolemia, and hypotension. Hypernatremia may produce secondary
neurologic symptoms, including stupor, coma, and seizures. The clinical consequences of hypernatremia are most
serious at the extremes of age and when hypernatremia develops abruptly. Brain shrinkage may damage delicate
cerebral vessels, leading to subdural hematoma, subcortical parenchymal hemorrhage, subarachnoid hemorrhage
(SAH), and venous thrombosis. Polyuria may cause bladder distention, hydronephrosis, and permanent renal
damage.
Although many patients who have undergone transphenoidal pituitary surgery may drink sufficient fluids to
prevent dehydration, those who do not have sufficient oral intake may require volume expansion in hypovolemic
patients and replacement of endogenous ADH. In hypovolemia secondary to DI, hypernatremia will virtually always
accompany volume deficits. Hypovolemia should be corrected promptly with 0.9% saline, after which the TBW
deficit can be replaced. The TBW deficit can be estimated from the plasma [Na +] using the equation:
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TBW deficit = 0.6 (weight in kg) [(actual [Na +] – 140)/140)]
Hypernatremia must be corrected slowly because of the risk of neurologic sequelae such as seizures or
cerebral edema.30 The water deficit should be replaced over 24-48 hr, and the plasma [Na +] should not be reduced by
more than 1-2 mEq•L-1•hr-1. Once hypovolemia has been corrected, water can be replaced orally (if the patient can
drink fluids), enterally, or with intravenous hypotonic fluids.
Replacement of exogenous ADH can be accomplished with either aqueous vasopressin (5-10 units iv or im)
or desmopressin (DDAVP) 1-4 mcg subcutaneously, or 5-20 mcg intranasally every 12-24 hr. Incomplete ADH
deficits (partial DI) may respond to agents, such as chlorpropamide and clofibrate, or a thiazide diuretic, to stimulate
ADH release or enhance the renal response to ADH.
Cerebral Aneurysms and Vasospasm. Patients who present for surgery after rupture of a cerebral aneurysm
require careful consideration of fluid management. Cerebral vasospasm is a leading cause of morbidity in these
patients, producing death or severe disability in approximately 14% of patients who survive rupture of their
aneurysm; angiographic evidence of vasospasm occurs in as many as 60-80% of patients after SAH.31 Arteriography
in patients who have vasospasm demonstrates luminal irregularities in large conducting vessels, although these are
not the major site of precapillary resistance. CBF is not reduced until the angiographic diameter of the cerebral
arteries is decreased by 50% or more compared to normal. The intraparenchymal cerebral resistance vessels tend to
dilate after the onset of spasm of the larger vessels, thus partially compensating for increased upstream resistance.
ICP and cerebral blood volume may actually increase during vasospasm, owing to dilation of cerebral capacitance
vessels (veins) and accumulation of tissue edema resulting from cerebral ischemia.32
The incidence of vasospasm peaks between the fourth and tenth days after SAH. Symptomatic vasospasm
is often heralded by disorientation and drowsiness, developing over a period of hours. Focal deficits may follow.
Vasospasm is presumed to be the cause if recurrent hemorrhage, mass lesions, intracranial hypertension, meningitis,
or metabolic encephalopathy can be excluded. The diagnosis may be confirmed by angiography or documentation of
high-velocity flow patterns by Doppler examination of the cerebral vessels.
Two therapeutic interventions – calcium entry blockers and hypervolemic-hypertensive-hyperdynamic

(triple H) therapy – have been proposed to decrease the incidence or severity of vasospasm. Anecdotally, in patients
suffering from neurologic impairment secondary to vasospasm, volume loading in conjunction with inotropic
support and pressors can reverse or reduce neurologic symptoms. 33 Pressor-induced hypertension, which can only be
used after a ruptured aneurysm is clipped or coiled, may improve cerebral blood flow and brain tissue oxygenation
more effectively than volume loading.34 Normovolemic hypertension may well be the most appropriate goal for
patients with vasospasm after definitive therapy for a ruptured intracranial aneurysm. 35 Therapeutic expansion of
blood volume or elevation of systemic blood pressure may also provide diagnostic information; of 95 patients with
symptomatic vasospasm in whom symptoms improved in response to volume expansion or pressure elevation, death
and disability were much less likely.36 A well-designed clinical trial is necessary to distinguish between the
influence of hypervolemia and increased arterial blood pressure on outcome after subarachnoid hemorrhage 37.
Summary
Appropriate fluid therapy for patients with neurologic disorders requires an understanding of the basic
physical principles that govern the distribution of water between the intracellular, interstitial and plasma
compartments. In the intact CNS, unlike peripheral tissues, osmolar gradients are major determinants of the
movement of water. In addition to management of intravascular volume, fluid therapy often must be modified to
account for disturbances of [Na+], which are common in patients with neurologic disease. Because of the limited
amount of data to guide perioperative fluid therapy, current management is often empirical and based on inferences
from basic research or clinical trials in related populations.
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LOWER EXTREMITY PERIPHERAL NERVE BLOCKS

Prof. Admir Hadzic/Micheline Heylen Genk, Belgium
The focus of this review is on techniques and applications of lower extremity (LE) nerve
blocks, new developments in LE PNBs, and update in ultrasound-guided PNBs. The review
will also include practical aspects of nerve block techniques and protocols for their successful
implementation in everyday practice. This review is organized into A) Techniques to four most
common LE PNBs reproduced from the NYSORA’s International Standardized Techniques
Educational Posters http://www.nysora.com/educational-tools/3222-nysora-educational-
posters.html) and B) Other more common PNBs for LE anesthesia and analgesia.
A) MOST COMMON LOWER EXTREMITY PERIPHERAL NERVE BLOCKS

FEMORAL NERVE BLOCK
• Indications:
surgery on femur,
anterior thigh and knee,
patella fracture,
quadriceps tendon repair,
analgesia for hip and
femur fractures
• Patient position: supine
• Transducer: linear
• Needle: 22G, 5-10cm short bevel
• Common EMR
obtained: quadriceps
muscle
contraction
• Local anesthetic: 10-20 mL
• Ultrasound technique: Transducer placement
- Initial transducer Figure 1: Transducer placement
placement: femoral
crease, parallel and
inferior to inguinal
ligament, Figure 1. Must
identify the femoral
artery and femoral nerve
lateral to it, Figure 2.
- Initial depth setting: 4 cm
Ultrasound image
- Landmarks:
common femoral artery
and fascia iliaca (Figure
2: White arrows)
- Ideal view:
Femoral nerve lateral to
femoral artery. Below
fascia iliaca, above
departure of profunda
femoris artery
Ultrasound guided technique

- Technique:
needle insertion in
plane, lateral to
medial.
Alternatively out of plane
- Ideal spread of local anesthetic: Under the fascia iliaca
around the femoral nerve Figure 2: Ultrasound image of FM and
- Number of fascia
injections: One. Bolus-
Observe-Reposi- tion
(BOR)
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- Tips: Obtain
view proximal to
bifurcation of the femo-
ral artery. Tilt the probe
cranially/caudally to
optimize the image of
the nerve. Puncture the
fascia iliaca lateral to
the edge of the femoral
nerve. Beware: motor
weakness of the
quadriceps muscle can
occur; risk of falls.
Figure 3: Reverse ultrasound anatomy
Figure 4: Anatomy
Abbreviations: SAIS: Superior Anterior Iliac Spine

IL: Inguinal Ligament FA: Femoral Artery
IPM: Iliopsoas Muscle FV: Femoral Vein
FI: Fascia Iliaca TFL: Tensor Fascia Lata
SaM: Sartorius Muscle IPM: Iliopsoas Muscle
FN: Femoral Nerve LFCN: Lateral Femoral Cutaneous Nerve
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SAPHENOUS NERVE BLOCK AT THE ADDUCTOR CANAL
• Indications: analgesia for knee surgery as a component

of multimodal analgesia. In combination with sciatic nerve block
for surgery below the knee.
• Patient position: supine with leg abducted
and
externally rotated
• Transducer: linear
• Needle: 22G, 5-10 cm short bevel
• Common EMR obtained: if used, paresthesia of medial
aspect of lower leg or vastus medialis twitch can be elicited
• Ultrasound technique
- Initial transducer placement: transverse view at medial
aspect of lower thigh to mid-thigh level (Figure 5)
- Initial depth setting: 4 cm
Figure 5: Transducer placement
Ultrasound image
- Landmarks: sartorius muscle, femoral artery (Figure 6)

- Ideal view: femoral artery in the subsartorius plane at the
medial edge of the vastus medialis
- Technique: needle insertion in plane or out of plane,

lateral to medial (Figure 7)
- Ideal spread of local anesthetic: in the fascial plane
underneath sartorius muscle on both sides of the artery (Figure 6:
arrows)
- Number of injections: one. Bolus-Observe-Reposition
- Tips: when localization of femoral artery proves difficult,
use power Doppler and/or start scanning at the level of the
femoral crease and follow the course of the femoral artery distally
into the canal. Figure 6: Ultrasound image
Figure 7: Reverse ultrasound anatomy Figure 8: Anatomy
Abbreviations:
ALM: Adductor Longus Muscle SaM: Sartorius Muscle
AMM: Adductor Magnus Muscle SaN: Saphenous Nerve
FA: Femoral Artery VMM: Vastus Medialis Muscle
FV: Femoral Vein VMN: Vastus Medialis Nerve
RFM: Rectus Femoris Muscle
Refresher Course Lectures Anesthesiology 2016 © American Society of Anesthesiologists. All rights reserved. Note: This publication contains material copyrighted
by others. Individual refresher course lectures are reprinted by ASA with permission. Reprinting or using individual refresher course lectures contained herein is
strictly prohibited without permission from the authors/copyright holders.
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SCIATIC NERVE BLOCK, SUBGLUTEAL LEVEL

• Indications: anesthesia and analgesia for surgery on
femur, at and below the knee
• Patient position: prone, lateral or oblique (Figure 9)
• Transducer: linear. Curved in larger patients
• Needle: 22G, 8-10 cm short bevel
• Common EMR obtained: twitch of calf or foot
- Initial transducer placement: gluteal crease (Figure 9). Scan
cephalad-caudal until the best view of the oval-shaped sciatic
nerve and the muscular tunnel in which it travels are visualized
regardless of the level.
- Initial depth setting: 4-5 cm
Ultrasound image
- Landmarks: Sciatic nerve, gluteus maximus, fascia

underneath gluteus maximus
- Ideal view: sciatic nerve in common connective tissue sheath
(intermuscular tunnel, Figure 10)
- Technique: needle insertion in plane, lateral to medial.

Alternatively out of plane
- Ideal spread of local anesthetic: around the nerve, within the
common connective tissue sheath (Figure 10)
- Number of injections: one. Bolus observe reposition
- Tips: avoid inferior gluteal artery. Needle should enter the
sheath of the sciatic nerve either at the lateral or medial aspect of
the nerve. Transducer pressure and tilt often required to obtain the
adequate view.
Figure 10: Ultrasound image
Figure 9:
Transducer placement
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Abbreviations:
AMM: Adductor Magnus Muscle
BFM: Biceps Femoris Muscle
FL: Fascia Lata
GMM: Gluteus Maximus Muscle
IGA: Inferior Gluteal Artery
ScN: Sciatic Nerve
SCIATIC BLOCK, POPLITEAL LEVEL

• Indications: anesthesia and analgesia for surgery below
the knee
• Patient position: prone. Oblique (Figure 13) or
supine with the knee flexed
• Transducer: linear. Curved in larger patients
• Needle: 22G , 5-10 cm short bevel
• Common EMR obtained: Twitch of calf, foot, or toes
• Local anesthetic: 20 mL
- Initial transducer placement: transverse. 4-5 cm above the
popliteal crease
- Initial depth setting: 4-5 cm
Ultrasound image
- Landmarks: popliteal artery and vein, femur, biceps femoris

muscle Figure 13:Transducer placement
- Ideal view: sciatic nerve with tibial nerve and common
peroneal nerve slightly diverged within common connective
tissue sheath of sciatic nerve (Figure 14: arrows).
Figure 14: Ultrasound image

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- Technique: needle insertion in plane, from lateral or medial; alternatively out of plane when more convenient.
- Needle tip position: inside the common connective tissue sheath, between and around tibial nerve and common peroneal nerve
- Number of injections: one. Bolus-Observe-Reposition
- Tips: if imaging the division of the sciatic nerve proves difficult, start scanning at the popliteal crease, where the tibial nerve
is located postero-lateral to the popliteal vein. After injection, scan proximally-distally to assure the local anesthetic spread around the
tibial nerve and common peroneal nerve. Catheter is placed within the sheath (Figure 16, arrows)
Abbreviations:
BFM: Biceps Femoris Muscle
CPN: Common Peroneal Nerve
PA: Popliteal Artery
PV: Popliteal Vein
ScN: Sciatic Nerve
StM: Semitendinosus Muscle
TN: Tibial Nerve
B) OTHER MORE COMMON PERIPHERAL NERVE BLOCKS

LUMBAR PLEXUS BLOCK
• Major branches of the lumbar plexus: genitofemoral, lateral femoral cutaneous, femoral
nerve, obturator nerve, iliohypogastric, ilioinguinal
• Provides anesthesia/analgesia to: anterolateral thigh, medial thigh, knee, portions of the
hip
• Indications: minimally invasive hip, anterior thigh and knee surgery
• Patient position: lateral decubitus position with slight forward tilt. Foot to be blocked
positioned over the dependent leg
Nerve Stimulator Technique

- Prep/drape and inject LA into the skin and paravertebral muscles
- Set nerve stimulator at 1.5 mA
- Place fingers of palpating hand firmly against the paravertebral muscles to stabilize the landmarks and to decrease the
skin-nerve distance
- Advance needle – should feel local twitches of paravertebral muscles
- Advance further until:
- Quadriceps muscle twitches are noted or
- Transverse Process (TP) is contacted. If TP is contacted, walk off TP superiorly or inferiorly
- Usual depth of needle placement: 6 – 8 cm
- Don’t need current less than 0.5 mA (Dural sleeves thickly envelop the roots of the LP; motor stimulation with low current
may indicate placement of needle inside a dural sleeve – can lead to LA spread to epidural or subarachnoid space = epidural or
spinal anesthesia)
- Inject LA: 25-35 ml slowly with frequent aspirations
• Tips
- Skin – LP distance ranges 6.1-10.1 cm in men and 5.7-9.3 cm in women
- Distance from TP to LP is typically less than 2 cm, independent of BMI or gender
- Contact with TP provides consistent landmark to avoid excessive needle penetration during this
block
- Once the TP is contacted, walk off the bone either superiorly or inferiorly approx 2 cm deeper – but not deeper
- Do not inject forcefully (<15 psi)) – this could indicate an intraneural intrafascicular or intradural
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cuff needle placement

- 3 Potential Problems:
- Epidural Spread: Reports of ≥15% and higher
- Inject slowly and aspirate frequently; avoid fast, forceful injections
- Systemic toxicity
- Monitor the patient closely for signs of LA toxicity, hypotension and high spinal blockade
Ultrasound guidance
- Visualization of TP and estimation of the surface landmarks and depth of needle placement always possible
- Psoas muscle and lumbar plexus and in-plane needle guidance possible in slim patients
- At present time, US mostly used as US-assisted, rather then real-time guided LPB
- Out of plane technique (US-assisted) may me more practical in patients with less then ideal
anatomy.
- Nerve stimulation concomitantly used with US by most clinicians.
Figure 17 and 18: ultrasound anatomy

The lumbar paravertebral region is typically imaged between L3 and L4 transverse processes. Levels can be localized by
scanning the respective transverse processes on posterior longitudinal paravertebral view. Lumbar plexus is not always clearly
visualized in adults; the psoas major muscle is often used as a surrogate US landmark. The lumbar plexus lie within the medial
and posterior 1/3 of the psoas major muscle.
ANKLE BLOCK
Quick facts
1. Ankle block requires blockade of
- Four branches of the sciatic nerve: deep femoral, superficial peroneal nerve,
ural nerve
- One cutaneous branch of the femoral nerve
- Saphenous nerve
2. Indications: surgery on toes, surgery on distal ½ to ⅓ of foot
3. Patient position: supine with legs extended, foot supported on footrest
• Landmarks
1. Deep nerves
- Deep Peroneal Nerve: immediately lateral to DP artery, lateral to
tendon of extensor hallucis longus muscle
- Posterior Tibial nerve: immediately posterior and lateral to PT artery,
halfway the medial malleolus and the Achilles tendon
2. Superficial nerves
- Superficial Peroneal: ring subcutaneous injection
- Sural nerve: lateral malleolus
- Sapgenous nerve: medial malleolus
1. Deep nerves Figure 19. Tibial Nerve block

- Deep Peroneal Nerve:
immediately lateral to DP artery,
lateral to tendon of extensor
hallucis longus muscle
- Posterior Tibial nerve:
immediately posterior and lateral
to PT artery, halfway the medial
malleolus and the Achilles tendon
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Figure 20. Saphenous Nerve block Figure 21. Deep Peroneal Nerve block
2. Superficial nerves
- Superficial Peroneal nerve block: Ring subcutaneous injection (Fig 23)
- Sural nerve: lateral malleolus (Figure 22)
- Saphenous nerve: medial malleolus (Figure 20)
• Technique
1. Cleanse skin with antiseptic solution
2. Sedate for comfort
3. Local with 25G neelde attached
- Deep peroneal (Figure 21)
• Place finger on DP (dorsalis pedis) pulse or lateral to tendon of
extensor hallucis longus (if
pulse not readily palpable) Figure 22. Sural Nerve block
• Advance needle until the bone is contacted
• Withdraw needle 1-2 mm, inject 2-3 ml of local anesthetic
Figure 23. Superficial Peroneal Nerve block
• Without completely removing needle from skin, use a fan technique to
redirect needle 30º
medially and laterally and injecting 2-3 ml of local in both directions
- Posterior tibial (Figure 19):
• Place finger on PT (posterior tibial) pulse midway between medial
malleolus and Achilles
tendon
• Advance needle directly posterior to the pulse until bone contacted
• Withdraw needle 1-2 mm, inject 2-3 ml of local anesthetic
• Use the same fan technique as deep peroneal nerve
- Blocks of the superficial peroneal, sural, and saphenous nerves:
• Block of all three nerves accomplished by a simple circumferential, SQ
injection of local
anesthetic subcutaneously at the level of the medial and lateral malleolus
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Tips:
- This block involves up to five needle injections, which can be uncomfortable to patients. Sedate with 2-4mg of midazolam
and 250-750 µg of alfentanil for patient comfort. Epinephrine controversial. Typical onset 10-25 minutes. Esmarch bandage or
tourniquet at ankle level is well-tolerated.
• Ultrasound Technique
- Primarily used for posterior tibial nerve and
deep peroneal nerve blocks
- Tibial nerve is visualized easily in the
immediate vicinity of the posterior tibial
artery (Figure 24)
US-guided Technique of anesthetizing all other

nerve blocks in ankle block consists of
identification of individual nerves and targeted
injections of 3-5 ml of local anesthetic into the
tissue fascia that contains the nerve of interest.
Figure 24. US-Guided Posterior Tibial Nerve Block
EQUIPMENT AND MONITORING FOR LE PERIPHERAL NERVE BLOCKS
REFERENCE
Complete references can be downloaded at www.nysora.com
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Information Management Systems to Assist with Patient Blood

Management
Daryl J. Kor, MD, MSc Rochester/Minnesota
Introduction
Increasingly, health care delivery has been recognized as risky business. Awareness of these risks came to
a razor focus following the 2000 publication of To Err Is Human when it was estimated adverse events occur in 2.9
to 3.7% of all U.S. hospitalizations.1 It was further suggested that between 44,000 and 98,000 potentially avoidable
deaths were related to such events.1 Beyond such risks, we have also begun to appreciate the inefficiencies and
unnecessary waste that exist in our current health care system. To this point, it has been estimated that
approximately $0.30 to $0.40 of every dollar spent on health care (> $500,000,000,000 per year) is spent on costs
associated with overuse, misuse, and overall inefficiencies in care delivery.2
What does this have to do with transfusion practices? To begin, it has been estimated that the total annual
transfusion expenditures may approach $10.5 billion just for red blood cells in the U.S. alone. 3,4 Increasingly, we
have also begun to appreciate the extreme variability in transfusion practices and overall liberal approach to the
administration of blood component therapies.5,6 These liberal approaches often do not adhere to the present
understanding of best transfusion practices. In addition to unnecessarily putting patients at risk of transfusion-
related complications, the inappropriate administration of blood component therapies greatly contributes to the
economic strain experienced in our health care system. Indeed, the American Hospital Association (as well as many
other quality advisory groups) has identified blood transfusion as one of the most over-used resources in all of health
care.7
In an effort to improve transfusion practices, increasing interest and emphasis has been placed on the
development of programs that are designed to optimize the care of patients who might need transfusion. Such
programs are generally termed “patient blood management (PBM).”8,9 As with the larger issue of suboptimal value
throughout the health care sector, a core element believed to carry potential for improving the value of care delivery
is the development and implementation of innovative informatics solutions.2 In this portion of this refresher course
lecture, we will outline the importance of information management systems and clinical informatics as they relate to
the topic of PBM.
Clinical Informatics and Patient Blood Management
Recently, the American Association of Blood Banks (AABB) published recommendations for best
practices for a PBM program.10 In this document, information systems were identified as a key component needed
to ensure the success of a PBM program. Key processes that an information system should support include:
1. Guideline dissemination and integration into the clinical practice, particularly in the form of
computerized clinical decision support.
2. Monitoring of transfusion practice with particular emphasis on issues such as:
a) patient outcomes
b) physician blood ordering
c) blood utilization
d) preoperative optimization of coagulation
e) preoperative anemia management and autologous donation.
Additional possibilities with robust transfusion-related information systems also include syndrome
surveillance (e.g., transfusion-related acute lung injury, transfusion-associated circulatory overload) as well as
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predictive and prescriptive analytics. Examples of resources and proven strategies which can address the
informatics needs of a PBM program are highlighted below.
Information Systems and Clinical Informatics
Informatics Infrastructure
Though the promise of clinical informatics has long been understood, numerous challenges have limited the
impact of related activities in the health care environment. Examples include issues relating to data availability,
quality, standardization, and interoperability. Challenges with scalability, timeliness, and representation also persist
as does the general disconnect between those in the more traditional informatics space and clinician’s providing care
at the bedside. These challenges are only amplified in environments such as the intensive care unit and operating
room where impressive amounts of data are generated on diverse patients rapidly and continuously. The complexity
of health care data, and the variety of platforms on which data are sourced and retained frequently exceed the
capacity of clinicians to generate meaningful and actionable information. 11 Therefore, while the implementation of
the electronic medical record (EMR) into clinical practice creates significant opportunity, it also presents a challenge
to provide information to practitioners, educators, researchers, patients, and families in a meaningful and
consumable way. Importantly, most systems incompletely capture data from disparate source databases such as the
laboratory, imaging department, physician orders, and pharmacy. The result is an incomplete record that cannot
fully implement complex event reporting and decision support algorithms.
Two significant opportunities to address the limitations noted above include 1) targeted collaborations with
vended EMR products (e.g., Cerner, Epic) to provide transfusion-related EMR solutions, and 2) the development of
institutional data warehouses and data marts that can be leveraged to support the needs of the PBM program. In
regards to the former, significant impact can be achieved with the development of meaningful computerized clinical
decision support.12-14 To address the monitoring and analytic needs of our PBM program, we have also developed a
transfusion data mart. This is a robust data environment that contains highly granular information which details the
experience of every transfusion episode that occurs at Mayo Clinic. In addition to highly granular transfusion data,
relevant data from additional disparate source databases contained within the EMR also are included. This includes
information from the laboratory information systems, demographic data, procedural details, and coding and billing
information.15 This data mart provides unique opportunities for developing highly granular transfusion reports
detailing most essential aspects of the transfusion practice at Mayo Clinic as well as allowing opportunities for
innovative analytics work.
Clinical Decision Support
As the complexity of the health care environment has increased, the importance of well-thought,
meaningful clinical decision support has increased. When evaluating the individual components of a PBM program,
implementation of well-thought electronic clinical decision support tools have been shown to meaningfully impact
transfusion behaviors.13,14 Clinical decision support implemented at the time of order entry can assist clinicians by
helping to guide them towards appropriate transfusion behaviors or alternatively steering them away from the
administration of blood components when potential recipients are unlikely to benefit. Even apparently simple
interventions such as defaulting the transfusion “dose” to a single unit of red blood cell (RBC), as opposed to
multiple units, can have very meaningful impacts on overall transfusion practice. 13 A recent systematic review
highlighted the impact of electronic decision support on transfusion practice. 14 Although the Mayo Clinic
transfusion practice has noted a significant impact with the meaningful implementation of clinical decision support
for all of the major transfusable blood components, the published evidence in support of non-RBC blood
components is less robust than it is with RBC transfusions.12,14
Transfusion Monitoring and Analytics
Data-Driven Approaches in Patient Blood Management. Health care providers often have
perceptions regarding their clinical practice. However, when quality data are available, it often contradicts
these clinical impressions. As with so many other areas of health care, data-driven approaches to
understanding the transfusion landscape can prove impactful. 16 Moreover, data detailing the impact of
specific PBM interventions can add significant value to a PBM program. Recently, Crohn and colleagues
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have shown a data-driven approach to PBM can markedly reduce the proportion of inappropriate
transfusion orders and the number of overall transfusion events. 17 Whenever possible, data detailing the
transfusion practice, adherence to best practice guidelines, and occurrence of adverse events should be
made available to help guide the PBM program.
Transfusion Performance Metrics. Generally speaking, clinicians are competitive individuals

who continually strive to outperform. This competitive nature can be leveraged to support meaningful
change in transfusion practice. To this end, data can be a powerful driver of change. Indeed, multiples
studies have highlighted the importance of providing data back to the practice on how they are performing
in terms of optimizing transfusion practices.17 As with the clinical decision support approaches outlined
above, delivery of meaningful transfusion performance metrics or quality indicators to the clinical service-
lines appears to be a very key element to optimizing transfusion practice.
Precision Medicine in PBM. In addition to supporting clinical decision support and performance
metric activities, robust information systems can also help us to refine our understanding of appropriate
indications (or contraindications) for blood component therapies. Although clinical trial results continue to
guide changes in transfusion practice, the increased availability of “big data” infrastructure and
methodologies open the door to new approaches for refining our understanding of “best transfusion
practice.” In addition to supporting more data-driven transfusion practices today,18-20 these innovative data
science approaches can also be used to more precisely define the optimal transfusion practice of
tomorrow.21,22
Summary
Despite a growing emphasis on the appropriate management of patients who may need hematologic
support, practice frequently remains inconsistent, anecdotal, and far too often inappropriate. Patient blood
management carries the potential for meaningful change in transfusion practices. Development and implementation
of innovative informatics approaches in support of the PBM program can greatly facilitate these improvements in
transfusion practice.
References
1. Institute of Medicine (US): Committee on Quality of Health Care in America; Kohn LT, Corrigan JM,
Donaldson MS (eds): To Err is Human: Building a Safer Health System. National Academies Press:
Washington, DC, 2000, pp 287.
2. Institute of Medicine and National Academy of Engineering: Committee on Engineering and the Health
Care System; Reid PP, Compton WD, Grossman JH, Fanjiang G (eds): Building a Better Delivery System:
A New Engineering/Health Care Partnership, National Academies Press: Washington, DC, 2005, pp 276
3. Shander A, Hofmann A, Ozawa S, Theusinger OM, Gombotz H, Spahn DR: Activity-based costs of blood
transfusions in surgical patients at four hospitals. Transfusion 2010; 50: 753-65
4. Whitaker BI, Henry RA: US Department of Health and Human Services: The 2011 National Blood
Collection and Utilization Survey. US Department of Health and Human Services: The 2011 National
Blood Collection and Utilization Survey 2011.
https://www.aabb.org/research/hemovigilance/bloodsurvey/Documents/11-nbcus-report.pdf (accessed
6/14/2016).
5. Bennett-Guerrero E, Zhao Y, O'Brien SM, Ferguson TB, Peterson ED, Gammie JS, et al: Variation in use
of blood transfusion in coronary artery bypass graft surgery. JAMA 2010; 304:1568-75
6. Qian F, Osler TM, Eaton MP, Dick AW, Hohmann SF, Lustik SJ, et al: Variation of blood transfusion in
patients undergoing major noncardiac surgery. Ann Surg 2013; 257: 266-78
7. Combes J, Arespacochaga E: Appropriate Use of Medical Resources. American Hospital Association's
Physician Leadership Forum: Washington, D.C., 2013, pp 1-20
8. Society for the Advancement of Blood Management. http://www.sabm.org (accessed 6/14/2016).
9. AABB: Patient Blood Management. http://www.aabb.org/pbm/pages/default.aspx (accessed 6/14/2016).
10. American Association of Blood Banks: Standards for a Patient Blood Management Program, 1st Edition.
March 14, 2014, pp 33
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11. Ahmed A, Chandra S, Herasevich V, Gajic O, Pickering BW: The effect of two different electronic health
record user interfaces on intensive care provider task load, errors of cognition, and performance. Crit Care
Med 2011; 39: 1626-34
12. Dunbar NM, Szczepiorkowski ZM: Hardwiring patient blood management: harnessing information
technology to optimize transfusion practice. Curr Opin Hematol 2014; 21: 515-20
13. Goodnough LT, Shieh L, Hadhazy E, Cheng N, Khari P, Maggio P: Improved blood utilization
using real-time clinical decision support. Transfusion 2014; 54: 1358-65
14. Hibbs SP, Nielsen ND, Brunskill S, Doree C, Yazer MH, Kaufman RM, et al: The impact of electronic
decision support on transfusion practice: a systematic review. Transfus Med Rev 2015; 29: 14-23
15. Herasevich V, Kor DJ, Li M, Pickering BW: ICU data mart: a non-iT approach. A team of clinicians,
researchers and informatics personnel at the Mayo Clinic have taken a homegrown approach to building an
ICU data mart. Healthc Inform 2011; 28: 42, 44-5
16. Frank SM, Resar LM, Rothschild JA, Dackiw EA, Savage WJ, Ness PM: A novel method of data analysis
for utilization of red blood cell transfusion. Transfusion 2013; 53: 3052-9
17. Cohn CS, Welbig J, Bowman R, Kammann S, Frey K, Zantek N: A data-driven approach to patient blood
management. Transfusion 2014; 54: 316-22
18. Jia Q, Brown MJ, Clifford L, Wilson GA, Truty MJ, Stubbs JR, et al: Prophylactic plasma transfusion for
surgical patients with abnormal preoperative coagulation tests: a single-institution propensity-adjusted
cohort study. Lancet Haematol 2016; 3: e139-48
19. Warner MA, Jia Q, Clifford L, Wilson G, Brown MJ, Hanson AC, et al: Preoperative platelet transfusions
and perioperative red blood cell requirements in patients with thrombocytopenia undergoing noncardiac
surgery. Transfusion 2016; 56: 682-90
20. Warner MA, Woodrum DA, Hanson AC, Schroeder DR, Wilson GA, Kor DJ: Prophylactic plasma
transfusion before interventional radiology procedures is not associated with reduced bleeding
complications. Mayo Clin Proc 2016; 91: 1045-55
21. Murphree D, Ngufor C, Upadhyaya S, Madde N, Clifford L, Kor DJ, Pathak J: Ensemble learning
approaches to predicting complications of blood transfusion. Conf Proc IEEE Eng Med Biol Soc 2015;
7222-5
22. Ngufor C, Murphree D, Upadhyaya S, Madde N, Kor D, Pathak J: Effects of plasma transfusion on
perioperative bleeding complications: a machine learning approach. Stud Health Technol Inform 2015;
216: 721-5
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What’s New in RBC Transfusion Therapy. Any New TRICC's?
C. David Mazer MD, FRCPC Toronto, ON Canada
Introduction: The management of perioperative bleeding with cardiac surgery is an important clinical challenge.
Cardiopulmonary bypass (CPB) predisposes to perioperative bleeding and transfusion because of thrombocytopenia,
functional platelet defects, activation of fibrinolysis, hemodilution and depletion of coagulation factors. As a result,
up to 30% of patients develop significant microvascular bleeding after cardiac surgery, accounting for 10% of all red
cell transfusions. Although there is much variability in transfusion practice, the following factors have been
independently associated with increased risk of transfusion: age, anemia, female gender, body size, preoperative use
of antithrombotic therapy, significant systemic disease, CPB time, and type and urgency of procedure1-6.
Rationale for Blood Conservation: The cost and risks associated with allogeneic transfusion are significant 7.
Several studies have shown that bleeding, anemia and transfusion of allogeneic blood are all important predictors of
adverse outcome8,9. Multi-disciplinary blood conservation programs have been shown to reduce red blood cell
transfusion and associated adverse outcomes including infection and length of hospital stay in CABG patients 10-12.
Moskowitz et al. utilized propensity matching to compare outcomes in 586 patients from a center with an
established blood conservation program relative to other centers representing standard of care (common practice of
transfusion)12. They demonstrated a significant reduction in RBC transfusion rate (10.6% versus 42.5%; p < 0.0001),
and mortality (0.8% vs. 2.5%; p=0.02). Thus, blood conservation can reduce risks associated with transfusion.
“Blood conservation” is but one part of an overall blood management program, the goals of which are to improve
patient outcomes with appropriate use of blood products13,14. The focus of most blood management programs is
optimization of red cell mass and avoidance or reduction of allogeneic red blood cell transfusion, but similar
considerations should apply to other blood components as well. Blood management spans the entire perioperative
period, and has the goals of optimizing preoperative hemoglobin levels and hematopoiesis, correcting underlying
coagulopathy, minimizing intra- and post-operative blood loss, and maximizing tissue oxygen delivery. All
institutions can benefit, even those with below average transfusion rates.
Adaptive Physiology of Anemia: As the degree of anemia increases, the normal physiologic response is to increase
cardiac output (CO) and vital organ blood flow (brain, heart) and increase oxygen extraction. At some point, these
compensatory mechanisms become exhausted and a state of inadequate oxygen delivery for tissue needs is
reached15. Although some older reports have suggested that tissue hypoxia does not occur in the brain and heart
until the hemoglobin (Hb) is very low, newer studies with non-invasive oxygen sensing methodology have
demonstrated that brain microvascular PO2 decreases progressively below Hb values of 9 g/dL. In addition, there is
clear evidence that tissue hypoxia occurs earlier in tissues such as the kidney and liver, relative to the brain and
heart. Activation of hypoxic mechanisms has been observed at hemoglobin thresholds as high as 9 g/dL in
experimental models16,17.
Risks of Anemia: The physiological and clinical consequences of anemia are well documented, with several
studies demonstrating an association between decreasing hemoglobin concentration and adverse outcome.
Preoperative anemia has been recognized as a significant risk factor for adverse outcome and mortality in patients
undergoing non-cardia and cardiac surgery 4,6,8,18,19. One meta-analysis has demonstrated that anemia was associated
with increased mortality (OR 2⋅90; p <0⋅001), acute kidney injury (OR 3⋅75; p <0⋅001) and infection (OR 1⋅93; p
=0⋅01)19. More recent studies have suggested that even mild to moderate degrees of anemia are associated with
increased perioperative morbidity and mortality9,20. Lowest hematocrit during cardiopulmonary bypass has also been
associated with severe adverse outcomes including AKI, stroke, and mortality5,21. While preoperative anemia may
identify a patient at risk, it remains to be determined whether or not treating anemia prior to surgery with either
transfusion or hematopoietic therapy improves outcome.
Transfusion Risks: Over the last 60 years, a wide variety of bacterial, viral and parasitic agents have been spread
via blood transfusion causing hepatitis, HIV, malaria, syphilis, West Nile, and other infectious diseases22-25.
Although transmission of infection is widely believed to be a common risk of transfusion, modern screening and
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testing procedures have significantly reduced these risks to approximately 1 in 2-10 million for viral agents. Current
literature suggests that the most common transfusion related side-effects include TRALI (Transfusion Associated
Lung Injury), TACO (Transfusion Associated Circulatory Overload), febrile non-hemolytic transfusion reactions
and other immunologic reactions. In the past, TRALI (30%) eclipsed ABO Incompatibility (20%) and Transfusion
Associated Sepsis as the leading cause of known and reported allogeneic blood transfusion related death. Donor
plasma from multiparous women is thought to be an important risk factor for TRALI and it has been suggested that
the preferential use of male donor plasma has resulted in a significant reduction in the incidence of TRALI. On the
other hand, Welsby et al reported that female donor plasma recipients had a lower incidence of pulmonary
dysfunction and a lower incidence of prolonged hospitalization compared to male donor recipients26, suggesting the
potential for other mechanisms being involved.
Risks of Transfusion
Infectious Non-infectious
HIV 1:2-10 million Febrile reaction 1-10:1,000
Hepatitis B 1:155,000-1.7 million TRALI 1-20:100,000
Hepatitis C 1:2-7 million TACO 1.9:10,000
HTLV 1:3-4.3 million Acute Hemolysis 1-7.9:100,000
Bacterial contamination 0.03-3.3:100,000 Anaphylactic reaction 8:100,000
Other (eg Yersinia, West Nile, 1:1 million Death 1:200,000-5.6 million
malaria)
Sources: SHOT, NHLBI, O’Brien et al23, Vamvakas et al22, Delaney et al24
Costs of Transfusion: There are many costs associated with transfusion, including recruitment and donor
collection, infectious agent testing, manufacturing, shipping, handling, labeling, pre-transfusion testing, transfusion
costs, post-transfusion sequelae and regulatory and legal costs. The overall cost for a hospital to administer one unit
of blood to a patient may be more than 3 times the cost of its actual acquisition. An activity-based costing model in
surgical patients from 2 US and 2 European hospitals found the per-unit RBC cost to be USD$ 760.82 (+/-$293.74)7.
The total annual per hospital expenditures for blood and transfusion related activities ranged from $1,618,780 to
$6,030,589 just for surgical patients.
While the range of options for patient blood management may be similar for most hospitals, each institution should
pick its own combination of approaches to produce the best solution. It is important to remember that the options
are not mutually exclusive: each option may result in up to 1-2 units of blood saved per patient, and some options
may, in fact, be better in combination. The incremental benefit of individual strategies varies between institutions.
Similarly, although expert opinion and outside advice may be helpful, an internal and institution-specific approach
to blood management is usually best. A database or data management system is essential to provide accurate
baseline institution-specific data. An institution-specific estimate to predict risk of transfusion for different types of
procedures can be developed or previously published prediction rules can be adapted27,28.
It is extremely useful to engage the administrative leadership of the hospital in the process. In addition to the
benefits of transfusion reduction and patient outcome, other positive outcomes such as cost reduction, fewer surgical
cancellations, quality improvement, and marketing opportunities may also be attractive to the CEO, CFO, Board of
Directors and Medical/Nursing leaders. It may also be seen as a patient safety initiative with associated potential for
improvement in patient outcomes and liability reduction. Comparison of centers that utilize patient blood
management programs to those who do not, suggests that such programs can reduce RBC transfusion, severe
adverse events and mortality11,12.
Effect of Storage on RBCs: The shelf life of RBCs is determined by a minimum 24-hour post-transfusion survival
of 75% of the transfused red cells. Additional criteria are related to free hemoglobin (<1.0%) and white blood cell
levels (<1 million/unit in leukoreduced blood). Storage improvement techniques have increased the shelf-life of
blood from 21 to the current 42 days. It has been estimated that 20-40% of all stored RBC units are >28 days old at
the time of transfusion, and with supply fluctuations, up to 40% of blood may be within 3 days of expiration.
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RBCs undergo many complex biochemical, environmental, structural and biomechanical changes during storage.
The shape of the red cell is transformed from a normal biconcave disc to a spiculated and crenated echinocyte, then
to a swollen sphereocyte. There is also a rapid and marked fall in 2 bioactive forms of RBC nitric oxide (Hb-bound
NO, and S-nitrosohemoglobin), as well as their effector response, RBC mediated hypoxic vasodilation 29.
Prolonged storage time has been associated with increased morbidity and mortality in a wide variety of clinical
settings, including patients with trauma, sepsis, and critical illness. For cardiac surgery, length of RBC storage has
been correlated with death, renal dysfunction and ICU length of stay and a large clinical report of the effect of RBC
storage in over 6000 cardiac surgery patients found that patients given older blood (>14 days) had significantly
worse composite and individual clinical outcomes, including renal failure, prolonged intubation, sepsis, in-hospital
and 1-year mortality30,31. However, 2 recent large randomized controlled trials have not substantiated this
observational data. The Red Cell Storage Duration Study (RECESS) randomized 1481 cardiac surgical patients to
receive leukoreduced red cells of ≤10 day vs ≥21 days of storage. There were no differences in the primary outcome
(Multi-organ dysfunction score (MODS) day 7 postop), mortality or key secondary outcomes although the average
age of administered blood was 7.8±4.8 vs 28.3±6.7 days32. Similarly, in the ABLE Study, 2430 patients in the
Intensive Care Unit were randomized to receive either standard-issue red cells (stored for 22.0±8.4 days) or fresh red
cells (6.1±4.9 days storage)33. Ninety day mortality was similar between groups (35.3% vs 37.0%), and there were
no significant between-group differences in any of the secondary outcomes (major illnesses; duration of respiratory,
hemodynamic, or renal support; length of stay in the hospital; and transfusion reactions). While these RCTs clearly
show no advantage of receiving fresh/new blood compared to standard issue blood, they unfortunately do not answer
the question of whether old blood may confer a worse outcome.
Treatment of Preoperative Anemia: Anemia is the most frequent hematologic abnormality in the preoperative
patient. In non-cardiac surgical procedures, 2 large databases have found a significant increase in the odds ratio for
mortality associated with moderate anemia (1.44 - 1.99)20,34. Because it is associated with increased risk of
allogeneic transfusion, morbidity and mortality, preoperative anemia should be evaluated, its cause identified and
treatment initiated as soon as practical. The commonest cause of preoperative anemia is iron restricted anemia,
which can have either a nutritional (iron deficiency) or functional component. Vitamin B12 or folate deficiency can
also cause preoperative anemia. In functional iron deficiency a protein produced in response to inflammatory
processes (Hepcidin) interferes with normal iron absorption, iron metabolism and bone marrow function.
Intravenous iron appears to be more effective than oral preparations in overcoming functional iron deficiency, and
several products and short-term dosing regimens of IV iron (200-1000 mg) have been used35-37. Meta-analyses have
indicated that IV iron can be efficacious in raising hemoglobin levels, improving iron values and reducing
transfusion; questions exist about the incidence of infusion reactions and infection 38,39. Similarly, several studies
have also demonstrated that erythropoiesis stimulating agents (ESAs), combined with or without IV iron, can
increase hemoglobin levels and reduce allogeneic transfusion in cardiac and non-cardiac surgery40-42. However, the
potential for thrombotic complications and other serious adverse events have raised concerns about the safe
application of this therapy. Several large RCTs are currently, or about to begin, recruiting patients to assess the
impact of IV iron and IV iron plus EPO on RBC transfusion and other important outcomes following non-cardiac
and CV surgery.
Transfusion Triggers: Given the competing risks of anemia and transfusion, the decision about when to transfuse
RBCs should be based on an evaluation of when the risks of anemia outweigh the risks of transfusion. Such
assessments are generally based on hemoglobin levels or clinical/physiological parameters such as hemodynamics,
chest pain, lactate or venous oxygen saturation. While this may be intuitively attractive in the age of personalized
medicine, the superiority of such an approach or any of these parameters has not been demonstrated in well
conducted trials. Clinical transfusion guidelines are frequently based on results of RCTs in which patients are
randomized to either a restrictive or liberal hemoglobin based transfusion trigger. For example, the ASA and
STS/SCA guidelines suggest that RBC transfusion may be indicated when the hemoglobin level is less than 7 g/dL
and should generally not be done when the hemoglobin is greater than 10 g/dL2,43. Several large randomized
controlled trials in patients without cardiac disease non-cardiac surgery have demonstrated that restrictive
transfusion results in less allogeneic blood exposure without adverse clinical outcomes. A recent meta-analysis of
RCTs highlighted the potential importance of clinical context in applying hemoglobin transfusion triggers. They
assessed infectious and ischemic events in RCTs of restrictive vs liberal transfusion according to clinical settings
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and patient characteristics44. They reported a trend toward higher ischemic outcomes in patients undergoing
cardiac/vascular procedures and in elderly patients undergoing orthopedic procedures randomized to restrictive
transfusion, but a lower rate of infectious outcomes. There were no differences in outcomes for ICU patients. On
the other hand, a recent meta-analysis of restrictive vs liberal transfusion strategies in patients with cardiovascular
disease in a non-cardiac surgery setting found no difference in mortality and divergent clinical outcomes favoring
liberal transfusion for ischemic outcomes but restrictive transfusion for acute pulmonary edema 45. In the cardiac
surgery setting, a single center RCT of 502 patients found significantly reduced transfusion rates in the restrictive
group but no difference compared to liberal transfusion in a variety of clinical outcomes 46. The more recently
published TITRe2 trial, randomized 2007 ICU patients to a liberal or restrictive transfusion strategy after cardiac
surgery and assessed the impact on serious infectious or ischemic events 47. There was no difference between the
liberal and restrictive arm in either this primary or most other secondary outcomes. However, a significant
difference in mortality at 90 days postoperatively favoring liberal transfusion was observed (4.2% vs. 2.6%; hazard
ratio, 1.64; 95% CI, 1.00 to 2.67; p = 0.045). Although the study is limited by lack of intraoperative randomization
and the mechanism of increased mortality has not been defined, the data support the need for further investigation
into the optimal transfusion threshold for patients undergoing cardiac surgery 48. This question is currently being
addressed in at least one large multicenter RCT. TRICS III (Transfusion Requirements in Cardiac Surgery III -
NCT02042898) is a global study involving 4500 moderate-high risk patients undergoing cardiac surgery in which
patients are randomized to either restrictive (transfuse if Hb <9.5 g/dL) or liberal (<9.5 g/dL in OR and ICU; <8.5 on
ward) transfusion from start of surgery until hospital discharge or day 28, whichever comes first. The primary
outcome is a composite of death, MI, stroke or dialysis, and secondary outcomes include transfusion amounts and
other important clinical outcomes. With recruitment over 3300 patients as of June 2016, results are anticipated
within 12-18 months.
Conclusions: Both perioperative anemia and red blood cell transfusion are risk factors associated with increased
morbidity and mortality after cardiac and non-cardiac surgery. The decision about when to transfuse RBCs should
be based on an evaluation of when the risks of anemia outweigh the risks of transfusion. Multidisciplinary patient
blood management programs can be very successful at minimizing blood loss, optimizing erythropoiesis and
reducing allogeneic transfusion. Recent large trials examining age of blood have found similar outcomes with
newer compared to standard issue red cells. Restrictive transfusion strategies result in less allogeneic blood exposure
and improved outcome in several observational studies. The safety of restrictive transfusion in patients with
cardiovascular disease or those undergoing cardiac surgery has not been established in randomized controlled trials
so the preferred RBC transfusion strategy in such patients is still the subject of debate. Ongoing studies such as
TRICS III may help define the optimal red blood cell transfusion practice.
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16. Tsui AK, Marsden PA, Mazer CD, et al. Priming of hypoxia-inducible factor by neuronal nitric oxide
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19. Fowler AJ, Ahmad T, Phull MK, Allard S, Gillies MA, Pearse RM. Meta-analysis of the association
between preoperative anaemia and mortality after surgery. Br J Surg 2015;102:1314-24.
20. Musallam KM, Tamim HM, Richards T, et al. Preoperative anaemia and postoperative outcomes in non-
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21. Loor G, Li L, Sabik JF, III, Rajeswaran J, Blackstone EH, Koch CG. Nadir hematocrit during
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22. Vamvakas EC, Blajchman MA. Transfusion-related mortality: the ongoing risks of allogeneic blood
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25. Chapman CE, Stainsby D, Jones H, et al. Ten years of hemovigilance reports of transfusion-related acute
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26. Welsby IJ, Troughton M, Phillips-Bute B, et al. The relationship of plasma transfusion from female and
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33. Lacroix J, Hebert PC, Fergusson DA, et al. Age of transfused blood in critically ill adults. N Engl J Med
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35. Munoz M, Gomez-Ramirez S, Cuenca J, et al. Very-short-term perioperative intravenous iron
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36. Johansson PI, Rasmussen AS, Thomsen LL. Intravenous iron isomaltoside 1000 (Monofer(R)) reduces
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39. Susantitaphong P, Alqahtani F, Jaber BL. Efficacy and safety of intravenous iron therapy for functional
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41. Yoo YC, Shim JK, Kim JC, Jo YY, Lee JH, Kwak YL. Effect of single recombinant human erythropoietin
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42. Voorn VM, van der Hout A, So-Osman C, et al. Erythropoietin to reduce allogeneic red blood cell
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44. Hovaguimian F, Myles PS. Restrictive versus Liberal Transfusion Strategy in the Perioperative and Acute
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45. Docherty AB, O'Donnell R, Brunskill S, et al. Effect of restrictive versus liberal transfusion strategies on
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46. Hajjar LA, Vincent JL, Galas FR, et al. Transfusion requirements after cardiac surgery: the TRACS
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47. Murphy GJ, Pike K, Rogers CA, et al. Liberal or restrictive transfusion after cardiac surgery. N Engl J Med
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Minimizing Transfusions for the Cardiac Surgery Patient: Tricks of the Trade
Point of Care Testing - What is the Ideal Algorithm?
Jacob Raphael, MD Charlottesville, Virginia
Cardiopulmonary bypass-induced coagulopathy is a serious complication that may result in massive

bleeding requiring transfusion of multiple units of red blood cells and pro-coagulant products. Up to 10% of cardiac
surgery patients suffer from massive blood loss [chest tube bleeding > 2000 ml over the first 24 hours after surgery,
or the need to transfuse 10 red blood cells (RBC) units, or more, over a 24-hour period]1 and up to 5% of all patients
having cardiac surgery require emergent chest re-exploration to achieve hemostasis2-4. Thus, timely control of
coagulopathy is of prime importance in order to avoid excessive blood loss that will result in transfusion of multiple
units of red blood cell and other pro-coagulant products, as well as, unplanned surgical re-explorations. A significant
body of evidence has associated allogeneic blood transfusions during cardiac surgery with increased risk of
perioperative morbidity and mortality, prolonged hospitalization and increased hospital resource utilization 5-7.
Nonetheless, despite this evidence base regarding the various risks that are associated with blood and coagulation
products transfusions8-10, the publication of transfusion guidelines11-13, and acceptance of lower transfusion
triggers14,15, transfusions still occur in as many as 50% of the cardiac surgery patients16, thus exposing them to the
sequelae of excessive bleeding and elevated risks of postoperative complications including mortality. The STS/SCA
Guidelines for Blood Conservation in Cardiac Surgery13 suggest a Class I recommendation for “A multimodality
approach involving multiple stakeholders, institutional support, enforceable transfusion algorithms supplemented
with point-of-care testing, and all of the already mentioned efficacious blood conservation interventions will limit
blood transfusion and provide optimal blood conservation for cardiac operations”. (Level of evidence A)”.
The Etiologies of CPB-Induced Coagulopathy:

The pathophysiology of Cardiopulmonary bypass-induced coagulopathy is complex and multifactorial.
Upon initiation of cardiopulmonary bypass a complex interaction between the coagulation, fibrinolytic and
inflammatory systems begins17,18. This may result in coagulopathy and excessive bleeding, as well as activation of
systemic inflammation19. The causes of cardiopulmonary bypass (CPB)-induced coagulopathy are multifactorial and
include increased fibrinolysis, as well as, a decrease in coagulation factors as a result of increased consumption and
hemodilution by the CPB priming solution20-22. Other factors include thrombocytopenia and decreased platelets
function due to hemodilution, sequestration, destruction and consumption23,24. Moreover, the hypothermia that is
frequently induced with CPB also contributes to decreased activity of platelets and coagulation factors25. In addition,
a bleeding diathesis maybe further exacerbated by patients’ comorbidities (e.g. renal or hepatic failure, hemophilia
and other coagulopathies) or the perioperative consumption of anticoagulants and/or platelet inhibitors (especially in
patients who receive dual anti-platelet therapy) and, of course, the administration of heparin on CPB (to prevent
devastating, life-threatening, thrombosis while the patient is on CPB). In addition, bleeding may be further
exacerbated by the complexity of the surgery (complex aortic surgery, double valve procedures), the duration of
cardiopulmonary bypass and in emergent procedures or redo operations26,27.
Monitoring coagulation during and after CPB:

There is a delicate balance between the need for anticoagulation during CPB and proper hemostasis after
CPB. Several laboratory tests are available to assist the clinician in the management of a known or suspected
coagulopathy. Numerous studies demonstrate a reduction in transfusion needs when an algorithm-based transfusion
strategy is used28-30. Nevertheless, regardless of the algorithm used and which coagulation tests are obtained, a non-
bleeding patient needs no therapeutic intervention. That said, in most algorithms a transfusion is indicated when
bleeding is associated with a prothrombin time (PT) / activated partial thromboplastin time (aPTT)  1.5 times
normal, a platelet count lower than 100,000/L or a fibrinogen concentration below 150 mg/dL11,13,31. Quantification
of D-dimers or fibrin split products is also available to determine whether hyperfibrinolysis is present32.
It is well known that standard coagulation test are not helpful in directing treatment for the bleeding cardiac surgery
patient33,34. These tests were designed to assess deficiencies in clotting factors and to evaluate the effects of
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anticoagulants on the coagulation system. These tests were not designed to predict the risk of bleeding or to guide
hemostatic therapy in the context of perioperative hemorrhage. Furthermore, these tests do not measure indices such
as platelet function and fibrinolysis, which are very important factors in perioperative hemostasis. In addition the
considerable time delay associated with traditional coagulation tests (up to one hour), forcing clinicians to start
empiric therapy before laboratory test results are available, may result in inappropriate transfusion of erythrocytes
and/or coagulation products. This has led to focus on the use of “point of care” (POC) tests that can be performed
on-site with a mean turnaround time of 20 minutes or less in most cases 30,35. These tests are performed on whole
blood and evaluate the dynamic changes in the clot strength or platelet function as a force is applied. Several
prospective randomized trials30,36-38 and one large, retrospective analysis39 have examined the use of POC-based
transfusion algorithms in cardiac surgery patients, demonstrating decreased transfusion requirements and/or fewer
surgical re-explorations. In addition a reduction in hospital costs30,39,40 and a significant decrease in the use of
recombinant factor VIIa as a rescue therapy for excessive bleeding 30,40,41 has also been reported. Based on this data
the European Society of Anesthesiology guidelines for the “Management of severe perioperative bleeding” give a
class I recommendation for the use of “standardised haemostatic algorithms with predefined intervention triggers”
(Level of evidence A)12
The use of viscoelastic tests such as thromboelastography (TEG) and rotational thromboelastometry
(ROTEM) has been the focus of extensive research in these algorithms the management of bleeding after cardiac
surgery2,32,41,42. These are useful guiding tools for the clinician and algorithms based on their use have been shown to
decrease transfusion requirements. Although multiple randomized trials have demonstrated their efficacy in reducing
transfusion requirements, these devices are still not widely available in every medical center. Possible reseans for
the non-universal adoption of POC viscoelastic technology include quality control and laboratory regulatory
requirements, which can be easily managed. Now that TEG and ROTEM both have cartridge-cased assays available,
user variability and laboratory quality control issues will be minimal.
Platelet dysfunction is also an important cause of perioperative bleeding after cardiac surgery and may be
the result of preoperative use of anti-platelet agents such as clopidogrel or the more novel thienopyridines, prasugrel
and ticagrelol43. In addition CPB has been reported to down-regulate glycoprotein (GP) Ib and GPIIb/IIIa receptors
and inhibit platelet aggregation44. Conventional laboratory tests for platelets number have limited value, as they do
not provide qualitative information on platelet function. The viscoelastic tests TEG and ROTEM can evaluate
qualitative platelet function as well as several other devices that measure platelet function at the point of care. Most
of these devices are based on evaluation of platelet aggregation in response to an agonist such as collagen, thrombin,
adenosine diphosphate (ADP) or arachidonic acid 32. The platelet response to ADP is specifically relevant in
evaluating the impairment in platelet function as a result of the anti-platelet thiopyridine drugs. The ADP
responsiveness tests are accurate for measuring drug-induced platelet inhibition, but are generally too sensitive to
detect platelet dysfunction in the context of CPB. It is also important to remember, that these devices have been
developed primarily to measure the response to antiplatelet medications and to identify individuals who are “poor
responders” to these agents and not to monitor platelet function in the context of surgery and CPB45. Nevertheless,
several recent publications have reported that abnormal platelet function measured by POC tests after CPB, predicts
excessive bleeding and the need for increased transfusion postoperatively 46-49. Thus, the integration of a POC
platelet test in the evaluation of hemostasis in patients after cardiac surgery with CPB is crucial and may be
beneficial in identification and early treatment of patient who are at high risk for excessive bleeding after CPB.
The Effects of POC Coagulation Tests and Transfusion Algorithms on Patient Outcomes
Most studies demonstrated reduced bleeding and transfusion requirements when POC tests and transfusion
algorithms are used during or after cardiac surgery. In a meta-analysis that included 8507 cardiac surgery patients,
Gorlinger et al reported a reduction in bleeding and allogeneic blood transfusion when POC tests were used
compared to routine laboratory clotting tests and clinician discretion27. Others have also reported reduction in
surgical re-explorations50,51 and a significant reduction in hospital costs 30,39,40. Furthermore, several investigators
have recently demonstrated non-inferiority 30,39,40 when POC tests were utilized and fibrinogen concentrates and 4-
factor PCC administered as first line therapy. Görlinger et al39 published in 2011 a retrospective single-center 5-year
experience of the use of POC-based transfusion algorithm in cardiac surgery. The investigators used an algorithm in
which ROTEM and platelet analysis were integrated. They reported a significant decrease in the use of any
allogeneic blood transfusion, of erythrocytes, and of FFP, while the amount of platelets transfused as well as the
administration of fibrinogen concentrate and PCC increased significantly. As a result the incidence of massive (≥ ten
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units of packed RBCs) transfusion and unplanned re-explorations decreased significantly, despite an increase in the
use of dual antiplatelet therapy. In-hospital mortality, however, remained unchanged. Of special interest is the study
by Weber et al30, who reported a single-center randomized trial involving 100 patients undergoing complex
cardiovascular procedures. The authors have reported a significant difference in allogeneic blood transfusion in the
POC tests group compared to the routine-tests group. An interim analysis demonstrated that secondary outcome
parameters, composite adverse events rate, costs, and 6-month mortality were lower in the POC group. Although the
study was not designed to detect differences in mortality between the two patient groups, the reported difference in
6-months survival between the groups has led to the early termination of the study. It is important to note, though,
that the 6-month mortality rate in the conventional group was 20%. This is a high mortality rate even after complex
cardiovascular surgeries, and does not represent the general cardiac surgery patient population. A recent study by
Karkouti et al52 evaluated retrospectively the implementation of a POC-based transfusion algorithm (combining
ROTEM and platelet function test) on transfusion requirements in patients undergoing cardiac surgery with CPB.
The investigators reported that transfusion requirements of erythrocytes, plasma and platelets (but not
cryoprecipitate) were significantly reduced after the institution of their algorithm, thus suggesting that a relatively
simple POC-based transfusion algorithm improves the management of patients with CPB-induced coagulopathy.
In summary, excessive bleeding due to CPB-induced coagulopathy is complex and multifactorial and could result in
a higher complication rate, as well as, increased mortality. A growing body of data suggests that individualized goal-
directed hemostatic approach that is based on POC-guided algorithms has been associated with decreased allogeneic
blood transfusion requirements, fewer operations, lower hospital costs. Additional research is needed to identify the
ideal cost-effective combination of POC testing and hemostatic therapies that will reduce bleeding and transfusion in
high-risk cardiac surgery patients and improve patient outcomes.
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Early Fibrinogen Use in Cardiac Surgery and Trauma
Kenichi Tanaka, MD, MSc. Baltimore, Maryland
Body-Times New Roman 10 point-Headers Times New Roman 10 point Bold

8 Pages Maximum
Transfusion of allogeneic plasma and platelets has been a life-saving measure for decades in
patients with severe trauma, and those suffer from major blood loss after cardiac surgery. The
safety of allogeneic blood components has improved in terms of pathogen transmissions, but
empirical uses of plasma and platelets can be associated with serious complications including
anaphylaxis, circulatory overload, and infrequently transfusion-related acute lung injury
(TRALI).
The prime example of empirical transfusion can be found in the ratio-based administration of
plasma and platelet concentrate according to the requirement of packed red blood cells (PRBCs)
in the major trauma setting. This so-called “damage control resuscitation (DCR)” was originally
advocated for battlefield resuscitation in which laboratory testing and transfusion resources were
limited. In the prospective randomized trial of 1:1:1 vs. 1:1:2 ratio of plasma, platelets, and RBC
administration to major trauma patients were compared for any difference in 24-hour and 30-day
all cause mortality. Although no difference in the mortality was found between groups, improved
hemostasis was more frequently observed in the 1:1:1 group in which larger amounts of plasma-
containing products were given (median 19 units of plasma plus platelets vs. 11 units in the 1:1:2
group) (Holcomb 2015). This study failed to point to the optimal ratio (or volume) of plasma and
platelet transfusion. In their study, fibrinogen or fibrin polymerization was not continuously
monitored, and cryoprecipitate was seldom used in neither group of patients (median, 0 unit).
Reduced fibrinogen or fibrin polymerization has been associated with increased mortality in
major trauma, and cardiac surgery (Trauma)(Cardiac Karkouti). Continuous monitoring of
fibrinogen or fibrin polymerization allows early diagnosis of hypofibrinogenemia, and
subsequent changes following hemorrhage, resuscitative fluid administration, and/or hemostatic
interventions.
Role of fibrinogen monitoring

Conventional fibrinogen assessment has been done in plasma separated from the citrated whole
blood, but a long turn-around time (TAT) of 30–90 min made it difficult to use in acute bleeding
management (Tanaka 2013). Fibrin polymerization can be quickly assessed in the whole blood
using fibrin-specific viscoelastic tests including FIBTEM on rotational thromboelastometry
(ROTEM; TEM Innovations, Munich), and functional fibrinogen on thrombelastography (TEG;
Haemonetics, Niles, IL). In these assays, test reagents contain platelet inhibitors, which exclude
platelets from binding to fibrin, and thus fibrin-specific clot firmness (or amplitude) can be
demonstrated (Fig. 1A).
ROTEM traces (Fig. 1B-D) depict changes in fibrin polymerization patterns during therapeutic
plasma exchange (TPE) prior to the lung transplantation. After 6.6 L of albumin for TPE,
FIBTEM amplitude at 10 min (A10) decreased from 24 to 4 mm (83.3% reduction; Fig. 1B, C).
Corresponding plasma fibrinogen levels, which were reported 20–30 min after FIBTEM were
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344, and 84 mg/dL, respectively (75.6% reduction). TPE was subsequently continued using 12
units of allogeneic plasma (~33.9 ml/kg), achieving plasma fibrinogen of 169 mg/dL, and
FIBTEM-A10 of 7 mm at the end (Fig. 1D). This case clearly demonstrates the utility of FIBTEM
in rapid detection of lowering plasma fibrinogen levels, and inefficacy of plasma in restoring
plasma fibrinogen.
Nakayama, et al. recently reported a prospective randomized study (n=100) of conventional vs.
ROTEM-guided hemostatic intervention in cardiac surgery for infants (median age, 10–13
months) [16]. Platelets and plasma (FFP) were only two products available for hemostatic
therapy at their institution. In the conventional group, platelets and plasma were transfused when
platelet count was below 80,000 per µL, and post-protamine ACT was over 150 sec.
Corresponding indications in the ROTEM group were platelets for EXTEM-A10) (10-min
amplitude) below 30 mm, and plasma for FIBTEM-A10) below 5 mm. The amount of
intraoperative plasma transfusion was higher in the ROTEM group than the convention (median,
21 ml/kg vs. 14 ml/kg; P<0.005). This resulted in higher fibrinogen levels in the ROTEM group
immediately after surgery (165 vs. 125 mg/dL; P<0.001). Reduced postoperative blood loss,
PRBC transfusion, and duration of ICU stay in the ROTEM group suggest that early plasma
transfusion to maintain fibrin polymerization may be more effective than conventional
management focused on clotting time (e.g., PT/INR, aPTT or ACT).
Fibrinogen concentrate and cryoprecipitate

Plasma fibrinogen is normally in the range of 150 to 350 mg/dL for adults, but it is generally
below 150 mg/dL in patients with severe bleeding after trauma or cardiac surgery. Allogeneic
plasma products contain fibrinogen at around 200 mg/dL, but post-transfusion fibrinogen levels
achievable in a patient is only about 60% of the original product level even after a massive
plasma transfusion (i.e., 100 to 140 mg/dL) [54].
The threshold fibrinogen level for hemostasis after CPB is reported to be >200 mg/dL [55, 56] in
contrast to 100 mg/dL in isolated fibrinogen deficiency (e.g., afibrinogenemia) [57]. Rannuci, et
al. conducted a single-center, prospective randomized study of the plasma-derived fibrinogen
concentrate vs. placebo in moderately complex cardiac surgery patients (n=116) with expected
CPB time over 90 min [23]. They applied to both groups the rigorous transfusion criteria for
PRBC (Hgb <7–8 g/dL), platelet (<50 x103/µL), and plasma (INR >1.5 or TEG reaction time
>12 min). The intervention group received the median 4 (IQR, 3–6) g of fibrinogen to the target
level of 22 mm on FIBTEM-MCF immediately after protamine administration. Plasma
fibrinogen levels were 367 (IQR, 329–410) vs. 242 (IQR, 199–300) mg/dL in the intervention
and placebo group, respectively (P=0.001). For the primary endpoint of blood transfusion in 30
days, PRBC use was less frequent in the intervention compared to the placebo (32.8% vs. 55.2%;
P=0.015). Four out of 5 patients who bled more than 1 L within the first 12 hrs belonged to the
placebo group. None of the fibrinogen-treated patients required platelet or plasma transfusion,
but 6.9% and 13.8% of placebo-treated patients received platelet and plasma transfusion,
respectively (P=0.006 for plasma). Although their study may be criticized for implementing a
hemostatic intervention without the clinical evidence of micorvascular bleeding, the results show
the advantage of maintaining fibrinogen at mid–high normal ranges to reduce post-CPB
bleeding.
Clinical use of fibrinogen concentrate is limited to hereditary afibrinogenemia and
hypofibrinogenemia in the US, but cryoprecipitate can be used for perioperative fibrinogen
replacement. Plasma-derived fibrinogen concentrate is treated with several pathogen reduction
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processes, and is free of ABO antibodies. However, cryoprecipitate is not treated with a
pathogen reduction procedure, and thawing and blood-type compatibility are prerequisite for
transfusion. There is a relative paucity of data on the efficacy of cryoprecipitate, but a
preliminary clinical comparison of fibrinogen concentrate (n=30) and cryoprecipitate (n=33) in
the infants (6–8.4 kg) demonstrated that both products were comparable in post-dose fibrinogen
increments in the management of post-CPB hypofibrinogenemia (<100 mg/dL) [58]. The effects
of fibrinogen concentrate (60 mg/kg) and cryoprecipitate (10 ml/kg) were similarly demonstrated
on FIBTEM-MCF as the median increase of 4 mm. The volume requirement to increase
FIBTEM-MCF by 1–1.5 mm would be much higher with plasma (11–13 ml/ kg) as previously
shown in the infants after CPB [16]. An exposure to multiple donors (e.g., multiparous female)
in the pooled cryoprecipitate remains as a potential concern for serious immune responses
including TRALI in adults [59]. It is thus important to diagnose intraoperative
hypofibrinogenemia in real time, and to promptly replace fibrinogen in the case of bleeding.
There is no universal FIBTEM-A10 (or MCF) threshold for fibrinogen replacement that is
applicable to all types of patients. FIBTEM-MCF between 8 and 10 mm (A10, 5 to 7 mm) is a
commonly used cut-off, but fibrinogen replacement to achieve as high as 22 mm has been
considered in a few clinical trials of fibrinogen replacement. It should be cautioned that a higher
target may result in overdosing of fibrinogen in some cases in which bleeding is due to
coagulation factor(s) other than fibrinogen. In complex cardiac surgical cases, reduced thrombin
generation can simultaneously occur with hypofibrinogenemia, and bleeding may not be readily
reversed by fibrinogen replacement alone [60, 61]. In addition, it is important to consider the
timing of fibrinogen replacement because reported positive results were primarily associated
with early interventions, and not with a late use in refractory bleeding after conventional
therapies [62, 63].
There is a paucity of safety data on fibrinogen concentrate and cryoprecipitate in cardiac surgery
because most clinical studies involving fibrinogen replacement therapies had not been powered
for safety outcomes [10, 23, 58, 61]. A recent propensity-score analysis on the adult cardiac
surgical cases showed that the use of fibrinogen concentrate targeting fibrinogen level of 200
mg/dL was not associated with increased mortality, major cardiac events, or thromboembolic
events within 1 yr compared to the cohort without fibrinogen replacement [15].
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Drugging the Drugged: Practical Clinical Pharmacology for the Elderly

Shamsuddin Akhtar, MD New Haven, CT
Learning Objective 1: 1) Review current theories regarding aging and unconsciousness;

Learning Objective 2: 2) Identify how to improve anesthetic dosing in the elderly patients;
Learning Objective 3: 3) Recognize drugs that treat delirium.
I. Introduction
The aging process is characterized by significant level of complexity, which makes the
perioperative care of the elderly patients extremely challenging. Typically, elderly patients suffer from
multiple morbidities and are often taking multiple medications. Polypharmacy is the norm in the elderly.
Effects of drug interactions are substantially magnified with advanced age. It is also well recognized that
sicker patients require less anesthetics. Frequently, elderly patients also suffer from geriatric syndromes, for
example, falls, malnutrition, delirium, mild cognitive dysfunction etc. Against this background of reduced
reserve (frailty), multi-morbidity, and polypharmacy, geriatric patients present for surgical and anesthetic
care.
Practitioners also need to recognize the effect of administering simultaneously multiple anesthetics
and their interactions with non-anesthetic medications. This lecture will address; 1) current theories
regarding aging and unconsciousness; 2) identify how to improve anesthetic dosing in the elderly patients;
and 3) discuss the pharmacology of drugs that are used to treat delirium.
2. Current theories regarding aging and unconsciousness:

Cellular and molecular mechanisms underlying induction of general anesthesia are well
understood. All anesthetic agents are similar in decreasing neuronal firing, either through the enhancement
of inhibitory currents or the reduction of excitatory currents within the brain. Gamma-amino-butyric acid
type A (GABAA) and N-methyl-D-aspartate (NMDA) receptors in the cortex, thalamus, brainstem, and
striatum appear to be the most important targets of anesthesia. Given that nearly all anesthetics decrease
global cerebral metabolism in a dose-dependent manner, it was generally accepted that a general (e.g., non-
specific) reduction in metabolism was the common mechanism for producing anesthesia-induced loss of
consciousness. However, newer research using EEG, functional MRI and other imaging techniques has
shown that unconsciousness is more complicated than simple ‘global depression’. Different regions of the
brain are intricately connected to each other and are constantly communicating with each other. The human
brain has a highly organized network of communication pathways between functionally related regions.
This network is also called ‘connectivity’, which executes the basic functions of the brain. ‘Functional
connectivity’ refers to the temporal relations between different regions of the brain, and lead to functionally
related neurophysiological events. It is this inherent ‘functional connectivity’ that sustains a conscious
state. Various functional networks in the brain have been identified. Default Mode Network (DMN) is one
such network. Anterior part of the DMN is the prefrontal cortex. During the process of development
frontal lobe is the last part of the brain to get myelinated and during senescence it is the first part where
demyelination occurs. It is active in the resting state. Conversely, when a task is being performed there is a
decrease in activity in the DMN. More challenging the task greater is the deactivation of DMN. This
decrease in DMN activity during the execution of a task helps shift attention and focus on the task. In
elderly subjects there is decrease in activity in the DMN in the resting state and the ability to decrease
DMN activity during a task is less. It is this change in DMN function, which results in inability to quickly
change focus and difficulty in dual task performance in elderly subjects. Executive function is also
impaired in the elderly for the same reason. There is a correlation between chronological age, activity in the
anterior part of the DMN, and cognition.
Anesthetics modify functional connectivity within and between resting-state cortical networks.
Though anesthetics clinically cause generalized ‘unconsciousness’, the effect of anesthetic agents differ in
their specific regions of the brain and networks. The thalamus is a second common site of action for most
anesthetics, and it was accepted that the thalamus was the primary region mediating loss of consciousness
during anesthesia. However, newer studies show that the decreased thalamic activity during induction of
anesthesia follows both cortical depression and loss of consciousness. Indeed, it is now widely held that the
cortex is the primary site of anesthetic action, whereas subcortical structures are suppressed secondary to
decreased excitatory cortico-thalamic feedback. Although there are some inconsistencies in the different
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studies the prevalent view is that unconsciousness during anesthesia arises as a consequence of the
disruption of cortico-cortical connections. With deepening anesthetic induced sedation, sensory information
processing in cortex is sequentially impaired from more to less complex, in a dose-dependent manner.
Brain activation declines first in higher-order, or association, cortices before responses in primary cortical
areas are attenuated. Conversely, recovery of consciousness following anesthesia is accompanied by the
restoration of functional coupling between lower-order areas, including subcortical and limbic regions, and
frontal and inferior parietal cortices.
To date, increased sensitivity to anesthetics in the elderly has been attributed to loss of neuronal
tissue or poorly defined changes in receptor functions. Progressive changes in ‘functional connectivity’
with aging and varying effects of anesthetics provides another tantalizing explanation for increased
sensitivity in the elderly. In addition to anesthetic toxicity, it may also explain the mechanism behind
cognitive dysfunction, associated with anesthetics.
3. Anesthetic dosing in the elderly patients

It is well recognized that elderly patients required less anesthetics. This is often attributed to
progressive pharmacokinetic and pharmacodynamic changes that occur with aging. Though
pharmacokinetic changes have been well characterized, the data is typically from healthy elderly patients
(ASA I/II) or patients who are less than 80 years old.6 Most of the pharmacological data is extrapolated to
older octogenarians and nonagenarians.
Inhalational anesthetics
The minimum alveolar concentration (MAC) required to achieve adequate anesthetic depth is
progressively decreases with age. By some estimates, MAC values decrease by 6% per decade after 40 yrs
for volatile anesthetics and about 7.7% per decade for nitrous oxide. The pharmacodynamic correlate for
increased volatile anesthetic and nitrous oxide sensitivity in the elderly is unknown it may be related to
progressive changes in functional connectivity in the elderly. The effect of volatile anesthetics is additive.
Thus, an 80 yr old patient who is on 66% nitrous oxide will require only 0.3% sevoflurane to achieve 1
MAC anesthetic concentration. The hemodynamic impact of excessive anesthetic administration is well
recognized.
Propofol
Pharmacology of propofol is significantly altered with aging. Both, pharmacodynamics and
pharmacokinetic aspects of propofol pharmacology are affected. Age-related changes have been found for
both induction doses and infusions. In one study, EC50 values for loss of consciousness were 2.35, 1.8 and
1.25 µg per mL in healthy volunteers who were 20, 50 and 75 years old, respectively. This reflects a nearly
50% decrease in dosing. For the same fixed those of anesthesia elderly patients develop deeper EEG stages,
needed more time to reach deeper anesthetic stages (as determined by EEG) and also required more time
for recovery. Older patients also needed less propofol for steady state maintenance, for a defined stage of
hypnosis as detected by EEG, than the younger patients. For the same plasma concentration of propofol, the
drop in blood pressure with propofol administration is significantly higher in the elderly than young
patients. 38 Infusing a bolus over a longer period of time can minimize this greater hemodynamic effect of
propofol in the elderly.
Propofol infusion rates required to achieve a persistent level of moderate sedation are lower in the
elderly. Current literature suggests a 20% reduction in the induction dose of propofol and some have
recommended doses as low as 0.8-1.2 mg/kg in the elderly patients. Though, the drug has been extensively
studied, the investigations have been limited to relatively healthy older patients. In one landmark study,
elderly patients were not administered more than 1 mg/kg for induction ‘due to safety reasons’. Similarly,
in a study analyzing 21 previously published datasets on the anesthetic induction agent propofol - 660
patients total - only 6 patients were above 80 years old. Practitioners should recognize that the current
practice for anesthetic care of the very elderly is based upon extrapolation from younger, and relatively
healthier, patients.
Etomidate
Etomidate is an anesthetic and amnestic, but not an analgesic. It is considered an ideal drug in an
elderly because it is associated with less hemodynamic instability than propofol or thiopental. However, a
smaller initial volume of distribution and reduce clearance in the elderly, as well as, significant increase in
anesthetic sensitivity has been shown. Like propofol much lower induction doses are recommended in the
elderly. Elderly patients require 0.2 mg/kg for induction, as opposed to 0.3-0.4 mg/kg for young adults.
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Midazolam
Elderly patients are significantly more sensitive to midazolam than younger patients, primarily
because of pharmacodynamics differences. However the exact mechanism of this pharmacodynamic
difference is not known. Furthermore, the duration of effect may last much longer and can potentially
contribute to post-operative delirium. Benzodiazepines should be avoided in the elderly patients. In
addition, pharmacokinetics of midazolam is significantly altered in the elderly patients. Midazolam
clearance is reduced in the elderly by as much as 30% due to loss of functional hepatic tissue and probably
decreases in hepatic perfusion. Furthermore, midazolam is metabolized to a pharmacologically active
metabolite, hyroxymidazolam, which is excreted by the kidneys and may accumulate in patients with
diminished renal function. A 75% reduction in dose from a 20-year-old to a 90-year-old has been
recommended.
Opioids
Pharmacodynamic changes within the opioid receptor system have been noted with aging.44
Receptor density, receptor affinity and binding may change with aging. Though increased sensitivity to
opioids is attributed to pharmacodynamics changes to the effect of opioids, age related pharmacokinetic
changes, especially opioid metabolite pharmacokinetic changes, affect the choice of opioids that are used in
the elderly. The liver mainly metabolizes opioids and the kidneys excrete the metabolites. Metabolites of
some opioids (codeine, morphine, meperidine) are pharmacologic active, accounting for both persistent
analgesia and many side effects. The primary risk of opioids is respiratory depression, the incidence of
which is markedly increased with age.45
Fentanyl
Fentanyl is a highly selective mu receptor agonist. Earlier studies suggested that terminal half-life
of fentanyl was prolonged in the elderly. However, subsequent studies have not found significant influence
of aging on fentanyl pharmacokinetics. Age has a greater effect on a fentanyl pharmacodynamics than
pharmacokinetics. The EC50 required for the suppression of electroencephalogram (EEG) - a measure of
fentanyl potency- was decreased by approximately 50% from ages 20 to 85 yrs,46 suggesting a 50%
increase in potency of fentanyl in the octogenarians. Elderly patients are significantly more sensitive to
fentanyl and therefore should receive reduced intravenous doses. Fentanyl can be administered either
through oral mucosa, or transdermally. Though clearance of fentanyl is not affected, transdermal
absorption of fentanyl is delayed in the elderly.
Remifentanil
Remifentanil is an ultra-short-acting synthetic opioid and is metabolized by nonspecific tissue and
plasma esterases. This makes it an ideal drug for use in the elderly as it has a short half-life and not
dependent on liver and renal function, which are affected with aging. Remifentanil pharmacology has been
well studied in different age groups. In one study, volume of central compartment decreases by
approximately 25% and clearance decreases 33%, from age 20-85 yrs. Elderly patients are also more
sensitive to remifentanil. The EC50 and plasma effect-site equilibration constant decreased by
approximately 50% over the age arrange of 20 yrs to 85 yrs. The onset and offset of remifentanil is also
slower in elderly individuals, although the blood concentrations were similar to younger patients. The peak
drug effect after a bolus injection occurred at 2-3 minutes in elderly patients, as opposed to the expected
effect in about 90 seconds in younger individuals. Elderly subjects need about half of the bolus dose as
younger subjects for the same drug effect. As with fentanyl and alfentanil, this is because of increased
pharmacodynamics sensitivity in the elderly rather than pharmacokinetic changes. Elderly subjects require
an infusion rate about one third that of younger subjects, because of the combined impact of increased
sensitivity and decreased clearance.
Meperidine
The meperidine is a relatively weak mu agonist with only approximately 10% effectiveness of
morphine. It is metabolized in the liver to normeperidine, which is excreted by the kidneys. The half-life of
normeperidine is 15-30 hours and it can cause agitation and seizures at high concentrations. Meperidine
also has negative inotropic properties and intrinsic anticholinergic properties and its use has been
associated with development of postoperative delirium in elderly patients.49 Meperidine is not
recommended in the elderly patients except in very small doses to manage postoperative shivering.
Neuromuscular blocking drugs
The pharmacodynamics of neuromuscular blocking drugs is not significantly altered with age.
Studies of relationship between depth of neuromuscular blockade and plasma to concentration show little if
any difference with age. The ED95 of neuromuscular blocking is essentially the same for young and old
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patients. In contrast, the pharmacokinetics of neuromuscular drugs is significantly altered with age. The
onset to maximal block may be delayed by 30 seconds to a minute. As these drugs are metabolized by the
liver and excreted by the kidney, hepatic and renal dysfunction can significantly prolong their effects. The
recovery time from the neuromuscular blockade could be increased by 50%.50 Furthermore the impact of
residual neuromuscular blockade (0.7 to 0.8 train of four ratios) on pharyngeal function can be in
significantly marked in the elderly.51 As cisatracurium is not dependent on hepatic or renal function for
clearance, it is considered.
Improving care in the elderly
Three recent studies have shown that elderly patients are typically overdosed with anesthetics,
while undergoing general anesthesia, in contemporary anesthetic practice. There is significant room for
improvement in how we care for our elderly patients. Causal relationship between anesthetic overdosing,
delirium, cognitive dysfunction and other morbidities and mortality needs to be established using large
databases.
4. Drugs that treat delirium
Neuro-cognitive dysfunction is very common in the elderly after cardiac and non-cardiac surgery.
This has been most clearly demonstrated after coronary artery bypass surgery [20 to 40%]. The incidence
of cognitive dysfunction is about 3 to 9 times higher more frequent after non-cardiac surgery compared to
their nonsurgical counterparts.
Delirium is an acute disorder of disturbed attention that fluctuates with time. It effects 15-55% of
hospitalized older patients. It is characterized by the following features: 1) rapid decline in the level of
consciousness with difficulty focusing, shifting or sustaining attention; 2) cognitive change, for example,
incoherent speech, memory gaps, disorientation, hallucination, which are not explained by dementia and a
medical history suggestive of pre-existing cognitive impairment frailty and comorbidity. The mechanism
of postoperative delirium remains elusive, but it has been hypothesized that the stress of surgery and the
associated inflammatory response resulting in leukocyte migration into the central nervous system may
play an active role in the pathophysiology of postoperative delirium. Most patients with postoperative
delirium experience complete recovery, but this disorder is far from benign. Hospitalized patients with
delirium demonstrate up to a 10-fold higher risk of developing other medical complications and have
longer hospital stays, increased medical costs, increased need for long-term care, and a higher 1-year
mortality rate.
The strongest predisposing factor for delirium is preexisting dementia. Other factors that can
contribute to delirium include dehydration, alcohol consumption (or withdrawal), psychoactive drugs,
visual and hearing deprivation. Stressful conditions that can precipitate delirium include surgery,
anesthesia, persistent pain, sleep deprivation, immobilization, hypoxia, malnutrition, metabolic and
electrolyte derangements and treatment with opioids, narcotics and anticholinergic agents. Unfortunately,
though it is common condition, substantive preventive measures are lacking. Early identification,
supportive measures and symptomatic treatment for delirium is the rule. Short term use of haloperidol can
be considered to control symptoms of agitation, paranoia, fear and delirium. However prophylactic use of
antipsychotic medications has not shown to improve outcomes and is not recommended. Use of
antipsychotic medications in patients with dementia has been associated with increased mortality.
4. Summary
Aging involves changes in several physiologic processes that lead to decreased volumes of
distribution, slowed metabolism and increased end-organ sensitivity to anesthetic drugs. These changes
generally result in increased potency. Though it is well known that elderly patients require significantly less
anesthetic medications, the true extent of reduction is under appreciated and less uniformly practiced. The
impact of potential anesthetic drug overdosing on intermediate and long-term outcomes is not fully
appreciated. Larger database studies are beginning to demonstrate the consequences of even short-term
hemodynamic perturbations in the perioperative period. These perturbations are probably of higher
consequence in frail, elderly patient with reduced reserves. Dosing anesthetics is totally in control of
anesthesiologists and the impact of anesthetic overdosing should be recognized. Just because ‘hypotension’
can be treated readily with vasopressors and fluids, it does not mean that it should be allowable. Fluid
therapy and vasopressor therapy are not inconsequential and may potentially contribute to morbidity in the
elderly. Prevention is better than cure.
With the increasing population of patients over the age of 65 years, it may be necessary to look at
age as a continuous variable when considering anesthetic drug dosing in older patients rather than treating
“adult” versus “elderly” patients. Very little is known about the pharmacodynamics differences in those
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aged >80 years old, and this is one of the fastest growing populations in the United States. Further
pharmacological studies are required in very elderly population (>80 yrs). They will help to delineate the
PK/PD differences in this population beyond what has been studied for those patients over the age of 65
yrs. Practice of anesthesia, though very safe, can still be improved for this vulnerable population.
BIBLIOGRAPHY
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21. Akhtar S, Liu J, Heng J, Da F, Schonberger RB, Burg MM. Does intravenous induction dosing
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Anesthesia for Cesarean Delivery
Paloma Toledo, MD/MPH Chicago, IL
Cesarean Delivery in the United States

Childbirth is the most common reason for admission to a hospital in the United States (US),1 and cesarean deliveries
are one of the most commonly performed surgeries. There has been an increase in the rate of cesarean deliveries,
and this has become an issue of increasing public health concern. In a study by investigators from the Consortium on
Safe Labor, data from 228,668 deliveries were weighted to represent a national sample and the overall cesarean
delivery rate was 30.5%.2 This rate has been increasing since the mid-1990s, and while the cause of this increase is
multifactorial, one important contributor was a sharp decrease in the number of women who attempted a trial of
labor after cesarean delivery (TOLAC).3 Professional guidelines by the American Society of Anesthesiologists
(ASA) and American College of Gynecologists state the need for “immediate availability” of anesthesia and surgical
personnel, limiting the number of hospitals that provide TOLAC services. Other important contributors to the
increasing cesarean delivery rate include increasing rates of obesity, multiple gestation, and advanced maternal age. 2
Projections estimate a continued increase in the cesarean delivery rate over time. Therefore, attention to the
anesthetic management of these patients will continue to be of increasing importance.
Role of anesthesia in preventing of cesarean delivery

The incidence of breech presentation is approximately 3-5%, and cesarean delivery is usually recommended over
vaginal delivery when the fetus is in a breech presentation.4 External cephalic versions (ECV) are often performed in
an attempt to avoid cesarean delivery. The use of neuraxial anesthesia may increase the success of external cephalic
versions, and thus have a role in decreasing the overall cesarean delivery rate. A meta-analysis of all of the
randomized controlled trials evaluating neuraxial compared to no anesthesia (or systemic analgesia) for external
cephalic version identified a possible dose-response relationship between the density of the block and ECV success.5
Four studies that used analgesic dosing found no difference in the success of versions, while anesthetic dosing was
associated with an increased success rate.5 The proposed mechanism for the higher success rates is possibly through
improved muscle relaxation and improved maternal comfort during the procedure. 6 To date, no published study has
compared anesthetic to analgesic dosing for neuraxial blocks; however, the impact of anesthetic dosing (7.5 mg
intrathecal bupivacaine) compared to no anesthesia or systemic opioids is profound (87% success rate in the
anesthetic group compared to 58% in the control group, P= 0.012).7
Anesthetic management for routine cesarean deliveries

While the specific management of any case should be decided on an individual basis, the typical sequence of events
for providing anesthesia for cesarean deliveries is as follows:
1. Preoperative assessment and consent
2. Aspiration prophylaxis
3. Placement of monitors
4. Administration of antibiotics
5. Patient positioning
6. Anesthetic options for surgical anesthesia
7. Fluid co-loading
8. Management of hypotension
9. Administration of uterotonics
10. Postoperative analgesia planning
1. Preoperative assessment:
A thorough preoperative assessment should be performed for all cases. The Practice Guidelines for Obstetrical
Anesthesia from the ASA state that specific attention should be given to relevant obstetric issues that may
complicate the surgery (e.g., obesity, hypertensive disorders of pregnancy, and number of previous cesarean
deliveries).8 Physical examination should include an examination of the back if neuraxial anesthesia is planned. 8 If
the patient has been laboring, or a significant interval of time has elapsed since the original preoperative evaluation,
reassessment of the airway should be performed, as studies have shown that there may be changes in the class of the
airway as pregnancy/labor progresses.9 The decision to obtain routine laboratory analysis prior to a cesarean
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delivery remains controversial. Routine laboratory analysis is not necessary for all patients; however, in high-risk
patients, such as those patients who have symptoms or medical conditions that may be consistent with coagulation
disorders, a platelet count and/or coagulation studies should be obtained.
A sample of the patient’s blood should be sent to the blood bank for all cesarean deliveries. The decision to type and
screen or type and cross match blood should be made based on the likelihood of requiring a blood transfusion.
Consent:
Patients should be informed of the risks and benefits of the anesthetic planned for the procedure. While there are no
specific guidelines as to what information needs to be communicated, generally the most common risks should be
discussed. For neuraxial anesthesia these should include infection, bleeding, risk of postdural puncture headache,
hypotension, and patchy/failed block requiring conversion to general anesthesia.
2. Aspiration prophylaxis:
The American Society of Anesthesiologists recommends withholding clear liquids for 2 hours prior to elective
cesarean deliveries and withholding solids for 6-8 hours, depending on the fat content of the meal.8 Controversy has
recently arisen around whether laboring women should be allowed to eat light meals during labor. A Cochrane
review evaluating oral intake in labor found no difference in labor or neonatal outcomes when low-risk patients were
allowed liquid/solid intake,10 and concluded that low-risk patients should be allowed to eat/drink, yet none of the
studies included in the meta-analysis were powered to assess maternal aspiration as a primary outcome. The ASA
Practice Guidelines for Obstetrical Anesthesia state that solid foods should be avoided during labor. 11
Prior to cesarean delivery, pharmacologic aspiration prophylaxis should be given. Three classes of drugs are
routinely used: non-particulate antacids, H2-receptor antagonists, and dopamine antagonists. Of the three, in an
emergency cesarean delivery, the most important to administer is the non-particulate antacid as it has the fastest
onset and decreases gastric acidity.
3. Monitors:
As for all surgical procedures, ASA standard monitors are required. Invasive hemodynamic monitoring is not
required for routine cesarean deliveries, but should be considered on a case-by-case basis for high-risk deliveries or
patients with cardiopulmonary disease. The American College of Obstetrics and Gynecology states that fetal heart
rate should be documented prior to surgery.
4. Antibiotics:
The American College of Obstetrics and Gynecology recommends that antibiotic prophylaxis be administered
within 60 minutes of the start of a cesarean delivery.12 Antibiotic administration should not be delayed until after
umbilical cord clamping as several randomized controlled trials have demonstrated that there is a decrease in
endometritis and/or wound infection when antibiotics are administered prior to incision, as opposed to umbilical
cord clamping, with no increased adverse events for the mother or the fetus. In the event of an emergency cesarean
delivery, antibiotics should be administered as soon as they are available.
5. Patient positioning:
Left uterine displacement (a minimum of 15-degree leftward tilt) should be utilized to prevent aorto-caval
compression syndrome. After delivery of the infant, the left tilt may be removed.
6. Anesthetic options for surgical anesthesia:

Neuraxial anesthesia (spinal, epidural, or combined spinal-epidural anesthesia) remains the most common type of
anesthesia used for cesarean delivery.13 Alternatives to neuraxial anesthesia include general anesthesia and local-
infiltration anesthesia. The type of anesthesia selected for cesarean deliveries needs to be tailored to the patient
situation. To a certain extent, the anesthetic plan is determined by the urgency of the cesarean delivery.
Neuraxial anesthesia:
The majority of cesarean deliveries are performed using neuraxial anesthesia, with the most common anesthetic
being a single-shot spinal. A T4-T6 dermatomal level should be established prior to commencement of the surgery,
otherwise the patient may experience breakthrough pain and require supplemental opioids, or conversion to general
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anesthesia. The assessment of sensory level should be to touch/pinprick as the discrepancy between cold and touch
may exceed two dermatomes.14
Common regimens for spinal anesthesia include a local anesthetic agent with a short acting opioid. The addition of
the opioid allows for a reduction in the local anesthetic dose, thus decreasing the incidence of hypotension and other
local anesthetic-related side effects. For patients without clinical contraindications, morphine is often added for
postoperative analgesia. In patients in whom the duration of surgery is anticipated to exceed the duration of the
spinal, epinephrine may be added to the spinal, or alternatively, an epidural or combined spinal-epidural technique
may be chosen.
Epidural anesthesia may be chosen for the initiation of anesthesia (de-novo placement), or used in laboring women
with an in-dwelling epidural catheter.
Choice of local anesthetic in patients with in-dwelling labor epidural catheters:

The clinical situation will influence the decision for what local anesthetic is used. In emergency cesarean deliveries,
(those in which there is an immediate threat to the life of the mother or fetus), 3% chloroprocaine is the most
expeditious choice.15 In the absence of fetal compromise, or when there is fetal compromise that responds to
therapy, a slower-onset local anesthetic such as 2% lidocaine may be chosen. The advantage of lidocaine over
chloroprocaine is that it appears that chloroprocaine interferes with the efficacy of epidural morphine. 16 The
mechanism of this interaction is not completely understood.
General anesthesia
General anesthesia is required in emergency situations where there is insufficient time for placement of neuraxial
anesthesia, or when patients have contraindications to neuraxial anesthesia. A rapid sequence intubation is indicated
for parturients undergoing cesarean delivery, as all patients undergoing general anesthesia are considered full
stomachs. General anesthesia is associated with a shorter decision-to-incision interval when compared to neuraxial
anesthesia. The trade-off is increased neonatal depression, lower Apgar scores, and an increased likelihood of
postpartum hemorrhage.17
The following is a common approach to general anesthesia.18 Induction and intubation should occur after surgical
site antisepsis and confirmation that the surgical team is prepared to proceed with surgery. The patient should
initially be ventilated with 100% oxygen and 1 MAC of a potent inhalational agent. Following delivery of the infant,
nitrous oxide may be added, and the concentration of volatile agent should be reduced in order to mitigate the effect
of the volatile agent on uterine tone. Benzodiazepines and opioids may now also be administered. As the risk of
hemorrhage is increased with general anesthesia,19 the dose of oxytocin administered after delivery should be
increased.20,21 Other actions should include decompression of the stomach with an orogastric tube and temperature
monitoring. Patients should be extubated awake and monitored in the post-anesthetic recovery unit.22
Local-only anesthesia:
In situations where anesthesiologists are not readily available, a cesarean delivery may be preformed under local
anesthesia. Lidocaine (0.5%) is used to sequentially anesthetize the skin, subcutaneous tissues, fascia, and
peritoneum. The obstetrician should make a vertical abdominal incision and not exteriorize the uterus.
7. Fluid co-loading:
Hypotension is the most common complication of spinal anesthesia following cesarean delivery. 23 Side effects of
hypotension could include nausea/vomiting, loss of consciousness, maternal cardiac arrest, and decreased
uteroplacental perfusion resulting in neonatal acidosis. Current evidence suggests that crystalloid preloads are
ineffective at preventing hypotension and instead co-loading should be performed to reduce hypotension and
vasopressor requirements.24 Colloids may possibly be more effective than crystalloids when given as a co-load;25
however consideration to the side effects of colloid should be given (pruritus, coagulation abnormalities, and severe
allergic reactions).
8. Management of hypotension:
Phenylephrine and ephedrine are the two most commonly used vasopressors for treatment of hypotension in
cesarean deliveries. Higher doses of vasopressors are required for treatment of hypotension in pregnant women
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compared to non-pregnant women due to the physiologic dependence on the sympathetic nervous system and down-
regulation of adrenergic receptors.
Phenylephrine is the preferred vasopressor in obstetrics as ephedrine crosses the placenta which results in in fetal
tachycardia and possible neonatal acidosis.26 The ED90 for bolus administration phenylephrine following spinal
anesthesia has been shown to be 150 mcg (95% CI: 98-222 mcg).27 A suggested starting dose for ephedrine would
be 10 mg. Current evidence does not support the use of a fixed-rate phenylephrine infusion;28 however, if an
infusion is to be used, clinicians should start with lower doses (25-50 mcg/min), as these doses are associated with
less reactive hypertension.
9. Administration of uterotonic agents:

Oxytocin is considered the first-line agent for prevention of postpartum hemorrhage following cesarean delivery.
The optimal dose and route of delivery are not established. Recent evidence suggests that adequate uterine tone can
be achieved with bolus doses as low as 0.5-3 IU.20 Bolus administration of oxytocin has been associated with many
undesirable cardiovascular side effects, such as hypotension, tachycardia, and electrocardiogram changes that may
be suggestive of myocardial ischemia.29 Many institutions have therefore transitioned to the use of oxytocin
infusions following umbilical cord clamping at cesarean delivery. The ED 90 for oxytocin delivered as an infusion
has been estimated to be 0.4 IU/min using an up-down sequential allocation with a biased-coin design.21 There does
not appear to be a benefit from administration of a bolus of oxytocin prior to initiation of an oxytocin infusion. 30
Higher doses of oxytocin may be necessary after prolonged labor with oxytocin induction/augmentation, as animal
evidence suggests that there is receptor desensitization with increasing doses of oxytocin. 31Although transient
hypotension is common after the bolus administration of oxytocin, EKG changes, particularly ST-segment
depression, are concerning side effects.32 While the electrocardiogram changes are likely not reflective of
myocardial ischemia,32 it is prudent to use the lowest effective dose of oxytocin in order to avoid possible iatrogenic
injury.
Postpartum hemorrhage is one of the leading causes of maternal mortality worldwide. Mortality from hemorrhage in
part is due to difficulty recognizing the amount of blood lost, 33 and delay in initiating treatment for the hemorrhage.
In the setting of postpartum hemorrhage due to atony, additional uterotonic agents may be necessary. In addition to
oxytocin, the two most commonly used classes of agents are ergot alkaloids and 15-methyl prostaglandin F2α.
10. Postoperative analgesia management:

There are two components to postoperative pain, the somatic (incisional) and visceral (uterine) pain. Options for
postoperative analgesia are described below.
Neuraxial opioids:
Neuraxial morphine is the gold standard for achieving postoperative analgesia due to its ability to treat visceral and
somatic pain. Spinally administered morphine acts primarily at the mu receptors in the spinal cord, whereas
epidurally-administered morphine acts through spinal and supraspinal opioid receptors. 34 The duration of action of
neuraxially administered morphine is between 12-24 hours. An extended-release epidural morphine has been
developed; however, the increased monitoring requirements (48-hours) and the pharmacologic interaction with
epidural local anesthetics limit its clinical use.35 Patients who receive neuraxial opioids should receive scheduled
parenteral non-steroidal anti-inflammatory agents (NSAIDs) postoperatively for treatment of visceral pain.
Parenteral Analgesia:
Intravenous narcotics and NSAIDs should be administered to patients who do not receive neuraxial opioids.
Transversus abdominis plane blockade:

The transversus abdominis plane (TAP) block is an adjuvant analgesic technique for post-cesarean delivery
analgesia. Local anesthetic is deposited in the fascial plane between the transversus abdominis and the internal
oblique. Several nerves lie in the transversus abdominis plane: the lower thoracic nerves (T7-T11), the subcostal
nerve, and the two branches of the first lumbar nerve (the iliohypogastric and ilioinguinal nerves). While intrathecal
morphine is the most efficacious technique for providing postoperative analgesia due to its ability to provide somatic
as well as visceral analgesia, TAP blocks should be considered for women who undergo general anesthesia for
cesarean delivery, for women who did not receive neuraxial morphine, and for those who experience breakthrough
incisional pain despite having received neuraxial morphine.36
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Complications of anesthesia:
Aspiration:
Aspiration is one of the feared complications of general anesthesia. While the incidence is decreasing, aspiration
prophylaxis should be taken in all parturients undergoing cesarean delivery, even if under regional anesthesia,
because of the risk of intraoperative conversion to general anesthesia.
Difficult Intubation:
Due to the physiologic changes of pregnancy (increased capillary engorgement with resultant decreased internal
tracheal diameter), there is the potential for increased difficulty with intubation in pregnant patients.
Awareness:
The incidence of awareness following general anesthesia in the obstetric patient population is low, with current
estimates of 0.1-0.2%.37
High spinal:
If a patient experiences a high spinal, it is important to assist with ventilation or intubate, maintain left uterine
displacement, and treat hypotension until the level recedes.
Local anesthetic systemic toxicity:

Local anesthetic systemic toxicity (LAST) may occur in following the initiation of epidural anesthesia or with
transversus abdominis plane blockade. Providers should be aware of the signs and symptoms of LAST and treatment
algorithms.38
Neonatal depression:
Infants delivered under general anesthesia have a higher incidence of fetal acidemia and lower 1-minute Apgar
scores than those delivered under neuraxial anesthesia.17 With prolonged uterine incision-to-delivery intervals (>3-
minutes), there is a higher incidence of acidosis and neonatal depression. 39
REFERENCES
1. Top Five Most Common Reasons for Hospital Admission in 1996.
http://www.ahrq.gov/data/hcup/charts/5admiss.htm. Accessed on: August 4, 2010.
2. Zhang J, Troendle J, Reddy UM, Laughon SK, Branch DW, Burkman R, Landy HJ, Hibbard JU, Haberman
S, Ramirez MM, Bailit JL, Hoffman MK, Gregory KD, Gonzalez-Quintero VH, Kominiarek M, Learman
LA, Hatjis CG, van Veldhuisen P. Contemporary cesarean delivery practice in the United States. Am J
Obstet Gynecol 2010;203:326 e1- e10
3. Guise JM, Denman MA, Emeis C, Marshall N, Walker M, Fu R, Janik R, Nygren P, Eden KB, McDonagh
M. Vaginal birth after cesarean: new insights on maternal and neonatal outcomes. Obstet Gynecol
2010;115:1267-78
4. Hannah ME, Hannah WJ, Hewson SA, Hodnett ED, Saigal S, Willan AR. Planned caesarean section versus
planned vaginal birth for breech presentation at term: a randomised multicentre trial. Term Breech Trial
Collaborative Group. Lancet 2000;356:1375-83
5. Lavoie A, Guay J. Anesthetic dose neuraxial blockade increases the success rate of external fetal version: a
meta-analysis. Can J Anaesth 2010;57:408-14
6. Sullivan JT, Grobman WA, Bauchat JR, Scavone BM, Grouper S, McCarthy RJ, Wong CA. A randomized
controlled trial of the effect of combined spinal-epidural analgesia on the success of external cephalic
version for breech presentation. Int J Obstet Anesth 2009;18:328-34
7. Weiniger CF, Ginosar Y, Elchalal U, Sela HY, Weissman C, Ezra Y. Randomized controlled trial of
external cephalic version in term multiparae with or without spinal analgesia. Br J Anaesth 2010;104:613-8
8. Practice guidelines for obstetric anesthesia. An updated report by the American Society of
Anesthesiologists Task Force on Obstetric Anesthesia. Anesthesiology 2007;106:843-63
9. Boutonnet M, Faitot V, Katz A, Salomon L, Keita H. Mallampati class changes during pregnancy, labour,
and after delivery: can these be predicted? Br J Anaesth 2010;104:67-70
10. Singata M, Tranmer J, Gyte GM. Restricting oral fluid and food intake during labour. Cochrane Database
Syst Rev 2010:CD003930
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11. Practice guidelines for obstetric anesthesia: an updated report by the American Society of Anesthesiologists
Task Force on Obstetric Anesthesia. Anesthesiology 2007;106:843-63
12. Antimicrobial prophylaxis for cesarean delivery: timing of administration. Committee Opinion No. 465.
American College of Obstetricians and Gynecologists. . Obstet Gynecol 2010;116:791-2
13. Traynor AJ, Aragon M, Ghosh D, Choi RS, Dingmann C, Vu Tran Z, Bucklin BA. Obstetric Anesthesia
Workforce Survey: A 30-Year Update. Anesth Analg 2016;122:1939-46
14. Russell IF. A comparison of cold, pinprick and touch for assessing the level of spinal block at caesarean
section. Int J Obstet Anesth 2004;13:146-52
15. Gaiser RR, Cheek TG, Gutsche BB. Epidural lidocaine versus 2-chloroprocaine for fetal distress requiring
urgent cesarean section. Int J Obstet Anesth 1994;3:208-10
16. Toledo P, McCarthy RJ, Ebarvia MJ, Huser CJ, Wong CA. The interaction between epidural 2-
chloroprocaine and morphine: a randomized controlled trial of the effect of drug administration timing on
the efficacy of morphine analgesia. Anesth Analg 2009;109:168-73
17. Tonni G, Ferrari B, De Felice C, Ventura A. Fetal acid-base and neonatal status after general and neuraxial
anesthesia for elective cesarean section. Int J Gynaecol Obstet 2007;97:143-6
18. Scavone BM, Toledo P, Higgins N, Wojciechowski K, McCarthy RJ. A randomized controlled trial of the
impact of simulation-based training on resident performance during a simulated obstetric anesthesia
emergency. Simul Healthc 2010;5:320-4
19. Chang CC, Wang IT, Chen YH, Lin HC. Anesthetic management as a risk factor for postpartum
hemorrhage after cesarean deliveries. Am J Obstet Gynecol 2011;205:462 e1-7
20. Butwick AJ, Coleman L, Cohen SE, Riley ET, Carvalho B. Minimum effective bolus dose of oxytocin
during elective Caesarean delivery. Br J Anaesth 2010;104:338-43
21. George RB, McKeen D, Chaplin AC, McLeod L. Up-down determination of the ED(90) of oxytocin
infusions for the prevention of postpartum uterine atony in parturients undergoing Cesarean delivery. Can J
Anaesth 2010;57:578-82
22. Mhyre JM, Riesner MN, Polley LS, Naughton NN. A series of anesthesia-related maternal deaths in
Michigan, 1985-2003. Anesthesiology 2007;106:1096-104
23. Cyna AM, Andrew M, Emmett RS, Middleton P, Simmons SW. Techniques for preventing hypotension
during spinal anaesthesia for caesarean section. Cochrane Database Syst Rev 2006:CD002251
24. Dyer RA, Farina Z, Joubert IA, Du Toit P, Meyer M, Torr G, Wells K, James MF. Crystalloid preload
versus rapid crystalloid administration after induction of spinal anaesthesia (coload) for elective caesarean
section. Anaesth Intensive Care 2004;32:351-7
25. McDonald S, Fernando R, Ashpole K, Columb M. Maternal cardiac output changes after crystalloid or
colloid coload following spinal anesthesia for elective cesarean delivery: a randomized controlled trial.
Anesth Analg 2011;113:803-10
26. Ngan Kee WD, Khaw KS. Vasopressors in obstetrics: what should we be using? Curr Opin Anaesthesiol
2006;19:238-43
27. George RB, McKeen D, Columb MO, Habib AS. Up-down determination of the 90% effective dose of
phenylephrine for the treatment of spinal anesthesia-induced hypotension in parturients undergoing
cesarean delivery. Anesth Analg 2010;110:154-8
28. Allen TK, George RB, White WD, Muir HA, Habib AS. A double-blind, placebo-controlled trial of four
fixed rate infusion regimens of phenylephrine for hemodynamic support during spinal anesthesia for
cesarean delivery. Anesth Analg 2010;111:1221-9
29. Thomas JS, Koh SH, Cooper GM. Haemodynamic effects of oxytocin given as i.v. bolus or infusion on
women undergoing Caesarean section. Br J Anaesth 2007;98:116-9
30. King KJ, Douglas MJ, Unger W, Wong A, King RA. Five unit bolus oxytocin at cesarean delivery in
women at risk of atony: a randomized, double-blind, controlled trial. Anesth Analg 2010;111:1460-6
31. Magalhaes JK, Carvalho JC, Parkes RK, Kingdom J, Li Y, Balki M. Oxytocin pretreatment decreases
oxytocin-induced myometrial contractions in pregnant rats in a concentration-dependent but not time-
dependent manner. Reprod Sci 2009;16:501-8
32. Svanstrom MC, Biber B, Hanes M, Johansson G, Naslund U, Balfors EM. Signs of myocardial ischaemia
after injection of oxytocin: a randomized double-blind comparison of oxytocin and methylergometrine
during Caesarean section. Br J Anaesth 2008;100:683-9
33. Toledo P, McCarthy RJ, Hewlett BJ, Fitzgerald PC, Wong CA. The accuracy of blood loss estimation after
simulated vaginal delivery. Anesth Analg 2007;105:1736-40
34. Gadsden J, Hart S, Santos AC. Post-cesarean delivery analgesia. Anesth Analg 2005;101:S62-9
307
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35. Atkinson Ralls L, Drover DR, Clavijo CF, Carvalho B. Prior epidural lidocaine alters the pharmacokinetics
and drug effects of extended-release epidural morphine (DepoDur(R)) after cesarean delivery. Anesth
Analg 2011;113:251-8
36. McMorrow RC, Ni Mhuircheartaigh RJ, Ahmed KA, Aslani A, Ng SC, Conrick-Martin I, Dowling JJ,
Gaffney A, Loughrey JP, McCaul CL. Comparison of transversus abdominis plane block vs spinal
morphine for pain relief after Caesarean section. Br J Anaesth 2011;106:706-12
37. Robins K, Lyons G. Intraoperative awareness during general anesthesia for cesarean delivery. Anesth
Analg 2009;109:886-90
38. Toledo P. The role of lipid emulsion during advanced cardiac life support for local anesthetic toxicity. Int J
Obstet Anesth 2011;20:60-3
39. Datta S, Ostheimer GW, Weiss JB, Brown WU, Jr., Alper MH. Neonatal effect of prolonged anesthetic
induction for cesarean section. Obstet Gynecol 1981;58:331-5
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Situational Awareness, Crisis Management and Patient Safety in Anesthesia Practice

Amanda Burden, MD Camden, NJ
Anesthesiology is a complex and dynamic field
The operating room is a dynamic and complex environment; critical events can happen without warning. When
these events occur, the anesthesiologist must both lead an interprofessional team whose members have varying
levels of training and at the same time care for a critically ill patient. At any time, one or more factors, including
patient comorbidity, procedural or equipment challenges may combine and lead to a crisis that threatens the patient’s
well-being or life.1-5 Anesthesiologists must be able to identify, understand and manage the rapidly changing patient
and situation information while leading the team.
Crisis resource management (CRM), a paradigm first designed to improve aviation safety6 and later adapted by
Gaba et. al, to anesthesiology and healthcare provides tools that help the anesthesiologist and the team manage the
critical situation.1-2 CRM is designed to focus the attention of individuals and the entire team on factors aimed at
improving patient safety by reducing the causes of adverse events and improving responses to evolving events.
While medical knowledge and technical skills are essential components to patient care in a crisis, nontechnical skills
such as leadership, communication and situational awareness are equally critical for the safe care of the patient.1-2,7
To manage the crisis effectively, the anesthesiologist must manage the full situation. Gaba describes a set of
principles and actions that comprise effective CRM (Table 1).2 Situational awareness is an essential element of
CRM.
Table 1. CRM Key Points – borrowed with permission from Gaba et. al.
Dynamic Decision Making Team Management

Know the environment Call for help early
Anticipate and plan Designate leadership
Use all available information Establish role clarity
Allocate attention wisely Distribute the workload
Mobilize resources Communicate effectively
Establish situational awareness and a shared mental
Use cognitive aids
model
Adverse Events in anesthesiology are associated with “human factors”
Human Factors (HF) is a discipline that addresses human behavior, abilities, limitations, and their relationship to the
work environment. HF applies these considerations to the design and evaluation of safer and more effective tools,
machines, systems, tasks, jobs, and environments.8 These issues may be physical, organizational or even cultural.
HF aims to optimize the human and environmental factors to enhance safety.
Situational awareness is a key component of human factors; all decision making and action flows from this
awareness. SA involves the anesthesiologist’s perception and understanding of the dynamic information that is
present in his or her environment. It is also the process of integrating relevant information from the environment into
a concise picture. SA involves perception as well as understanding and integration of information from the dynamic
environment into clear decisions and actions. Situational awareness includes having team awareness and being
aware of what other members of the team are doing.9 It is a process the anesthesiologist must work through while
she or he quickly detects, integrates and interprets data gathered from the environment and the resulting knowledge
or awareness of the situation.10-12
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Potential patient safety impact of gaps in Situational Awareness
What are the benefits of being able to assess a situation well and having “good situational awareness?” How would
you build and maintain adequate situational awareness? What are the risks associated with having an incomplete or
even a wrong situational assessment and awareness? What can be done in order to assure adequate situational
awareness? Is it possible to avoid the pitfalls associated with having inadequate situational awareness? Situational
awareness is an everyday occurrence, we use it for routine events like driving; it is also part of more complicated
and risky situations (e.g., a physician assessing a potentially septic patient or a pilot assessing the potential of
landing gear problems during final approach). Situational awareness involves several cognitive functions such as
perceiving, understanding, reasoning, and thinking, all of which influence decisions and actions.
Importance of Situational Awareness in Healthcare
Situational awareness was first discussed and studied in aviation and aerospace, in the mid=1990s, Gaba et. al.,
wrote that situational awareness is an equally important factor in the complex, dynamic, and risky field of
anesthesiology.13 Situational awareness is now thought to be one of the most essential nontechnical skills for the
achievement of safe anesthesia practice.14 As such, there is a need for a better understanding of situational awareness
and the development of new ways to learn about and acquire situational awareness in healthcare settings. The World
Health Organization recently cited situational awareness as critical in all areas of healthcare.15 Since its origin in
aviation psychology literature, situational awareness is now considered central to safe and effective decision-making
and performance in high hazard areas and domains. Situational and environmental conditions can combine with
tasks that are unstable, time-pressured, have high stakes, and involve multiple team members. This dynamism and
complexity can alter judgments and can impact both individual and team decision-making.16 Reason stressed the
importance of contextual based decision-making where the situation and environment are recognized as playing an
influential role in the decision-making process.17 As such, any degradation or loss of situational awareness is cited
very often as being associated with environmental or situational conditions in addition to the more obvious human
(individual and team) and performance issues.
The theory of situational awareness is frequently used to explain how decision makers are able to incorporate
information from the environment in a way that allows them to “know what is going on around them” and make
critical decisions.18 Jones and Endsley suggest that well-informed decisions require that all relevant elements in the
environment are understood.19 It is also important for decision makers to understand how these elements interact and
impact the situation over time. Endsley suggests that situational awareness can be decomposed into three levels:
perception, comprehension and projection.20 The integration of these three levels is best defined as the “perception
of the elements in the environment within a volume of time and space, the comprehension of their meaning, and the
projection of their status in the near future.20”
It is essential to both understand what situational awareness is and to also understand how to achieve situational
awareness in practice. Guidance on how to attain this knowledge and assess the situation is critical.21 This
assessment requires understanding of the environment and the task, the capabilities and limitations of the team
members and how those factors may affect behavior and performance. There are many factors all of which may
ultimately influence the performance of the individual team members and the team as a whole. 1-5 When analyzing a
situation with many factors that influence performance, start with the basic elements of the situation – the physical
and human environments. The physical environment includes aspects of the physical space where the situation
occurs, the devices and other conditions such as lighting, noise, temperature, etc. The human environment includes
any other healthcare workers. The human environment also includes organizational aspects such as shift work and
handovers. These can include: staffing, management and authority gradients, policies and protocols as well as
training and supervision of residents. In addition to the environment, the capabilities and limitations of the
individuals or teams must also be considered. All of these issues act together in an interdependent fashion and may
produce distractions, interruptions, fatigue, workload, and stress.22-24
Strategies to prevent gaps in Situational Awareness and Improve Patient Safety

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CRM principles are designed to help the anesthesiologist prevent gaps in Situational Awareness. Ideally addressing
the situation will begin early, before the situation unfolds. In this preliminary and preparatory phase, activities such
as briefing and planning should be performed. The preparation phase should be considered as the first critical step in
building adequate situational awareness. During this time, as many situational elements as possible can be identified:
Who is the patient? What do we know about the patient? Where are we going to treat the patient? What is available
there in terms of devices and tools? Who is going to work with me? What is the procedure we are supposed to
perform? When do we start? How long has the patient been in this state? Identifying these points and briefing the
team about the patient and the plan in advance can help the team prepare to manage the patient.
As the situation unfolds, the key is to build and maintain situational awareness in an effort to assure patient safety.
Building situational awareness requires continuously scanning the procedural room and the patient to identify
what is occurring, understanding any changes, and thinking ahead. This allows the anesthesiologist to anticipate
and plan for events as they unfold. This process is cyclical and allows the anesthesiologist to continuously acquire
the most up to date knowledge to eventually implement and, if needed, revise decisions and actions. This process
also includes continuing to survey the situation to look for any obstacles to building and maintaining situational
awareness. Once the situation is terminated, participants may reflect and debrief on what happened. The process of
using CRM principles to continuously maintain an awareness of the patient is a crucial tenant of the practice of
anesthesiology and allows for safe care of the patient.
References:
1. Gaba DM, Fish KJ, Howard SK. Crisis Management in Anesthesiology. New York, NY: Churchill
Livingstone; 1994
2. Gaba DM, Fish KJ, Howard SK, Burden AR. Crisis Management in Anesthesiology Second Edition.
Phila Elsevier; 2014
3. Gaba D, Evans D, Patel V: Dynamic decision-making in anesthesiology: cognitive models and training
approaches, Advanced Models of Cognition for Medical Training and Practice. Berlin, Springer -
Verlag, 1992, pp 122
4. Gaba DM, Howard SK, Fish K, et al. Simulation-based training in anesthesia crisis resource
management (ACRM): a decade of experience. Simulation Gaming 2001; 32:175–93.
5. Howard SK, Gaba DM, Fish KJ, et al. Anesthesia Crisis Resource Management Training: teaching
anesthesiologists to handle critical incidents. Aviat Space Environ Med 1992; 63:763 –70.
6. Cooper GE, White MD, Lauber JK: Resource Management on the Flightdeck: Proceedings of a
NASA/Industry Workshop. NASA CP-2120 1980: Moffett Field, CA: NASA-Ames Research Center
7. Gaba DM, Howard SK, Small SD. Situation awareness in anesthesiology. Human Factors: The Journal of
the Human Factors and Ergonomics Society 1995;37(1), 20-31.
8. Wickens CD, Lee J, Liu YD, Gordon-Becker S. An Introduction to Human Factors Engineering (2nd ed.)
Pearson/Prentice Hall Publishing 2004.
9. Tenney Y, Adams M, Pew R, Huggins A, Rogers W. A principal approach to the measurement of

situation awareness in commercial aviation (NASA Contractor Report 4451) Washington, DC:
National Aeronautics and Space Administration 1992.
10. Gosbee J. Human factors engineering and patient safety. Qual Saf Health Care. 2002;11, 352–354.
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11. Helmreich, RL, Davies, JM. Human factors in the operating room: Interpersonal determinants of safety,
efficiency, and morale. In: Aitkenhead AA, (Ed). Balliere's Clinical Anaesthesiology. (pp. 277-296)
London: BalEere Tindall 1999.
12. Karsh BT, Holden RJ, Alper SJ, Or CK. A human factors engineering paradigm for patient safety:
designing to support the performance of the healthcare professional. Qual Saf Health Care 2006;15, 159-
165.
13. Gaba DM, Howard SK, Small SD. Situation awareness in anesthesiology. Human Factors: The Journal of
the Human Factors and Ergonomics Society 1995;37(1), 20-31.
14. Campbell PC, Eng P, Des M, Frank JR. Situational Awareness and Patient Safety. Royal College of
Physicians and Surgeons of Canada 2011.
15. Flin R, Winter J, Sarac C, Raduma M. Human Factors in Patient Safety: Review of Topics and
Tools.WHO/IER/PSP/2009.05. Geneva: World Health Organization
16. Kobus D, Proctor S, Holste S. Effects of experience and uncertainty during dynamic decision making.
International Journal of Industrial Ergonomics 2001;28, 275–290.
17. Reason J. Human error. Cambridge: Cambridge University Press 1990.
18. Endsley MR, Garland DG. Situation awareness analysis and measurement. Mahwah, NJ: Lawrence
Erlbaum Associates 2000.
19. Jones DG, Endsley MR. Use of real-time probes for measuring situation awareness. The International
Journal of Aviation Psychology, 2004;14(4), 343-367.
20. Endsley MR. Proceedings of the National Aerospace and Electronics Conference (NAECON): Situation
awareness global assessment technique (SAGAT), 1988;789–795. New York: IEEE.
21. Prince C, Salas E. Training and research for teamwork in the military aircrew. In Wiener EL, Kanki BG,
Helmreich RL (Eds.), Cockpit Resource Management, (pp. 337-366). Orlando: Academic Press 1993.
22. Chisholm CD, Collison EK, Nelson DR, Cordell WH. Emergency Department Workplace Interruptions:
Are Emergency Physicians “Interrupt-driven” and “Multitasking”?. Academic Emergency Medicine,
2000;7(11), 1239-1243.
23. Jeanmonod R, Boyd Molly, Loewenthal M, Triner W. The nature of emergency department interruptions
and their impact on patient satisfaction. Emergency Medicine Journal, 2010;27(5), 376-379.
24. Rivera-Rodriguez AJ, Karsh B-T. Interruptions and distractions in healthcare: review and reappraisal.
Quality and Safety in Health Care, 2010;(19)4, 304-312.
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Neurologic Disease and Non-Neurologic Surgery

Jeffrey J. Pasternak, MS, MD Rochester, MN
Patient co-morbidities often complicate anesthetic management. Neurologic diseases can impact systemic
physiology. Likewise, aberrations in systemic physiology can adversely impact the injured nervous system. This
refresher course will focus on common neurologic diseases and review their pathophysiology and major
perioperative implications.
1) Explain the pathophysiology of some common neurologic diseases
2) Describe the impact of these diseases on perioperative care
3) Formulate an appropriate management plan for patients with common neurologic diseases requiring
anesthesia for non-neurologic surgery.
Stroke
Stroke is the onset of new neurologic deficits as a result of ischemia within the brain (88% of strokes) or
hemorrhage within the brain or cranial vault (12% of strokes). In 2012, stroke was the second leading cause of
death worldwide after heart disease and a major source of morbidity and consumption of health care resources by
survivors of stroke.1 Stroke related mortality is decreasing in the United States in recent years due to better control
of contributing co-morbidities (ie, hypertension, hyperlipidemia, diabetes mellitus), smoking cessation, and greater
awareness of stroke and risk factors for stroke. This session will focus on ischemic stroke.
The risk factors for ischemic stroke include (but are not limited to): increased age, male sex, African-
American race, hypertension, hyperlipidemia, diabetes mellitus, smoking, personal or family history of stroke,
obesity, and inactivity. A stroke should be strongly suspected in a person who develops focal neurologic deficits
over the course of minutes to hours. Persons who have sustained a transient ischemic attack, ie, stroke symptoms
that complete resolve within 24 h, should be considered at very high risk for developing a stroke. The signs and
symptoms of stroke depend on the regions of brain affected by ischemia.
The risk of ischemic stroke in the perioperative period depends on the surgical procedure, with cardiac,
major vascular, and neurosurgical procedures carrying the greatest risk. Exclusive of this high risk population, the
overall risk of perioperative stroke in the general surgical population is about 0.1%, with patients having
amputations at highest risk (0.8 – 1.1% depending on age).2 Consistent risk factors for perioperative stroke include
advanced age, renal failure, and a prior history of stroke. 2,3 Perioperative stroke is associated with an 8-fold increase
in mortality at 30 d following surgery.2
Recent data confirm that institution of high dose beta-blocker drugs, especially metoprolol, in the
perioperative period may increase the risk for stroke. 4-6 Therefore, beta-blocker drugs should be started with caution
and titrated to effect in pharmacologically naïve patients.
In most circumstances, general anesthesia and regional anesthesia result in similar perioperative stroke
risk.2,7 However, in orthopedic patients having total joint arthroplasty, regional anesthesia may be associated with a
lower risk of perioperative stroke.8,9 Overall, intraoperative hypotension, anemia, hypoglycemia, and hyperglycemia
should be avoided. In patients with pre-operative neurologic deficits, succinylcholine should be used with caution
due to risk for hyperkalemia. Further, assessment of neuromuscular block with train-of-four stimulation should be
avoided on weak extremities due to altered resistance to muscle relaxation with upper motor neuron injury.
Perioperative strokes may present as delayed emergence from anesthesia, inappropriate alterations in
consciousness, or new neurologic deficits. In those with suspected stroke, brain oxygenation and perfusion should be
optimized and a non-contrast computerized tomogram of the head should be obtained, along with an emergent
neurology consult.
Spinal Cord Injury

Each year, there are an estimated 12,500-17,000 new cases of acute spinal cord injury in the United States
and about 276,000 Americans living with chronic spinal cord injury. 10,11 Both acute and chronic spinal cord injury
can have diffuse physiologic manifestations that can impact peri-procedural anesthetic management.
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Anesthesiologists may be responsible for the care of patients with suspected or definitive acute spinal cord
injury for non-neurosurgical procedures such as radiologic studies or for procedures related to other injuries. Spinal
cord injuries are classified grossly as incomplete or complete injuries depending on where or not there is some
degree of sensory or motor function below the level of injury. Most patients with acute injury enter a phase of spinal
shock immediately following the injury that typically can last for 1-3 weeks. This consists of flaccid paralysis and
can be accompanied by loss of sympathetic function below the level of injury. This latter phenomenon can lead to
vasomotor paralysis and hypotension. For lesions in the cervical cord, loss of cardiac accelerator nerve function
(usually derived from T1-4) can lead to unopposed parasympathetic activity and bradycardia, exacerbating systemic
hypotension. Hypotension in this setting can be detrimental as it serves to decrease perfusion to the injured spinal
cord.
The respiratory system can also be affected in acute cord injury. For high thoracic or low cervical cord
injuries, loss of intercostal muscle function can make ventilation dependent on phrenic nerve activation of the
diaphragm. For high cervical cord injuries, loss of phrenic nerve function, derived from C3-5, can result in
significant impairment or loss of ventilatory function.
Key points relevant to the care of patients with suspected or known acute spinal cord injury include:
a. Cervical spinal cord injury should be suspected in any patient who sustained major trauma, especially those
with head trauma, ie, any force sufficient to injure the head can potentially injure the neck and vice versa.
b. Plain radiographs or computerized tomography of the cervical spine are not sensitive for detecting
ligamentous injury. Thus, due to ligamentous instability, patients may be at risk for sustaining a cervical
cord injury upon neck movement despite unremarkable plain radiographs or computerized tomographic
scans.
a. Efforts should be made to minimize neck movement during laryngoscopy and positioning for
procedures.
b. Hard cervical collars minimize but do not completely limit neck motion.
c. Hypotension should be treated to maintain perfusion to the injured cord.
d. Nitrous oxide should be used with caution if there is concern for breach of anatomic spaces such as
pneumothorax or pneumocephalus.
e. Succinylcholine should be used with caution, especially > 24 h following injury due to risk for
hyperkalemia.
f. Maintenance of normal body temperature may be challenging due to loss of sympathetic function and
normal physiologic temperature regulation.
g. Avoid objects placed in the nose due to concerns for basilar skull fracture.
Chronic Spinal Cord Injury

Several weeks following spinal cord injury, cord reflexes return and patients enter a more chronic phase of
their disease. The chronic state of spinal cord injury is characterized by:
a. A conversion from flaccid paralysis to spastic paralysis.
b. Increased risk for heightened autonomic reflexes (discussed later)
c. Impaired respiratory muscle function and the inability to effectively cough increases risk for hypoxemia,
aspiration, and pneumonia in those with cervical or upper thoracic cord injuries
d. Incomplete bladder emptying that can lead to renal calculi and increase risk for infections that, in turn, can
predispose to renal dysfunction
e. Pressure ulcers, muscle contractures, and increased risk for deep venous thrombosis
f. Depression and chronic pain
In addition to these considerations, the anesthesiologist should be aware that there is continued increased risk
for hyperkalemia following the use of succinylcholine. Therefore, non-depolarizing neuromuscular blocking drugs
should be considered if muscle relaxation is required. Further, monitoring muscle relaxation via train-of-four
stimulation in weak limbs can lead to a false appearance of resistance to neuromuscular blockade. Drugs used to
treat spasticity (ie, baclofen, benzodiazepines) should be continued in the perioperative period due to the risk of
withdrawal.
Enhanced autonomic reflexes can be a major source of morbidity and mortality in patients with chronic
spinal cord injury. The risk for autonomic hyperreflexia increases with higher levels of spinal cord injury.
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Specifically, patients with a spinal cord injury level at of higher than T6 are at highest risk whereas the risk is very
low in those with injuries below T10.12
Somatic or visceral stimuli, such as pain or distention of the blader or rectum, initiate increased afferent
activity into the spinal cord. In patients with an intact spinal cord, this activity is modulated by higher centers. In
those with spinal cord injury, these stimuli lead to enhanced autonomic efferent activity below the level of the spinal
cord injury resulting in significant vasoconstriction. As a result, systemic hypertension develops along with reflex
bradycardia. In response to systemic hypertension, vasodilation occurs in regions innervated by cord segments
above the level of the spinal cord injury. Patients may complain of headache, nasal congestion, and blurred vision. If
severe, the patient may develop heart failure, pulmonary edema, or intracranial or retinal hemorrhages.
Management of autonomic hyperreflexia should focus on prevention. Painful procedures should not be
performed on insensate regions of the body without anesthesia, to best ensure avoidance of autonomic hyperreflexia.
General, neuraxial, or regional anesthesia are all possibilities, depending on the general health of the patient and the
planned surgical intervention. For example, topical local anesthesia within the urethra is not adequate during
cystoscopic procedures because bladder muscle proprioceptors may be stimulated during bladder distention. During
labor and delivery, there is a theoretical advantage of spinal anesthesia over epidural anesthesia as sacral sparing
with epidural anesthesia may increase the risk for autonomic hyperreflexia during delivery.
The anesthesiologist should be prepared to treat episodes of autonomic hyperreflexia. In patients receiving
general anesthesia, deepening the anesthesia state may reduce to severity of the episode. For persistent hypertension,
the patient should be treated with vasodilators such as sodium nitroprusside or hydralazine. Episodes of autonomic
hyperreflexia may manifest after the procedure when anesthetic drug effects begin to wane. 13
Multiple Sclerosis
Multiple sclerosis is the most common autoimmune disorder affecting the central nervous system, however
the exact etiology of the disease is still unclear.14 Approximately 2-2.5 million people are affected by multiple
sclerosis worldwide, with women being affected twice as commonly as men. There appears to be a genetic
predisposition and an increased incidence among persons living farther from the equator. Other associations include
infections, stress, and smoking.15-17
Multiple sclerosis most commonly presents in patients in the third and fourth decades of life and is
characterized by multiple relapses of symptoms. Although there may be improvement of symptoms following
relapses, complete resolution of symptoms is rare. The pathophysiology consists of the combination of
inflammation, demyelination, and axonal injury in diffuse areas of the brain and spinal cord, but not within the
peripheral nervous system. Given the diffuse nature of the disease, clinical signs and symptoms depend on the
locations of demyelination.
Making the diagnosis of multiple sclerosis can be quite difficult. Currently, diagnosis is based on the
McDonald Criteria, 18 that depend on clinical signs and symptoms, findings on magnetic resonance imaging scans of
the brain and spinal cord, and biochemical findings in cerebrospinal fluid. The classic finding on imaging is the
presence of multifocal white matter lesions indicating demyelination. Oligoclonal bands are often found in the
cerebrospinal fluid, indicating the production of immunoglobulins in the central nervous system.
Currently, there is no curative treatment for multiple sclerosis and management is targeted on symptom
control and attenuation of the rate of disease progression. Generally, corticosteroids are the mainstay of treatment
for acute relapses due to their antiinflammatory and immunomodulatory effects as well as their positive effect on
blood brain barrier integrity. Although corticosteroids attenuate acute symptoms, their effect on long-term function
and prognosis is unclear. Other immunomodulatory treatments for multiple sclerosis include interferon-β, glatiramer
acetate, mitoxantrone, and azathioprine.
Anesthetic management of patients with multiple sclerosis can be complex. Patients should be made aware
that anesthesia and surgery can increase their risk for a relapse. This may be due to increased physiologic stress,
activation of the inflammatory cascade, fever, or, infection.19,20 Increased temperature can exacerbate neurologic
deficits due to multiple sclerosis, possibly due to decreased nerve conduction velocity at higher core temperatures.
Many patients with multiple sclerosis require chronic corticosteroids. As such, these patients may require
additional steroid supplementation in the perioperative period. Further, the use of chronic steroids can predispose to
hyperglycemia, electrolyte abnormalities, fragile skin, and infection. Use of other immunomodulatory drugs can also
increase risk for infection. The clinician should be aware of side effects of specific drugs used to treat multiple
sclerosis.
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In patients with multiple sclerosis having general anesthesia, there is no current evidence to suggest a
benefit or detriment to the use of specific inhalational or injectable medications. However, the clinician should be
aware of concerns about the use of muscle relaxants. In patients with multiple sclerosis and evidence of upper motor
neuron injury, the use of succinylcholine can predispose to hyperkalemia.21 Also, resistance to muscle relaxation
with non-depolarizing drugs can occur in affected extremities.22
In patients with multiple sclerosis who may be a candidate for regional anesthesia, there is concern that
spinal anesthesia may increase the risk for relapse of symptoms. This has been attributed to direct toxicity of local
anesthetics on the spinal cord already injured by multiple sclerosis and is based on limited data. However, spinal
anesthesia has been used safely in patients with multiple sclerosis.23,24 There is also risk for exacerbation of multiple
sclerosis by epidural anesthesia,25 although epidural analgesia has also been used safely in patients with multiple
sclerosis.26
Seizure Disorder
A seizure is an abnormal excessive synchronous electrical discharge of groups of neurons in the brain.
Approximately 5-10% of the population will have at least 1 seizure in their lifetime. 27 Epilepsy, a predisposition to
recurring seizures, occurs in 4-10 per 1000 people worldwide, and there is an increased prevalence among those
living in developing countries and of lower socioeconomic status. 28 Seizures are more common in individuals in
extremes of age: in the very young, seizures are often due to congenital, metabolic, or infectious causes, or a genetic
predisposition, whereas in the very old, neoplastic and vascular disorders are often the cause of seizures.
Seizures are broadly classified based on 2 characteristics: 1) whether the seizure affects part (partial) or all
of the brain (generalized) and 2) whether there was (complex) or was not (simple) a loss of consciousness associated
with the seizure. This broad classification leads to 3 primary types of seizures:
1) Simple partial seizures – no loss of consciousness and there is clinical evidence for only part of the brain
being affected by the seizure (eg, rhythmic motor activity in only 1 limb). These seizures can undergo
secondary generalization to affect the entire brain.
2) Complex partial seizures – generally affect the temporal lobe. Often consist of automatisms (eg, lip
smacking, tugging at clothes) with loss of consciousness.
3) Generalized seizures – affect the entire brain and are always associated with an alteration of consciousness.
Examples of generalized seizures include:
a. Tonic-clonic seizures
b. Absence seizures
c. Myoclonic seizures
d. Drop attacks.
Seizures should be considered as a sign of an underlying abnormality. Various drugs can increase risk for
seizures (ie, ketamine) and seizures can occur during withdrawal of various drugs (ie, alcohol, benzodiazepines).
Systemic conditions such as severe hypertension, preeclampsia, hepatic encephalopathy, porphyria, and uremia can
increase risk for seizures. Of note, a specific cause for seizures is often not identified in many patients.
The relationship between anesthetic drugs and seizures is complex and not always additive. Drugs
commonly associated with seizures include ketamine, enflurane, and sevoflurane. However, drugs associated with
seizures or spike-and-wake electroencephalographic activity can often interrupt seizures once they have started (ie,
substituted ether anesthetics, ketamine). In contrast, drugs known to be highly suppressant of seizures (eg,
thiopental, inhaled anesthetics) can rarely be associated with seizure activity during anesthesia induction and
elsewhere. 29,30
Conditions that can mimic seizures include tics, torticollis, myoclonus, syncope, extrapyramidal reactions,
and pseudoseizures. Pseudoseizures, or psychogenic seizures, represent a psychiatric disorder. Factors that could
suggest a pseudoseizure include:
a. Resistance to antiepileptic drugs or response to a placebo
b. Events occur only in the presence of an audience (and not during sleep)
c. The apparent seizure can be categorized as simple generalized (ie, based on clinical presentation, the
seizure appears to be affecting the entire brain but there is no alteration of consciousness)
d. There is a normal respiratory pattern with apparent generalized seizures
e. The apparent seizure consists of asynchronous movements.
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The first line treatment for seizures generally involved trying to identify (and treat) the primary cause. In
addition, pharmacologic therapy may also be utilized. Some patients may require multiple drugs to control seizures.
Additionally, some patients may also be a candidate for surgery, especially if a focal region of brain thought to be
the primary source of seizure generation can be identified. In patients with refractory epilepsy, other options include
corpus callosotomy (to minimize seizure spread to the contralateral hemisphere) or vagal nerve stimulation.
Perioperative management of patients with epilepsy includes continuation of antiepileptic medications,
awareness of side effects of specific antiepileptic medications, and avoidance or minimization of drugs that lower
the seizure threshold, if possible. The clinician should inquire about seizure phenotypes and frequency pre-
operatively so that post-operative risk for seizures can be estimated and surveillance for seizures can occur in the
perioperative period. Chronic use of antiepileptic drugs, especially phenytoin and carbamazepine, can shorten the
duration of action of non-depolarizing muscle relaxants.31 In patients with a vagal nerve stimulator, the cautery
grounding pad should be placed far away from the device. Also, a vagal nerve stimulator should be deactivated in
patients requiring magnetic resonance imaging.
Management of perioperative seizure should include:
1. Maintenance of airway, breathing, and circulation
2. Cessation of the seizure: consider benzodiazepines or other hypnotic drugs
3. Identification of a cause if this is a new seizure
4. Prevention of further seizures: treat the cause (if possible) and consider antiepileptic drugs
such as levetiracetam
References
1. World Health Organization: The top 10 causes of death,
http://www.who.int/mediacentre/factsheets/fs310/en/, 2014, accessed June 1, 2015
2. Mashour GA, Shanks AM, Kheterpal S: Perioperative stroke and associated mortality after noncardiac,
nonneurologic surgery. Anesthesiology 2011; 114: 1289-96
3. Sharifpour M, Moore LE, Shanks AM, et al: Incidence, predictors, and outcomes of perioperative stroke in
noncarotid major vascular surgery. Anesth Analg 2013; 116: 424-34
4. Ashes C, Judelman S, Wijeysundera DN, et al: Selective beta1-antagonism with bisoprolol is associated
with fewer postoperative strokes than atenolol or metoprolol: a single-center cohort study of 44,092 consecutive
patients. Anesthesiology 2013; 119: 777-87
5. Devereaux PJ, Yang H, Yusuf S, et al: Effects of extended-release metoprolol succinate in patients
undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. Lancet 2008; 371: 1839-47
6. Mashour GA, Sharifpour M, Freundlich RE, et al: Perioperative metoprolol and risk of stroke after
noncardiac surgery. Anesthesiology 2013; 119: 1340-6
7. Lewis SC, Warlow CP, Bodenham AR, et al: General anaesthesia versus local anaesthesia for carotid
surgery (GALA): a multicentre, randomised controlled trial. Lancet 2008; 372: 2132-42
8. Memtsoudis SG, Sun X, Chiu YL, et al: Perioperative comparative effectiveness of anesthetic technique in
orthopedic patients. Anesthesiology 2013; 118: 1046-58
9. Mortazavi SM, Kakli H, Bican O, et al: Perioperative stroke after total joint arthroplasty: prevalence,
predictors, and outcome. J Bone Joint Aurg. e 2010; 92: 2095-101
10. National Spinal Cord Injury Statistics Center: Spinal Cord Injury Facts and Figures at a Glance,
https://www.nscisc.uab.edu/PublicDocuments/fact_figures_docs/Facts%202012%20Feb%20Final.pdf. Birmingham,
AL, 2012, accessed June 1, 2015
11. Jain NB, Ayers GD, Peterson EN, et al: Traumatic Spinal Cord Injury in the United States, 1993-2012.
JAMA 2015; 313: 2236-2243
12. Krassioukov AV, Furlan JC, Fehlings MG: Autonomic dysreflexia in acute spinal cord injury: an under-
recognized clinical entity. J Neurotrauma 2003; 20: 707-16
13. Sharpe EE, Arendt KW, Jacob AK, Pasternak JJ: Anesthetic management of parturients with pre-existing
paraplegia or tetraplegia: a case series. Int J Obstet Anesth 2015; 24: 77-84
14. Berer K, Krishnamoorthy G: Microbial view of central nervous system autoimmunity. FEBS Letters 2014;
S0014-5793 (14): 00293–2
15. Dyment DA, Ebers GC, Sadovnick AD: Genetics of multiple sclerosis. Lancet. Neurol 2004; 3: 104-10
16. Compston A, Coles A: Multiple sclerosis. Lancet 2008; 372: 1502-17
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17. Ascherio A, Munger KL: Environmental risk factors for multiple sclerosis. Part II: Noninfectious factors.
Ann Neurol 2007; 61: 504-13
18. Polman CH, Reingold SC, Banwell B, et al: Diagnostic criteria for multiple sclerosis: 2010 revisions to the
McDonald criteria. Ann Neurol 2011; 69: 292-302
19. Ridley A, Schapira K: Influence of surgical procedures on the curse of multiple sclerosis. Neurology 1961;
11: 81-2
20. Dickerman RD, Schneider SJ, Stevens QE, et al: Prophylaxis to avert exacerbation/relapse of multiple
sclerosis in affected patients undergoing surgery. Surgical observations and recommendations. J Neurosurg Sci
2004; 48: 135-7
21. Levine M, Brown DF: Succinylcholine-induced hyperkalemia in a patient with multiple sclerosis. J Emerg
Med 2012; 43: 279-82
22. Brett RS, Schmidt JH, Gage JS, et al: Measurement of acetylcholine receptor concentration in skeletal
muscle from a patient with multiple sclerosis and resistance to atracurium. Anesthesiology 1987; 66: 837-9
23. Oouchi S, Nagata H, Ookawa H, et al: [Spinal anesthesia for cesarean section in a patient with multiple
sclerosis]. Masui. Japanese J Anesthesiol 2013; 62: 474-6
24. Bouchard P, Caillet JB, Monnet F, Banssillon V: [Spinal anesthesia and multiple sclerosis]. Annales
francaises d'anesthesie et de reanimation 1984; 3: 194-8
25. Warren TM, Datta S, Ostheimer GW: Lumbar epidural anesthesia in a patient with multiple sclerosis.
Anesth Analg 1982; 61: 1022-3
26. Bader AM, Hunt CO, Datta S, et al: Anesthesia for the obstetric patient with multiple sclerosis. J Clin
Anesth 1988; 1: 21-4
27. Wilden JA, Cohen-Gadol AA: Evaluation of first nonfebrile seizures. Amer Fam Phys 2012; 86: 334-40
28. World Health Organization. Epilepsy Fact Sheet, http://www.who.int/mediacentre/factsheets/fs999/en/,
2015, accessed June 1, 2015
29. Modica PA, Tempelhoff R, White PF: Pro- and anticonvulsant effects of anesthetics (Part II). Anesth Analg
1990; 70: 433-44
30. Modica PA, Tempelhoff R, White PF: Pro- and anticonvulsant effects of anesthetics (Part I). Anesth Analg
1990; 70: 303-15
31. Soriano SG, Martyn JA: Antiepileptic-induced resistance to neuromuscular blockers: mechanisms and
clinical significance. Clin Pharmacokinetics 2004; 43: 71-81
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Regional Anesthesia Registries: Is There Value and What Have We Learned
Michael Barrington Ph.D. Melbourne, Victoria, Australia
Introduction
Overall it is estimated that only 15 - 20% of medical practices are based on rigorous scientific data that establishes
their effectiveness.1 Clinical registries provide a snap shot into how healthcare performs. The focus of clinical
registries is to capture real-world clinical practice, for example native hospital behaviour, in large patient
populations independent of the environment of a controlled clinical trial. Clinical conditions, procedures, therapies
or entire populations can be systematically studied. In the context of modern healthcare expectations where all
procedures that we offer our patients should be evidenced-based, clinical registries provide a valuable tool to
evaluate what works and what does not. In this context, a registry of a surgical or anesthetic procedure is
complimentary to the perioperative surgical home model. Registries are increasingly attracting the attention of
funders, regulators and administrators as health care systems seek more information on the quality and safety of our
clinical care. This refresher course lecture will review the methodology and logistics of a registry, it will compare
registries with other study types and will demonstrate how regional anesthesia registries and reports with similar
methodologies add value to healthcare and assist in our clinical decision making. Registries are an example of a
prospective cohort study where patients who are exposed to a specific risk (e.g. surgery, anesthesia, a specific
procedure) are studied for the development of predefined outcomes.
Methodology
At a basic level the concept of a registry is simple, a place where records are kept. Clinical Registries systematically
and uniformly collect information from people who undergo a procedure, are diagnosed with a disease or use a
health care resource.2 The American Heart Association defines a clinical registry as a prospective observational
database of a clinical condition, procedure, therapy or population, in which there are no registry-mandated
approaches to therapy and relatively few inclusion and exclusion criteria.3 This is very different to the conduct of a
controlled-clinical trial where often, rigid filters in the form of inclusion and exclusion criteria are applied before
sampling can occur. Clinical registries are important for monitoring and benchmarking the quality of clinical care
providing a basis for clinical practice improvement.4 Clinical registries can serve multiple functions such as public
health surveillance, vehicles for quality-improvement, performance assessment, evaluation of trends in clinical
practice and to monitor the safety and effectiveness of a drug, device or procedure. Registries aim to have complete,
or almost complete capture of all eligible procedures, thereby minimizing selection and enrolment bias.2 Capturing a
complete, or near complete patient population with sequential enrolment is the goal. Population-based studies using
existing large databases and other data sources have features that are similar to a registry protocol with the aim of
enrolment of an entire patient population.
The data elements that registries collect need to be carefully considered and should be epidemiologically sound,
meaning that the data should be simple, objective and reproducible. The dataset for a registry should be simple and
only data that are required to address the question or issue of interest should be collected. Examples of appropriate
data to collect include patient demographics, surgical characteristics, anesthetic type and dosage, other practice
patterns, clinical effectiveness outcomes and adverse events. The data elements need not be static, but rather change
according to the important clinical questions. Logistically the data should be simple enough that physicians can
efficiently enter information in a database in the context of a busy clinical practice. An online interface for entering
data that will then be transferred and stored securely in a remote database is valuable for a multicenter registry.
Methods of collecting registry data will vary depending on the outcome. For example, a registry investigating
neurologic complications of PNB would require the following. 1. Systematic postoperative contact with patients and
proactively seeking complications. A systematic proactive approach to capturing complications is associated with
more reliable capture of complications compared to a passive approach 5 2. A defined follow-up and neurologic
referral and investigative pathway. A standardized questionnaire for detecting patients with potential complications
may assist. 3. Clear definition for nerve injury. 4. Robust neurologic evaluation with a focused history and
examination. Electromyography and imaging studies are important for this outcome.
Registries, because they contain uncontrolled observational measurements, hold a higher risk for unrecognised bias
and incorrect conclusions about cause and effect than controlled clinical studies. This stems from the influence that
unmeasured or unknown confounders may have on the results.6 The analysis of an observational dataset may be
more complex than that required for a randomised controlled trial (RCT). The controlled clinical trial aims to
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randomise a sufficiently large sample to eliminate significant baseline differences between study groups and reduce
bias from residual confounders. RCTs represent the gold standard for evidence of causality. The analysis of
observational datasets may establish association but not causality, however this type of finding may be significant
when large samples are involved. The large sample size may add to the credibility of the finding. The results of
observational studies are generally considered exploratory, non-definitive and generate a hypothesis to be tested in a
subsequent RCT. However, this is an impractical paradigm when one realizes that serious outcomes may occur so
infrequently that the conduct of a subsequent RCT may require such large patient numbers that it would not be
feasible.
What have we learned from clinical registries of regional anesthesia and similar projects such as population
based studies?
Registries have documented the incidence of infrequently occurring complications facilitating risk assessment and
informed consent. In certain surgical populations, registries have identified that regional anesthesia is not associated
with an increased risk of perioperative nerve injury (PNI).7,8 Fortunately, block-related neurological complications
with severe long-term sequelae directly related to peripheral nerve block (PNB) or neuraxial anesthesia (NA) occur
very infrequently or rarely. In one registry report, patients who met the criteria for referral to a neurologist were 9
times more likely to have a cause unrelated to PNB, than they were to have symptoms/signs attributable to PNB.9
Without careful evaluation, patient’s postoperative neurologic features can be incorrectly attributed to regional
anesthesia. The potential for these scenarios are similar to obstetric studies where regional anesthesia is often
blamed but rarely responsible.10 Registries of PNB, because of their large sample size have been able to determine
the incidence of PNI with reasonable certainty.11,12 Similarly, registries and large-scale population studies have
provided contemporary estimates of complications and risk factors associated with neuraxial anesthesia. 13 Practice
patterns and complications in pediatric practice have been documented systematically in registries. 14,15 The
investigators of a pediatric registry have demonstrated that performing regional anesthesia under general anesthesia
does not present additional risk to the patient compared to if the patients were awake or lightly sedated. 16 These
insights provide information that can be used in practice guidelines.
Monitoring the quality and safety of regional anesthesia is also important because clinical practice is continually
evolving. Registries have documented the safety of therapies such as ultrasound-guided regional anesthesia. One
registry reported the incidence of pneumothorax following ultrasound-guided supraclavicular block to be 0.4 per
1000 PNB.17 In real-life practice, a registry of PNB has documented reduced doses of ropivacaine when ultrasound-
guided PNB was compared to non-ultrasound techniques [1.48 (0.73 – 2.71) versus 1.63 (0.74 – 2.88) mg/kg
respectively, doses presented as median (10th – 90th centile)].18 Reduced local anesthetic dosage may reduce the risk
of local neural and systemic toxicity and reduce the incidence of side effects such a phrenic nerve paralysis
following interscalene blockade.
In 2010, following a review of published cases of local anesthetic systemic toxicity (LAST) over a 30-year period,
the author’s commented: “we lack a precise and accurate portrayal of the clinical spectrum of LAST and its optimal
treatment. This deficiency begs for the development of a prospective data collection tool in the form of a robust,
comprehensive registry of LAST events designed to avoid the many shortcomings of retrospective literature review”.
19
Fortunately, since that comment several registries have evolved and their results indicate that severe local
anesthetic systemic toxicity (LAST) occurs infrequently. One single-center study recorded an incidence of seizures
of 0.92 per 1000 PNB in a practice where landmark, nerve stimulator and ultrasound-guided techniques were used.20
All of seizures occurred in patients where either landmark or nerve stimulator techniques were used. 9 In a follow-up
study at the same institution, one further seizure occurred, again in a patient receiving a non-ultrasound technique.11
In a multicenter registry of 8189 PNB there were five and four episodes of minor and severe LAST respectively.
The overall incidence of LAST was 0.98 per PNB with no significant difference in incidence of LAST between
ultrasound-guided and non-ultrasound techniques.9 In 2012, using a single-centre registry there were zero
documented cases of severe LAST (seizures) from a cohort of 12,668 ultrasound-guided PNB.12 In 2013, data
(25,336 PNBs from 20,021 patients) was analysed from the Australian and New Zealand Registry of Regional
Anaesthesia. The results demonstrated that ultrasound-guidance was significantly associated with a reduced risk of
LAST.18 The risk of LAST was reduced by 60 – 65% when ultrasound was used compared to use of nerve
stimulation or landmark techniques for PNB. In this report, the overall incidence of LAST was 0.87 per 1000 PNB.
Importantly, this study also identified factors associated with an increased risk of LAST including site of injection
(upper limb blockade, paravertebral), local anesthetic dosage, local anesthetic dosage per weight, and reduced
patient body weight. Independent of factors related to ultrasound and those identified in the abovementioned studies,
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it is generally accepted that patient comorbidities and individual susceptibility to local anesthetic may increase the
risk of LAST.
Patient rated outcomes can be included in a registry to reflect the importance of patient centred care and recording
patients’ perceptions of the care they received. In one registry report, 94.6% of respondents were willing to have a
repeat PNB. Ninety percent of respondents were satisfied or completely satisfied with the information provided
about the nerve block, as well as the anesthesiologist-patient interaction. Patients who were dissatisfied with either
of these domains (ie, information provision or professional interaction) were less willing to undergo repeat PNB, as
were patients who reported significant pain during the nerve block procedure. These findings have practical
implications for conduct of PNB.21
Existing databases, registries and population-based observational studies with large surgical cohorts report that
neuraxial anesthesia may provide perioperative outcome benefits compared to general anesthesia in orthopedic and
general surgical patients. Although controversial, there appear to be consistent trends in outcome benefits with
neuraxial anesthesia compared to general anesthesia in the following categories: pulmonary morbidity, blood
transfusion and resource use (critical care services, length of hospital stay). Reports of mortality benefits from
neuraxial anesthesia are inconsistent. Table 1 summarizes outcomes obtained from registries and population based
studies.
Registries provide value
Clinical registries and the actions of our professional groups add value to healthcare reporting by: 1. Developing
epidemiological tools to enhance the knowledge base about quality and safety; 2. Establishing voluntary reporting
tools to identify and learn from errors; 3. Raising the standards and expectations in patient safety; 4. Contribute to
building and maintaining a culture of safety; 5. Providing an opportunity for local leadership and 6. Proactively
monitor for adverse events.
Registries add value by providing the infrastructure to support ongoing data collection and providing insights into
long-term efficacy and safety that a single trial may not be able to detect. Time series data can validate earlier
findings and detect trends in practice. Patterns in time series data contain important information that other traditional
statistical methods reliant on averages or summary statistics can mask. Improvement is a temporal event and
incorrect claims of improvement or efficacy become apparent with time.6 Science and the practice of medicine move
quickly and the original clinical environment of a trial may no longer exist by the time its results are being applied.
A registry, because of its longevity, is more flexible in terms of identifying trends in practice and results relevant to
contemporary care.
Conclusions
Registries and related population-based studies including a variety of surgical cohorts have provided essential
insights into the quality of healthcare, providing opportunities to report and improve outcomes that both physicians
and patients consider important. The incidence of major morbidity related to PNB or neuraxial anaesthesia is
fortunately uncommon or rare. Neuraxial anesthesia may decrease morbidity and requirement for critical care
services when compared with general anesthesia. Registries provide an important tool to report perioperative
outcomes required for the modern healthcare paradigm. Registries of regional anesthesia are instrumental for
defining the quality and safety of clinical practice.
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Table 1. Summary of results from registries and population-based studies

Author, Year Anesthesia type N, cohort Outcomes Main results
Barrington, PNB 8189 PNB Neurological complication, Nerve injury, 0.4 per
20099 LAST 1000; LAST, 0.98 per
1000 PNB
Liu, 201022 Interscalene/ 1169 Nerve injury 0% incidence of
supraclavicular permanent nerve injury
blocks
Jacob, 20118 PNB 12,329 TKA Nerve injury Nerve injury not
associated with PNB or
anesthesia type
Jacob, 20117 PNB 12,998 THA Nerve injury Nerve injury not
associated with PNB or
anesthesia type
Orebaugh, 201211 PNB 9069 US Nerve Injury US and NS blocks: No
guided Seizure difference in nerve
5436 NS injury rate, increased
guided seizures with NS blocks
Sites, 201212 PNB 12,668 PNBs Nerve injury, LAST Event rate:1.8 per 1000,
Pneumothorax major complications
Vascular trauma occurred rarely
Polaner, 201215 All RA types 14,917 PNB Practice patterns and No complications >3
complications in pediatric months. 95% of PNB
practice were placed under GA
PNBs used in 35%
Sviggum, 201223 Interscalene 1569 TSA Nerve Injury PNB associated with
reduced risk for nerve
injury
Barrington, PNB 25,336 PNB LAST LAST, 0.87 per 1000
201318 PNBs. Ultrasound
guidance was
associated with reduced
incidence of LAST.
Sites, 201424 PNB 23,271 PNB Safety and effectiveness Immediate
complication, 2.2%
All cause 60-day
neurological sequelae,
0.83%,
Taenzer, 201416 PNB 53,564 Nerve injury/symptoms Neurological symptoms
:0.93/1000 (0.7–1.2)
under GA; 6.82/1000
(4.2–10.5), in
sedated/awake patients,
(95% CI)
Long, 201414 TAP blocks 1994 Morbidity Complications: 0.1%
(0.02%–0.3%, 95% CI)
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Population-based studies
Chang, NA 3081 TKA Surgical site infection SSI 1.8%
201025 GA (SSI) GA associated with
increased risk of SSI
Stundner, NA, GA, 15,687 Blood transfusion NA: reduced risk of
201226 Combined NA/GA bilateral transfusion
TKA
Neuman, NA 18,158 Mortality, NA: reduced risk of
201227 GA femoral neck Morbidity pulmonary
fractures complications, no
difference in mortality
Memtsoudis, NA, GA, 528,495 Utilisation of critical care NA: decreased need for
201228 Combined NA/GA TKA, THA services critical care services
Memtsoudis, NA, GA, 40,316 TKA Morbidity NA or combined
201329 Combined NA/GA ,THA Mortality NA/GA: reduced risk of
complications
Memtsoudis, NA (11%) 382,236 Morbidity Reduced mortality,
201330 Combined NA/GA TKA, THA Mortality pulmonary outcome,
(14%), GA (75%) length of stay with NA
Liu, NA 16,555 TKA Morbidity Mortality was 0.24%
201331 GA Mortality NA: associated with
reduced infection
Bateman, 201313 Epidural catheters 62,450 Epidural hematoma Laminectomy
perioperative (perioperative):
79,837 1:22,189 to 1:4330
obstetric (95% CI)
Pugely, Spinal, General 14,056 30-day Morbidity 43% Spinal
201332 TKA Mortality 57% GA
GA associated with
increased risk of
complications, (OR 1.1)
Memtsoudis, NA, Combined 795,135 Major complication, NA: decreased risk for
201433 NA/GA, GA TKAs or Resource use major complications
THAs and resource utilization
irrespective of age and
comorbidity burden
Patorno, GA, RA, 73,284 Mortality In-hospital all cause
201434 Combined RA/GA femoral neck mortality, 2.2, 2.1,
fractures 2.4%. No difference
between groups
Fleischut, 201535 GA, NA, RA 108 625 Practice patterns 10.9%, 31.3%, and
TKAs 57.9% were performed
under RA, NA, and
GA, respectively.
Chen, 201536 GA, NA 7977 THA Length of stay NA: reduced treatment
costs and a shorter
length of stay.
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Ozbek, 201537 Combined NA/GA, 19843, open AMI NA/GA: lower

GA lung incidence of AMI,
resections pulmonary
complications, blood
transfusion
Memtsoudis, NA, Combined 795,135 Major complication, NA: decreased risk of
201433 NA/GA, GA TKAs or Resource use major complications,
THAs resource utilization
irrespective of age and
comorbidity burden
Hausman, 201538 NA, GA 5288 Morbidity GA: higher incidence
Mortality of pneumonia,
ventilator dependence
Poeran, 201439 Combined NA/GA, 98,290, open Major morbidity Combined NA/GA:
GA colectomies decreased risk of VTE
events, increased risk
of AMI, transfusion
and ICU admission
Seitz, 201440 GA, RA 6135, hip Morbidity No difference in
fracture Mortality outcomes except GA
surgery associated with higher
rates of ICU
admissions.
Neuman, 201441 NA, GA 56729, Hip Mortality, length of stay NA associated with
fracture shorter length of stay,
surgery no difference in
mortality
Cicek, 201342 NA, GA 1004, PCNL Length of stay NA: shorter Length of
Blood transfusion stay and reduced rates
of transfusion
Ghanami, 201343 NA, GA 5462,Vascular Morbidity No difference in
surgery Mortality outcomes
Edwards, 201144 GA, NA 6009, Morbidity GA: increased
Endovascular Mortality pulmonary morbidity
aortic Length of stay and length of stay; no
aneurysm difference in mortality
repair
Wiis, 201445 GA, NA 822 Vascular Mortality No difference in
surgery outcome
Nash, 2015 46 Combined NA/GA, 29,743 Morbidity No difference in
GA Mortality outcome
PNB = peripheral nerve block; NA; neuraxial anesthesia: GA, general anesthesia; RA, regional anesthesia; Local
Anesthetic Systemic Toxicity, LAST; TKA, total knee arthroplasty; THA, total hip arthroplasty; SSI, surgical site
infection, AMI, Acute myocardial infarction; VTE, venous thromboembolism.
References
1. Hannenberg AA, Warner MA: The registry imperative. Anesthesiology 2009; 111: 687-689
2. McNeil JJ, Evans SM, Johnson NP, Cameron PA: Clinical-quality registries: their role in quality
improvement. Med J Aust 2010; 192: 244-245
3. Bufalino VJ, Masoudi FA, Stranne SK, et al.: The American Heart Association's recommendations for
expanding the applications of existing and future clinical registries: a policy statement from the American Heart
Association. Circulation 2011; 123: 2167-2179
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4. McNeil JJ, Evans SM, Johnson NP, Cameron PA: Clinical-quality registries:their role in quality
improvement. Med J Aust 2010; 192: 244-245
5. Liguori GA: Complications of regional anesthesia: nerve injury and peripheral neural blockade. J
Neurosurg Anesthesiol 2004; 16: 84-86
6. Pronovost PJ, Nolan T, Zeger S, Miller M, Rubin H: How can clinicians measure safety and quality in
acute care? Lancet 2004; 363: 1061-1067
7. Jacob AK, Mantilla CB, Sviggum HP, Schroeder DR, Pagnano MW, Hebl JR: Perioperative nerve injury
after total hip arthroplasty: regional anesthesia risk during a 20-year cohort study. Anesthesiology 2011; 115: 1172-
1178
8. Jacob AK, Mantilla CB, Sviggum HP, Schroeder DR, Pagnano MW, Hebl JR: Perioperative nerve injury
after total knee arthroplasty: regional anesthesia risk during a 20-year cohort study. Anesthesiology 2011; 114: 311-
317
9. Barrington MJ, Watts SA, Gledhill SR, et al.: Preliminary results of the Australasian Regional Anaesthesia
Collaboration: a prospective audit of more than 7000 peripheral nerve and plexus blocks for neurologic and other
complications. Reg Anesth Pain Med 2009; 34: 534-541
10. Holdcroft A, Gibberd FB, Hargrove RL, Hawkins DF, Dellaportas CI: Neurological complications
associated with pregnancy. Br J Anaesth 1995; 75: 522-526
11. Orebaugh SL, Kentor ML, Williams BA: Adverse outcomes associated with nerve stimulator-guided and
ultrasound-guided peripheral nerve blocks by supervised trainees: update of a single-site database. Reg Anesth Pain
Med 2012; 37: 577-582
12. Sites BD, Taenzer AH, Herrick MD, et al.: Incidence of local anesthetic systemic toxicity and postoperative
neurologic symptoms associated with 12,668 ultrasound-guided nerve blocks: an analysis from a prospective clinical
registry. Reg Anesth Pain Med 2012; 37: 478-482
13. Bateman BT, Mhyre JM, Ehrenfeld J, et al.: The risk and outcomes of epidural hematomas after
perioperative and obstetric epidural catheterization: a report from the Multicenter Perioperative Outcomes Group
Research Consortium. Anesth Analg 2013; 116: 1380-1385
14. Long JB, Birmingham PK, De Oliveira GS, Jr., Schaldenbrand KM, Suresh S: Transversus abdominis
plane block in children: a multicenter safety analysis of 1994 cases from the PRAN (Pediatric Regional Anesthesia
Network) database. Anesth Analg 2014; 119: 395-399
15. Polaner DM, Taenzer AH, Walker BJ, et al.: Pediatric Regional Anesthesia Network (PRAN): a multi-
institutional study of the use and incidence of complications of pediatric regional anesthesia. Anesth Analg 2012;
115: 1353-1364
16. Taenzer AH, Walker BJ, Bosenberg AT, et al.: Asleep versus awake: does it matter?: Pediatric regional
block complications by patient state: a report from the Pediatric Regional Anesthesia Network. Reg Anesth Pain
Med 2014; 39: 279-283
17. Abell DJ, Barrington MJ: Pneumothorax after ultrasound-guided supraclavicular block: presenting features,
risk, and related training. Reg Anesth Pain Med 2014; 39: 164-167
18. Barrington MJ, Kluger R: Ultrasound guidance reduces the risk of local anesthetic systemic toxicity
following peripheral nerve blockade. Reg Anesth Pain Med 2013; 38: 289-297
19. Di Gregorio G, Neal JM, Rosenquist RW, Weinberg GL: Clinical presentation of local anesthetic systemic
toxicity: a review of published cases, 1979 to 2009. Reg Anesth Pain Med 2010; 35: 181-187
20. Orebaugh SL, Williams BA, Vallejo M, Kentor ML: Adverse outcomes associated with stimulator-based
peripheral nerve blocks with versus without ultrasound visualization. Reg Anesth Pain Med 2009; 34: 251-255
21. Ironfield CM, Barrington MJ, Kluger R, Sites B: Are patients satisfied after peripheral nerve blockade?
Results from an International Registry of Regional Anesthesia. Reg Anesth Pain Med 2014; 39: 48-55
22. Liu SS, Gordon MA, Shaw PM, Wilfred S, Shetty T, Yadeau JT: A prospective clinical registry of
ultrasound-guided regional anesthesia for ambulatory shoulder surgery. Anesth Analg 2010; 111: 617-623
23. Sviggum HP, Jacob AK, Mantilla CB, Schroeder DR, Sperling JW, Hebl JR: Perioperative nerve injury
after total shoulder arthroplasty: assessment of risk after regional anesthesia. Reg Anesth Pain Med 2012; 37: 490-
494
24. Sites BD, Barrington MJ, Davis M: Using an international clinical registry of regional anesthesia to identify
targets for quality improvement. Reg Anesth Pain Med 2014; 39: 487-495
25. Chang CC, Lin HC, Lin HW, Lin HC: Anesthetic management and surgical site infections in total hip or
knee replacement: a population-based study. Anesthesiology 2010; 113: 279-284
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26. Stundner O, Chiu YL, Sun X, et al.: Comparative perioperative outcomes associated with neuraxial versus
general anesthesia for simultaneous bilateral total knee arthroplasty. Reg Anesth Pain Med 2012; 37: 638-644
27. Neuman MD, Silber JH, Elkassabany NM, Ludwig JM, Fleisher LA: Comparative effectiveness of regional
versus general anesthesia for hip fracture surgery in adults. Anesthesiology 2012; 117: 72-92
28. Memtsoudis SG, Sun X, Chiu YL, et al.: Utilization of critical care services among patients undergoing
total hip and knee arthroplasty: epidemiology and risk factors. Anesthesiology 2012; 117: 107-116
29. Memtsoudis SG, Stundner O, Rasul R, et al.: Sleep apnea and total joint arthroplasty under various types of
anesthesia: a population-based study of perioperative outcomes. Reg Anesth Pain Med 2013; 38: 274-281
30. Memtsoudis SG, Sun X, Chiu YL, et al.: Perioperative comparative effectiveness of anesthetic technique in
orthopedic patients. Anesthesiology 2013; 118: 1046-1058
31. Liu J, Ma C, Elkassabany N, Fleisher LA, Neuman MD: Neuraxial anesthesia decreases postoperative
systemic infection risk compared with general anesthesia in knee arthroplasty. Anesth Analg 2013; 117: 1010-1016
32. Pugely AJ, Callaghan JJ, Martin CT, Cram P, Gao Y: Incidence of and risk factors for 30-day readmission
following elective primary total joint arthroplasty: analysis from the ACS-NSQIP. J Arthroplasty 2013; 28: 1499-
1504
33. Memtsoudis SG, Rasul R, Suzuki S, et al.: Does the impact of the type of anesthesia on outcomes differ by
patient age and comorbidity burden? Reg Anesth Pain Med 2014; 39: 112-119
34. Patorno E, Neuman MD, Schneeweiss S, Mogun H, Bateman BT: Comparative safety of anesthetic type for
hip fracture surgery in adults: retrospective cohort study. BMJ 2014; 348: g4022
35. Fleischut PM, Eskreis-Winkler JM, Gaber-Baylis LK, et al.: Variability in anesthetic care for total knee
arthroplasty: an analysis from the anesthesia quality institute. Am J Med Qual 2015; 30: 172-179
36. Chen WH, Hung KC, Tan PH, Shi HY: Neuraxial anesthesia improves long-term survival after total joint
replacement: a retrospective nationwide population-based study in Taiwan. Canadian Journal of Anaesthesia 2015;
62: 369-376
37. Ozbek U, Poeran J, Mazumdar M, Memtsoudis SG: Patient Safety and Comparative Effectiveness of
Anesthetic Technique in Open Lung Resections. Chest 2015; 148: 722-730
38. Hausman MS, Jr., Jewell ES, Engoren M: Regional versus general anesthesia in surgical patients with
chronic obstructive pulmonary disease: does avoiding general anesthesia reduce the risk of postoperative
complications? Anesthesia & Analgesia 2015; 120: 1405-1412
39. Poeran J, Yeo H, Rasul R, Opperer M, Memtsoudis SG, Mazumdar M: Anesthesia type and perioperative
outcome: open colectomies in the United States. Journal of Surgical Research 2015; 193: 684-692
40. Seitz DP, Gill SS, Bell CM, et al.: Postoperative medical complications associated with anesthesia in older
adults with dementia. Journal of the American Geriatrics Society 2014; 62: 2102-2109
41. Neuman MD, Rosenbaum PR, Ludwig JM, Zubizarreta JR, Silber JH: Anesthesia technique, mortality, and
length of stay after hip fracture surgery. JAMA 2014; 311: 2508-2517
42. Cicek T, Gonulalan U, Dogan R, et al.: Spinal anesthesia is an efficient and safe anesthetic method for
percutaneous nephrolithotomy. Urology 2014; 83: 50-55
43. Ghanami RJ, Hurie J, Andrews JS, et al.: Anesthesia-based evaluation of outcomes of lower-extremity
vascular bypass procedures. Annals of Vascular Surgery 2013; 27: 199-207
44. Edwards MS, Andrews JS, Edwards AF, et al.: Results of endovascular aortic aneurysm repair with
general, regional, and local/monitored anesthesia care in the American College of Surgeons National Surgical
Quality Improvement Program database. Journal of Vascular Surgery 2011; 54: 1273-1282
45. Wiis JT, Jensen-Gadegaard P, Altintas U, Seidelin C, Martusevicius R, Mantoni T: One-week
postoperative patency of lower extremity in situ bypass graft comparing epidural and general anesthesia:
retrospective study of 822 patients. Annals of Vascular Surgery 2014; 28: 295-300
46. Nash DM, Mustafa RA, McArthur E, et al.: Combined general and neuraxial anesthesia versus general
anesthesia: a population-based cohort study. Canadian Journal of Anaesthesia 2015; 62: 356-368
311
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The Morbidly Obese Patient is a Bigger Anesthetic Challenge: Fat or Fiction?
Ashish Sinha MD PhD MBA ` Philadelphia, PA
Introduction:
This review will address the anesthetic issues in obesity along with epidemiological
factors which attempt to explain how we got here in the last thirty or so years. The issues
of the large patient can be challenging in all aspects of medical care, but this review will
focus on the perioperative issues as they are more relevant to us.
1. Defining obesity
Is weight and or BMI the primary consideration of ‘obesity’? No; there are many large
but healthy people who may be heavy and would be considered ‘obese’ in a weight-
based-sense, with measures of BMI (weight in kilograms/height in meters2). BMI (or
Quintets index) does have its advantages; it is culture, age and gender independent.
Another advantage of BMI is that it only incorporates two easily assessed low tech
objective measures: height and weight. The major disadvantage of using BMI as a sole
predictor of health status is that it doesn’t take into consideration variations between lean
body mass, particularly muscle mass. Looking at some professional athletes, as in the
NFL, players with only the height and weight metrics would classify half of them as
obese and a quarter as extremely obese, even though they average a very healthy 14%
body fat.
There are at least two ways of looking at obesity and BMI, the simplistic version,
recommended by the WHO involves defining the obese as those patients having a BMI
>30 kg/m2, while sub classifying those with BMI between 30 and 35 as Class I, 35 and 40
as Class II and more than 40 as Class III.
BMI ‘Defined’ class

<18.5 kg/m2 Underweight
18.5 to 24.9 kg/m2 Normal
25 to 29.5 kg/m2 Overweight
30 to 34.9 kg/m2 Obese
35 to 40 kg/m2 Severely Obese
40 to 50 kg/m2 Morbidly Obese
50 to 60 kg/m2 Super morbidly obese
60 to 70 kg/m2 Super-duper morbidly obese
>70 kg/m2 Ultra obese (suggested class)
Different groups use different definitions and cutoffs with BMI and obesity classes. The
US Government and the WHO use cutoffs points of 30 for obesity and 40 for severe
obesity, whereas the FDA uses a BMI of 30 or even 27, with comorbid conditions, for
reviewing pharmaceutical products for the treatment of obesity. As people of Asia
develop negative consequences of obesity at lower BMIs than Caucasians, Japanese
clinicians define obesity at BMI of >25 kg/m2, the Chinese at 28 kg/m2. Waist
Circumference has been discussed alone or in combination with BMI to identify obesity
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related health risks in general and for type 2 diabetes and cardiovascular risk in
particular.
BMI in specific populations
It is noteworthy that not all adipose tissue is identical. Visceral Adipose Tissue or VAT is
more metabolically active than other adipose tissue sites and appears to contribute to
many metabolic abnormalities associated with excess body weight. VAT is measured by
waist circumference or waist-hip ratio. Some research suggests that BMI and waist
circumference do not adequately measure visceral fat in different racial and ethnic
groups. Therefore BMI is highly useful for population studies but it does not measure fat
mass or percentage of fat mass for which there are no clearly defined cutoffs. In a
recently published study, Okorodudu et al(1) performed a meta-analysis of the correlation
of BMI with body fat percentage and concluded that BMI has high specificity but low
sensitivity to identify obesity since BMI fails to identify half of the people with excess
body fat percentage.
2. Demographics
According to the Centers for Disease Control (CDC), the current map of obesity in
USA is shown below in Figure 1
Unquestionably, obesity has increased dramatically from 1990 through 2013. In 2013
nineteen states had an obesity prevalence of 30% to 35% and two states had an obesity
rate of >35% obese, Mississippi and West Virginia. Correspondingly, nationally over a
third of U.S. adults (34.9%) are obese. Obesity is higher among middle age adults, 40-59
years old (39.5%) than among younger adults, age 20-39 (30.3%) or adults over 60 or
above (35.4%) adults.
Non-Hispanic blacks have the highest age-adjusted rates of obesity (47.8%) followed by
Hispanics (42.5%), non-Hispanic whites (32.6%), and non-Hispanic Asians (10.8%).
Among non-Hispanic black and Mexican-American men, those with higher incomes are
more likely to be obese than those with low income. Higher income women are less
likely to be obese than low-income women. There is no significant relationship between
obesity and education among men. Among women, however, there is a trend—those with
college degrees are less likely to be obese compared with less educated women.
3. Epidemiology
Even though obesity is a complex condition with genetic, environmental, social,
behavioral and biological influences, the primary causes of obesity in the US are
individual behaviors and environmental factors; mostly excess calorie intake and not
enough exercise.
‘Sinha’s Dirty Dozen’ Factors affecting weight increase
Excess Calorie Intake Inadequate Physical Activity

Increased consumption of beverages with Limited physical activity through work
added sugar day
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Increased frequency of snacking Increased media use

Larger portion sizes Limited access to recreational areas
Food is more calorie dense Labor saving technology
Increased meals away from home Limited recess and PE in school
‘Value sizing’ of less nutritious food Automobile-centered society
4. Surgeries
After failure of medical attempts at weight loss, many patients arrive at the surgical
option. These procedures may be restrictive or mal-absorptive. Multiple options exist
for the surgeon including gastric banding, Gastric sleeve, Roux en Y and others. Though
many anesthetic issues are common these selections may have anesthetic implications.
Laparoscopic surgery can have issues with pneumo peritoneum; open weight loss surgery
patients may have different pain issues than laparoscopically treated patients. According
to Angrisani et al(2), within the last two years the number of weight loss surgeries being
performed around the world is close to half a million with almost 150,000 being
performed in the US (REF). Almost all of these procedures are performed
laproscopically. Roux-en-Y gastric bypass continues to the most common, with almost
half of all procedures being of this type. The trend over the last decade has been a
decrease in adjustable gastric banding, with sleeve gastrectomy procedures growing most
rapidly. The anesthetic knowledge and practice that may originate in the bariatric surgery
operating room is applicable, to a large extent, in other settings of surgery in the obese
and morbidly obese patients.
5. Morbidly obese patients in Ambulatory surgery centers

Why is morbid obesity an issue in ambulatory surgery centers? Two reasons: ASCs are
viable financial models and therefore almost two thirds of all surgical procedures are
performed in this setting and there are few guidelines which would allow us to demarcate
patients as ‘safe’ or ‘unsafe’, so the proceduralists, whether endoscopists or podiatrists,
urologists or ENT surgeons, are all continuously trying to push the envelope in inviting
larger, older and sicker patients for ASC care. ASA recently put out a position statement
with regards to morbid obesity and ASC care.(3)
6. Pre anesthetic evaluation

Airway issues and cardiopulmonary issues are paramount for the evaluation of morbidly
obese patients. Anecdotally, about a tenth of these patients are difficult to mask ventilate
and about one percent are difficult to intubate.(4) Due to the negative components of both
FRC and metabolic demand, the former being low and the latter large, these patients give
us a shorter time to apnea. Common comorbidities include diabetes mellitus,
hypertension, dislipidemia and sleep apnea; rarer ones of osteo arthritis, hypothyroidism,
and others. Assessment of pulmonary hypertension is difficult due to difficulty in
assessing the physical signs of tricuspid regurgitation and pulmonary hypertension. In
the ultra-obese, raised JVP, hepatomegaly, pulmonary crackles, limb edema and added
heart sounds are all difficult to assess secondary to body habitus.
7. IV access challenges and solutions.
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Expectedly, intravenous access is almost the first challenge faced on the day of surgery.
Thinking outside the antecubital box, patience and a little luck helps find access in most
cases. In the event of near impossibility with standard peripheral access, ultrasound
guided antecubital access is preferable to central cannulation.
8. Induction and intubation

Significant challenges with induction and intubation are avoided by starting in a 30°
head up position. This causes the external auditory meatus to be in line with the
sternal notch, as measured by a line parallel to the floor. This is also referred to as the
HELP (head elevated laryngoscopy position) position. Thorough conventional
preoxygenation of 3 minutes of 100% oxygen, when performed in a 25° head up
position adds 80 mm Hg to PaO2 and increase of apnea time by about a minute.(5) If
this preoxygenation is performed with pressure support of 10 cms and PEEP of 10
cms, for 5 minutes, this can add up to a 140 mm Hg to the PaO2, improving the apnea
time by another minute.(6) Approach to laryngoscopy is preceded with an appropriate
dose of narcotic, anesthetic and muscle relaxation. Laryngoscopy can be attempted
with many tools; from the Macintosh blade to fiber optics and many tools in between
9. Anesthetic drug selection and dosing

Drug Dosing Reasoning
Propofol Induction: LBW Lipophilic; increased affinity for well perfused organs; Total
Maintenance: clearance and Vd at SS ~ TBW
TBW
STP LBW Obesity w/ increased Vd, longer elimination t½. But total
clearance normal
Etomidate LBW ~ Propofol & STP
Dexmed LBW Analgesic adjuvant (min respiratory side effects)
Midazolam TBW (single Increased Vd, longer elimination t½ ; duration dependent on

dose) distribution (not clearance)
LBW
(maintenance)
Vec/Roc IBW PK&PD unaltered; prolonged duration if dosed on TBW
Cisatracurium IBW Hoffman degradation; ideal in obesity; prolonged duration if

dosed on TBW
Pancuronium IBW Sub optimal in obesity; dose increased to maintain twitch status
Succinylcholine TBW Increased TBW : increased pseudo cholinesterase activity
Sugammadex TBW Dose based on depth of blockade (2-16mg/kg) Faster reversal

with TBW Vs IBW/LBW
Fentanyl LBW Based on ‘pharmacokinetic mass’ ~ clearance; TBW overdoses
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Sufentanil LBW Increased Vd, longer elimination t½ ~ obesity; clearance

unchanged; dose to effect
Remifentanil LBW PK&PD unaltered; short CS ½ time
Choice of drugs in obese with altered ratio of lean mass to fat mass is guided
significantly by the nature of drug. Pharmacologically simplifying the concept drugs
can be categorized into lipophilic or hydrophilic.
a. Lipophilic
Lipophilic drugs are more significantly affected in the obese. As the fat mass is
disproportionately higher the volume of distribution of these drugs increases
disproportionately. Most of the available drugs dosing guidelines are based upon
population nomograms of non-obese. Alterations in drug dose requirements are more
evident in the loading doses of lipophilic drugs. This translates from the fact the loading
dose is calculated as a product of effect size concentration and volume of distribution.
For these drugs volume of distribution is much higher. As a rough guide, most of
lipophilic drugs should thus be initiated based on actual body weight, indirectly
compensating for the disproportionately higher fat mass. Further, the maintenance doses
should eventually be determined based upon drug clearance values available in the obese.
Often a generalization for the redoing based upon pharmacokinetics alone is erroneous.
The reason being that pharmacodynamics maybe unpredictably altered in obese. Most of
the sedatives and anesthetics are lipophilic molecules. Although their loading doses may
be higher (based on volume of distribution) but for one must consider increased
sensitivity in obese towards these drugs. Thus the maintenance dose based solely on total
body weight and clearance alone may actually go overboard on clinical effects. It is
recommended that narrow therapeutic index drugs should be re-dosed based upon clinical
studies based evidence. However, if no data is available, lean body mass based
maintenance dose can be used with caution.(7)
b. Hydrophillic
As the BMI increases the proportionate mass of non-fat tissue (hydrophilic content) goes
down. For non-lipophilic/hydrophilic drugs the volume of distribution compared to total
weight decreases. Thus loading doses of these drugs are actually lower than expected. As
a rough guide loading doses for such doses can be estimated based upon the lean body
mass rather than actual weight. Again estimates for maintenance doses of these drugs are
more complicated. Commonly included drugs under this class are antibiotics and
neuromuscular blocking agents. Drug penetrance into tissue in obese may actually be
lower for antibiotics and thus concentrations attained may be lower than needed
Minimum inhibitory concentration (MICs).(8) Therefore required doses for antibiotics
may be higher than expected. On the contrary, obese are more predisposed to residual
effects of neuromuscular blockers and thus may require lower target site concentrations.
A generalized weight (ideal/total/lean) body weight based drug dosing may thus be
unpredictable unless clinical outcome related data is available for the obese, especially
for maintenance doses.
c. Volatile agent debate
Des may be slightly better with average extubation time and predictability of offset
(and therefore extubation time)(Meta analysis of 29 RCTs, 32,000 cases)
d. Opioid sparing approach Multimodal, low or non narcotic
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10. Ventilation and maintenance challenges

Volume versus pressure control, both appropriate, personal preference is
VC; 5-6 cc/kg of IBW TV; 6-8 cms H2O for PEEP and Respiratory rate of
10-12 for starters; adjust as needed
11. Extubation
a. On OR table versus stretcher
b. 30 degree head-up
c. Multiple extubation criteria
d. What to do if difficult placement of ETT? Leave bougie in airway, taped
to cheek, for 30 minutes, watch for stability. If unstable use bougie to
rapidly control airway if needed post op with half to one size smaller ETT
used in OR
12. Post-operative pain management

The approach to post-operative pain begins intraoperatively. Multimodal approach is
the key to staying away from opioid induced respiratory depression and arrest. Local
anesthetics in tissue as well as an infusion, α2-agonists, NSAIDs and small doses of
narcotics, if needed, are the key to success.
References
1. Okorodudu DO, Jumean MF, Montori VM, Romero-Corral A, Somers VK, Erwin PJ,
et al. Diagnostic performance of body mass index to identify obesity as defined by
body adiposity: a systematic review and meta-analysis. Int J Obes (Lond). 2010
May;34(5):791–9.
2. Angrisani L, Santonicola A, Iovino P, Formisano G, Buchwald H, Scopinaro N.

Bariatric Surgery Worldwide 2013. Obes Surg. 2015 Oct;25(10):1822–32.
3. American Society of Anesthesiologists Task Force on Perioperative Management of

patients with obstructive sleep apnea. Practice guidelines for the perioperative
management of patients with obstructive sleep apnea: an updated report by the
American Society of Anesthesiologists Task Force on Perioperative Management of
patients with obstructive sleep apnea. Anesthesiology. 2014 Feb;120(2):268–86.
4. Wadhwa A, Singh PM, Sinha AC. Airway management in patients with morbid
obesity. Int Anesthesiol Clin. 2013;51(3):26–40.
5. Dixon BJ, Dixon JB, Carden JR, Burn AJ, Schachter LM, Playfair JM, et al.
Preoxygenation is more effective in the 25 degrees head-up position than in the
supine position in severely obese patients: a randomized controlled study.
Anesthesiology. 2005 Jun;102(6):1110–5; discussion 5A.
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6. Gander S, Frascarolo P, Suter M, Spahn DR, Magnusson L. Positive end-expiratory

pressure during induction of general anesthesia increases duration of nonhypoxic
apnea in morbidly obese patients. Anesth Analg. 2005 Feb;100(2):580–4.
7. Sinha AC, Singh PM. Optimal Drug Dosing in the Obese--Still Many Years Ahead.
Obes Surg. 2015 Nov;25(11):2159–60.
8. Janson B, Thursky K. Dosing of antibiotics in obesity. Curr Opin Infect Dis. 2012
Dec;25(6):634–49.
Figure 1
http://www.cdc.gov/obesity/data/prevalence-maps.html
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The Geriatric Outpatient: Postoperative Cognitive Impairment and Other Concerns
Kathryn E. McGoldrick, M.D., F.C.A.I.(Hon) Valhalla, New York
Introduction
The elderly (≥65 yr) are a rapidly growing demographic segment in the United States as well as in many other parts
of the developed world. This reality has profound implications for anesthesiologists and surgeons. Aging, for
example, increases the probability that an individual will require a surgical procedure. Whereas approximately 12%
of those aged 45 to 60 yr undergo surgery annually, this number increases to >21% in the elderly (1). Although
operative mortality has decreased in the geriatric population in recent decades, perioperative morbidity continues to
be more common in the elderly and perioperative mortality rates, especially in the presence of co-existing disease,
remain higher than those encountered with younger patients. Using the Cox proportional hazards model, the risk of
postoperative long-term mortality increases 1.42 times per decade of age (2). Clearly, as an ever-increasing
proportion of the surgical outpatient population falls into the geriatric category, anesthesiologists are becoming
geriatric subspecialists to a certain extent. Thus, it seems appropriate to summarize our current knowledge about the
physiology of aging and to discuss the implications of these issues for the perioperative management of the elderly
outpatient.
Physiology and Pathophysiology of Aging

Age alters both the pharmacokinetic and pharmacodynamic aspects of anesthetic management. As an individual
ages, he or she experiences a loss of reserve and a diminished ability to tolerate stress. The functional capacity of
organs declines and co-existing disease further contributes to this decline. Advanced age, in conjunction with
comorbidity, is a risk factor for increased perioperative mortality, and age itself may further amplify the negative
prognostic value of impaired physical status (3).
The effects of aging at the subcellular level are ubiquitous, and these effects are apparent when one considers organ
function in the elderly. In terms of cardiac function, it is well known that geriatric patients have reduced beta-
adrenergic responsiveness, and they experience an increased incidence of bradyarrhythmias and hypertension.
Fibrotic infiltration of cardiac conduction pathways and replacement of myocardial elastic fibers render the elderly
individual vulnerable to conduction delay and to atrial and ventricular ectopy. Postoperative atrial arrhythmias, and
atrial fibrillation (AF) and flutter specifically, are seen in 6.1% of elderly patients undergoing noncardiothoracic
surgery and in 10% to 40% of patients after cardiothoracic operations (4-7). Because reliance on atrial “kick” is
critically important for older adults, should we prophylactically treat high-risk patients to prevent postoperative AF?
If so, should we use rate control or rhythm control drugs? Elderly patients also have an increased reliance on the
Frank Starling mechanism for cardiac output. It is important, therefore, to consider fluid as a drug that the elderly
individual may or may not need. In the noncompliant older heart, small changes in venous return will produce large
changes in ventricular preload and cardiac output. Owing to reduced diastolic myocardial function, baroreceptor-
mediated heart rate control, adrenergic receptor responsiveness, and vascular compliance, the elderly person
compensates poorly for hypovolemia. Similarly, overtransfusion is also poorly tolerated.
COPD, pneumonia, and sleep apnea are common in the elderly. Closing volume increases with age, and FEV1
declines 8% to 10% per decade owing to reduced pulmonary compliance and muscle power (8). Arterial oxygen
tension decreases progressively with age-induced V/Q mismatch, diffusion block, and anatomical shunt (9). [Owing
to these abnormalities in gas exchange, it is recommended that elderly patients be transported to the PACU with 2-4
L/min of oxygen via nasal cannula, even after relatively minor ambulatory surgery (10)]. Given these deleterious
changes, it is not surprising that postoperative respiratory complications are common in geriatric patients. However,
the most important clinical predictor of adverse pulmonary outcome is the site of surgery, with thoracic and upper
abdominal surgery having the highest pulmonary complication rates (11, 12).
Because the central nervous system is the target for so many of our drugs, age-related alterations in nervous system
function have extremely compelling implications for anesthetic management. Indeed, aging universally produces a
reduction in total nervous system tissue mass, neuronal density, and concentration of neurotransmitters, as well as
various receptors. Drug interactions are a very real concern in the elderly because senior citizens typically undergo
physiologic changes related to disease as well as to normal aging. Moreover, although elders represent
approximately 13% of the population in the United States, they consume one-third of all medications and are seven
times more likely to experience an adverse drug reaction than their younger counterparts. In fact, the elderly account
for 50% of all medication-related deaths. Important to an understanding of geriatric pharmacokinetics is an
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appreciation of the role that reduced drug excretion plays in adverse interactions. With advancing age, the number of
functioning glomeruli declines, as do glomerular filtration rate and renal blood flow.
Intraoperative Management
Because of the pulmonary changes discussed previously, it is imperative to appreciate that desaturation occurs faster
in older adults. Additionally, elderly patients are more vulnerable to desaturation-related cardiac events. Therefore,
proper preoxygenation is critical. Benumof points out that maximal preoxygenation is achieved with 8 large breaths
of 100% oxygen within 60 sec with an oxygen flow of 10 L/min (13).
Advanced age is associated with a reduction in median effective dose requirements for all agents that act within the
central nervous system regardless of whether these drugs are administered via the oral, parenteral, or inhalational
route. Indeed, the ED50 equivalent for anesthetics falls linearly with age, such that the “typical” reasonably healthy
80-yr-old will require only about one-half to two-thirds of the anesthetic dose needed to produce comparable effects
in a young adult. An octagenarian with notable comorbidities will require even lower doses. This reduction in
anesthetic requirement is agent-independent and probably reflects fundamental neurophysiologic changes in the
brain, such as reduced neuronal density or altered concentrations of neurotransmitters. Elderly patients require less
propofol (and other agents) for induction, and it is also important to appreciate that the concurrent use of midazolam,
ketamine, and/or opioids with propofol synergistically increases the depth of anesthesia. Even with an appropriate
dose reduction of propofol, hypotension is common. Less hypotension has been reported with appropriately titrated
administration of mask sevoflurane for induction compared with a propofol infusion (14). Interestingly, gender
differences have been described in the pharmacokinetics of propofol given by continuous infusion in elderly patients
(15).
Several neuromuscular blocking agents, including vecuronium and rocuronium, have an increased onset time in
elderly patients, possibly as a result of a less dynamic circulation and, thus, an increased transfer time to the effector
site (16). The time required for clinical recovery from neuromuscular blockade is markedly increased in older adults
for nondepolarizing agents that undergo organ-based clearance from plasma, but is minimally different for
atracurium, cisatracurium, or mivacurium because they undergo hydrolysis in plasma. Those neuromuscular
blockers with prolonged duration of action in the elderly are associated with delayed elimination, which may be a
result of the reduced total body water and decreased liver mass that often accompany aging. The likelihood of
postoperative respiratory complications after long-acting muscle relaxants increases with advanced age. It is not
unusual for patients who meet rigorous extubation criteria in the OR to deteriorate in the PACU. Hence, it seems
advisable to administer a short- or intermediate-acting muscle relaxant to any elderly patient for whom extubation is
planned at the end of the surgical procedure. Importantly, sugammadex has been shown to facilitate rapid reversal
from moderate rocuronium-induced neuromuscular blockade in adults of all ages, but recovery to a train-of-four
ratio of 0.9 is 0.7 min faster in young and middle-aged adults compared with patients ≥65 yr (17).
In planning an expeditious emergence, anesthesiologists should be aware that end-tidal gas monitoring
underestimates the brain concentration of the more soluble agents. Failure to appreciate this hysteresis effect leads to
prolonged emergence. Moreover, MAC awake is more favorable if the vaporizer is turned down gradually rather
than turned off abruptly (18). Not surprisingly, it has been reported that use of shorter-acting drugs (propofol,
desflurane, sevoflurane), in conjunction with BIS monitoring, can provide more rapid emergence in geriatric patients
and facilitate PACU bypass (19). Whether this approach will have a favorable effect on longer-term outcomes
remains to be determined.
When one considers selection of anesthetic technique, it is important to appreciate that there are no controlled,
randomized studies in elderly patients to show that regional anesthesia is clearly superior to general anesthesia for
ambulatory surgery. In fact, neuraxial, plexus, or peripheral nerve blocks (PNBs) in the elderly may be associated
with an increased risk of persistent numbness, nerve palsies, and other neurological complications. It has recently
been demonstrated that age is a major determinant of duration of complete motor and sensory blockade with PNB,
perhaps reflecting increased sensitivity to conduction failure from local anesthetic agents in peripheral nerves in the
elderly (20). That said, PNBs offer some appealing features, especially in terms of postoperative pain control.
Clonidine is a valuable adjunct that enhances both local anesthetic and narcotic efficacy, and its addition to the local
anesthetic mixture may afford some hemodynamic advantages compared with epinephrine. However, one should
select a dose of clonidine that will not produce postoperative sedation or hypotension. When administering epidural
blockade to elderly patients, it is important to remember that a given dose will produce a higher level of block in
seniors, and is typically accompanied by a greater incidence and degree of hypotension and bradycardia as well as a
longer duration of anesthesia (21). Sedation requirements are dramatically reduced under conditions of central
neuraxial block. Sensory input to the brain is attenuated and the BIS50 is shifted to a higher index. Although recent
data have supported a relaxation of the requirement for voiding before discharge after outpatient neuraxial blockade
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with short-acting drugs for low-risk surgical procedures in low-risk patients, it is important to appreciate that elderly
patients do not meet these criteria (22). Current thinking is that elderly (≥70 yr) patients who received neuraxial
block, regardless of the duration of the block, should be required to void before discharge.
Postoperative Management
Perioperative hypothermia is prevalent in both young and elderly surgical patients, but it is more frequent,
pronounced, and prolonged in the elderly, who have compromised ability to regain thermoregulatory control
quickly. Adverse consequences of postoperative hypothermia include cardiac ischemia, arrhythmias, increased
blood loss, wound infection, decreased drug metabolism, and prolonged hospitalization. Indeed, it has been shown
that maintaining normothermia decreases cardiac morbidity by 55 percent (23).
Postoperative pain increases the risk of adverse outcome in geriatric patients by contributing to tachycardia,
hypertension, cardiac ischemia, and hypoxemia. Effective analgesia can decrease the incidence of myocardial
ischemia and pulmonary complications, accelerate recovery, promote early mobilization, shorten hospital stay, and
reduce medical costs. However, postoperative pain control often is inadequate in the elderly because of concerns
about drug overdose, adverse response, drug interactions, and other issues. Pain control is further complicated by the
fact that the patient’s perception and expression of pain may be affected by changes in mental status. Current
postoperative analgesic techniques include the use of opioids by various routes, nonsteroidal anti-inflammatory
drugs, local anesthetic techniques (neuraxial, intra-articular, PNB, etc), and nonpharmacologic (transcutaneous or
percutaneous electrical nerve stimulation, acupuncture, acupressure, etc) methods. Pre-emptive, multimodal
approaches have been favored to minimize the risk of such opioid-related side effects as hypoxemia, constipation,
and pruritus. However, the recent discovery of data fabrication by a major researcher in the area of pre-emptive
analgesia has far-reaching and serious consequences. There is, for example, no longer unequivocal evidence
supporting the pre-emptive effect of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors.
Additionally, the ability of a multimodal pre-emptive analgesic regimen to prevent the development of chronic pain
after major orthopedic surgery remains unproven (24).
Postoperative Cognitive Impairment

Reports of postoperative cognitive deterioration in elderly patients surfaced several decades ago, and anesthesia
had often been implicated as a possible cause or contributing factor. Although improvements in surgical techniques
and anesthetic agents and methods have led to improved outcomes in the elderly, a troubling proportion of these
patients experience postoperative cognitive impairment (25-28), at least on a short-term (~3 months) basis.
The syndrome of postoperative cognitive impairment can be classified into two main categories: postoperative
delirium and postoperative cognitive dysfunction (POCD)(29). Delirium is defined as an acute change in cognitive
function that develops over a brief period of time, often lasting for a few days to a few weeks and typically having a
fluctuating course. It is characterized by inattention, as well as either disorganized thinking and/or altered
level of consciousness. Prospective studies have cited an incidence of delirium that ranges from 3% to >50% and is
dependent upon the type of surgery, the patient's preoperative physical and cognitive status, and the age of the
patient (29). Recently, Rudolph and Marcantonio reported an incidence of postoperative delirium ranging from 35%
to 65% for hip fracture repair, down to 4% for cataract surgery (30). In general, older patients undergoing
emergency or long, complex surgical procedures tend to have a higher frequency of delirium, which appears to be
less problematic in outpatients who recover in their familiar home environment. Delirium is a costly complication
that has been associated with increased postoperative morbidity and mortality. Although the risk factors for
postoperative delirium vary among studies, greater preoperative age, alcohol use, major comorbidities, and cognitive
impairment are generally thought to confer a higher risk of postoperative delirium. Recently, Smith et al (31)
reported that preoperative executive dysfunction and depression are independent risk factors for postoperative
delirium.The etiology of delirium is probably multifactorial and may include drug intoxication or withdrawal, drug
interactions, anticholinergic agents, metabolic disturbances, hypoxia, abnormal carbon dioxide levels, sepsis,
inadequate analgesia, and organic brain disease (32). Neurotransmitter imbalances involving acetylcholine,
dopamine, and gamma-aminobutyric acid appear to be heavily involved in the multifactorial pathophysiology of
delirium. Recent evidence suggests that deregulation in the homeostasis of tryptophan, the precursor to serotonin,
may have a critical role in the pathogenesis of postoperative delirium (33). Because abnormalities in the regulation
of serotonin have consistently been linked with depression (34), this may have important implications for explaining
the association of depression with delirium. It has also been suggested that occult white matter damage to the
frontal-striatal areas of the brain predisposes some patients to develop delirium (31). It is perhaps possible that this
mild loss of white matter could manifest preoperatively as impaired executive performance and/or greater levels of
depression (31). Interestingly, the use of melatonin to treat delirium has produced some benefit, presumably by
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resetting the circadian sleep-awake cycle of older surgical patients (35). Although common in the elderly, the
incidence of postoperative delirium may be reduced by protocol-driven perioperative treatment. Marcantonio and
colleagues reported a reduction in postoperative delirium in hospitalized patients by more than one-third, and of
severe delirium by more than one-half, by adherence to multifaceted recommendations that included elimination or
minimization of benzodiazepines, anticholinergics, antihistaminics, and meperidine, as well as encouraging early
mobilization and providing appropriate environmental stimuli (36). The importance of adequate postoperative
analgesia has become increasingly recognized.
POCD is defined as a deterioration of intellectual function detected by a battery of neuropsychological tests and is
characterized by deficits in working memory and executive function. Other neuropsychological domains, including
perceptual organization, language, attention, and psychomotor function, may be affected. Moller and
colleagues (25) evaluated cognitive function in patients aged 60 yr or older after major abdominal and orthopedic
surgery. These investigators found that approximately 25% of the patients had measurable cognitive dysfunction a
week after their surgery and 10% had cognitive changes 3 months postoperatively. This finding contrasted with a
3% incidence of cognitive deterioration in healthy control subjects in the same age range who did not undergo
anesthesia and surgery. Interestingly, neither perioperative hypoxemia nor hypotension correlated with the
occurrence of prolonged cognitive dysfunction. The identified risk factors for early (1 week) postoperative cognitive
dysfunction were increasing age and duration of anesthesia, low education level, a need for a second operation,
postoperative infection, and respiratory complications. The major risk factor for late (3 months) postoperative
cognitive dysfunction was age. Although the incidence of late postoperative cognitive dysfunction was 14% for
patients >70 yr, this rate decreased to only 7% for patients between the ages of 60 to 70 yr.
An additional large, prospective study conducted by Monk and colleagues evaluated the relationship of age to
POCD (28). Using the same methodology as the first multinational study (25), Monk and colleagues reported that
cognitive decline occurred in 16% of patients aged 60 yr or older at 3 months after major noncardiac surgery, but
was present in only 3% to 5% of younger patients (28). This study also determined that rates of cognitive decline
were higher in those >70 yr compared with younger elderly patients. More recently (2008), Monk explored the
predictors of cognitive dysfunction after major noncardiac surgery (37). Independent risk factors for POCD at 3
months after surgery were increasing age, lower educational level, a history of previous CVA without residual
impairment, and POCD at hospital discharge. Patients who had POCD at both hospital discharge and 3 months
after surgery were more likely to die in the first year after surgery, but whether this suggests a causal link or is
related to patients’ comorbidities is unknown (37).
There are few prospective studies on long-term cognitive outcomes after outpatient surgery, but an analysis of
cognitive recovery after major and minimally invasive surgery exists. Monk classified the type of surgical procedure
as minimally invasive (laparoscopic or superficial surgery), major intra-abdominal surgery, or orthopedic surgery
(28). The incidence of POCD was significantly greater for patients undergoing major abdominal or orthopedic
procedures compared with minimally invasive surgery. Because outpatient surgery is usually minimally invasive,
these results suggest that outpatients may have a better cognitive outcome than patients who require hospitalization.
The International Study of Postoperative Cognitive Dysfunction (ISPOCD) group, however, recently conducted a
longitudinal study comparing the incidence of POCD after inpatient versus outpatient surgery in patients older than
60 yr (38). At 7 days after surgery, the incidence of POCD was substantially lower in the outpatient group, but this
difference was not detected 3 months later. These results suggest that elderly outpatients have better cognitive
outcomes at discharge than elderly inpatients, but we currently have no explanation for the difference. Possible
explanations for the improved early outcome in outpatients include the healthier status of patients who qualify for
outpatient surgery, the briefer surgical and anesthesia times, the minimally invasive nature of most outpatient
procedures, or avoidance of hospitalization. Interestingly, a recent (2011) study by Evered et al found that POCD
was independent of the type of surgery and anesthetic (39). Specifically, at 3 months post procedure, 21% of
geriatric patients having coronary angiography under sedation had POCD. The incidence of POCD in geriatric
patients who underwent either total hip replacement or CABG surgery was 16% in each group.
It is important to understand that full return of cognitive function to preoperative levels may require several days,
even after ambulatory surgery in young, healthy patients (32, 40). Indeed, Lichtor (41) has suggested that even
young adults may be sleepy for 8 hr after receiving IV sedation with midazolam and fentanyl, and the elderly
outpatient suffering from balance disturbances or age-related gait impairment may be at high risk of falling owing to
residual drowsiness. Nonetheless, it remains unclear which patient populations are most vulnerable and what the
causative factors might be for POCD. Although we have much to learn about postoperative delirium and cognitive
decline, it is clear that pre-existing subclinical decrements in functional status may become evident during the
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perioperative period. Indeed, if a cognitive deficit is noted preoperatively, it may be a harbinger of further
postoperative decline. The data on the predictive value of preoperative cognitive status for the development of
delirium (42) and the ability of that assessment to result in successful intervention (as may be the case with delirium)
(36) offer compelling reasons to conduct a simple, brief mental status examination as part of the preoperative
interview. Indeed, Evered and colleagues recently identified that 20% of patients ≥60 hr having total hip
replacement had preexisting cognitive impairment, and 22% had amnestic mild cognitive impairment (MCI); 7%
had both (43). These findings underscore the need for a robust, reproducible, practical tool to assess preoperative
cognitive function in our elderly patients (44). Additionally, Vaurio and colleagues recently demonstrated that
elevated levels of preoperative pain and a postoperative increase in pain levels are independent predictors of
postoperative delirium in elderly surgical patients (45). These findings suggest that elderly surgical patients with
substantial preoperative pain should be targeted for more intensive pain control postoperatively.
It must be acknowledged that many studies of postoperative cognition have serious methodological limitations,
which include retrospective design, lack of a consensus definition of POCD, too permissive a definition of POCD,
failure to detect preoperative cognitive impairment, lack of suitable (nonsurgical) control groups, dissociation of
cognitive outcomes from surgical outcomes, suboptimal statistical analysis, and insufficient long-term follow up.
Our current understanding of POCD suggests the etiology is multifactorial and may include the preoperative
status of the patient, as well as intraoperative events related to surgery (e.g., microemboli), and anesthetic factors.
The potential roles of inflammation and anesthetic depth remain to be more fully determined. However, recent
prospective studies that have combined neuroimaging, pain, and functional assessments have shown that when
surgery successfully treats chronic pain and inflammation, cognition improves and gray matter volume increases in
areas such as the dorsolateral prefrontal cortex, the anterior cingulate gyrus, and the amygdala after several months
(46). Thus, when surgery alleviates symptoms and improves quality of life, postoperative cognitive improvement can
be a very real and possible outcome. Indeed, perhaps the most important determinants of postoperative cognitive
trajectory are the preoperative cognitive trajectory, the success of the surgery, and events in the perioperative period
(47). Recently, Kawano et al hypothesized that an old brain is more vulnerable than a young one to surgery-induced
inflammation (48). These investigators theorized that preoperative environmental enrichment consisting of both
physical and cognitive activity might attenuate neuroinflammation and mitigate postoperative cognitive impairment.
Exercise is thought to have systemic anti-inflammatory effects, upregulate neurotrophic factors, stimulate
neurogenesis, and enhance neuroplasticity.
A group of scientists and physicians met in Stockholm in 2014 to discuss the most recent advances in the assorted
varieties of POCD. There was strong consensus that the nomenclature pertaining to POCD is confusing to the point
of creating a barrier to progress. It was proposed that a consensus panel be created to draft a comprehensive
nomenclature for what could be considered a postoperative cognitive dysfunction syndrome (POCDS), with a view
toward fostering enhanced comparisons among studies and better precision when discussing these entities and
assessing potential risk factors and mechanisms (49). The importance of preexisting cognitive vulnerability was
recognized, underscoring the value of a simple preoperative cognitive assay. The ability of any specific anesthetic
agent or perioperative adjunct to lower the risk of POCDS remains conjectural at best, but it is exciting to postulate
that preoperative environmental enrichment with cognitive training and, especially, physical exercise might have a
positive impact on geriatric surgical outcomes.
Finally, it should be mentioned that interest has grown recently in exploring a potential relationship between
anesthesia and the onset and progression of such neurodegenerative conditions as Alzheimer’s disease (50). Our
knowledge in this area is limited, and anesthesia has been both implicated and exonerated. There is, however, some
laboratory evidence that anesthesia may affect the processing of amyloid beta peptide. It has also been speculated
that risk factors for POCD may overlap with those for Alzheimer’s disease, although any shared mechanism remains
conjectural. Available human studies on anesthesia and Alzheimer’s disease have been inconclusive because they
are under-powered or confounded by coexisting disorders, independent risk factors for dementia, and, of course,
surgery (51-53). A recent robust retrospective case-control study found no association between exposure to general
anesthesia after 45 years of age and subsequent development of dementia (54). Moreover, studies on the impact of
the apoE 4 allele on cognitive outcomes after surgery have been inconsistent. Increasingly, we are realizing that
many of our elderly patients have MCI at baseline. The cognitive loss of some of these patients may not be readily
apparent preoperatively, and is unmasked by the perioperative experience. Perhaps the concerning cognitive changes
that are identified postoperatively indicate more about our patients than about our anesthetic agents.
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Interestingly, in April 2011, the first new diagnostic guidelines released in 27 years in the United States for
Alzheimer’s disease recognized MCI as a precursor to Alzheimer’s disease. The National Institute on Aging and the
Alzheimer’s Association now describe the disorder as a disease that occurs gradually over many years, starting with
changes in the brain, then mild memory problems, and finally progressing to florid dementia. This preclinical stage,
happening about a decade before dementia develops, may be the best place to intervene in the disease, with many
researchers believing that most Alzheimer’s drugs have been disappointing because they were tried in people whose
disease was too advanced to be halted or reversed. Although not yet ready for prime time, the development of new
imaging agents for PET scans, spinal fluid tests, and other biomarkers that predict or detect Alzheimer’s in its
earliest stages will be increasingly important to researchers, drug companies, and clinicians. Of note, a recent study
by Evered and colleagues suggested that patients with Alzheimer disease neuropathology, identified by low CSF
levels of amyloidβ, may be at increased risk of POCD even in the absence of clinically detectable symptoms of
Alzheimer disease (55). One could argue that this study gives credence to the concept that individuals with loss of
cognitive reserve, even when subclinical, may be more vulnerable to the development of POCD.
Summary
Elderly patients are uniquely vulnerable and particularly sensitive to the stresses of trauma, hospitalization, and
surgery/anesthesia in ways that are only partially understood. The ambulatory environment offers many potential
benefits for geriatric patients having elective procedures. Accordingly, minimizing perioperative risk in the
elderly population requires thoughtful preoperative assessment of organ function and reserve, meticulous
intraoperative management of coexisting disorders, maintenance of normothermia, and vigilant postoperative
monitoring and pain control.
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49. Terrando N, Eriksson LI, Eckenhoff RG. Perioperative neurotoxicity in the elderly: Summary of the 4 th
International Workshop. Anesth Analg 2015;120:649-52.
50. Baranov D, Bickler PE, Crosby GJ, et al. Consensus statement: International workshop on anesthetics and
Alzheimer’s disease. Anesth Analg 2009; 108:1627-30.
51. Bohnen N, Warner MA, Kokmen E, et al. Alzheimer’s disease and cumulative exposure to anesthesia: A case-
control study. J Am Geriatr Soc 1994;42:198-201.
52. Bohnen N, Warner MA, Kokmen E, Kurland LT. Early and midlife exposure to anesthesia and age of onset of
Alzheimer’s disease. Intern J Neurosci 1994;77:181-5.
53. Knopman DS, Petersen RC, Cha RH, et al. Coronary artery bypass grafting is not a risk factor for dementia or
Alzheimer disease. Neurology 2005;65:986-90.
54. Sprung J, Jankowski CJ, Roberts RO, et al. Anesthesia and incident dementia: a population-based, nested, case-
control study. Mayo Clin Proc 2013;88(6):552-561.
55. Evered L, Silbert B, Scott DA, et al. Cerebrospinal fluid biomarker for Alzheimer disease predicts
postoperative cognitive dysfunction. Anesthesiology 2016;124:353-361.
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PERIOPRATIVE AUTONOMIC NERVOUS SYSTEM

DYSFUNCTION
A case based learning module
Cristina Barboi M.D. Chicago/IL

What is a successful anesthetic? Lack of recollection, abolition of noxious stimuli, and maintenance of
autonomic functions in the face of surgical stress. Some of the preexisting perioperative pathology however
is associated with impaired perioperative autonomic functions and may or may not be recognized
beforehand.
How is perioperative autonomic dysfunction (AD) recognized? One in 1000 patients suffer from severe
AD (1,2). Diagnosis may be obtained clinically or through autonomic testing (3). Clinical attention to blood
pressure (BP) and heart rate (HR) variability, pupillary light reflexes, skin color and temperature may yield
a diagnosis. Autonomic testing can help establish the diagnosis of abnormal autonomic function, grade it
and help further localize the disease process (4).
1. Heart rate (HR) response to the Valsalva maneuver
2. Heart rate response (HR) to standing up (30:15 ratio)
3. Heart rate response (HR) to deep breathing
4. Blood pressure (BP)response to standing up or tilt table testing
5. Power spectral analysis of heart rate variability
6. Imaging Myocardial Sympathetic Innervation
What then is the role of cardiovascular reflex testing in the preoperative evaluation of the patient with
possible autonomic dysfunction?
PERIOPERATIVE MANAGEMENT OF DIABETIC PATIENT WITH DIABETIC AUTONOMIC

NEUROPATHY (DAN) (case discussion)
DAN is the result of complex interactions among the degree of glycemic control, disease duration, age-
related neuronal attrition, and systolic and diastolic blood pressure. The 5-year mortality rate is 16-50% in
type 1 and type 2 diabetes, with a high proportion attributed to sudden cardiac death.
The causes of an increase in mortality in diabetics are: asymptomatic cardiac ischemia, respiratory arrest,
prolongation of QT interval, abnormalities in sympathetic-vagal and BP circadian rhythms, denervation
super sensitivity responsible for excessive responses to both antihypertensive and vasopressor agents.
 Both somatic and autonomic diabetic neuropathy influences the clinical manifestations and
prognosis of cardiovascular disease in diabetics. Patients have: “defective anginal warning” due to
the loss of afferent nerve fibers in ischemic areas, acute myocardial infarction without symptoms,
chronic silent ischemia.
 The severity of heart failure in diabetic patients correlate with degree of cardiovascular autonomic
impairment.
 Patients have resting tachycardia, 90-100 bpm and nonexistent HR response to breathing, changes
of posture, Valsalva maneuver, or carotid sinus pressure due to early cardiac vagal neuropathy.
Extension of denervation to the Sympathetic Nervous System (SNS), produces a fixed HR and
myocardial electrical instability. Heterogeneous SNS innervation, with reduced innervation in the
left ventricle but relative proximal myocardial sympathetic excess innervation, may be associated
with malignant ventricular arrhythmias and sudden cardiac death.
 Sudden death occurs in one-third of diabetics with DAN due to cardiac denervation super
sensitivity, arrhythmias, QT interval abnormalities, silent infarction, sleep apnea, an abnormal
ventilatory response to hypoxia, in association with lung infection, surgery and anesthesia.
 DAN is associated with LV diastolic dysfunction at rest, that may progress to heart failure, mainly
with preserved LV systolic function (diastolic heart failure).
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 Unexpected sympathetic hypo responsiveness manifests as reduced distal vasoconstrictor tone,

localized sympathetic cardiac hyper innervation, or a sympatho-vagal imbalance, that leads to
arrhythmias, orthostatic hypotension with fall in SBP greater than 50 mmHg on standing.
 Prolongation of the QT interval is thought to be the result of an imbalance between right and left
sympathetic innervation, (under activity of the right stellate ganglion and over activity of the left
stellate ganglion) leading to ventricular arrhythmias.
 One in four diabetic patients with autonomic neuropathy have obstructive sleep apnea (impaired
vagal input to inspiratory phasic dilator muscles) and reduction in hypoxic drive
 Awareness of hypoglycemia may be absent or blunted, and impaired cognition may the first sign
of a drop in blood glucose level.
Preoperative evaluation: Exercise intolerance, orthostatic hypotension, EKG – QT interval, RR variation.

Pre-operative medications: ACE inhibitors, Calcium channel blockers, beta-blockers and insulin could
influence cardiac manifestations on induction. Diabetic patients with DAN experience a more profound
decrease in HR and arterial blood pressure during induction of anesthesia compared with non-diabetic
individuals. 35% of diabetic patients with DAN require vasopressors such as phenylephrine to treat
hypotension.
PATIENT WITH MULTIPLE SYSTEMS ATROPHY PRESENTS FOR LAPAROSCOPIC

CHOLECYSTECTOMY (case discussion)
Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by a
combination of symptoms that affect both the ANS and movement. The symptoms reflect the progressive
loss of function and death of different types of nerve cells in the brain and spinal cord. Symptoms of
autonomic failure that may be seen in MSA include fainting spells and problems with heart rate, erectile
dysfunction, and bladder control (7). Motor impairments (loss of or limited muscle control or movement, or
limited mobility) may include tremor, rigidity, and/or loss of muscle coordination as well as difficulties
with speech and gait.
MSA includes disorders that historically had been referred to as Shy-Drager syndrome, olivo-ponto-
cerebellar atrophy, and striato-nigral degeneration.
MSA is dived into two different types, depending on the most prominent symptoms at the time an
individual is evaluated:
Parkinsonian type (MSA-P) similar to Parkinson’s disease and cerebellar type (MSA-C) - primary
symptoms featuring ataxia (problems with balance and coordination), difficulty swallowing, speech
abnormalities or a quavering voice, and abnormal eye movements.
A distinguishing feature of MSA is the accumulation of the protein alpha-synuclein in glia and primary
degeneration of the preganglionic lateral horn neurons of the thoracic spinal segments. Clinical picture
consists of autonomic and urinary dysfunction, cerebellar and corticospinal dysfunction.
 Hypotension due to loss of sympathetic and parasympathetic tone in these patients is profound.
Recumbent hypertension develops in many patients with autonomic failure due to defective
baroreceptor reflexes, super-sensitivity of denervated blood vessels to circulating catecholamine,
and fluid shifts from the periphery to the central compartment.
 Disordered thermoregulation, unequal pupils, stridor, and difficulty in speaking and swallowing
are reported. Respiratory centers are also affected.
One of the primary concerns in the perioperative period is the autonomic failure associated with MSA.
In the preoperative period management goals are aimed at optimal BP maintenance while avoiding volume
over expansion and volume overload.
Atropine and ephedrine will provide little clinical response and agents such as phenylephrine are effective.
The mineralocorticoid, 9-alpha-fluorohydrocortisone has been used to help maintain plasma volume
through its sodium-retaining properties but will cause supine hypertension, hypokalemia and edema.
Vasopressors should be used cautiously because of possible risk of an exaggerated hypertensive response
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reflecting denervation hypersensitivity.

Induction agents that produce minimal cardiovascular changes should be chosen. Volatile anesthetic agents
can cause exaggerated hypotension due to the absence of carotid sinus activity in these patients. Positive
pressure ventilation may profoundly decrease cardiac output. Maintenance of anesthesia may be
complicated by the absence of autonomic “signs” of depth of anesthesia. Intra-operative hyperpyrexia due
to anhidrosis, and sluggish pupillary reflexes or unequal pupils may be identified. The latter finding should
be recognized preoperatively to avoid making an erroneous diagnosis of a severe neurological insult. Vocal
cord paralysis has been reported in MSA: it is usually a bilateral abductor paralysis with resultant glottic
obstruction and ventilatory failure.
Postoperative course will be marked by large BP variability worse with positional changes and influenced
by pain.
CAROTID ENDARTERECTOMY IN A PATIENT WITH HISTORY OF HODGKIN’S

LYMPHOMA IN ADOLESCENCE TREATED WITH RADIATION THERAPY (case discussion)
The baroreflexes normally serve to buffer against excessive rise or fall in blood pressure. Baroreflex failure
(BRF) occurs when afferent baroreceptive nerves or their central connections become impaired with loss of
buffering ability, and wide excursions of blood pressure and heart rate ensue (8).
With acute BRF, a hypertensive crisis is the most common presentation. Over succeeding days to weeks, or
in the absence of an acute event, volatile hypertension with periods of hypotension occurs and may
continue for many years, usually with some attenuation of pressor surges and greater prominence of
depressor valleys during long-term follow-up. With incomplete loss of baroreflex afferents, a mild
syndrome of orthostatic tachycardia or orthostatic intolerance may appear. Finally, if the BRF occurs
without concomitant destruction of the parasympathetic efferent vagal fibers, it may lead to malignant
vagotonia with severe bradycardia, hypotension, and episodes of sinus arrest.
Causes of BRF include: trauma, CEA, anterior neck surgery for other pathology, brain stem stroke, tumors
of chromaffin tissue next to N IX, carotid paraganglioma, neck radiation, impaired function of Nucleus
Tractis Solitarius/Leigh syndrome.
Manifestations of BRF:
1. HTN crisis SBP> 300, typically >250, diaphoresis, apneic spells, requires urgent treatment.
2. Volatile HTN is the most commonly encountered presentation. It may develop insidiously after an
extended period of time during which the baroreflex function gradually declines. Baseline blood
pressure may be normal to elevated, marked abrupt increases or surges of blood pressure lasting
minutes to hours occur and are accompanied by tachycardia. Mild and transient elevations in
plasma glucose have also occasionally been seen. Intraocular pressure may also increase. Plasma
norepinephrine may increase to levels >1000 mg/mL, as encountered in pheochromocytoma.
Values >2000 pg/mL are occasionally seen. Patients with volatile hypertension can have
hypotensive valleys as well as pressor peaks, especially during periods of quiet, sedation, or sleep,
when sympathetic outflow is diminished.
3. Orthostatic tachycardia defined as an increase in heart rate by >30 bpm from the supine to upright
position, is one of the most common findings. Some patients have neuropathic postural
tachycardia syndrome.
4. Malignant vagotonia manifested as severe bradycardia and asystole attributable to increased
parasympathetic tone are rarely encountered in BRF. Selective BRF (Jordan syndrome) exibits
interrupted afferent baroreflex input from the carotid sinus to the nucleus tractus solitarii with
intact efferent sympathetic and parasympathetic output to the heart and blood vessels. Patients
with this form of AD may have episodes of hypotension with a systolic pressure <50 mm Hg,
asystole during rest, lasting for 20 seconds or more, mandating the placement of a cardiac
pacemaker.
THERAPY
 Goal of therapy of patients with baroreflex failure is to reduce the frequency and magnitude of
life-threatening surges in blood pressure and heart rate and to attenuate symptomatic hypotensive
episodes.
 In patients with selective baroreflex failure, pacemaker placement may be necessary.
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 Treatment for blood pressure surges t is clonidine.

 Agents that prevent release of norepinephrine- Guanadrel- are effective.
 Fludrocortisone prevents hypotension, because patients with baroreflex failure may have reduced
plasma volume.
 Yohimbine, at modest doses (1 to 5 mg ) should be introduced when excessive α2-agonist effect
has been elicited, with consequent prolonged hypotension.
 If severe bradycardia (<40 bpm) is detected the placement of a pacemaker may be necessary.
 Agents that reduce the breakdown of norepinephrine, such as monoamine oxidase inhibitors,
should be avoided.
 Amphetamines and cocaine should also be avoided.
AUTOIMUNE AUTONOMIC NEUROPATHY (AAG) (case discussion)

In this condition, the nicotinic receptor in the autonomic ganglia is the target of the autoimmune attacks so
both sympathetic and parasympathetic cholinergic and adrenergic transmission is affected (9). It is often
associated with high titers of ganglionic (neuronal) acetylcholine receptor antibody (g-AChR antibody), can
impact people of all ages. Prior names for AAG include acute pan-dysautonomia, autoimmune autonomic
neuropathy and idiopathic sub acute autonomic neuropathy.
Symptoms of AAG reflect generalized sympathetic and parasympathetic failure and include:
-severe orthostatic hypotension (SBP drop > 20 and DBP drop >10 mmHg within 3 min of standing).
- fixed heart rates, severe hypotension, severe bradycardia/asystole
- constipation and moderate to severe GI dysmotility, gastro paresis
- urinary retention (neurogenic bladder)
- fixed and dilated pupils
- dry mouth, dry eyes, anhidrosis
- cold feet and hands with color or trophic skin changes
About 50% of patients with AAG have high titers of g-AChR antibodies. Antibody levels correlate with the
severity of autonomic dysfunction. The remaining 50% of AAG patients have no detectable levels of g-
AchR antibodies. Some patients with AAG have a para neoplastic form of the disease.
Perioperatively patients should continue their medications (midodrine) and if continue to be hypotensive
they benefit from direct vasoconstrictors. Aspiration prophylaxis is warranted, as is mucosal protection due
to profound dryness. Intraoperatively they may need direct vasoconstrictor agents and volume replacement
may be anticipated.
References:
1. Mustafa, HI et al. Dysautonomia. Perioperative implications. Anesthesiology 2012;116:205-15
2. McGrane, S et al. Perioperative implications of the patient with autonomic dysfunction. Current
Opinions in Anesthesiology 2014;27:365-370
3. Aslanidis, T. Perspectives of autonomic nervous system perioperative monitoring-focus on
selected tools. International Archives of Medicine 2015;8:1-9
4. Low, PA et al. Laboratory evaluation of autonomic failure. In Low PA, Benarroch EE, editors.
Clinical autonomic disorder (3rd ed.). Baltimore-Philadelphia: Lippincott Williams &
Wilkins;2008. P. 130-63
5. Pearce, W. The cardiovascular autonomic nervous system and anesthesia. Southern African J of
Anesthesia & Analgesia 2002;8:3, 8-24
6. Vinik, AI et al. Diabetic autonomic neuropathy. Diabetes Care 2003; 26(5):1553-1579
7. Iodice, V et al. Autopsy confirmed multiple system atrophy cases: Mayo experience and role of
autonomic function tests. JNNP 2012;83:453-459
8. Ketch, T eat al. Four faces of baroreflex failure. Circulation 2002;105:2518-2523
9. Winston N, Vernino S. Recent advances in autoimmune autonomic ganglionopathy. Current
Opinions in Neurology, 201;23:514-518
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New Innovations in Spinal Cord and Dorsal Root Ganglion Stimulation
Timothy Deer, MD, FIPP, DABPM Charleston, West Virginia, USA
INTRODUCTION
Since we last met 12 months ago, we have seen many innovations in Neuromodulation as it relates to clinical
practice in the United States and among our international colleagues. In the United States we have had the
presentation of three studies achieving level-one evidence. This clinical research has led to approval of the use of
Dorsal Root Ganglion Spinal Stimulation, High Frequency Spinal Cord Stimulation (HF10), and Burst Waveform
(also known as DeRidder Burst). This is truly a golden era for Neuromodulation and for the patients who may
benefit. This session strives to give the reader an overview of best uses of these new tools.
SAFE
As with previous treatment options, new interventional therapies should be based on careful selection and logical
thought progression. The introduction of the SAFE algorithm should be applied to these techniques. This is an
acronym for the requirements that should be applied to interventional treatments: they should be relatively safe,
appropriate, fiscally neutral and efficacious.
CLASSIC OR TONIC SPINAL CORD STIMULATION (SCS)
SCIENTIFIC PRINCIPLE
Implantation of a SCS system is performed in two stages; a temporary implant which allows the patient to evaluate
their response to the therapy and a permanent implant in which both stimulating electrodes are placed over the spinal
target and then connected to an implanted programmable computer and power source. By using a programmable
generator, the amplitude, rate, frequency and shape of the electrical field can be manipulated to create pain relief.
The mechanism of neural effect has been theorized to change the balance of inhibitory to excitatory fiber activity by
the gate control process, which is determined by the shape of the electrical field determined by the electrodes.
Conventional stimulation involves a tonic waveform with frequency usually being delivered between 40 and 100
Hz. (figure 1). This current creates a parasthesia that results in a “pacing” type sensation that many patients find to
be pleasant and often creates pain relief. In order to reduce pain, most scientists believe the parasthesia must cover
the dermatomal pattern of pain. In the past year the development of wireless trialing to the smart phone type device
has improved patient comfort and compliance.
Figure 1. Tonic Waveform
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LOGICAL PROGRESSION OF PAIN TREATMENT
The algorithmic treatment of pain is currently the standard of care for improving pain levels, function, and quality of
life. In recent years, many experts have recommended the use of SCS much earlier in the algorithm; namely before a
second spine surgery in neurologically stable patients, before chronic opioids in patients with mixed or neuropathic
pain, and in some cases prior to the first back surgery in patients with multi-level disease or uncertain surgical
outcomes. The change in the algorithm is due to several factors including the simplification of stimulation trialing,
improvement of programming, and diversity of arrays. Evidence based medicine also is favoring SCS over other
strategies, shown nicely in three randomized studies with primary investigators Kapural, Deer and Levy. Kapural
and colleagues showed superior pain relief of HF10 over conventional SCS. Deer and Levy led the ACCURATE
study, which showed superiority of DRG stimulation as compared to tonic stimulation for nerve pain of the groin
and lower extremity. Deer, Slavin, Staats and North led a study that showed superiority of the Burst waveform as
compared to tonic stimulation with the patient as a self control.
In addition to improved evidence the desire to avoid opioids and addiction is leading to an interest in these methods.
INDICATIONS AND PATIENT SELECTION:
In the United States, the FDA has approved this therapy for the treatment of moderate to severe pain in the trunk or
limbs. The specific indications for which these devices are most commonly used have been well defined. The most
common indication for spinal cord stimulation is failed back surgery syndrome. Other common reasons patients
undergo these surgeries include radiculitis, complex regional pain syndrome, peripheral neuropathies, post herpetic
neuralgia, ischemic limb pain, angina, pelvic pain and other neuropathic and visceral pain syndromes. In recent
months we have published the results of a pain registry that lends further support to the use of SCS in the cervical
spine to treat diseases of the head, neck and upper extremities.
A recent consensus group, the Neuromodulation Appropriateness Consensus Conference (NACC), has commented
on proper uses of SCS for neuropathic pain, vascular diseases and angina. The NACC has also published on
contraindications and improving safety. These papers will be an important guide for patient safety. Additional
consensus groups are currently working on guidance regarding bleeding, infection, and neurological safety.
SPINAL CORD STIMULATION: THE PROCEDURE
GENERAL PRINCIPLES
After appropriate patient selection and education the patient should undergo preoperative evaluation for
perioperative risks. Once cleared for trialing, the patient should be interviewed by the anesthesiologist and
stabilized. Preoperative antibiotics are based on local pathogens and susceptibilities. Most common antibiotics
include intravenous vancomycin or a third generation cephalosporin preoperatively, bacitracin or kantrex,
intraoperatively. Intraoperative prepping and draping should be broad and extend well beyond the surgical field.
Positioning should facilitate surgical technique and patient safety and comfort.
IMPLANT METHOD
The use of a percutaneous lead or surgical paddle lead is at the discretion of the implanting physician. Percutaneous
leads are introduced in a less invasive and less dangerous method so are usually preferable, but in some cases, such
as those with complex spinal disease, extensive scar tissue, or primary axial back pain a paddle lead may be a better
choice. In those who obtain a percutaneous lead, whether using a cylindrical lead or new paddle constructs, a needle
must be placed appropriately prior to delivering the device.
NEEDLE PLACEMENT
Prior to implanting a device physicians should consider planning the needle placement including the level of entry,
the side of entry and the angle. In the lumbar spine needles are usually placed into the epidural space at 30 to 45
degrees. A paramedian approach is preferred, with a skin entry site one and half to two levels below the desired
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entry space. The needle entry into the epidural space should be two to three levels below the final lead target. In the
cervical spine the needle entry should be below the T1 vertebral level. Lead placement for DRG stimulation is
paramedian and contralateral.
LEAD PLACEMENT
Lead placement has evolved in recent years. Classically the lead is placed into the posterior epidural space and
confirmed on AP and Lateral fluoroscopy. The targets are noted in the tables below.
EPIDURAL LEAD TARGET
The physician should understand the target for the led to achieve proper stimulation. Table 1 provides general
targets for spinal cord stimulation.
DRG stimulation is mapped somewhat differently since the target is at the level closest to the impacted dermatome.
DRG stimulation also has the major advantage of divergence and convergence at the spinal level, which allows the
clinician to stimulate the DRG at a level that may be within 2 to 3 levels from the area of the pain generator.
Table 1. Lead Placement for Tonic Stimulation
Region Position Target

Cervical C2 Lateral Mandible, Neck, Shoulder
C2-3 Shoulder, Arm
C4-6 Arm, Hand
C7-T2 Anterior Shoulder, Chest
Thoracic T3-T6 Abdominal, Thoracic, Visceral Organs
Thoracic T1-3 Angina, Chest

T4-6 Visceral Abdomen
T7-9 Axial Back
T10 Knee, Hip
T11-12 Leg, Foot
Lumbar L1 Foot, Possible Pelvic Organs

L5-S1 Foot
Nerve Root
Sacral S2-4 Pelvis, Rectum, Perineum
LEAD PROGRAMMING
The field of stimulation or the array is influenced by the number of the cathode (negative) and anode (positive)
electrodes and the orientation of each contact. Current is driven into the neural tissue based on the presence of a
cathode. The optimal current delivery occurs when a cathode is surrounded or “guarded” by an anode on each side.
New lead arrays have been developed using percutaneous, percutaneous paddle and paddle leads. Cross talk
between leads, program cycling and isolated electrode programs may impact the outcomes. Programming for DRG,
Burst and HF 10 requires a new skill set and physician and nurse training to these new methods will be important.
LEAD ANCHORING
In analysis of complications of SCS, the possibility of lead movement is always a major concern. The advent of
new “mechanical” or locking anchors has reduced this problem. Other factors appear to be moving the anchor into
the ligament, angle of needle entry, and suture methods. Making an incision into the ligament around the needle
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prior to removal may allow the new longer mechanical anchors to slide into the ligament and reduce the strain on the
materials that may reduce migration. Paddle implants have less migration, but that must be balanced against the
difficulty of revising the lead, lead fracture and the increased risk of major neurological deficits.
POCKET FORMATION
The position of the pocket is based on patient preference and body habitus. Options include the buttock, abdominal
wall, flank, and chest wall. The depth of the pocket should be appropriate to avoid skin erosion, but should also
assure good communication with telemetry. The implanter should consider sleeping patterns, shoulder mobility and
patient clothing preferences when planning the pocket.
COMPLICATIONS OF SCS
The most common complications of spinal cord stimulation include lead migration, superficial infection, impedance
abnormalities, wet tap, and nerve irritation. More serious problems include epidural hematoma, epidural abscess,
paraplegia, and death. The NACC papers look at each of these problems and discuss possible ways to mitigate
complications. Best practices should reduce these complications.
INNOVATIONS IN STIMULATION OF THE CENTRAL NERVOUS SYSTEM
STIMULATION OF THE DORSAL ROOT GANGLION
The anatomy of the DRG makes it an attractive target for neuromodulation. The structure is a sensory neural body
that contains the soma from primary sensory neurons. The ganglion is located within the bony structure of the spine
just below the pedicle where it reliably lies in all patients, and both transmits and influences sensory neural impulses
traveling from the periphery. The ganglion contains multiple cell types including neurons and glial cells that
change and become hyperexcitable in chronic pain conditions. (Figure 2, with permission of Jeff Kramer, PhD) The
DRG has been a target for injection, surgical interventions and radiofrequency in the past, but with no long-standing
efficacy. The development of new novel leads, delivery tools and multi-channel generators has led to the use of
DRG stimulation as a major advance in the treatment of intractable pain syndromes. The lead shape allows for
selective stimulation of the DRG without encompassing the surrounding structures. (Figure 3) Approval of this
therapy has now been given in the European Union, and a multi-center randomized prospective study is enrolling in
the United States. Based on the European study data, DRG-SCS has expanded the field of stimulation for patients
traditionally not good candidates for SCS. These patients include patients suffering from phantom limb pain, foot
pain, chest wall pain and groin pain.
Figure 2. The presence of hyperexcitable fibers in the DRG appears to lead to selective stimulation of the abnormal
areas of the pain transmission and avoids the over stimulation of fibers that may lead to motor stimulation.
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Figure 3. Lead Placement
HIGH FREQUENCY METHODS OF SCS
Low frequency has been standard in clinical neurostimulation. It has been rare for patients to be treated with
frequencies greater than 100 Hz. This concept has recently been challenged. Work done in the United States,
Europe and Australia has suggested that the use of High Frequency Stimulation (HFS) may give significant relief in
those who have primary axial back pain, cervical pain, or complex patterns or those with inability to tolerate the
feeling of parasthesia with conventional stimulation. HFS involves the use of leads, similar to conventional systems,
placed based on anatomical strategies noted above. The frequency used in these devices approach 10, 000 Hz, but
may also be used to deliver more standard frequencies. Recent work on using 5,000 Hz did not show efficacy
suggesting that the higher frequency may be more efficacious. Recent animal data suggests that frequencies over the
8,000 Hz leads to a change in nerve firing and responsiveness of the pain pathways. Figure 4 shows a representation
of a typical high frequency waveform.
Figure 4 – High Frequency Waveform 10,000 Hz
BURST STIMULATION
The use of tonic stimulation in both high and low frequency ranges have shown good outcomes in thousands of
patients. Recent work by DeRidder and colleagues have suggested using rapid non-tonic bursts of high frequency
signal rotated with periods of electrical silence to produce pain relief without parasthesia. This concept has great
potential to salvage those failing traditional low frequency tonic stimulation and is attractive that using the same
generator you could use both tonic and burst stimulation to optimize outcomes. A recent multi-center prospective
comparative study showed improved efficacy with Burst as described by DeRidder. Scientific work has shown a
dissociation of pain response and suffering. This dissociation may lead to improved function and reduction of other
treatments including opioids. Figure 5 shows an artist rendering of a burst waveform.
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Figure 5. Burst Waveform
CONDITIONAL APPROVAL OF MRI
At the time of this lecture all commercial devices have some ability to undergo an MRI. Some devices have
indications for the brain or limbs only, while others have total body. The implanting doctor should weigh the ability
to obtain a good outcome verses the need for an MRI and personalize patient care.
PERCUTANEOUS PADDLE DELIVERY
The choice of delivering a cyndrilical lead via a needle approach or a paddle lead via a laminotomy open approach
has been complicated based on the risk to benefit ratio. The ability to delivery new waveforms and to stimulate the
DRG may reduce the need for paddle lead placement.
CLOSED LOOP AND FEEDBACK MECHANISMS
This year, we will focus on feedback loops to more efficiently and accurately provide stimulation. This concept
allows the device to fire at the precise time to achieve optimal stimulation. A major study is planned in the United
States in 2016 and 2017 to evaluate the importance of this method in both parasthesia and non-parasthesia based
systems.
SUGGESTED READING
1. Deer T, Masone R. Selection of Spinal Cord Stimulation Candidates for the Treatment of Chronic Pain.
Pain Medicine, Volume 9 Issue S1, Pages S82-S92
2. Deer T., Atlas of Implantable Therapies for the Treatment of Pain. Editor. Deer Springer 2011.
3. Deer, T. Atlas of Implantable Therapies for the Treatment of Pain. Editors Deer and Pope. Springer, 2015.
4. North R, Kidd D, Farraokhi F, Piantadosi S. Spinal cord stimulation versus repeated lumbosacral spine
surgery for chronic pain: a randomized, controlled trial. Neurosurgery. 2005;56(1):98-106.
5. Mekhail N, Aeshbach A, Stanton-Hicks M. Cost Benefit analysis of neurostimulation for chronic pain. Clin
J Pain. 2004 Nov-Dec: 20(6): 462-8.
6. Kumar. K, Taylor RS, Jacques L, et. al., Spinal Cord Stimulation versus conventional medical management
for neuropathic pain: A Multicenter randomized controlled trial in patients with failed back surgery
syndrome. Pain (2007); doi:10.1016/j.pain.2007.07.028
7. Taylor R, Van Buyten J, Buscher E. Spinal cord stimulation for complex regional pain syndrome: a
systematic review of the clinical and cost-effectiveness literature and assessment of prognostic factors. Eur
J Pain. 2006 Feb;10(2):91-101
8. Deer, T. Current and future trends in spinal cord stimulation for chronic pain. Current pain and headache
reports 2001, (5): 503-509.
9. Kumar K, Rizvi S, Nguyen R, Abbas M, Bishop S, Murthy V. Impact of Wait times on Spinal Cord
Stimulation Therapy Outcomes.. Pain Pract. 2013 Oct 25.
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10. Deer T., Ioannis M., Skaribas, MD, et. al Effectiveness of Cervical Spinal Cord Stimulation for the
Management of Chronic Pain. Neuromodulation . Volume 17, Issue 3, pages 265–271, April 2014
11. Shechter R, Yang F, Xu Q, Cheong YK, et.al. Conventional and kilohertz-frequency spinal cord
stimulation produces intensity- and frequency-dependent inhibition of mechanical hypersensitivity in a rat
model of neuropathic pain. Anesthesiology. 2013 Aug;119(2):422-32
12. Fields, R. D. (2009). "New culprits in chronic pain." Sci Am 301(5): 50-57.
13. Deer T, Bowman R, Schocket SM, et. al. The prospective evaluation of safety and success of a new
method of introducing percutaneous paddle leads and complex arrays with an epidural access system.
Neuromodulation. 2012 Jan-Feb; 15(1):21-9; discussion 29-30.
14. Krames, E., Poree, L., Deer, T. and Levy, R. (2009), Implementing the SAFE Principles for the
Development of Pain Medicine Therapeutic Algorithms That Include Neuromodulation Techniques.
Neuromodulation: Technology at the Neural Interface, 12: 104–113.
15. Deer T, Mekhail N, Provenzano D, Pope J, et. al. The Appropriate Use of Neurostimulation: Avoidance
and Treatment of Complications of Neurostimulation Therapies for the Treatment of Chronic Pain.
Neuromodulation. Accepted for publication December, 2013
16. Deer T, Krames E, Mekhail, N, Pope J, et. al. The Appropriate Use of Neurostimulation: New and
Evolving Neurostimulation Therapies and Applicable Treatment for Chronic Pain and Selected Disease
States. Neuromodulation. Accepted for publication February, 2014.
17. Deer T, Mekhail N, Provenzano D, Pope J, et. al. The Appropriate Use of Neurostimulation of the Spinal
Cord and Peripheral Nervous System for the Treatment of Chronic Pain and Ischemic Diseases: The
Neuromodulation Appropriateness Consensus Committee. Neuromodulation. Accepted for publication
February 2014.
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MACRAs Physician-Focused Alternative Payment Model (PF-APM) Options:

A Multispecialty Perspective
Asa Lockhart Tyler/TX
BACKDROP
The Medicare Access and Chip Reauthorization Act (MACRA) replaced the Sustainable Growth Rate
(SGR), which had been renewed numerous times with a series of patches. MACRA created two options for
compliance. The first path, which does not require assumption of insurance risks, is the Merit-based
Incentive Payment System (MIPS) that consolidated existing quality programs and added clinical practice
improvement. The other fork in the new highway is the Alternative Payment Model (APM) with one
subgroup variant being Physician Focused (PF-APM) where the physician accepts some level of risk for
services and expenses over which they have some control. One should be aware that another variant is the
Hospital Focused (HF-APM), but this presentation is focused on PF-APMs with an emphasis on potential
multispecialty models that in a particular community enable anesthesiology practices to participate; so the
goal of this presentation is to increase awareness of subtle opportunities that may be developed by others in
the community where anesthesia may play a role. Other presentations at this meeting will focus on more
anesthesia specific options (e.g., Perioperative Surgical Home). While physicians may have a wide range
of experience with the MIPS elements, most have (at a minimum) a grasp of the basic concepts and
foundations. In contrast at the other end of the numerical spectrum, few physicians have any idea how
APMs might apply to their practice. Some APM options such as the Patient Centered Medical Home have
been around for some time yet have not penetrated the market in many parts of the country, especially in
smaller practices that may lack infrastructure or feel they have too many immediate production pressures to
take the time to apply the concept.
Our current system is oriented towards intervention and is often focused on the anecdotal, and what is
possible, while emerging models emphasize prevention and evidence-based or experientially-based
utility. Neither camp wants to harm patients; they just have a different idea of how to get there. The
HMOs of the 90s were viewed as being solely focused on finances (Just say no!), and the models now
under discussion are focused on balancing optimization of outcomes, costs, and patient satisfaction. While
we may do a great job of diagnosing, managing, and treatment of chronic diseases, we do not do as well
preventing their development, managing or preventing their complications, and differentiating the efficacy
of various options. There are multiple reasons. There ae silos of care where the emphasis on focused on
the part a particular physician or specialty may play. There may be disconnects between the consumer (the
patient) and the producer (not limited to physicians) so questions of costs and utility are often not
asked. Does the test need to be done? Before one commits to a procedure, the questions of how often it
meets expectations, at what costs, and at what risks are not valued by the current system. Additionally,
there is no prerequisite that the patient has an affirmative responsibility to optimize their personal health.
And finally, the system itself is a barrier.
BARRIERS
The driving concepts behind APM begin with the realization that existing models do not address barriers to
redesigning services that provide a higher-value of healthcare. Before one can innovate, they must have the
latitude to reallocate precious, but limited, resources and have space to make the transition. Two
commonly mentioned barriers are either no or inadequate payment for many high value services and
financial penalties for delivering a different mix of services that result in a lower costs to society.
There are many services that may benefit patients either through enhanced personal time in an alternative
model or the freedom to pursue lower cost options with improved or neutral outcomes. We are not paid to
take the time to counsel patients on lifestyle and the various options available to them that are time-
intensive or require relational databases that may not exist and would be expensive to establish. Physicians
are best positioned to evaluate alternative delivery systems, optimize cost delivery settings, and different
combinations of services and providers. But that takes time, requires support resources (human and
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financial capital) that are not made available currently, and alignment of incentives that focus more on
outcome, utility, and coordination rather than component production and what is merely possible.
During the transition from the current model to the emerging models, one still has to keep the doors open;
this is one laudable goal not supported by United Way! If the current transactional practice revenue
decreases by delivering fewer or lower cost services, a transitional strategy will be necessary to shield
operating losses since the changes will not likely be proportional and may be even be higher in a temporary
dual system.
There are a number of examples where no or inadequate payment for high-value services are a barrier by
both Medicare and private health plans for services that would benefit patients and help reduce avoidable
spending. For example, responding to a phone call about a symptom or problem might help patients avoid a
more expensive ER visit. There is no recognition for the value of coordination between primary care
physicians and specialists or taking ownership for the coordination of care and time spent to avoid ordering
duplicate tests and prescribing conflicting medications. There are no incentives for the time that it takes
community and emergency physicians to facilitate discharge planning in emergency departments that could
enable patients to be safely discharged without hospitalization. Some high-risk patients might respond to a
proactive early-stage telephone call that would optimize preventive care and lower comorbidities.
Deconditioned patients in particular, and many patients in general, would benefit from prehabilitation but
there is no support for development of this intervention. Smoking cessation reduces respiratory
complications and length of stay as well as improvement in wound dehiscence. Current paradigms do not
recognize these benefits while a well-designed APM would embrace such opportunities.
There are several ways that financial penalties for delivering a different mix of services may pose a
transitional risk to physicians. As the health of patients improve, they will require fewer services and may
avoid developing a disease. They would be expected to have fewer complications or lower comorbidities
that require intervention. Even though there may be fewer or less costly procedures, the cost of running a
practice generally does not decrease; rent and utilities are not pegged to quality of care or resource
utilization. Since most of the savings to the system from APMs do not come from physician payments, the
savings can be realized without financially targeting and implicit penalization of physician practices for
delivering a societal goal. With healthier patients, physician practices would receive less income under
current approaches. This could be the greatest conflict with our current FFS system, and one essential
foundation and question that must be answered if we are to make substantial progress as APM options are
developed.
With these barriers, what are the prerequisites for successfully creating new options? The Center for
Healthcare Quality and Reform has identified three characteristics for enabling change:
1. Flexibility in Care Delivery

In order to overcome the barriers discussed above, an APM must provide enough innovative
flexibility—with a patient centric focus—to deliver a mix of services that makes sense but is not
covered within today’s payment methodologies so that we can provide a new path to efficiency
and effectiveness.
2. Adequacy and Predictability of Payment

As one contemplates navigating the coming changes, this characteristic is essential so that the
financial resources will be available to start the process with confidence that the return on
investment (ROI) will be there. The fear at the end of the dance is that we will be out there
alone. If we are successful, there is a concern that some politician will award our victory to a
political crony. So the rules of engagement must deliver adequate and predictable resources to
allow physicians to create the alternative structures that will identify high-quality service
opportunities whose costs include both start-up and transitional financial risk to physicians. The
exposure must be both risk-adjusted to recover their investment yet be within an acceptable
financial risk corridor for small businesses and medical practices.
3. Accountability for Costs and Quality That Physicians Can Control
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The program design must be structured to assure non-provider stakeholders, (patients and payers)
that the outlays will be controlled or reduced with the implicit assumption that quality will at a
minimum be maintained if not improved. However, the beauty of the “Physician-Focused
Payment Models” is that individual physicians should only be at risk for those aspects of spending
and quality they can materially control or influence. This is similar to Activity-Based Accounting
where one has to have control over the activity for it to be in that cost center.
EXAMPLES OF POTENTIAL MODELS
In the document A Guide to Physician-Focused Alternative Payment Model prepared by the AMA and the
Center for Healthcare Quality and Payment Reform, they identify seven potential models. Since this is an
emerging concept and there are no other resources that synthesize the material as well as this publication, I
will rely upon the following excerpts from that comprehensive document to stimulate your evaluation of
how one of these models could benefit your practice and your community:
“APM #1: Payment for High Value Services where physicians are paid for delivering desirable services
that are not currently billable in order to avoid the need for patients to receive other, more expensive
services… A physician practice would bill and be paid for the time and resources needed to apply
appropriate use criteria and engage in an education/shared decision-making process with patients in order
to determine the most appropriate diagnostic tests to use… In contrast to a typical shared savings program,
an individual physician practice’s payments would not be explicitly tied to how much money that practice
saved the payer. Instead, the physician practice would be paid adequately to deliver appropriate services,
and the payer would save money by spending less on avoidable services (for the patients in all participating
practices).” Could such a program be a component of an early stage PSH (e.g., pre-op testing protocols,
prehabilitation, smoking cessation)?
“APM #2: Condition-Based Payment for Physician’s Services … where a physician has the flexibility to
use the most appropriate diagnostic or treatment option for a patient’s condition without reducing the
operating margins of the physician’s practice… the practice would have the flexibility to use the payments
for whatever combination of services were most effective –office visits, phone calls, emails, support from
non-physician staff, etc.” These would replace E&M codes limitations with monthly payments targeted to
chronic conditions. For a primary care physician with global risk, potentially a seamless transition into a
PSH may become an opportunity or smoking cessation achieved as a result of a PSH may enhance the
management of a COPD patient.
“APM #3: Multi-physician Bundled Payment…where the goal is to give multiple physicians who are
providing services to the same patient the flexibility and resources needed to redesign their services in
coordinated ways that will improve quality and reduce the costs of diagnosis or treatment… Patients would
benefit because the physicians delivering their care could work together in a more coordinated way and use
the additional resources and/or flexibility under the bundled payment to deliver different types or
combinations of services that cannot currently be provided. The payer would benefit because the new
payment would enable the physicians to deliver care more efficiently, order fewer or lower-cost services
from other providers, and/or reduce the number of complications for their patients. The physician practices
would benefit by having the resources and flexibility to deliver the most appropriate services to patients in
a coordinated way without concern about which services will generate more revenue for the individual
practice.” This model has a very high potential as well as likelihood for participation by anesthesiologists
since it offers major benefits and aligns incentives for all stakeholders to coordinate care by virtue of shared
risks and rewards. This model would allow acceptance of risks for professional services, especially in
circumstances where the facility partner is unable or unwilling to participate.
APM #4: Physician-Facility Procedure Bundle… where the goal is to give physicians greater ability to
choose the most appropriate hospital or other facility to deliver a particular procedure and to work with the
facility to improve efficiency and quality in delivering that procedure...The patient would benefit by being
able to receive high quality care at the lowest-cost facility and to receive coordinated and efficient care
from the physician and facility staff. The payer would benefit because the Alternative Payment Entity
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could accept a lower payment for the bundle than the total amounts that would have been paid separately to
the physician and facility under current payment systems. The physician practice could benefit by using
the bundled payment to cover the costs of services that are not current billable or do not receive adequate
compensation, and by receiving compensation for changes in the physician’s services that reduce the costs
of the services delivered by the facility.” This model has a very high potential as well as likelihood for
participation by anesthesiologists since it offers major benefits and aligns incentives for all stakeholders for
both surgical and obstetrical management. I would note that the marked variability in hospital charges will
be a significant driver and an opportunity to engage payers in many communities. Since anesthesiologists
may cover multiple sites and know the inside baseball, they may be in a unique position to help select the
most efficient or progressive facilities (e.g. stable facilities with good policies and procedures versus one
with high turnover and poor/unenforced policies).
APM #5: Warrantied Payment for Physician Services…where the goal is to give physicians adequate
payment and flexibility to redesign care in a way that will prevent complications and reduce the spending
needed to treat them… In contrast to penalties that reduce payments when complications occur, the
warranty approach provides greater upfront resources so that care can be redesigned to reduce
complications. In addition, although no additional payment is made when complications occur, the cost of
treating some complications is built into the warrantied payment amount, so the physician practice is not
financially penalized when a small number of complications occur, but it is rewarded if it can eliminate
most or all complications.” This could be a potential variant of a monetization strategy for a PSH.
APM #6: Episode Payment for a Procedure… where the goal is to give physicians and other providers the
ability to deliver all of the care during and after delivery of a particular procedure or treatment in a
coordinated, efficient way… all of the costs involved in performing hip or knee surgery during an inpatient
hospital admission, delivering rehabilitation services after surgery, and treating any post-operative
complications. The payment amount would be higher for patients with comorbidities and functional
limitations that would require more inpatient or post-acute care. The payment amount would be adjusted
based on measures of quality and outcomes for the patients.” This essentially takes Models 4 and 5 plus
adds the post-discharge management and re-admission risk components. While optimally this might be a
later more mature option after experience in Models 4 and 5, market and political pressures may make this
the initial option. The current Comprehensive Care Joint Replacement (CJR) has some of the elements of
this APM but it is currently limited to hospitals. It could be revised so that the episodes could be managed
by physicians ; however, at the time of this draft, it is not on the APM list under the proposed rules!
APM #7: Condition-Based Payment… gives physicians and other providers who are delivering care to
patients for an acute or chronic condition the flexibility and accountability to deliver the most appropriate
treatment for the patient’s condition in a coordinated, efficient, high-quality manner.” One of the examples
was for a Condition-Based Payment for Post-Acute Care Following a Hospitalization for spine surgery.
This model may be a separate initiative, perhaps with different provider groups, as either an early stand-
alone or as an independent but complementary part of Model 3 or 4, but an integral part of Model 6. The
post-discharge management of a PSH patient could be a stand-alone approach in some communities and
circumstances. In the procedural arena, I do not see this as a long term option and would predict a rapid
integration with one of the other models.
IN CONCLUSION
As this document is drafted in June, we are in the initial phase of rule-making and the ASA and AMA have
several units diligently studying options to preserve your future. There are multiple system options, which
may be payer-designed, facility-designed, or physician-designed. Close your eyes and make a guess; of
those three options, which avenue is most likely to design an optimal system that treats our colleagues and
our patients in the most equitable manner? The options presented above will in all likelihood evolve with
both the final rulemaking and system adaptation.
I would like to acknowledge briefing materials contained in the publication A Guide to Physician-Focused
Alternative Payment Models jointly produced by the AMA and the Center for Healthcare Quality and
Payment Reform that provided the generous excerpts, direction and resources for this article. In particular,
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I would like to thank Sandra Marks (AMA) and Harold Miller (CHQPR) for their copyright permission in
general and allowed use of generous excerpts and edits in particular. For a deeper understanding on how
you can take control of your future, this excellent resource may be accessed at: [Note to AMA: specify
link or preferred method of access]
Asa C. Lockhart, MD, MBA

903-521-6728
aclhart@aol.com
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Cesarean Delivery Pain Management for the Breastfeeding Mother
Brendan Carvalho MBBCh, FRCA. Stanford/CA
Lecture Synopsis:
The lecture summarizes various multi-modal analgesic options to optimize pain management after cesarean delivery
(CD), specifically the role of neuraxial opioids, non-steroidal anti-inflammatories (NSAIDs), acetaminophen,
dexamethasone, gabapentin, ketamine, wound infiltration, transversus abdominis plane (TAP) block. Analgesic drug
exposure in breastfeeding neonates, and techniques to minimize the transfer of analgesics into breast milk will be
considered. Patient-centered pain management options will also be discussed.
Introduction:
Pain associated with CD is the most important concern for expectant mothers (Table 1), 1 and is often incompletely
relieved by pain management protocols. Pain after CD is described as moderate to severe, and equivalent to that
after abdominal hysterectomy.2 Postoperative pain goals proposed by the Joint Commission (pain scores of
consistently <3 out of 10),3 are infrequently attained after CD.4 Good post-CD analgesia improves maternal
functional ability, enhances recovery, improves interaction with newborn infants, and decreases likelihood of
persistent opioid use.5,6
Outcome Rank† Relative Value‡

Pain during cesarean 8.4 ± 2.2 27 ± 18 Table 1: Patient preferences for anesthesia
Pain after cesarean 8.3 ± 1.8 18 ± 10 outcomes prior to cesarean delivery3
Vomiting 7.8 ± 1.5 12 ± 7
Nausea 6.8 ± 1.7 11 ± 7 Data are mean ± standard deviation; †Rank = 1 to
Cramping 6.0 ± 1.9 10 ± 8 10 from most (1) to least desirable (10) outcome; ‡
Itching 5.6 ± 2.1 9±8 Relative value = dollar value patients would pay to
Shivering 4.6 ± 1.7 6±6 avoid outcome (e.g., pay $18 of a theoretical $100
Anxiety 4.1 ± 1.9 5±4 to avoid postoperative pain).
Somnolence 2.9 ± 1.4 3±3
Neuraxial Opioids:
In the United States, most CD are performed with neuraxial anesthesia (spinal, epidural, or combined spinal-epidural
techniques),7 with the vast majority performed with spinal anesthesia. 8 Neuraxial opioids provide superior
postoperative pain relief compared to intravenous opioids, 9,10 and is recommended by the American Society of
Anesthesiologist’s Obstetric Anesthesia and American Pain Society’s Clinical Practice Guidelines practice
guidelines.11,12
Neuraxial morphine is currently the “gold-standard” single-dose neuraxial post-CD opioid and provides effective
and prolonged analgesia. The duration of post-CD analgesia after intrathecal (IT) or epidural morphine is 14-36
hours,10,13-15 and is dose dependent. Time to first request for additional analgesia of 9.7-26.6 hours for IT morphine
doses of 50-100 mcg versus 13.8-39.5 hours for doses >100-250 mcg.15
Intrathecal vs. epidural morphine: Both IT and epidural administration provide similar efficacy and duration of
post-CD analgesia.16,17 However, IT morphine is considered the preferred route because of a faster onset of
analgesia, and requires a smaller dose with potentially less neonatal effects.
Optimal neuraxial morphine dosing: Optimal dosing is difficult to determine because of variability in patient
response to neuraxial opioids. Neuraxial morphine appears to have an analgesic ceiling (50-200 mcg intrathecally18
and 2-4 mg epidurally19). Larger doses may increase side effects without providing significant additional analgesic
benefit. Patients experience a lower incidence of nausea/vomiting (OR 0.44) and pruritus (OR 0.34) when receiving
lower (50-100 mcg) versus higher (>100-250 mcg) IT morphine doses for CD.
Lipophilic opioids (e.g., IT fentanyl and sufentanil) improve intraoperative analgesia (especially during uterine
exteriorization). Lipophilic opioids have a very quick onset, whereas neuraxial morphine requires 45-60 minutes to
achieve peak effect. IT fentanyl or sufentanil reduce intraoperative nausea and vomiting, decrease local anesthetic
requirements (less hypotension), and provide a better postoperative transition to other pain medications during
recovery from neuraxial anesthesia.20-22 However IT fentanyl 10-50 mcg provides limited post-CD analgesia, with a
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median analgesic duration of 2-4 hours.13,14 A combination of a quick-acting lipophilic IT opioid (e.g., fentanyl 10-
20 mcg) with a long-acting hydrophilic opioid (e.g., morphine 100-200 mcg) is commonly utilized,8 with the aim of
optimizing both intraoperative and postoperative analgesia.
Hydromorphone has an intermediate lipid solubility (between that of morphine and fentanyl). The analgesia and side
effects with hydromorphone is similar to that observed with morphine; 23,24 although its onset is quicker and duration
is slightly shorter.25,26 The dose ratio of IT morphine to IT hydromorphone in the post-CD setting is 2:1.24
Continuous or patient-controlled epidural analgesia (PCEA) with neuraxial opioids such as fentanyl, sufentanil,
hydromorphone, meperidine ± local analgesics has been used with some success after CD. 27,28 However, these
catheter-based analgesic techniques decrease maternal mobility, increase nursing workload, may increase catheter-
related complications (e.g., hematoma, infection) and add additional costs in comparison with single-dose neuraxial
morphine.29 PCEA may be worthwhile for patients with high postoperative analgesic requirements (e.g., chronic
pain sufferers). No consensus currently exists regarding optimal continuous epidural or PCEA regimens.
Maternal and neonatal side effects: All opioids have the potential for placental transfer and therefore it is preferable
to utilize small IT doses or to administer epidural opioids after cord clamping. Although neuraxial opioids provide
superior post-operative analgesia compared to systemic opioids, certain maternal opioid-related side effects (such as
pruritus) may be more frequent.30,31 However, patients prior to CD rank pain relief above side effects such as nausea,
vomiting or pruritus (Table 1).1 Prophylactic metoclopramide and 5-HT3 receptor antagonists reduce the incidence
of postoperative nausea and vomiting and the need for rescue antiemetic treatment in women receiving IT opioids
for CD.32,33 Combination regimens may be more effective than individual antiemetic agents in treating nausea and
vomiting. Opioid antagonists particularly nalbuphine 2.5 to 5 mg are considered first choice measure for managing
opioid-related pruritus.34 Antihistamines are less effective than the opioid antagonists.35 5-HT3 receptor antagonists
may be useful prophylaxis for neuraxial opioid-induced pruritus after CD.36 The analgesic benefits derived from
small doses of neuraxial opioids outweigh the rare risk of associated respiratory depression. 37,38
Multimodal Analgesics:
There is over-reliance on opioids for the management of post-operative pain. Although neuraxial analgesia offers
excellent postoperative analgesia, the majority of women will require additional analgesics after CD. Multimodal
analgesic approaches should be used to augment the analgesic effects of neuraxial opioids. 39,40
NSAIDs: A number of studies have shown NSAIDs are very effective for post-CD pain, especially in relieving
visceral cramping pain.41 The pain relief numbers needed to treat (NNT) for NSAIDs range from 1.8-2.7. NSAIDs
also reduce the need for opioid analgesics by 30-50%,42,43 and decrease opioid-related side-effects (such as nausea,
pruritus, sedation).44 There are no comparative studies between various NSAIDs in the post-CD setting, and
selection should be based on hospital availability and breast-feeding compatibility.
COX-2 inhibitors (e.g., celecoxib) have been shown to be effective perioperative analgesics with pain relief NNT of
4.2 (200 mg) and 2.5 (400 mg).45,46 Although there are potential advantages in using COX-2 inhibitors in this setting
(no effect on platelet function, less risk of bleeding), the routine use of these drugs is not currently recommended
because studies evaluating the drug’s use for CD showed limited analgesic benefit. 47-49 In patients that are intolerant
of NSAIDs, celecoxib can be considered.49
Acetaminophen is an effective analgesic with a 20% opioid-sparing effect.50 Around-the-clock scheduled

acetaminophen rather than combination opioid/acetaminophen pills is preferable to minimize opioid use and avoid
exceeding recommended maximum daily acetaminophen doses of 3,250 mg. 51 Intravenous acetaminophen
preparations are useful in women unable to take oral medications, but should not replace oral formulations given the
higher cost and lack of clear evidence for improved analgesia.52 Acetaminophen and NSAIDs have an additive effect
when used together for post-CD analgesia. 53,54 and therefore scheduled acetaminophen and NSAIDs for 2-3 days
after CD is recommended.
Gabapentin and pregabalin have been shown to be useful perioperative analgesics and to have an opioid-sparing
effect in the acute postoperative period.55,56 In the CD setting, gabapentin (single dose 300 or 600 mg after delivery
or a 2-3 day course) has shown limited analgesic efficacy.57-59 The high umbilical vein to maternal vein ratio (0.86),
potential breast milk transfer and sedation limits routine gabapentin use as a pre-emptive and post-operative drug in
the CD setting.57,60 In selected patients with pain that is difficult to manage, gabapentin may be a suitable analgesic.
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Ketamine: Sub-anesthetic doses (10-15 mg) of IV ketamine have been shown to reduce opioid use for 24 hours after
general surgery.61 Analgesic benefit has been demonstrated after CD under general anesthesia, however limited
analgesic efficacy was reported with ketamine 10 mg IV after CD with neuraxial opioids and multimodal
postoperative analgesia.62 Ketamine may be better suited in selected patients with increased pain management needs.
Dexamethasone in a single perioperative doses ranging from 1.25 to 20 mg has been shown to decrease post-
operative pain, reduce opioid consumption and decrease postoperative nausea and vomiting without increasing
wound infection or healing.63-65
Intrathecal and epidural adjuncts (e.g., clonidine, neostigmine) do not appear to offer substantial improvement in
acute postoperative pain over that of neuraxial opioids. Many of these neuraxial adjuvants are also associated with
side-effects that has limited the routine use of these drugs.66 However, these drugs may decrease pain sensitization
and therefore may have a role in reducing persistent post-operative pain.67
Local anesthetics:
Wound infiltration: Studies investigating the analgesic benefit of local anesthetic wound infiltration in the obstetric
populations have shown mixed results, and the analgesic effect is generally limited to the early post-operative period
following general anesthesia.68 Single-dose wound infiltration at the time of surgery is not usually effective
following spinal anesthesia since the local anesthetic effect may not last beyond the duration of the neuraxial
anesthesia (especially if an IT opioid is added).
A continuous irrigation of local anesthetic into the wound can prolong analgesia and decrease opioid consumption
for 48 hour post-CD.68-70 If continuous irrigation of local anesthetic is utilized, sub-fascial insertion of the wound
catheter appears more effective than subcutaneous placement.71 Continuous irrigation of local analgesia into the
wound has been proposed as an alternative to an epidural technique,72 however analgesic efficacy is limited to
incisional analgesia and reliability is variable.68,69 Neuraxial opioids provide incisional and visceral analgesia, and
are particularly effective after abdominal surgery.73 Local anesthetic infiltration or irrigation techniques should be
considered as adjuvants for and not as replacements for neuraxial opioids or NSAIDs.
Incisional wound administration of drugs other than local anesthetics such as diclofenac, ketorolac, dexamethasone
and opioids, have been demonstrated analgesic benefits post-CD.74,75 Once the biological implications of wound
administration are better understood, wound administration of adjuvant drugs may become a valuable analgesic
alternative to systemic administration but with less potential side effects.
Transversus abdominis plane (TAP) block decreases pain and analgesic consumption in women who undergo CD
under general anesthesia, and spinal anesthesia without IT morphine, however minimal additional analgesic benefit
has been found with TAP blocks in women already receiving IT morphine with multimodal analgesia. 76,77 TAP
blocks in this setting are usually performed after skin closure prior to transfer to recovery. Another proposed
indication for TAP blocks for CD is for rescue analgesia to manage breakthrough pain after offset of spinal
anesthesia, and to reduce the need for escalating opioid doses (with its associated side effects) following cesarean
delivery.78 Differentiation between somatic incisional and visceral cramping pain is important before offering TAP
blocks since this technique is likely only effective for incisional pain. The duration of analgesia after TAP blocks
with a single dose of ropivacaine or bupivacaine is limited to 8-12 hours.79 Studies comparing TAP blocks to IT
morphine have found that IT morphine provides better analgesia but more opioid-related side effects. 76,77 High
local anesthetic blood concentrations are reported after TAP blocks, 80 and several cases of local anesthetic toxicity
have been reported in this setting.81,82 A case series suggests a role for continuous TAP block following CD. 83
Adjuvants such a clonidine, sufentanil and fentanyl offer limited additional analgesic benefit beyond the local
anesthetic used for TAP block.84 Quadratus lumborum block after CD with spinal anesthesia (without IT morphine)
has been found to reduce opioid requirements and pain scores.85
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Breastfeeding Considerations:
The vast majority of women in the United States attempt breastfeeding in the early postpartum period. 86 Neonatal
drug exposure depends on a number of maternal, drug and neonatal factors (Figure 1). A relative infant dose (RID)
>10% is generally considered a level of concern.87,88 Most post-operative analgesics are fortunately well below this
level (Table 2).
Table 2: Relative Infant

Analgesics Dose (RID, %)
Acetaminophen 1.3-6.4
Ibuprofen 0.1-0.7
Ketorolac 0.2-0.4
Celecoxib 0.3
Dexamethasone No data
Gabapentin 1.3-6.5
Hydrocodone 1.6-3.7
Oxycodone 1.5-8
Tramadol 2.4-2.9
Fentanyl 0.9-3
Morphine 5.8-10.7
Neonatal drug exposure can be minimized by: utilizing the lowest effective maternal drug dose; using the most
effective route of administration (IT vs. IV or oral opioids); understanding breastfeeding physiology and drug
transfer (avoiding breastfeeding at peak drug concentrations or breastfeeding before drug administration); selecting
drugs with low breast milk transfer, short half-life, inactive metabolites and a long safety record in this setting.
All opioids enter the breast milk, transfer to the feeding infant, and may cause neonatal sedation and opioid-related
side-effects. Fentanyl exhibits low breast milk transfer (RID 0.9-1.7%), has a short half-life and is rapidly
redistributed, and is a preferred IV opioid in the breastfeeding setting. 89,90 Morphine has a low oral bioavailability
that limits neonatal exposure.91 Meperidine is metabolized to active normeperidine with a very long half-life (t ½±70
h) and is associated with neurobehavioral effects. Meperidine is best limited to small doses (e.g., 10-25 mg for
shivering) in this setting.89 Oxycodone and hydrocodone have been used extensively in nursing women with no
reports of significant adverse effects to breastfed neonates, and are a better oral opioid than codeine after CD. 89,92
Due to their large molecular size and high degree of protein binding, there is minimal transfer of NSAIDs to
breastfed neonates compared to opioids. The American Academy of Pediatrics and Academy of Breastfeeding
Medicine considers most NSAIDs compatible with nursing mothers.89,90 NSAIDs with short half-lives, long history
of safe use, and minimal breast milk transfer such as ibuprofen (RID 0.1-0.7%, half-life of 2 hours) and ketorolac
(RID 0.2-0.4%) are well-suited for breastfeeding women.88,91,93 Celecoxib (a COX-2 inhibitor) also has minimal
transfer to breast milk (RID 0.3%) and is considered safe if breastfeeding. 94 Acetaminophen is a drug with an
excellent side-effect profile, a RID 1.3-6.4%, and no reported cases of neonatal harm. Acetaminophen is considered
compatible with breastfeeding, although caution should be exercised in preterm neonates or neonates with liver
dysfunction.89,90 Gabapentin has a RID 1.3-6.5% and may result in sedation,57,60 therefore caution should be
exercised with the routine use of high-dose gabapentin. Local anesthetics result in very limited breast milk transfer;
Ropivacaine (highly protein bound and very low breast milk transfer) is probably the best suited long-acting local
anesthetic.95
Conclusions:
There is currently no analgesic “wonder drug” and post-CD pain must be managed using a multimodal analgesic
approach as outlined by a suggested analgesic protocol (Table 3). Multimodal analgesia should include neuraxial
morphine in conjunction with scheduled NSAIDs and acetaminophen should be administered in all appropriate
women undergoing CD. The majority of women will require additional analgesics, and breakthrough pain is best
managed with oral opioids (e.g., oxycodone, hydrocodone) while reserving IV opioids for severe or refractory pain.
Local anesthetic wound instillation, TAP blocks, dexamethasone, gabapentin and ketamine are additional analgesic
options in select patients or as rescue analgesia following CD (Table 3). In the future, standardized treatment plans
may be replaced with individual plans that utilize treatments tailored around specific patient needs. 96,97 Additional
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studies are needed to better understand the development of chronic pain after CD, and refine treatments that can
reduce the occurrence of persistent incisional pain.39
Table 3: Drug Dose and Route Prescribing Information

Routine Neuraxial IT morphine 150 µg With IT hyperbaric bupivacaine 12 mg +
care* morphine or fentanyl 15 µg
Epidural morphine 3 mg
NSAIDs Ibuprofen 600 mg PO (or Every 6 h for 48–72 h
ketorolac 15 mg IV if NPO)
Acetaminophen Acetaminophen 650 mg PO Every 6 h for 48–72 h
(or IV if NPO/vomiting)
Oral opioids Oxycodone 5–10 mg PO As needed for breakthrough pain
Ongoing or IV opioids IV morphine, fentanyl, or Intermittent IV boluses or IV patient-
severe pain hydromorphone controlled analgesia
Regional Bilateral TAP block 0.25% ropivacaine 20–25 mL each side
anesthesia Single-shot ± catheter
Oral adjuvants Gabapentin 600 mg PO single dose
(300 mg PO every 8 h for ongoing pain)
Dexamethasone 4-8 mg IV single dose
*For women identified at risk for severe postoperative pain (e.g. chronic pain, opioid tolerant), consider
postoperative patient-controlled epidural analgesia (with local anesthetic and opioid); or local anesthetic wound
instillation (0.5% ropivacaine 5 mL/h subfascially for 48–72 h post-CD); dexamethasone 4-8 mg after delivery; or
ketamine 10–15 mg IV after delivery of the baby.
Based on the analgesic protocol utilized at Lucile Packard Children’s Hospital, Stanford University, California.
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Upper Extremity Regional Anesthesia: Essentials for Your Practice
Joseph M. Neal, MD Seattle, Washington
Dr. Neal has no conflicts of interest related to this presentation and receives no financial support from any entity
other than his employer
Upon completion, participants will be able to:
1. Distinguish those techniques that can improve block success
2. Recognize the nuances of local anesthetics and additives used for upper extremity blocks
3. Identify the prevention and treatment of block-related complications
Regional anesthesia for shoulder and arm/hand ambulatory surgery improves early outcome measures such as better
analgesia, decreased opioid-related side effects, earlier readiness for discharge, and reduced frequency of unplanned
hospital admission. After single injection blocks, these advantages do not exceed 24 hours and may be accompanied
by significant rebound pain upon block resolution. Continuous perineural catheters consistently improve analgesia,
and may facilitate earlier hospital discharge and rehabilitation after major shoulder surgery. This information is
important, because it provides objective data that brachial plexus regional anesthesia can positively affect outcome
in patients undergoing upper extremity surgery.
This refresher course lecture focuses on the selection of approaches to the brachial plexus, techniques to improve
block quality, important pharmacologic considerations, and complications associated with upper extremity neural
blockade. Because of time and space constraints, actual techniques of performing upper extremity blocks will not be
discussed. Participants are referred to classic textbooks and atlases for this information.
APPROACHES TO THE BRACHIAL PLEXUS
Knowledge of surgical site and brachial plexus anatomy combine to determine one’s approach to the brachial
plexus. The interscalene approach is ideally suited for shoulder surgery, but less appropriate for surgery distal to the
elbow because of its propensity to spare the lower trunk (ulnar distribution). The supraclavicular approach is
appropriate for most upper extremity surgery, although shoulder surgery may require supplemental supraclavicular
nerve (C3-C4) block. The infraclavicular approach provides anesthesia distal to the shoulder and is consistently
superior to the axillary approach for hand and arm surgery, in part because it more efficiently anesthetizes the
axillary and musculocutaneous nerves. The axillary approach provides anesthesia for surgeries of and distal to the
elbow, but specific blockade of the musculocutaneous nerve is advised if the surgical field involves the volar radial
forearm.
TECHNIQUES THAT IMPROVE BLOCK SUCCESS
Nerve Localization
Despite over a century experience with brachial plexus blockade, studies have failed to identify a superior method to
localize nerves. Indeed, block success (a term that unfortunately encompasses multiple definitions) plateaus at 90-
98% regardless of whether nerves are localized using peripheral nerve stimulation, paresthesia, or in the case of
axillary block, perivascular techniques. When compared to peripheral nerve stimulation, randomized clinical trials
variably show that the use of ultrasound-guided regional anesthesia (UGRA) improves block onset, reduces block
performance time and the number of needle passes, and results in more reliable blockade of the lower trunk via the
interscalene approach. However, rates for surgical readiness and block success are similar. With the exception of
reduced local anesthetic systemic toxicity (LAST), studies of UGRA have yet to prove increased safety as compared
with other localization techniques.
Ideal Number of Injections

Regardless of how a nerve is located, the ideal number of injections to optimize block quality is block- and
localization technique-specific. Ultrasound-guided blocks are typically multiple injection techniques that
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surround the nerves with local anesthetic. Nerve stimulator-guided interscalene and supraclavicular approaches to
the brachial plexus achieve reliable blockade after a single injection. As the brachial plexus architecture begins to
diverge into more widely spaced components, the value of increasing the number of local anesthetic injections
becomes evident. Double or triple ultrasound-guided injection leads to faster supraclavicular block onset.
Infraclavicular brachial plexus block is improved with double rather than single injection, particularly when one of
the stimulations involves the posterior cord. A single posterior injection appears adequate for UGRA techniques.
Landmark-based axillary blocks are improved by using three, but not four, injections. Injecting near the radial nerve
is most important for attaining optimal anesthesia using the axillary approach, while injecting near the ulnar nerve is
least important. Recent studies suggest that a two-injection ultrasound-guided technique (injecting at the
musculocutaneous nerve and at the 6 o’clock position below the axillary artery) may be equally efficacious to a
triple- or quadruple-injection nerve stimulation technique.
Continuous Perineural Catheters

Extended analgesia can be accomplished with continuous perineural catheters. Particularly for painful shoulder
surgeries, continuous perineural catheters provide superior analgesia, limit opioid-related side effects, and improve
patient satisfaction and sleep. This technology has proven useful and safe for outpatients. There is less evidence that
perineural catheters improve economically-sensitive parameters such as earlier return to work, long-term
rehabilitation, or other health-related quality of life measures.
PHARMACOLOGIC CONSIDERATIONS
Local Anesthetics
Local anesthetic selection for upper extremity regional anesthesia is determined primarily by the desired anesthetic
and analgesic duration. There is no inherent advantage of one local anesthetic over another with regard to block
quality, although limited data suggest that ropivacaine infusion preserves motor function better than bupivacaine.
For single-injection brachial plexus blockade, bupivacaine 0.5% is equipotent to ropivacaine 0.75%, which implies
that the advantage of reduced cardiotoxicity with ropivacaine may be offset if an increased mass (concentration x
volume) of ropivacaine is required to overcome its reduced potency. There is no advantage to mixing a long-acting
and an intermediate-acting local anesthetic—block onset is similar, but duration is shorter than would be achieved
with the long-acting local anesthetic alone.
While it is intuitive to increase local anesthetic mass to optimize block characteristics, existing evidence suggests
that doing so does not provide clinically relevant improvements when using traditional volume techniques, i.e., 20
mL or greater. Indeed, increasing local anesthetic concentration, volume, or total dose does not hasten block onset,
improve quality, or prolong analgesia. Instead, increased concentration correlates with neurotoxic injury, while
increased mass worsens LAST. Thus, modifying local anesthetic characteristics to facilitate neural blockade is
ineffective, but conceivably places the patient at increased risk should nerve injury or LAST occur. Ultrasound-
guidance further supports this concept, as excellent block characteristics are attainable using lower volumes of local
anesthetic. However, there is emerging evidence that block duration may be reduced when extremely low volumes
(less than 10 mL) are used. In the setting of continuous perineural analgesic techniques, evidence suggests that
initial bolus dosing can be accomplished with relatively low volumes and concentrations of local anesthetic, e.g., 20
mL of 0.375% ropivacaine for interscalene block, followed by 0.2-0.3% ropivacaine infusion.
Additives
In the absence of continuous perineural techniques, limited prolongation of analgesia is achievable with local
anesthetic additives. Yet despite a myriad of choices, only epinephrine, clonidine, and buprenorphene reliably
prolong blockade from intermediate-acting local anesthetics. Those adjuvants do not significantly affect long-acting
local anesthetics, whereas dexmedetomidine 150 mcg has been shown to increase the duration of ropivacaine
interscalene blockade by about 4 hours. Dexmedetomidine as a perineural additive is an off-label use in the United
States and has received limited human study; in one study its perineural effect was similar to that associated with
intravenous administration. Epinephrine prolongs peripheral nerve blockade by reducing clearance of the local
anesthetic, in addition to serving as a marker of intravascular injection. Epinephrine 2.5 mcg/mL (1:400,000)
achieves nearly the same block prolongation as 5 mcg/mL (1:200,000), but with less tachycardia and less reduction
in peripheral nerve blood flow. Clonidine 0.5 mcg/kg prolongs anesthesia and analgesia by 50% for intermediate-
acting local anesthetics, but <20% for long-acting agents (~2 hr. prolongation for either epinephrine or clonidine).
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However, clonidine can cause sedation (NNH 5) or hypotension (NNH 10) and lacks epinephrine’s ability to signal
intravascular injection. Clonidine is significantly more expensive than epinephrine; it is unclear if one is superior to
the other or if indeed their actions are synergistic. Neither epinephrine nor clonidine improves sensory block quality
when used during continuous infusion. Buprenorphene 0.3 mg prolongs duration of analgesia after axillary block.
Dexamethasone has been shown in limited studies with widely variable results to prolong the duration of
mepivacaine analgesia to a degree similar to epinephrine or clonidine (~50%). However, recent commentary raises
concerns about neurotoxicity with dexamethasone, particularly in diabetic patients or in doses that exceed 1 mg.
Furthermore, dexamethasone studies that incorporate a systemic injection control group generally find little
advantage of perineural injection as compared to intravenous injection. Other additives—opioids, neostigmine,
hyaluronidase, tramadol, and calcium channel blockers—serve no useful purpose in brachial plexus blockade, are
reported without comparison to a systemic control group, or are incompletely studied with regards to neurotoxicity.
Alkalinization of intermediate-acting local anesthetics does not accelerate brachial plexus block onset, despite its
usefulness in hastening the onset of epidural block. Moreover, alkalinization has been shown in animals to actually
reduce block duration and intensity. The use of liposomal bupivacaine around a neural plexus remains off-label and
the dearth of published data limit any recommendation at this time.
COMPLICATIONS OF BRACHIAL PLEXUS BLOCKS
Local Anesthetic Systemic Toxicity

Two unique circumstances related to brachial plexus blockade affect LAST. First, seizures associated with local
anesthetic injection are five times more likely to occur with peripheral nerve block than with epidural block. Second,
brachial plexus approaches are particularly prone to systemic toxicity because they are often placed near arteries that
directly supply the brain, thus seizures can occur after remarkably small doses of local anesthetic, e.g., 2.5 mg
bupivacaine injected into the vertebral artery during the interscalene approach. Case reports document episodes of
LAST despite the use of UGRA, although recent studies report ~65% decrease in the incidence of LAST when
ultrasound-guidance is used rather than peripheral nerve stimulation. In accordance with the ASRA Practice
Advisory on Local Anesthetic Systemic Toxicity, lipid emulsion should be readily available to treat local anesthetic
toxicity wherever upper extremity blocks are performed.
Unintended Destinations of Local Anesthetics

Needles can be placed unintentionally near the
neuraxis during interscalene block by advancing too
far medial into the epidural, subdural, or subarachnoid
space. The distance from the skin overlying the
interscalene groove-to-the neuraxis is 23-35mm. Local
anesthetic can also enter the subarachnoid space if a
needle (seemingly placed at the proper depth)
punctures a particularly long dural root sleeve. (Figure
1) When local anesthetic reaches the neuraxis, high
spinal anesthesia or massive epidural anesthesia
develops, which may be particularly difficult to
diagnose in an anesthetized patient. If this happens,
patients may present with unexpectedly high, and
bilateral, sensory and motor block, bradycardia,
hypotension, or asystole. Treatment is the same as for
hypotension / bradycardia following spinal anesthesia,
and includes early epinephrine to increase heart rate,
contractility, and coronary perfusion pressure. Figure 1. Neal & Rathmell, 2013
Unintended destinations of local anesthetics can also result in nuisance symptoms such as Horner’s syndrome from
blockade of the cervicothoracic sympathetic trunk, or hoarseness from blockade of the vagus and/or recurrent
laryngeal nerves. These symptoms dissipate with resolution of local anesthetic blockade.
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Hypotension / Bradycardia
Awake or mildly/moderately sedated patients who

undergo interscalene brachial plexus block and are
placed in the beach-chair position are reported to
develop sudden hypotension and bradycardia in 13-
24% of cases. These hemodynamic changes typically
occur about an hour after block placement. The
etiology of this condition is unclear, but is believed to
involve relative preload deficit (from the sitting
position) plus increased ventricular contractility (from
exogenous and endogenous epinephrine), both
combining to (arguably) activate the Bezold-Jarisch
reflex. (Figure 2) Incidence can be reduced with
metoprolol pre-treatment, but not glycopyrrolate.
Figure 2. Neal & Rathmell, 2013

Inadequate Cerebral Perfusion
Rare cases of cerebrovascular accident have

been reported in patients undergoing shoulder
surgery in the beach chair or upright position.
Although not specifically a complication of
upper extremity regional anesthesia,
practitioners should be aware of this
complication, the etiology of which is not
entirely certain, especially its association with
hypotension. Nevertheless, issues of particular
concern include measuring blood pressure at the
appropriate site or performing hydrostatic
calculations to accurately reflect pressure at the
level of the brain (1.33cm from cuff to brain =
1mmHg reduced pressure at the brain). (Figure
3) Some experts argue that patients in the beach
chair position should maintain mean arterial
pressures of at least 75 mmHg (measured at the
arm).
Pneumothorax
Pneumothorax can occur with the supraclavicular approach; less so with the interscalene and infraclavicular
approaches. Importantly, symptoms may not become noticeable for 8-12 hours following the block, particularly in
the absence of positive pressure ventilation. Pleuritic chest pain is the most common presenting symptom, not
dyspnea. Development of techniques designed in part to avoid the pleura, such as the plumb bob or subclavian
perivascular approaches, or UGRA, have likely reduced the incidence of pneumothorax significantly, although no
large studies confirm this impression. Based on reported cases, the risk of pneumothorax associated with ultrasound-
guided supraclavicular block is 1:1000 (calculated upper limit, 95% confidence interval).
Vascular and Muscle Injury

Minor bruising occurs in up to a quarter of patients after axillary block. Serious vascular conditions—compressing
hematoma, vasospasm, or arterial dissection—are rare, but should be considered in patients with postoperative
neurologic impairment. The ASRA Consensus Conference on Anticoagulation and Regional Anesthesia suggests
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that deep brachial plexus blocks, e.g., cervical paravertebral or infraclavicular, not be undertaken in anticoagulated
patients. Temporary myotoxicity can happen when local anesthetic, particularly bupivacaine, is infused into muscle.
Hemidiaphragmatic Paresis
All landmark-based interscalene blocks and ~50% of supraclavicular blocks result in temporary hemidiaphragmatic
paresis (HDP) secondary to anesthesia of the phrenic nerve. During interscalene anesthesia, a small subset of
patients experience 25-32% reduction in pulmonary spirometric values. Pulmonary function is unaffected in healthy
volunteers whose hemidiaphragm is paretic following supraclavicular block, but this may not be the case in patients
with compromised pulmonary function. The incidence and severity of HDP can be reduced, but not completely and
predictably eliminated, when local anesthetic volumes are decreased to 5-10 mL using UGRA. The ultrasound-
guided approach probably blocks the phrenic nerve because of its proximity to the C5 nerve root. (Figure 4) Above
the clavicle blocks are relatively contraindicated in patients unable to withstand a ~30% reduction in pulmonary
function. Hemidiaphragmatic paresis following infraclavicular block is rare with the coracoid approach, but ~25%
of patients who undergo the (more medial) vertical infraclavicular approach develop HDP with an accompanying
30% reduction in spirometric values.
Refresher Course Lectures Anesthesiology 2016Figure 4. Neal

© American & Rathmell,
Society 2013
of Anesthesiologists. All rights reserved. Note: This
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Peripheral Nerve Injury

The use of an interscalene block does not increase the baseline risk of nerve injury associated with total shoulder
arthroplasty. Permanent peripheral neuropathy associated with brachial plexus block is a decidedly rare event (95%
confidence interval, 0–16 / 10,000 patients). Depending on how it is defined, temporary nerve dysfunction in the
early postoperative period may occur in up to 19% of patients and typically presents within the first 48 hours. Most
symptoms resolve by 6 weeks; well less than 0.1% remain after a year. Up to 10% of upper extremity elective
orthopedic surgery patients will experience a transient (and rarely, permanent) injury inherent to the surgical
procedure itself. When a patient sustains a peripheral nerve injury after brachial plexus block it is crucial the
anesthesiologist recognize that the vast majority of these incidents are related to surgical factors—direct nerve
trauma, positioning injury, stretch injury, or compressive etiologies from hematoma, edema, or the application of
constrictive tourniquets, casts, or dressings. When motor function is impaired, the injury appears to be progressive,
or improvement is not obvious after a few postoperative days, early neurological consultation is advised. Although
abnormalities on neurophysiologic studies (EMG, nerve conduction studies) are most apparent 2 to 3 weeks after
injury, earlier evaluation may be beneficial when injuries meet the above noted criteria. Early, bilateral neurologic
evaluation may establish baseline, document pre-existing conditions, or identify reversible lesions.
Factors associated with anesthesia-related peripheral nerve injury are poorly understood. No human data exist to
guide our choice of short- vs. long-beveled needles in preventing injury. The relationship of paresthesia elicitation to
peripheral nerve injury is equally unclear. Pain on injection of local anesthetic is generally regarded as a sign of
potential nerve damage, but case reports suggest that this is an inconsistent warning sign. Not all pain on injection is
associated with clinical injury. In contrast, there are reports of injury occurring when pain on injection was
immediately followed by discontinuation of injection, implying that even if a warning occurs, the damage may
already be done. There is no evidence that using UGRA reduces the incidence or severity of nerve injury, but there
are case reports of injury despite the use of ultrasound. Two risks specific to brachial plexus regional anesthesia
deserve comment. Reports of intramedullary spinal cord injection during interscalene block under general anesthesia
while using the classic interscalene groove approach suggest that this practice may be dangerous. Furthermore,
reports of peripheral nerve injury after supplemental selective nerve block performed at the elbow or wrist in
patients with incomplete proximal brachial plexus blockade suggest that this practice too may be risky. There are no
data to confirm or refute the contention that UGRA can reduce these risks.
In the absence of those rare instances when a

needle fully or partially transects a nerve,
anesthesia-related nerve injury is believed to result
from a combination of factors. First, harmful
needle contact or intrafascicular (subperineurium)
injection damages the nerve-blood barrier. Once
this protective barrier is breached, normally
innocuous local anesthetics can cause

neurotoxicity, which in turn can be worsened if
epinephrine impairs clearance of local anesthetic
from the perineural area and/or causes ischemia to
the injured nerve. (Figure 5) Peripheral nerve
injury may also occur in the setting of a ‘double
crush’ phenomenon. This theory suggests that
when nerves already compromised by an existing
subclinical injury, e.g., cervical disc disease,
diabetes mellitus, or neurotoxic chemotherapy, are
then exposed to a second relatively minor injury,
e.g., surgical positioning or a minor needle injury,
significant clinical injury becomes manifest. There
is clinical evidence to both confirm and refute the
role of “double crush” in peripheral nerve injury.
We inadequately understand these rare and usually
temporary, but occasionally devastating,
peripheral nerve injuries associated with brachial
plexus regional anesthesia.
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Complications of Continuous Perineural Blocks

Continuous perineural catheters do not appear to consistently increase complication rates as compared to single-
injection techniques. Within the limitations of relatively few published studies, nerve injury does not appear to be
increased. Similar to single-injection interscalene block, nerve injury has been associated with catheter placement in
anesthetized patients. While the incidence of bacterial colonization is high (~39%), actual abscess formation is low
(0.07%).
SELECTED READINGS1-24
1. Abdallah FW, Johnson J, Chan V et al. Intravenous dexamethasone and perineural dexamethasone
similarly prolong the duration of analgesia after supraclavicular brachial plexus block. A randomized,
double-blind, placebo-controlled trial. Reg Anesth Pain Med 2015;40:125-132.
2. Abdallah FW, Halpern SH, Aoyama K, Brull R. Will the real benefits of single-shot interscalene block
please stand up? A systematic review and meta-analysis. Anesth Analg 2015;120:1114-1129.
3. Abdallah FW, Dwyer T, Chan VWS et al. IV and perineural dexmedetomidine similarly prolong the
duration of analgesia after interscalene brachial plexus block. A randomized, three-arm, triple-masked,
placebo-controlled trial. Anesthesiology 2016;124:683-695.
4. Barrington MJ, Kluger R. Ultrasound guidance reduces the risk of local anesthetic systemic toxicity
following peripheral nerve blockade. Reg Anesth Pain Med 2013;38:289-297.
5. Bernuci R, Gonzalez AP, Finlayson RJ, Tran DQH. A prospective, randomized comparison between
perivascular and perineural ultrasound-guided axillary brachial plexus block. Reg Anesth Pain Med
2012;37:473-477.
6. Borgeat A, Ekatodramis G, Kalberer F, Benz C. Acute and nonacute complications associated with
interscalene block and shoulder surgery. A prospective study. Anesth Analg 2001;95:875-880.
7. Capdevila X, Dadure C, Bringuier S et al. Effect of patient-controlled perineural analgesia on rehabilitation
and pain after ambulatory orthopedic surgery. A multicenter randomized trial. Anesthesiology
2006;105:566-573.
8. Dwyer T, Henry PDG, Cholvisudhi P, Chan VWS, Theodoropoulos JS, Brull R. Neurological
complications related to elective orthopedic surgery. Part 1: Common shoulder and elbow procedures. Reg
Anesth Pain Med 2015;40:431-442.
9. Fritsch G, Danninger T, Allerberger K et al. Dexmedetomidine added to ropivacaine extends the duration
of interscalene brachial plexus blocks for elective shoulder surgery when compared with ropivacaine alone.
A single-center, prospective, triple-blind, randomized controlled trial. Reg Anesth Pain Med 2014;39:37-
47.
10. Gadsden J, Hadzic A, Gandhi K et al. The effect of mixing 1.5% mepivacaine and 0.5% bupivacaine on
duration of analgesia and latency of block onset in ultrasound-guided interscalene block. Anesth Analg
2011;112:471-476.
11. Handoll HHG, Koscielniak-Nielsen ZJ. Single, double or multiple injection techniques for axillary brachial
plexus block for hand, wrist or forearm surgery. The Cochrane Database of Systematic Reviews 2006;Art.
No.: CD003842:DOI: 10.1002/14651858.CD14003842.pub14651852.
12. Horlocker TT, Wedel DJ, Rowlingson JC et al. Regional anesthesia in the patient receiving antithrombotic
or thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based
Guidelines (Third Edition). Reg Anesth Pain Med 2010;35:64-101.
13. Ilfeld BM. Continuous peripheral nerve blocks: A review of the published evidence. Anesth Analg
2011;113:904-925.
14. McCartney CJ, Brull R, Chan VW et al. Early but no long-term benefit of regional compared with general
anesthesia for ambulatory hand surgery. Anesthesiology 2004;101:461-467.
15. Neal JM, Gerancher JC, Hebl JR et al. Upper extremity regional anesthesia. Essentials of our current
understanding, 2008. Reg Anesth Pain Med 2009;34:134-170.
16. Neal JM, Bernards CM, Butterworth JF et al. ASRA practice advisory on local anesthetic systemic toxicity.
Reg Anesth Pain Med 2010;35:152-161.
17. Neal JM, Rathmell JP: Complications in Regional Anesthesia and Pain Medicine. 2nd ed. Philadelphia:
Lippincott Williams & Wilkins, 2013.
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18. Neal JM, Barrington MJ, Brull R et al. The second ASRA practice advisory on neurologic complications
associated with regional anesthesia and pain medicine: Executive summary, 2015. Reg Anesth Pain Med
2015;40:401-430.
19. Neal JM, Brull R, Horn JL et al. The second ASRA evidence-based medicine assessment of ultrasound-
guided regional anesthesia. Executive summary of 2015 update. Reg Anesth Pain Med 2016;41:181-194.
20. Neal JM. Ultrasound-guided regional anesthesia and patient safety: Update of an evidence-based analysis.
21. Parrington SJ, O'Donnell D, Chan VWS et al. Dexamethasone added to mepivacaine prolongs the duration
of analgesia after supraclavicular brachial plexus block. Reg Anesth Pain Med 2010;35:422-426.
22. Sites BD, Chan VW, Neal JM et al. The American Society of Regional Anesthesia and Pain Medicine
(ASRA) and The European Society of Regional Anaesthesia and Pain Therapy (ESRA) Joint Committee
recommendations for education and training in ultrasound guided regional anesthesia. Reg Anesth Pain
Med 2010;35:S74-S80.
23. Sviggum HP, Jacob AK, Mantilla CB, Schroeder DR, Sperling JW, Hebl JR. Perioperative nerve injury
after total shoulder arthroplasty: assessment of risk after regional anesthesia. Reg Anesth Pain Med
2012;37:490-494.
24. Williams BA, Schott NJ, Mangione MP, Ibinson JW. Perineural dexamethasone and multimodal perineural
analagesia: How much is too much? Anesth Analg 2014;118:912-914.
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Failed laryngoscopy—what now?
Richard M. Cooper, BSc, MSc, M.D., FRCPC. Toronto/ON Canada
What do we mean by failed laryngoscopy?
A “difficult airway” includes problems encountered performing one or more of 1) laryngoscopy, 2) intubation, 3)
ventilation by facemask or supraglottic device or 4) an emergent surgical airway. Difficulty may also be encountered
in re-establishing an airway following extubation.
Successful laryngoscopy and intubation may be related but they are not interchangeable. As airway managers, our
purpose in performing laryngoscopy is to enable visualized placement of an endotracheal tube. If we fail to visualize
the larynx, then laryngoscopy has failed. Blind placement of an endotracheal tube may be a successful intubation but
it should be understood to be a failed laryngoscopy. On the other hand, when laryngoscopy provides a good
laryngeal view but intubation can’t be achieved, it’s of limited value to the anesthesiologist. Inherent in the
distinction between successful laryngoscopy and intubation is the belief that blind intubation is more likely to be
injurious than a visually controlled intubation. The current ASA Airway Task Force Practice Guidelines generally
regard an airway event as difficult when a conventionally trained anesthesiologist requires “multiple attempts.” 1
How often does failed laryngoscopy occur?
We are advised to conduct a thorough bedside airway evaluation prior to initiating airway management although
these guidelines also state that there is insufficient evidence supporting the value of this assessment in predicting
difficulty.1 Often forgotten is that these bedside predictors for laryngoscopy were developed specifically for direct
laryngoscopy (DL) and may not be relevant when other techniques are used. Indeed, most studies fail to even
describe the device employed. A meta-analysis of 35 studies involving 50,760 adults with seemingly normal airway
anatomy found that the commonly performed bedside tests had only moderate predictive value and a Cormack-
Lehane grade III view (“failed laryngoscopy”) was seen in 5.8% of patients.2 Even more worrisome is a Danish
study that looked at a national database of 188,064 adults intubated for anesthesia. Anesthesiologists were required
to indicate whether difficulty was anticipated (Y/N). They found that 93% of “difficult intubations” performed by
DL were unanticipated, requiring more than 2 attempts, rescue with an alternative device or failing outright.3
Intubation difficulty is probably better described along a continuum. 4 An intubation difficulty scale (IDS) looks at
parameters including the laryngeal view, number of attempts, number of operators, alternative techniques and the
amount of applied force. Minor airway difficulty was encountered in 37% of routine anesthetics; moderate
intubation difficulty (IDS>5) was encountered in nearly 8% of 1171 consecutive anesthetized patients.5
Furthermore, moderately difficulty was encountered more than twice as frequently when intubation was attempted
outside of the operating room.6,7 In the operating room, three or more attempts using DL have been required in about
1-2% of patients.8
What do we do when DL fails?
DL frequently fails because of our inability to achieve a direct line of sight (see figure 1). This may be dealt with in
several ways: repeated attempts9 with increasing force, positional adjustments, adjuncts (e.g. stylets, tracheal
introducers), external laryngeal manipulation, a call for assistance, the use of alternative devices (e.g. video
laryngoscopes, optical stylets, flexible endoscopy), reversion to face mask or supraglottic ventilation, waking the
patient or performance of a surgical airway.
There is evidence that multiple intubation attempts incur incremental risk. Mort has demonstrated that outside the
operation room more than two laryngoscopy attempts significantly increased the risk of SpO2 <70% 14-fold,
esophageal intubation 6-fold, regurgitation 7-fold and cardiac arrest 7-fold.10 In the emergency department, the
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Figure 1 (from Cormack and Lehane 1984, with permission of the publisher)
number of adverse events increased with multiple attempts. From the first to the fourth intubation attempt the
percentage of patients suffering adverse events increased from 14%, 47%, 64% and 71% respectively. 11
More than one attempt at tracheal intubation was a significant predictor of one or more adverse events (adjusted OR-
7.52, CI 5.86-9.63). Although these studies were performed outside the operating room, they likely apply to
critically ill patients in any location and may be relevant to healthy surgical patients as well. They suggest that we
should minimize the number of required intubation attempts and strive to achieve first pass success (FPS). 7,12,13
“Never fail to prepare for failure”14
An airway manager’s overall objective is maintaining oxygenation, whether by facemask, supraglottic airway,
tracheal tube or an emergent surgical airway. Patient harm is more likely to occur as a result of persistence with
ineffective techniques.
Our first intubation attempt should be optimal using a familiar device, proper patient and operator positioning, an
appropriate tracheal tube (with a pre-inserted or immediately available stylet or tracheal tube introducer) and
suitable drugs. If in spite of this, we fail to view the larynx, we should reassess the situation. We might now know
that DL will not succeed—multiple attempts are not only unnecessary but possibly harmful. Oxygenation can be
more objectively assessed than the adequacy of ventilation; believe the oximeter since ventilation is frequently
misjudged in stressful circumstances.
The ASA Difficult Airway Algorithm may be educationally helpful and conceptually formulating a strategy, but it is
complex and may produce cognitive overload in an emergency. Furthermore, these and other guidelines represent a
concerted effort to be evidence-based but high-quality evidence is often lacking. For the most part they are a
consensus of expert opinions.8,15-18 They were not intended to dictate practice but rather to guide the decisions made
by thoughtful care providers. Perhaps a more appropriate device is a “cognitive aid” such as the Vortex Airway
which does not compete with existing algorithms but rather serve as a checklist that can be posted and read aloud
when airway problems are encountered (Figure 3).19 This tool, or one like it, will ensure that details have not been
overlooked. Perhaps even more useful, is the simplified construct
of a “vortex” wherein critical decisions must be made with
increasing rapidity as oxygenation deteriorates (Figure 2). In the
“green zone,” there is time to consider moving between a face
mask, supraglottic airway or limited attempts at laryngoscopy with
adjustments in position, adjuncts, a different laryngoscope blade,
the addition of a stylet, external laryngeal manipulation etc. In the
“blue zone,” failing oxygenation makes immediate rescue
essential. It should be recognized, declared and preparations
initiated for an emergency surgical airway, even if ultimately not
required. A delay in recognizing such a situation may have a
catastrophic outcome.
Figure 2 (Vortex Airway Approach©—reproduced with permission

from Nicholas Chrimes)19
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Failed laryngoscopy with adequate oxygenation
If oxygenation is adequate, there is time to consider other options, which may include the use of a supraglottic
airway, using the supraglottic airway as a conduit for intubation, waking the patient and postponing surgery or
managing the airway awake.1,8,16 It is best to declare the proposed strategy aloud. This prepares the team and
maximizes their value to the airway manager. Ancillary equipment can be prepared so that it is immediately
available. It may also reduce fixation errors, summon additional expertise and a difficult airway cart. The difficult
airway cart reduces subsequent delays and may serve as an additional cognitive aid. The options are visibly and
physically before our eyes. It is important to balance the operator’s airway experience, clinical judgment and
maintain an openness to alternative suggestions. Ego is an obstacle to a good outcome.
Figure 3 (Reproduced with permission from Nicholas Chrimes)
Oxygenation and protection from aspiration are always of paramount importance. If no laryngeal view is obtained,
simple adjustments may be considered, but the probability of success should be weighed against the time required to
perform them. For example, external laryngeal pressure20 (or BURP) and/or head elevation21 can be considered,
taking little time. A blade change may be considered though this is likely to be helpful in limited circumstances. A
tracheal tube introducer (aka “bougie”) can be attempted if its coudé tip can be visually positioned beneath the
epiglottis and directed through the vocal cords.8
The availability of video laryngoscopy and optical stylets has dramatically changed airway management. Because
these devices are not reliant upon a line-of-sight (figure 1), when positioned at the tongue base, they often provide
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an excellent glottic view, converting a blind procedure into one that can be visually controlled. This does require
additional skills to deliver and advance a tracheal tube.22 Such skills are best acquired by routine practice, not when
attempting to rescue a failed airway. When oxygenation can be maintained and intubation is deemed appropriate,
efforts should be made to perform this under visual guidance. 16
Aziz and co-workers examined the electronic anesthetic records at two centers and found 2,004 instances wherein
the GlideScope Video Laryngoscope (GVL, Verathon Medical, Bothell WA) had been used. This represented 2.8%
of intubations attempted, most of these patients having features predictive of a difficult DL. Of particular relevance
to this discussion is the subset of patients in whom the GVL was used after DL had failed. This consisted of 239
patients. The success rate for a rescue was high but it differed at the two centers: 143/148 vs. 81/91. At the center
with the higher success rate, the providers had performed a median of 19 GVL-assisted intubations compared with 6
at the other center.23 Beyond proving its value in the rescue of failed DL, this study demonstrated that performance
improves with experience. Numerous studies in a variety of settings, including emergency departments, critical care
and obstetrical units have demonstrated the effectiveness of various VL in patients predicted to be difficult DL.24-32
The CAFG Guidelines concluded that “incremental risk must be assumed with each failed attempt such that a
second or third tracheal intubation attempt should only occur if a different tactic is used with a reasonable
expectation of success. Proceeding with more than three attempts at tracheal intubation requires compelling
justification.”8 The Difficult Airway Society (DAS) Guidelines recommend a maximum of three attempts, a fourth
being acceptable if undertaken by a more experienced person. 16
Although exacting science may not support a specific limit on the number of attempts, it sets the goal posts,
increasing the likelihood that efforts will not be wasted with ineffective methods that may cause incremental risk to
the patient. If tracheal intubation cannot be achieved within three attempts, but oxygenation is adequate, the choices
are to 1) awaken the patient, 2) continue anesthesia with a facemask or SGA, 3) call for help bringing additional
equipment and assistance or 4) when surgery cannot be deferred and alternative strategies are unlikely to succeed, to
proceed with a surgical airway despite the adequate oxygenation.1,8
Failed intubation with non-reassuring oxygenation
Clinicians frequently fail to appreciate the inadequacy of ventilation. Failing oxygenation may be more readily
identified. The shape of the oxy-hemoglobin dissociation curve is such that as SpO2 declines, further deterioration
may be precipitous and the time required to remedy the situation may be insufficient to prevent serious patient harm.
Non-reassuring oxygenation implies that the situation is worsening and it mandates prompt action: 1) recognition, 2)
a call for additional help and 3) preparation for surgical access. In this setting, the provider should ensure that
neuromuscular blockade is adequate as this may facilitate both ventilation and laryngoscopy. 16
The advent of an induction technique permitting the rapid recovery of spontaneous ventilation has the potential of
being a game-changer. Strategies such as succinylcholine, inhalation induction with low-solubility volatile agents
and ultra-short acting narcotics (remifentanil) without neuromuscular blocking agents, have been disappointing in
this context. Sugammadex offers the possibility of very rapid reversal of rocuronium-induced paralysis. However, its
value may be limited by the time required to identify the “can’t intubate-can’t oxygenate” (CICO), to obtain and
prepare the drug and the possibility of pre-existing or induced airway obstruction. These may prevent adequate
oxygenation despite a resumption of spontaneous respiratory efforts. 33
If resources permit, an additional attempt to place a SGA may be made if it does not delay preparations for surgical
access. If oxygenation and ventilation can be re-established with a SGA, a medical emergency may have been
averted and a thoughtful approach to the next step can be made. This might include a wake-up of the patient,
persistence with the SGA or use of the SGA as a conduit for tracheal intubation. The latter approach should be part
of the airway armamentarium of all airway managers and practiced in non-urgent situations.34
The method chosen to achieve surgical access has been widely debated but most anesthesiologists agree that the site
is not a matter for debate—a cricothyroidotomy can be performed more quickly than a tracheotomy, with less risk of
vascular injury.35 The NAP4 report demonstrated that anesthesiologists in the UK performed this task poorly. 14
Indeed, 58 of 133 serious complications of airway management involved an attempted emergent surgical airway
with a failure rate of nearly 60%. Given that cognitive and motor performance declines in high-stress settings, and
notwithstanding the lack of evidence favoring one method over another, the recent DAS Guidelines endorsed the
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training of a standardized technique consisting of a #10 scalpel/ coudé-tipped introducer/ and 6mm cuffed tube
through the cricothyroid membrane.16 This procedure is performed infrequently but it is incumbent upon
anesthesiologist to be familiar with the equipment and technique.
The cricothyroid membrane is frequently incorrectly identified by palpation, particularly in females and obese
patients.36 If the space is incorrectly identified, positive pressure ventilation or jet ventilation will quickly result in
barotrauma, obscuring the landmarks, compromising subsequent attempts. The barotrauma may itself be fatal. The
cricothyroid membrane can be more accurately identified by ultrasound if time permits and the operator is
experienced.35 This argues for practicing the technique electively, when an ultrasound is available; when awake
intubation is planned, the site can be punctured to instill local anesthesia and the correct location can be visually
confirmed.
When difficulties have been encountered, it is our responsibility to ensure that we communicate with those
providing the subsequent care to minimize the risk of recurrence. Ideally, detailed clinically relevant information
should be accessible 24/7 from anywhere, even when the patient is insufficiently informed or unable to
communicate. This can be achieved by explaining to the patient and family the value of transmitting the information
and promoting registration in an accessible database.37
Despite our focus on management of the failed airway, we have actually made great strides. Advanced Airway
Management is emerging as a subspecialty with fellowships and relevant societies around the world. The first World
Airway Management Meeting took place in Dublin in November 2015. New pre-oxygenation strategies have been
shown to extend tolerance of apnea;38 there has been a proliferation of supraglottic airways providing more effective
ventilation and better protection from aspiration; video laryngoscopes are widely available and often provide good
laryngeal exposure when DL fails. Remote monitoring, mentoring and clinical documentation will potentially
improve clinical outcomes.39-41 Better selection of patients requiring awake intubation has been demonstrated by an
preoperative endoscopic airway assessment.42 This author is of the opinion that video laryngoscopy will emerge as
the standard of care for intubation. But it is not suitable for every situation and over-reliance on a single method will
undoubtedly lead to a decline in our performance with other essential tools. We must practice with a range of
devices, utilizing them whenever possible to ensure that we acquire and maintain the required skills to provide safe
care.
Key points
 The goal of airway management is the optimization of oxygenation and protection from aspiration.
 The airway should be assessed and whenever possible, previous records consulted in an effort to anticipate
difficulties with airway management. Bedside assessment is at best moderately sensitive and specific.
These apply specifically to DL and have limited relevance when alternative techniques are used.
 DL frequently fails to reveal the larynx. Simple maneuvers such as external laryngeal pressure, head lift of
the use of a tracheal introducer may be tried.
o Multiple attempts incur incremental risk and should only be made if there is a reasonable
expectation of success.
o A limit on the total number of permitted attempts increases the likelihood that unhelpful and
possibly harmful efforts will be reduced or eliminated.
o Failed laryngoscopy can often be rescued by indirect/video laryngoscopy in practiced hands.
o Oxygenation is a more objective management outcome than the adequacy of ventilation.
o Insertion of a supraglottic airway may restore ventilation/oxygenation but this may be
compromised by multiple intubation attempts.
o A well-seated supraglottic airway may function as an adequate airway or serve as a conduit for
endoscopic-assisted intubation.
o When failed laryngoscopy is encountered, the choices include a wake-up, ventilation by facemask
or supraglottic airway, an alternative device and a call for help.
 When failed laryngoscopy and non-reassuring oxygenation are encountered, time is limited. A cognitive aid
may reveal overlooked opportunities.
o Call for help and a difficult airway cart.
o Ensure adequate neuromuscular blockade to facilitate both ventilation and laryngoscopy.
o A single attempt at insertion of a supraglottic airway is appropriate.
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o Quickly consider whether Sugammadex is a viable option

o Preparation must be made for an emergency surgical airway.
 Communicate with subsequent care providers and encourage enrollment in a difficult airway registry
References
1. Apfelbaum JL, Hagberg CA, Caplan RA, Blitt CD, Connis RT, Nickinovich DG, Hagberg CA, Caplan RA,
Benumof JL, Berry FA, Blitt CD, Bode RH, Cheney FW, Connis RT, Guidry OF, Nickinovich DG, Ovassapian A:
Practice guidelines for management of the difficult airway: an updated report by the American Society of
Anesthesiologists Task Force on Management of the Difficult Airway. Anesthesiology 2013; 118: 251-70
2. Shiga T, Wajima Z, Inoue T, Sakamoto A: Predicting difficult intubation in apparently normal patients: a
meta-analysis of bedside screening test performance. Anesthesiology 2005; 103: 429-437
3. Norskov AK, Rosenstock CV, Wetterslev J, Astrup G, Afshari A, Lundstrom LH: Diagnostic accuracy of
anaesthesiologists' prediction of difficult airway management in daily clinical practice: a cohort study of 188 064
patients registered in the Danish Anaesthesia Database. Anaesthesia 2015; 70: 272-81
4. Benumof JL: Intubation difficulty scale: anticipated best use. Anesthesiology 1997; 87: 1273-1274
5. Adnet F, Racine SX, Borron SW, Clemessy JL, Fournier JL, Lapostolle F, Cupa M: A survey of tracheal
intubation difficulty in the operating room: a prospective observational study. Acta Anaesthesiol.Scand. 2001; 45:
327-332
6. Adnet F, Borron SW, Racine SX, Clemessy JL, Fournier JL, Plaisance P, Lapandry C: The intubation
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intubation. Anesthesiology 1997; 87: 1290-1297
7. Natt BS, Malo J, Hypes CD, Sakles JC, Mosier JM: Strategies to improve first attempt success at intubation
in critically ill patients. British Journal of Anaesthesia 2016; 10.1093/bja/aew061
8. Law JA, Broemling N, Cooper RM, Drolet P, Duggan LV, Griesdale DE, Hung OR, Jones PM, Kovacs G,
Massey S, Morris IR, Mullen T, Murphy MF, Preston R, Naik VN, Scott J, Stacey S, Turkstra TP, Wong DT: The
difficult airway with recommendations for management - Part 1 - Difficult tracheal intubation encountered in an
unconscious/induced patient. Canadian Journal of Anesthesia 2013; 60: 1089-1118
9. Rose DK, Cohen MM: The airway: problems and predictions in 18,500 patients. Can.J.Anaesth. 1994; 41:
372-383
10. Mort TC: Emergency tracheal intubation: complications associated with repeated laryngoscopic attempts.
Anesthesia Analgesia 2004; 99: 607-613
11. Sakles JC, Chiu S, Mosier J, Walker C, Stolz U, Reardon RF: The Importance of First Pass Success When
Performing Orotracheal Intubation in the Emergency Department. Academic Emergency Medicine 2013; 20: 71-78
12. Bernhard M, Becker TK, Gries A, Knapp J, Wenzel V: The First Shot Is Often the Best Shot: First-Pass
Intubation Success in Emergency Airway Management. Anesthesia and analgesia 2015; 121: 1389-93
13. Griesdale DE, Chau A, Isac G, Ayas N, Foster D, Irwin C, Choi P: Video-laryngoscopy versus direct
laryngoscopy in critically ill patients: a pilot randomized trial. Canadian journal of anaesthesia = Journal canadien
d'anesthesie 2012; 59: 1032-9
14. Cook TM, Woodall N, Frerk C: Fourth National Audit Project of the Royal College of Anaesthetists and
Difficult Airway Society. Major complications of airway management in the United Kingdom. Report and
Findings., Royal College of Anaesthetists London 2011 http://www.rcoa.ac.uk/nap4
15. Law JA, Broemling N, Cooper RM, Drolet P, Duggan LV, Griesdale DE, Hung OR, Jones PM, Kovacs G,
Massey S, Morris IR, Mullen T, Murphy MF, Preston R, Naik VN, Scott J, Stacey S, Turkstra TP, Wong DT: The
difficult airway with recommendations for management - Part 2 - The anticipated difficult airway. Canadian Journal
of Anesthesia 2013; 60: 1119-1138
16. Frerk C, Mitchell VS, McNarry AF, Mendonca C, Bhagrath R, Patel A, O'Sullivan EP, Woodall NM,
Ahmad I: Difficult Airway Society 2015 guidelines for management of unanticipated difficult intubation in adults.
British journal of anaesthesia 2015; 115: 827-48
17. Frova G, Sorbello M: Algorithms for difficult airway management: a review. Minerva Anestesiol 2009; 75:
201-9
18. Heidegger T, Gerig HJ, Henderson JJ: Strategies and algorithms for management of the difficult airway.
Best.Pract.Res.Clin.Anaesthesiol. 2005; 19: 661-674
19. Chrimes N, Fritz P: The Vortex Approach: Management of the Unanticipated Difficult Airway.
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20. Benumof JL, Cooper SD: Quantitative improvement in laryngoscopic view by optimal external laryngeal
manipulation. J.Clin.Anesth. 1996; 8: 136-140
21. Levitan RM, Mechem CC, Ochroch EA, Shofer FS, Hollander JE: Head-elevated laryngoscopy position:
improving laryngeal exposure during laryngoscopy by increasing head elevation. Ann.Emerg.Med 2003; 41: 322-
330
22. Levitan RM, Heitz JW, Sweeney M, Cooper RM: The Complexities of Tracheal Intubation With Direct
Laryngoscopy and Alternative Intubation Devices. Ann Emerg Med 2011; 57: 240-247
23. Aziz MF, Healy D, Kheterpal S, Fu RF, Dillman D, Brambrink A: Routine Clinical Practice Effectiveness
of the Glidescope in Difficult Airway Management: An Analysis of 2,004 Glidescope Intubations, Complications,
and Failures from Two Institutions. Anesthesiology 2011; 114: 34-41
24. Noppens RR, Mobus S, Heid F, Schmidtmann I, Werner C, Piepho T: Evaluation of the McGrath Series 5
videolaryngoscope after failed direct laryngoscopy. Anaesthesia 2010; 65: 716-20
25. Healy DW, Maties O, Hovord D, Kheterpal S: A systematic review of the role of videolaryngoscopy in
successful orotracheal intubation. BMC Anesthesiology 2012; 12: 32
26. Griesdale DE, Liu D, McKinney J, Choi PT: Glidescope(R) video-laryngoscopy versus direct laryngoscopy
for endotracheal intubation: a systematic review and meta-analysis. Canadian Journal of Anesthesia 2012; 59: 41-52
27. Sakles JC, Mosier JM, Chiu S, Keim SM: Tracheal intubation in the emergency department: a comparison
of GlideScope(R) video laryngoscopy to direct laryngoscopy in 822 intubations. J Emerg Med 2012; 42: 400-5
28. Sakles JC, Mosier JM, Patanwala AE, Dicken JM, Kalin L, Javedani PP: The C-MAC(R) video
laryngoscope is superior to the direct laryngoscope for the rescue of failed first-attempt intubations in the emergency
department. J Emerg Med 2015; 48: 280-6
29. Aziz MF, Kim D, Mako J, Hand K, Brambrink AM: A Retrospective Study of the Performance of Video
Laryngoscopy in an Obstetric Unit. Anesth Analg 2012; 115: 904-6
30. Jungbauer A, Schumann M, Brunkhorst V, Borgers A, Groeben H: Expected difficult tracheal intubation: a
prospective comparison of direct laryngoscopy and video laryngoscopy in 200 patients. Br J Anaesth 2009; 102:
546-50
31. Silverberg M, J., Li N, Acquah S, O. , Kory P, D. : Comparison of video laryngoscopy versus direct
laryngoscopy during urgent endotracheal intubation: a randomized controlled trial. Crit Care Med 2015; 43: 636-641
32. Hypes CD, Stolz U, Sakles JC, Joshi RR, Natt B, Malo J, Bloom JW, Mosier JM: Video Laryngoscopy
Improves Odds of First-Attempt Success at Intubation in the Intensive Care Unit. A Propensity-matched Analysis.
Annals of the American Thoracic Society 2015; 13: 382-390
33. Kopman AF, Kurata J: Can't intubate, can't ventilate: is "rescue reversal" a pipe-dream? Anesth Analg
2012; 114: 924-926
34. Wong DT, Yang JJ, Mak HY, Jagannathan N: Use of intubation introducers through a supraglottic airway
to facilitate tracheal intubation: a brief review. Canadian Journal of Anesthesia 2012; 59: 704-15
35. Kristensen MS, Teoh WHL, Baker PA: Percutaneous emergency airway access; prevention, preparation,
technique and training. Br J Anaesth 2015; 114: 357-361
36. Aslani A, Ng S-C, Hurley M, McCarthy KF, McNicholas MFFR, McCaul CL: Accuracy of Identification
of the Cricothyroid Membrane in Female Subjects Using Palpation: An Observational Study. Anesthesia &
Analgesia 2012; 114: 987-992
37. Feinleib J, Foley L, Mark L: What We All Should Know About Our Patient's Airway: Difficult Airway
Communications, Database Registries, and Reporting Systems Registries. Anesthesiology clinics 2015; 33: 397-413
38. Patel A, Nouraei SAR: Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE): a
physiological method of increasing apnoea time in patients with difficult airways. Anaesthesia 2015; 70: 323-329
39. Cooper RM: Icteric Vocal Cords Recorded during Video Laryngoscopy. Anesthesiology 2013; 119: 1469
40. Telgarsky B, Cooper RM, Monteiro E, de AJR: Epiglottic melanosis. Canadian Journal of Anesthesia 2015;
62: 1221
41. Sakles JC, Mosier J, Hadeed G, Hudson M, Valenzuela T, Latifi R: Telemedicine and Telepresence for
Prehospital and Remote Hospital Tracheal Intubation Using a GlideScope Videolaryngoscope: A Model for Tele-
Intubation. Telemedicine journal and e-health : the official journal of the American Telemedicine Association 2011
42. Rosenblatt W, Ianus AI, Sukhupragarn W, Fickenscher A, Sasaki C: Preoperative Endoscopic Airway
Examination (PEAE) Provides Superior Airway Information and May Reduce the Use of Unnecessary Awake
Intubation. Anesthesia & Analgesia 2011; 112: 602-607
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Patient Blood Management: Improving Both Sides of the Value

Equation
Daryl J. Kor, MD, MSc Rochester/Minnesota
Introduction
Preoperative anemia has been consistently associated with adverse perioperative outcomes in
patients undergoing both cardiac and noncardiac surgical procedures. 1 Historically, red blood cell (RBC)
transfusion was viewed as an effective and acceptably safe intervention for the management of anemia.
Similarly, platelet and plasma therapies have been viewed as safe and necessary interventions for the
management of thrombocytopenia and altered coagulation parameters, respectively. However, blood
transfusion has more recently come under increased scrutiny. 2-4 The three primary drivers of this renewed
concern relate to questionable efficacy of some transfusion practices for the major blood component
therapies (RBCs, plasma, platelets);5-7 underappreciated risks of blood transfusion including life-
threatening respiratory complications such as transfusion-related acute lung injury (TRALI) and
transfusion-associated circulatory overload (TACO);8-10 and increased recognition of the substantial
associated health care costs (estimated to exceed $10 billion in the U.S. for RBC transfusions alone). 11 In
aggregate, these concerns have resulted in increased interest in the optimization of transfusion practice.
In this refresher course lecture, we will outline the current state of blood component utilization and
patient blood management (PBM) with specific emphasis on the perioperative environment. We will
further identify gaps in our current understanding relating to both the risks and benefits of transfusion
therapies, and we will advocate for PBM as a cornerstone for optimizing future transfusion practices. The
presentation will provide specific examples of PBM approaches that have led to meaningful change in
transfusion practice with substantial impact of the quality of care delivered.
Perioperative Anemia
Background and Epidemiology
Anemia is defined as a total reduction in erythrocyte number, reduced amount of circulating

hemoglobin, or decreased circulating RBC mass, resulting in a pathological state where the oxygen-
carrying capacity of blood is insufficient to meet physiological demand. The World Health Organization
defines anemia as a hemoglobin level of less than 12.0 g/dL in non-pregnant adult women, less than 11.0
g/dL in pregnant adult women, and less than 13.0 g/dL in adult men. 12
Anemia is a common finding in preoperative patients, with a prevalence ranging from 5% to 76%
depending on patient age, presenting condition, and the planned operation.13 Several large observational
studies have associated preoperative anemia with increased risk of perioperative morbidity and 30-day
postoperative mortality. Evidence further suggests the utilization of RBC transfusion to treat anemia
further contributes to increased perioperative morbidity and mortality. 14,15 The administration of RBC
transfusion for the treatment of anemia has also been associated with increased cost when compared with
preoperative elevation of the hemoglobin concentration with pharmacologic interventions (e.g.,
erythropoiesis-stimulating agents).1
Management of Preoperative Anemia
The American Society of Anesthesiologists Task Force on Perioperative Blood Management

recommends erythropoietin with or without iron as an effective measure for reducing a patient’s exposure
to allogeneic RBC transfusions (Category A1-B evidence).16 In contrast, the Task Force notes insufficient
evidence to evaluate the efficacy of erythropoietin with iron compared with erythropoietin without iron.
Furthermore, equivocal findings were noted when comparing preadmission iron supplementation to either
placebo or no iron with the outcomes of preoperative hemoglobin levels and perioperative allogeneic RBC
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transfusions (Category A2-E evidence).16
Red Blood Cell Transfusion
The number of RBC units transfused annually approaches 14 million in the U.S. alone. 17 More
than a quarter of these transfusions occur in the perioperative environment. Despite a growing number of
clinical trials and evidence-based guidelines supporting restrictive RBC transfusion policies, liberal RBC
transfusion practices remain commonplace. Furthermore, there remains tremendous variability in RBC
transfusion practices, both for cardiac and non-cardiac surgical procedures.18,19
From a physiologic perspective, RBC transfusions are administered with the intent of improving
end-organ oxygenation. Interestingly, the majority of basic physiologic studies fail to show improvements
in physiologic parameters such as oxygen consumption or lactate clearance following RBC transfusion. 20
RBC Transfusion Guidelines
A growing body of clinical trials evaluating RBC transfusion practices has now been completed
and their results published. Although a recent clinical trial suggested the potential for improved outcomes
with more liberal RBC transfusion practices in the setting of cardiac surgery,29 the vast majority of trials
support the safety of more conservative RBC transfusion practices. 22 These results appear robust, with
similar results being consistently reported in a variety of surgical and medical populations including those
undergoing orthopedic and cardiac surgery, as well as those with traumatic brain injury, sepsis, and more
heterogeneous critically ill populations.23-28 In summary, the preponderance of data (both observational and
experimental) support the implementation of restrictive RBC transfusion practices in hemodynamically-
stable non-hemorrhaging patients.
Current guidelines recommend a hemoglobin threshold of 7 g/dL for RBC transfusion in

hemodynamically-stable, nonbleeding patients.29 A higher threshold of 8 g/dL is often recommended for
those with documented coronary artery disease or symptomatic anemia (e.g., active ischemia; orthostatic
hypotension, syncope or tachycardia unresponsive to fluid therapy; congestive heart failure). For actively
bleeding patients, RBC transfusion decisions should be based on the overall clinical context rather than
strict adherence to a specific hemoglobin threshold.
Plasma
Nearly 4 million units of plasma are transfused each year in the U.S. alone.17 A large proportion
of these transfusion episodes occur in the perioperative environment, particularly in the setting of cardiac
surgery. Despite efforts to educate care providers on the appropriate indications for plasma administration
and limit the number of inappropriate transfusions, liberal plasma transfusion practices remain common.
Indeed, it has been suggested that up to 50% of plasma transfusions occur outside of published
guidelines,30,31 with the most commonly cited reason for plasma transfusion being the correction of
abnormal coagulation tests prior to an elective invasive procedure. 32 Importantly, the preponderance of
studies performed to date have failed to show a consistent correlation between mild-to-moderate
coagulation abnormalities (i.e., international normalized ratio [INR] < 2) and bleeding complications in
patients undergoing elective invasive percutaneous procedures.7 In addition, plasma transfusion does not
reliably normalize mild-to-moderate elevations in the INR.33 As studies have failed to demonstrate a clear
relationship between mild-to-moderate elevations in INR and increased procedural bleeding, plasma
administration aimed at normalizing an elevated INR for the prevention of bleeding complications remains
theoretical at best. Indeed, the available literature does not support prophylactic plasma transfusion in this
setting.11
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Plasma Transfusion Guidelines
Perioperative plasma product transfusion guidelines were recently published by the American
Society of Anesthesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies.16
Indications for plasma administration in the perioperative setting include active bleeding related to
coagulation factor deficiencies for which specific concentrates are not available as well as trauma-related
massive hemorrhage as part of a fixed-ratio transfusion resuscitation protocol (e.g., 1:1:1,
RBC:plasma:platelet). Additional clinical scenarios where plasma therapy may be warranted include the
reversal of warfarin anticoagulation in a patient with active bleeding or need for emergency surgery (when
prothrombin complex concentrates are not available) or the correction of excessive microvascular bleeding
in the presence of an INR > 2.0. Plasma administration is also recommended as a replacement fluid when
providing plasmapheresis for specific clinical indications (e.g., thrombotic thrombocytopenic purpura). As
noted above, plasma transfusion is not recommended for the treatment of mild-to-moderate elevations in
the INR (INR < 2) when clinically significant bleeding is not present.
Platelets
More than 2 million platelet units were transfused in in the U.S. in 2011.17 This number represents
a 7% increase in platelet utilization when compared to 2008 and continued a steady trend of increased
annual platelet utilization. An estimated 20% to 25% of these platelet transfusions occurred in the
perioperative environment with the majority being delivered in the setting of cardiac surgery. 17 In the
recent observational study of Glance et al. evaluating patients undergoing noncardiac surgery,
thrombocytopenia was present in 1 in 14 patients without clinical indications for preoperative platelet
testing.34 Thrombocytopenic patients were more likely to be transfused and had greater than 30-day
mortality when compared to those with normal preoperative platelet counts. Less clear is the impact of
perioperative platelet transfusion on mitigating these risks. A recent large observational study in the setting
of noncardiac surgery failed to identify reductions in bleeding complications or improved clinical outcomes
when comparing those who received preoperative platelet transfusions to those who did not. 35
Platelet Transfusion Guidelines
Although a number of clinical trials have evaluated platelet transfusion thresholds in the setting of
hematologic disorders in patients undergoing chemotherapy or stem cell transplantation, surprisingly few
studies have evaluated the impact of platelet transfusion on bleeding complications in the perioperative
environment.6 For those with hematologic disorders, platelet counts of 10 x 10 9/L (20 x 109/L for those on
heparin or with evidence of increased platelet destruction) are advocated as transfusion thresholds.
Although similar trials have not been performed in the perioperative setting, most guidelines recommend a
platelet count transfusion threshold of 50 x 109/L (100 x 109/L for procedures involving a closed anatomic
space) in this environment.16 A lower threshold of 20 x 109/L is recommended for prophylactic platelet
transfusion in a patient undergoing an elective central line placement (although lower platelet counts may
be safely tolerated if the venous puncture site is compressible [e.g., internal jugular, femoral] and real-time
ultrasonography is being used). Of note, evidence supporting the efficacy of platelet transfusion for the
reversal of antiplatelet medication effects is very limited, and significant uncertainty remains regarding the
benefit of this practice.6
Transfusion Risks
As with all medical therapies, blood transfusion is not without risk. Historically, concerns have
been centered on the vertical transmission of infectious disease. Although significant progress has been
made in mitigating the risk of transfusion-associated infectious complications, additional risks have since
come to light. TRALI remains the leading cause of transfusion-related deaths in the U.S.10 This is closely
followed by a second transfusion-related pulmonary complication known as TACO. While the incidence of
TRALI is believed low (< 1%), the condition has significant associated mortality, estimated to range from
15% to 20%.36 TACO is a more frequent complication with an estimated incidence of approximately 4%. 8
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Though TACO’s attributable mortality is less well defined, clear associations with increased respiratory
support requirements, intensive care unit admission, and length of hospital stay have been noted. 8
Importantly, a growing body of literature has begun to highlight concerns associated with under-diagnosis
and under-reporting for both TRALI and TACO.37
Additional transfusion-related complications can include febrile transfusion reactions (the most
common transfusion-related complication with rates reported up to 30% with platelet transfusions), allergic
and anaphylactic reactions, hypotensive transfusion reactions, and hemolytic transfusion reactions (acute
and delayed). Additional rare transfusion complications include transfusion-associated sepsis, graft-versus-
host disease and post-transfusion purpura.
Transfusion Costs
Expenses related to the acquisition of a blood component (acquisition costs) represent a fraction of
the overall costs associated with a transfusion episode. Additional transfusion-related costs include those
associated with labor, component processing and storage, and supplies for storing, testing, and
administering the blood component. These “activity-based” or “direct variable” costs have been quantified
and reported by Shander et al.38 Results of these analyses suggest that total transfusion costs can be up to
4.8-fold greater than the cost of simply acquiring the blood component. Notably, these cost considerations
also fail to account for expenses related to transfusion-related adverse events. Regardless, with an
estimated cost of $761 per RBC unit (activity-based costs), it is estimated that total annual RBC transfusion
expenditures may approach $10.5 billion in the U.S. alone.17,38 Prior observational studies have associated
liberal perioperative transfusion practices with significant excess perioperative costs. 39 Similarly, after
adjusting for potentially confounding variables, the administration of transfusion(s) to multiday acute care
inpatient admissions was associated with 1.83-fold higher mean inpatient costs.40 Though the precise
impact of PBM activities on overall institutional economics is often difficult to determine, it is clear that
the impact can be significant.
Transfusion Education
Perioperative training programs have done a poor job of incorporating PBM education into the
medical curriculum. It has been reported that less than 20% of anesthesiology residents receive formal
training in PBM.17 The frequency of formal training in best transfusion practice is only slightly improved
at institutions with PBM programs, estimated at less than 30%. 17 Similar numbers have been reported for
our surgical colleagues as well. Clearly, education of health care providers on optimal transfusion practices
remains a knowledge gap and an essential element of PBM programs. 41
Patient Blood Management for the Optimization of Transfusion Practice
Definitions
American Association of Blood Banks (AABB): PBM is an evidence-based, multidisciplinary

approach to optimizing the care of patients who might need transfusion. PBM encompasses all aspects of
patient evaluation and clinical management surrounding the transfusion decision-making process, including
the application of appropriate indications, as well as minimization of blood loss and optimization of patient
red cell mass.42
Society for the Advancement of Blood Management (SABM): PBM is the timely application of
evidence-based medical and surgical concepts designed to maintain hemoglobin concentration, optimize
hemostasis and minimize blood loss in an effort to improve patient outcome.43
Pillars of Patient Blood Management
Perioperative PBM generally focuses on three pillars of care in surgical patients: 1) the detection
and treatment of hematologic derangements (e.g., anemia, thrombocytopenia, or coagulopathy); 2) the
reduction of perioperative blood loss; and 3) harnessing and optimizing the patient-specific physiological
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reserve of anemia, thrombocytopenia, and coagulopathy (including restrictive transfusion triggers and use
of pharmacologic hematologic adjuncts such as prothrombin complex concentrates when appropriate).44
Pillars of a Patient Blood Management Program
Clinical Champions and Institutional “Buy-In”: A key element with most all of health care’s
change management initiatives is the identification of a clinical champion who can lead the effort. This
individual will serve many key roles in the PBM process as they must convince institutional leadership of
the importance of the effort while “selling” PBM as the approach to address the problem. This initial effort
should not be under appreciated as it is required to garner the resources needed for the success of the PBM
program. The clinical champion will also oversee the interactions with the clinical practice. Effective
leaders must be skilled in many areas including business acumen (vision, strategic planning, human
resource management), change management (project management, problem solving, decision making),
interpersonal skills (communication, team building, negotiations), and health care leadership (operational
excellence, health care policy, health care quality).45
Organizational Structure: Implementation of a PBM program must take into account the key
stakeholders. Success depends on a robust PBM “team” inclusive of members who represent the clinical
service lines that will be impacted by PBM-related interventions. Examples of key stakeholders include:
emergency medicine, internal medicine/family practice, surgery (e.g., cardiothoracic, trauma, orthopedic),
anesthesiology, critical care medicine, hematology/oncology, transplantation, transfusion medicine,
pediatrics, and nursing. Additional stakeholders also include administrative partners and information
technology personnel. These participants will have unique and essential perspectives on the “culture” of
the environments that they represent. Changes to clinical workflows are often better accepted when the
rationale is delivered by a respected colleague. These key stakeholders can also greatly facilitate the
dissemination of best practices guidelines, performance metrics, and quality concerns.
Data-Driven Approach to Understanding Transfusion Practices: Health care providers often have
perceptions regarding their clinical practice. However, when valid clinical data are available, it often
contradicts these clinical impressions. As with so many other areas of health care, data-driven approaches
to understanding the transfusion landscape can prove impactful. 46 Moreover, data detailing the impact of
specific PBM interventions can add significant value to a PBM program. Recently, Crohn and colleagues
have shown a data-driven approach to PBM can markedly reduce the proportion of inappropriate
transfusion orders and the number of overall transfusion events. 47 Whenever possible, data detailing the
transfusion practice, adherence to best practice guidelines, and occurrence of adverse events should be
made available to help guide the PBM program.
Defining and Disseminating Best Practices: Having developed and implemented the necessary
infrastructure to support a PBM program (e.g., people, processes, technology), a key early PBM activity is
the development of best-practice guidelines that can be disseminated to the clinical practice. In addition to
best-practice guidelines for preoperative evaluation/optimization and use of blood components therapies,
consideration of strategies that can minimize perioperative blood loss and reduce the risk of exposure to
allogeneic blood products should be considered. Examples of evidence-based intraoperative interventions
include point-of-care testing and pharmacologic interventions (e.g., antifibrinolytic therapies, prothrombin
complex concentrates, topical hemostatics) as well as additional strategies such as acute normovolemic
hemodilution and intraoperative autologous RBC recovery.16 These strategies should be specifically
considered in patient at high risk for excessive bleeding (e.g., major cardiac, orthopedic, thoracic, or liver
surgery). Information related to the risks of blood transfusion as well as the economic implications of
liberal transfusion practices should also be disseminated broadly.
Optimizing Clinical Decision Support and Implementing Innovative Informatics Approaches:

When evaluating the individual components of a PBM program, implementation of well-thought electronic
clinical decision support tools have been shown to meaningfully impact transfusion behaviors. Clinical
decision support implemented at the time of order entry can assist clinicians by helping to guide them
towards appropriate transfusion behaviors or alternatively steering them away from the administration of
blood components when potential recipients are unlikely to benefit. Even apparently simple interventions
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such as defaulting the transfusion “dose” to a single unit of RBC, as opposed to multiple units, can have
very meaningful impacts on overall transfusion practice. 48 A recent systematic review highlighted the
impact of electronic decision support on transfusion practice. 49 Although the Mayo Clinic transfusion
practice has noted a significant impact with the meaningful implementation of clinical decision support for
all of the major transfusable blood components, the published evidence in support of non-RBC blood
components is less robust than it is with RBC transfusions.49,50
Operationalizing Performance Metrics and Quality Indicators: Generally speaking, clinicians are
competitive individuals who continually strive to outperform. This competitive nature can be leveraged to
support meaningful change in transfusion practice. To this end, data can be a powerful driver of change.
Indeed, multiples studies have highlighted the importance of providing data back to the practice on how
they are performing in terms of optimizing transfusion practices. 47 As with the clinical decision support
approaches outlined above, delivery of meaningful transfusion performance metrics or quality indicators to
the clinical service-lines appears to be a very key element to optimizing transfusion practice.
Relating the Intervention to Patient-Important Outcomes: Ultimately, health care personnel strive
to provide the best outcomes possible for their patients. As such, an essential final component for PBM
programs is the development of strategies which connect changes in transfusion practice back to patient-
important outcomes. Though seemingly straightforward, linking PBM activities to clinically relevant
outcomes can be challenging and remains underdeveloped in most PBM programs. As we move forward,
key steps include identifying the relevant outcomes to assess as well as the appropriate methods for their
measurement. Candidate outcomes include mortality, morbidity, level and duration of care, and resource
utilization.51 Notably, multiple groups are currently working to further identify key outcomes to be
assessed in this domain.
References
1. Baron DM, Hochrieser H, Posch M, Metnitz B, Rhodes A, Moreno RP, et al: Preoperative anaemia is
associated with poor clinical outcome in non-cardiac surgery patients. Br J Anaesth 2014; 113: 416-
23
2. Kor DJ, Gajic O: Blood product transfusion in the critical care setting. Curr Opin Crit Care 2010; 16:
309-16
3. Marwaha N, Sharma RR: Consensus and controversies in platelet transfusion. Transfus Apher Sci
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9. Clifford L, Jia Q, Subramanian A, Yadav H, Wilson GA, Murphy SP, et al: Characterizing the
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15. Baron DM, Hochrieser H, Posch M, Metnitz B, Rhodes A, Moreno RP, et al: Preoperative anaemia is
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2014; 312: 36-47
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higher hemoglobin threshold for transfusion in septic shock. N Engl J Med 2014; 371: 1381-91
29. Carson JL, Grossman BJ, Kleinman S, Tinmouth AT, Marques MB, Fung MK, et al: Red blood cell
transfusion: a clinical practice guideline from the AABB. Ann Int Med 2012; 157: 49-58
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34. Glance LG, Blumberg N, Eaton MP, Lustik SJ, Osler TM, Wissler R, et al: Preoperative
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36. Looney MR, Roubinian N, Gajic O, Gropper MA, Hubmayr RD, Lowell CA, et al: Prospective study
on the clinical course and outcomes in transfusion-related acute lung injury. Crit Care Med 2014; 42:
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blood transfusions in surgical patients at four hospitals. Transfusion 2010; 50: 753-65
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Res Clin Anaesth 2013; 27: 161-172
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Enhanced Recovery Principles for the Ambulatory Patients
Tong J. Gan, M.D., F.R.C.A., M.H.S. Stony Brook, New York
Enhanced recovery After Surgery (ERAS) are multimodal perioperative care pathways designed to attenuate the
stress response during the patients’ journey through a surgical procedure, facilitate the maintenance of preoperative
bodily compositions and organ function, and in doing so achieve early recovery. ERAS integrate a range of
perioperative interventions to maintain physiologic function and facilitate postoperative recovery.
There are several elements of ERAS that are new and specific to this approach, bringing together 2 best practices: 1)
organization of care and 2) clinical management, while making sure that patients receive evidence-based care. In the
2000s, ERAS pathways in colorectal surgery were applied throughout Europe. Since then, ERAS pathways have
been adopted worldwide, and pathways and guidelines have been published for other major procedures because the
principles of ERAS apply to all patients undergoing major surgery.
Increasingly, many surgical procedures that were considered major a number of years ago are increasingly being
performed on an ambulatory basis (including 23 hours stay). These include abdominal and vaginal hysterectomies,
laminectomies, prostatectomies, total joint replacements, and even colectomies.
Successful implementation of ERAS pathways requires collaboration between surgery, anesthesia, and perioperative
nursing to provide optimal perioperative care. Anesthesiologists play a vital role in facilitating recovery because
they routinely carry out some of the key elements of ERAS (i.e., preoperative assessment and patient education,
perioperative fluid management, optimal multimodal analgesia, prevention of postoperative nausea and vomiting
(PONV) and other opioid related side effects.
In this presentation, I will focus on the optimal management of pain and PONV for patients undergoing surgery in
an ambulatory setting as part of the ERAS strategy.
Postoperative nausea and vomiting (PONV) and pain are two of the most common and unpleasant side effects
following anesthesia and surgery. Although both are predictable part of the postoperative experience, inadequate
management of these symptoms is common and can have profound implications. Unrelieved postoperative pain may
result in clinical and psychological changes that increase morbidity, mortality, costs as well as decrease quality of
life and potentially increase the incidence of chronic pain1. Negative clinical outcomes resulting from ineffective
postoperative pain management include deep vein thrombosis and pulmonary embolism, coronary ischemia and
myocardial infarction, pneumonia, poor wound healing, insomnia and demoralization 2,3. Associated with these
complications are economic and humanistic implications such as extended lengths of stay, readmissions, and patient
dissatisfaction with medical care.4,5 A recent study suggests that pain in ambulatory surgical patients is still
undermanaged and the incidence of moderate to severe pain remains high.6
The overall incidence of PONV has decreased from 60 % when ether and cyclopropane were used, to approximately
30% more recently.7 However, in certain high-risk patients the incidence is still as high as 70%. It is estimated that
an episode of vomiting prolongs PACU stay by about 30 min.8 Furthermore, it is estimated that approximately 0.2%
of all patients may experience intractable PONV, leading to unanticipated hospital admission following ambulatory
surgery, thereby increasing medical costs. The estimated cost of PONV to a busy ambulatory surgical unit was
estimated to range from $0.25 million to $1.5 million per year in lost surgical revenue. 9
The results of several studies suggest that patients not only rank the absence of PONV and pain as being important 10
but also rank it more important than an earlier discharge from an ambulatory surgical unit. 11 Because patients
convalesce at home after surgery, pain and nausea and vomiting must be effectively assessed, monitored, and treated
within the surgical setting and anticipated during the recovery at home. This article will discuss the management of
PONV and pain following ambulatory surgery, the use of an effective, multimodal and novel therapy as well as
recommendations for the prophylaxis and treatment of PONV and pain.
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Management of Postoperative Pain

Pharmacological Options
Opioids
Opioids are effective analgesics for moderate to severe pain. They act on opioid receptors in the peripheral 12,13 and
central nervous system. However their efficacy is limited by side effects. Opioids and/or NSAIDs combined with
local anesthetic infiltration or regional block has proven to be a useful technique for controlling pain in patients after
ambulatory surgery and should be considered whenever possible. In most studies local anesthetic infiltration with
systemic opioids or NSAIDs showed improvement in analgesia, better recovery 14 and shortening of discharge time
from day surgery unit. 15,16
Acetaminophen
Acetaminophen (Paracetamol) is an effective analgesic for mild to moderate pain with favorable side effect profile.
17
It is an effective adjuvant to opioid analgesia and a reduction in opioid requirement by 20-30% can be achieved
when combined with a regular regimen of IV, oral or rectal acetaminophen. It has been shown that 1 g of
propacetamol results in significant reduction in postoperative morphine consumption over 6 h period. 18 A meta-
analysis of analgesic efficacy suggested that acetaminophen and tramadol is an effective analgesic combination in
dental and post surgical pain. However, more patients experienced side effects like dizziness, nausea and vomiting
with this combination.19 IV acetaminophen, commonly used in Europe, has the flexibility of being able to be used in
the perioperative period and may be a viable alternative to NSAIDs in minor surgery and a useful adjunct in
conjunction with other analgesics.18,20
Non-Steroidal Anti-inflammatory Drugs and Cyclo-oxygenase (COX-2) Inhibitors

Non-steroidal anti-inflammatory drugs (NSAIDs) have become the cornerstone in the treatment of acute pain in the
early postoperative period because of its opioid sparing effect. 21 Administration of ibuprofen and oxycodone in
combination provides superior and effective analgesia in the postoperative period. 22 The combination of ibuprofen
and acetaminophen has also been reported to reduce the need for early analgesia up to 34% in children undergoing
tonsillectomy.23 The use of COX-2 inhibitors have been shown to be an effective opioid adjunct in the perioperative
period without the increased risk of bleeding. Recently data suggest that oral regimen of ibuprofen (1200 mg/d) or
celecoxib (400 mg/d) improves analgesia and quality of recovery in ambulatory patients.24 The recent availability of
IV ibuprofen may provide further option of administration in the perioperative setting.
Tramadol and Tapentadol

Tramadol is a synthetic, centrally acting analgesic with a weak opioid action. It also inhibits serotonin and
noradrenaline reuptake. 25 The tramadol metabolite, O-desmethyl tramadol is a more potent analgesic than tramadol.
26
Unlike other opioids, it lacks the respiratory depressant effects and exhibits lower risk of bowel dysfunction 27 at
conventional doses. A meta-analysis 28 of acetaminophen and tramadol combination confirmed superior analgesia
without additional toxicity. The most common adverse effects noted were dizziness, headache, nausea and vomiting.
Combination of tramadol with acetaminophen increases tolerability. 29 More recently, tapentadol has been approved
in the US for the treatment of acute pain, It acts on opioid receptors as well as by inhibiting norepineprine pathway.
More studies are needed to define its clinical utility in an ambulatory setting.
Ketamine
Ketamine acts as an antagonist on the NMDA receptor. Used more widely as an anesthetic before the availability of
newer induction and maintenance agents, it has received renewed interest for its role in enhancing postoperative
analgesia. Several studies have focused on demonstrating use of subanesthetic doses of ketamine for various surgical
procedures to enhance pain relief and reduce total analgesic consumption. 30-35 Central excitatory neurotransmitters
acting on N-methyl-D aspartate receptor (NMDA) have been identified in the development and perpetuation of
pathologic pain states causing hyperalgesia and allodynia.36
There is ample evidence to suggest that ketamine has opioid sparing effect and may confer advantage in patients
where large amount of postoperative opioid consumption is anticipated. At low doses ketamine can provide
analgesia in opioid resistant pain. 37 Continuous infusion of ketamine has been used perioperatively. Adam et al.,
evaluated IV ketamine with an initial bolus (0.5 mg/kg) followed by continuous infusion of 3 mcg/kg/min
intraoperatively in combination with continuous femoral nerve block in patients undergoing total knee arthroplasty.
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In this multimodal approach, ketamine group required significantly less morphine and tolerated early mobilization of
knee.38 These drugs have to be used with caution in the ambulatory setting due to its potential side effects including
sedation and hallucinatory effects in some individuals, though administering only a bolus dose and avoiding the
infusion regimen can reduce the incidence of adverse events.
Wound infiltration with local anesthetics

Infiltration of surgical wound with local anesthetics is probably the simplest method of achieving wound analgesia.
This method has been shown to be effective in providing analgesia in patients undergoing inguinal hernia repair and
other ambulatory procedures. There is lack of evidence for any clinically useful effect for other more extensive
abdominal procedures. 39 For example, wound infiltration does not provide beneficial effect on pulmonary function
after surgery in one study. 40 Inadequate dosing and relatively short duration of action of the local anesthetics may
explain the poor results in some trials. Prolonged release technology of local anesthetics (e.g. depobupivacaine) has
recently approved for clinical use. In two pivotal studies, depobupivacine (Exparel®) would infiltration has been
shown to improve postoperative analgesia and reduced opioid consumption in bunionectomy and hemorrhoidectomy
surgery.41,42 Further trials on its efficacy for peripheral nerve blocks are on-going. The role of other adjuvants to
local anesthetics is unclear. For example, wound infiltration of bupivacaine and ketamine has not shown a decrease
in pain score or the need for rescue analgesia but the duration of analgesia has been reported to be prolonged by the
addition of ketamine.43
Intra-articular analgesics
There are conflicting reports about the efficacy of intra-articular analgesics in the literature. 44-46. In a systematic
review Moiniche S et al. 47 observed that the effect of intra-articular local anesthetics seemed to provide moderate
pain relief of short duration. Although the pain relief in the early postoperative period was statistically significant,
evidence was not overwhelming in favor of intra-articular local anesthetics because majority of the studies did not
demonstrate improved pain relief beyond the immediate postoperative period.
Peripheral Nerve Blocks (PNB)

Appropriate nerve blocks depending on the site of surgery are useful in providing short to intermediate-term pain
relief after surgery. Direct visualization of neural tissue with ultrasound technology and the utility of stimulating
catheters has made placement of indwelling catheters safer and more accurate. Continuous infusion of local
anesthetics through a peripheral nerve catheter is becoming increasingly popular in both hospital and ambulatory
setting to achieve prolonged analgesia.48,49 For example, continuous femoral nerve block has been shown to reduce
duration of hospital stay and the frequency of serious complications. 50 Similarly, several other studies have
demonstrated the benefits of PNB including reduced length of stay and costs, 49 decreased incidence of PONV 51
and lower rates of unexpected hospital admissions after ambulatory surgery. 49,50,52 Systemic agents co-administered
during PNB such as opioids and clonidine have been found to enhance intraoperative and postoperative analgesia.
Two systematic reviews of 15 studies that used opioids as adjuvant, six reported a statistically significant benefit in
analgesia. Of the six studies that evaluated clonidine, 53 five found improvement in analgesia.
Other Pharmacological and Non-Pharmacological Options

Numerous other adjunctive analgesia including gabapentin, pregabalin, corticosteroids, neostigmine, magnesium
have some usefulness in an ambulatory settings but more evidence need to be gathered to determine their specific
roles. A recent study suggests that patients anesthetized with propofol was associated with less pain compared to
sevoflurane anesthesia although the exact mechanism is not known.54 Non-pharmacological therapy should be
considered as complimentary to pharmacological options for postoperative pain management. They may provide
additional benefits in reducing the total dose of analgesics required and therefore minimizing the adverse effects of
the analgesics. Techniques include acupuncture, hypnosis, relaxation, music therapy, etc. 55,56
Rationale for multimodal analgesia

The ideal analgesic regimen would provide effective pain relief, reduce opioid related side effects and surgical stress
response and improve clinical outcome e.g. morbidity, mortality and hospital stay. The concept of multimodal
analgesia was introduced to achieve these goals by combining various analgesic techniques and different classes of
drugs to improve postoperative outcome. 57 However, available data are conflicting and do not necessarily resulted
in improved outcome and concomitant reduction in adverse effects of opioids. 58-60 The failure to improve clinical
outcome may be due to inappropriate combination and dosing of analgesics. Apart from adequate analgesia,
postoperative morbidity and hospital stay depend on other factors such as initiation of early nutrition, mobilization
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and comprehensive rehabilitation program. 61 Although, there is insufficient evidence to recommend pre-emptive
analgesia routinely it is prudent to attenuate postoperative pain as effectively as possible during the intraoperative
period and initiating effective analgesic therapy in the early phase of perioperative period.
The effectiveness of individual analgesics is enhanced by the additive or synergistic effect of two or more drugs
acting by different mechanisms. For example, the synergism between alpha-adrenergic and opioid systems has been
demonstrated. 62 Similarly, combination of acetaminophen and non-steroidal anti-inflammatory drugs provides
additive analgesic effect in mild to moderate acute pain. 63 The addition of COX-2 inhibitors or NSAIDs reduces
opioid requirements by 20-30% with the reduction of opioid related side effects and better analgesia. Similarly,
ketamine has been shown to reduce the pain scores and lower analgesic requirement when added to a multimodal
epidural analgesia. 64 Adding ketamine in patient controlled epidural analgesia along with morphine, bupivacaine
and epinephrine has been demonstrated to result in enhanced analgesic effect. Chia et al. 65 showed that the mean
visual analogue score in the ketamine group during movement and cough were lower than the control group. The
cumulative total analgesic consumption in the ketamine group was lower by 30% than the control group 24 h
following surgery. In another study, it was demonstrated that the combination of intraoperative ketamine and
epidural analgesia may confer a long-term benefit in reducing incidence of chronic pain.66
Management of PONV
Risk factors for PONV
Identification of patients at high risk for PONV enables targeting prophylaxis to those who will benefit most from it.
Universal PONV prophylaxis is not cost effective, is unlikely to benefit patients at low risk for PONV and would
put them at risk from the potential side effects of antiemetic agents. Patient, anesthesia, and surgery related risk
factors have been identified. Anesthesia related risk factors include the use of volatile agents 67, nitrous oxide68,
opioids67,69 and high doses of neostigmine (>2.5 mg) for the reversal of neuromuscular blockade. 70 Patient related
factors include female gender69,71, history of PONV or motion sickness 69,71,72, and non-smoking status.69,71 High
levels of anxiety and postoperative pain, especially of pelvic or visceral origin, may also be associated with a higher
incidence of PONV.73-75
A recent systematic review of the results of all available studies suggest that the phase of the menstrual cycle has no
impact on the occurrence of PONV.76 An increased Body Mass Index (BMI) is not a risk factor for PONV. 77
However, long surgical duration71 and certain types of surgery also carry a greater risk of PONV. 71,78,79 In adults,
high incidences of PONV are found in intra-abdominal surgery, major gynecological surgery, laparoscopic surgery,
breast surgery, neurosurgery, eye and ENT surgery. Pediatric operations at high risk for PONV include strabismus,
adenotonsillectomy, hernia repair, orchidopexy, penile surgery and middle ear procedures. 80-82 However, in a
prospective validation study, an association between type of surgery and the risk of PONV was not apparent. 69 It
was suggested that the high incidence of PONV after certain operations might be caused by the involvement of high
risk patients. The incidence of PONV increases after the age of 3 years with a peak incidence of about 40 % in the
11 –14 year age group.69,83,84 Prior to puberty, gender differences for postoperative vomiting have not been
identified. 85 A recent study suggests black South African as an independent factor in reducing PONV risk.86
A number of PONV risk scoring systems have been developed. Apfel et al developed a simplified risk score
consisting of four predictors: female gender, history of motion sickness or PONV, non-smoking status and the use of
opioids for postoperative analgesia.69 A recent study identifies five independent predictors for postdischarge nausea
and vomiting: female sex, age<50 years, history of PONV, opioid use in the PACU, and nausea in the PACU.87
Reduction of Baseline Risks

There are several effective strategies which can be easily employed to reduce the baseline risk for PONV. Adequate
hydration is simple and inexpensive and has been shown to reduce the incidence of PONV. 88 Liberal fluid regimen
is associated with a lower incidence of vomiting and improved pulmonary function in patients undergoing knee
arthroplasty compared with restricted fluid regimen.89 While earlier studies suggest a protective effect of higher
concentration of oxygen, a recent meta-analysis concluded that 80% FiO2 should no longer be considered an
effective or reliable method to reduce overall PONV. 90 Reducing the use of opioid by adding other adjunctive
analgesia, e.g. NSAID, COX-2 inhibitor, acetaminophen, local anesthetic infiltration, gabapentin etc can lower
incidence of PONV.91 Avoidance of deep inhalational anesthesia guided by bispectral index has also been shown to
reduce the risk of PONV. Dexmedetomidine infusion (0.2–0.8 µg · kg–1 · h–1) has recently been shown to reduce
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rescue antiemetic use in bariatric surgical patients.92 Most importantly, the use of propofol as the maintenance
anesthetic have the greatest impact in further reducing the incidence. 93
Combination Antiemetic Therapy

There are at least four major receptor systems involved in the etiology of PONV. The concept of combination
antiemetic therapy was first introduced in 1988 in chemotherapy induced nausea and vomiting (CINV).94 Its success
prompted similar research in the field of PONV. Over 100 randomized controlled trials have been published
comparing the relative efficacy of combination versus single agent antiemetic prophylaxis. Most of these studies
suggested better efficacies against PONV can be achieved by the use of two or more antiemetics acting at different
receptors compared with monotherapy.95-97 The choice of combination is not critical. In a meta-analysis, Habib et al.
found no statistically significant difference in the incidence PONV when a 5-HT3 receptor antagonist was combined
with either droperidol or dexamethasone. Both combination regimens provided significantly better PONV
prophylaxis compared with 5-HT3 receptor antagonists alone.98.
In a large prospective study using a multifactorial design, Apfel et al. evaluated 3 antiemetic interventions
(ondansetron 4 mg, droperidol 1.25 mg, dexamethasone 4 mg) and 3 anesthetic interventions (TIVA with propofol,
omitting nitrous oxide, and substituting remifentanil for fentanyl) for the prophylaxis of PONV. The data suggest
that antiemetics with different mechanisms of action have additive rather than synergistic effects on the incidence of
PONV. Each antiemetic reduced the risk of PONV by about 25 %. When combinations of interventions were used,
the benefit of each subsequent intervention was always less than that of the first intervention. 95. Interestingly, a
recent study showed superior efficacy in reducing vomiting when aprepitant was combined with dexamethasone
instead of ondansetron-dexamethasone combination in neurosurgical patients.99
Multimodal Approach
In addition to using a combination of anti-emetics acting at different receptor sites, the multifactorial etiology of
PONV might be better addressed by the adoption of a multimodal approach other than pharmacotherapy. This is
especially important in patients at high risk for PONV.
Scuderi et al reported a multimodal approach to the management of PONV in females undergoing outpatient
laparoscopy. Their multimodal algorithm consisted of total intravenous anesthesia with propofol and remifentanil,
avoiding nitrous oxide and neuromuscular blockade, aggressive intravenous hydration (25 ml/kg), triple
prophylactic antiemetics (ondansetron 1 mg, droperidol 0.625 mg and dexamethasone 10 mg), and ketorolac 30 mg.
Multimodal management resulted in a 98% complete response rate (no PONV and no antiemetic rescue) in
PACU.100 More recently, a multimodal approach incorporating TIVA with propofol, a combination of ondansetron
and droperidol, and omitting nitrous oxide, was associated with a higher complete response rate and greater patient
satisfaction in the PACU, compared to similar antiemetic prophylaxis with isoflurane/nitrous oxide based
anesthetic.98 A combination of ondansetron and transdermal scopolamine (TDS) proves to be effective in reducing
PONV up to 48 hours after ambulatory surgery.101 A recent meta-analysis suggests a similar effective reduction in
PONV with both early (the night before surgery) and late patch (same day of surgery) application. Apart from a
higher prevalence of visual disturbances after surgery with TDS, there was no difference in the other anticholinergic
side effects when compared to placebo.102
Droperidol
Following the FDA “black box” warning on droperidol due to concerns of prolonged QTc interval, its use has
declined dramatically. A recently published pro and con debate weighed the justification of the FDA’s action 103,104.
Increasingly, clinicians begin to use haloperidol, another drug in the butyrophenone class, due to its lack of “black
box” warning”. Haloperidol in doses of 1 mg has been shown to be effective without significant side effects.105,106
Its efficacy is enhanced when combined with dexamethasone. 107
Novel Antiemetics
Neurokinin-1 Antagonists
Substance P, a member of the tachykinin family of neuropeptides, is an important neurotransmitter in afferent
pathways of emesis.108 Substance P may be released from enterochromaffin cells in the stomach and intestine (e.g.
postoperative trauma) or from sensory neurons (e.g. radiation, chemotherapeutic agents).108 Tachykinin peptide
activity is tied to at least three G-protein–coupled receptor subtypes found in the peripheral or central nervous tissue:
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neurokinin receptor subtype 1 (NK1), type 2 (NK2), and subtype 3 (NK3). The NK1 receptors are located in the area
postrema and are thought to play a particularly important role in emesis. However, NK 1 receptor antagonists (NK1
RAs) are thought to exert their mechanism of action on neurons in the “afferent relay station” situated between the
medial NTS and the central pattern generator for vomiting. 108 The potential NK1 receptor blocking activity located
deeper in the brain stem is thought to prevent both acute and delayed emesis, whereas 5-HT3 RAs are largely
effective against acute emesis,108 leading to considerable interest in the use of NK1 RAs for prophylaxis of PONV.
NK1 receptor antagonists are effective for the prophylaxis and treatment of PONV.109,110 In one study in females
undergoing gynecologic surgery, an NK1 receptor antagonist, CP-122,721 provided better prophylaxis against
vomiting compared with ondansetron. The combination of both agents also significantly prolonged the time to the
need for rescue compared with either drug alone, and was associated with a low incidence of emesis (2 %).110
Aprepitant is the only NK-1 receptor antagonist currently approved by the FDA for the prophylactic management
for PONV. It is available in oral capsule in 40 mg to be administered between 1-3 hours before surgery. It has a long
half-live of about 48 hours. It appears to have better efficacy in the prevention of PONV when compared with
ondansetron. In two identically designed, randomized, double-blind, active-controlled studies, patients scheduled for
mostly major gynecological surgery under general anesthesia were randomized to either aprepitant 40 mg, aprepitant
125 mg or ondansetron 4 mg. In the combined analysis, aprepitant 40 mg was superior to ondansetron for no nausea
(39.6% v 33.1%), no vomiting (86.7% v 72.4%), and no nausea, no vomiting, and no use of rescue (37.9% v 31.2%)
(p<0.05 for the odds ratio for each comparison). 111,112 Rolapitant, with a half-life of 180 h, also has superior efficacy
in the reduction of postoperative emesis when compared with ondansetron. 113 There are a number of other NK-1
antagonists currently under development.114
Long Acting Serotonin Antagonist

Palonosetron has the longest elimination half-life of all the currently available serotonin antagonists at about 40
hours.115 Its long duration of action can also be explained by its high binding affinity for 5-HT3 receptors.116
Polanosetron was first introduced into the US market in for the management of (CINV) and it is also recently
approved for PONV. Recent studies suggest palonosetron 0.075 mg i.v. is effective for the reduction of the
incidence of nausea and vomiting in patients up to 72 h postoperatively. Palonosetron also reduces nausea severity
and interference in postoperative patient functioning due to PONV 117. It would be interesting to see if the longer
half-life of this drug translates into prolonged clinical efficacy when compared with other serotonin antagonists.
Recommended strategy for PONV prophylaxis

The management strategy for PONV has been summarized by a recent SAMBA sponsored PONV consensus
guidelines.85 First, the risk of PONV should be estimated for each patient. No prophylaxis is recommended for
patients at low risk for PONV except if they are at risk for medical consequences from vomiting e.g. patients with
wired jaws, aesthetic procedures or at patient’s request. For patients at moderate to high risk for PONV, regional
anesthesia should be considered. If this is not possible or contraindicated and a general anesthetic is used, strategies
to minimize the baseline risk of PONV should be adopted, e.g. minimize the use of opioids, avoid high dose
neuromuscular reversal drugs and the use of propofol maintained anesthesia. Second, the use of combination
antiemetic therapy and more appropriately a multimodal approach in high-risk patients is recommended. However,
the best available combination and the optimum doses of antiemetic agents when used in combination are yet to be
established. Ondansetron should be considered in any prophylactic regimen as it is now generic and hence has a low
acquisition cost.
Recommendations for the treatment of established PONV

There is a paucity of data on the use of antiemetics for the treatment of PONV in patients who failed prophylaxis or
did not receive prophylaxis. This is due to the difficulty in performing such studies since a large number of patients
would need to be recruited in order to obtain the required number of patients who eventually experience PONV.
The 5-HT3 receptor antagonists were the most commonly tested drugs in rescue clinical trials. Similar to their use in
PONV prophylaxis, the anti-vomiting efficacy of the 5-HT3 receptor antagonists is more pronounced than their anti-
nausea efficacy. There is no evidence of dose-responsiveness for these agents when used for rescue. As ondansetron
is now generic, a 4 mg dose is recommended.
In patients who fail ondansetron prophylaxis, there is evidence to suggest that the use of ondansetron for rescue is no
more effective than placebo. A drug acting at a different receptor might be more effective in this case. 118 Droperidol
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was not different from ondansetron when used for the treatment of established PONV. 119 On the other hand,
ondansetron 4 mg was more effective than metoclopramide 10 mg in this setting.85,120,121
When evaluating PONV following surgery, the role of medication and mechanical factors should be considered first.
Such contributing factors might include opioids, blood draining down the throat, or bowel obstruction. Then rescue
therapy should be initiated as soon as possible. If PONV occurs within 6 hours postoperatively, patients should not
receive a repeat dose of the prophylactic antiemetic; a drug from a different class should be used for rescue. Beyond
6 hours, PONV can be treated with any of the antiemetics used for prophylaxis except dexamethasone and
scopolamine, which are longer acting.
In summary, PONV and pain are very common following ambulatory surgery and should be managed aggressively.
The thorough understanding of the mechanism of these common symptoms and a careful assessment of risk factors
provide a rationale for appropriate management of PONV and pain. The adoption of a comprehensive and
multimodal approach for both symptoms are part of the enhanced recovery strategy.
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Risk stratification tools from the preoperative to the postoperative period
Lee A Fleisher Philadelphia, PA
Since the development of the original Cardiac Risk Index by Lee Goldman in the 1970s, there has been a long
standing goal of developing risk stratification tools to help guide perioperative management. 1 These tools usually are
developed in the form of multivariate indices in which individual risk factors are given weights based upon their
ability to predict specific outcomes. Before discussing specific tools, it is important to understand the methodology
for their development, approach to utilizing them for care and their limitations.2
Development of Risk Stratification Tools and their Limitations
In developing such tools, it is important to understand the purpose for which they will be utilized. Preoperative tools
may be utilized to determine the need for testing as has been incorporated into the American Heart
Association\American College of Cardiology Guidelines on Perioperative Cardiovascular Evaluation. 3 In such
instances, the tool establishes a probability of an event and the clinician could use this probability to determine the
need for further evaluation or in some cases the appropriate intraoperative or postoperative location for care.
Incorporation of intraoperative variables can be utilized for postoperative triage. A higher baseline assessment of
risk does not dictate specific care but helps the clinician develop a plan for care.
Risk stratification tools may be utilized to compare patient populations. This was the original purpose of The
American Society of Anesthesiologists Physical Status Classification. The ASA Classification has been utilized to
assess the rate of complications including death for a given individual or population and determine if local rates are
different than the general population.4 There are numerous surgical risk indices which can be used in a similar
manner. It also has been utilized to compare groups in trials to ensure that randomization was successful.
With respect to methodology, it is important to understand both the inputs and outputs of the tools Outcomes of
interest have varied greatly and can include death, cardiac morbidity, respiratory complications, length of stay and
other less morbid complications. In developing these tools, it is important to define how the outcome of interest is
being assessed since perioperative endpoints have varied greatly between studies. Additionally, the manner in which
complications are detected, either through routine surveillance or by retrospective chart review can lead to bias and
influence these tools.
The most common method of developing a risk index is by collecting data on risk factors and outcomes and
modeling the independent influence of each factor on outcome using multivariate techniques. The risk factors should
be included in the model based upon a conceptual framework for being associated with the outcome of interest. If
the number of patients is sufficiently large that some factors may predict outcome at a P < 0.05 but this correlation
may simply be by chance. If there is no conceptual model for the relationship, most investigators will not include
that variable. The population studied also significantly affects which factors are included in the model. It is
important to recognize that if the study population does not have patients in sufficient numbers with specific risk
factors, then the risk factors may not be significant in the final model. A classic example in the area of cardiac risk is
the lack of inclusion of unstable angina since this factor rarely is observed in patients undergoing elective surgery. It
is therefore important to validate risk models in different populations to determine if the model behaves in a similar
fashion to the population in which it was developed. Some investigators split the population into a derivation and
test set but this still relies on the same population of patients (ie. Same hospital). Understanding these issues can
help the clinician determine how to utilize any risk tool.
Another use of risk models is the determination of the observed to expected (O:E) ratio. Based upon the risk factors,
the expected rate of a known complication can be calculated within some confidence intervals. The observed rate of
that complication for a given institution, practice, or individual surgeon or anesthesiologist can be determined. If the
O:E ratio is greater than 1 then outcomes are worse than expected and the cause of these worse outcomes needs to be
determined in drive improvement. A high O:E ratio (>1) may be due to 1) poor coding of baseline factors and
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therefore a lower than actual expected number or 2) higher observed mortality signaling true quality problems. In
either case, it is important to utilize the information provided by the model or tool to develop quality improvement
programs. An O:E ratio <1 denotes high quality care. Many of the models must be refreshed over time as hospitals
and physicians continue to improve care and therefore the expected rate of complication gets better. The one caveat
is that the O:E ratio may not help define the best location care for an individual patient. The ratio provides
information for the hospital or physicians for the population who are seen at that hospital but one cannot necessarily
extrapolate the determination of the quality of care to individual who is never or rarely seen at that hospital. Newer
techniques of matching may provide better ways of determining the quality of care for an individual patient. 5,6
Risk Indices Currently Available and Used in Practice
Preoperative cardiovascular risk prediction has been an area of active interest for the last 40 years. This area can be
divided into the patient undergoing cardiac surgery and the patient undergoing noncardiac surgery. In the cardiac
surgery arena, the Society for Thoracic Surgeons (STS) developed and then continuously refined risk calculators for
individual surgical procedures.7-10 Specifically, models for coronary artery bypass grafting, isolated valve disease,
and combined procedures have been published and are frequently updated. The STS models are highly effective in
determining how an individual center or surgeon compares to other institutions. The models predict O:E ratios.
Since the original manuscript by Goldman and colleagues in 1977 describing a Cardiac Risk Index, multiple
investigators have validated various clinical risk indices for their ability to predict perioperative cardiac
complications.1 The Revised Cardiac Risk Index (RCRI) was developed in a study of 4315 patients aged 50 years or
greater undergoing elective major noncardiac procedures in a tertiary-care teaching hospital. Six independent
predictors of complications were identified, and included in the RCRI: high-risk type of surgery, history of ischemic
heart disease, history of congestive heart failure, history of cerebrovascular disease, preoperative treatment with
insulin, and preoperative serum creatinine >2.0 mg/d, with increasing cardiac complication rates noted with
increasing number of risk factors. The RCRI has become the standard tool in the literature in assessing the prior
probability of perioperative cardiac risk in a given individual and has been used to direct the decision to perform
cardiovascular testing and implement perioperative management protocols, and has recently been validated for both
short- and long-term outcomes.11
National Surgical Quality Improvement Project (NSQIP)
The NSQIP was started in the Veterans Administration (VA) because of federal concerns about quality for our
veterans. Preoperative data was collected on the selected population of noncardiac surgical patients at the VA and
nurses were utilize to determine 30 day outcomes.12,13 Data on the O:E ratio of various outcomes were distributed
back to the VA hospitals and the use of this information was associated with a marked improvement in outcomes
over the course of the initial implementation phase. Based upon the success in the VA, the American College of
Surgeons (ACS) released a private version of the NSQIP and a number of hospitals enrolled. There are now several
risk calculators derived from the NSQIP available with multiple outcomes of interest to help the clinician inpatient
selection and care provision.
The ACS-NSQIP risk calculator was developed using data from the American College of Surgeons National
Surgical Quality Improvement Project (ACS-NSQIP). (http://site.acsnsqip.org)14 It is based on 1,414,006 patients
encompassing 1,557 unique surgical codes. It includes an enhanced set of variables such ASA classification,
procedure specific CPT code and age which are not been included in other preoperative risk screening tools.
Importantly, the risk calculator allows the clinician to select overall mortality as well as specific outcomes of
interest. Although the model was built with over 1 million patients, it has not been prospectively validated. The risk
calculator has been utilized by anesthesiologist in the preoperative clinic and surgeons in the preoperative visit to
discuss the risk of surgery and the decision to proceed versus a non-surgical approach. While the risk calculator
offers distinct advantages over simpler indexes by incorporating more factors and outcomes, its proprietary nature
and complex algorithm make it more difficult to apply in clinical practice. The software is currently only available
on the web and therefore has not been incorporated at this time into the electronic medical record.
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The NSQIP database was used to determine risk factors associated with intraoperative/postoperative myocardial
infarction or cardiac arrest. A simplified calculator using only the greatest risk variables was developed (Figure 3)
(http://www.qxmd.com/calculate-online/cardiology/gupta-perioperative-cardiac-risk).15 Among > 200,000 patients
who underwent surgery in 2007, 0.65 % developed perioperative MICA. 15 On multivariate logistic regression
analysis, five factors were identified as predictors: (1) Type of Surgery (2) Dependent functional status (3) Elevated
Creatinine (4) American Society of Anesthesiologists’ physical status score, and (5) Increased age (Figure 3). The
risk model was developed using these 5 factors and subsequently validated on a 2008 data set (n=257,385). The risk
model had a relatively high predictive accuracy (C-statistic of 0.874) and outperformed the RCRI (C-stat of 0.747).15
Other Risk Indices
Dr. Moonesinghe and colleagues recently performed a systematic assessment of risk stratification pools for
predicting morbidity and mortality in adult patients undergoing major surgery you they identified 27 study notes and
evaluating 34 with stratification's tools.16 The Portsmouth – Physiology and Operative Severity Score for the
enUmeration of mortality (P-POSSUM) and the Surgical Risk Scale were found to be the most accurate. The
Surgical Risk Score developed by Donati and colleagues incorporates only preoperative data from the general
surgical population and assesses inpatient mortality.17 It is a useful tool for preoperative risk stratification but has
limitations including the use of the ASA – physical status score. It also incorporates a surgical severity coding which
is not intuitive and the Score has only been validated in single centers in the United Kingdom.
Risk Calculators incorporating intraoperative variables
As stated above, risk stratification tools can also be utilized to dictate postoperative care. For example, the extent of
postoperative monitoring in an intensive care unit or step down unit can be modified based upon intraoperative
events. As anesthesiologist, we frequently triage patients to different levels of postoperative monitoring based upon
our interpretation of the intraoperative events. With increasingly limited resources and a focus on cost containment,
it is important to utilize these resources more effectively. Several risk indices have been developed to incorporate
intraoperative events as a predictor of postoperative complications.
Gwande and colleagues have recently introduced the Surgical Apgar Score which incorporates three simple items
including estimated blood loss, lowest intraoperative heart rate and lowest intraoperative mean arterial pressure
using a 10 point scoring system.18 Reynolds and colleagues subsequently validated the score using intraoperative
data from 123,864 procedures across multiple subspecialties. 19 Lower surgical Apgar scores were associated with an
increased risk of death, although the magnitude of this association varied by subspecialty. The Score remained valid
even after adjusting for ASA classification.
The POSSUM scoring system was developed in the United Kingdom and has subsequently been validated in other
countries.20,21 It includes both pre-and intraoperative variables. The P-POSSUM was subsequently developed in
general surgical patients evaluating 30 day mortality.22 It contains 18 variables with an output of the predictive
percentage risk value. The POSSUM and P-POSSUM both overestimate risk in low risk patients.23,24
Summary
In summary, risk indices can be very helpful in both identifying high-risk patients as well as benchmarking rates of
morbidity and mortality based on a series of pre-and intraoperative variables. Their usefulness depends on how the
information will guide perioperative decisions or as a benchmark for quality improvement. All the models have
limitations and therefore it is important to understand those limitations.
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References
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Gerhard-Herman MD, Holly TA, Kane GC, Marine JE, Nelson MT, Spencer CC, Thompson A, Ting HH, Uretsky
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5. Silber JH, Rosenbaum PR, Ross RN, Ludwig JM, Wang W, Niknam BA, Hill AS, Even-Shoshan O, Kelz
RR, Fleisher LA: Indirect Standardization Matching: Assessing Specific Advantage and Risk Synergy. Health Serv
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6. Silber JH, Rosenbaum PR, Ross RN, Ludwig JM, Wang W, Niknam BA, Saynisch PA, Even-Shoshan O,
Kelz RR, Fleisher LA: A Hospital-Specific Template for Benchmarking its Cost and Quality. Health Serv Res 2014
7. Badhwar V, Rankin JS, Jacobs JP, Shahian DM, Habib RH, D'Agostino RS, Thourani VH, Suri RM, Prager
RL, Edwards FH: The Society of Thoracic Surgeons Adult Cardiac Surgery Database: 2016 Update on Research.
Ann Thorac Surg 2016; 102: 7-13
8. Shahian DM, Edwards FH, Jacobs JP, Prager RL, Normand SL, Shewan CM, O'Brien SM, Peterson ED,
Grover FL: Public reporting of cardiac surgery performance: Part 1--history, rationale, consequences. Ann Thorac
Surg 2011; 92: S2-11
9. Shahian DM, Edwards FH, Jacobs JP, Prager RL, Normand SL, Shewan CM, O'Brien SM, Peterson ED,
Grover FL: Public reporting of cardiac surgery performance: Part 2--implementation. Ann Thorac Surg 2011; 92:
S12-23
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McDonald DE, Grover FL: The society of thoracic surgeons national database. Heart 2013; 99: 1494-501
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Poldermans D: Preoperative cardiac risk index predicts long-term mortality and health status. The American journal
of medicine 2009; 122: 559-65
12. Khuri SF: The NSQIP: a new frontier in surgery. Surgery 2005; 138: 837-43
13. Khuri SF, Daley J, Henderson W, Hur K, Demakis J, Aust JB, Chong V, Fabri PJ, Gibbs JO, Grover F,
Hammermeister K, Irvin G, 3rd, McDonald G, Passaro E, Jr., Phillips L, Scamman F, Spencer J, Stremple JF: The
Department of Veterans Affairs' NSQIP: the first national, validated, outcome-based, risk-adjusted, and peer-
controlled program for the measurement and enhancement of the quality of surgical care. National VA Surgical
Quality Improvement Program. Ann Surg 1998; 228: 491-507
14. Bilimoria KY, Liu Y, Paruch JL, Zhou L, Kmiecik TE, Ko CY, Cohen ME: Development and evaluation of
the universal ACS NSQIP surgical risk calculator: a decision aid and informed consent tool for patients and
surgeons. J Am Coll Surg 2013; 217: 833-42 e1-3
15. Gupta PK, Gupta H, Sundaram A, Kaushik M, Fang X, Miller WJ, Esterbrooks DJ, Hunter CB, Pipinos, II,
Johanning JM, Lynch TG, Forse RA, Mohiuddin SM, Mooss AN: Development and validation of a risk calculator
for prediction of cardiac risk after surgery. Circulation 2011; 124: 381-7
16. Moonesinghe SR, Mythen MG, Das P, Rowan KM, Grocott MP: Risk stratification tools for predicting
morbidity and mortality in adult patients undergoing major surgery: qualitative systematic review. Anesthesiology
2013; 119: 959-81
17. Donati A, Ruzzi M, Adrario E, Pelaia P, Coluzzi F, Gabbanelli V, Pietropaoli P: A new and feasible model
for predicting operative risk. Br J Anaesth 2004; 93: 393-9
18. Gawande AA, Kwaan MR, Regenbogen SE, Lipsitz SA, Zinner MJ: An Apgar score for surgery. J Am Coll
Surg 2007; 204: 201-8
19. Reynolds PQ, Sanders NW, Schildcrout JS, Mercaldo ND, St Jacques PJ: Expansion of the surgical Apgar
score across all surgical subspecialties as a means to predict postoperative mortality. Anesthesiology 2011; 114:
1305-12
20. Jones DR, Copeland GP, de Cossart L: Comparison of POSSUM with APACHE II for prediction of
outcome from a surgical high-dependency unit. Br J Surg 1992; 79: 1293-6
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21. Jones HJ, de Cossart L: Risk scoring in surgical patients. Br J Surg 1999; 86: 149-57.
22. Whiteley MS, Prytherch DR, Higgins B, Weaver PC, Prout WG: An evaluation of the POSSUM surgical
scoring system. Br J Surg 1996; 83: 812-5
23. Brooks MJ, Sutton R, Sarin S: Comparison of Surgical Risk Score, POSSUM and p-POSSUM in higher-
risk surgical patients. Br J Surg 2005; 92: 1288-92
24. Organ N, Morgan T, Venkatesh B, Purdie D: Evaluation of the P-POSSUM mortality prediction algorithm
in Australian surgical intensive care unit patients. ANZ J Surg 2002; 72: 735-8
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Multi-Disciplinary Teams: What Perioperative Medicine Can Learn from the

ICU Experience
Michael A. Gropper, MD, PhD San Francisco, CA
Introduction
Critical care has embraced multidisciplinary care in an effort to provide both quality and value to critically ill
patients. Perhaps in no other hospital setting does is the functioning of a “team” more important in providing
patient-centered outcomes. Much work has been done to develop teamwork in the operating room, with the recent
development of the “time out”, postoperative debrief, and the advent of teamwork training among various
perioperative providers. However, the operating room remains well behind the ICU in truly leveraging the entire
transdisciplinary team. This discussion will highlight the best practices of what is now referred to as
“transdisciplinary care”, recognizing the importance of overlapping responsibilities and communication.
The Transdisciplinary ICU Team
The transdisciplinary ICU team is based on the premise that the highest functioning organizations are able to achieve
the best results when a “horizontal” power structure recognizes the equally important contributions of multiple
members of a team. It is a basic tenet of safety culture that everyone involved in care should feel free to speak up if
they observe potential danger to the patient. At the same time, the ICU team is made up of multiple experts, who
should be allowed to practice at the “top of their profession”. For example, why should a physician struggle to
understand complex drug interactions in a patient with severe sepsis and renal failure, when the team has a Pharm.D,
who is highly trained in understanding and treating those specific problems? Why would an intern try to remember
the overnight events that affected a patient, when the bedside nurse is present on rounds and can give an updated
summary, in addition to the most current medication doses? The traditional model of hospital care relied on
“heroism”, where the physician was expected to be all-knowing. This model has obvious limitations, and fails to
leverage the unique talents and skills of the transdisciplinary team, and just as importantly, fails to leverage
technology to prevent hospital-acquired harms. 1 Observations of ICU rounding behavior shows that while
substantial progress has been made, there is still room for improvement. 2-4
Intensivists: There is strong evidence that trained intensivists improve outcomes in critically ill patients, reducing
both mortality and length of stay.5 However, the specific effect of the intensivist is unclear. I would argue that in
addition to experience gained from fellowship training in critical care and caring for multiple, critically ill patients,
perhaps the greatest impact of the intensivist comes from their ability to build these transdisciplinary teams, and
more importantly, build a culture of safety and mutual respect. Interestingly, the impact of the intensivist does not
appear to depend on continuous presence (which would be expected with a “hero”), but rather ICU’s that had
daytime intensivists still had reduced mortality at night, when the intensivist was not present. This would argue that
the intensivist serves to create a safe environment of care, rather than being a superior diagnostician or clinician.
The intensivist “leads” the ICU team, but I would argue that the role is as much “conductor” as it is leader, making
sure that each member of the transdisciplinary team is heard.
Bedside Nurses: ICU’s are defined as a unit with a high nurse:patient staffing ratio. Therefore, the critical
component of the ICU is the critical care nurse. These highly trained professionals provide high-intensity,
continuous care, and are THE essential element of the ICU. ICU rounds at UCSF begin with the bedside nurse, who
updates the team on overnight events and current medications and concerns. Ethnographic studies show that
physicians tend to form a circle at the bedside, excluding non-physicians, and especially nurses, outside the circle.
This is a sign of an ICU culture that doesn’t fully respect the role of the most critical providers in the ICU.
Nurse Practioners/Physician Assistants: Increasingly, care is delivered by advanced healthcare practitioners

(AHP’s), who have high-level training to provide direct patient care. Although there are clear differences in training
between MD’s and NP’s/PA’s, there is significant overlap. We leverage AHP’s to help provide care for a large
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number of ICU patients, working as a transdisciplinary group with residents, fellows, and intensivists. This
relationship is not unlike that of the team-based care model in the OR, where physician anesthesiologists supervise
nurse anesthetists (CRNA’s) or anesthesia assistants (AA’s). Increasingly, CRNA’s lobby and obtain the ability to
practice independently, however, this remains a highly controversial area of practice. Interestingly, NP’s and PA’s
working in the ICU have not lobbied for similar independence. There is some data on outcomes of patients cared for
by NP/PA’s in the ICU, suggesting that outcomes are similar.6 However, this data would be expected to be
consistent with that of Pronovost and others showing that intensivist staffing of the ICU is the key determinant in
patient outcomes.
Pharmacists: There is no patient care setting where medication management is as complex as in the ICU. Patients
are receiving numerous medications while in the throes of critical illness. Although intensivists are well trained in
them management of drug interactions, there is no question that PharmD’s are more intensively trained, especially
when they have had advanced training in critical care. In addition, there are innumerable studies showing that
pharmacists are key stakeholders in ICU quality improvement projects including sepsis diagnosis and treatement,
antimicrobial stewardship, and delirium prevention. Personal experience shows that ICU pharmacists are an
essential element of the team, both preventing adverse drug reactions, and optimizing therapeutics. While most
OR’s have a pharmacist in a satellite pharmacy, anesthesiologists remain the only physicians who continue to
compound medications. I believe that this practice contributes to medication errors and adverse patient outcomes.
While there has been gradual movement towards less individual medication preparation by anesthesiologists, there is
still much work to be done.
Respiratory Therapists (RT’s): RT’s are an essential component of any ICU. Complex management of
mechanically ventilated patients, provision of CPAP/BiPAP, delivery of inhaled medications, and general
management of patients with respiratory insufficiency or failure is a complex task. Perhaps no RT contribution is
greater than the organized approach to providing protective mechanical ventilation, and the coordinated weaning
patients receiving mechanical ventilation. The ARDSnet trial was the seminal trial showing that a lung protective
ventilation strategy could result in substantial reduction in mortality and duration of mechanical ventilation. Equally
important, perhaps, to the use of low tidal volume, was the use of ventilation protocols and protocolized weaning.7
Prior to the ARDSnet trial, Ely et al showed that by allowing RT’s and bedside RN’s to manage protocolized
weaning (as opposed to all ventilator changes driven by MD order), duration of mechanical ventilation could be
substantially reduced.8
Physical/Occupational Therapists: One of the most noticeable changes in critical care over recent years has been
the advent of early mobilization.9 Whereas patients were up until recently, heavily sedated, studies have shown that
early mobilization leads to substantially improved outcomes, including reduced delirium, earlier extubation,
shortened length of hospital and ICU stay, and increased patient satisfaction. This effort has been led by both
intensivists and physical therapists (PT’s). PT’s are now considered an essential component of any modern ICU.10
Although in concept simple, this intervention is a true test of culture, as it requires careful coordination of care by
multiple providers, including RN’s, MD’s, RT’s, and PT’s. This is perhaps the most impactful change in modern
ICU practice to date.
Family Members: Ironically, the last member to be added to the transdisciplinary treatment team is the family. We
have moved from a paternalistic model of patient care to one of shared decision making. In the ICU, this has
occurred in multiple ways: family participation in bedside rounds, family participation in mobilization and basic
patient care, presence during procedures and codes, shared decision making, and patient-family advisory councils
(PFAC’s).11 PFAC’s are organized meetings consisting of former patients and family members along with ICU
providers. Interaction between these groups outside of the ICU setting provides powerful information to inform and
improve patient care. In particular, these occasions educate providers on how to provide care to ICU patients with
respect and dignity. This is an evolving area in critical care, but is a natural avenue of pursuit for those whose
practice is in the OR.
Conclusions: Critical care has made substantial process in transdisciplinary care. The outcomes and satisfaction of
patients in the ICU has improved substantially in recent years. The reasons for these improved outcomes are almost
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entirely due to improved communication and application of basic practices. There has been no “miracle” drug
developed to reduce mortality in these patients. The OR has much to learn from transdisciplinary practice in the
ICU. Although the OR is a unique environment, it too, has providers from multiple specialties attempting to
function as a synergistic unit. The challenge will be to identify the best opportunities for transdisciplinary care in
the OR, and make them a routine part of our practice.
1. Pronovost PJ, Bo-Linn GW, Sapirstein A. From heroism to safe design: leveraging technology.
Anesthesiology. 2014 Mar;120(3):526-9.
2. Curtis JR, Cook DJ, Wall RJ, Angus DC, Bion J, Kacmarek R, Kane-Gill SL, Kirchhoff KT, Levy M,
Mitchell PH, Moreno R, Pronovost P, Puntillo K. Intensive care unit quality improvement: a "how-to"
guide for the interdisciplinary team. Crit Care Med. 2006 Jan;34(1):211-8.
3. Paradis E, Leslie M, Gropper MA, Aboumatar HJ, Kitto S, Reeves S. Interprofessional care in intensive
care settings and the factors that impact it: results from a scoping review of ethnographic studies. J Crit
Care. 2013 Dec;28(6):1062-7.
4. Paradis E, Leslie M, Gropper MA. Interprofessional rhetoric and operational realities: an ethnographic
study of rounds in four intensive care units. Adv Health Sci Educ Theory Pract. 2015 Dec 24.
5. Pronovost PJ, Angus DC, Dorman T, Robinson KA, Dremsizov TT, Young TL. Physician staffing patterns
and clinical outcomes in critically ill patients: a systematic review. JAMA. 2002 Nov 6;288(17):2151-62.
6. Landsperger JS, Semler MW, Wang L, Byrne DW, Wheeler AP. Outcomes of Nurse Practitioner-
Delivered Critical Care: A Prospective Cohort Study. Chest. 2016 May;149(5):1146-54.
7. Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with
traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med
2000;342:1301-8.
8. Ely EW, Baker AM, Dunagan DP, Burke HL, Smith AC, Kelly PT, Johnson MM, Browder RW, Bowton
DL, Haponik EF. Effect on the duration of mechanical ventilation of identifying patients capable of
breathing spontaneously. N Engl J Med. 1996 Dec 19;335(25):1864-9.
9. Lipshutz AK, Gropper MA. Acquired neuromuscular weakness and early mobilization in the intensive care
unit. Anesthesiology. 2013 Jan;118(1):202-15.
10. Engel HJ, Needham DM, Morris PE, Gropper MA. ICU early mobilization: from recommendation to
implementation at three medical centers. Crit Care Med. 2013 Sep;41(9 Suppl 1):S69-80.
11. Kon AA, Davidson JE, Morrison W, Danis M, White DB; American College of Critical Care Medicine;
American Thoracic Society. Shared Decision Making in ICUs: An American College of Critical Care
Medicine and American Thoracic Society Policy Statement. Crit Care Med. 2016 Jan;44(1):188-201.
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New Developments in Thoracic Anesthesia
Edmond Cohen New York, N.Y.

A variety of thoracic surgical procedures, such as lobectomy, pneumonectomy, esophago-gastrectomy, pleural
decortication, bullectomy and bronchopulmonary lavage are commonly performed. Customarily they are
classified either as absolute or as relative. LUNG ISOLATION include life-threatening complications, such as
massive bleeding, sepsis and pus, where the non diseased contra lateral lung, must be protected from
contamination. Broncho-pleural and broncho-cutaneous fistulae are absolute indications since they offer a low
resistance pathway for the delivered tidal volume during positive pressure ventilation. Giant unilateral bullae may
rupture under positive pressure and ventilatory exclusion is mandatory. Finally, during bronchopulmonary lavage
for alveolar proteinosis or cystic fibrosis, prevention of the contra lateral lung from drowning is necessary. Video
assisted thoracoscopy (VAT) brought to the practice of surgery for diagnostic and therapeutic procedures required
a well collapse lung and should be included in the absolute indication for OLV category. LUNG SEPARATION
which includes lobectomies (particularly right upper), pneumonectomy, and thoracic aortic aneurysm repair, are
primarily for surgical exposure. Lower or middle lobectomy and esophageal resection are of lower priority. In
practice, the majority of the procedures where DLT is used, are in essence relative indication, and only a small
fraction are absolute. The use of OLV for relative indications rely on the surgeon-anesthesiologist practice and
preference.
METHODS OF LUNG SEPARATION :In the past, bronchial blockers and the single-lumen endobronchial
tubes have been utilized to achieve lung isolation. These tubes are seldom used today due to technical obstacle,
inability to remove secretions from the non-ventilated lung, and less than satisfactory performance. In modern
practice, endobronchial double-lumen tubes (DLTs) are most widely employed. These tubes have a fixed
curvature, are without a carinal hook to avoid tracheal laceration, and reduce the likelihood of kinking. The
original non-disposable Robertshaw red rubber tubes are presently available in small, medium and large sizes.
Numerous manufacturers produce clear disposable PVC Robertshaw design DLTs, which are available in French
sizes 35-41. (Mallinckrodt, Rusch, Sheridan). Essentially, they consist of similar features and modify in cuff
shape and location. A colored bronchial cuff, commonly blue, permits easy identification by fiberoptic
bronchoscopy. The right endobronchial cuff is donut-shaped, and allows the right upper lobe ventilation slot to
ride over the right upper lobe orifice. Most authors refrain from using right-sided DLT simply to avoid potential
obstacle. A 37Fr DLT can be used in most adult female, while 39 Fr are used in the average adult male. These
types of PVC tubes are currently considered the foremost and are most extensively used to obtain lung separation.
In recent years, 28 F and 32F DLT’s were introduced for small adults.
Positioning of Double-Lumen Tubes: Following intubation the tracheal cuff should be inflated first and equal
breath sounds should be confirmed. To ensure from mucosal damage from excessive pressure applied by the
bronchial cuff, the cuff is inflated with incremental volume to seal air leaks around the bronchial cuff into the
tracheal lumen. Inflation of the bronchial cuff seldom requires more than 2 ml of air. Bilateral breath sounds
should be re-checked to confirm that the bronchial cuff is not herniating over to impede the ipsilateral lung
ventilation. An important step is to verify that the tip of the bronchial lumen is located in the designated
bronchus. One simple way to check is to first clamp the tracheal lumen (always at the level of the connector!),
observe and auscultate. Usually, inspection will reveal unilateral ascent of the ventilated hemithorax. Following
proper auscultation, the bronchial lumen is clamped to ventilate the tracheal lumen. Each time a right-sided DLT
is used, appropriate ventilation of the right upper lobe should be ensured. This can be accomplished by careful
auscultation over the right upper lung field or more accurately by fiberoptic bronchoscope. When a left-sided
DLT is used, the risk of occluding the left upper lobe bronchus by the bronchial tip advanced far into the left main
bronchus should be kept in mind. If peak airway pressure is of 20 cm H 2O during two-lung ventilation, for the
same tidal volume, that pressure should not exceed 40cm H2O on OLV.
Perhaps the most important advancement in confirming the proper positioning of DLTs is the introduction of
fiberoptic bronchoscopy to clinical practice. It has been recently shown that DLTs, thought to be correctly
positioned by inspection and auscultation, subsequent fiberoptic bronchoscopy revealed malposition in 20-48%.
The simplest method to evaluate proper positioning of a left sided DLT is bronchoscopy via the tracheal lumen.
The carina is then visualized, while only the proximal edge of the endobronchial cuff should be identified just
below the tracheal carina. Herniation of the bronchial cuff over the carina to partially occlude the ipsilateral main
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bronchus should be excluded. The bronchial blue cuff of the clear disposable PVC DLT is easily visualized, while
the non-disposable rubber DLTs contains yellow bronchial cuffs somewhat more difficult to recognize.
Bronchoscopy should then be performed via the bronchial lumen to identify the patent left upper lobe orifice.
When using a right-sided DLT, the carina is visualized through the tracheal lumen. More importantly, the right
upper lobe bronchial orifice must be identified while the bronchoscope is passed through the right upper lobe
ventilating slot This is somewhat complex to accomplish and requires a relatively skilled endoscopist. Several
sizes of bronchoscope are available for clinical use: 5.6, 4.9, and 3.9 mm of external diameter (Olympus Co.).
The 3.9mm-diameter bronchoscope can easily pass through a 37 Fr or larger tube, while it a tight fit through a 35
Fr tube.
An airway may be termed difficult when conventional laryngoscopy reveals a grade III view (just epiglottis) or a
grade IV view (just soft palate). Furthermore, depending on the type and the length of surgery, the degree of fluid
shift during surgery, an airway that initially was not classified as difficult may become difficult secondary to
facial edema, the presence of secretion and laryngeal trauma from the initial intubation. A logical approach to lung
separation is described in Figure 1. When the separation of the lung is strictly indicated, use of tubes that are
difficult to insert such as DLT or a Univent tube cannot be avoided despite the presence of a difficult airway. If
the patient has a recognized difficult airway awake Intubation with fiberoptic bronchoscopy (FOB) can be
attempted using DLT / Univent /or a SLT. The same approach may be use for the patient with an unrecognized
difficult airway and a failure to intubate with conventional laryngoscopy. When using a DLT over a fiberoptic
bronchoscope (FB) one should keep in mind that it is a bulky tube with a large external diameter, and because the
length of the DLT, only a limited part of the FB is available for manipulation. In addition, the mismatch between
the flexibility of the FOB and the rigidity of the DLT make it harder to pass over the FOB. (5) The Univent tube
has the same bulky external diameter and is also often hard to pass through the vocal cords particularly in an
awake patient. In some cases advancing the bronchial blocker of the Univent tube can serve as an introducer to
facilitate the passage through the larynx. Following a successful intubation with a DLT or a Univent tube, OLV
can be immediately established. If these difficult tubes cannot be inserted over a FOB, than a SLT should be use
to establish an airway.
The use of a tube exchanger: Several tube exchangers are available: (Cook Critical Care, Bloomington, IN.). All
of these airway guides are commercially made, are depth marked in centimeters, are available in a wide range of
ODs, and are easily adapted for either oxygen insulation or jet ventilation. The airway guide may be used for
inserting an SLT, changing an SLT to one of the difficult tubes, or simply inserting a difficult tube. Critical details
to keep in mind to maximize benefit and minimize risk of airway guides are as follows: First, the size of the
airway guide and the size of the difficult tube must be determined and should be tested in vitro before the use of
the airway guide. Second, the airway guide should never be inserted against a resistance; the clinician must
always be cognizant of the depth of insertion. Two reported perforations of the tracheobronchial tree have
occurred. Third, a jet ventilator should be immediately available
DLT/Airway Exchange Catheter Figure 2 in case the new tube does not follow the airway guide into the
SMALL MEDIUM LARGE
DLT Size
(N 11) (N 14) (N 18) trachea, and the jet ventilator should be preset at 25 psi by the
35F
use of an additional in-line regulator. Finally, when passing any
SATISFACTORY
tube over an airway guide, a laryngoscope should be used, to
37F BORDERLINE facilitate passage of the tube over the airway guide past
IMPOSSIBLE supraglottic tissues. Because of the potential injury to the
39F bronchial tree from the stiff tip of the tube exchanger, a new
catheter is been designed that have a soft tip to reduce the risk of
41F
trauma.
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ENDOBRONCHIAL BLOCKERS Over time, it has become clear that modern thoracic anesthesiologists need
an alternative to DLT’s. In the past, Fogarty embolectomy catheters were used to achieve lung isolation.
Placement may be difficult, due to its lack of
directing mechanism and communication
channel in the center; therefore suctioning or
INDICATION FOR THE USE OF ENDOBRONCHIAL BLOCKERS oxygen insufflation is unachievable. Finally,
 Lung Isolation Vs Lung Separation due to the high pressure low volume spherical
Video Assisted Thoracoscopy ; Increase the Number of Patients Who Required OLV
Avoid the Need for Tube Exchange shaped cuff, the elliptic shape of the bronchus
is poorly occluded. Today, Fogarty catheters
The Difficult Airway
Patients With a Difficult Airway ( Mllampatti 3 or 4) have no use in thoracic anesthesia practice
 Patients Post Laryngeal/Pharyngeal surgery In modern thoracic anesthesia, three
 Patients with Tracheotomy
independent 9F endobronchial blockers (EBB)
Patients with Distorted Bronchial anatomy from aneurysm compression or intraluminal tumor
were introduced to clinical practice. The
 Patients who Requires Nasotracheal Intubation clinical indications for the use of
 Patients with a Immobility or Kypjhoscoliosis
endobronchial blockers are out line in a recent
Surgical Procedure Non-Evolving the Lung Pro debate by Cohen. (See table). The Arndt
 Esophageal surgery blocker (Ardnt , Cook Inc., Bloomington IN).
 Spine Surgery that Required Transthoracic Approach
 Minimally Invasive Cardiac Surgery The FB is passed through the loop and guided
into the desired bronchus than the BB is slide
Management:
over the FB into the select bronchus.
 VAT procedures where a quick look or simple wedge of chest exploration is planned
 Possible Segmental blockade in patient intolerable to OLV Bronchoscopic visualization confirms blocker
 Morbidly obese
 Small size adult or pediatrics placement and occlusion. The string may than
 Patients who requires intraoperative lung isolation removed and a 1.8mm lumen may be used as a
 Patients who arrive intubated to the OR from the ICU
suction port or for oxygen insufflation. In the
first generation of this device it was not
The need to teach the new generation and for practice for the present generation
possible to reinsert the string once it have been
pulled out losing the ability to redirect the BB
if necessary. A recent modification in the
string design overcomes the problem. Finally, the external diameter is somewhat larger which requires a large size
SLT (at list 8.0 mm) to be able to accommodate the BB. Te Ardnt blocker is available in 7F and in a pediatric
size . More recently a new endobronchial blocker has been approved by the FDA for clinical use. The Cohen
Flexitip Endobronchial Blocker is designed for use as independent BB through a standard ET with a small 4.0
mm fiberoptic bronchoscope. The most important feature of the blocker is that it uses a flexible soft tip that can be
deflected to more than 90 degrees and easily directed into the desired bronchus needed to be blocked. As
demonstrated by the figure, the deflection of the tip is achieved by rotation of the wheel that is located at the
proximal part of the BB. The blocker cuff is a high volume, low-pressure balloon that have appear shape that
provides adequate seal of the bronchus. The blocked contain a lumen (1.6mm) that allow suctioning of the lung to
facilitate deflation, a limited suctioning of secretion and insufflation of oxygen to the collapsed lung in case of
hypoxia. (Cook Inc., Bloomington Indiana)
The Univent Tube: The Univent tube (Univent, Fuji Systems Corp., Tokyo, Japan) is a novel, relatively new
means of achieving bronchial blockade. The bronchial blocker technique has been modified so that the bronchial
blocker is passed along a single-lumen endobronchial tube. The bronchial blocker is housed in a small anterior
lumen containing a thin (2 mm internal diameter) tube with a distal balloon (blocker tube). The Univent tube has
the advantage of using a single lumen tube instead of a DLT, and there no need to change over at the end of the
procedure if postoperative ventilatory support is required. It is also possible to suction through the blocker lumen
or to apply CPAP to improve oxygenation in case of hypoxia. The disadvantages of the tube are: The enteral
diameter is relatively large, the blocker can dislocate during surgical manipulation, and satisfactory bronchial seal
and lung separation are sometimes hard to achieve. Finally, like other endobronchial blockers, the relative small
diameter of the blocker lumen makes it more difficult to remove secretion, and prolong the time required to
achieve a complete deflation of the non-dependent lung. The new generations TCB Univent (Torque control
blocker) are made out of silicone are easier to manipulate to the selected bronchus. The Univent tube blocker is
now available as an independent blocker to be inserted through a standard ET tube (Uniblocker), which is
available in 9F and 5F for pediatric patients..The EZ Blocker (Teleflex Life Sciences Ltd, Athlone, Ireland) is
a 7.0 F endobronchial blocker recently introduced into clinical practice. The catheter designed with a Y-
shaped 2 distal extensions; both have inflatable cuffs and a central lumen. Intended to overcome the
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need to steer the blocker to a selected main bronchus, this bifurcated catheter rides over the carina and
each lung can be selectively deflated
MANAGEMENT OF OLV: Once the patient has been placed in the lateral decubitus position, proper DLT
position should be re-checked, since dislocation during position change is not uncommon. Two-lung ventilation
should be maintained for as long as possible. When OLV is required, a Fi02 of 1.0 provides a high margin of
safety to protect against possible hypoxemia. With a FiO2 of 1.0, assuming an intact hypoxic pulmonary
vasoconstriction (HPV) response, PaO2 during OLV should be between 150-210 mmHg. The patient should be
ventilated with a tidal volume of 10-12 ml/kg at a ventilatory rate to maintain a PaCO2 of 35+3 mmHg that can be
estimated from the end-tidal CO2 value. Low tidal volume might produce atelectasis in the ventilated lung
(reduced FRC) and increases in the degree of shunt. High tidal volume might shift blood flow into the non-
dependent lung (similar to the application of PEEP) to increase the transpulmonary shunt. Following the initiation
of OLV, PaO2 can continue to decrease for up to 45 minutes, hence, close monitoring of arterial blood gases
and/or the use of a pulse oximeter are indispensable. Should hypoxia occur, proper positioning of the DLT should
be re-conform by fiberoptic bronchoscopy. Several techniques can be employed to improve oxygenation. The
most effective maneuver for improving PaO2 is the application of a continuous positive airway pressure of 10 cm
H2O (CPAP10) to the non-dependent lung. It consists of insufflation of oxygen under positive pressure to keep a
“quiet” lung, while preventing it from collapsing completely. The beneficial effect of CPAP 10 is not secondary to
the positive pressure effect, potentially causing blood flow diversion to the dependent perfused lung, but from
distending the alveoli with oxygen to allow gas exchange. Hyperinflation of nitrogen under positive pressure into
the non-dependent lung failed to improve PaO2. Most studies confirmed that dramatic improvement in PaO2
values with the application of CPAP10. PEEP may be added to the dependent lung, or in combination with
CPAP10 to the non-dependent lung. PEEP10 alone added to the dependent lung, resulted in either no change or in
a decrease in PaO2 values. Most probably, the beneficial effects of PEEP to the dependent lung, assumed to be
subsequent to expansion of atelectatic alveoli, are offset by the increased blood flow diverted to the non-ventilated
lung from the continuous positive pressure. In summary, the preferred method to manage hypoxemia during OLV
is by application of CPAP to the non-dependent lung with a search for an optimal combination of PEEP and
CPAP (between 5-10 cm of H2O). In exceptional cases, despite all of these maneuvers, PaO2 will fail to improve
and intermittent ventilation of the non-dependent lung should be reinstituted with the surgeon’s collaboration.
Depending on the stage of the surgery, if a pneumonectomy is planed, ligation of the pulmonary artery will
eliminate the shunt through that lung. Should doubt arise as to the stability of the patient, (patient becomes
hypotensive, dusky, or tachycardic), two-lung ventilation should be resumed until the problem is settled.
Recently, more attention is directed toward the protection of the ventilated lung. Data form studies conducted in
the ICU recommended the use of low tidal volume (TV) to avoid acute lung injury (ALI). That concept stimulated
a debate over the optimal TV that should be used during OLV. A recent Pro and Con editorial argued that large
TV of 12ml/Kg during OLV may cause over distention and stretching of the lung parenchyma and therefore
would increase the risk of ALI. On the other hand, low TV of 6ml/Kg would predispose the formation of
atelectasis in the depended lung. Furthermore, low TV with PEEP may cause dynamic hyperinflation secondary to
the increase in respiratory rate to maintain PaCO2.
Other important issues are: the use of frequent recruiting maneuvers to reduce the amount of atelectasis in the
dependent lung. The limitations of fluid administration during the procedure to avoid fluid overload which may
increase lung capillary permeability. The risk of ALI and fluid overload increases proportionally to the extension of
the lung parenchyma resection. Finally, total intravenous anesthesia (TIVA) would least inhibit the protective effect
of hypoxic pulmonary vasoconstriction and decrease the transpulmonary shunt through the ventilated lung. A
recent study by Yang et al, compared a group of patients who were ventilated using protective lung ventilation
regime ( TV 6/ml/kg , PEEP 5 Cm H2O, pressure-controlled, Fio2 0.5) compared to conventional ventilation ( FiO2
1.0, TV 10 ml/Kg, Zero PEEP, Volume–controlled.). They found a better oxygenation intra and pos-operatively and
less post operative pulmonary complications in the protective lung ventilation group.
A recent review by Karzai W, addressed the, prediction prevention and treatment of hypoxemia during one lung
ventilation.
VIDEO ASSISTED THORACOSCOPY
The improvements in video endoscopic surgical equipment and a growing enthusiasm for minimally invasive
surgical approaches brought VAT to the practice of surgery for diagnostic and therapeutic procedures. Most of these
procedures required a well-collapsed lung and should be included in the absolute indication for OLV category. The
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patient population tends to be either very healthy, undergoing diagnostic procedures, or high-risk patients who are
undergoing VAT to avoid the stress of a thoracotomy. The patients with advanced cardiopulmonary disease should
have an extensive pre-operative evaluation and interaoperative monitoring the same as for thoracotomy. Small
incision in the chest wall permits the insertion of the video camera and the surgical instruments. In most cases
general anesthesia with one lung ventilation is required. The lung should be well collapsed to allow the surgeon an
optimal view of the surgical field and to palpate the lesion in the lung parenchyma. Because it may take 30 minute
for the lung to collapse it is advisable to initiate OLV immediately following endobronchial intubation. In some
cases, CO2 is insufflated to facilitate visualization, at pressure <10 mm H 2O with a flow of less than 2 L/min.
Higher pressure may cause mediastinal shift with cardiovascular compromise. In a very small selected group of
patients to avoid the need for endobronchial intubation, VAT may be performed under regional anesthesia using an
intercostals block or epidural. The patients for regional VAT should be carefully selected and the risk benefit should
be considered.
PROTECTIVE LUNG VENTILATION with a TV less than that used for two lung ventilation and
accomplishing ventilation with the lowest feasible peak airway pressure, I: E ratio of 1:1, with a rapid respiratory
rate. Alternatively, one may use pressure control ventilation. Patients with COPD may have difficulties if PEEP
leads to dynamic hyperinflation secondary to the increase in respiratory rate to maintain a satisfactory
PaCO2.Recruiting maneuvers should be used to reduce the amount of atelectasis in the dependent lung. They
should be applied with sustained peak pressure of 40 cm H 20 to be effective. One should limit fluid
administration during thoracic surgery procedures to avoid fluid overload. Finally, a balanced anesthetic
technique with inhalational agents and adjuvants (propofol infusion, opioids) to reduce the required
concentration of potent inhaled agent, appears the best choice during OLV. In an interesting recent prospective
randomized study by De Conno et al., 58 patients undergoing thoracic surgery were divided to receive either
propofol of sevoflurane. The sevoflurane group showed not only an attenuated inflammatory reaction at the
organ level in the lung undergoing OLV, but also an improved postoperative course with significantly lower
overall number of adverse events. In a randomized study during elective lobectomy by Yang et al, patients
were ventilated with a high VT of 10 ml/kg without PEEP compared to a low VT of 6 ml/kg with 5 cmH2O of
PEEP and pressure controlled ventilation. The lung-protective ventilation was associated with a lower
incidence of lung infiltration or atelectasis (2 versus 10) and of cases of hypoxemia (1 versus 8). At
review by Karzai W et al., discussed prevention and treatment of hypoxemia during one lung ventilation.
In a recent multicenter randomized controlled trial by Beck-Schimmer et al, a. Patients scheduled for
lung surgery with OLV were randomly assigned to one of two parallel arms to receive either propofol
or desflurane as general anesthetic. Patients and surgeons were blinded to group allocation. Time to
occurrence of the first major complication was defined as primary during hospitalization or
secondary,6-month follow-up endpoint. The authors enrolled 460 were randomized and analyzed (n =
230 for each arm). Incidence of major complications during hospitalization was 16.5% in the propofol
and 13.0% in the desflurane groups vs. propofol, 0.75; 95% CI, 0.46 to 1.22; P = 0.24). Incidence of
major complications within 6 months from surgery was 40.4% in the propofol and 39.6% in the
desflurane groups vs. propofol, 0.95; 95% CI, 0.71 to 1.28; P = 0.71). The authors concluded that no
difference between the two anesthesia regimens was evident.
Clinical approach to OLV management

1. Use Fio2 of 1.0
2. Ventilate with a TV of 6-8 ml\Kg with PEEP 5 cm H2O
3. Respiratory rate to maintain PaCO2 between 35-40 mmHg
4. Check the DLT/endobronchial blocker position subsequent to the lateral decubitus positioning
5. If peak airway pressure exceeds 40 mmHg during OLV, DLT/endobronchial blocker

malposition should be excluded.
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6. For hypoxemia, apply CPAP10 cm H2O to the non-dependent lung. (not during VAT)
7. If additional correction of hypoxemia is necessary add PEEP 5-10 cmH2O to the ventilated
lung.
8. Frequent recruiting maneuvers
9. Avoid fluid over-load
10. TIVA may be preferable to inhalation anesthetics
11. If necessary, intermittently inflate and deflate the operated lung
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comparison of two types. Anesthesiology 63:734-740, 1988.
-Smith G, et al. Sight and sound. Can double-lumen endotracheal tubes be placed accurately without fiberoptic
bronchoscopy? Br J Anaesth 58:1317, 1987.
-Cohen, E, et al. Fiberoptic Evaluation of Endobronchial tube position: red rubber vs. polyvinylchloride. Anesth
Analg 68: S1-S321, 1989.
-Cohen, E, et al. Oxygenation and hemodynamic changes during one-lung ventilation. J Cardiothoracic Anesthesia:
2:134-40, 1988.
-Karande SV. A new tube for single lung ventilation. Chest 92:761-763, 1987.
-Campos JH, et al. Is there a better right-sided tube for one-lung ventilation? A comparison of the right-sided
double-lumen tube with the single-lumen tube with right-sided enclose bronchial blocker Anesth Analg. 86 (4) 696-
700, 1998.
-Arndt GA, Kramer PW, Rusy DA, et al: Single lung ventilation in a critically ill patient using a fiberoptically
directed wire-guided endobronchial blocker. Anesthesiology. 90: 1484-6, 1999.
- Prabhu MR, Smith JH. Use of the Arndt wire-guided endobronchial blocker: Anesthesiology 97: 1325, 2002.
-Campos JH, Kernstine KH. A comparison of a left-sided Bronco-Cath with the torque control blocker Univent and
the wire-guided blocker. Anesth Analg. 96: 283-9, 2003.
-Campos JH: Progress in lung separation. Thorac Surg Clin. 15, 71-83, 2005.
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- Cohen E; The New Bronchial Blockers are Preferable to Double-Lumen Tubes for Lung Isolation J Cardiothor asc
Anesth December, 2008
-Cohen, E, et al. Oxygenation and Hemodynamics changes during one-lung ventilation. J Cardiothoracic
Anesth.2:134-40, 1988.
-Capan LM, et al. Optimization of arterial oxygenation during one-lung anesthesia. Anesth Analg. 59:847, 1980.
-Rees DI, et al. One-lung anesthesia and arterial oxygen tension during continuous insufflation of oxygen to the
non-ventilated lung. Anesth Analg. 61:501, 1982.
Alfery D, et al. Improving oxygenation during one lung ventilation: The effects of PEEP and blood flow
restoration of the non-ventilated lung. Anesthesiology 55:381, 1981.
--Benumof JL, et al: : Halothane and isoflurane only slightly impair arterial oxygenation during one-lung
ventilation in patients undergoing thoracotomy. Anesthesiology. 67:910, 1987.
-Katz JA, et al. Pulmonary oxygen exchange during endobronchial anesthesia: Effect of tidal volume and
PEEP. Anesthesiology 56:164, 1982.
-Allen MS. Video-Assisted thoracic surgical procedures: The Mayo experience. Mayo Clin Proc. 71:351, 1996.
-Rodney J, et al. Video-Assisted Thoracoscopic Surgery: Basic Technical Concepts and Intercostal Approach
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-Slinger P, Low tidal volume is indicated during one-lung ventilation: Anesth & Analg. 103(2):268-270, 2006
-Gal T. Low tidal volume is not indicated during one lung ventilation: Anesth & Analg. 103(2):271-273, 2006
-Duggan M, -Duggan M, Kavanagh BP. Pulmonary atelectasis. Anesthesiology 102: 838-54, 2005
-Tusman G, Bohm SH, Sipmann FS, Maisch S. Lung recruitment improves the efficiency of ventilation and gas
exchange during one-lung ventilation anesthesia. Anesth Analg. 98:1604-9, 2004
-Fernandez ER, Keegan MT, Brown DR. Intraoperative tidal volume as a risk factor for respiratory failure after
pneumonectomy. Chest 128:129, 2005.
-Nakata M, Saeki H, Yokoyama N, et al. Pulmonary function after lobectomy: video-assisted thoracic surgery versus
thoracotomy. Ann Thorac Surg. 70:938-41, 2000
-Ferson PF. The Role of Video-Assisted Thoracoscopy in Pulmonary Metastases: Chest Clin N Am. 8:59-76, 1998.
-Mukaida T, et al. Thoracoscopic operation for secondary pneumothorax under local and epidural anesthesia in high
risk patients. Ann. Thorac Surg. 65:924-926, 1998.
-Booth J, et al. Effect of unilateral inhaled NO during selective ventilation in anesthetized human (abstract).
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-Wilson WC, et al. Inhaled nitric oxide (40 ppm) during one-lung ventilation, in the lateral decubitus position, does
not decrease pulmonary vascular resistance or improve oxygenation in normal patients. J Cardiothorac
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-Moutafis M, et al. The effect of inhaled nitric oxide and its combination with intravenous Almotrine on PaO 2
during one-lung ventilation in patients undergoing thoracoscopic procedures. Amnesty Analg. 85:1130-5, 1998.
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acute lung injury and ARDS. Cleve Clin J Med 2008: 75:42-48.
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response to one-lung ventilation. Anesthesiology 2009: 110:1316-1326.
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complications after lung cancer surgery? A randomized controlled trail. Chest 2011: 139: 530-537.
Karzai W, Schwarzkopf K : Hypoxemia during OLV: Prediction, prevention and treatment. Anesthesiology 110:6
2009, 1402-1411
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Mortality in Lung Surgery? A Multicenter Randomized Controlled Trial. Anesthesiology. 2016 May 20.
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Anesthesia for the Patient with a Mediastinal Mass
Peter Slinger, MD, FRCPC Toronto, ON
The risk of life-threatening or fatal airway obstruction or cardio-vascular collapse during induction of
anesthesia in patients with an anterior mediastinal mass has been recognized since the 1970’s1. Over the subsequent
30+ years Anesthesiologists have become very aware of the high risk associated with general anesthesia in these
patients2. It seems that the perioperative management of these patients has improved, judging by the rarity of recent
case reports of intra-operative fatalities and by the low morbidity reported in current retrospective surveys3.
The anesthetic considerations for patients with a central airway obstruction will vary according to the individual
anatomy, pathology and the proposed surgical procedure. Thus, although there are general principles of safe
anesthesia for these patients, there is the need to individualize management on a case-by-case basis. Masses may be
benign or malignant tumors or cysts or aneurysms and may arise from the airway, lung, pleura or any of the
components of the anterior mediastinum. The commonest diagnoses in adults are: lymphoma (Hodgkin’s or non-
Hodgkin’s), thymoma, germ cell tumor, granuloma, bronchogenic carcinoma, thyroid tumors, bronchogenic cyst and
cystic hygroma4 (the commonest diagnoses in children are essentially the same and vary only in order of frequency).
Possible diagnostic or therapeutic surgical procedures include bronchoscopy, sternotomy, thoracotomy, cervical
mediastinoscopy, anterior para-sternal mediastinoscopy, video-assisted thoracoscopic biopsy or biopsy of an extra-
thoracic mass. Occasionally a patient with a central airway obstruction will present for anesthesia for another related
or non-related emergent surgical indication such as ascending aortic aneurysm 5 or labor and delivery6.
Patients may present with signs or symptoms which include dyspnea, chest pain or fullness, cough, sweats,
SVC obstruction, hoarseness, syncope or dysphagia. Or patients may be asymptomatic and have a mass diagnosed
on a screening chest X-ray or CT scan. Among the signs and symptoms which should alert the Anesthesiologist to
an increased perioperative risk are increased dyspnea (orthopnea) or cough when supine (increased risk of airway
complications) and syncopal symptoms or pericardial effusion (increased risk of cardiovascular complications).
Symptoms are graded mild, moderate or severe according to the patient’s tolerance of the supine position. Patients
with severe symptoms will not voluntarily lie supine even for a short duration.
All patients with a central airway obstruction should have a chest X-ray and a CT scan prior to any surgical
procedure and the Anesthesiologist must look at the imaging him/herself to plan the airway management. The CT
scan will show the site, the severity, and the extent of the airway compromise. With modern fast CT scanners this
can be accomplished with scan times <20sec. In addition the patient’s head and chest can be elevated to 30 degrees
without affecting scan quality. Alternatively, the scan can be done in the lateral or even prone position if necessary.
Patients with cardiovascular symptoms, or those patients unable to give an adequate history should also have trans-
thoracic echocardiography to assess for cardiac, systemic or pulmonary vascular compression.
There are important differences in the management of children versus adults. Anesthetic deaths have
mainly been reported in children7. The deaths may be the result of the more compressible cartilaginous structure of
the airway in children and/or because of underestimation of the severity of the airway compression in children due
to the difficulty in obtaining a clear history of positional symptoms. Even with proper management, children with
tracheo-bronchial compression greater than 50% cannot safely be given general anesthesia8. Securing the distal
airway with awake fiberoptic intubation and placement of an endotracheal tube distal to a tracheal obstruction,
which is an option for some adults with masses compressing the mid-trachea, is not an option in most children.
While it is possible to induce and maintain anesthesia with spontaneous ventilation to a depth sufficient to perform
rigid bronchoscopy in a child, this is difficult in an adult. In an adult after induction with spontaneous ventilation
and assuring the ability to manually ventilate the patient, then a short acting muscle relaxant and intravenous
anesthesia may be given for the rigid bronchoscopy if required.
An important part of the anesthetic assessment for these patients is to consider whether the proposed procedure
is diagnostic or therapeutic. To obtain tissue for diagnosis in children or adults who are unsafe for general anesthesia
a common procedure is an awake CT-guided needle biopsy. This can be done with local anesthesia and sedation as
required, with a diagnostic accuracy >90%9. In adults other useful options are awake fiberoptic bronchoscopy or
anterior mediastinoscopy with local anesthesia. Cytometric and immuno-cytochemical studies of pleural fluid can
also be used to secure a diagnosis10. This is particularly useful in lymphoblastic lymphoma which is associated with
a high incidence of pleural effusions. Like needle biopsy, diagnostic thoracentesis can be done with ultrasound
guidance in the sitting position with minimal or no sedation. Endobronchial ultrasound guided biopsy is increasingly
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used to make a tissue diagnosis11. However, once the diagnosis has been confirmed and if the surgery is for
therapeutic excision of a central airway obstruction, then a management plan of safe anesthesia needs to be
developed.
Patients with a central airway obstruction who require general anesthesia need a step-by-step induction of
anesthesia with continuous monitoring of gas exchange and hemodynamics. Maintaining spontaneous ventilation
until either the airway is definitively secured or the procedure is completed is a safe and popular strategy 12.
Anesthetic induction can be inhalational with a volatile agent such as sevoflurane, or by intravenous titration of
propofol, with or without ketamine, or dexmedetomidine13. Awake intubation of the trachea before induction is a
possibility in some patients if the CT scan shows an area of non-compromised distal trachea to which the
endotracheal tube can be advanced before induction. If muscle relaxants are required, assisted ventilation should
first be gradually taken over manually to assure that positive-pressure ventilation is possible and only then can a
short-acting muscle relaxant be administered. Development of airway or vascular compression requires that the
patient be awakened as rapidly as possible and then other options for surgery can be explored. Intraoperative life-
threatening airway compression has usually responded to one of two therapies: either repositioning of the patient (it
should be determined before induction if there is one side or position that causes less symptomatic compression) or
rigid bronchoscopy and ventilation distal to the obstruction. This means that an experienced bronchoscopist and
rigid-bronchoscopy equipment must always be available in the operating room at induction and throughout these
cases .
Flow–volume loops are commonly ordered as part of the preoperative assessment for patients with a central
airway obstruction. Specifically, an increased mid-expiratory plateau when changing from the upright to the supine
position is thought to be pathognomonic for a variable intra-thoracic airway obstruction and an indicator of patients
who are at risk for airway collapse during induction of anesthesia 14. Apart from sporadic case reports, studies of
flow-volume loops have shown a poor correlation with the degree of airway obstruction 15 and have not
demonstrated usefulness in managing these patients16. One study of 25 patients with intra-thoracic masses due to
Hodgkin’s Disease found that no patient showed the pathognomonic pattern of variable intra-thoracic obstruction on
flow-volume loop even though 9/25 patients had moderate or severe intra-thoracic tracheal compression on CT
scan17. Also of note in this study, 7/25 patients showed an inspiratory plateau on flow-volume loop typical for an
extra-thoracic airway obstruction in spite of the fact that none of the patients actually had an extra-thoracic
obstruction on imaging. The myth of the usefulness of flow-volume loops in the assessment of patients with a
central airway obstruction is well established in standard anesthesia texts and on anesthesia specialty exams.
However, in clinical practice, flow-volume loops do not add any useful information beyond that which is obtained
from the chest imaging.
Another myth which exists in the standard texts and reviews of management of patients with a central airway
obstruction is the usefulness of cardiopulmonary bypass as a “standby” during induction of anesthesia 18. The
establishment of cardiopulmonary bypass by femoral cannulations prior to induction of anesthesia has been safely
performed in adult patients19. However, once airway or cardiovascular collapse has occurred it will require at least
5-10 min. to cannulate and establish adequate circulation and oxygenation 20, even with a primed pump and a
prepared team. In such a scenario it is probable that a young patient can be resuscitated but will suffer neurological
injury21. Patients with extremely severe positional symptoms due to airway or cardiovascular compression cannot be
safely given induction of general anesthesia, even with maintenance of spontaneous ventilation, unless an alternative
technique to maintain oxygenation and/or circulation (extra-corporeal membrane oxygenation or cardiopulmonary
bypass) has been established.
References
1
SlingerP, Karsli C. Management of the patienst with a large anterior mediastinal mass: recurring myths. Curr
Opinion Anaesthesiol 2007, 20: 1-3
2
Slinger P. Management of the patient with central airway obstruction. Saudi J Anesth 2011, 5: 241-3
3
Acker SN, Linton J, Tan GM, et al. A multidisciplinary approach to the management of anterior mediastinal
masses in children. J Ped Surg 2015, 50: 875-8
4
Ferguson Mk, Lee E, Skinner DB, Little AG. Selective operative approach for diagnosis and treatment of anterior
mediastinal masses. Ann Thorac Surg 1987; 44: 583-6
5
Tominaga R, Tanaka J, Kawachi Y, et al. Surgical treatment of respiratory insufficiency due to tracheo-bronchial
compression by aneurysms of the ascending aorta and innominate artery. J Cardiovasc Surg 1988; 29:413-7
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6
Kanellakos G. Perioperative management of the pregnant patient with an anterior mediastinal mass.
Anesthesiology Clinics 2012, 30: 749-58
7
Pearson JK, Tan GM. Pediatric anterior mediastinal mass. Sem Cardiothorac Vasc Anesth 2015, 19: 248-54
8
Hack HA, Wright NB, Wynn RF. The anesthetic management of children with anterior mediactinal masses.
Anaesthesia 2008, 63: 837-46
9
Chait P, Rico L, Amaral J, et al. Ultrasound guided core biopsy of mediastinal masses in children. Pediatric
radiology 2005; 35:s76
10
Chaignuad BE, Bosnal TA, Kozakewich HP, et al. Pleural effusions in lymphoblastic lymphoma: a diagnostic
alternative. J pediatr Surg 1998; 33: 1355-7
11
Gilbert CR, Chen A, Akulian JA, et al. The use of convex probe ultrasound-guided transbronchial needle
aspiration in a pediatric population. Pediatric Pulmonology 2014, 49: 807-15
12
Frawley G, Low J, Brown TCK. Anaesthesia for an anterior mediastinal mass with ketamine and midazolam
infusion. Anaesth Intens Care 1995; 23:610–612.
13
Abdelmalak B, Marcanthony N, Abdelmalak J, et al. Dexmedetomidine for anesthetic management of anterior
mediastinal mass. J Anesth 2010, 24: 607-10
14
Neuman GG, Weingarten AE, Abramowitz RM, et al. The anesthetic management of a patient with an anterior
mediastinal mass. Anesthesiology 1984; 60: 144-7
15
Torchio R, Gulotta C, Perbondi A, et al. Orthopnea and tidal expiratory flow limitation in patients with euthyroid
goiter. Chest 2003; 124:133-40
16
Hnatiuk OW, Corcoran PC, Sierra P. Spirometry in surgery for anterior mediastinal masses. Chest 2001; 120: 1152-
6
17
Vander Els NJ, Sorhage F, Bach AM, et al. Abnormal flow volume loops in patients with intrathoracic Hodgkin’s
Disease. Chest 2000; 117:1256-61.
18
Pullerits J, Holzman R. Anaesthesia for patients with mediastinal masses. Can J Anaesth 1989; 36:681-8
19
Soon J-l, Poopalalingham R, Lim CH, et al. Peripheral cardiopulmonary bypass-assisted thymoma resection. J
Cardiothorac Vasc Anesth 2007, 21: 867-9
20
Takeda S, Shinichiro M, Omori K, et al. Surgical rescue for life-threatening hypoxemia caused by a mediastinal
tumor. Ann Thorac Surg 1999; 68:2324-6
21
Turkoz A, Gulcan O, Tercan F. Hemodynamic Collapse Caused by a Large Unruptured Aneurysm of the
Ascending Aorta in an 18 Year Old. Anesth Analg 2006; 102:1040-2
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Patient Selection for Ambulatory Surgery: Can Any Patient Be an Outpatient?

Girish P. Joshi, MBBS, MD, FFARCSI Dallas, Texas
Introduction
Ambulatory surgery accounts for about 65-70% of all elective surgical procedures performed in the United
States [1]. Improvements in surgical and anesthetic techniques as well as modifications in postoperative care have
further increased the number of procedures being performed on an outpatient basis. In fact, surgical procedures
(e.g., total knee arthroplasty) and patient populations that were once considered inappropriate are increasingly being
done in an outpatient setting [2]. Given the changing pattern of health care reimbursement, the expansion of
ambulatory surgery is likely to continue. However, there is an uncertainty amongst anesthesiologists, who must
determine patient suitability for ambulatory surgery.
For day surgery to be safe and efficient, careful selection of patients and procedures is crucial [3]. Clearly,
identifying suitability for an ambulatory procedure is a dynamic process that depends on a complex interplay
between surgical procedure, patient characteristics, expected anesthetic technique (e.g., local/regional vs. general
anesthesia), and social factors, as well as the ambulatory setting, which will influence the ability to manage complex
patients based upon the availabilities of personnel and equipment (Table 1). Although it may be difficult to
quantify, appropriateness of patient selection may also depend on the experience and skill of the surgeon and the
anesthesiologist. Therefore, attempts to address individual factors without consideration of others is fraught with
flaws.
This article will discuss the current literature that can guide rational selection for ambulatory surgery in high-
risk adults patients.
Evidence Assessing Outcome Ambulatory Surgery

It is well recognized that appropriate patient selection would minimize perioperative complications. The
outcome measures influenced by patient selection are presented in table 2. Several studies have used large
administrative and/or clinical databases to assess outcome after various types of ambulatory surgical procedures.
All studies have reported a low incidence of serious adverse outcomes and death; most likely because traditionally
ambulatory surgery involved relatively healthy patients (i.e., American Society of Anesthesiologists [ASA] physical
status 1 and 2) undergoing low-risk surgical procedures [4-11]. Of note, even if the incidence of a cetrian
complication (e.g., postoperative oxygen desaturation) is significantly higher in a certain population or after a
certain surgical procedure, it is not of clinical consequence if it does not influence unplanned hospital admission.
Thus, the outcome measures of consequence with regards to clinical decision-making include unplanned hospital
admission rate, readmission rate, and death.
The limitations of the observational studies include small sample size, as the incidence of complication rate is
very low, which leads to their inability to detect clinically meaningful risk factors. Although several studies have
attempted to determine the predictors of postoperative morbidity, they provide only an association and not the
causation. Furthermore, these retrospective analyses may not always be relevant in the current rapidly changing
surgical and anesthetic practice environment. Thus, the literature that could guide optimal patient selection for
ambulatory surgery is sparse and of limited quality.
American Society of Anesthesiologists Physical Status

As ambulatory surgery expands, surgical patients with significant preexisting diseases are more likely to pesent
in an outpatient setting. Although the available evidence is limited, there is a general agreement that patients with a
high burden of comorbidities, particularly those with poorly stabilized medical conditions are not suitable for
ambulatory surgery. For any patient who is not completely healthy, the nature of any preexisting condition, its
stability and functional limitation should be evaluated. Also, rather than attributing risk to a specific disease process
and considering comorbid conditions in isolation, it is better to consider interactions between the constellation of
diseases.
The ASA physical status is a overall marker of perioperative risk. However, one of the criticisms of the ASA
physical status scoring is that it has significant inter-rater variability. Despite its inherent subjectivity, the ASA
physical status has moderate inter-rater reliability in clinical practice and could be used as a marker of preoperative
health status [12]. There is a general agreement that ASA physical status 3 patients (i.e., patients with severe
systemic disease or disease from whatever cause) may be considered acceptable candidates for outpatient surgery if
their medical conditions are optimized preoperatively. On the other hand, patients with a ASA physical status 4 may
not suitable for ambulatory surgery, particularly if the surgical procedure requires administration of general
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anesthesia.
Elderly
One of the questions commonly posed is: Is there an age limit for ambulatory surgery? The prevalence of
cardiovascular, cerebrovascular, and pulmonary diseases as well as diabetes mellitus increases with age [13].
Interestingly, even though the risk of intraoperative events such as hypotension, hypertension, and arrhythmias,
appears to be higher in the elderly, they are not at an increased risk for postoperative complications. A retrospective
review of elderly (>70 years) patients (n=1647) undergoing ambulatory surgery over a two-year period found no
increased risk of complications with the overall unanticipated admission rate of 1.6% [14]. Another retrospective
study of elderly patients undergoing ambulatory surgery (n=564,267) noted that the overall risk for hospital
admission was low; however, patients of advanced age (age >85) as well as a history of hospitalization within the
preceding 6 months were at an increased the risk of readmission [15]. Other studies have reported that the age
greater than 80 years is an indicator of increased perioperative risk [10].
Retrospective analysis of the ACS-NSQIP database between 2007 and 2010 assessed the safety of ambulatory
laparoscopic cholecystectomy in patients greater than 65 years (outpatients, n=7499 [48.9%] and inpatients, n=7799
[51.1%]) [16]. Independent predictors of inpatient admission and mortality included congestive heart failure, ASA
physical status 4, bleeding disorder, and renal failure requiring dialysis. Also, some procedures may be inappropriate
for ambulatory surgery in the elderly such as transurethral resection of bladder tumors, which is associated with high
admission rates.
A scoring system for estimating the possibility of unplanned hospital admission after ambulatory surgery has
been proposed [17]. This includes one point each for age (>65 years), operating time longer than 120 minutes,
cardiac diagnoses, peripheral vascular disease, cerebrovascular disease, malignancy, seropositive findings for HIV,
and regional, and two points for general anesthesia. Increasing scores were associated with higher odds of
readmission. For scores of 4 or higher, the odds ratio was 31.96, and 2.8% of these patients were discharged to the
hospital.
Overall, age alone should not be used to determine suitability for ambulatory surgery. In fact, in comparison to
inpatient, outpatient setting seems to reduce the risk of postoperative cognitive impairment [18-20]. Of note, elderly
outpatients may require a greater degree of post-discharge supervision and are more likely to have social issues (e.g.,
elderly or debilitated spouse) that need to be considered. Furthermore, recovery of fine motor skills and cognitive
function is slowed with increasing age.
Obesity
Several studies have identified obesity, which is associated with an increased prevalence of comorbidities, as a
risk factor for perioperative complications after ambulatory surgery [9, 10]. Thus, one of the clinical questions
posed with respect to selection of obese patients for ambulatory surgery is: Is there is a weight (or BMI) limit above
which ambulatory surgery is not appropriate?
A propensity matched analysis of the 2006 National Survey of Ambulatory Surgery database evaluated the
overall characteristics and perioperative outcomes in morbidly obese and non-obese patients undergoing ambulatory
surgery in the United States [21]. This study found that the prevalence of ambulatory surgery in the morbidly obese
was low (0.32%). The morbidly obese were significantly younger but had a higher burden of comorbidities, were
more likely to undergo the procedure in hospital based outpatient facilities (80.1% vs 56.5%), and had significantly
shorter procedures than the nonobese (average 28 vs. 42 min). The incidences of postoperative hypertension,
hypotension, hypoxia, cancellation of surgery, and unplanned hospital admissions did not differ significantly
between groups. Similarly, adjusted rates of delayed discharge were similar in morbidly obese and nonobese
patients.
A systematic review revealed that BMI alone did not influence perioperative complications or unplanned
admission after ambulatory surgery [22]. Although all the studies included in this systematic review were
observational, they were representative of broad clinical practice and included both bariatric and non-bariatric
surgical procedures. This systematic review revealed that there was a conservative approach to patient selection for
non-bariatric surgical procedures, as the average BMI was only 30 kg/m2. In contrast the patients undergoing
bariatric surgery had a BMI of around 40 kg/m2, which is known to have a higher burden of comorbid conditions
including obstructive sleep apnea. However, the bariatric surgical population had rigorous preoperative evaluation
and optimization of comorbid conditions. It was concluded that weight or BMI should not be the sole determinant
of patient selection for ambulatory surgery; however, patients with BMI <40 kg/m 2 may be suitable for ambulatory
surgery assuming that their comorbid conditions, if any, are optimized [22]. Also, it is necessary to consider the
presence of sleep disordered breathing (i.e., OSA and obesity-related hypoventilation syndrome), as it has been
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associated with increased perioperative complications [23]. The super obese (i.e., BMI >50 kg/m2) should be
chosen carefully as they have higher incidence of perioperative complications. For patients with BMI between 40
and 50 kg/m2, thorough preoperative assessment is necessary to identify obesity-related comorbid conditions (e.g.,
OSA, obesity-related hypoventilation syndrome, and pulmonary hypertension, as well as resistant hypertension,
coronary artery disease, and cardiac failure).
Obstructive Sleep Apnea

It is well documented that patients with OSA are at high risk of perioperative complications [23]. Therefore,
suitability of ambulatory surgery in patients with known or suspected OSA remains controversial. Can a patient
with known or presumed (clinical) diagnosis of OSA undergo ambulatory surgery?
The ASA recently published updated guidelines regarding perioperative management of OSA patients,
including selection for ambulatory surgery [24]. Of note, the previous recommendation that ambulatory surgery is
not recommended in OSA patients undergoing airway surgery or upper abdominal surgery has been eliminated [24].
The ASA guidelines also propose a scoring system, based on the severity of OSA, the invasiveness of the surgery,
the type of anesthetic technique, and the need for postoperative opioids, that may be used to estimate whether an
OSA patient is at increased risk of perioperative complications, and thus determine the suitability for ambulatory
surgery. However, clinical utility of this scoring system is questionable, as it has not yet been validated.
A systematic review of published literature assessing perioperative complications in patients with OSA
undergoing ambulatory surgery revealed that OSA patients with inadequately treated co-morbid conditions are not
suitable for ambulatory surgery [25]. Based upon this systematic review, the Society for Ambulatory Anesthesia
(SAMBA) consensus statement recommends that patients with a known diagnosis of OSA, who are typically
prescribed positive airway pressure [PAP] therapy, may be considered for ambulatory surgery if their comorbid
medical conditions are optimized and they are able to use a PAP device in the postoperative period. It appears that
postoperative PAP therapy may be protective against opioid-induced respiratory complications. On the other hand,
patients who are unable or unwilling to use PAP device after discharge may not be appropriate for ambulatory
surgery. Patients with a presumed diagnosis of OSA, based on screening tools such as the STOP-Bang
questionnaire, can be considered for ambulatory surgery if their comorbid conditions are optimized and if
postoperative pain relief can be provided predominantly with non-opioid analgesic techniques. It is also
recommended that a screening tool be incorporated in a routine preoperative evaluation. The STOP-Bang
questionnaire is simple to use; however, it is recommended that a higher ‘cut-off’ (e.g., ≥ 5 or 6 positive indicators)
should be used to determine presumption of OSA, rather than the original suggestion of a ‘cut-off’ of ≥3 [25-27].
Of note, the SAMBA consensus statement did not provide any guidance for OSA patients undergoing upper
airway surgery due to limited evidence [25]. However, there is some recent evidence suggesting that airway surgery
in this patient population can be performed in an ambulatory setting with complication rates similar to the inpatient
population [28-31]. A recent systematic review of 18 publications with 2160 patients assessed postoperative
complication rates after OSA surgery performed on same day basis [30]. There were no deaths or major
catastrophic events. The overall incidence of any adverse event was 5.3%, with the respiratory-related events rate of
less than 1.5%. Most of the respiratory events were related to oxygen desaturations, which were not clinically
significant. Exclusion of oxygen desaturation significantly reduced the overall adverse event rates. All the adverse
events were related to the surgical procedure and not specifically to OSA. The re-admission rate was only 0.4%.
The author concluded that OSA surgery performed on outpatient basis is generally safe and routine hospital
admission is not necessary, except for patients undergoing tongue base surgery, those with a higher preoperative
apnea/hypopnea index, or those with high postoperative opioid requirements. Other studies have also reported that
most serious airway complications occur early after surgery (i.e., within 2 to 3 hours postoperatively) [31]. Potential
postoperative complications include airway obstruction, post-obstructive pulmonary edema, and cardiac arrhythmia.
Diabetes Mellitus
Insulin dependent diabetics are at increased risk for perioperative complications such as cardiac, respiratory,
and surgical site infections. Although patients with diabetes mellitus often have several comorbidities, it does not
appear to be an independent predictor of complication rate after ambulatory surgery. Nevertheless, it is necessary
that the surgical facilities caring for this patient population have the necessary equipment to monitor blood glucose
levels.
The Society For Ambulatory Anesthesia (SAMBA) has published a consensus statement on perioperative blood
glucose management [32], which provides some guidance to address the question: Is there a preoperative blood
glucose level (BGL) above which one should postpone elective surgery? Although there is insufficient evidence to
specifically recommend a ‘cut-off’ BGL above which elective ambulatory surgery should be postponed, it may be
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acceptable to proceed with surgery in patients with preoperative hyperglycemia but with adequate long-term
glycemic control, barring any significant complications of hyperglycemia such as ketoacidosis and hyperosmotic
states. In patients with chronically poorly controlled diabetes mellitus, the decision to proceed with ambulatory
surgery should be made in conjunction with the surgeon and take into account patient comorbidities and the risks of
surgical complications.
Cardiac Disease
Due to advances in medical and interventional cardiac care, patients with cardiac disease (e.g., hypertension,
coronary artery disease [CAD], arrhythmia (e.g., atrial fibrillation), valvular heart disease, congestive heart failure
[CHF], cardiomyopathy, cardiac implantable electronic devices [CIED], coronary artery stents, and congenital heart
disease) are increasingly presenting for ambulatory surgery.
Individuals at high risk for perioperative cardiac events, including brittle or poorly controlled hypertension,
unstable or severe angina (Canadian class III or IV), recent MI, noncompensated heart failure, symptomatic
arrhythmias (high-grade atrioventricular block, supraventricular arrhythmias with uncontrolled ventricular rate,
symptomatic ventricular arrhythmias), and significant valvular heart diseases (severe aortic or mitral valve stenosis)
may not be suitable for procedures in an ambulatory setting [33]. With technological advances in the management
of acute MI, elective surgical procedures may be considered at 30 days post-MI, depending on the patient’s
symptoms and functional status [34]. Interestingly, patients with heart failure and atrial fibrillation (AF) were found
to be at a higher risk of perioperative complciations than those with CAD [34]. Several studies have reported a
increased incidence of perioperative morbidity and mortality in patients with new onset AF [35, 36]. Symptoms
associated with AF include fatigue, dizziness, lightheadedness, syncope, palpitations, chest pain or tightness, and
shortness of breath. Overall, patients with symptomatic new onset AF may not be suitable for ambulatory surgery.
Most patients with aortic stenosis remain asymptomatic until fifth decade. Once symptomatic (angina pectoris,
dyspnea on exertion, or syncope), life expectancy declines with survival limited to approximately 5 years after the
presentation of angina and 2 years after the onset of CHF. Patients with hemodynamically significant or
symptomatic aortic stenosis may not be appropriate candidates for ambulatory surgery.
Typically, ambulatory surgery carries a low risk of perioperative cardiac complications (defined by a cardiac
risk of <1%). The risk of perioperative myocardial infarction or cardiac arrest (MICA) can be calculated by using a
cardiac risk calculator (http://www.surgicalriskcalculator.com), derived from the ACS-NSQIP database. It
incorporates patient variables (i.e., age, ASA physical status, functional status, and preoperative serum creatinine)
and surgical procedure [37-39]. The predictive performance of this cardiac risk calculator is reported to be superior
to that of the Revised Cardiac Risk Index (RCRI), which includes variables such as diabetes mellitus requiring
insulin, creatinine ≥2 mg/dL, history of cerebrovascular accident or transient ischemic attack, ischemic heart disease
and heart failure [40, 41]. The presence of ≤2 clinical risk factors is considered at low risk of MACE [40]. Patients
at an elevated risk should be assessed for functional status, and those with a functional status of <4 METs or in
whom functional capacity cannot be assessed should be considered for pharmacologic stress testing, if it will impact
perioperative decision making or care [33].
Patients with CIED may be at risk of perioperative arrhythmia and asystole. Also, in the case of implantable
cardioverter defibrillators (ICD) there is a concern that electromagnetic interference may be misinterpreted as an
arrhythmia leading to inappropriate shock. The recommendations of the Heart Rhythm Society jointly developed
with the ASA, in collaboration with the American College of Cardiology (ACC), the American Heart Association
(AHA), and the Society of Thoracic Surgeons (STS) provide excellent guidance for the management of patients with
CIED [33, 42]. Overall, patients with CIED may safely undergo ambulatory surgery assuming that appropriate
equipment and support is readily available. However, the controversy in management of patients with CIED it
related to the use of magnet to disable the ICD and the need for reprogramming (i.e., suspend ICD and pacemaker
function), which requires an expert (e.g., a cardiologist, electrophysiology nurse, or device representative) and who
may not be always available. Patients with cardiac implantable electronic devices may undergo ambulatory surgery
assuming that appropriate support is readily available.
Another challenging group of patients include those with coronary artery stents. The controversy in this patient
population surrounds the need to continue the dual antiplatelet therapy to prevent coronary artery thrombosis. It is
recommedned that patients with acute percutaneous cardiac intervention (PCI) or bare metal coronary stents (BMS)
should have their elective surgery delayed for 30 days, while those with drug eluting stents (DES) should have their
elective surgery delayed for 365 days [33]. However, controversy surrounds regarding scheduling of patients with
newer (second and third genration) DES in whom the dual antiplatelet therapy is maintained for arround 6 motnhs
[43]. Recent data suggests that elective surgery performed within 6 months of placement of new generation DES is
safer than that with BMS and old generation DES [43, 44]. Overall, elective surgery should be postponed until the
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patient is on dual antiplatelet therapy. If necessary, consultation with the patient’s cardiologist and the surgeon is
recommended to address issues such as timing of surgery, management of anticoagulation, and other potential risk
reduction strategies. Because urgent PCI is the best management for acute perioperative stent thrombosis, access to
interventional cardiology should be considered in the selection criteria for higher risk patients seeking ambulatory
surgery.
Summary
As older and sicker patients undergo more complex surgical procedures in an ambulatory setting, patient
selection has become the cornerstone of safe and efficient perioperative care. Developing and implementing
protocols (or clinical pathways) for patient selection is the best way to improve perioperative outcome. This
requires a multidisciplinary approach in which the anesthesiologist should take a lead in collaborating with the
surgeons and the perioperative nurses. Rather than considering the factors in isolation, the interaction of any
disease(s) with the planned surgical procedure should also be considered.
The first step in determining appropriate patient selection includes preoperative assessment and identification of
any comorbid conditions, which should be optimized to minimize risks. For any patient who is not completely
healthy, the nature of any preexisting condition, its stability and functional limitation should be evaluated. The
social situation should be evaluated to determine whether the patient has help at home for postoperative care.
Education of the patients and their caregivers regarding the need for increased vigilance after discharge home is
critical [45]. Outpatients should be capable of understanding instructions for pre- and postoperative care, and should
be accompanied home by a responsible escort. Someone should also be available to care for the patient during the
first night after surgery and be able to assist them in obtaining emergency medical care if needed.
The anesthetic technique chosen should provide optimal intraoperative conditions, while ensuring a rapid return
of consciousness and protective reflexes upon completion of the operation, minimal residual sedative effects (so-
called “hangover” effect), little impairment of postoperative cognitive function, and the absence of side effects
during the early recovery period. A pragmatic question to ask is: Will postoperative hospitalization influence patient
care or perioperative outcome? If no improvement would be achieved, then the patient should undergo the
procedure on an ambulatory basis. In the future, as more patients and surgical procedures are moved from inpatient
facilities to outpatient facilities, it will be appropriate to develop exclusion criteria, rather than inclusion criteria, for
patients that are not candidates for ambulatory surgery.
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2. Lovald S, et al. J Surg Orthop Adv 2014; 23: 2-8.
3. Lermitte J, Chung F. Curr Opin Anaesthesiol 2005; 18:598-602.
4. Warner MA, et al. JAMA 1993; 270: 1437-41.
5. Fortier J, et al. Can J Anaesth 1998; 45: 612-9.
6. Ansell GL, Montgomery JE. Br J Anaesth 2004; 92: 71-4.
7. Engbaek J, et al. Acta Anaesthesiol Scand 2006; 50: 911-9.
8. Majholm B, et al. Acta Anaesthesiol Scand 2012; 56: 323-331.
9. Mathis MR, et al. Anesthesiology 2013; 119: 1310-21.
10. Whippey A, et al. Can J Anaesth 2013; 60: 675-83.
11. Rosero E, Joshi GP. Abstract IARS 2016
12. Sankar A, et al. Br J Anaesth 2014; 113: 424-32.
13. White PF, et al. Anesth Analg 2012; 114: 1190-215.
14. Aldwinckle RJ, Montgomery JE. Anaesthesia, 2004; 59: 57-9.
15. Fleischer LA, et al. Arch Surg 2004; 139: 67-72.
16. Rao A, et al. J Am Coll Surg 2013; 217: 1038-43.
17. Fleisher et al: Ann Surg 2007;142: 263-8
18. Canet J, et al. Acta Anaesthesiol Scand 2003; 47: 1204-10.
19. Mattila K, et al. Am J Surg 2011; 201: 179-85.
20. Bettelli G. Curr Opin Anesthesiol 2010; 23: 726-31.
21. Rosero E, Joshi GP. J Clin Anesth 2014; 26: 191-8.
22. Joshi GP, et al. Anesth Analg 2013; 117: 1082-91.
23. Joshi GP. Curr Anesthesiol Rep 2014; 4: 284-9.
24. Anesthesiology 2014; 120: 268-86.
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26. Farney RJ, et al. J Clin Sleep Med 2011; 7: 459-65.

27. Chung F, et al. Br J Anaesth 2012; 108: 768-76.
28. Baugh R, et al. Otolaryngology-Head and Neck Surgery 2013; 148: 867-72.
29. Mahboubi H, Verma SP. JAMA Otolaryngol Head Neck Surg 2013; 139: 28-31.
30. Rotenberg B.. Curr Anesthesiol Rep 2014; 4: 10-8.
31. Spiegel JH, Raval TH.. Laryngoscope 2005; 115: 167-71.
33. Fleisher LA, et al. Circulation. 2014. doi:10.1161/CIR.0000000000000105.
34. van Diepen S, et al. Circulation 2011; 124: 289-96.
35. Christians KK, et al. American J Surg 2001; 182: 713-5.
36. Sohn GH, et al. Korean Circ J 2009; 39: 100-4.
37. Gupta PK, et al. Circulation 2011; 124: 381-7.
38. Cohen ME, et al. J Am Coll Surg 2013; 217: 336-46.
39. Bilimoria KY, et al. J Am Coll Surg 2013; 217: 833-42.
40. Lee TH, et al. Circulation. 1999; 100: 1043-9.
41. Ford MK, et al. Ann Intern Med 2010; 152: 26-35.
42. Crossley GH, et al. Heart Rhythm 2011; 8: 1114-54.
43. Saia F, et al. Circ Cardiovasc Qual Outcomes. 2016; 9: 39-47.
44. Holcomb CN, et al. J Am Coll Cardiol 2014; 64: 2730-9.
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Theory, Practice, and Results of the U.S. and Australia/New Zealand Incident Reporting Systems
Patrick J. Guffey, M.D. Aurora, CO and Alan F Merry, M.B. Ch.B., F.A.N.Z.C.A., F.F.P.M.A.N.Z.C.A,
Auckland, New Zealand.
Introduction
We can’t fix what we can’t detect. Quality improvement begins with an understanding of the current state of patient
harm and unsafe conditions. Incident reporting began as a local activity, typically surrounding unexplained deaths.
This expanded over time to cases of patient harm, and cases where patients were almost harmed (near miss) by an
unsafe condition. Flanagan described the first cases of critical or incident reporting in 1954, and this technique was
introduced in the United States by Cooper in 1978 and into Australia and New Zealand by William Runciman in the
early 1990s. Incident reporting is designed to improve patient safety by identifying hazards and actions for their
improvement. This paradigm has been in use in other industries for much longer than healthcare and typically in
highly reliable applications, such as aviation and nuclear power.
Theory
All clinicians learn from experience in their day-to-day practice. However, this approach has limitations. First, it is
seldom either possible or valid to draw conclusions from a single event. Root cause analysis is time consuming and
costly if done well, and results may have greater local than general applicability. In general, it would be better to
learn from near misses before an event finally results in the death or injury to patients. In short, there is a better way.
Incident reporting seeks to amalgamate information from multiple events involving morbidity, mortality, near
misses and unsafe conditions, and to use this information to improve patient safety.
Many medical errors are without consequence because the accident trajectory that follows any injury is
multifactorial and it typically takes several errors to result in harm to a patient. Near misses are much more frequent
than harmful events. Heinrich introduced the concept of the safety pyramid to capture this idea. He found there are
approximately 300 near misses for each case of harm. This was verified by Bird in 1956, Conoco-Philips in 2002,
and the Department of Anesthesia at UCSF in 2009. By reporting near misses as well as incidents in which harm
actually occurs, more data can be collected and corrective actions identified and taken to address unsafe conditions
and improve patient safety. For rare events, near misses may be all an institution sees until a serious case of harm
occurs.
Many serious events in anesthesia are extremely rare. Incident reporting allows the aggregation of events across
multiple sites and may result in earlier detection and reduction of harm. This requires a broad spectrum of
individuals to report and a robust system of reviewing cases. It is possible for a system to become too broad. The
first incident reporting system in Australia became less effective when it expanded beyond the field of
anesthesiology because it lost its focus and became less relevant to anesthesiologists. In general, physicians are more
likely to engage in a craft-specific system of incident reporting, and more general systems may end up being used
predominantly by nursing staff.
Incident reporting is not designed to monitor progress over time, notably because denominator data are not usually
captured, but also because the reports are typically voluntary. However, changes in the patterns of incident reports
may provide an indication of improvement. For example, hypoxic events are less commonly reported since the
introduction of improved monitoring.
Development
Incident reporting began locally in the 1930s. The initial focus was mortality, but, gradually, reporting evolved to
capture morbidity and then near misses and unsafe conditions as well. Many departments use paper systems to track
cases for discussion at morbidity and mortality conferences. However, formal processes with high rates of event
capture and reliable event reporting have been uncommon.
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In order to allow for more robust data analysis, detection of rare events, and to leverage economies of scale,
aggregation of events at the national level is desirable. To this end, an initiative by the Australian and New Zealand
College of Anesthetists, The Australian Society of Anesthetists and the New Zealand Society of Anesthetists led to
the development of WebAIRS, which is governed by the Australian and New Zealand Triparate Anesthesia Data
Committee (ANZTADC). In 2011, the Anesthesia Quality Institute (Schaumberg, IL) developed and launched the
anesthesia incident reporting system (AIRS) in the United States. This system was based on the anesthesia specific
taxonomy developed by ANZTADC as well as the very robust local systems in place at the University of California,
San Francisco, and the Children’s Hospital Colorado affiliated with The University of Colorado.
Incident reporting in anesthesia, and medicine in general has a poor rate of adoption. In order to develop an effective
reporting system, it is important to address the incentives and disincentives to reporting. The following two tables
summarize the reasons healthcare practitioners do not choose to report, and factors that positively influence
reporting. Tables are adapted from Guffey, Culwick, and Merry 2014.
Disincentives for reporting adverse events

Poor education about what constitutes an event
Concern over legal or credentialing consequences
Personal shame
Fear of implicating others
Time consuming processes
Systems that are difficult to access
Lack of anonymity
Potentially discoverable information
Slow infrastructure
Arduous, poorly designed interfaces
Lack of feedback and follow up, no perceived value to the department
Factors that incentivize reporting

Secure and non-discoverable data
Quick entry time (less than one minute) and ease of use
Accessibility of the system
The capture of both near misses and incidents of patient harm
An option of anonymity for near misses
Data searchable by the department QI committee
Summary reports to department & hospital
Legal Issues
A requirement of any healthcare reporting system is a legal framework, which protects the users, practices,
institutions, and the entity hosting the reporting system. The following table summarizes the legal and ethical issues.
Legal and ethical issues Considerations

Collection of health data Relevant legislation
- HIPAA Privacy Rule
- PSQIA
Patient Safety Organisations (PSOs)
Security and Discoverability of the data Data security principles
Legal Discoverability
Searchable by department QI committee
Ethical use of the data Moral and legal obligations
Avoidance of Harm
Consent for data to be used for particular purposes
Possible publication of the data
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Transparency and open disclosure

Option of anonymity for particular reports
In 2005 the Patient Safety and Quality Improvement Act (PSQIA) became law in the United States. This law
authorized the creation of Patient Safety Organizations (PSO), of which the AQI as the hosting entity of AIRS is a
member. PSOs are fully authorized by federal law to collect patient data and protect it from disclosure to support
quality improvement work. This law was absolutely critical to the development of AIRS. Data from AIRS is de-
identified, and in accordance with the PSQIA, reported to the agency for healthcare research and quality (AHRQ)
which allows the reports generated by AIRS to be used to improve healthcare overall in the United States.
Results
A demonstration of AIRS and WebAIRS will occur at the Annual Meeting. Interested users may enter an AIRS test
case at http://aqiairs.org and a WEbAIRS case at http://www.anztadc.net/demo/mobile.aspx. More information on
AIRS and the AQI is available at http://aqihq.org and for WebAIRS at
https://www.anztadc.net/Publications/webAIRS%20ASM%20Flyer%20A4%20P2_20150421.pdf
Actual results from WEbAIRS and AIRS will be presented at the annual meeting. Currently, there are thousands of
cases in both systems.
Of note, a significant number of trends have been detected in the AIRS database. Specifically:
 Air embolus during ERCP
 Drug errors due to shortages
 Importance of teamwork
 Effectiveness of cognitive aids
 Hazards of Electronic Medical Records (EMR) and Anesthesia Information Management Systems (AIMS)
o Charting on the wrong patient
o System failures
o Failure to record vital signs
o Failure of pharmacy dispensing systems
o Incorrect calculations
o Incorrect decision support
Newsletter Articles
An important output of the AIRS system is monthly newsletter articles summarizing a case and the lessons learned.
The AIRS committee members search for interesting and notable cases or trends and through a peer-reviewed
process at the committee level produce an article for the ASA newsletter, which has a circulation of approximately
50,000 exclusive of individuals who access it over the internet. The complete list of all case reports is available at
https://www.aqihq.org/casereportsandcommittee.aspx. The articles may be read without subscription at this address.
Local Deployment
AIRS is now available for local deployment. This allows for collection of protected health information at the local
level and features bulk upload to the national database. This may be advantageous for some institutions.
Conclusions
 Incident reporting is a valid way to learn, classify, and act on patient harm in anesthesiology
 Near misses provide a potential window into future cases of harm
 Incident reporting detects system errors which may be addressed
 Strong system design leads to better reporting
 National databases allow aggregation and may lead to earlier detection of events
 PSOs provide a legal framework for anesthesiologists and anesthetists to feel comfortable reporting events
Selected References
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 Bird, F. and G. Germain, Loss Control Management: Practical Loss Control Leadrship. 1996, USA: Det
Norske Veritas.
 Beecher, H.K. and D.P. Todd, A study of the deaths associated with anesthesia and surgery. Annals of
Surgery, 1954. 140(1): p. 2-34.
 Cooper, J.B., et al., Preventable anesthesia mishaps: a study of human factors. Anesthesiology, 1978.
49(6): p. 399-406.
 Cullen, D.J., et al., The incident reporting system does not detect adverse drug events: a problem for
quality improvement. Jt Comm J Qual Improv, 1995. 21(10): p. 541-8.
 Flanagan, J.C., The critical incident technique. Psychological Bulletin, 1954. 51(4): p. 327-58.
 Gibbs, N.M., Milestones in anaesthesia-related mortality and morbidity reporting in Australia. Anaesthesia
and Intensive Care, 2010. 38(5): p. 807-8.
 Guffey, P., et al., Design and implementation of a near-miss reporting system at a large, academic
pediatric anesthesia department. Paediatr Anaesth, 2011. 21(7): p. 810-4.
 Guffey, P. and J. Caldwell, Current results of an anonymous near-miss reporting system at a large,
academic, multi-campus anesthesia department., in Association of University Anesthesiologists. 2010:
Denver, CO.
 Guffey, P., Culwick, M., Merry A., Incident Reporting at the Local and National Level. Int Anesthesiol
Clin. 2014 Winter; 52(1):69-83.
 Hansen, M., C. McAndrews, and E. Berkeley History of Aviation Safety Oversight in the United States -
Final Report. 2008.
 Heinrich, H.W., Industrial Accident Prevention: A scientific approach. 1950, New York, NY: McGraw-
Hill.
 Holland, R., Special committee investigating deaths under anaesthesia. Report on 745 classified cases,
1960-1968. Med J Aust, 1970. 1(12): p. 573-94.
 The IAEA/NEA Incident Reporting System - Using Operating Experience to Improve Safety. 2008.
 Kaldjian, L.C., et al., Reporting medical errors to improve patient safety: a survey of physicians in teaching
hospitals. Arch Intern Med, 2008. 168(1): p. 40-6.
 Leape, L.L., Reporting of adverse events. N Engl J Med, 2002. 347(20): p. 1633-8.
 Milch, C.E., et al., Voluntary electronic reporting of medical errors and adverse events. An analysis of
92,547 reports from 26 acute care hospitals. J Gen Intern Med, 2006. 21(2): p. 165-70.
 Reason, J., Human Error. 1990, New York: Cambridge University Press.
 Rowin, E.J., et al., Does error and adverse event reporting by physicians and nurses differ? Jt Comm J
Qual Patient Saf, 2008. 34(9): p. 537-45.
 Runciman, W.B., The Australian Patient Safety Foundation. Anaesthesia & Intensive Care, 1988. 16(1): p.
114-6.
 Runciman, W.B., et al., The Australian Incident Monitoring Study. Errors, incidents and accidents in
anaesthetic practice. Anaesthesia & Intensive Care, 1993. 21(5): p. 506-19.
 Runciman, W.B., A.F. Merry, and F. Tito, Error, blame, and the law in health care--an antipodean
perspective. Annals of Internal Medicine, 2003. 138(12): p. 974-9.
 Safren, M.A. and A. Chapanis, A critical incident study of hospital medication errors. Hospitals, 1960. 34:
p. 32-4; passim.
 Summary of the HIPPA Privacy Rule. OCR Privacy Brief 2003 4/17/13 4/17/13]; Available from:
http://www.hhs.gov/ocr/privacy/hipaa/understanding/summary/privacysummary.pdf.
 Taylor, J.A., et al., Use of incident reports by physicians and nurses to document medical errors in
pediatric patients. Pediatrics, 2004. 114(3): p. 729-35.
 The Patient Safety and Quality Improvement Act of 2005. June 2008, Agency for Healthcare Research and
Quality: Rockville, MD.
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Transfusion Therapy: Optimal Use of Blood Products

Stephen Surgenor, M.D. Lebanon, New Hampshire
Introduction
Despite decades of effort, transfusion therapy practice remains suboptimal. This review will examine the
risks and benefits of red blood cell (RBC), platelet, and fresh frozen plasma (FFP) transfusions, as well as strategies
to optimize transfusion practice for each of these components. The American Association of Blood Bankers 2011
Nationwide Blood Collection and Utilization Survey Report describes the current status of blood utilization in the
United States. Key findings include that for the first time in two decades the annual number of transfusions has
decreased, and that collection of autologous and directed blood is decreasing and now represents less than 2 percent
of total donation. In addition, the use of leukocyte reduction continues to increase and now 80 percent of RBC units
are treated. Figure 1 describes the collection and transfusion of blood nationally.
Figure 1. Allogeneic whole blood and red blood cell collections and transfusions: 1989 – 2008.
Source: American Association of Blood Bankers 2009 Nationwide Blood Collection and Utilization Survey Report.
Variation in Transfusion Practice

Tremendous variation in the indications for and timing of transfusions exists. Large variations in the
indications for and timing of RBC transfusion have been documented for many years among coronary artery bypass
graft (CABG) surgery patients1 2. Importantly, this variation is not explained by patient or surgical variables, but
rather by differences in provider and institutional preferences3. More recently, another observational study
demonstrates that variation continues across institutions in Canada despite new knowledge about the benefits and
risks of RBC transfusions4. Such variation is not limited to just RBC transfusions. Similar observations have been
made for use of platelets and plasma during CABG surgery in Veterans Administration hospitals 5. The presence of
significant variation in transfusion rates implies that the best practice has yet to be identified, and that indications for
transfusions are not consistent among providers.
Guidelines
This variation persists despite the availability of practice guidelines. One of the oldest guidelines for RBC
transfusion is the “10/30” rule which originated from comments made by Adams and Lundy in 1942 6. Several RBC
transfusion guidelines have been published based on best available evidence by the National Institute of Health
(1988), the American College of Physicians (1992), the Blood Management Practice Guidelines Conference (1995),
as well as the American Society of Anesthesiologists. Most recently, a comprehensive guideline has been developed
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by the Society of Cardiovascular Anesthesiologists for the cardiac surgery population7. There has been less activity
to develop guidelines for platelet and plasma therapies; the only one was developed by the College of American
Pathologists in 19948. The American Society of Clinical Oncology has developed guidelines for platelet therapy
among the oncology population, which are not easily generalized to either peri-operative or critically ill patients9.
While medical guidelines are believed to be an efficacious method to improve medical care, they have been
relatively ineffective in reducing unwarranted transfusions for several reasons. Specific to RBC transfusion, one
prescribed trigger is not appropriate for all patients and clinical settings, because a consistent physiologic
deterioration in is not observed among all patients at the same hemoglobin level. Second many physicians remain
unaware of available transfusion guidelines.
This past year, Dartmouth Hitchcock Health system implemented a transfusion decision support tool in our
electronic health record that is based on the current evidence yet allows clinicians flexibility to use blood for
appropriate indications. The results of this effort are presented in Figures 2 & 3. This type of approach likely
generalizable to other institutions, and represents one approach to effectively implement evidence based medicine in
general, but specifically for transfusion medicine as well.
Figure 2 Results of an Electronic Health Record Transfusion Decision Support Tool.

Source: Unpublished Data from Dartmouth Hitchcock Health
Figure 3 Results of an Electronic Health Record Transfusion Decision Support Tool.

Source: Unpublished Data from Dartmouth Hitchcock Health
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Red Blood Cell Transfusions

Risks of Anemia
There are numerous reports of severe anemia being well tolerated in healthy subjects. Acute normovolemic
hemodilutional anemia has been safely performed with animal models with dogs and baboons, as well as with
human subjects with and without surgery. Data from patients who decline RBC transfusion for religious reasons
suggests that mortality is more related to substantial blood loss than a low preoperative hematocrit per se.
Importantly this effect was significantly more pronounced among patients with cardiovascular disease10.
Studies from several prospective observational cardiac surgical databases have reported associations of
hemodilutional anemia during cardiopulmonary bypass (CPB) with increased risk of renal failure, stroke, and
mortality during coronary artery bypass graft (CABG) surgery. Plausible explanations for these observations
include direct injury as a result of exposure to hemodilutional anemia or alternatively that these associations a a
marker for another unmeasured process. One such process could be exposure to intra-operative RBC transfusions
administered as treatment for anemia.
A report by the Northern New England Cardiovascular Disease Study Group observed that among patients
managed without intra-operative RBC transfusion, exposure to hemodilutional anemia during CPB was associated
with Low Output Failure (increased need for prolonged inotropes, post-CPB intra-aortic balloon pumps, and return
to CPB after initial separation) (Figure 4)11. These observations support the concept that intraoperative anemia
reduces the oxygen supply available to the tissues to adequately meet demand, leading to ischemic tissue injury and
subsequent adverse outcomes.
Figure 4. Crude risk of Low Output Failure by quartiles of lowest hematocrit during cardiopulmonary bypass
stratified by RBC transfusion.
Benefits of RBC Transfusion to treat Anemia

The long standing belief for RBC transfusion is that giving back blood will reverse the ill effects of anemia.
We now have three prospective trials comparing liberal and restrictive transfusion strategies among critically ill and
peri-operative patients.
The first prospective trial of RBC transfusion therapy in critically ill patients without active bleeding was
published in 199912. The Canadian Transfusion Requirements in Critical Care, or TRICC trial, evaluated a
restrictive strategy of maintaining hemoglobin between 7 and 9 g/dL versus a liberal strategy of maintaining
hemoglobin between 10 and 12 g/dL. Inclusion criteria included anemic euvolemic patients who were not actively
bleeding. Patients with chronic anemia of following cardiac surgery were excluded, and a large number of patients
with significant coronary artery disease were not enrolled in the study at the discretion of the attending physician.
This study showed that the restrictive strategy was “at least as effective as and possibly superior to a liberal
transfusion strategy.” Furthermore, subgroup analysis showed an association of improved 30 day survival in
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patients younger than 55 years old or those with APACHE II scores lower than 20 managed with the restrictive
strategy.
A more recent prospective trial of RBC transfusion during cardiac surgery was completed in Brazil 13.
Among 500 patients undergoing cardiac surgery with CPB, a restrictive transfusion strategy of tolerating anemia to a
hematocrit of 24% was just as efficacious as a more liberal goal of maintaining hematocrit above 30%. The rate of
RBC transfusion was 78 percent vs. 47 percent in the liberal versus restrictive groups. These finding are consistent
with the TRICC trial conclusions.
Finally there is a prospective trial of liberal (greater than 10 g/dL) vs. restrictive (less than 8.0 g/dL)
strategies among high risk patients after hip surgery14. Similar to the previously mentioned trials, there was no
outcome benefit, as measured by death or inability to walk without assistance, to patients from a more liberal
approach to transfusion. Nearly 97 percent of patients in the liberal group were transfused withRBCs. In the
restrictive group, far less blood was administered, and only 40 percent of these patients were exposed to RBC
transfusions.
There is one other randomized trial that provides some evidence regarding the role of RBC transfusion as
part of early goal directed fluid therapy for treatment of sepsis or septic shock. Rivers et al. randomized septic
patients to either standard resuscitation or an explicit goal-directed protocol15. RBC transfusions were indicated in
the goal-directed protocol to maintain central venous oxygen saturation greater than 70 percent, if the hematocrit
was less than 30 percent. Patients in the early goal directed group experienced superior hospital, 28-day, and 60 day
mortality compared to patients managed with standard resuscitation. Because there were multiple interventions used
in this protocol, it is not possible to separate the relative importance of RBC transfusion to the survival benefit.
Risks of RBC Transfusion

During the 1990s, the risks of RBC transfusion seemed to be well characterized. For example, there are
well defined risks of viral transmission for cytomegalovirus, hepatitis C, hepatitis B, HIV and HTLV via
transfusions16. Currently, for these viral risks, sophisticated patient screening, combined with laboratory detection
methods have become quite effective. As a result, the risks for these viral transmissions have decreased
dramatically over time (Figure 5). Transfusion has been estimated to be as safe as anesthetizing ASA I patients 17 .
However, screening tests are costly, and contribute to the rising costs of blood therapy. There are emerging
infectious risks that will require attention going forward, including Chagas disease, West Nile virus, Malaria, and
Creutzfeldt-Jakob disease.
1:100
HIV
HBC
HCV
1:1000
Transmission risk,
per unit
1:10 000
1:100 000
1:1 000 000
1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004
Figure 5. Evolution of Viral Risks Related to Transfusion over Time.
For current management of peri-operative or critically ill patient, the risk of viral infections is not among
the major concerns. One issue that is of more consequence for the critically ill patient is the accumulating evidence
that blood transfusion may have profound negative effects on the immune system. Clearly in an environment like
the operating room or the intensive care units, where much of the morbidity and mortality is directly related to
infection, if blood transfusion does in fact increase the risk for infection it is of major concern. In the late 1970's, it
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was observed that renal transplant outcome was improved among patients receiving blood transfusions before the
transplant surgery. There have been a large number of observational studies regarding the association of RBC
transfusions with infection, immunosuppression, and mortality.
Several studies have suggested that exposure to RBC transfusion increases the risk of postoperative
infection. Taylor et al recently observed that patients in a medical-surgical combined ICU experienced nearly a ten
percent increased risk of nosocomial infection with each unit of transfused RBCs18. Chelemer et al made similar
observations among patients undergoing CABG surgery19. There is also observational data that suggest decreased
long-term survival after exposure to RBC transfusion during CABG surgery 20.
Other studies support the concept that transfusions induce immunomodulation in recipients. Fransen et al
observed that intra-operative allogeneic blood transfusions were associated with increased concentrations of
inflammatory mediators as well as increased postoperative morbidity21 . Moore et al. reported the results of a
prospective cohort study of trauma patients 22. They found that there was a dose response relationship between early
blood transfusion and later development of multiple organ failure. This was independent of other measures of
shock. The mechanism for these associations remains unclear, but mediation by allogeneic white blood cells is the
most likely etiology. These donor white blood cells may directly impact the recipient’s immune function, or cause
the release of mediators of immunomodulation into the stored RBC unit 23.
There are also observational data that suggest an association of RBC transfusions and increased risk of
acute respiratory distress syndrome 24. This observation is of interest when considered together with transfusion
related acute lung injury (TRALI). TRALI is a non-specific constellation of dyspnea, hypotension, non-cardiogenic
pulmonary edema, and fever, which has large potential overlap with ARDs, which is defined clinically as dyspnea,
bilateral infiltrates, hypoxemia, and non-cardiogenic edema. Importantly, the mortality rate from TRALI is likely
low, in contrast with ARDs. The predominant hypothesis is that donor anti-leukocyte antibodies react with white
blood cells within the recipient25. A recent analysis of healthy volunteers receiving autologous RBC transfusions
demonstrates consistent impaired gas exchange after transfusion 26. This suggests that RBC transfusions have
important immune effects on the respiratory system in the majority of recipients, not just those with obvious TRALI
events. More discussion regarding TRALI can be found in the sections regarding plasma blood products.
The association of decreased long term survival and exposure to red blood cell transfusion after cardiac surgery has
been reported by several investigators27 28. The mechanism for this decreased survivorship is not well understood,
and is likely not explained by infectious events alone. Transfusion exposure may merely be a marker for conditions
that limit survival, such as peri-operative hemorrhage. Alternatively, RBC transfusions may exert a long-lasting
alteration of a recipient’s immune function, thereby impacting long-term survival. The Northern New England
Cardiovascular Disease Study Group recently compared long-term survival for patients who were exposed to
smaller quantities of RBC transfusions (1 or 2 units) to those who were never exposed to RBC transfusion during
their index CABG admission. As a result, this analysis includes patients who were more likely transfused as
treatment for stable peri-operative anemia, thereby reducing the potentially confounding factor of substantial blood
loss or other hemorrhagic complications. Exposure to small doses of RBC transfusions (1 or 2 units) during
admission for cardiac surgery was associated with a 16 percent increased adjusted risk of 5 year mortality in this
regional cohort of cardiac surgical patients. The impact on survival was most pronounced in the first 6 months
following surgery, with an adjusted hazard ratio of 44 percent (Figure 4). This adverse impact on survival after
exposure to RBC transfusion was not explained by differences among patients who received blood nor by
procedural characteristics. This was confirmed using propensity score analysis.
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Figure 4. Adjusted Survival by Red Blood Cell Exposure among 9,079 Cardiac Surgical Patients.
Leukoreduction
Because of the concern that donor white blood cells are problematic when administered to the donor during
RBC transfusion, strategies to reduce the presence of these unwanted white blood cells have been considered.
Leukoreduction has been hypothesized to be capable of reducing the previously described morbidity and mortality
related to RBC transfusion. However, meta-analyses of randomized controlled trials on this topic fail to justify
universal application of this therapy beyond previously accepted situations 25. It is important to note that this meta-
analysis supported a benefit of leukoreduction in the cardiac surgical population, based on 4 randomized controlled
trials. While some have questioned whether the available data at this point supports the considerable expense
associated with the universal adoption of this change in transfusion practice, leukoreduction has recently been
adapted in Europe and Canada, and is being increasingly adopted in the US29 30.
Storage of RBCs
A final consideration with RBC transfusions is the “Storage Lesion”. This concept considers the
predictable changes to red blood cells during storage31. There are emerging data that question the efficacy of stored
RBCs because of these changes. The goal of administering a RBC transfusion is to increase the hemoglobin
concentration and therefore improve oxygen delivery to the tissues. Normal RBCs have a biconcave shape and are
quite capable of deforming as they pass through capillaries. During storage, RBCs lose their biconcave shape and
become irregular in shape. As a result of these morphologic changes, stored RBCs are less deformable, and more
adherent to endothelium32. Stored RBCs also become depleted of ATP and 2,3-DPG and these changes may
contribute to decreased function. The clinical significance of the storage lesion is not certain.
Platelet Transfusions
A recent review of evidence based indications for platelet and plasma has been completed for the critically
ill patient33. Stored units of platelets are can be collected by two methods. Regardless of collection technique, units
of platelets must be stored at room temperature, kept in constant motion, which results in a short shelf life. They are
stored in a special permeable plastic, as they continue to respire during storage. If respiration were not to occur, the
platelets would become anaerobic, produce lactate which may not be able to be buffered by the small quantity of
plasma in the stored unit, become acidotic and ultimately die.
Transmission of bacterial infection is a significant risk of platelet therapy, and is several orders of
magnitude more frequent than transmission of viral infections, as mentioned previously34. In addition, the fatality
rate due to bacterial contamination of platelets is several orders of magnitude greater than the transmission rate of
viral infections, such as HIV or hepatitis C. For the peri-operative or critically ill patient, transmission of bacterial
infections via platelet administration is a serious concern.
Potential sources of bacterial contamination of platelet units include the skin of the donor at the time of
collection. Less likely sources are bacteremia of the donor, contamination of the collection bag, or contamination
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during processing of the unit. The risk of bacterial transmission is greater with platelet units compared to other
blood products which are stored at cold temperatures. Currently the risk of bacterial contamination is estimated at
1:2000 to 1:3000. Blood banks currently culture stored platelet units to detect units that are contaminated with
bacteria. While this is helpful for reducing the risk of bacterial infection, there are ongoing concerns about both
false positive and false negative results. A recent observational study from the American Red Cross reported a
confirmed positive contamination rate of 1:5,399, from a pool of all positive cultures (crude rate of all positive
cultures was 1:1,641)35. In other words, only 30% of all positive cultures from these aphereis platelet units were
ultimately confirmed positive. This illustrates the limitation of this screening methodology.
Other risks related to platelet transfusions include TRALI, febrile reactions, and transfusion associated
circulatory overload. There are also observational data from CABG surgery patients that describe an association of
platelet transfusion with increased risk of stroke, inotrope use, pulmonary dysfunction, as well as death. These
associations were significant after adjustment for patient and disease characteristics36.
Interpreting these risks of platelet transfusions is challenging, because the data to support a benefit for
platelet transfusion is lacking. What limited data there is derives from the management of non critically ill
hematology and oncology patients who develop thrombocytopenia as a result of chemotherapy. A recent review
regarding platelet therapy summarizes the available literature37. This review suggests generalizing those guidelines
developed for the oncology patients does not make sense. Therefore the decision to use prophylactic transfusions
(i.e, keep the platelet count above a certain threshold) or therapeutic transfusions (i.e., transfuse only for active
bleeding or immediately prior to a procedure) in the operating room or intensive care unit is not currently clear. In
addition what dose of platelets is necessary is not well characterized either.
Fresh Frozen Plasma & Cryoprecipitate
Fresh frozen plasma (FFP) is often administered to patients with elevated prothrombin time (PT) or
activated partial thromboplastin time (PTT). FFP does contain fibrinogen, so this product can also be administered
to patients with a low fibrinogen. Cryoprecipitate is made from FFP, and contains higher concentrations of
fibrinogen, von Willebrand factor, and factor VIII. As such cryoprecipitate is indicated to replete deficiency of
these factors. These indications based on abnormal laboratory coagulation studies are most appropriate prior to an
invasive procedure that is associated with bleeding risks or during an episode of active hemorrhage. These
indications are most often viewed as inappropriate when used to prevent spontaneous bleeding. Also use of FFP as
a volume expander is viewed as inappropriate. Unfortunately, none of these indications are evidence-based.
Furthermore, there is incomplete evidence that first, the correction of abnormal coagulation studies with FFP is
transient in nature (i.e., lasts only 2 to 4 hours), and second that abnormal coagulation studies do not necessarily
predict bleeding risk during procedures32.
While the indications for and benefits of these plasma blood products remain uncertain, some risks related
to their use are more clearly understood. Like all the blood products discussed in this review, use of plasma carries
risks of infection, allergic reactions, hemolysis, and circulatory volume overload. Data from the United Kingdom
(Serious Hazards of Transfusion) Hemovigilance Systems (SHOT) document that allergic reactions are more
common with plasma units compared to RBC units38. Hemolysis from ABO incompatibility is also possible,
because plasma may contain anti-A and anti-B antibiodies that react within the recipient. The “universal donor” is
AB type plasma. Recent data from the French and the United Kingdom (Serious Hazards of Transfusion)
Hemovigilance Systems document that the risk of transfusion related acute lung injury (TRALI) is also much higher
with “plasma-rich” blood components, such as fresh frozen plasma and platelets, compared to RBC transfusions 36.
SHOT data suggests a risk of 1 in 60,000 per unit for plasma transfusion. Interestingly, these data found a strong
association of TRALI and female gender of the donor. It is hypothesized that pregnancy may induce human
leukocyte or human neutrophil antibodies among these female donors. This has led to the preferential use of male
derived plasma for fresh frozen plasma products in some countries.
Massive Transfusion
Observational evidence from Operation Iraqi Freedom and Trauma Centers is informing changes to
Massive Transfusion Protocols at many trauma centers39. One major change has been the suggested ratio of red
blood cell to fresh frozen plasma (FFP) transfusions during resuscitation of the most severely injured and
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uncontrollably hemorrhaging trauma patients. An association between red cell to FFP ratios and mortality has led to
the recommendation of administering a ratio o f 1:1 or 1:2 for these patients 40. A randomized trial of these ratios is
clearly needed to further investigate whether these observations are indeed valid. Other important considerations
during management of these patients include vigilance for and management of hypothermia, acidosis, and
hypotension.
General Considerations
Currently, there are three predominate risks to consider when deciding to use blood products: 1.
transfusion related acute lung injury (TRALI); 2, bacterial contamination of platelets; and 3. ABO incompatibility.
TRALI and bacterial contamination of platelets have been described above. Administration of an incompatible unit
of blood is not a new problem, but remains a significant risk today. For example, errors with blood specimens and
samples labeled with the wrong patient information are not rare41. ABO incompatibility is most frequently related to
transfusion of RBCs, but can also occur with platelets and plasma products. Sixty percent of the transfusion related
deaths reported to the FDA during 1990-1998 were hemolytic reactions. Every year one to two dozen patients will
die simply from getting the wrong blood in the United States. Of note, transfusion of ABO incompatible blood
products has recently been introduced as a one of the mistakes that will prohibit payment for hospital care of patients
in some states.
Today we are better positioned to optimize our use of transfusions than we have been in the past. This is
possible because of a rapid growth in our understanding of not only the risks of anemia, but the risks and benefits of
RBC unit storage and transfusion over the last decade. By understanding the current evidence regarding the
treatment of anemia with RBC transfusion, we can significantly decrease the local, regional, and national variation
currently witnessed for transfusions. Specific to the use of fresh frozen plasma (FFP) and platelets, the risks and
benefits of transfusion are less certain. However, there is growing evidence regarding the risks of transfusing FFP
and platelets that are relevant when making decisions to administer these products.
In conclusion despite significant advances in the safety of blood therapy, there remain significant risks
related to their use. Variation in the utilization of blood products that are not explained by differences in patient and
disease characteristics suggest that provider behavior is driving at least some of our national use of blood products.
Given the risks to patients that still exist when they are transfused, careful and judicious use of blood products is
appropriate.
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Amalberti R, Auroy Y, Berwick D, Barach P. Five System Barriers to Achieving Ultrasafe Health Care. Ann
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Taylor RW, O’Brien J, Trottier J, et al. Red blood cell transfusions and nosocomial infections in critically ill
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Chelemer SB, Prato S, Cox PM er al. Asssociation of bacterial infection and RBC transfusion after coronary
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Engoren MC, Habib RH, Zacharias A. Effect of blood transfusion on long term survival after cardiac operation.
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Vamvakas EC. White blood cell containing allogeneic blood transfusion and postoperative infection or mortality:
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Gajic O, Dzik WH, Toy P. Fresh frozen plasma and platelet transfusion for nonbleeding patients in the intesive
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Schrezenneier H, Walther-Wenke G, Muller TH, et al. Bacterial contamination of platelet concentrates: results of
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Ongjen G, Dzik WH, Toy P. Fresh frozen plasma and platelet transfusion for nonbleeding patients in the
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Hemodynamics of Neuraxial Anesthesia: Contemporary Concepts

Virendra K Arya MD, FRCPC PGIMER-Chandigarh/India
University of Manitoba/ Canada
Hemodynamics of Neuraxial Anesthesia: Contemporary Concepts

Neuraxial anesthesia (NA) i.e. spinal and epidural has a long-standing history of success. Anesthesiologists master
this technique early during their training, with achievement of technical competence (> 90% success rate) after as
few as 45 and 60 attempts at spinal and epidural anesthesia, respectively 1. This ease of performance and established
successfulness of NA may therefore erroneously give the impression of simplicity. However, much has been learned
over the more than 100 years of its widespread use about the complexity of the anatomy, physiology, pharmacology
and applications of NA in various clinical situations. In this refresher course lecture, several models of the
circulatory system will be discussed to help elucidate the cardiovascular effects of NA. The application of NA
anesthesia in patients with cardiovascular diseases will be discussed. Finally, an approach to hemodynamic
management after NA will be outlined in terms of the current literature.
Theories of hemodynamic changes associated with neuraxial anesthesia
The reported incidence of hypotension and bradycardia after spinal anesthesia is 36.8% and 4.9% respectively,
increasing age and analgesic level being the risk factors2. There were a number of early theories to explain this
phenomenon, much of which has subsequently been refuted 3. These included: The direct circulatory effects of local
anesthetics. However, the vascular absorption of local anesthetic from cerebrospinal fluid or epidural space does not
result in blood levels sufficient to cause any direct circulatory effects; Relative adrenal insufficiency as a
consequence of adrenal sympathectomy. However, the acute circulatory changes after NA have been shown to be
relatively unrelated to changes in adrenal hormone levels; Skeletal muscle paralysis was postulated to cause pooling
of blood, but the reduction in skeletal muscle tone does not fully explain the observed changes; Ascending
medullary vasomotor block with concurrent respiratory insufficiency. However, it is not possible because the local
anesthetic concentration in the cerebrospinal fluid is insufficient to cause direct medullary, vasomotor and
respiratory depression. Respiratory insufficiency is attributable to medullary ischemia resulting from the associated
hypotension and diminished brain stem perfusion.
Subsequent to these theories, it was postulated that the primary cause of NA-induced hypotension was blockade of
the preganglionic sympathetic nerves. Early studies from 1940 to 1970 conducted in animals, human volunteers and
patients showed the following consistent hemodynamic changes after NA3,4,5 : systemic vascular resistance (SVR) is
reduced by 5-20%; stroke volume (SV) is reduced by 5-25%; heart rate (HR) is reduced by 5-25% ; cardiac output
(CO) is reduced by 10-30%; and arterial blood pressure (BP) is reduced by 15-30%. It was proposed that the extent
of sympathetic blockade influences the magnitude of change in SVR. The sympathetic outflow from the spinal cord
is widespread in thoracolumbar origin (T1 to L5). Hence, the circulatory effects of NA are variable depending on the
level and extent of the NA block. NA limited to sacral and lumbar dermatomes will not be expected to cause major
circulatory alteration, whereas blocks up to the mid-thoracic levels will cause partial sympathetic denervation. Even
higher levels of NA may cause complete sympathetic blockade, including sympathetic outflow to the heart, which
typically arises from the T1-T4. We know that BP = CO  SVR (systemic vascular resistance). Variables affecting
CO include preload, afterload, contractility and HR. Sympathetic blockade limited to the lower or mid-thoracic
region causes vasodilation in lower extremities, with compensatory vasoconstriction in the upper extremities
mediated by carotid artery and aortic arch baroreceptors in response to the fall in BP 6. Thus, the net effect is no
change in calculated SVR. As the sympathetic blockade extends to include the entire thoracolumbar outflow, it
becomes impossible for compensatory vasoconstriction to occur. Therefore, a low calculated SVR would be an
invariable finding after a spinal blockade where the sensory level extends above the T4 level 7. It is known that in the
absence of augmented metabolic requirement, homeostatic mechanisms maintain CO relatively constant despite
large induced changes in the heart rate. However, when metabolic demands are increased by muscular exercise, or
the circulation is stimulated by catecholamines, CO can rise through an increase in stroke volume (SV), even when
alterations in the heart rate are prevented8. So, CO is function of heart rate and SV. As previously mentioned, earlier
studies reported a decrease in CO and SV after NA4,5. Since there was no evidence that cardiac contractility was
depressed by NA and the reduction in CO was disproportionate to decrease in HR, the only remaining explanation
for the decrease in CO could be a reduction in venous return (VR). This conclusion was supported by the
observations of a decrease in pulmonary artery wedge pressure (PAWP) or central venous pressure (CVP); these
were surrogates for volume changes. Thus, these early observations of reduction in PCWP and CVP with NA in
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1970’s lead to the genesis of the “preload reduction theory” to explain the hemodynamic effects of NA. This was
consistent with Guyton’s suggestion9 that VR is an independent variable for determination of CO. Subsequent
animal and human studies demonstrated venodilation and reduced VR after spinal block and therefore corroborated
this conclusion10,11. Unlike the arterial system, the venous system retains little vascular tone when its sympathetic
nerve supply is interrupted. Consequently, it was proposed that this lower pressure system depends on gravitational
forces to return blood to the heart and that VR and cardiac preload are both sensitive to mechanical and positional
influences during NA. This explanation for NA-induced hypotension was unable to explain the observations in some
early studies showing an increase in CO despite a decrease in cardiac filling pressures and hypotension after
NA5,12,13. The preload reduction theory proved not to be the answer.
An alternate model that describes different vascular beds within the body, each with its unique vascular resistance,
has been proposed14. According to this model, some vascular beds have long time constants where blood takes a
longer time to traverse the bed and return to the heart (e.g., splanchnic circulation). Other vascular beds have fast
time constants, with short blood transit times (e.g., heart, brain, and muscle). Changes in arterial tone alone may
cause a redistribution of blood from slow to fast beds, thus increasing VR and CO. As a result of this redistribution,
the observed increase in CO after NA would be explained. This redistribution of blood away from the slow
splanchnic circulation to faster beds has been shown after T5 spinal anesthesia in healthy young volnteers 15.
Radionuclide studies during epidural anesthesia have also shown that there is a reduction in the blood volume of
thorax, abdomen and arms, and an increase in the blood volume in the denervated legs 16. Clearly, this model of the
redistribution of blood volume between the different vascular beds precludes the simplistic explanation of
venodilation and preload reduction as the main cause of hemodynamic side-effects following NA. However, this
model also does not fully explain the observed effects during NA.
Apart from hypotension, reduction in HR is the second most common observation during NA 3,4. The simplest
explanation for bradycardia during NA could be the loss of sympathetic input to the heart, leaving the heart with
unopposed vagal parasympathetic innervation. However, the finding of elevated resting HR in denervated,
transplanted hearts indicates that under normal resting conditions, the basal parasympathetic tone exceeds basal
sympathetic tone17. Thus, sympathetic tone is not generally required to maintain normal resting HR (70-80/min),
which is less than the intrinsic automatic firing rate of the sinoatrial node (110-120/min). This fact is further
supported by the observation that conventional doses of beta-adrenergic receptor blockade have little influence on
the resting HR in the normally innervated heart, but markedly attenuate exercise-induced tachycardia. These
observations suggest that the blockade of cardio-accelerator sympathetic nerves is not the cause of bradycardia
during NA unless vagal tone to the heart is also activated. Bradycardia during NA block is very responsive to
atropine administration. This points to the critical influence of increased vagal tone in the genesis of the reduced
HR18. In light of this, it appears that observed factors causing increased vagal tone, including situations such as
young age, anxiety and patients with known vagotonia etc. can have a reflex reduction in HR. These factors are of
greater importance than the inhibition of sympathetic cardio-accelerator fibers19. In addition to the aforementioned
vagal mechanisms, there are important intrinsic cardiac reflexes that are volume sensitive. One of these is the local
Bezolt Jarisch reflex that causes an acute reduction in SA node output in response to decreased LV stretch 20.
Another reflex involved is the reverse Bainbridge reflex that causes an increase in vagal tone in response to reduced
RA stretch21. Further un-named intrinsic cardiac reflexes which result in bradycardia through intrinsic chronotropic
stretch receptors in the heart are also in effect. The apparent benefit of these regional survival reflexes to the heart is
that with decreased volume load, the heart will need to do less work (decrease HR). However, these HR-reducing
reflexes in response to acute preload reduction manifest only in the absence of an activated sympathetic nervous
system by baroreceptor reflex (tachycardia response to hypotension). This bradycardia response can also be seen in
conditions of spinal shock in the setting of spinal cord injury. Preload reduction theory was used to explain
bradycardia associated with NA on the basis of decreased VR triggering these reflexes in absence of increased
sympathetic tone.
Based on the “inaccurate” concept of preload reduction as the primary mechanism for hypotension and bradycardia,
the management of NA-induced hypotension conventionally included preload augmentation with prehydration, head
down position of 10-150, left uterine displacement in pregnant patients as primary intervention and the use of
vasopressors and atropine if HR was reduced as secondary interventions. Also based on these misguided concepts
was the teaching to avoid NA in obstructive cardiac lesions (aortic stenosis, mitral stenosis, hypertrophic obstructive
cardiomyopathy), complex congenital disorders, severe pulmonary hypertension and volume-depleted states such as
pregnancy-induced hypertension4. Since the maintenance of preload and afterload is critical in these conditions, the
main concern has been that these patients would become hemodynamically unstable due to rapid preload reduction.
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Contemporary concepts of hemodynamics associated with Neuraxial Anesthesia

1. There is no decline in CO after NA.
Despite earlier studies on the hemodynamic effects of NA conducted in human volunteers reporting a 10-30%
decrease in CO, CVP and BP 4,5,15,22,23 some investigators12 at this time also refuted the decrease in CO as a possible
mechanism of hypotension after NA. However, these were not considered important because the prevailing opinion
at the time remained that CO was reduced secondary to preload reduction4. In these studies, CO was measured
intermittently either by the direct Fick principle (O2 uptake technique) or dye dilution method and hypotension was
treated only if subjects became symptomatic. Bonica and colleagues observed unexpected increases in CO, HR and
SV with high T2-3 blocks, which they considered to be unexplained 12.
Spinal anesthesia in the obstetric population has been an important technique to improve maternal and neonatal
safety. Post-spinal hypotension has remained a common problem and therefore has been an important area of
investigation. In obstetric patients, the theory of caval compression and supine hypotension leading to preload
reduction was based largely on a study measuring CO by dye dilution in eight unanesthetized patients24. Overall, CO
was 12% less in the supine compared with the lateral position in this study. It was then proposed that compression of
the inferior vena cava (IVC) by the gravid uterus caused hypotension after spinal anesthesia because VR was
reduced and thus CO was decreased25. Marx and colleagues developed the concept that blood was trapped in the
legs, and introduced the treatment strategy of ‘acute hydration’ supported by a widely cited illustrative case
history26. Subsequently, fluid administration before spinal anesthesia became the standard ‘prophylaxis’ and an
almost universal therapy27.
The proponents of the preload reduction theory suggested three ways to prevent NA associated hypotension: 1)
Infusion of crystalloid or colloid to compensate for the venous blood trapped in the legs. However, initial reports of
success in preventing hypotension28 were not replicated in subsequent studies, despite volumes up to
30ml/kg29,30,31,32; 2) Leg compression: This has proven to be quite ineffective, despite the success of the anti-G suit
in preventing lower limb pooling and hypotension in aerospace medicine 33; 3) Lateral uterine displacement to reduce
IVC compression. Although widely used, this procedure is variably applied 34, and does not reliably prevent
hypotension after spinal anaesthesia32,35. It is therefore clear that therapies based primarily on the concept of preload
and CO reduction do not reliably prevent hypotension after NA.
The answers have become clearer over the last 20 years with the advent of newer, often non-invasive technologies
that measure CO and the associated parameters such as preload. These include transthoracic echocardiography
(TTE), trans-esophageal echocardiography (TEE), suprasternal aortic Doppler and uterine artery Doppler
ultrasound. These modalities have been used in studies during obstetric NA and have provided valuable new
information on maternal-fetal well-being and hemodynamics. The studies on hemodynamic changes after spinal
anesthesia in severe preeclampsia have shown that these patients are far less likely to develop hypotension than
normal pregnant or non-pregnant women. Despite the contracted blood volume in these pre-eclamptic patients, CO
is increased after the spinal block36,37. Remarkably, studies done in the 1950s38 showed similar findings in pregnant
women with severe preeclampsia. However, for some reason the proponents of preload reduction theory prevailed.
In the last three decades, many studies have shown that CO increases after NA in volume replete subjects, and
further volume loading can further increase CO by up to 43% above baseline. Despite this, arterial hypotension will
still occur14,12,30,31,39,40. Initial studies on high spinal for cardiac surgery have also revealed that CO and preload are
increased following NA. Lee et al.41 studied hemodynamic consequences of high-dose bupivacaine spinal anesthesia
in patients undergoing cardiac surgery. Patients who received high spinal showed a trend toward a higher CI in the
pre-CPB period and significantly higher CI after separation from CPB, with mean arterial pressure and systemic
vascular resistance index being significantly lower in the this group during the pre-CPB period. There is an
unjustified perception that high level regional anesthesia with total body sympathectomy could cause profound
hypotension and bradycardia leading to cardiovascular collapse. While it is true that some degree of hypotension is
often present, both bradycardia and hypotension are easily managed by the use of the Trendelenburg position and/or
by using small doses of vasoactive drugs such as dopamine or phenylephrine. There is no need to preload patients
with intravenous fluids prior to spinal injection.42
These observations when considered collectively have led to the focus on the arterial circulation as a source for
post-NA hypotension in the fluid-replete patients; hypotension after spinal anesthesia primarily reflects a decreased
arterial resistance and not a reduction in CO (due to preload reduction). In most cases, VR is maintained and there is
a compensatory increase in CO, mediated by an increase in SV and even HR sometimes. SVR is therefore primarily
reduced after NA.
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2. The Guytonian concepts are not applicable in explaining post-NA hypotension

It has taken almost 50 years to appreciate that it is afterload reduction that is the cause of NA-associated
hypotension. The underlying mechanism for post-NA hypotension in the preload reduction theory was that a
reduction in CVP would reduce CO, and thus reduces arterial BP. This hypothesis was based on the view that CVP
controls CO, as suggested by the experimental studies by Paterson, Starling and Guyton 9,43. Starling’s studies were
conducted in an isolated heart preparation, supplied with blood from a venous chamber, which could be raised or
lowered to adjust the right atrial pressure (RAP). In this ‘open’ system, CO was related to the RAP and not to the
supply to the venous reservoir, which was externally adjusted by the investigator to keep the RAP constant. By
elevating the height of the reservoir, inflow pressure increased the stretch of the ventricular muscle, and thus
ejection volume was increased. Under these circumstances, RAP regulated CO, but this did not mean that the
increased flow from the venous reservoir had increased the CO. Similarly, the studies of Guyton in which he related
RAP/CVP and VR, were equally artificial. Guyton’s studies used an adjustable pump that controlled VR. When the
pump rate and thus the experimentally controlled VR was increased, a limit was reached where a decrease in RAP
occurred and VR did not change, implying upstream flow limitation 16. In the whole body, the circulation exists as a
loop where the two factors of VR and CO are of course linked; what is pumped out has to return, and neither is the
cause or effect of changes in CO or CVP/RAP 44. A decreasing RAP/CVP could be reflective either of an increasing
pump function or a decreasing VR due to depleting circulating volume. Hence, Guyton and Starling considering
RAP/CVP to be an independent variable in their highly artificial experiments is unlikely to be applicable to the
intact animal45.
The other way of understanding the circulation is that in health, the heart is always kept “submerged” in a blood
pool, irrespective of body posture, so that it can generate required CO. The sympathetic nervous system is crucial in
maintaining the required “squeeze” on the circulatory system so that the required blood level can be maintained to
keep the heart submerged in the blood, despite a change of body posture. On the arterial side this squeeze is more
relevant in determination of arterial pressure, thereby reflecting afterload to left ventricle. On the venous side it is
more relevant to regulate the capacitance of the venous system, thereby VR or preload to the heart. The relationship
between CVP and CO has been re-evaluated46,47. It is important to correct the common misconception that a
decrease in RAP will act to increase blood flow through the veins against some venous resistance48. The important
feature of the venous system is its compliance, not its resistance, and we can relate the RAP/CVP to the volume held
in the venous side of circulation49. A recent helpful view is that the volume in the venous system is more relevant
than the pressure, and that ‘venous excess’ or ‘stressed volume’ is the important regulating factor on the venous side
of the circulation50. Venous capacitance and stressed volume are regulated by sympathetic tone in various clinical
conditions, such as changing body posture and hemorrhage; these result in reflex increase in sympathetic outflow.
After NA, venodilation will be maximal, depending on the location of the veins. If the veins lie below the right
atrium, gravity will cause pooling of the blood peripherally, and if the veins are above, there is back-flow of the
blood into the heart by gravity. Venous return to the heart, or preload, therefore will depend on patient positioning
during NA.
The supine posture in humans is unique and different from other mammals. In humans the supine position of the
IVC is gravity dependent, and gravity will help drain blood into the IVC from liver, spleen and mesenteric veins,
even if sympathetic squeeze on this splanchnic venous reservoir system is lost due to NA. Only the kidneys and
lower limbs lie below the IVC in the human supine position. The lower limbs can trap blood after sympathectomy in
supine position because femoral veins pass through inguinal canal, which lie anterior to the IVC and lower limb
veins. Trendelenburg positioning of 10-200 will facilitate the VR from lower limbs in humans. Hence, the
experiments done in dogs showing a reduction in VR after spinal anesthesia, are not applicable to humans. 11 Dogs
will lie only in lateral position where the splanchnic circulation will be more dependent in relation to the IVC and
pooling of blood will therefore result after the sympathetic block. In pregnant woman lying supine, the splanchnic
component of this capacitance will drain directly into the IVC via the hepatic veins. These veins are not compressed
by the uterus and will therefore not affect VR. However, in the head-up position during NA, there will be an
augmentation of the impact of arterial dilatation associated hypotension (due to venous pooling leading to VR
reduction). In this situation, the reduction in cardiac filling pressure due to decreased VR may trigger the
intracardiac stretch receptors to cause bradycardia in absence of opposing baroreceptor reflex.
3. Sympathectomy after NA is not complete
In healthy patients, with a high thoracic block, the heart rate and cardiac index responses to a stress applied to an
unanesthetized dermatome remain intact. Stevens et al.51 have shown that in the absence of hypovolemia and beta
block, the heart appears to be able to respond normally to stress during extensive spinal anesthesia. The
sympatholytic effects of spinal anesthesia are more complete on the innervation of the adrenal medulla and less
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complete on the cardio-accelerator fibers. The sympathetic block after NA is rarely complete; some preservation of
sympathetic reflexes remains. Endogenous pressor responses seem to be mediated by norepinephrine, which is
released by peripheral nerve terminals running along the arterioles that become blocked at the spinal level. Arterial
tone is consequently reduced after NA. Preganglionic sympathetic outflow to the adrenals is not completely blocked
despite T6 to L2 sensory and motor block and postural reflexes remain partially intact.52
Risk factors for Neuraxial Anesthesia associated hypotension
A high incidence of NA-induced hypotension has been reported in the following patient populations and scenarios:
chronic alcohol consumption; patients with hypertension on chronic antihypertensive therapy; sensory block ≥ T6
with in 10 min of procedure; body mass index; urgency of surgery53. The sympathetic nervous system is affected in
chronic alcoholics, because of neuropathy, leading to orthostatic dysregulation54. Arterioles of hypertensive are
capable of greater vasodilation because medial hyperplasia and there is a central redistribution of total blood
volume. Moreover, diuretics used to treat chronic hypertension can lower plasma volume 55. In obese patients, the
amount of local anesthesia needed for sufficient blockade is more difficult to estimate. Increased abdominal pressure
with compression of the subarachnoid cavity and a reduction of the cerebrospinal fluid could offer an explanation 56.
Nevertheless, the extent of sensory block correlates with lumbosacral cerebrospinal fluid volume and not with body
habitus57. In emergency surgery there is increased stress, which can lead to increased sympathetic tone and can
effect amount of hypotension after spinal anesthesia. High baseline HR, HR variability and high baseline perfusion
index (derived from a pulse oximeter), may predict high incidence of hypotension after spinal anesthesia 58,59,60. High
baseline HR and HR variability indicate a relatively high sympathetic tone or hypovolemia and may help to predict
obstetrical patients in whom pre or co-hydration would be beneficial58,59. Baseline perfusion index may reflect basal
peripheral arterial tone that is decreased by NA induced sympathectomy. High levels of preoperative anxiety have
been shown to have a positive correlation with hypotension after spinal anesthesia in women undergoing caesarean
delivery61. Serious bradycardia may be seen in patients with autonomic neuropathy, spino-vagal reflex, sitting
posture, hypoxia of CNS/ heart secondary to hypoventilation or shunting in complex congenital disorders and if
initial hypotension is neglected53.
Neuraxial anesthesia is safe in cardiac disease
The traditional cardiac contraindications for NA, especially for spinal anesthesia, have been based on the preload
reduction theory and have not been evidence-based. With the new understanding that primary mechanism for
hypotension after NA is a reduction in arterial resistance, NA can be given in any cardiac condition, as long as
invasive arterial pressure monitoring is used, the physiology is understood, and appropriate treatment is available for
the afterload reduction. In critical cardiac conditions, low dose infusions of vasopressors/ inotropes such as
phenylephrine (0.2 mcg/kg/min) or norepinephrine (0.02mcg/kg/min) or epinephrine (0.02mcg/kg/min especially in
patients with dilated left ventricle with poor ejection fraction) can be initiated while spinal anesthesia is being
performed and can be titrated to BP. Patient position is maintained in the supine position with 10-150 head down tilt.
If the anesthesiologist is particularly concerned about rapid afterload reduction, the NA technique may be modified
by using an intrathecal or epidural catheter to allow a more controlled onset 62. However, based on the experience
from single shot, high-dose spinal anesthesia in patients with mitral and aortic stenosis undergoing cardiac surgery
(with prophylactic vasopressor infusion titrated to invasive BP), sudden severe hemodynamic instability has not
been reported63,64. Most anesthesiologists have considered GA to be safer in these patients. However, the induction
of general anesthesia similarly produces a degree of central sympathectomy (due to reduced central sympathetic
outflow). In addition, positive pressure ventilation and PEEP reduce VR. Induction agents for general anesthesia
may have direct myocardial depressant effects. This is not the case with NA. Cardiac anesthesiologists who induce
critically ill cardiac patients are well aware of the practice of using prophylactic vasopressor/inotrope infusions and
invasive monitoring during the induction of general anesthesia. The same principles should be applied while
planning NA in critically ill cardiac patients. Hence, it is largely a myth that general anesthesia is safer than NA in
patients with critical cardiac lesions. Both techniques can be safely performed as long as there is invasive BP
monitoring and pharmacological dose titration to predetermined hemodynamic endpoints. Currently, high spinal
anesthesia has been given safely in cardiac surgery patients for coronary revascularization, severe mitral stenosis for
mitral valve replacement and critical aortic stenosis for aortic valve replacement 41,42.
In patients with complex congenital cardiac lesions who must remain in balanced parallel circulations e.g. single
ventricle patients, NA could easily be argued to be advantageous for non-cardiac surgery. These patients require a
balance between their pulmonary vascular resistance and SVR to allow for proportionate blood flow through the
lungs and systemic circulation63,64. There should be proportionate mixing of oxygenated and deoxygenated blood
that is reflected by arterial oxygen saturations between 80-90%. NA below the level of T4 will reduce SVR without
affecting pulmonary vascular resistance and cardiac contractility, as long as adequate spontaneous respiration is
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maintained. Anesthesiologists in this situation will have to manage only one physiological parameter, namely
afterload. However, with general anesthesia, all the three hemodynamic variables i.e. pulmonary vascular resistance,
SVR and cardiac contractility will affect. They will all need to be managed appropriately. NA has been reported to
be safe in patients with severe primary and secondary pulmonary hypertension, severe peripartum cardiomyopathy,
and complex congenital cardiac disorders undergoing non-cardiac obstetric surgery63,64,65,66,67,68,69,70.
The admonition to avoid the use NA in patients with critical cardiac disease has been largely opinion based and is
not rooted in the contemporary understanding of NA-associated physiology4,5,23,70,71. Many of the adverse outcomes
during NA and cardiac disease were during the period of the preload dominant theory and lacked careful invasive
monitoring and understanding of cardiac lesion pathophysiology while performing NA 71.
Management of hemodynamic changes after Neuraxial Anesthesia
The current literature suggests that NA-induced hypotension reflects decreased arterial vascular resistance.
Therefore, in fluid-replete supine patients, VR is maintained and consequently CO is maintained or increased and
there will be an increase in SV and HR. In this situation, a rapid acting alpha-agonist such as phenylephrine is the
best option to restore baseline hemodynamics. Preloading the patient with intravenous fluids will further increase in
CO, SV and CVP, but the increases are short-lived. The arterial vasodilatation, as is the primary cause of
hypotension, remains uncorrected. Moreover, intravenous fluid could cause even further decreases in SVR by
hemodilution. It is logical to administer fluid before and whilst the block is evolving in relatively volume deplete
patients. However, vasopressors should stay as the primary therapeutic option and should be administrated in small
intravenous boluses or by infusion to achieve the desired goals; intravenous infusions of these vasopressors is likely
more efficient and avoids the sudden peaks and valleys in BP.
Recent evidence has suggested that phenylephrine is a good choice with pharmacologically appropriate action and
rapid treatment of hypotension due to spinal anesthesia in obstetrics. The administration of ephedrine may actually
cause increased fetal metabolism and lead to fetal metabolic acidosis. However, ephedrine may be more appropriate
if maternal hypotension and bradycardia occurs simultaneously72. The use of 100 mcg phenylephrine boluses for the
treatment of hypotension has been associated with a lower incidence of intraoperative nausea and vomiting than was
6-10 mg boluses of ephedrine, despite a similar incidence of hypotension. The lower incidence of nausea and
vomiting may be related to the faster onset of the pressor effect of phenylephrine (mean onset 61 seconds vs 89
seconds), leading to the more rapid correction of hypotension73. Phenylephrine has also been shown to be effective
for the treatment of hypotension in elderly patients with a T8/T10 block without causing bradycardia. The addition
of phenylephrine 10 mcg/min to an ephedrine infusion at 2 mg/min resulted in a significantly lower incidence of
hypotension with associated nausea and vomiting than did ephedrine alone. In contrast, the addition of ephedrine to
a phenylephrine infusion did not result in any added benefit over phenylephrine alone. Prophylactic phenylephrine
infusions reduce the risk of hypotension induced by spinal bupivacaine, before and after caesarean delivery, as well
as the risk of nausea and vomiting. The dose of prophylactic phenylephrine remains controversial. However, most
studies recommend 50-75 mcg /min. Higher doses are associated with episodes of hypertension, slow HR and a
decrease in CO. Infusions of metaraminol, epinephrine and norepinephrine have also been successfully used 74.
However, the problem remains about ready access to standard dilute formulations suitable for operating room use.
Proper positioning of the patient and concomitant sedation must be emphasized. Spontaneous respiration should be
monitored. Both bradypnea and bradycardia should be aggressively managed, as these two have been observed as
precursors to cardiac arrest reported during spinal anesthesia. Bradycardia seems to be more reflex mediated and
responsive to atropine (0.4-0.6 mg). Episodes of bradycardia may occur suddenly and unpredictably, with
hemodynamics apparently stable up to the event. Those patients at risk for the reflex have been discussed above26.
Some studies have advocated for the early use of epinephrine (0.1-0.2 mg) for the treatment of severe bradycardia
under NA75,76. Recently ondansetron given prior to the onset of spinal blockade has been shown to reduce the
incidence of hypotension and bradycardia by abolishing the Bazold Jarisch reflex, which may be mediated through
the 5-HT receptors in the heart77,78.
Conclusion
There is paradigm shift from preload reduction theory to afterload reduction as the primary mechanism of NA-
induced hypotension. Vasopressors administered as infusions or as titrated boluses are now considered first line
therapy in the management of hemodynamic instability secondary to NA. Fluids are only given for volume
replacement in hypovolemic patients. There is no myocardial depression with NA. The origin of bradycardia is
multifactorial, often has a reflex component, and is usually responsive to atropine. Bradycardia should be treated
aggressively before the low CO becomes severe, which may in turn delay the circulatory response to therapy.
Bradycardia has been identified as the main precursor of cardiac arrest during NA. The early use of epinephrine in
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severe bradycardia is recommended.

The effect of gravity must be considered both for the spread of the block and for its effect on hemodynamics. There
seems to be no absolute cardiac contraindications for NA with invasive pressure monitoring, careful positioning and
appropriate vasopressor administration. Maintaining adequate spontaneous respiration is crucial for hemodynamic
stability after NA.
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Perioperative Management of Cardiovascular Implantable Electronic Devices

(CIEDs)
Annemarie Thompson, MD Durham, North Carolina
OVERVIEW
The rapidly expanding technology of cardiovascular implantable electronic devices (CIEDs) as well as their
widespread use not only for bradyarrhythmia and tachyarrhythmia management, but also for congestive heart failure
management has ushered in an era where patients who experience long-term benefit from such therapy are
presenting for both cardiac and noncardiac surgery. With approximately one million patients worldwide receiving a
pacemaker or implantable cardioverter defibrillator (ICDs) every year, patients with CIEDs are a growing
population in the perioperative arena. As “internists of the operating room” who routinely manage complex, life-
threatening medical illnesses such as diabetes, anesthesiologists are increasingly asked to address the perioperative
management of patients with CIEDs. Until recently, there was little guidance, confusing literature, and frank
misinformation regarding the perioperative management of CIEDs.
The July 2011 Heart Rhythm Society (HRS)/American Society of Anesthesiologists (ASA) Expert Consensus
Statement on the perioperative management of patients with CIEDs has sought to inform perioperative physicians
and encourage responsible communication between the CIED team that typically manage patients with devices and
the perioperative team. 1 The HRS/ASA Expert Consensus Statement on the perioperative management of CIEDs
has also been endorsed by the AHA, ACC, and STS. Due to its relatively recent publication in the leading
electrophysiology journal, most anesthesiologists are not familiar with the document or its details. Additionally, due
to the technical complexity of CIEDs, the rapidly evolving field, and the dearth of education regarding these devices
in clinical training programs, many advanced perioperative physicians find it challenging to learn about the
perioperative management of CIEDs.
PERIOPERATIVE CONSIDERATIONS
Preoperative assessment
Basic terminology/codes for pacemakers and ICDs are reviewed in Tables 1 and 2 respectively.
The need for two-way communication between the CIED team that usually cares for the patient and the operative
team was emphasized by the Heart Rhythm Society (HRS)/American Society of Anesthesiologists (ASA) Expert
Consensus Statement published in July 2011. The most effective means of caring for the patient with a CIED will
occur when the CIED team that usually manages the patient’s device is given the necessary details of the operative
procedure in order to create an individualized, perioperative prescription. The details are summarized in Tables 3
and 4.
Electromagnetic interference
Pacemakers and ICDs present challenges in the perioperative setting due to electromagnetic interference (EMI),
which is external interference with pacemaker or ICD function. Although there are several potential sources of
electromagnetic interference, the major source is monopolar electrocautery, particularly if the source of EMI is
within 6 inches (15 cm) of the generator. Bipolar electrocautery is usually not a concern, as the electrical current is
limited to the two poles at the end of the stylus. Monopolar electrocautery is the most frequently used type of
electrocautery, as it has both cutting as well as coagulation capabilities. Modern CIEDs have evolved to produce
better shielding from EMI. The importance of EMI is not the potential to induce a “reset” mode, but rather the
potential to induce oversentsing in the CIED. Oversensing in a pacemaker means the pacemaker “sees” the EMI as
intrinsic cardioelectrical activity and therefore, does not initiate a paced rhythm. Such failure to initiate a paced
rhythm can
negatively affect hemodynamics in a pacemaker-dependent patient. If oversensing occurs in an ICD, EMI may be
misinterpreted by the ICD as a malignant tachyarrhythmia, which may cause the patient to receive an inappropriate
shock.
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In contrast to the ASA Practice Advisory2, the HRS/ASA Consensus Statement suggests that due to the unlikelihood
of EMI when surgery is below the umbilicus, the patient should proceed to surgery with no magnet application to
the device or reprogramming. However, there should be a magnet available with the magnet function of the device
known in case of a change in surgical plan or unexpected EMI. Alternatively, a magnet can be applied if
perioperative physicians feel more comfortable with that approach, provided the perioperative team is aware of the
magnet function for that particular device. A suggested algorithm to assist clinicians in the management of patients
who present for elective surgery is shown in Figure 1. This figure is provided to help clinicians understand a
method for managing these devices and is not intended to replace consultation with a CIED team regarding a
patient’s specific device and functionality.
Magnets
Interestingly, magnets were never developed for perioperative use, although they are now widely considered for
shielding of EMI or treatment of CIED emergencies. Magnets were initially used to determine battery life in
CIEDs. However, both magnet application and reprogramming are options for eliminating EMI. The choice of
reprogramming versus magnet application largely depends on the type of surgery, patient position, accessibility of
programmer, and knowledge of magnet function of a particular patient’s device. It should be emphasized that
magnet application to an ICD generally inhibits tachyarrhythmia therapy (shocks), but does not change the mode of
the underlying pacemaker. Therefore, a magnet placed over an ICD will not induce asynchronous mode in the
underlying pacemaker. For patients with an ICD who are pacemaker-dependent, reprogramming is the preferred
option if EMI is a significant concern.
For a few ICDs, notably the PRIZM series (Boston Scientific – Guidant), the magnet mode can be changed to induce
suspension of tachyarrhythmia therapy only after the magnet is applied for 30 seconds. Tachytherapy will be
reactivated when the magnet is reapplied for 30 seconds. For any device, the magnet response should be confirmed
with the CIED team prior to magnet application. While most pacemakers will convert to asynchronous mode when
a magnet is applied to the generator, some devices have a programmable magnet function that can prevent
conversion to asynchronous mode when a magnet is placed over the generator. For this reason, it
is important to consult with the patient’s CIED team to determine a particular device’s magnet response.
Electrical reset
One of the most misunderstood issues is the concept of electrical reset. In the perioperative setting, this is thought to
very rarely occur when an energy surge directly contacts the pulse generator, resulting in a major hardware/software
failure. The reset mode is unique to each manufacturer and serves as a safety backup in the case of catastrophic
failure. The most common cause of electrical reset is therapeutic radiation, not electrocautery or external
cardioversion/defibrillation. Neither magnet application nor reprogramming will prevent electrical reset. The best
prevention of electrical reset is to direct energy away from the pulse generator (>15 cm) and to place the dispersive
electrode (“Bovie pad”) to prevent current flow across the generator.
Emergency protocol
Patients with CIEDs may present for urgent/emergent surgery, leaving little to no time for device interrogation or
CIED team consultation. In such instances, identification of the device is important. If the patient does not know
the type of device (pacemaker, ICD, Biventricular pacemaker, Biventricular ICD, etc.), then chest radiography can
be used to help identify the device. A suggested emergency protocol is displayed in Figure 2.
An electrocardiogram or rhythm strip should be examined for pacing spikes. If pacing spikes are noted before most
or all of either p-wave or qrs complexes, then the patient should be treated as if pacemaker dependent. All
pacemaker-dependent patients and patients with ICDs should have transcutaneous pacing and defibrillator pads
placed during emergency cases. A magnet should always be available and its use is recommended in the
pacemaker-dependent patient as well as the patient with an ICD. Regardless of the type of device, interrogation of
the CIED under the direction of a physician knowledgeable in the function of devices should occur as soon as
possible. The emergency protocol is described in the HRS/ASA Expert Consensus Statement.
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Table 1: NASPE/BPEG Generic Pacemaker Code
I II III IV V
Chamber paced Chamber sensed Response to sensing Rate responsive Multisite pacing
O = none O = none O = none O = none O = none
A = atrium A = atrium T = triggered R = rate modulation A = atrium

V = ventricle V = ventricle I = inhibited V = ventricle
D = dual (A+V) D = dual (A+V) D = dual (T+I) D = dual (A+V)
S = single (A or V) S = single (A or V)
Table 2: NASPE/BPEG Generic Defibrillator Code
I II III IV
Antitachycardia Pacing Tachycardia Antibradycardia
Shock Chamber
Chamber Detection Pacing Chamber
O = None O = None E = Electrogram O = None
A = Atrium A = Atrium H = Hemodynamic A = Atrium
V = Ventricle V = Ventricle V = Ventricle
D = Dual (A+V) D = Dual (A+V) D = Dual (A+V)
Table 3: Essential information to be given to the CIED team by the perioperative team
1) Type of procedure
2) Anatomic location of procedure
3) Patient position during procedure
4) If and where monopolar electrocautery will be used
5) Any other sources of EMI
6) Any planned cardioversion or defibrillation
7) Surgical venue (operating room, office-based procedure, etc.)
8) Postprocedural plan (hospital admission, discharge within 12 hours, etc.)
9) Unusual circumstances (surgery encroaching upon device leads or generator, etc.)
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Table 4: Essential elements to be communicated to the perioperative team by the CIED team
1) Date of last device interrogation -- recommend within 6 months for ICD or cardiac resynchronization
therapy (CRT) device, 12 months for pacemaker
2) Device type, manufacturer, and model
3) Indication for device placement
4) Battery longevity
5) Any leads placed within the last 3 months
6) Current programming
7) Is the patient pacemaker-dependent?
8) Device response to magnet placement
9) Any alert status on device? (such as manufacturing issues)
10) Last pacing threshold
11) Individualized perioperative recommendation/prescription based on patient information, device

characteristics, and surgical factors
Figure 1: CIED Algorithm Guide for Patients Undergoing Elective Surgery
Figure 2: CIED Algorithm for Emergency Surgery
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References
1. Crossley GH, Poole JE, Rozner MA, et al. The Heart Rhythm Society (HRS)/American Society of
Anesthesiologists (ASA) Expert Consensus Statement on the perioperative management of patients with implantable
defibrillators, pacemakers and arrhythmia monitors: facilities and patient management this document was developed
as a joint project with the American Society of Anesthesiologists (ASA), and in collaboration with the American
Heart Association (AHA), and the Society of Thoracic Surgeons (STS). Heart Rhythm 2011;8:1114-54.
2. Practice advisory for the perioperative management of patients with cardiac implantable electronic devices:
pacemakers and implantable cardioverter-defibrillators: an updated report by the american society of
anesthesiologists task force on perioperative management of patients with cardiac implantable electronic devices.
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Top 10 Respiratory Anesthesia Practices That Drive Me Crazy

David O. Warner, M.D. Rochester, MN
As ever-more sophisticated ventilators are incorporated into anesthesia machines, there is increasing confusion
regarding both the physiological principles pertinent to perioperative respiratory management and their clinical
implications. Many of the practices commonly employed have little or no evidence to support them, nor are they
supported by a convincing physiological rationale. This lecture is my opportunity to vent about some of our
irrational or sloppy practices, and is designed to be deliberatively provocative. The conclusions may be open to
debate, but hopefully any such debate will help you consider your practice on the basis of evidence and
physiology, rather than on the basis of “that’s how we’ve always done it”. Here are my personal top 10 (in no
particular order).
1. Wimpy preoxygenation
Preoxygenation prior to anesthesia induction is a time-honored procedure applied routinely in anesthesia practice.
When properly performed, it prolongs the duration that apnea can be maintained without arterial oxygen
desaturation, a useful outcome if unanticipated airway difficulties arise. However, proper technique is often not
applied. For example, the facemask is lightly placed on the patient’s face, such that there is significant
entrainment of room air around the edges of the mask. The facemask seal must be sufficient so that all the inspired
gas comes from the anesthesia circuit and bag, rather than via room air entrainment. .Because peak airflow during
inspiration may approach 60 L/min, with typical fresh gas flows of 6 L/min the effective inspired oxygen fraction
is approximately 40% if a proper seal is not obtained. This will significantly reduce the apneic time prior to
desaturation. Many ventilatory maneuvers during preoxygenation have been described, ranging from normal tidal
breathing to vital capacity inspiration, most of them equally efficacious, but all depend on an adequate mask fit.
One way to objectively evaluate the quality of preoxygenation is to monitor the end-tidal oxygen fraction – aim for
at least 80% prior to proceeding.
So take the time to do it right, every time – and monitor the efficacy of your technique.
2. “Routine” ventilator settings

Many anesthesiologists were taught in training to use the following ventilator settings intraoperatively: tidal
volume = 10 ml/kg and rate = 10-12/min. These settings will routinely produce significant hyperventilation. The
rationale for these settings includes:
1) higher tidal volumes will prevent atelectasis and improve oxygenation;
2) respiratory rates of 10-12 are physiologic, and;
3) hypocarbia is good, hypercarbia is bad.
However…..
1) High tidal volumes, at least in the ranges used to maintain ventilation in modern practice, do not prevent or
reverse atelectasis and do not consistently improve gas exchange. Resolution of intraoperative atelectasis requires
“recruitment maneuvers” (prolonged, high airway pressures), not higher tidal volumes – as we will see in point #5
below. Indeed, higher tidal volumes certainly hurt lungs that are already injured, and may have deleterious effects
in even normal lungs.
2) Because metabolic demands are decreased during anesthesia, it is not necessary to maintain an “awake”
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respiratory rate…which in any event widely varies among individuals;
3) Other than for some neurosurgical cases, hypocapnia is not beneficial. Indeed, there is some evidence that
hypercarbia may be beneficial. For example, hypercarbia causes peripheral vasodilation and increases tissue
oxygenation, which could help prevent wound infection (although this remains to be shown). There is also
fascinating study (which to my knowledge has not been repeated) suggesting that intraoperative hypocapnia delays
emergence.
So consider using lower tidal volumes (in the 5-6 ml/kg range) and lower breathing frequencies that will maintain
at least normocarbia.
3. “Routine” use of mechanical ventilation and paralysis

Anesthesiologists in the US frequently employ pharmacologic paralysis and mechanical ventilation, even for cases
in which neuromuscular blockade is not required to accomplish the procedure, or cases in which patients could
easily maintain spontaneous breathing. Indeed, when patients move after the induction of anesthesia, the first
response is often to administer a neuromuscular blocking drug. After all, the surgeons will be happier and won’t
yell if the patients don’t move, I can use less anesthetic drugs which avoids hypotension and hastens emergence,
and in fact we always do it that way. And if I just turn on the ventilator, I don’t have to worry about whether the
patient will be adequately ventilated – it’s a “ventilator”, right? Plus, succinylcholine is now “persona non grata”
at many institutions, committing patients to extended paralysis if nondepolarizing neuromuscular blocking drugs
are used to facilitate endotracheal intubation.
Here are a few reasons to reconsider “routine” mechanical ventilation/paralysis:
1) Positive pressure ventilation requires a more-or-less secure airway. Endotracheal intubation is not a benign
intervention; if the only indication for an endotracheal tube is to provide mechanical ventilation, consider whether
you really need mechanical ventilation. Many use positive pressure ventilation with supraglottic airways such as
the LMA, but remember that unless properly seated, the gas may be delivered to locations you do not wish to
receive it (e.g., the stomach).
2) When patients move, they are generally telling you “please give me more anesthesia” rather than “please
paralyze me”. Use of neuromuscular blocking drugs is a risk factor for intraoperative awareness, which is rare
(but not unheard of) in a patient who is not paralyzed. There are many other risks associated with neuromuscular
blocking drugs, including anaphylactic and anaphylactoid reactions and postoperative respiratory complications
associated with incomplete reversal of block.
3) Just like our anesthetic forefathers (and foremothers), you can learn a lot by watching patients breathe. For
example, parameters such as end-tidal CO2 maintained during spontaneous breathing depend on anesthetic depths,
such that central respiratory control mechanisms can serve as an excellent integrated neurophysiology monitor for
overall anesthetic effects. This can be a useful tool to help administer anesthesia, for example to titrate opioid
supplementation at the end of cases to facilitate smooth, painless emergence. There also may be situations in
which gas exchange is better maintained if physiologic diaphragmatic contraction is also maintained, as
spontaneous breathing can be associated with improved ventilation-perfusion matching during anesthesia.
So use mechanical ventilation/paralysis because it is specifically indicated for a patient, not as a matter of
routine….or as a substitute for adequate anesthesia…
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4. “Assisted” ventilation
Patients breathing spontaneously under anesthesia often receive “assistance” – a squeeze on the bag every now and
then to augment tidal volume, or in today’s world one of numerous modes of pressure support, again designed to
augment tidal volumes. Patients with supraglottic airway devices routinely receive “assisted” ventilation via this
mechanism, which may cause entry of gas into the stomach if a less than perfect seal is achieved. The rationales
behind “assisted” ventilation are that increased tidal volumes will improve atelectasis, and that this practice will
augment minute ventilation and prevent hypercapnia.
However, there are inconvenient truths that make this reasoning suspect. We have already discussed that
increasing tidal volumes, at least to the relatively modest degree used in “assisted” ventilation, does not improve
atelectasis or oxygenation. And is it possible to significantly augment minute ventilation during spontaneous
breathing under anesthesia, and still maintain spontaneous ventilatory effort? When patients are breathing
spontaneously under volatile anesthesia, there is an “apneic threshold” – a value of arterial PCO2 below which
ventilatory effort (i.e., respiratory muscle activity) ceases. This threshold is 4-5 cm below the arterial PCO2
maintained during spontaneous breathing, largely independent of anesthetic or the depth of anesthesia. So if you
want to maintain your patient’s respiratory effort, you can only achieve modest decreases in PCO 2 with “assisted”
ventilation.
So although “assisted” ventilation may keep your hand (or your anesthesia ventilator) busy and make you feel like
you are doing something useful, the reasoning supporting its use is questionable at best.
5. PEEPed out
General anesthesia nearly always causes atelectasis in dependent areas of the lung, which represents a major (but
not the only) source of gas exchange abnormalities during anesthesia. When combined with other abnormalities of
chest wall mechanics such as obesity, intraoperative hypoxemia may occur. A frequent response is to simply dial
in 5-10 cm H2O of positive end-expiratory pressure (PEEP) – which sometimes seems to help in ICU patients,
right? Unfortunately, the isolated application of PEEP is unlikely to reverse intraoperative atelectasis. Rather,
“recruitment” maneuvers are required, involving sustained (30-40 seconds), high (approximately 40 cm H2O)
airway pressures. PEEP applied after recruitment maneuvers can help prevent the reformation of atelectasis.
Also, a high inspired fraction of O2 can accelerate the reoccurrence of atelectasis – so keep the FIO2 below 80% if
possible. Intraoperative atelectasis can also persist into the postoperative period and cause impairment of gas
exchange, so it is worth considering recruitment maneuvers prior to extubation at the end of the case.
The “lung protective” strategy of recruitment maneuvers followed by PEEP and reduced tidal volume benefits
critically-ill patients with acute lung injury, and it has been suggested that this may be beneficial even in patients
with normal lungs undergoing major procedures. The literature is contradictory as to whether benefit is achieved,
but there is certainly no evidence of harm.
So intraoperative hypoxemia is often caused by dependent lung atelectasis, which is best treated by recruitment
maneuvers followed by PEEP – don’t just turn on the PEEP.
6. Mode madness
Newer generations of anesthesia machines are equipped with sophisticated ventilators that provide many of the
same features of those ventilators utilized in intensive care units. These are touted by their manufacturers as major
advances in anesthesia technology, and it is indeed fun to play with the dials (or rather the touchscreen) for those
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who are mechanically inclined.
However, keep three things in mind.
1) There is little to no evidence that any mode of intraoperative ventilation has any effect on outcomes, despite
multiple attempts to prove benefits of the latest “mode-of-the-month”. This has largely been true even in the
intensive care unit – all we really know is that high tidal volumes are bad.
2) The multiple modes of ventilation available on modern anesthesia machines provide multiple opportunities for
confusion and misuse. Anecdotal experience suggests that many providers do not really understand how the
ventilators operate, and this lack of knowledge can have consequences. For example, providers may assume that
the patient is breathing spontaneously with a pressure-support mode, and not recognize the absence of spontaneous
ventilatory effort. This can make for an interesting extubation experience.
3) In their zeal to optimize the performance of their ventilators, manufacturers have compromised abilities basic to
the functioning of the anesthesia machine (in my opinion). For example, allowing pediatric patients to breathe
spontaneously with some modern machines results in significant rebreathing of CO 2.
So if you choose to indulge in mode madness, please recognize that it is for your benefit, generally not for the
benefit of your patients, and make sure you understand how that fancy ventilator works.
7. Why is my vaporizer broken?

Now that the monitoring of inhaled and exhaled gases is widespread, anesthesia personnel have noted apparent
discrepancies between the set volatile anesthetic concentration and the actual inspired anesthetic concentration,
sometimes prompting concerns that there is a malfunction of the machine.
However….remember that anesthesia circle systems allow rebreathing of exhaled gas, with the amount of
rebreathing dependent on the balance between fresh gas flow into the circuit and minute ventilation. With lower
flows, more rebreathing occurs. If this happens say early in induction, the rebreathed gas will be relatively poor in
anesthetic, and the inhaled anesthetic concentration will be less than the set anesthetic concentration. The opposite
consideration applies during emergence. This phenomenon is as old as the use of volatile agents and circle
systems – but only recently have we had the technology to see it routinely!
So remember that if you wish to rapidly change the inspired concentration of a volatile anesthetic (or to wash out
agent at the end of the case), you need to use high fresh gas flows – and don’t worry, the vaporizer is fine…..
8. What, no pediatric circuit?

For smaller children, we often use anesthesia circuits with small diameters, and smaller anesthesia bags. Do we
really need to use smaller circuit equipment for smaller people? When asked why, people often mumble something
about dead space….
However….remember that the dead space in a circle system extends only distal to the Y-junction – the diameter of
the tubing leading to and from the Y-junction makes no difference to dead space. There is the concept of
“compression volume” that applies during positive pressure ventilation. This represents ventilation that is “lost”
due to the increase in pressure that occurs in the limbs of the ventilator circuit. The lower the volume of each limb
of the circuit, the lower the “compression volume”. However, the magnitude of this effect is trivial – for normal
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airway pressures used during intraoperative ventilation, only about 2% of the delivered volume is “lost”. So this is
not much of a reason to use smaller circuit equipment. It is true that with a smaller anesthesia bag, it is easier for
the “educated hand” to detect changes in compliance, tidal volume, etc.
So use whatever circuit you wish for your smaller patients – but don’t panic if the “pediatric” circuits are not
available.
9. Two puffs is enough

When patients develop intraoperative bronchospasm, they are often treated using aerosolized drugs such as
albuterol. However, it can be quite challenging to administer aerosols to anesthetized patients via an endotracheal
tube. Even under the best of conditions in ambulatory patients, only a minority of the total amount of drug
administered by a metered dose inhaler actually reaches the small airways. Even less is delivered when
administered via an endotracheal tube, with only 5-10% of an administered dose being delivered to the airways.
Thus, simply attaching a metered dose inhaler to the elbow of the breathing circuit and administered two puffs
(hopefully at the right portion of the respiratory cycle) is unlikely to produce an adequate therapeutic effect.
Suggestions to improve drug delivery include: 1) consider using nebulizers rather than metered dose inhalers if
available in a timely fashion; 2) use a spacer device in the inspiratory limb of the circuit, and; 3) increase the
number of puffs to account for decreased efficiency of delivery.
Usually two puffs is not enough – so don’t be afraid to administer more puffs to obtain the necessary therapeutic
effect.
10. Don’t stop smoking!

One of the most pernicious and persistent myths in perioperative medicine is that quitting smoking shortly before
surgery will actually increase the risk of pulmonary complications, supposedly because of increased cough and
sputum production. Multiple studies have now shown that this is absolutely not true – quitting smoking at any
time prior to surgery will not increase the rate of any complication, although it is true that it may take several
weeks to realize the full benefits of smoking cessation in terms of reducing the risk of pulmonary complications.
Anesthesiologists are in a unique position to help their patients quit smoking, and should take every opportunity to
help them do so. Surgery serves as a “teachable moment” for smoking cessation, as having major surgery can
double the chances that patients can quit successfully. This will improve both immediate perioperative outcomes
and long term health. For more information, see www.asahq.org/stopsmoking.
So any time is the right time for patients to quit smoking – even shortly before surgery.
In summary…
You may or may not agree with all these points, but hopefully this presentation will help you consider the
evidence and the physiology that underlies these and other practices in perioperative respiratory management so
that you can make your own rational choices.
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Highly selected references (#s refer to which point is addressed)
McGowan P, Skinner A: Preoxygenation--the importance of a good face mask seal. Br J Anaesth 1995; 75: 777-8
(#1)
Cai H, Gong H, Zhang L, Wang Y, Tian Y: Effect of low tidal volume ventilation on atelectasis in patients during
general anesthesia: a computed tomographic scan. J Clin Anesth 2007; 19: 125-9 (#2)
Fleischmann E, Herbst F, Kugener A, Kabon B, Niedermayr M, Sessler DI, Kurz A: Mild hypercapnia increases
subcutaneous and colonic oxygen tension in patients given 80% inspired oxygen during abdominal surgery.
Anesthesiology 2006; 104: 944-9 (#2)
Hovorka J: Carbon dioxide homeostasis and recovery after general anaesthesia. Acta Anaesth Scand 1982; 26:
498-504 (#2)
Futier E, Marret E, Jaber S: Perioperative positive pressure ventilation: an integrated approach to improve
pulmonary care. Anesthesiology 2014;121:400-408 (#2, #5)
Futier E, et al. A trial of intraoperative low-tidal-volume ventilation in abdominal surgery. NEJM 2013;369: 428-
437 (#2, #5)
High vs. low positive end-expiratory pressure during general anesthesia for open abdominal surgery (PROVHILO
tiral: a multicenter randomized controlled trial. Lancet 2014; 384:495-503 (#2,#5)
Plaud B, Debaene B, Donati F, Marty J: Residual paralysis after emergence from anesthesia. Anesthesiology 2010;
112: 1013-22 (#3)
Mahour G, Orser BA, Avidan MS: Intraoperative awareness: from neurobiology to clinical practice.
Anesthsiology 2011; 114: 1218-1233 (#3)
Hickey RF, Fourcade HE, Eger EI, 2nd, Larson CP, Jr., Bahlman SH, Stevens WC, Gregory GA, Smith NT: The
effects of ether, halothane, and Forane on apneic thresholds in man. Anesthesiology 1971; 35: 32-7 (#4)
Duggan M, Kavanagh BP: Pulmonary atelectasis: a pathogenic perioperative entity. Anesthesiology 2005; 102:
838-54 (#5)
Warner DO, Warner MA, Ritman EL: Atelectasis and chest wall shape during halothane anesthesia.
Anesthesiology 1996; 85: 49-59 (#5)
Benoit Z, Wicky S, Fischer JF, Frascarolo P, Chapuis C, Spahn DR, Magnusson L: The effect of increased FIO(2)
before tracheal extubation on postoperative atelectasis. Anesth Analg 2002; 95: 1777-81 (#5)
Tusman G, Belda JF: Treatment of anesthesia-induced lung collapse with lung recruitment maneuvers. Curr
Anaesth Crit Care 2010; 21: 244-249 (#5)
Aldenkortt M, Lysakowski C, Elia N, Brochard L, Tramer MR: Ventilation strategies in obese patients undergoing
surgery: a quantitative systematic review and meta-analysis. Br J Anaesth 2012; 109: 493-502 (#6)
Crogan SJ, Bishop MJ: Delivery efficiency of metered dose aerosols given via endotracheal tubes. Anesthesiology
1989; 70: 1008-10 (#9)
Shi Y, Warner DO: Brief preoperative smoking abstinence: is there a dilemma? Anesth Analg 2011; 113:1348-
1351 (#10)
Warner, DO: Helping surgical patients quit smoking: why, when, and how. Anesth. Analg.2005; 101: 481-487
(#10)
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Working Hard – Hardly Working:

Measuring Clinical Productivity of Individual Anesthesiologists
Amr Abouleish, MD, MBA Galveston, Texas
Preface
At the 2001 ASA Annual Meeting, I was fortunate to give a refresher course lecture on this topic for the first time.
At that time, anesthesiology groups were focused on primarily providing surgical anesthesia care. Hospitals and
payers were only valuing this type of clinical care from anesthesiologists. Since then, there has been a shift, that is
accelerating the past several years, from only valuing surgical anesthesia care to also including other activities (both
clinical and organizational) and quality care. Today, it is essential for anesthesiologists and their groups to do more
than simply “pass gas”. Therefore, in this refresher course lecture I still cover issues of measuring surgical
anesthesia care, but I have added the second half focusing on possible incentives (that is behavior modification
system) for other activities that groups need to promote or value to be successful now and in the future.
Introduction
In science, the “observe effect” refers to changes caused by the act of observation or measurement. In behavior
theory, this effect is also known as the Hawthorne effect and defined as the process where human subjects of an
experiment change their behavior simply because they are be being studied. A similar process often occurs when
one measures an individual’s activities (or behavior). One of the goals of measuring behavior, in this case clinical
productivity, is to increase productivity and reward those that do more work. In other words, the measurement
system can be viewed as behavior modification system.
In any behavior modification system, among the important components is to identify the behavior one wants to
promote, to determine how to measure it, and then communicate the process to the individual. In other words, the
measurement should value the behavior the group feels is important to the group’s success and devalue the activities
that are not important or undermines the group’s success.
In this presentation, I will first examine the traditional clinical productivity measurements – focused on surgical
anesthesia. Then I will discuss behavior modification systems and how they could be applied to not only surgical
anesthesia care but to other activities that groups now must perform in order to be successful.
Measuring Surgical Anesthesia Productivity of Individual Anesthesiologists
Two important concepts that one should understand before looking at measuring clinical productivity are (1)
individual measurements are not necessarily the same as group measurements, and (2) the difference between
internal comparisons and external (benchmarking) comparisons.
Individual and group measurements are not the same thing. The difference is an important concept to understand.
Unfortunately, it is not uncommon for comparisons of groups to apply group measurements as benchmarks for work
done by an individual. Further, the measurements used to compare groups may not be applicable to comparing
individuals as illustrated in this following example using team sports. In basketball, individual measurements
include many different statistics for each position, such as assists for point guards, rebounds for power forwards, and
blocked shots for centers. In contrast, the meaningful external team comparison (i.e., team comparison) is simply the
win-loss record. Anesthesiologists understand this concept well. Within a group, every anesthesiologist does not
need to be expert in every subspecialty, as well as quality reporting, contract review, or leadership activities. The
best group is a group where leaders have matched demand with the correct individual. That is the pediatric
anesthesiologist is providing pediatric anesthesia while the cardiac anesthesiologist is assigned adult patients with
cardiac comorbidities or having cardiac surgery – not the other way around. Similarly, with the concept of
Perioperative Surgical Home (PSH), not every anesthesiologist needs to do every component of PSH, but the group
needs to have anesthesiologist who are experts (or champions) of different aspects.
Further, when comparing individual work, a group wants to compare individuals WITHIN the group and not with
anesthesiologists outside the group (i.e., internal comparisons). That is for a private-practice group, measurements of
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individual work are used to determine how much of the revenue each individual WITHIN the group will receive.
Because of this essential characteristic, the group can choose their own unique internal measurements and
comparisons that will allow the group to best succeed. In contrast, comparisons of group productivity can be done
WITHIN a group over time (i.e., internal comparisons) or can be done with OTHER groups (i.e., external
comparisons). The internal comparisons of group work can be similarly defined as the group wishes. In contrast,
external comparisons need to be standardized among all the groups and allows for benchmarking. (Note. I will not
be covering group productivity measurements in this presentation.)
Why is Measuring Surgical Anesthesia Productivity Not Simple?
Although educational, research, and administrative productivity may be measured similarly in anesthesiology and in
non-anesthesiology specialties, measuring clinical (surgical anesthesia) productivity in the discipline of
anesthesiology, either for individuals or departments, poses unique challenges because of the need to staff operating
rooms (ORs), which is independent of workload, the different billing system, the need to use the right "full-time
equivalent (FTE)," and confounding factors.
STAFFING NEEDS AND WORKLOAD

One of the goals for measuring clinical productivity is to determine the proper staffing needed to perform a set
amount of work. Unfortunately, for the specialty of anesthesiology, this approach is not logical because workload or
productivity measurements cannot be used directly to determine the number of anesthesiologists needed. To
illustrate this disconnect between staffing needs and workload, the reader should answer the following question for
his/her group: For the next month, what determines the number of anesthesiologists the group needs to staff its
anesthetizing sites? The primary determinants of staffing needs are the number of clinical sites to be staffed and the
staffing ratio (i.e., concurrency). Other determinants include whether or not a second shift is needed in the evening
and the number of staff who are on-call or post-call.(4) Workload and productivity measurements do not determine
the number of staff a group needs. In other words, if an anesthesiology group needs to provide care for 20 ORs at
7:30 AM, the number of anesthesiologists required is no different if all the ORs finish at noon or 3 PM! Instead of
determining staffing needs, workload or productivity measurements should be used to determine the appropriate
number of ORs needed—assuming this decision is based solely on these two variables.
CONFOUNDING FACTORS – ANESTHESIA-INDEPENDENT FACTORS

Confounding factors affect productivity measurements and make comparisons of the measurements less accurate. In
measuring the productivity of anesthesia care providers, many times these confounding factors are independent of
the anesthesiologist’s discretion and hence are also known as "anesthesia-independent" factors. To illustrate the
confounding factors of surgical duration, type of surgery, schedule "not full," and obstetric anesthesia care, a
hypothetical OR suite will be used as an example. In this OR suite, the anesthesiology group must staff four ORs as
well as a labor and delivery suite. For the example, work performed from 7:30 AM to 4:30 PM and the resultant
billed ASA units will be examined.
If one assumes that any anesthesiologist can staff any of the rooms, then differences in billed units (base, time, and
total units) are related to non-anesthesiologists. Between OR 1 and OR 2, speed of surgery accounts for the
differences. Between ORs 1 and 3, type of surgery is the factor. OR 4 represents situation where the surgeon cannot
be in the OR after 12 noon. Hence, the OR is open but unused. The difference in billed units between OR 4 and OR
2 has to do with the schedule not being full. Finally, obstetric anesthesia is not billed the same as OR care. In this
example, only "face-to-face" time is billable and hence only 1 hour of a 6-hour epidural is billed. (Table 1)
Measuring Surgical Anesthesia (Clinical) Productivity of Individual Anesthesiologists
Because only internal measurements are used for individual measurements, each anesthesiology group can develop
and choose productivity measurements of individual anesthesiologists that work best for helping the group be
successful. The real question facing the group concerns which measurement is the best indicator of productivity. The
answer to this question is different for every group. The right measurement is the measurement that will value
services that will help the group succeed and meet its clinical obligations. It is essential that the group’s leadership
understand what each productivity measurement values and devalues before determining which measurement is
right for the group.
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Individual Productivity Measurements for Surgical Anesthesia
For the specialty of anesthesiology, individual productivity measurements for Surgical Anesthesia can be
categorized into three general groups: total charges (or total ASA units [tASA]), time, or shift-worked. Examples of
total charges or tASA billed are the compensation distribution plans of many private-practice groups. If a partner is
responsible for 20% of the charges or tASA billed, then that partner receives 20% of the revenue. Because
anesthesia care is billed using time units, time-based measurements offer an attractive method for tracking work
done by each anesthesiologist. Two different methods, time units billed (TU) and billable time units, have been
described previously. Under either of these systems, if a partner bills 20% of the time units, then the partner would
receive 20% of the revenue. In the last category, anesthesiologists are credited with working shifts. Some
anesthesiology groups use a complex point system with different values for different calls (or late shifts) and
different day schedules. However, a more simple system has been described. A "shift-worked" measurement
addresses the major daily clinical challenge for any anesthesiology group—having enough anesthesiologists
available to be able to provide care at all the anesthetizing sites.
Utilizing Table 1's hypothetical OR suite, we will assume that the anesthesiology group is a physician-only group,
and that each physician covers only one anesthetizing site. Therefore, the billed units per OR equals the billed units
per FTE. (The issue of concurrency will be discussed later.) For a detailed evaluation of each of these
measurements, the reader is referred to reference 1.
Total Charges or tASA Billed Measurements. For this category, the measurement tASA/FTE will be used to
demonstrate what is valued and devalued by this group of measurements. Assuming the anesthesiologist group is a
physician-only practice, each FTE or anesthesiologist will care for only one room. Therefore, tASA/FTE equals
tASA billed for the ORs. The highest tASA/FTE is OR 3—this illustrates that specialty care with high base units is
valued by this measurement. The second highest value is OR 1, which has the fast surgeon. The faster the surgeon,
the more cases can be done, and hence, the more base units can be billed for the same amount of time. The lowest
values are found in OR 4, where downtime is not billed, and in labor and delivery. Both are undervalued with this
measurement.1 If all the ORs could be covered by any anesthesiologist in the group, then the differences in
tASA/FTE for the one day would be dependent on the "luck of assignment."
Time Measurements. For this category, TU/FTE will be used to demonstrate what is valued and devalued.
Again, assuming that we are dealing with a physician-only group, TU/FTE for one day equals the TU billed for the
OR. In contrast to tASA/FTE, specialty care (OR 3) no longer has the highest value, and, on the contrary, is
devalued because base units are not included in this measurement. In addition, the slowest surgeon (OR 2) now has
the highest value, a fact which illustrates that minimum downtime (less turnover time) is valued over the number of
cases done. Analogously, downtime in the schedule (OR 4) is undervalued. Finally, obstetric care is very
undervalued because of the methodology of billing time units. Again, if any anesthesiologist in the group could
cover any of the ORs, then the differences in TU/FTE for one day would be dependent on the "luck of assignment."
Shift-Worked Measurements. In this category, a point system is used to value the shifts worked by an
anesthesiologist. The system may be very complex, with different point-values for different shifts as well as other
functions (e.g., schedule runner or administrative day for the president of the group). A simple system that values all
the shifts the same uses the measurement clinical days worked per FTE (CD/FTE). A CD is defined as working a
day providing clinical services independent of billing methods. So unlike tASA/FTE and TU/FTE, this measurement
includes anesthesiologists working in a day surgery preoperative clinic (DSU preop), a pain management clinic, an
intensive care unit, and a recovery room. If one anesthesiologist were to cover each room, then the CD/FTE would
be equal to one for each site. This measurement places the highest value on the anesthesiologist being available at
the start of the day to cover clinical sites—the primary day-to-day challenge of any anesthesiology group. Since all
services are equal, specialty care (base units) is devalued. On the other hand, because the type of surgery, surgical
duration, or downtime do not affect this measurement, "luck of assignment" is not an issue.
Concurrency and Individual Productivity Measurements

Unlike other medical specialties, an anesthesiologist can bill professional services on more than one patient at the
same time (i.e., an anesthesiologist can provide concurrent care through the medical direction of an anesthesia care
team). The staffing ratio, or concurrency, is defined as anesthetizing sites (OR sites) per anesthesiologist.
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Differences in concurrency confound the productivity measurements of individuals and groups. The effect on
individual measurements is illustrated below, and the effect on group comparisons will be discussed later.
Using the hypothetical OR suite in Table 1, let us assume that ORs 1, 2, and 4 (all laproscopic cholecystectomy
surgery) are cared for by one anesthesiologist ("Dr. A") and three other providers (a certified registered nurse
anesthetist [CRNA], an anesthesia assistant [AA], or a resident), while the other anesthetizing sites are personally
performed by anesthesiologists ("Dr. B" and "Dr. C"). As a result of different concurrencies, "Dr. A" now has the
highest tASA/FTE and TU/FTE because all billed units for OR 1,2, and 4 are credited to "Dr. A," while "Dr. B" and
"Dr. C" only have one anesthetizing site credited to each of them. In contrast, CD/FTE is not influenced by
concurrency differences and each anesthesiologist has the same value (i.e., one). Therefore, the total charges
measurements (tASA/FTE) and the time measurements (TU/FTE) both value a high concurrency or staffing ratio.
Behavior Modification Systems and

Incentives for Activities beyond Surgical Anesthesia performed by Individual Anesthesiologists
As noted earlier, an anesthesiology group cannot be successful or even retain hospital contracts if all they do is
provide surgical anesthesia. Groups now need to perform activities beyond surgical anesthesia including, but not
limited to, to also provide care in preoperative and postoperative periods (e.g., perioperative surgical home
components), lead clinical improvement activities (including OR throughput), demonstrate high quality of care, and
provide physician leadership to hospital committees and activities. Therefore, group leaders find themselves trying
to measure these activities. There is wide spread “frustration” because there is no standard measurements for many
of these activities. But this should not be a major issue since the group’s goal is to value these activities and promote
individuals to do more of these activities. By definition, the group is seeking to change individual’s behavior and
hence looking for “measurements” for behavior modification. Further, behavior modification system are very
specific to each group and hence, industry standard measurements are not necessary.
Differences between Variable Pay and Incentive Systems
Incentive pay systems are focused on rewarding or compensating activities that would not necessarily be done
(considered a “hardship”) but are essential for the group’s success. In this system, the incentive pay is a smaller part
of the overall compensation (e.g., 20%), where the majority of compensation is found in a non-variable base salary.
The advantages of the incentive system is that it is simpler to set-up, manage and understand as well as providing
more timely feedback. (4)
In contrast, a variable pay system has a very small non-variable base salary and the majority of the compensation is
variable. In this system, the variable pay system measures all activities, not only the ones that people don’t want to
perform. In other words, much of the pay system will not change behavior but “pays for work done” – even if one
would do it if paid a base salary.
The discussion below on behavior modification systems will focus on incentive pay systems only.
Behavior Modification Systems
In the simplest terms, an incentive pay system is an example of a behavior modification system. That is a behavior
modification is often viewed as a three-part system (Figure 1): antecedent (manager and employee set a goal),
employee behavior (does the employee meet the goal), and consequence/contingent reinforcement (No –
consequence, Yes – consequence). But effective behavior modification systems are more complex than a simply
setting goals. Further, although financial compensation is often viewed by leaders as how to change behavior but as
discussed below, this is not necessarily the best method.
A more complete diagram of Behavior Modification Systems can be seen in Figure 2. The basic three-parts are still
seen in the diagram.
Antecedent. “Identifying relevant behavior” is one of the major challenges in a behavior modification system.
Group leaders need to ask themselves “What new behaviors/activities do we need individuals to focus on?” Be very
careful answering this question. First, the common adage “If it ain’t broke, don’t fix it” should be followed. If there
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is no problem with the behavior, don’t try to measure it and reward it. Second, beware of the concept of “The folly
of rewarding A, hoping for B.” (6) Once the relevant behavior is identified, then measuring and charting the
behavior needs to be done to validate the measurements to both the leaders and the employees.
Contingent Reinforcement. In the simple model, the manager and employee agree on a goal and then the employee
is rewarded when he/she meets the goal. This is the definition of contingent reinforcement – a response is contingent
on the behavior – but does not fully describe the possible reinforcements that exist. Reinforcements can be done to
maintain or increase the frequency of a desirable behavior OR can be done to decrease or eliminate the frequency of
an undesirable behavior.
Positive Reinforcement. Goal: To increase frequency of desirable behavior. This is the most effective and most
common reinforcement type. In the work place, money or compensation is often thought to be the most
effective, but in reality, money is not always the most effective reward. Non-financial rewards include verbal
approval from leader, assignment to desired tasks, titles/promotion, extra time off, and more employee control
of activities (ownership of workflow, independence, input on decision making). It is important to note that the
highest job satisfaction will occur not when the compensation is highest, but instead when compensation is at
market value (median) and the work environment is rewarding.
Negative Reinforcement. Goal: To increase frequency of desirable behavior. It is important to differentiate

Negative Reinforcement from Punishment (see below). Negative reinforcement is used to increase desirable
behavior, while punishment is used to eliminate undesirable behavior. Negative reinforcement can be very
effective. You have also seen it’s power everyday – think about when you get into the driver’s seat and forget to
put on your seatbelt. The annoying alarm (verbal or beeping) will remind you to put on the seatbelt and often
continues if you don’t. What do you do when you hear the alarm. You don’t get a reward, but you do get the
alarm to turn off. This alarm is a great example of negative reinforcement. In practice management, negative
reinforcement can be used to change behavior without having to provide monetary compensation. For example,
distribute among all your physicians a weekly report of incomplete documentation (number of cases that are
incomplete and have not been billed). You will easily see that each physician does not want their name on the
list. Similarly, if the group is receiving incentive payments from the hospital to meet turnover time goals,
publishing daily a turnover report and including the anesthesiologist’s name can make meeting turnover time
important to every member of your group.
Omission. Goal: To decrease frequency of undesirable behavior by removing all “reinforcing behavior”. Three
steps to Omission: (1) identify the behavior to be reduced or eliminated, (2) identify the reinforcer that
maintains the behavior, and (3) stopping the reinforcer. The best example of omission is on-time meeting start.
(1) The behavior to be eliminated is showing up late for a group meeting. (2) The reinforcer is waiting for
people to show up to start. (3) Start the meeting at the time scheduled.
Punishment. Goal: To decrease frequency of undesirable behavior. Punishment should be reserved as a last
resort and only in cases of serious behavior. To be effective, the punishment needs to be linked directly to the
undesired behavior, immediate in feedback, and appropriate for the behavior. The reason punishment should be
used sparingly is that there are potential short-term and long-term negative effects to the employee being
punished as well as other employees including apathy, high turnover or absenteeism, and aggressive or
disruptive behavior. Further “learned helplessness” can occur with punishment.(7)
Reassessment of Behavior Modification System. Unlike the simple model, the more complex model reflects that
periodic reassessment of the effectiveness of the behavior modification system is essential. If the problem is solved
(increase in the desired behavior or decrease in the undesired behavior), then continue with the system unchanged. If
it is not solved, then reassess the behavior identified, the method of measuring the behavior, and the reinforcements
are correct or need to be changed.
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References
1. Abouleish AE et al. Measurement of individual clinical productivity in an academic anesthesiology department.
2. Abouleish AE, Zornow MH. Estimating How Many Anesthesia Providers Do Our Group Needs? ASA
Newsletter 2001;65(8):14-16
3. Abouleish AE. Developing a staffing model: Estimating the number of anesthesia providers your group needs –
An update. ASA Monitor 2013;77(1):10-13
4. Lubarsky DA. Incentivize everything, incentivize nothing. Anesth Analg 2005; 100:490-2
5. Hellriegel D, Slocum JW, Woodman RW. “Chapter 4: Learning and Reinforcement” in Organizational
Behavior 8th ed, South-Western College Publishing (Cincinnati, OH) 1998, pp. 102-33
6. Kerr S. On the folly of rewarding A, while hoping for B. Academy of Management Executives. 1995;9:7-14
7. Abouleish AE. The struggling resident: Avoiding Pygmalion and learned helplessness by using nontechnical
performance assessment systems. Anesthesiology 2010;112:1067-9
Table 1: Confounding Factors or Anesthesia-Independent Factors

#
Anesthesia Turnover Base/case TU/case (total tASA
Surgery cases
Time (hr) (min) (total billed) (total billed) billed)
done
OR 1 Lap Chole (fast) 1 20 7 7 (49) 4 (28) (77)
OR 2 Lap Chole (slow) 2 20 4 7 (28) 8 (32) (60)
OR 3 CABG 2.5 30 3 20 (60) 10 (30) (90)
OR 4 Lap Chole (golf) 2 20 2 7 (14) 8 (16) (30)
L&D Labor Epidural 6 n/a 3 5 (15) 4 (12) (27)
Hypothetical OR suite and labor and delivery (L&D). The anesthesiology group staffs the anesthetizing sites from 7:30 AM to 4:30
PM. Confounding factors affect billed units can be seen by comparing billed units for different ORs: surgical duration (OR 1 and 2),
type of surgery (OR 1, 3), schedule “not full” or downtime (OR 2 and 4), and obstetric anesthesia (L&D and OR 2 and 4). For OR 4,
the surgeon must leave at noon and hence no cases are available to be done after this time. For labor epidural, only “face-to-face” time
billed, i.e. 1-hour for 6-hour epidural analgesia. See text for details.
OR = operating room; base = base units; TU= time units; tASA = total ASA units; lap chole = laproscopic cholecystectomy; CABG =
coronary artery bypass graft.
Figure 1: Simple Behavior Modification System
Manager is silent or
reprimands employee
Manager Does No
and Employee
Employee meet
Set Goal Goal?
Yes Manager compliments
(rewards) employee for
accomplishment
Employee Consequence
Antecedent Contingent
Task Reinforcement
Behavior
TBD
Page 7
Maintain
Reinforcement
Positive
Maintain or Reinforcement
Desirable Yes
Increase
Frequency
of Behavior
by
Negative
Reinforcement
Adapted from Figure 4.6 (Reference 5)
Is the
Identify
Charting Behavior Problem
Relevant
Behavior Desirable Solved?
Behavior(s)
?
Omission
Decrease or No
Eliminate
Undesirable Frequency Change
Reinforcement
Figure 2: Behavior Modification Systems more than “Simply Setting Goals”
of Behavior
Punishment
Yes
No
Reidentify
Desired
Behavior
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Perioperative Care of the Elderly Cancer Patient: Special Anesthetic Considerations
Vijaya Gottumukkala, M.B.B.S., M.D. (Anes) FRCA Houston, Texas
Over 60 years demographic is the largest growing segment of our patient population in the US. It is projected that
20% of the U.S. population will be over 65 years of age by 2030. Given that age is the single most important risk
factor for cancer, it is expected that 70% of cancers and 85% of all cancer-related deaths will occur in this patient
population. In 2005, cancer was the leading cause of death in women 40 to 79 years old and in men aged 60 to 79
years old. In-addition, age-adjusted mortality rates indicate that cancer was the leading cause of death in both men
and women less than 85 years old.1, 2 Solid tumors are common in this patient population, and surgery in appropriate
patients remain the mainstay for control of tumor burden. However, age related higher incidence of co-morbid
burden in this patient population, decreasing physiologic reserve, inability to rapidly recover from postoperative
complications due to decreased physiologic reserve, frailty, alterations in pharmacokinetic and pharmacodynamics
effects of medications, and higher incidence of postoperative delirium and cognitive abnormalities put these patients
at higher risk for postoperative morbidity and mortality. However, the current data on the operative mortality and
morbidity after complex cancer surgery in older patient population is conflicting.3-5 While some single center studies
of elderly patients undergoing major cancer surgery reported an operative mortality rate of less than 5%,6-10 a few
larger observational studies reported a substantially higher risk for worse operative outcomes.11,12 Given the
conflicting data about operative outcomes in this age group, it is vital to understand the differences between the
physiology of normal aging from the higher incidence of disease burden in older patients. In a recent report of major
cancer surgery in the elderly, the authors report that older patients were more likely to have preoperative
comorbidities and to receive intraoperative blood transfusions. Increased age was also associated with higher
operative mortality (4.83% for > 75 years vs. 1.09% for ages 40–55 years), a greater frequency of major
complications, and more prolonged hospital stays—all of which persisted after multivariable adjustments. However,
despite its strong association with 30-day operative mortality, the authors reported that the impact of older age was
comparable to other preoperative risk-factors predictive of short-term operative outcomes.13 Age alone should
therefore not be a reason to withhold adjuvant, neo-adjuvant, curative, or palliative treatment options in this patient
population.
A good understanding of preoperative, intraoperative and postoperative factors that may contribute to outcomes in
this patient population will help develop appropriate care strategies to minimize perioperative risk for worse short-
term operative outcomes. Despite its association with increased perioperative morbidity and mortality, chronological
age alone is not a good gauge of the physiology of aging and its effects on perioperative outcomes in a particular
patient. Due to significant inter individual variability in the biology of aging, comorbid burden, frailty and functional
status; the detailed assessment of each individual patient as well as establishing clear goals of therapy (curative
intent, or palliation of symptoms) becomes critical in the elderly patient with cancer. As with any surgical patient,
medical optimization of co-morbid burden is vitally important. Overall, burden of comorbidity is associated with
worse survival in patients with cancer. 14-18 It is becoming evident that concomitant diseases impact not only overall
survival but also the behavior of the cancer itself. For example, diabetes decreases the 8-year DFS (Disease Free
Survival) of stage III colon cancer patients to an extent similar in magnitude to the beneficial effect of
fluorouracil/levamisole adjuvant therapy. 19 Similarly, hyperinsulinemia is associated with a worse disease specific
survival in patients with prostate cancer,20 colon cancer,21 and breast cancer.22 Obesity is also associated with a
worse progression-free survival (PFS) and OS (Overall survival) in patients with ovarian cancer.23 Frailty is now
widely regarded as an independent risk factor for poor outcomes in the elderly patient with cancer. Most recently,
two independent investigators have concluded that frailty was an independent predictor of discharge to a supported
facility, the number of complications, and length of stay.24,25 Both authors concluded that adding frailty index to
either the ASA physical status or other indices of risk such as either the Lee or Eagle would similarly increase the
area under the ROC (Receiver Operating Characteristic) curve to about 0.86 to predict surgical complications and
discharge to an assisted or skilled nursing facility.26 A spectrum of cognitive abnormalities occurs after major
complex surgery in the elderly patient population. These range from delayed emergence, emergence delirium,
postoperative delirium (24–72 hours after surgery), and postoperative cognitive dysfunction (POCD). Postoperative
delirium (POD) is seen in a significantly higher number of older surgical patients. Hempenius et al. have concluded
that preoperative cognitive functioning and the severity of the surgical procedure are independent risk factors for
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POD in elderly undergoing elective surgery for solid tumors.27 While POD has been associated with higher
incidence of postoperative complications, prolonged length of hospital stay and increased risk for mortality28, the
level of functional impact of POCD is less clear. However, it is reported that POCD has an impact on functional
outcomes such as ADLs (Activities of Daily Living) and IADLs (Instrumental ADLs). 29 IADLs are functional
activities which let an individual live independently in a community. Postoperative cognitive dysfunction may
resolve with time. Currently, it seems the incidence of initial cognitive decline in older patients is high (25% at 2–10
days) with gradual resolution (10% at 3 months, 5% at 6 months, 1% at 1 year). At 1 year, the cognitive decline is
indistinguishable from matched controls.30 The observed link between exposure to anesthetics and development of
clinical dementia in laboratory observations has not been clearly established in clinical practice.31 There is some
evidence to suggest that avoiding sedative medications, providing adequate pain relief, avoiding deep anesthesia,
maintaining diurnal rhythms in sleep cycle, minimizing disruption to patient’s usual daily routines as much as
possible, maintaining contact with familiarity to friends and family, early control of infectious and metabolic
derangements can decrease the incidence of delirium.32 Identifying patients at high risk for POD, employing
perioperative measures to minimize POD, having a high index of suspicion and instituting timely interventions in
the postoperative period will help improving outcomes for this high risk patient population.
Perioperative care of the elderly patients require recognition of special considerations of the contracted intravascular
volume status, higher vascular tone (sympathetic dominance), left ventricular hypertrophy and diastolic dysfunction,
all of which lead to higher risk for hypotension at induction of anesthesia. Furthermore, they are dependent on their
heart rate to maintain their cardiac output secondary to diastolic dysfunction. A large retrospective33 and case
controlled34 studies have independently reported an increased incidence of 30 day mortality and postoperative
ischemic stroke respectively with intraoperative hypotension. While in the former study there was a relationship
between the area under threshold (AUT) for blood pressure deviations based on the population as well as individual
patient related baseline data, the later study demonstrated hypotension best defined as a decrease in mean blood
pressure relative to a preoperative baseline value. Goal directed fluid therapy and hemodynamic optimization based
on regulating vascular content, tone, and integrity may have value in patients undergoing complex surgery with risk
for major blood loss.35 An extension of the importance of avoiding intraoperative hypotension is perhaps the concept
of “triple low”. The triple-low condition consists of mean arterial pressure (MAP) <75 mm Hg, BIS <45, and an
end-tidal volatile anesthetic concentrations in minimum alveolar concentration (MAC) equivalents of <0.8.
Cumulative duration of triple low was shown to be associated with perioperative mortaility.36 In a subsequent study,
patients enrolled in the B-Unaware, BAG-RECALL, and in the Michigan Awareness Control Study were evaluated
for cumulative concurrent duration of MAC less than 0.8, MAP less than 75 mmHg, and BIS less than 45 (triple
low).37 Triple low in this study was independently associated with an increased risk of 30- and 90-day postoperative
mortality even after controlling for patient comorbidity through propensity matching. It could be speculated that
perhaps triple low identifies patients who are sensitive to anesthesia secondary to poor cerebral reserve (age, frailty,
systemic disease and illness) and, possibly at risk of brain hypoperfusion.
Tahiri et al have demonstrated that elderly patients who experience a greater number or more severe complications
take longer to return to their preoperative functional status following abdominal surgery. Of all statistically
significant predictors of recovery, the comprehensive complication index score was the only potentially modifiable
factor.38 Instituting evidence based perioperative care pathways to minimize symptom burden with a particular focus
on pain control and delirium prevention; early rescue to prevent cardiovascular, thrombotic, pulmonary, renal and
infectious complications; and improving functional recovery by early mobilization (with adequate fall precautions)
is key in this vulnerable patient population. Evidence from recent studies demonstrates that the domains evaluated in
a CGA (Comprehensive Geriatric Assessment) in the preoperative phase can predict perioperative morbidity and
mortality in older patients with cancer and improve functional outcomes. This is particularly true for IADLs and the
burden of comorbidities and poly-pharmacy. Recently there is increasing focus on functional assessment of the
patient than questionnaire-based assessments in the preoperative and planning phases of care strategies. Commonly
utilized performance-based measures of functional status include the “Timed Up and Go,” the 6-minute walk test,
and grip strength. Additional studies are needed to test the prognostic ability of performance-based measures of
functional status, frailty, and the correlation between objective and subjective measures of functional status in the
geriatric oncology patient. 39 An important component of the perioperative care continuum is patient preparation
including advanced care planning (ACP) and optimization for surgery, with particular focus on pre-habilitation
programs. As cancer therapies become more available and effective, and the number of cancer survivors grows in
this patient population, outcomes such as the quality of survival in addition to disease-free survival (DFS) and
overall survival (OS) will be important to measure. Recovery of functional status (IADLs in this patient population)
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is particularly important as it is one of the domains of recovery that takes the longest to return to baseline
(preoperative) levels following surgery. Furthermore, this becomes all the more relevant in discussions pertaining to
patient centered outcomes, and improving population health (triple aim) as many elderly patients value functional
independence more than life-saving therapy if it results in cognitive or functional impairment.
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5. Pope D, Ramesh H, Gennari R, et al. Pre-operative assessment of cancer in the elderly (PACE): a comprehensive
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6. Adam DJ, Craig SR, Sang CT, et al. Esophagectomy for carcinoma in the octogenarian. Ann Thorac Surg.
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7. Ellis FH Jr, Williamson WA, Heatley GJ. Cancer of the esophagus and cardia: does age influence treatment
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9. Sabel MS, Smith JL, Nava HR, et al. Esophageal resection for carcinoma in patients older than 70 years. Ann
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10. Sohn TA, Yeo CJ, Cameron JL, et al. Should pancreaticoduodenectomy be performed in octogenarians? J
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11. Finlayson E, Fan Z, Birkmeyer JD. Outcomes in octogenarians undergoing high-risk cancer operation: a national
study. J Am Coll Surg. 2007;205:729–734.
12. Riall TS, Reddy DM, Nealon WH, et al. The effect of age on short-term outcomes after pancreatic resection: a
population-based study. Ann Surg. 2008;248:459–467.
13. Waddah B. Al-Refaie, Helen M. Parsons,William G. Henderson, Eric H. Jensen, Todd M. Tuttle, Selwyn M.
Vickers, David A. Rothenberger, Beth A. Virnig. Major Cancer Surgery in the Elderly. Results From the
American College of Surgeons National Surgical Quality Improvement Program. Ann Surg 2010;251: 311–318
14. Extermann M, Balducci L, Lyman GH: What threshold for adjuvant therapy in older breast cancer patients? J
Clin Oncol 18:1709-1717, 2000
15. Frasci G, Lorusso V, Panza N, et al: Gemcitabine plus vinorelbine versus vinorelbine alone in elderly patients
with advanced non-small-cell lung cancer. J Clin Oncol 18:2529-2536, 2000
16. Firat S, Bousamra M, Gore E, et al: Comorbidity and KPS are independent prognostic factors in stage I non-
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17. Piccirillo JF, Tierney RM, Costas I, et al: Prognostic importance of comorbidity in a hospital based cancer
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18. Satariano WA, Ragland DR: The effect of comorbidity on 3-year survival of women with primary breast cancer.
Ann Intern Med 120:104-110, 1994
19. Meyerhardt JA, Catalano PJ, Haller DG, et al: Impact of diabetes mellitus on outcomes in patients with colon
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20. Hammarsten J, Hogstedt B: Hyperinsulinaemia: A prospective risk factor for lethal clinical prostate cancer. Eur J
Cancer 41:2887-2895, 2005
21. Goodwin PJ, Ennis M, Pritchard KI, et al: Fasting insulin and outcome in early-stage breast cancer: Results of a
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22. Pavelka JC, Brown RS, Karlan BY, et al: Effect of obesity on survival in epithelial ovarian cancer. Cancer
107:1520-1524, 2006
23. Extermann M: Interaction between comorbidity and cancer. Cancer Control 14:13-22, 2007
24. Robinson TN, Wallace JI, Wu DS, et al. Accumulated frailty characteristics predict postoperative discharge
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25. Makary MA, Segev DL, Pronovost PJ, et al. Frailty as a predictor of surgical outcomes in older patients. J Am
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26. Deiner S, Silverstein JH. Long-Term Outcomes in Elderly Surgical Patients. Mount Sinai Journal of Medicine.
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27. Hempenius L, Slaets JP, van Asselt DZ, Schukking J, de Bock GH, Wiggers T, van Leeuwen BL. Interventions
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surgery with special attention to the cognitive impaired patients. Eur J Surg Oncol. 2015 Jan;41(1):28-33
28. Robinson TN, Raeburn CD, Tran ZV, Angles EM, Brenner LA, Moss M. Postoperative delirium in the elderly:
risk factors and outcomes. Ann Surg 2009;249:173–8.
29. Steinmetz J, Christensen KB, Lund T, et al. ISPOCD Group. Long-term consequences of postoperative cognitive
dysfunction. Anesthesiology 2009; 110:548–555.
30. Abildstrom H, Rasmussen LS, Rentowl P, et al. ISPOCD Group. Cognitive dysfunction 1–2 years after
Noncardiac surgery in the elderly. International Study of Post-Operative Cognitive Dysfunction. Acta
Anaesthesiol Scand 2000; 44: 1246–1251
31. Baranov D, Bickler PE, Crosby GJ, et al. Consensus statement: First International Workshop on Anesthetics
and Alzheimer’s disease. Anesth Analg 2009; 108: 1627–1630.
32. Sieber FE, Gottshalk A, Zakriya KJ, et al. General anesthesia occurs frequently in elderly patients during
propofol-based sedation and spinal anesthesia. J Clin Anesth 2010; 22: 179–183.
33. Monk TG, Bronsert MR, et al. Association between Intraoperative Hypotension and Hypertension and 30-day
Postoperative Mortality in Noncardiac Surgery. Anesthesiology 2015; 123:307-19
34. Bijker,BJ, Persoon S et al. Intraoperative Hypotension and Perioperative Ischemic Stroke after General
Surgery. A Nested Case-control Study. Anesthesiology 2012; 116:658–64
35. Chawla LS, Ince C, Chappell D et al. Vascular content, tone, integrity, and haemodynamics for guiding fluid
therapy: a conceptual approach. British Journal of Anaesthesia 113 (5): 748–55 (2014)
36. Sessler DI, Sigl JC, Kelley SD, Chamoun NG, Manberg PJ,Saager L, Kurz A, Greenwald S: Hospital stay and
mortality are increased in patients having a “triple low” of low blood pressure, low bispectral index, and low
minimum alveolar concentration of volatile anesthesia. Anesthesiology 2012; 116:1195–203
37. Willingham MD et al. Concurrence of Intraoperative Hypotension, Low Minimum Alveolar Concentration, and
Low Bispectral Index Is Associated with Postoperative Death. Anesthesiology 2015; 123:00-85
38. Tahiri M et al. The impact of postoperative complications on the recovery of elderly surgical patients. Surg
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Cancer 104:1998-2005, 2005
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Pediatric Sedation: The Difficult, Big, and Small Patient
Joseph P. Cravero MD FAAP. Boston/MA
Pediatric Sedation continues to be a challenging area of anesthesia practice. The issues involve not only how to
deliver this care as anesthesiologists, but also who should provide this care? In addition, the variable settings in
which this care is provided requires more creativity and flexibility of the provider that standard OR anesthesia.
AAP - No lecture concerning pediatric procedural anesthesia care would be complete without the mention of
several excellent documents that offer guidelines for sedation care – primarily from the American Academy of
Pediatrics (AAP) written by Dr. Charles Coté and the AAP Committee on Drugs. (1-4) There have been several
iterations of these guidelines and, as technology and practice have evolved, so have these guidelines. Rather than
review all of the guidelines in this lecture – I recommend keeping them for a reference regarding appropriate
sedation practice by all different types of physicians and ancillary providers.
CMS - The Centers for Medicare and Medicaid Services (CMS) has issued clear directives on the nature of the
responsibilities that Anesthesia Departments have in assuring safe sedation in a facility. (5) The CMS directives are
notable for the fact that they do not limit the scope of care provided by physicians other than anesthesiologists, but
they do place specific responsibilities on the Anesthesiology Department at each institution:
 They define types of sedation/anesthesia services as ranging from minimal sedation to general anesthesia.
 All deep sedation and anesthesiology services must be organized under a single Anesthesia Service - which must
be directed by a qualified physician. (Logically the Chair of Anesthesiology – but not required to be an
anesthesiologist). Standards of care must be consistent across all areas where the sedation or anesthesia is
delivered.
 Hospitals must ensure that procedures are in place to rescue patients whose level of sedation becomes deeper
than initially intended.
 The anesthesia service is responsible for developing policies and procedures governing the provision of all
categories of anesthesia services – including the category of practitioner who is permitted to provide anesthesia
services that are not subject to the anesthesia administration requirements.
 The administration of anesthesia must be by a qualified anesthesiologist, a doctor of medicine or osteopathy,
dentist, oral surgeon, CRNA, or anesthesia assistant. This requirement does not apply to local anesthesia,
minimal or moderate sedation.
 Medical staff bylaws must include criteria for determining the anesthesia service privileges to be granted to an
individual practitioner.
 Delivery of anesthesia services must be consistent with recognized standards for anesthesia care including patient
consent, infection control, monitoring, safety practices, reporting requirements, documentation, and equipment
requirements
With these guidelines in mind, the balance of this lecture will use three cases to illustrate challenging sedation
scenarios for the anesthesiologist. We will consider not only the management of sedation with consideration of the
primary pathology for each patient, but also the decision as to who should be conducting the sedation.
Case #1
2.5 YO female with repaired Tetrology of Fallot and developmental delays. She needs to have dental caries filled.
This is not a full mouth rehabilitation, rather the removal of a couple of primary teeth and the filling of a few other
teeth. Expected duration is 40 minutes. She was noted to be cyanotic at 2 weeks of age – diagnosed with TOF and
underwent Blalock-Tausig shunt to improve pulmonary blood flow. She has a good exercise tolerance according to
mother (as much as she can tell). She is moderately delayed in her speech and motor development.
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Sedation questions to be addressed for this for this case – How does congenital heart disease impact sedation
planning? How do we decide who provides care for this child?
There are multiple issues that determine the risk of sedation with respect to sedation for a procedure such as this.
The first issue to be determined is the overall function of the ventricles. There is absolutely no question that
congenital heart disease patients (repaired or not) are over-represented in the population of children who have
perioperative/peri-sedation cardiac arrest. (6, 7) Patients with congenital heart disease can have progressive loss of
function over time. This is particularly true for patients with a single ventricle providing circulation for both
pulmonary and systemic circulation. It is also the case for those with an RV that has been set up to provide systemic
circulation – even if there is an LV is providing pulmonary circulation. Adverse changes over time also occur in
patients with volume or pressure overload on the right or left side.
It is also critical to determine if the circulation is still a shunt between the pulmonary and systemic circulation? Is
there any mixing going on between these circulations? If circulation is “shared” subtle changes in the systemic
vascular resistance vs. pulmonary vascular resistance will change the relative shunt fraction – and can decrease
oxygen saturation or encourage pulmonary over-circulation depending on the changes that take place.
Perhaps somewhat overlooked for patients who have had open CHD surgery is the fact that dysrhythmias are part of
the postoperative picture. Atrial flutter of other tachydysrythmias are most common. The history of such issues,
and the interventions that have been undertaken to treat such problems, are an important to review prior to beginning
a sedation or anesthetic.
The post-operative congenital heart patient may require antibiotic coverage that is different from other patients.
These recommendations have changed over time and it is critical that those providing sedation understand who
should be receiving antibiotics and those who should not. There is minimal risk associated with secundum ASD,
Post-repair ASD, VSD, PDA, MV prolapse, pacemakers and ICDs. There is high risk associated with prosthetic
heart valves, bacterial endocarditis, complex cyanotic CHD, and surgical systemic pulmonary shunts (like this case).
Antibiotic prophylaxis is recommended for dental procedures (with bleeding), mucosal surgery, T and A, rigid
bronchoscopy, GU surgery, and GI surgery.
Finally it should be noted that post-CHD surgery patients that are chronically hypoxic – have blunted chemoreceptor
responsiveness to hypoxia.
For this case, it should be remembered that Tetrology of Fallot – includes:

1. Severe Right Ventricular Outflow Tract obstruction – in this case repaired with a B-T shunt which brings
systemic arterial blood from the right subclavian artery into the pulmonary circulation.
2. Non-restrictive VSD
3. RVH
4. Overriding Aorta.
Implications for care:

1. The history of excellent exercise tolerance is encouraging but not completely reassuring. For patients who
actually can exercise seriously, a history that the child runs and keeps up with other children correlates with
good function. On the other hand, most of these patients are followed regularly by cardiology and should
have a history of their ejection fraction or shortening fraction. If poor function has been documented, then
sedation choices should appreciate this and agents that associated with significant depression of function –
such as large doses of propofol – should be avoided in favor of agents with less depression such as ketamine,
etomidate, midazolam, fentanyl, or even low doses of inhaled agents.
2. You want to avoid increasing O2 demand – control hypertension and tachycardia.
3. This child is doing well as baseline. The less things change the better. You want to maintain SVR and
systemic BP as well as PVR. This can be done with drugs like ketamine and or phenylephrine.
4. Avoid dehydration – especially if polycythemic. Chronically hypoxic CHD patients often come with elevated
Hgb as a physiologic response.
5. In the case of significant deterioration, one could minimize pulmonary outflow obstruction and PVR with
oxygen, beta blocker, nitroglycerin, phentolamine, tolazoline, prostaglandin E1, and (ultimately) nitric oxide.
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6. Circulations are connected – therefore air embolus is an issue, all lines should be de-aired and filters should
be in place.
7. Treating a “Tet Spell” = knee-chest position, O2, Morphine, phenylephrine, Beta blockade.
Provider: For cases involving CHD with ongoing shunting, compromised ventricular function, history of
dysrhythmia, or any case involving a patient with a single ventricle – anesthesiologists should provide the sedation.
Technique for this case = There are many options. If this is going to be a relatively brief procedure and you are not
providing GA with an endotracheal tube, it would be ideal to avoid sedation agents that depress cardiac contractility
or cause significant vasodilation. One might opt for oral midazolam premedication. This could be followed (or
accompanied) by intranasal dexmedetomidine (2-3mcg/kg)(8-11) or oral ketamine (4-6mg/kg). An IV can then be
placed without upsetting the child, and followed by low dose propofol 1 mg/kg bolus and infusion 75-
100mcg/kg/min. Small doses of ketamine or a dexmedetomidine could (alternatively) be used to maintain sedation.
Caution should be exercised using DEX in a patient who is post cardiac surgery and might have AV nodal
conduction delay.
Case #2
10 YO male is 6 days s/p lap appendectomy. He has intermittent fevers. There is a mass visible on CT scan and he
is being taken to IR for a CT guided biopsy. He is 99th % for BMI for age = 41. He snores a night. He is very
distractible during the day.
General issues to be addressed in this case – how does obstructive sleep apnea impact sedation planning, and who
should provide this care?
OSA is more common in children with increasing BMI percentile. It is also more common in those with enlarged
tonsils and adenoids. To determine the presence of OSA, parents can be questioned about sleep activity – such as
snoring and interruptions in breathing during sleep. (12) Does the child prefer an unusual position during sleep? (i.e.
does he need to be on his stomach to sleep at night). Has there been new onset of enuresis? Suspicion for OSA
should be raised in children with craniofacial syndromes associated with mid-face hypoplasia, micro/retrognathia,
macroglossia, and narrow facies – including Crouzons, Alpert’s, and Pfeiffer syndromes, Trisomy 21 , Treacher
Collins syndrome, Pierre Robin Sequence, Goldenhar syndrome, and achondroplasia. Neuromuscular diseases that
predispose to hypotonia or spasticity also predispose to OSA. It should be noted that parent’s assessment of a child
based on these questions is sensitive but not very specific for OSA. In other words – just about all OSA patient
snore, but not all who snore have OSA.
Children with severe OSA may have daytime somnolence, are distractible, irritable, and difficult to arouse in spite
of “adequate” sleep hours. OSA is characterized by sleep fragmentation, episodic apnea, and recurrent hypoxemia
and hypercarbia during sleep. The severity of OSA is assessed by the frequency and severity of the obstructive
respiratory events during sleep. For patients that have had a sleep study, the Apnea/Hypopnea index (AHI) also
known as the Respiratory Disturbance Index (RDI) – defines OSA as the presence of 1 or more event per hour with
a saturation below 92%. Other factors to be considered include the time spent below a threshold saturation, the
averaged value of the nadir saturation, and the saturation nadir of the entire sleep study.
Children with OSA may have failure to thrive or general growth issues. Cardiovascular abnormalities including
ventricular dysfunction and pulmonary hypertension can result. Lower respiratory tract infections in this group have
been linked to chronic aspiration during sleep. Children with OSA have a blunted response to hypercarbic challenge
during sedation. In these cases, consecutive hypercapnic challenge does not produce the progressive increase in
ventilation seen with normal children. This has clear implications for the post-procedural time frame.
Sleep (sedation) onset is associated with a loss of tonic neck activity. Passive flexion is associated with a decreased
dimension of the pharynx. Normally, activation of upper airway activity dilates the pharynx prior to initiation of the
primary respiratory muscles during the generation of negative pressure. Sleep – and sedation- inhibits the
responsiveness of both the tensor palatine and genioglossus muscles to the pharyngeal dilator reflex resulting in
collapse of the airway. Active REM sleep is associated with a heightened respiratory drive to the diaphragm and a
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lesser drive to the musclulature of the upper airway resulting in more collapse of the airway during REM sleep.
OSA patients are particularly prone to this airway collapse.
Propofol administration is associated with a dose dependent decrease in pharyngeal cross sectional area due to a
decrease in the anterior-posterior dimension. MRI studies show that during sedation children with OSA have
obstruction of the upper two-thirds of the pharyngeal airway and the smallest dimension is in the area of overlap
between the adenoids and tonsils. Large clinical observational studies have confirmed that obese children are more
likely to obstruct their airway during sedation than non-obese children. (13) The most logical way to manage this
issue is with airway adjuncts such as oro/nasopharyngeal airways that bypass the area of obstruction. In extreme
cases an LMA or endotracheal tube would be required. Alternatively the airway may be supported by the
application of CPAP or BiPAP. CPAP between 5-10cm H2O results in a marked increase in the dimension of
pharyngeal airway. Indeed the propofol-induced loss of airway caliber is reversed with the application of CPAP.
Positioning: Neck extension, sniffing position, and mouth opening maximize the caliber of the pharynx. The
lateral position with OSA markedly increases the dimension of the pharynx.
Opioids: Children with severe OSA exhibit recurrent hypoxemia, and the severity of hypoxemia correlates with the
sensitivity to opioids. Morphine dosage required to achieve a given analgesic endpoint in children with O2
saturation nadir of less than 85% was half that of children whose saturation nadir was greater than 85%. In one
study 46% of children with severe OSA experienced apnea with a standard dose of fentanyl vs. 4% of unaffected
children. (14, 15)
Discharge Criteria for patients with OSA need to be carefully considered. Criteria based on “street fitness” or “back
to baseline” are poorly suited for this children. Sleep onset may be associated with sleep disordered breathing which
may worsen under the effects of residual sedatives. Baseline sleep behaviors are so abnormal in these patients that
any expectation that parents could reliably detect problem states is ill conceived. Prolonged recovery observation
with a criteria for maintenance of wakefulness that approximates that of non-OSA patients should be considered.
Children who use sleep apnea therapy devices may be managed on ambulatory programs for sedation however
physiologic control and arousal mechanisms must be intact in the post-sedation period. Sleep apnea devices are not
life-sustaining and are not equipped with apnea alarms, therefore a sustained period of observation is critical in these
patients as well. As a general rule it is wise to make a contingency arrangement for admission of children with
severe OSA even if the procedure is relatively brief.
Strategies for this case:
1. Determine the degree of OSA – has the child been tested? Is there evidence of severe/chronic hypoxia hypopnea?
In general, if any of these are present or if the BMI is greater than 90% for age – this child should be sedated by
an anesthesiologist. Many institutions simply refer all children with a BMI over 30. In most cases (for the
anesthesiologist) deep sedation/anesthesia with an LMA or endotracheal tube in place is going to be the easiest
way to go.
2. Maximize local anesthesia beginning with topical and including injection infiltration. Maximize use of NSAIDS
and acetaminophen – IV modes are justified here.
3. Minimize opiate administration – remember issues related to sensitivity.
4. Beware of propofol in these cases due to pharyngeal collapse. This is less likely with a benzodiazepine or
ketamine based sedation technique. It is also less likely with a DEX based technique (16, 17) although if these
children obstruct during normal sleep they may well obstruct during DEX sedation as well. Specifically if we
were to choose sedation for this case, we would use a balanced technique including small doses of fentanyl
(0.5mg/kg) or ketamine 0.5-1mg/kg) and midazolam up front followed by a dexmedetomidine (1mcg/kg) bolus
and infusion to maintain sedation. A very small dose of propofol (0.5-1.0mg/kg) could be added if the DEX dose
did not result in adequate sleep. We would ask the proceduralist to use copious local anesthetic infiltration to
minimize stimulation.
5. Consider the use of home CPAP during light/moderate sedation. It is also logical (if giving GA) to extubate the
ET tube or LMA to CPAP directly during emergence and recovery.
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Case #3
A 3 MO 4kg female has had episodes of suspected seizure activity. She is scheduled for an MRI scan with sedation.
She failed an attempt at the scan with feeding and swaddling. Her past medical history is significant for birth at 29
weeks gestation requiring 1 month of mechanical ventilation – she remains on oxygen now.
General issues for this case – what are the implications of premature newborn status on sedation delivery and who
should provide sedation in this case?
Background: There are many issues related to sedation of newborns – including the question of “should we ever
sedate young infants for procedures?”. Actually there are competing interests at play. On the one hand we
continue to be concerned that sedation or anesthesia given for procedures or tests may be associated with
neuroapoptosis. Animal data continues to accumulate linking exposure to most of our sedatives and anesthetics to
neuroapoptosis. This data includes information from rat pups and primate models. Most of this evidence indicates
that longer exposures, repeated exposures, and exposures that are NOT associated with pain or stimulation is
associated with more significant neural injury. This data is supported by some human observational studies that
have found a correlation between anesthesia exposure early in life and subsequent learning disorders. In light of
this, it would seem prudent to avoid giving deep sedation/anesthesia to patients in this age group as much as
possible. On the other hand, copious evidence exists that indicates newborns and young infants who are exposed to
pain/stress early in life WITHOUT the benefit of sedation or analgesia are at risk for developing long-term
maladaptive behaviors. This data includes rat models that show increased pain behaviors and drug preference in
animals exposed to repeated painful experiences early in life. There is also evidence that human infants exposed to
painful stimuli without anesthesia (such as circumcision) – have heightened pain responses to painful stimuli
(immunization) later in life. We must balance need with treatment. The FDA and pediatric anesthesia experts have
advised that elective anesthesia/sedation is best avoided in children under 3 years of age until further information is
available on this topic. It is therefore appropriate to challenge our colleagues that ask for this kind of test “please
help me understand how the results of this scan will change the care of this child in the coming months”.
Physiologically it is important to remember that young infants do not have fully developed liver cytochrome systems
until approximately 6 months of age. Glomerular filtration rate is not at adult levels until approximately 1 year of
age. There is a higher percentage of body weight that is water. There are reduced levels of alpha-1 glycoprotein.
Along with these issues there is also a diminished responsiveness to hypoxia and an immature blood brain barrier.
All of these developmental issues decrease the margin of error for newborns and infants receiving
sedation/anesthesia – and this is reflected in a consistently reported increased incidence of severe adverse events in
this age group.
Sedation in former prematures has recently been studied and found to have an increase number of adverse events
throughout childhood and into young adult life. (18) Most sedation systems will refer former premature children
with a history of lung disease to the anesthesiology service for sedation, as would be appropriate in this case. If one
must care for a child in this situation there are a number of options. It may be easiest to simply approach this child
with a general anesthetic with an ET tube, but with the respiratory history involved here, a less invasive approach
may actually offer some significant benefits. Unfortunately there is not an abundance of data on techniques for
procedural sedation for neonates.
In terms of options I would offer these thoughts:
1. One would have to ask “how well did the previous providers attempt to do this without sedation?” In an ideal
situation, the child should be fed fully, offered a pacifier, swaddled with warm blankets, and allowed adequate
time to fall asleep before calling the effort a failure. There are many other helpful tools including “shrink
wrappers” – which are essentially a pneumatic beanbag that encircles the infant and conforms tightly to the body
leaving minimal room for movement. Appropriately applied a very high success rate with non-pharmacological
interventions has been reported.
2. Although it is not widely available at this time (and we do not generally recommend it), chloral hydrate (50mg/kg)
has a history of successful use and safety in this age group for non-painful procedures such as this and general
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ICU sedation. (19) When chloral hydrate was compared to no sedation, children who were sedated had scans
completed more efficiently and more successfully. On the other hand, it has also been documented that the
sedated patients would have prolonged effect (lasting up to 12 hours) and could have an increased number of
bradycardia spells in the peri-sedation period.
3. Midazolam has been used extensively in the ICN for sedation of ventilated patients. My own ongoing
observational trial has revealed that midazolam given in doses of 0.25mg/kg and repeated every 5 minutes until
sleep is induced- works well for 80% of these patients. Repeat dosing is not required during the actual scan.
Once they are asleep, they stay asleep for approximately an hour. Over 90 percent of those who are sedated wake
at the end of the scan when moved off of the scanner gantry.
4. Dexmedetomidine has a robust track record of use in the CT and MRI scanner environments. Most of the data
does not involve neonates, but the effectiveness of this sedative has been established in this age group. Most
importantly, the drug has not been associated with the same rate of neuroapoptosis as the other sedatives we
employ. In fact, the use of dexmedetomidine has been shown to be neuroprotective in some models. We start
with a relatively small bolus dose of 1mcg/kg followed by an infusion at 1mcg/kg/min. A repeat bolus dose
could be given if the initial dose fails to induce sleep. Dexmedetomidine causes little respiratory depression that
has been reported with its use. Side effects can include bradycardia and (initially) hypertension – thought partially
due to alpha-1 receptor stimulation. The drug should be avoided in children who have AV nodal conduction delay
or are on drugs that are associated with conduction delay such as Digoxin or Beta Blockers.
5. Propofol has been reported for use in neonates and is clearly effective as a sedative. At moderate doses, airway
patency is usually maintained when appropriate positioning is accomplished. It is important to remember that the
drug has been shown to have very different pharmacokinetic and pharmacodynamics properties in this age group.
This difference is likely due to many issues including a smaller central fat compartment for redistribution in this
age group as well as limited glucuronidation in the liver. Drug elimination can be very prolonged and dosing does
not follow the allometric relationships that exist for toddlers, children, and adults. We recommend the use of
small bolus doses – 0.25 - 1mg/kg and relatively low dose infusions for young infants. Close observation in the
recovery period is critical.
6. Small doses of ketamine (0.25-1mg/kg) would also provide adequate sedation in this case. The advantages of
ketamine are familiar to most anesthesiologists – including the fact that respiratory drive and airway tone would
be maintained. For this child, the bronchodilation that accompanies sedaiton with ketamine could also be helpful.
Unfortunately ketamine is the drug that has most prominently been associated with neruoapoptosis and would
thus not be a first choice in routine circumstances. Finally, ketamine is often accompanied by a small amount of
random movement that would not be ideal in this case.
7. A completely different approach for a child at high risk for respiratory complications would include the used of a
regional anesthetic. We have reported “sedation” for MRI with caudal and spinal anesthesia in very high-risk
newborns. (20) While this may seem or extreme, for those who perform these blocks regularly, the process is
actually quite quick and easy. The nerve block limits movement and after the block, most of the children will fall
asleep – particularly if they are given a sucrose pacifier after positioning. For caudals used in this way – 1cc/kg
of .25% Bupivacaine is administered. For spinals, 1mg/kg of bupivacaine is administered. Monitoring is
maintained as it would for a surgical procedure done with this technique.
Summary: Sedation remains an unavoidable fact of anesthesiologist’s lives. A seemingly endless number of
requests for these services from our radiology colleagues (and others) guarantees that this will continue to be the
case for many years to come. Anesthesiologists must be well versed in the guidelines for sedation as promulgated
by the AAP and CMS in order to participate constructively on institutional committees and to accomplish our
fiduciary responsibilities to our patients. On the other hand, we must appreciate the unique challenges that face us
from specific difficult sedation patients who will always come to anesthesiologists for their care. There are
situations where a well-delivered “sedation” actually may be preferable to an anesthetic and all options for care
should be considered.
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References:
1. Guidelines for the elective use of conscious sedation, deep sedation, and general anesthesia in pediatric
patients. Committee on Drugs. Section on anesthesiology. Pediatrics. 1985;76(2):317-21.
2. American Academy of Pediatrics Committee on Drugs: Guidelines for monitoring and management of
pediatric patients during and after sedation for diagnostic and therapeutic procedures. Pediatrics. 1992;89(6 Pt
1):1110-5.
3. Practice guidelines for sedation and analgesia by non-anesthesiologists. Anesthesiology. 2002;96(4):1004-
17.
4. American Academy of Pediatrics, American Academy of Pediatric Dentistry. Guideline for monitoring and
management of pediatric patients during and after sedation for diagnostic and therapeutic procedures 2006
[Available from: http://www.aapd.org/policies/.
5. Services CfMaM. Conditions of Participation: Anesthesia Services. CMS Manual System Pub 100-07 Stte
Operations Provider Certification 2011;Transmittal 74.
6. Flick RP, Sprung J, Harrison TE, Gleich SJ, Schroeder DR, Hanson AC, et al. Perioperative cardiac arrests
in children between 1988 and 2005 at a tertiary referral center: a study of 92,881 patients. Anesthesiology.
2007;106(2):226-37; quiz 413-4.
7. Baum VC, Barton DM, Gutgesell HP. Influence of congenital heart disease on mortality after noncardiac
surgery in hospitalized children. Pediatrics. 2000;105(2):332-5.
8. Yao Y, Qian B, Chen Y, Zhou L, Liu J. Intranasal dexmedetomidine premedication reduces the minimum
alveolar concentration of sevoflurane for tracheal intubation in children: a randomized trial. J Clin Anesth.
2014;26(4):309-14.
9. Yao Y, Qian B, Lin Y, Wu W, Ye H, Chen Y. Intranasal dexmedetomidine premedication reduces
minimum alveolar concentration of sevoflurane for laryngeal mask airway insertion and emergence delirium in
children: a prospective, randomized, double-blind, placebo-controlled trial. Paediatr Anaesth. 2015;25(5):492-8.
10. Yuen VM, Hui TW, Irwin MG, Yao TJ, Chan L, Wong GL, et al. A randomised comparison of two
intranasal dexmedetomidine doses for premedication in children. Anaesthesia. 2012;67(11):1210-6.
11. Yuen VM, Hui TW, Irwin MG, Yao TJ, Wong GL, Yuen MK. Optimal timing for the administration of
intranasal dexmedetomidine for premedication in children. Anaesthesia. 2010;65(9):922-9.
12. Patino M, Sadhasivam S, Mahmoud M. Obstructive sleep apnoea in children: perioperative considerations.
Br J Anaesth. 2013;111 Suppl 1:i83-95.
13. Scherrer PD, Mallory MD, Cravero JP, Lowrie L, Hertzog JH, Berkenbosch JW, et al. The impact of
obesity on pediatric procedural sedation-related outcomes: results from the Pediatric Sedation Research Consortium.
Paediatr Anaesth. 2015;25(7):689-97.
14. Brown KA, Laferriere A, Lakheeram I, Moss IR. Recurrent hypoxemia in children is associated with
increased analgesic sensitivity to opiates. Anesthesiology. 2006;105(4):665-9.
15. Brown KA, Laferriere A, Moss IR. Recurrent hypoxemia in young children with obstructive sleep apnea is
associated with reduced opioid requirement for analgesia. Anesthesiology. 2004;100(4):806-10; discussion 5A.
16. Mahmoud M, Gunter J, Donnelly LF, Wang Y, Nick TG, Sadhasivam S. A comparison of
dexmedetomidine with propofol for magnetic resonance imaging sleep studies in children. Anesth Analg.
2009;109(3):745-53.
17. Mahmoud M, Radhakrishman R, Gunter J, Sadhasivam S, Schapiro A, McAuliffe J, et al. Effect of
increasing depth of dexmedetomidine anesthesia on upper airway morphology in children. Paediatr Anaesth.
2010;20(6):506-15.
18. Havidich JE, Beach M, Dierdorf SF, Onega T, Suresh G, Cravero JP. Preterm Versus Term Children:
Analysis of Sedation/Anesthesia Adverse Events and Longitudinal Risk. Pediatrics. 2016;137(3):1-9.
19. Finnemore A, Toulmin H, Merchant N, Arichi T, Tusor N, Cox D, et al. Chloral hydrate sedation for
magnetic resonance imaging in newborn infants. Paediatr Anaesth. 2014;24(2):190-5.
20. Sites BD, Blike G, Cravero J, Andeweg S, Beach M. Single-dose caudal anaesthesia for two infants
undergoing diagnostic brain magnetic resonance imaging: high risk and nonhigh risk. Paediatr Anaesth.
2003;13(2):171-4.
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Clinical Evaluation and Treatment of Neuropathic Pain
Timothy Lubenow MD Chicago/Illinois
Objectives:
 To Review Neuroanatomy
 To Review Neurophysiology of Nociception
Neurophysiology of Pain:
 Afferent Peripheral Receptor Types
□ Special Receptors
□ Visceral Receptors
□ Deep Receptors
□ Superficial Receptors
Mechanorecepetors
 Mechanical stimuli
□ Touch, pressure, stroking
Mechanorecpetors
 Mechanical stimuli
□ Touch, pressure, stroking
□ Fast-adapting Receptors
Thermoreceptors
 Respond to temp and temp changes
 Slow-adapting structures
 Warm vs. cold receptor firing
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Nociceptors
 Transmit pain impulses
 Described as free nerve ending
 Stimulated by: Mechanical, Chemical, Thermal
Closer Analysis of those Receptors Involved in Pain Management
 A-delta
 A-beta
 C-fibers
Neurotransmitters in response to Stimulus
 Excitatory transmitters:
□ L-glutamate, Aspartate
□ Vasoactive intestinal peptide
□ Calcitonin gene-related peptide (CGRP)
□ Neuropeptide Y
Substance P
 Inhibitory transmitters:
□ Enkephalins, beta-endorphins
□ Glycine, Somatostatin
□ in the CNS, gamma amino butyric acid (GABA) appears to reign supreme. Over forty
percent of inhibition in the mammalian central nervous system is GABAergic.
Types of Nerve Damage
 Axon level (axonopathy) damage
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□ Axon and myelin sheath immediately distal to the injury site degenerate - "dying-
back," or length-dependent, neuropathy.
 Dorsal root ganglion damage,
□ Subsequent degeneration of the peripheral and central processes.
□ Recovery is often incomplete since the injury is at the cell body level
 Level of the myelin sheath (Myelinopathies):
□ Inflammatory or hereditary
□ For acquired demyelinating neuropathies: Injury is often patchy or segmental. Since
the axons are relatively spared, recovery is often rapid (weeks to months) and
complete.
 Hereditary abnormalities of myelin
□ Usually diffuse, with a slow progressive course.
Evaluation Leads to Correct Diagnosis/Patient Evaluation Process
 Initial Evaluation
□ Medical History and Physical Exam
□ Electromyographic and Nerve Conduction Studies (if not previously done)
 Newer Diagnostic Methodology will also be employed
□ Skin Biopsy for PN
□ QSART (If necessary)
Pharmacologic Approach
 Establish diagnosis and cause of NP and treat cause
□ Step 1: pregabelin, gabapentin, duloxetine
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□ Step 2: Secondary TCA, nortryptiline, desipramine, venlafaxine (SNRI)
□ Step 3: carbamazepine, oxcarbazepine, other anticonvulsants
 For localized pain – topical lidocaine
 Analgesics – tramadol
 Opioids
 Reassess for side effects
 Titrate dose
 Combine second drug of first line
 If insufficient pain relief add second or third line of drugs
(anticonvulsant, antidepressant)
Circumstances where opioids, tramadol can be use as first line treatment
 While titrating first line drug treatment
 Acute exacerbation of severe chronic pain
 Acute neuropathic pain
 Neuropathic pain associated with cancer
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Technological Advances in Anesthesia for Head and Neck Surgery
Vladimir Nekhendzy, M.D., Stanford/California
Learning Objectives
1. Define anesthetic considerations for transoral robotic surgery (TORS)

2. Review the advanced oxygenation techniques, such as Transnasal Humidified Rapid-Insufflation
Ventilatory Exchange (THRIVE), and its mechanism of action
3. Identify applications of THRIVE in head and neck anesthesia
4. Discuss advanced intubation and ventilation techniques in patients with partially obstructed airway
Transoral Robotic Surgery (TORS).
The range and precision of laryngologic surgical procedures have dramatically expanded over the last
decade. The patient outcomes have become favorably affected due to a plethora of technological advances, such as
the use of high-magnification operating microscopes and video endoscopes, instrument miniaturization, fiber-based
lasers, and the introduction of transoral robotic surgery (TORS). 1-6 Developed by surgeons Weinstein and O’Malley
from the University of Pennsylvania over 10 years ago, 7 TORS is gradually gaining ground as a technique of choice
for treating a wide range of oropharyngeal and laryngeal cancers, 8-10 and for performing multilevel surgery for
obstructive sleep apnea (OSA), such as reduction of tongue base (BOT) and uvulopalatopharyngoplasty (UPPP). 11-13
With TORS (the da Vinci Surgical System, Intuitive Surgical, Sunnyvale, California, USA), the surgeon
sits at a master console, remotely manipulating the endoscopic camera and two additional robotic arms with
miniaturized instruments that are placed intraorally. An assistant provides intraoral suctioning and other
manipulations that may be required to facilitate surgery. The anesthesiologist is able to visualize all steps of the
surgical procedure on the operating room (OR) video monitor.
TORS allows to perform the precision surgery with superior motor control in a very limited anatomical
space, which demands 3D visualization and a fully open surgical field. 7,8,14,15 With TORS, surgery proceeds from
the inside out, starting with the mucosal surface and extending outward, eliminating the need for skin incisions or
transmandibular access, and also decreasing the need for tracheostomy. 8,15 A highly magnified view of the surgical
pathology, increased depth perception and elimination of surgical tremor lead to shorter hospital stay and better
functional surgical outcomes affecting long-term speech and swallowing. 8,15,16 For OSA patients, TORS-assisted
BOT surgery (e.g. BOT resection, lingual tonsillectomy) and UPPP result in a statistically significant improvement
of apnea-hypopnea index (AHI), nocturnal oxygenation, and daytime somnolence. 11
The essential anesthetic requirements for precision TORS surgery include expert ability to safely share the
patient’s airway with the surgeon, enhanced situational awareness, a clear and still surgical field and absence of
patient movement to assure optimal preservation of function, and allocation of sufficient time to carefully complete
the procedure in a non-hurried manner. Anesthetic technique should assure a stable plane of anesthesia, non-
stimulating emergence, rapid return of consciousness and protective airway reflexes, and adequate prophylaxis of
postoperative nausea and vomiting (PONV).
The endotracheal tube (ETT) must be secured diligently: an immediate access to the patient’s airway is
impossible, as OR table is rotated 180° away from anesthesiologist. For TORS-assisted laser surgery, patients may
be intubated orally or nasally with the laser ETT. For other oropharyngeal surgery, a nasal intubation with a small
diameter (6.0 mm ID) microlaryngeal tracheal (MLT) tube is preferred, to facilitate an enlarged view and surgical
instrumentation. The MLT tube is sutured in place through the nasal septum by the surgeon, and the curved metal
ETT connector is used in lieu of the plastic one, to direct anesthesia circuit over the patient’s head to provide
unrestricted intraoral access for the surgeon. The anesthesiologist must assure sufficient depth of ETT placement, to
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prevent possible air leak caused by accidental withdrawal of ETT into the larynx during surgical manipulations
and/or extending patient’s head intraoperatively. A sudden air leak may immediately compromise the field during
precision surgery, and also create an airway fire hazard during the use of laser or electrocautery. The unrecognized
ETT displacement out of the trachea and into the glottis may prompt anesthesiologist to repeatedly add more air to
ETT cuff, which overtime may lead to compression of the anterior branch of the recurrent laryngeal nerve and vocal
cord (VC) injury. 17
The patient’s airway must be protected from blood, debris and irrigation fluid, and ventilation must also be
adequately controlled. Special attention should be directed to adequately protecting patient’s eyes with special safety
goggles, to prevent accidental injury due to heavy surgical instrumentation.
The increased situational awareness is required on the part of anesthesiologist at all times, as TORS is
performed with OR lights switched off. All the lines, anesthesia circuit, and patient’s positioning on OR table must
be secured and checked. Any intraoperative adjustment of equipment or OR bed by anesthesiologist should be
closely coordinated with surgeon, allowing the latter to first steer clear of the surgical field.
Provision of a stable plane of anesthesia and quiet surgical field can be achieved with the variety of
techniques. The hypnotic monitoring-guided total intravenous anesthesia (TIVA) with propofol and opioid
represents the author’s anesthetic technique of choice. The full synergistic effect of propofol with rapidly-acting
opioids, such as remifentanil, allows quick titration of anesthetic to the desired clinical effect. 18-24 TIVA produces
profound depression of pharyngeal and laryngeal musculature and reflexes, suppresses hormonal stress response to
surgery, and effectively blocks the catecholamine release and associated hyperdynamic cardiovascular responses,
thereby facilitating maintenance of moderate controlled hypotension (MAP 60-70 mmHg) and superior surgical
visibility. 19,22,25-32 Postoperatively, use of TIVA results in quicker recovery times, faster return of cognitive function,
and decreased incidence of PONV. 18,19,21,26-30,33-38
Remifentanil provides a predictable, rapid, and almost simultaneous recovery of consciousness and
protective airway reflexes, facilitating smooth emergence from anesthesia, while also blunting sympathetic
responses associated with extubation. 39,40 Current data indicate that EC95 of effect site concentration of remifentanil
for blunting tracheal reflexes after balanced desflurane and sevoflurane anesthesia is 2.3-2.9 ng/ml, 41-43 which
corresponds to the manual infusion rate 0.08–1.0 μg/kg/min. This is higher than that observed with TIVA, where a
target concentration of 1.5-2.1 ng/ml, corresponding manual infusion rate 0.05-0.07 μg/kg/min is usually
sufficient.40,44,45 Our experience corroborates that of others that lower blood target concentrations of remifentanil
during TIVA may be equally effective in that regard, 40,43,45,46 especially if additional opioids were administered.
Intermittent intravenous (IV) fentanyl or sufentanil boluses, as well as IV administration of acetaminophen

are warranted for supplementing propofol/remifentanil TIVA, as postoperative pain after TORS is usually moderate.
However, large doses of IV fentanyl/sufentanil should be avoided. PONV prophylaxis (e.g. dexamethasone,
ondansetron IV) is standard, even if TIVA was used.
The overwhelming majority of patients are extubated routinely after adequate reversal of neuromuscular
blockade. A staged extubation using airway exchange catheter (AEC) is rarely required. If postoperative airway
patency deemed problematic, e.g. significant intraoral or BOT edema, extensive laryngeal work, patient is left
intubated. Postoperative tracheostomy is very rarely indicated.
Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE).
THRIVE is a term coined by Patel and Nouraei 47 in their seminal paper that introduced anesthesiologists to
intraoperative delivery of humidified oxygen through specialized high-flow nasal cannula (HFNC). Several
commercial HFNC systems are available, e.g. Optiflow (Fisher & Paykel Healthcare, Auckland, New Zealand),
Comfort Flo Heated Humidification System (Teleflex Medical, Morrisville, North Carolina, USA), and others.
HFNC devices deliver fully conditioned, heated and humidified oxygen to the patient through specialized, wide-
bore, high-flow nasal cannula at rates up to 70 l/min.
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Advanced oxygenation technique utilizing HFNC has been successfully used for years outside of OR for
treatment of ARDS and respiratory failure in neonates and pediatric patients, for critically ill adult patients with both
hypoxemic and hypercapnic respiratory failure in intensive care unit (ICU) and emergency room (ER) 48-50 for
providing post-extubation respiratory support in ICU and improving oxygenation during reintubation attempts, 51-55
and also for patients with acute heart failure, central OSA, and for procedural sedation (e.g. interventional
bronchoscopy). 56,57
It was not until 2014 that Patel and Nouraei 47 have decided to bring this technology to OR and
prospectively evaluate THRIVE on 25 patients with compromised airways undergoing general anesthesia for
hypopharyngeal or laryngotracheal surgery. They demonstrated increased apnea window during airway management
(median time 14 (9–19 [5–65]) min (IQR [range]), and no instances of SpO2 desaturation < 90%. The calculated rate
of increase in end-tidal carbon dioxide (CO2) was 0.15 kPa/min (1.12 mm Hg/min), which was approximately 2.5-3
times less than that expected with classic apneic oxygenation. These findings were in line with other studies that
showed enhanced CO2 elimination with HFNC. 58
The CO2 elimination during THRIVE is promoted by flow-dependent flushing of anatomical dead space by
insufflated O2. 50,59,60 It is likely that in anesthetized and paralyzed patients, both apneic oxygenation and a flow-
dependent, mild increase in upper airway pressure (≤ 7 cm H2O) promote sustained oxygenation. 47,61-65 Increased
upper airway pressure results in alveolar recruitment, improved V/Q matching and reduced shunting. 47,59,64,66,67
Well-conditioned gas also reduces airway resistance, and high flow guarantees relatively constant FiO2
delivery. 59 It is important to note that despite the build-up of airway pressure in the nasopharynx, esophageal
pressure remains low at approximately 3 cm H2O, 68 thereby not increasing the risk of gastric insufflation during
THRIVE administration. The middle ear pressure also does not appreciably increase. 69
It is too early to tell whether THRIVE has a potential to significantly de-risk difficult airway management
by increasing apneic period, although early reports of its use during awake fiberoptic intubation are encouraging. 70
Nevertheless, the publication by Patel and Nouraei 47 has spurred clinical interest and research activity
focused on THRIVE applications for laryngologic surgery. Airway patency afforded by suspension laryngoscopy
allows for unimpeded THRIVE delivery and maintenance of superior patient oxygenation. THRIVE does not require
airway management beyond basic airway maintenance maneuvers (e.g. mask ventilation) on the part of
anesthesiologist, provides surgeon with enlarged, completely unobstructed laryngeal view, improves operating
conditions, and most likely speeds up surgery. The CO2 build-up and ensuing acute respiratory acidosis will
probably be the factors limiting use of THRIVE for prolonged procedures. The rate of CO2 rise, the strategies to
counteract it, as well as hemodynamic consequences of hypercapnia combined with TIVA administration need to be
clearly defined.
A number of trials are underway evaluating the safety and feasibility of THRIVE for laryngologic surgery.
The description of trials and intraoperative images/videos of procedures suitable for THRIVE administration are
provided and discussed.
OBSTRUCTED AIRWAY.
Patients with advanced airway obstruction and inspiratory stridor at rest comprise some of the most feared
and complicated cases for the anesthesiologist. 39,71 The incidence of difficult mask ventilation and impossible mask
ventilation among patients with severe stridor and upper airway obstruction > 75% of the lumen reaches 40% and
6%, respectively, 72 compared with 1.4% and 0.15% for the general surgical population. 73-75 These patients
frequently present for panendoscopy and microlaryngeal surgery on an emergent or semi-emergent basis, yet they
require a systematic and thoughtful approach by the anesthesiologist and the surgeon.
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The slow-growing upper airway tumors can cause a high-grade airway obstruction without significant
associated symptoms. Fully trained respiratory muscles can sustain adequate alveolar minute ventilation at rest
through a 3-mm orifice, but acute deterioration occurs when a critical narrowing is reached. 76 Drooling, dysphagia,
and expiratory snoring are the signs of marked pharyngeal restriction, 39,77 but inspiratory stridor at rest represents
the most worrisome sign, suggesting a reduction in airway diameter at the supraglottic, periglottic, or glottic level of
at least 50%. 71,78
Airway narrowing at the tracheal or tracheobronchial level is typically characterized by expiratory stridor,
whereas biphasic inspiratory-expiratory stridor usually points to obstructive subglottic disease. 79 In some cases,
preoperative examination of the flow-volume loops may be helpful. 80 Tracheal compression can occur as a result of
lesions within the trachea or compression by thyroid and mediastinal masses. The upper airway may be normal at
laryngoscopy, and it may be possible to pass ETT beyond the glottis but not beyond the obstruction. 76
The optimal technique for airway management of the stridorous patient with an advanced proximal airway
obstruction (i.e., supraglottic, glottic, and subglottic levels) remains a subject of controversy. An awake flexible
fiberoptic intubation, inhalation induction, and intravenous induction with muscle relaxants 39,71,72,81 have been used
successfully, but none should be considered fail-safe. The nature of the obstructing lesion (e.g., vascular,
submucosal, pedunculated, inflammatory) and its location (e.g., supraglottic, glottic, subglottic, midtracheal, lower
tracheal, and bronchial [mediastinal]) may require completely different intubation considerations and
approaches.39,71,80,82-85
A series of cases of partial airway obstruction, each requiring a different, complex, and sometimes
unorthodox or innovative approach, will be presented and discussed.
Conflict of interests: none.
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Coexisting Respiratory Disease in Infants and Children: Navigating the Difficult

Pathway to the Operating Room
Linda J. Mason, MD Loma Linda/California
Learning Objectives
As a result of completing this activity, the participant should be able to:
1. Discuss the pathophysiology of pediatric patients with asthma
2. Describe the current medical management of this disease state
3. Manage the child with sleep apnea with criteria for outpatient tonsillectomy
4. Describe an approach to the anesthetic management for pediatric patients with these coexisting diseases
Children with coexisting disease provide a special challenge for anesthesia and surgical procedures. In this
Refresher Course, two very common pediatric coexisting diseases, asthma and obstructive sleep apnea, are
discussed.
ASTHMA
Asthma is the most common chronic disease in children. A recent governmental report found that the asthma
prevalence in the United States is increasing: currently at 9.5% of children aged 0–17.1 Children less than 3 years
old frequently have episodic respiratory symptoms (cough, wheezing), but most do not go on to have a clinical
diagnosis of asthma.2 Asthma is defined by chronic inflammation of the airways, associated with airway
hyperresponsiveness, which leads to recurring episodes of wheezing, coughing, breathlessness, chest tightness, and
reversible airflow obstruction within the lung. Contributing factors include genetic predisposition, atopy, and
respiratory syncytial virus infection in infancy. Asthma patients carry a small but significantly increased risk for
operative and postoperative complications.3
Pharmacotherapy for Asthma

β-Adrenergic agonists are commonly used to provide rapid relief of acute bronchospasm (short-acting β agonists
[SABAs]) and are also used for chronic treatment (long-acting β agonists [LABAs]), but only in combination with
inhaled corticosteroids. When these drugs activate the β2 receptor, adenyl cyclase increases cyclic adenosine
monophosphate levels, which causes smooth muscle relaxation and increased mucociliary clearance.4 Although
these agents may be administered by oral or intravenous (IV) routes, inhalation administration provides faster peak
bronchodilatation and fewer systemic side effects.5
Inhaled corticosteroids are the foundation of treatment for asthma because they target the inflammation that
characterizes the disease. They have been shown to reduce airway reactivity, inhibit inflammatory cell migration and
activation, and block reactions to allergens.6 High-dose inhaled corticosteroids may have some systemic side effects,
but the oral thrush and hoarseness often seen in adults are rare in children. Systemic corticosteroids, either oral or
parenteral, are reserved for severe, uncontrolled asthma.
Leukotriene pathway modifiers are most commonly used as second-line controller medications.
Leukotrienes are produced by mast cells, eosinophils, and basophils inducing edema, stimulation of airway
secretions, and smooth muscle proliferation (by a nonhistamine mechanism).7 These orally administered drugs are
particularly useful in several specific areas, including exercise-induced, intermittent (viral-induced), and aspirin-
induced asthma.7
The anticholinergic ipratropium bromide inhibits mucus hypersecretion and decreases reflex
bronchoconstriction by targeting airway muscarinic cholinergic receptors. It may be administered by metered dose
inhaler (MDI) or nebulizer and is a quaternary amine with no significant systemic absorption or side effects.
Ipratropium is rarely used in chronic management of pediatric asthma patients. Several systematic reviews confirm
its benefit in the setting of severe, acute asthma when combined with other treatments.8
Theophylline is a methylxanthine that functions as a mild bronchodilator and antiinflammatory agent.
Because its effect is less than that of low-dose inhaled corticosteroids, it is seldom used as first-line therapy. It has
proved effective as a rescue medication in status asthmaticus.9 Because theophylline has a very low therapeutic
index, serum monitoring is essential. Side effects include nausea, vomiting, headache, and seizures.
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Preanesthetic Evaluation
Essential points to review in the preoperative evaluation are the level of asthma control and the current medication
regimen. In addition, review of the level of activity, use of rescue medications, hospital visits (if tracheal intubation
or IV infusions were required), allergies, and previous anesthetic history are important. Also, an inquiry regarding
cough and sputum production should occur. Although otherwise healthy children can often be anesthetized safely
during an acute upper respiratory infection, the risk of bronchospasm in asthmatic patients is very high.10,11 Ideally,
the procedure should be postponed for 4 to 6 weeks after such an event. Physical examination should include vital
signs, assessment for wheezing, cough, type of breath sounds, use of accessory muscles, and level of hydration.
Room air oxygen saturation is useful as a baseline measurement and for determining preexisting hypoxemia. Other
laboratory data are not usually necessary.
The diagnoses of atopy/eczema and allergic rhinitis often go hand in hand with a diagnosis of asthma, as
they are all thought to be conditions of chronic inflammation. 12 A family history of asthma and atopy also
contributes to intraoperative respiratory complications.10 As in adults, marked gastroesophageal reflux disease can
often be a trigger for asthma symptoms.13 Obese patients present a variety of anesthetic challenges. Relevant to this
discussion is not only the association of obesity and asthma, but also the increase in intraoperative bronchospasm
seen in obese children, even without a diagnosis of asthma.14 Exposure to secondhand smoke should be considered a
risk factor for poor asthma control as well as an independent risk factor for adverse respiratory events in children
under general anesthesia.15
Risk Factor Optimization

Preoperative preparation for a controlled asthmatic may include use of an inhaled β2-adrenergic agonist 1 to 2 hours
prior to surgery. For moderately controlled asthma, additional optimization with an inhaled corticosteroid and
regular use of inhaled β2 agonists can be instituted 1 week prior to surgery. Poorly controlled asthmatics may need
addition of one of the following: oral prednisone 1 mg/kg/day (maximum, 60 mg) 3 to 5 days before surgery, oral
dexamethasone 0.6 mg/kg (maximum, 16 mg), or oral methylprednisolone 1 mg/kg for 48 hours prior to surgery.16
Preanesthetic assessment and planning can reduce the risk for perioperative bronchospasm in asthmatics undergoing
general anesthesia (Figure 1).17 A stepwise approach to the preoperative treatment of asthmatic patients can also be
based on their degree of asthma control (Figure 2).17
Perioperative Management
Patients should continue all their controller medications as usual on the day of surgery. An extra dose of SABA may
be efficacious if deemed necessary from the preoperative evaluation. Giving a routine “extra dose” (in addition to
the patient’s scheduled dose) to all asthmatics regardless of the level of control may not be warranted, although the
beneficial effect of SABAs on reflex bronchoconstriction in response to tracheal intubation is clear.18,19
Premedication with oral midazolam, 0.5–1 mg/kg, is safe in asthmatics and may be indicated, given that anxiety may
precipitate acute bronchospasm.20 The use of systemic or high-dose inhaled corticosteroids currently or in the past 6
months is an indication for stress dose coverage.6 If indicated by the preoperative evaluation, it is still not too late to
give IV corticosteroids, as their beneficial effect will extend into the postoperative period.
If an IV catheter is in place prior to induction, several medications can be given to diminish the response to tracheal
intubation. Lidocaine may prevent reflex bronchoconstriction and has little toxicity at a dose of 1–1.5 mg/kg IV
given 1–3 minutes prior to tracheal intubation.21 Direct spraying of the airway may trigger airway reactivity, so the
IV route is preferable.22 Through their effect at muscarinic receptors, IV glycopyrrolate or atropine given along with
an IV induction or after an inhalational induction may decrease secretions and provide additional bronchodilatation
prior to tracheal intubation.
A number of clinical factors will often influence the choice between IV versus inhalational induction.
There is little compelling evidence to recommend one technique over the other in asthmatic children. If IV induction
is elected, propofol is the agent of choice in hemodynamically stable asthmatic patients. It has been shown in
multiple studies to attenuate the bronchospastic response to tracheal intubation in both asthmatic and nonasthmatic
patients.23,24 Its effect is likely mediated by suppression of vagally mediated stimulation of bronchial muscarinic
receptors.25 Recent animal research suggests that propofol may mediate bronchodilation by other pathways,
including airway smooth muscle GABA receptors and diminishing the effect of tachykinins on airway smooth
muscle.26 Neither thiopental nor etomidate will mediate the bronchospastic response to tracheal intubation as
effectively as propofol.24
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Ketamine is the induction agent of choice in hemodynamically unstable asthmatic patients. It likely
produces smooth muscle relaxation and bronchodilatation directly, by release of catecholamines, and through
vagally mediated mechanisms, although its bronchoprotective effect is not as pronounced as that of propofol.25 Its
mucus-stimulating effects can be ameliorated by pretreatment with atropine or glycopyrrolate.
Volatile anesthetics have long been known to depress airway reflexes to tracheal intubation and cause
direct airway smooth muscle relaxation.27 Sevoflurane appears to have the most pronounced effect of all the
inhalational anesthetics and is the agent of choice for mask induction. 28 As a word of caution: in children with
asthma, compared with nonasthmatic children, tracheal intubation with sevoflurane as the sole anesthetic (even at
5% concentration) causes an increase in respiratory system resistance. 29 Having an asthmatic child use a SABA prior
to induction with sevoflurane can decrease the risk of increased airway resistance and bronchospasm that occurs
with tracheal intubation.18 During maintenance of anesthesia, children with asthma have shown low airway
resistance with a propofol infusion, but in most asthmatic children, switching to sevoflurane further improved this
effect. In contrast, a switch to desflurane caused elevation in airway resistance in these susceptible children.30
Although some have questioned the mechanism by which desflurane increases airway resistance, it is clear that at
typical MAC-equivalent doses, desflurane does increase airway resistance.31
Because tracheal intubation is one of the most potent triggers for bronchospasm, choosing a laryngeal mask
airway (LMA) or simple mask may be useful.32 Little research has been done to define the risks of tracheal
intubation versus LMA in asthmatic children, but those with recent upper respiratory infection may benefit from the
use of an LMA.33 Should tracheal intubation be required, the use of cuffed tracheal tubes avoids the need for
multiple intubations due to air leak and allows more reliable end-tidal carbon dioxide waveform monitoring and the
use of lower fresh gas flows.34 Regional anesthesia should be considered whenever possible to avoid airway
manipulation, but may not be feasible for the uncooperative pediatric patient or for certain surgical situations.
Non-histamine-releasing muscle relaxants such as rocuronium, vecuronium, and cisatracurium are
acceptable for use in children with asthma. Reversal of neuromuscular blockade with acetylcholinesterase inhibitors
(e.g., neostigmine or edrophonium) may be undertaken with caution in asthmatics but carries the risk of residual
neuromuscular blockade and muscarinic side effects, including bronchospasm.
During mechanical ventilation, inspiratory pressures should be kept low and the expiratory time
lengthened. Careful attention should be paid to the avoidance of intrinsically developed positive end-expiratory
pressure.35 On a theoretical basis, extubation under deep anesthesia should decrease the risk of bronchospasm
evoked by coughing on the tracheal tube; however, little research has been done to answer this question for
asthmatic children.36
Treatment of Intraoperative Bronchospasm

Treatment of intraoperative bronchospasm in children presents a unique set of problems, particularly when the
spasm is severe. Inhaled β2 agonists are the treatment of choice, yet the delivery of inhaled medications via small
tracheal tubes is difficult. Previous research has shown that patients received only 2.5–12.3% of an albuterol dose
delivered by MDI into 3.0–6.0 mm ID tracheal tubes.37 Resourceful anesthesiologists have sought various ways to
overcome this problem, including actuating the MDI canister into a long, 19-gauge IV catheter advanced out of the
end of the tracheal tube.37 Although this method increases delivery of albuterol 10-fold, delivery of concentrated
medication and other components of the MDI may cause damage to the airway. 38 Both MDI spacers and nebulizers
have been modified in a variety of ways to fit into a ventilator circuit.
Occasionally, severe bronchospasm can make it difficult to deliver any inhaled medications, necessitating
an alternate route of administration. IV anticholinergic medications should be given and additional steroids (up to 2
mg/kg of hydrocortisone or methylprednisolone) may not have immediate effect but can aid in avoiding
postoperative bronchospasm. Intravenous or subcutaneous β agonists in the form of terbutaline (10 μg/kg over 10
min), epinephrine, or isoproterenol may be used if previous therapy is unsuccessful in terminating the
bronchospasm.39,40 IV theophylline (5–7 mg/kg over 20 min) can be added in refractory situations. 9,41 Magnesium
(50 mg/kg over 20 min) has been shown to benefit children with severe asthma already treated with β-agonists and
corticosteroids.42 The final option for patients failing all the previously described treatments is extracorporeal
membrane oxygenation. It has been used successfully, with minimal neurological outcomes, to treat refractory
asthma in children.43
OBSTRUCTIVE SLEEP APNEA

Sleep apnea in children is a sleep-related breathing disorder characterized by periodic cessation of air exchange with
apnea episodes lasting longer than10 seconds and an apnea/hypopnea index (AHI), representing total number of
obstructive episodes per hour of sleep, greater than 5.44 Airflow cessation is confirmed by auscultation or by oxygen
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saturation below 92%. Types of sleep apnea include central (absent gas flow, lack of respiratory effort), obstructive
(absent gas flow, upper airway obstruction, and paradoxical movement of the rib cage and abdominal muscles), and
mixed (caused by both central nervous system defect and obstructive problems). Diagnosis is made by clinical
assessment (a history of snoring and restless sleep), nocturnal pulse oximetry, or polysomnography studies.
Obstructive Sleep Apnea Syndrome

Obstructive sleep apnea syndrome (OSAS) is manifested by episodes that disturb sleep and ventilation. These
episodes occur more frequently during rapid eye movement (REM) sleep and increase in frequency as more time is
spent in REM sleep periods as the night progresses. OSAS occurs in children of all ages (about 2% of all children)
but more commonly in those between 3 and 7 years of age. It occurs equally among boys and girls but the
prevalence may be higher in African American children.45 Childhood obesity is increasing in modern societies and
OSAS is more frequent in children with obesity. Signs of OSAS are sleep disturbances (including daytime
sleepiness), failure to thrive from poor intake due to tonsillar hypertrophy, speech disorders, and decreased size
(from diminished release of growth hormone during disturbed REM sleep).
The syndrome can cause marked cardiac, pulmonary, and central nervous system impairment because of
chronic oxygen desaturation. Hypertension and diabetes occur at much higher rates in children with OSAS and
morbid obesity. Therefore, it is important to evaluate the cardiovascular status in this group of children prior to
surgery. Although right ventricular dysfunction is classic, biventricular hypertrophy can develop. It is more likely to
be seen in patients with severe OSAS, but has been reported in only mild cases.46 Pulmonary vasoconstriction can
increase pulmonary vascular resistance with resultant decrease in cardiac output from cor pulmonale. Relief of the
tonsillar/adenoidal obstruction can reverse many of these problems and prevent progression of others (i.e.,
pulmonary hypertension and cor pulmonale). Cardiac evaluation is recommended for any child with signs of right
ventricular dysfunction, systemic hypertension, or multiple episodes of desaturation below 70%. Electrocardiograms
and chest roentgenograms are not sensitive tools; echocardiography is recommended.47
The American Academy of Pediatrics Clinical Practice Guidelines45 give recommendations for inpatient
monitoring in patients with OSAS who are undergoing adenotonsillectomy and are at high risk for postoperative
complications (Table 1). In a recent analysis, children at risk for OSAS had more postoperative adverse events
associated with apnea compared with a large proportion of adverse events attributed to hemorrhage among all other
children undergoing tonsillectomy (Figure 3).48 Risk factors for complications post tonsillectomy are listed in Table
2.48
Monitoring
Children aged 1–18 years with mild sleep apnea (<15 obstructive events/h) and no underlying medical conditions,
neuromuscular disease, or craniofacial abnormalities will have improvement of their airway obstruction documented
by polysomnography the night of surgery and do not need to be monitored intensively. In these patients, a smaller
number of obstructive events and fewer severe oxygen desaturations occurred on the operative night. 49 Based on this
finding and other studies, it is possible to consider discharge to home for children aged 3–12 years if they meet these
criteria. However, in children with severe obstructive sleep apnea (AHI >16.4 events/h, oxygen saturation <85%),
obstructive events occurred more frequently on the first night after adenotonsillectomy, suggesting that overnight
monitoring with pulse oximetry is indicated.50
Postoperative respiratory complications were increased from 20% to 50% in OSAS patients with oxygen
saturation of 80% or less on preoperative nocturnal oximetry. Usually these children were younger (<2 years) and
had an associated medical condition.51
Children with severe OSAS who underwent adenotonsillectomy in the morning were less likely to have
postoperative desaturation than those who were operated in the afternoon. 52 The shortened interval between
postoperative morphine dosing and bedtime may contribute to the incidence of postoperative desaturation because of
an exaggerated respiratory depressive response to opioids that has been reported in children with severe OSAS.53
There is a strong possibility that the combination of opioids and sleep promotes desaturation in these patients.
Generally, children with OSAS may have a diminished ventilatory response to carbon dioxide rebreathing
compared with normal children.54 Therefore, drugs known to cause ventilatory depression (sedative hypnotics,
anxiolytics, narcotics, and inhaled anesthetic agents) must be used judiciously in these patients as they may be more
sensitive to their effects. Preoperative administration of midazolam 0.5 mg/kg in 70 children undergoing
adenotonsillectomy for OSAS (diagnosed as severe in 40% of subjects by polysomnography) resulted in 2 children
having respiratory events: one a self-limited desaturation event before surgery and the other a postoperative
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obstruction with desaturation requiring a nasal airway.55 Compared with the doses normally given to children
without OSAS, patients with OSAS can receive sedatives in reduced doses and often require respiratory monitoring
in the preoperative period.
During inhalational induction of anesthesia, children with OSAS are at high risk for airway obstruction
caused by relaxation of the genioglossus muscle. Upright or lateral positioning, use of the jaw thrust maneuver,
delivery of positive pressure by face mask, and placement of an oral airway may aid in relieving the obstruction. 56
Once anesthesia is induced and intravenous access is established, a single dose of IV propofol 1.5–2 mg/kg (lean
body weight) may facilitate tracheal intubation.57
Postoperative Considerations
Children with OSAS usually need pain medication after surgery, yet chronic hypoxemia renders them more
susceptible to the respiratory depressant effects of opioids. 58 Younger patients or those with preoperative nocturnal
oxygen saturation below 85% have a reduced morphine requirement, possibly owing to upregulation of central
opioid receptors consequent to recurrent hypoxemia.59 Compared with children whose minimal oxygen saturation
was 85% or greater, children whose minimum nocturnal saturation was less than 85% required one-half the dose of
opioids to achieve similar pain scores after adenotonsillectomy.60
One technique for opioid administration is that after tracheal intubation and spontaneous ventilation is
restored, small incremental aliquots of IV morphine (10–20 μg/kg) or fentanyl (0.2–0.5 μg/kg) can be given. If
apnea occurs after the first aliquot, the child may be considered opioid sensitive. If the child continues to breathe,
additional increments up to the standard total dose of 50–100 μg/kg of morphine can be administerd.57 Drugs for
pain management to decrease opioid use include ketamine 0.1 mg/kg IV 61 or peritonsillar infiltration of ketamine
0.5–1 mg/kg given 3 minutes before surgery,62 dexamethasone 0.0625–1 mg/kg (maximum, 25 mg) with an average
dose of 0.5 mg/kg, and IV acetaminophen 15 mg/kg (maximum, 75 mg/kg/d for children 2–12 years old).63,64
The possibility of postoperative bleeding associated with dexamethasone use in tonsillectomy patients was
raised in an article that compared three doses of dexamethasone: 0.05 mg/kg, 0.15 mg/kg, and 0.5 mg/kg. Of
concern was that both the 0.5 mg/kg dose and the 0.05 mg/kg dose were associated with a higher incidence of
postoperative bleeding. The problem with this study was the lack of standardization of surgeon, surgical technique,
and use of nonsteroidal antiinflammatory drugs (NSAIDs).65 In a more recent retrospective review, 2,788 children
aged 2–18 years undergoing tonsillectomy were given either 0.5 mg/kg or 1.0 mg/kg of dexamethasone. The study
was adjusted for age, sex, primary diagnosis (sleep-related disorder and infectious tonsillitis), and surgical
technique, either extracapsular electrosurgical tonsillectomy, extracapsular radiofrequency ablation tonsillectomy, or
intracapsular microdebrider tonsillectomy. Perioperative dexamethasone administration was not associated with a
dose-dependent elevation of postoperative hemorrhage.66 A recent Cochrane review of 19 randomized, placebo-
controlled, double-blinded studies concluded that children receiving a single intraoperative dose of dexamethasone
(dose range, 0.15–0.5 mg/kg) were half as likely to vomit in the first 24 hours and had less pain than the placebo
group.67
In a recent report of adenotonsillectomy for children who demonstrated recurrent episodes of profound
hypoxemia (<80% saturation) during their perioperative sleep study, major medical respiratory interventions were
reduced by more than 50% by the administration of dexamethasone 0.3 mg/kg (maximum, 10 mg) and titration of
morphine 0.02 mg/kg.68
NSAIDs have been avoided in posttonsillectomy patients because of reports of an association with
postoperative bleeding. However, a systematic review did not find an increased risk of reoperation for bleeding and
found less vomiting when NSAIDs were part of an analgesic regimen.69 The use of NSAIDs after attainment of
hemostasis is reasonable.70 A new study with administration of 10 mg/kg of IV ibuprofen prior to tonsillectomy
showed a significant narcotic-sparing effect with no increase in bleeding—further evidence that NSAIDs can be an
important component of a multimodal pain approach.71
Emergence delirium may be decreased with a single IV bolus dose of dexmedetomidine 0.5 μg/kg given 5
minutes before the end of surgery, thus providing a smoother transition to the postanesthesia care unit (PACU).72 In
a prospective study, 122 patients aged 2–10 years undergoing tonsillectomy with sevoflurane anesthesia received IV
dexmedetomidine 2 μg/kg over 10 minutes followed by 0.7 μg/kg/h. Compared with a group receiving IV fentanyl 1
μg/kg, the dexmedetomidine group needed less rescue analgesics with fentanyl, had a lower heart rate and systolic
blood pressure, and also required less morphine in the postoperative period. Severe emergence agitation on arrival at
the PACU was lower and its duration shorter in the patients who received dexmedetomidine.73
After completion of the procedure, patients should be awake and be able to maintain their upper airway
patency. Deep extubation is not recommended in patients with severe OSAS or those with comorbidities because
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they are at risk of persistent OSAS after surgery. Before extubation, a nasal airway can be placed in patients with
severe sleep apnea. The lateral decubitus or prone position can help relieve airway obstruction after extubation.
Postoperative admission to the intensive care unit is reserved for very severe OSAS, very young children (< 2
years of age), morbid obesity (BMI >40), and patients with comorbidities that cannot be managed in a regular unit.74
Patients with mild to moderate obstructive disease (AHI <10) and no comorbidities can usually be discharged home
the same day if they are over 3 years of age.
Deaths have occurred in children with OSAS given oral codeine for pain management at home, precipitating
a recent boxed warning and contraindication released by the FDA recommending against use of codeine in children
undergoing tonsillectomy. These children may be part of a group of extensive or ultra-rapid metabolizers who
produce increased amounts of potent morphine from its parent drug codeine. The genetic pattern occurs in 1–10% of
individuals of European descent and up to 30% of North African descent, and must be considered with codeine
use.75 Given this data and the increased use of IV acetaminophen during the operative procedure, a safer drug to give
in the PACU before discharge maybe oxycodone elixir (1 mg/mL preparation), 0.1 mg/kg up to a maximum dose of
5 mg, rather than acetaminophen with codeine. This also avoids the problem of acetaminophen excess in the
immediate postoperative period, although oxycodone is a drug that requires some metabolism to be effective. Other
options for postoperative pain management may be oral liquid opioids not metabolized by CYP2D6, such as
morphine or hydromorphone.
Although the respiratory distress index improves after adenotonsillectomy in children with severe sleep apnea
and in obese children with OSAS, OSAS may not resolve immediately in the majority of these children. In addition,
enlarged lingual tonsils were found to contribute to persistent OSAS after adenotonsillectomy in children and were
also found to be more prevalent in patients with Down syndrome.76 It is important to recognize that these children
may have increased anesthetic risk and need special care if they return for other operations.
CONCLUSIONS
Children with asthma or obstructive sleep apnea need special preparation and anesthetic management if they are to
achieve an optimal outcome after surgical procedures.
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69. Cardwell ME, Siviter G, Smith AF: Nonsteroidal anti-inflammatory drugs and perioperative bleeding in
paediatric tonsillectomy. Cochrane Database Syst Rev 2005; CD003591.pub2.
70. Dsida R, Cote CJ. Nonsteroidal anti-inflammatory drugs and hemorrhage following tonsillectomy: do we
have the data? [Correspondence]. Anesthesiology 2004; 100:749–51; author reply 751–2.
71. Moss JR, Watcha MF, Bendel LP, McCarthy DL, Witham SL, Glover CD: A multicenter, randomized,
double-blind placebo-controlled, single dose trial of the safety and efficacy of intravenous ibuprofen for
treatment of pain in pediatric patients undergoing tonsillectomy. Paediatr Anaesth 2014; 24:483–9.
72. Guler G, Akin A, Tosun Z, Ors S, Esmaoglu A, Boyaci A: Single-dose dexmedetomidine reduces agitation
and provides smooth extubation after pediatric adenotonsillectomy. Paediatr Anaesth 2005; 15:762–6.
73. Patel A, Davidson M, Tran MC, Quraishi H, Schoenberg C, Sant M, Lin A, et al.: Dexmedetomidine infusion
for analgesia and prevention of emergence agitation in children with obstructive sleep apnea syndrome
undergoing tonsillectomy and adenoidectomy. Anesth Analg 2010; 111:1004–10.
74. Leong AC, Davis JP: Morbidity after adenotonsillectomy for paediatric obstructive sleep apnoea syndrome:
waking up to a pragmatic approach. J Laryngol Otol 2007; 121:809–17.
75. Kelly LE, Rieder M, van den Anker J, Malkin B, Ross C, Neely MN, Carleton B, et al.: More codeine
fatalities after tonsillectomy in North American children. Pediatrics 2012; 129:e1343–7.
76. Fricke BL, Donnelly LF, Shott SR, Kaira M, Poe SA, Chini BA, Amin RS: Comparison of lingual tonsil size
as depicted on MR imaging between children with obstructive sleep apnea despite previous tonsillectomy and
adenoidectomy and normal controls. Pediatr Radiol 2006; 36:518–23.
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STILL NOT BEING RESPECTED AT WORK? PROFESSIONALISM AND

HOW IT AFFECTS YOU
SAUNDRA CURRY, MD NEW YORK/NY
In 2002 the European Federation of Internal Medicine, the American College of Physicians-American Society of
Internal Medicine (ACP-ASIM) and American Board of Internal Medicine (ABIM) collaborated to write Medical
Professionalism in the New Millennium: A Physician Charter 1. This charter laid out three fundamental principles
and ten commitments all which encompass the basis of medicine’s contract with society. The ASA, the ABA and
some 130 other societies worldwide have endorsed this charter, but there is precious little in the literature about how
practitioners are and should be applying this charter to their everyday work lives. As yet there is no definition of
professionalism that everyone agrees upon. Differing specialties view professionalism through their own eyes 2
which is appropriate since we all have different types of interactions with patients and colleagues. But
professionalism in anesthesia is still not well defined, an unfortunate situation, because it impacts us at every level in
our daily working lives. Each paragraph of the charter can be applied to what we do.
TENETS
Principles
Principle of primacy of patient welfare: There can be no argument about the importance of this statement. We
care for patients at their most vulnerable moments. They are ill, frightened, and for the most part, unconscious. We
as anesthesiologists are patient advocates and protectors in operating room and critical care environments. Nothing
should interfere with this duty to altruism.
Principle of patient autonomy: Again, we are protectors of patient rights. We have a duty to present the options
patients have for their care and cannot force them to have any type of anesthesia. They rely on us to use our best
judgment to provide the best of care, given the surgical situation. We can’t force regional or general on them, but
can only present the best options available to them. This also applies to DNI/DNR scenarios.
Principle of social justice: This principle may seem removed from the operating room, but in fact appears more
often than one would think. We take all comers to the operating room, and should delegate care based only on the
basis of the medical status of the patient, not their ability to pay, their standing in the community, or any other social
characteristic.
Commitments
Commitment to professional competence: The decisions made over ten years ago to require recertification on a
regular basis satisfies this commitment. And the recent changes to MOCA, requiring lifelong learning and
maintenance of clinical skills show the world at large that we acknowledge that modern medicine is an ever
changing field. Practicing with the skills learned long ago is not enough. Best practice requires keeping up to date
in everything.
Commitment to honesty with patients: Lying to patients about their care can only lead to disaster. Medical errors
need to be acknowledged so patients can be properly cared for. Patients suspect many things are done to them while
under anesthesia that they don’t know about and might not approve of. If students, vendors, etc. are going to be
around this needs to be agreed to ahead of time and then followed through. If a patient refuses this sort of contact,
that wish must be honored. If it can’t be, they must be told.
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Commitment to patient confidentiality: No one wants to hear about their case in elevator discussions. Electronic
media make this commitment even harder to adhere to. However, it again is our duty to protect our patients’
medical information, which extends from the type of surgery they are having to their diagnoses and genotype.
Commitment to maintaining appropriate relations with patients: Exploitation of any sort by practitioners of
their patients is wrong and cannot be tolerated.
Commitment to improving quality of care: Anesthesiologists have always been leaders in quality and safety.
This extends from maintaining competence, reducing errors and collaborating with other specialties to optimize
clinical outcomes.
Commitment to improving access to care: We need to strive to improve access to the best possible care that our
patients can receive. This includes supporting efforts to improve public health, such as the ASA’s initiative to stop
smoking.
Commitment to a just distribution of finite resources: As anesthesiologists we can aid in this commitment by
avoiding waste and applying the best cost effective care possible.
Commitment to scientific knowledge: This commitment may be one of the easier ones for anesthesiologists to
understand. Scientific research is the way our specialty will move forward. Not everyone is cut out to be a
researcher, but we can all read about and apply the advances shown to be improvements to patient care. We can also
support those who do research with time and money.
Commitment to maintaining trust by managing conflicts of interest: Full disclosure is the only way to go with
this commitment. Anesthesia is a specialty that draws clever people who are interested in new product and drug
development and who also know how to pursue these interests to potential financial markets. We need their know-
how, we and our patients just need to be clear that it is the patients’ best interest that is being maintained, not just the
bottom line of any new company.
Commitment to professional responsibility: This final commitment encompasses many duties, including
promoting the specialty, maximizing excellent patient care, self-regulate, respect one another, set educational
standards, as well as support organizations that promote the specialty on a national level. Much of how we practice
can be mandated at a national level and we need to be involved in those processes.
ADVERSE CONSEQUENCES TO PATIENTS
What happens if we don’t adhere to the principles and commitments? The consequences of not adhering to these
tenets may be easier to see than their daily application.
Patient welfare can be easily compromised if their best interest is not placed paramount. We could leave patients
alone under anesthesia. Anesthesia is so safe these days nothing would happen, right?
Patient autonomy is paramount. As an example, the DNR debate over the last 20 years has shown that patients
want their rights acknowledged and respected. Not to do this leads to patient mistrust and potential law suits.
Social injustice gives good care only to those who can afford it or to those we happen to like because of their race,
ethnic background, religion, or political affiliation.
Professional incompetence means that your colleague who hasn’t read a journal or attended an educational meeting
for the last ten years might be giving you anesthesia in an emergency. Or perhaps he has a substance abuse
problem…
Dishonesty with patients means that if a mistake was made and not reported, the mistake may be repeated (drug
reactions) or the patient may not get the appropriate care to rectify the new problem.
Lack of confidentiality - means that the world can hear about a patient’s issues. This can lead to job consequences,
marital discord, and other topics that are none of anybody else’s business.
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Inappropriate relations with patients can lead to wrong care, bullying, and professional blackmail.
Not improving the quality of care means we are taking care of today’s problems with yesterday’s solutions. This
may work for a while, but is doomed to failure eventually.
Not improving access to care means we end up having to care for sicker patients than we have to. If they don’t
have access to good primary care, our job is that much more difficult.
Unjust distribution of finite resources means that those who need care the most won’t get it when they need it.
Lack of scientific discovery - means that we never advance the specialty and cannot improve patient outcomes.
Not managing conflicts of interest means that we lose the public trust. This is another form of altruism where the
public needs to know that we are putting their needs above our own, not vice versa.
Not taking professional responsibilities seriously means no one else will either. If we don’t care enough to
support our major organizations as they fight for our rights in Congress, for example, why should Congress listen?
PERSONAL AND DAILY APPLICATIONS
Swick et.al.3 point out that one of the flaws of the Charter is that it concentrates on duties and not on values that are
virtue based. Their theory is that duties without values are very hard to stick to and one needs to absorb. Virtues
have the benefit of being inherent in people and not externally driven. Therefore they have better chance of sticking.
The other important benefit is that virtues are what people bring to any situation regardless of the context. The
operating rooms are inherently stressful with different groups of people working together. Each has their own
agenda. If everyone concentrates on the patient as being the key element that has brought them all together, focus
can be maintained on the only important person in the room. One of the common grumbles of anesthesiologists is
that they don’t get enough respect from surgeons and nursing staffs or even patients. Respect is earned, not
automatically granted. It is true that patients do not come to the hospital to get anesthesia. Surgeons bring them in
so there is an inherent dichotomy for everyone to deal with. However, it is unlikely that patients would come for
surgery if they thought they were not getting any of the services we provide, i.e., analgesia, amnesia, and
maintenance of life. Lesser et.al.4 bring up a slightly different emphasis. They focus on behaviors of individuals and
organizations because attitudes (values and virtues) are very hard to adjust. Behaviors are teachable, learnable and
can be assessed. Quoting Aristotle, “Excellence is an art won by training and habituation. We do not act rightly
because we have virtue or excellence but rather we have those because we have acted rightly. We are what we
repeatedly do. Excellence then is not an act but a habit.” It is virtually impossible to change other people. One can
only work on oneself.
Leape et al 5,6 looked at disrespectful behavior and noted how sort of behavior can seriously disrupt the work
environment. Making patients wait unreasonably for appointments is disrespectful to them. Demeaning behavior to
a nurses and ancillary staff is disrespectful. Abuse of residents, students and colleagues is disrespectful. All of
these can threaten patient safety by impacting collegiality and cooperation essential to teamwork.
Yet thinking of professionalism as a list of duties or values or even specific behaviors does not really get to the
point. Wynia et al7 noted that what is needed is a foundational understanding of what professionalism is all about.
The behaviors and lists created are derivative of the belief system of professionalism. Professionalism is the
motivational force that brings practitioners together to create and keep shared promises to the public. It ensures that
practitioners are worthy of patient and public trust. With professionalism as a belief system it becomes clear that
technical, interpersonal, communication, and knowledge skills are all interlocking promises that are what
professionalism is all about. True professionalism requires practitioners to work together across specialties and
divides to insure the promises to patients are kept. But it begins with individuals, us, to ensure that these promises
are kept. If we as individuals believe in professionalism and work individually and together to ensure the best for
our patients, we will gain the respect of our patients and colleagues alike. We will also be taken quite seriously as
patient outcomes improve and burnout among practitioners decreases. As so eloquently laid out in the March 2016
ASA Monitor8, “Without professionalism, the other core competencies simply lack effectiveness.”
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Here’s an approach that encompasses the some of the tenets of the Charter, includes personal virtues and behaviors.
I will place patient welfare above all else. I will have carefully planned my anesthetic for the case at hand, having
discussed the surgeon’s needs with him/her ahead of time. I will discuss plans and goals with the patient at a level
I will listen to the patient. Their concerns and desires are important in my plan for how I care for this patient. I
will show them compassion for their concerns. I do this every day but this may be the patient’s first encounter with
the OR’s.
I will give them the best care, regardless of their place in society.
I will strive for excellence in my profession, not just competence. That means that every day there is something
to learn and improve upon. My board certification was just a large stepping stone in my drive to become an
outstanding and expert clinician. Lifelong learning and professional development will be my tools.
I will be honest in my dealings with all maintaining integrity and accountability. This includes, patients, OR
staff, surgeons and consults. Honesty about mistakes, errors in judgment, as well as thoughts on chances of success
in a particular procedure will gain me the confidence of those with whom I work. I will also honor myself and not
abuse myself with drugs, lack of sleep, etc which may compromise my ability to care for my patients.
I will maintain the confidentiality of my patients and thus they will know they can count on me.
I will maintain strictly appropriate behavior with my patients.
I will take my professional responsibilities seriously. This includes supporting my national organizations who
speak for me to the public. But it also means treating colleagues of all specialties with the respect I expect from
them. I will confer with my surgical colleagues about upcoming cases so that an appropriate care plan can be
established. If I suspect a colleague in any specialty is behaving inappropriately (drugs, alcohol, behavior) I will
make sure it gets reported to the appropriate authorities. This shows compassion for the person and care of any
patients that may be in harm’s way.
Ultimately by adhering to these duties, virtues and responsibilities and acting on them we will earn the respect of all
with whom we work, take great care of our patients and honor our specialty and ourselves. Issues in professionalism
are here to stay.9 Surgeons are already on the bandwagon in their teaching of residents. 10 We need to get a head start
in our profession by adhering to these tenets now.
REFERENCES
1. Medical Professionalism in the New Millennium: A Physician Charter. Ann Int Med 2002; 136:243-246
2. Garfield JM, et al. Doctors in acute and longitudinal specialties emphasize different professional attributes:
implications for training programmes. Med Ed 2009; 43:749-756.
3. Swick HM, Bryan C, Longo LD. Beyond the physician charter. Perspectives in Bio and Med 2006;
49(2):263-275.
4. Lesser CS, et al. A behavioral and systems view of professionalism. JAMA 2010; 304(24):2732-2737Le
5. Leape LL, Shore MF, Dienstag JL, et al .A culture of respect, part 1: Nature and causes of disrespectful
behavior by physicians. Acad Med 2012; 87(7): 845-852.
6. Leape LL, Shore MF, Dienstag JL, et al .A culture of respect, part 2: creating a culture of respect. Acad
Med 2012; 87(7): 853-858.
7. Wynia MK, Papadakis MA, Sullivan WM, Hafferty FW. More than a list of values and desired behaviors: a
foundational understanding of medical professionalism. Acad Med 2014.89 (5): 712-714
8. Coolman DA, D’Hemecourt JP, Forth NE. Professionalism: a work in progress. ASA Monitor March
2016; 80(3): 10-11.
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9. JAMA 2015. May 12 issue

10. Nguyen N, Elliott JO, Watson WD, Dominguez E. Simulation Improves Nontechnical Skills Performance
of Residents During the Perioperative and Intraoperative Phases of Surgery . J Surg Educ. 2015 Apr 21
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Anaphylaxis, Allergy, and Adverse Drug Reactions: Perioperative

Considerations for Anesthesiologists
Jerrold H Levy, MD, FAHA, FCCM Durham/North Carolina
INTRODUCTION
Surgical patients receive multiple foreign substances in the perioperative period including drugs, blood products,
or environmental antigens such as latex. Because any substance can produce an allergic or adverse reaction,
clinicians must be ready to manage patients in this perioperative environment. The most life-threatening form of an
allergic reaction is anaphylaxis, however, the clinical presentation of anaphylaxis may represent different immune
and nonimmune responses.1 There is confusion in the literature about the term anaphylaxis, and multiple terms have
been reported to describe this reaction. In recent years, anaphylaxis has been redefined as a severe, life-threatening,
generalized or systemic hypersensitivity reaction, mainly mediated by immunoglobulin E (IgE) antibodies. 2 Further,
anaphylaxis represents a life-threatening allergic reaction that is rapid in onset and is associated with a significant
risk for mortality.3-6 The term anaphylactoid, often used to describe for non IgE-mediated reactions, is confusing
and probably should no longer be used. For the practicing clinician, anaphylaxis is best defined as a clinical
syndrome characterized by acute cardiopulmonary collapse following antigen (also called allergen) exposure. Much
of the confusion about anaphylaxis in the literature is because many older anesthetic agents (e.g., d-tubocurarine)
could directly degranulate mast cells. The incidence of immune-mediated anaphylaxis during anesthesia ranges from
1 in 10,000 to 1 in 20,000 based on mostly European reports.7 This presentation will define the spectrum of life
threatening anaphylactic and allergic reactions an anesthesiologist may encounter.
ADVERSE DRUG REACTIONS

Adverse drug reactions (ADRs) are common in hospitalized patients. Reports suggest the overall incidence of
serious ADRs was 6.7% and of fatal ADRs was 0.32% from data evaluating 39 prospective studies from US
hospitals.8,9 A recent study noted fatal adverse drug reactions account for nearly 3% of all deaths in the general
population, and noted hemorrhage is responsible for ~2/3 of the fatal adverse drug reactions and antithrombotic
agents are involved in more than half of the suspected fatal adverse drug reactions.10 Most serious predictable
adverse drug reactions are in fact not allergic mediated events and related to other causes that include the amount of
drug in the body (overdosage), unintended administration route, or known side effects (i.e., opioid related nausea).
However, some drugs have direct effects on inflammatory cells (i.e., heparin, histamine releasing agents).
Unfortunately, patients often refer to any adverse drug effects as being allergic in nature. Anesthetic drugs can also
produce hypotension via different mechanisms (e.g., propofol induced vasodilation) complicating the diagnosis of
perioperative adverse drug reactions. Allergic drug reactions are often differentiated from other adverse drugs
reactions because they are unpredictable and dose-independent (i.e., reactions due to latex allergy from latex
gloves).
ALLERGY AND ANAPHYLAXIS

Allergic reactions and anaphylaxis have the same pathophysiologic mechanisms, as both are immune mediated
and due to previous exposure to the antigen or a substance of similar structure. Richet and Portier first used the
word anaphylaxis (ana -against, prophylaxis - protection) to describe the marked shock and resulting death that
sometimes occurred in dogs immediately following a second challenge with a foreign antigen.11 The term “allergy”
was introduced in 1906, but is now often used to describe IgE-mediated allergic disease.6 The basis of acute allergic
reactions including anaphylaxis is the release of inflammatory mediators released by mast cells and basophils when
an allergen interacts with membrane-bound IgE.5,6
PATHOPHYSIOLOGY
Anaphylaxis and allergy result from the release of multiple inflammatory mediators including membrane-derived
lipids, cytokines, and chemokines.12 When the offending antigen and IgE bind on the surface of mast cells and
basophils, preformed storage granules are released that contain histamine and tryptase. 13 Other membrane derived
lipid mediators are released including leukotrienes, prostaglandins, and other factors. 13 These inflammatory
substances have a critical role in producing acute cardiopulmonary dysfunction, characterized by a symptom
complex of bronchospasm and upper airway edema in the respiratory system, vasodilation and increased capillary
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permeability in the cardiovascular system, and urticaria in the cutaneus system. 14-16 Cardiovascular collapse during
anaphylaxis results from the effects of multiple mediators on the heart and vasculature.17 The vasodilation seen
clinically can result from a spectrum of different mediators that interact with vascular endothelium and/or vascular
smooth muscle.1,18 Why some individuals develop severe cardiopulmonary dysfunction instead of minor cutaneous
reactions is unknown, but may relate to systemic compared to local release of inflammatory mediators. 19
Interestingly, the original description of anaphylaxis from sea anemone toxin represents an IgG-mediated response.
IgG mechanisms will be further discussed in protamine reactions that follow.
VASODILATORY SHOCK AND ANAPHYLAXIS

Vasodilatory shock occurs in anaphylaxis because of multiple mechanisms that include: excessive activation of
vasodilators that increase nitric oxide synthesis to activate soluble guanylate cyclase and increase cGMP, and
increased prostacyclin synthesis that activates soluble adenylate cyclase and produces cAMP. Collectively, this
produces vasodilation and shock.1,18 Nitric oxide and metabolic acidosis from shock also activate vascular
potassium channels to cause persistent vasodilatation despite catecholamine therapy. 1,18 Other mediators that are
released by non IgE mechanisms may also produce shock by different mechanisms (e.g., protamine induced acute
pulmonary vasoconstriction) and heparin will be discussed in non IgE mediated reactions. 1,18
RECOGNITION OF ANAPHYLAXIS
Because any parenterally administered agent can cause death from anaphylaxis, anesthesiologists must diagnose
and treat the acute cardiopulmonary changes that can occur. Studies from Europe suggest that perioperative drug
induced anaphylaxis may be increasing. The onset and severity of the reaction relate to the mediator's specific end
organ effects. Antigenic challenge in a sensitized individual usually produces immediate clinical manifestations, but
the onset may be delayed 2-20 minutes.14,20,21 The manifestations and course of anaphylaxis are variable, ranging
from minor clinical changes including urticaria to cardiopulmonary collapse including severe bronchospasm,
vasodilatory shock, and pulmonary vascular injury in certain cases, leading to death. The enigma of anaphylaxis is
the unpredictability of the event, the severity of the attack, and the lack of a prior allergic history. 14,20,21
NON-IgE MEDIATED REACTIONS

Other immunologic and nonimmunologic mechanisms release inflammatory mediators independent of IgE,
creating a clinical syndrome identical with anaphylaxis. Polymorphonuclear leukocyte (neutrophil) activation can
occur following complement activation by immunologic (antibody mediated: IgM, IgG-antigen activation) or non-
immunologic (heparin, protamine, endotoxin, cardiopulmonary bypass) pathways. 22,23,24 Complement fragments of
C3 and C5 (C3a and C5a) release histamine from mast cells and basophils, contract smooth muscle, and increase
capillary permeability. In addition, C5a binds receptors on neutrophils and platelets, causing chemotaxis,
aggregation, and activation.23,24 Aggregated leukocytes embolize to various organs producing microvascular
occlusion and liberation of inflammatory products including oxygen-free radicals, lysosomal enzymes and
arachidonic acid metabolites (i.e. prostaglandins and leukotrienes). IgG antibodies directed against antigenic
determinants or granulocyte surfaces can also activate leukocytes, and are thought to be responsible for the clinical
expressions of transfusion reactions, pulmonary vasoconstriction following protamine reactions, and transfusion
related acute lung injury (TRALI).25-27
HEPARIN, HIT, AND KININ GENERATION

Following heparin administration, IgG antibody formation is common. These antibodies bind heparin-PF4
complexes on the platelet surface to form immune complexes that activate platelets to promote thrombin formation
and thrombosis.22 This is the clinical manifestation of heparin induced thrombocytopenia (HIT). Nearly 7-50% of
heparin-treated patients form heparin-PF4 antibodies.22 However, recent reports about allergic reactions to heparin
from China were because of an oversulfated chondroitin sulfate contaminant that directly activated the kinin-
kallikrein pathway to produce bradykinin, a potent vasoactive mediator. In addition, this contaminant induced
generation of C3a and C5a.28 Angiotensin converting enzyme inhibitors also may potentially increase bradykinin
levels, and this is the mechanism of vasodilation, angioedema, and cough that can occur with their use. 1
ANGIOEDEMA
Angioedema is the rapid swelling of skin, mucosa, and submucosal tissues most commonly produced by allergic
reactions, but also by ACE inhibitors as noted above. 29 Oral, laryngeal, and pharyngeal swelling can occur with
acute airway compromise needing urgent airway control. There are also inherited qualitative and quantitative
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deficiencies of the complement C1 esterase inhibitor (C1-INH) called hereditary angioedema (HAE). Patients with
HAE also have recurrent episodes of gastrointestinal manifestations of the disease. Bradykinin plays a critical role
in angioedema as previously noted. Therapy of attacks includes symptomatic management and C1-INH from C1-
INH concentrates. Patients with this history and documented HAE need short-term prophylaxis before surgery or
dental treatment because tissue injury activates complement to increase C1-INH levels and also antifibrinolytics that
inhibit plasmin mediated activation. New therapies are also being studied in this life threatening disease. (16) A
C1-INH concentrate (Cinryze™) is currently FDA-approved indicated for routine prophylaxis against angioedema
attacks in adolescent and adult patients with Hereditary Angioedema (HAE). 29
NONIMMUNOLOGIC RELEASE OF HISTAMINE

Many diverse molecular structures administered during the perioperative period degranulate mast cells to release
histamine in a dose-dependent, nonimmunologic fashion.30-33 Intravenous administration of morphine, atracurium,
or vancomycin can release histamine, producing vasodilation and urticaria along the vein of administration.
Although the cardiovascular effects of histamine release can be treated effectively with intravascular volume
administration and/or catecholamines, the responses in different individuals may vary. 1 The newer neuromuscular
blocking agents (e.g., rocuronium and cisatracurium) lack histamine releasing effects but can produce direct
vasodilation and false-positive cutaneous responses that can confuse allergy testing and interpretation. 31,34 The
mechanisms involved in nonimmunologic histamine release represent degranulation of mast cells but not basophils
by cellular activation and stimulation of phospholipase activity in mast cells. 35
TREATMENT PLAN
Most anesthetic drugs and agents administered perioperatively have been reported to produce anaphylaxis. 1
Therefore, a plan for treating anaphylactic reactions must be established before the event.1 Airway maintenance,
100% oxygen administration, intravascular volume expansion, and epinephrine are essential to treat the hypotension
and hypoxia that results from vasodilation, increased capillary permeability, and bronchospasm. 1 A protocol for
management of anaphylaxis during general anesthesia should be considered by all clinicians. The standard
considerations of cardiopulmonary resuscitation with vasoactive therapy should be followed. Therapy must be
titrated to needed effects with careful monitoring. The route of administration of epinephrine and the dose depends
on the patient's condition. Rapid and timely intervention with common sense must be used to treat anaphylaxis
effectively. Management considerations are as follows:
Initial Therapy: Although it may not be possible to stop the administration of antigen, limiting antigen
administration may prevent further mast cell and basophil activation.
Maintain Airway and Administer 100% Oxygen: Profound ventilation–perfusion abnormalities producing
hypoxemia can occur with anaphylactic reactions. Administer 100% oxygen with ventilatory support as needed
including treating bronchospasms if it occurs.
Discontinue Anesthetic Drugs: Inhalational anesthetic drugs are not the bronchodilators of choice in treating
bronchospasm after anaphylaxis, especially during hypotension. These drugs interfere with the body’s compensatory
response to cardiovascular collapse, and direct acting bronchodilators should be administered if needed.
Volume Expansion: Hypovolemia rapidly follows during anaphylactic shock with up to 40% loss of intravascular
fluid into the interstitial space during reactions. Therefore, volume expansion is important along with epinephrine in
correcting the acute hypotension. Initially, 25 to 50 mL/kg of crystalloid or colloid solution, should be administered,
with an additional 25 to 50 mL/kg may be necessary if hypotension persists.
Administer Epinephrine: Epinephrine is the drug of choice when resuscitating patients during anaphylactic shock.
The α-adrenergic effects vasoconstrict to reverse hypotension; β2 receptor stimulation bronchodilates and inhibits
mediator release. The route of epinephrine administration and the dose depend on the patient’s condition. Rapid and
timely intervention is important when treating anaphylaxis. Of note is that patients under general anesthesia may
have altered sympathoadrenergic responses to acute anaphylactic shock, whereas the patient under spinal or epidural
anesthesia may be partially sympathectomized and may need even larger doses of catecholamines. In hypotensive
patients, 5- to 10-μg boluses of epinephrine should be administered intravenously and incrementally titrated to
restore blood pressure. (This dose of epinephrine can be obtained with 0.05 to 0.1 mL of a 1:10,000 dilution
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[100 μg/mL]. Additional volume and incrementally increased doses of epinephrine should be administered until
hypotension is corrected. Although infusion is an ideal method of administering epinephrine, it is usually impossible
to infuse the drug through peripheral intravenous access lines during acute volume resuscitation. With
cardiovascular collapse, Advanced Cardiopulmonary Life Support (ACLS) protocols should be following with full
cardiopulmonary resuscitative support. Epinephrine should not be administered intravenously to patients with
normal blood pressures.
Secondary Treatment
Antihistamines. Because H1 receptors mediate many adverse effects of histamine, the intravenous administration of
0.5 to 1 mg/kg of an H1 antagonist such as diphenhydramine may be useful in treating acute anaphylaxis.
Antihistamines do not inhibit anaphylactic reactions or histamine release, but compete with histamine at receptor
sites. H1 antagonists are indicated in all forms of anaphylaxis, but should be given slowly to prevent precipitous
hypotension in potentially hypovolemic patients.1 The indications for administering an H2 antagonist once
anaphylaxis has occurred remain unclear.
Catecholamines. Epinephrine infusions may be useful in patients with persistent hypotension or bronchospasm
after initial resuscitation.1 Epinephrine infusions should be started at 0.05 to 0.1 μg/kg/min (5 to 10 μg/min) and
titrated to correct hypotension. Norepinephrine infusions may be needed in patients with refractory hypotension due
to decreased systemic vascular resistance. It may be started at 0.05 to 0.1 μg/kg/min (5 to 10 μg/min) and adjusted to
correct hypotension51.
Bronchodilators. Inhaled ß-adrenergic agents including inhaled albuterol or terbutaline if bronchospasm is a major
feature54. Inhaled ipratropium may be especially useful for treatment of bronchospasm in patients receiving ß-
adrenergic blockers54. Special adaptors allow administration of bronchodilators through the endotracheal tube.
Corticosteroids. Corticosteroids have multiple antiinflammatory effects mediated by different mechanisms,

including altering the activation and migration of other inflammatory cells (i.e., PMNs) after an acute reaction. They
should be administered as adjuncts to resuscitative therapy when refractory bronchospasm or refractory shock
occurs. The exact corticosteroid dose and choice of methylprednisone versus hydrocortisone are unclear, starting
doses include 0.25 to 1 g of hydrocortisone, or equivalent doses of methylprednisone. Corticosteroids may also be
important in attenuating the late-phase reactions reported to occur 12 to 24 hours after anaphylaxis.
Airway Evaluation. The airway should be evaluated before extubation of the trachea because of the potential for
laryngeal edema. Persistent facial edema suggests airway edema. The trachea of these patients should remain
intubated until the edema subsides. Developing a significant air leak after endotracheal tube cuff deflation and
before extubation of the trachea is useful in assessing airway patency.
Refractory Hypotension. Reactions may be protracted with persistent hypotension, pulmonary hypertension and
right ventricular dysfunction, that persist 5 to 32 hours despite resuscitation. During general anesthesia patients may
have altered sympathoadrenergic responses to acute anaphylactic shock. Additional hemodynamic monitoring may
be needed when hypotension persists despite therapeutic interventions as listed. Following anaphylaxis, patients
should be carefully monitored for 24 hours as they may develop recurrence of manifestations following successful
treatment and covered with corticosteroids for the acute event.1
After the initial resuscitation, norepinephrine is also an effective agent that should be considered for treating
shock and dopamine should be avoided.37 Based on the efficacy of vasopressin in reversing vasodilatory shock, it
should also be considered in therapy of anaphylactic shock not responding to therapy. 1,18,38 There are increasing
laboratory and clinical reports supporting the use of vasopressin in anaphylactic shock.39,40 When available, the use
of transesophageal echocardiography in an intubated patient, or potentially transthoracic echocardiography can be
useful in diagnosing the cause of acute or persistent cardiovascular dysfunction.1 For the patient with undetectable
blood pressure or following a cardiac arrest, full ACLS protocol and resuscitation must be utilized.
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PRETREATMENT FOR ALLERGIC REACTIONS

Hypersensitivity reactions are more likely to occur in patients with a history of allergy, atopy, or asthma.
However, this does not make it mandatory to pretreat these patients with antihistamines and/or corticosteroid
because there is no data in the literature to suggest that pretreatment is effective for true anaphylactic reactions.
Most of the literature on pretreatment is from studies evaluating patients with previous radiocontrast media reactions
that are non-immunologic mechanisms. Although attempts to pretreat patients for anaphylaxis to latex have been
used, there is no data to support this as an effective preventative measure and removal of latex from the
perioperative environment is important. In fact, pretreatment may lull physicians into a false sense of security.
Further, even when large doses of corticosteroids have been administered, life threatening anaphylactic reactions
have occurred.41 Allergists have used immunospecific pretreatment therapies, but these are not practical for
perioperative use.
MANAGEMENT OF THE ALLERGIC PATIENT

Patients presenting with an allergic history need to be carefully evaluated. Patients may report allergy when the
reaction was a predictable adverse drug reaction. However, for practical and medico-legal purposes, that class of
drug should be avoided if possible when the history is consistent with an allergic reaction, and preservative free
alternatives should be chosen. The problem occurs whenever multiple drugs are simultaneously administered or
when patients present with muscle relaxant reactions because of the risk of cross reactivity to the biquarternary
ammonium ions in the molecule. In this situation, skin testing may be required to see what the patient is can safely
be administered.
EPIDEMIOLOGY OF ANAPHYLAXIS: AGENTS IMPLICATED

Although any molecule can produce anaphylaxis, the drugs typically associated with producing perioperative
anaphylaxis include antibiotics, blood products, neuromuscular blocking drugs (NMBDs), polypeptides (aprotinin,
latex, and protamine), and intravascular volume expanders. 1 During surgery, the risk of anaphylaxis is reported to
be between 1:3500 and 1:20,000, with a mortality rate of 4% and an additional 2% surviving with severe brain
damage.1,7 More recent data suggest the incidence of perioperative anaphylaxis is 1 in 10,000–20,000. 7 Patients
undergoing major surgery are an increased risk group, because of the multiple blood products, polypeptides, and
potential for impaired cardiovascular function. Mertes reported an epidemiological study from 99-01 of 789
reactions diagnosed by clinical history, skin tests, and/or specific IgE in 518 cases (66%) and nonimmune reactions
in 271 cases (34%).42 The most common causes were NMBAs (58.2%), latex (16.7%), and antibiotics (15.1%), of
which rocuronium (43%) and succinylcholine (22.6%) were the most common NMBAs reported. The positive
predictive value of tryptase for the diagnosis of anaphylaxis in their study was 92.6%; the negative predictive value
was 54.3%.42 The agents most often implicated will be discussed.
LATEX ALLERGY
Latex represents an environmental agent often associated as a cause of perioperative anaphylaxis. Health care
workers, children with spina bifida and urogenital abnormalities, and certain food allergies have also been
recognized as individuals at increased risk for anaphylaxis to latex. 43-45 Brown reported a 24% incidence of irritant
or contact dermatitis and a 12.5% incidence of latex-specific IgE positivity in Anesthesiologists.46 Of this group,
10% were clinically asymptomatic although IgE positive. A history of atopy was also a significant risk factor for
latex sensitization. Brown suggests these individuals are in their early stages of sensitization and perhaps, by
avoiding latex exposure, their progression to symptomatic disease can be prevented. 46
Patients allergic to both tropical fruits (e.g., bananas, avocados, and kiwis) and stone fruits have also been
reported to have antibodies that cross-react with latex.45,47 Multiple attempts have been made over the years to
reduce latex exposure to both healthcare workers and patients. If latex allergy occurs, then strict avoidance of latex
from gloves and other sources needs to be considered, following recommendations as reported.45 Latex however is
such a widespread environmental antigen, and patients often have concerns regarding this potential exposure.
NEUROMUSCULAR BLOCKING AGENTS

Neuromuscular blocking agents (NMBAs) have several unique molecular features that make them potential
allergens. All neuromuscular blocking drugs are functionally divalent and are thus capable of cross-linking cell-
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surface IgE and causing mediator release from mast cells and basophils without binding or haptenizing to larger
carrier molecules. 1 NMBAs have also been implicated in epidemiological studies of anesthetic drug-induced
anaphylaxis. Epidemiological data from France suggest that NMBAs are responsible for 62–81% of reactions,
depending on the time period evaluated.42,48 Rocuronium is the NMBA most reported from France. We and others
have reported previously that aminosteroidal compounds as well as benzylisoquinoline-derived agents produce
positive weal and flare responses when injected intradermally. 31,49,50 Estimates of anaphylactic reactions in
anesthesia vary, but data suggests that false-positive skin tests may overestimate the incidence of rocuronium-
induced anaphylactic reactions. 31,49,50 The differences noted in the incidence of reactions may reflect the potential
for false-positive weal and flare responses. 31,49,50 NMBAs can also produce direct vasodilation by multiple
mechanisms, which include calcium channel blockade. The false-positive skin tests that were reported to be biopsy-
negative for mast cell degranulation clearly confound interpreting skin tests in patients who have had life-
threatening cardiopulmonary collapse. Dilute solutions of NMBAs need to be used when skin testing for potential
allergic reactions to these agents. However, the exact concentration that should be used is unclear. Since skin-testing
procedures are important in evaluating potential drug allergies, the threshold for direct vasodilating and false-
positive effects must be determined whenever subjects are skin-tested for a particular drug.
POLYPEPTIDES AND BLOOD PRODUCTS

Polypeptides are larger molecular weight molecules that pose greater potential to be antigenic, and include
aprotinin, latex, and protamine. Diabetic patients receiving protamine containing insulin as neutral protamine
Hagedorn (NPH) or protamine insulin have a 10-30 fold increased risk for anaphylactic reactions to protamine when
used for heparin reversal, with a risk of 0.6-2% in this patient population.41,51 Because protamine is often given with
blood products, protamine is often implicated as the causative agent in adverse reactions, especially in cardiac
surgical patients. Platelet and other allogeneic blood transfusions can produce a series of adverse reactions by
multiple mechanisms, and blood products have a greater potential for allergic reactions including TRALI. 25
Although antigen avoidance is one of the most important considerations in preventing anaphylaxis, this is not always
possible, especially with certain agents where alternatives are not available. Protamine is an important example of
where alternatives are under investigation, but not currently available.
EVALUATING THE PATIENT FOLLOWING ANAPHYLAXIS

A detailed history is one of the most important considerations to evaluate a patient following anaphylaxis,
determining what agents were administered, and what the temporal sequence was.52 Also, after resuscitation collect
a red top tube (serum) for mast cell tryptase, preferably within 1-2 hours of the reaction, and then repeat 24 hours
later. Serum can also be collected postmortem, which may be important for you medico-legally. Most hospital
laboratories will need to send this test to a reference laboratory. If tryptase is positive, sending the patient for an
allergy consultation may be useful if the temporal sequence is confusing, and the agent responsible needs further
investigation. Often, a positive mast cell tryptase usually represents an IgE mediated reaction (i.e., anaphylaxis) but
vancomycin and other histamine releasers can also increase tryptase. 35 Negative mast cell tryptase tests are rarely
associated with positive skin tests and antibody tests. IgG reactions due to protamine, or blood products are unlikely
to increase tryptase. Few laboratory based tests are available for determining immunologic testing, so skin testing is
required if better differentiation of the agent responsible is required.
CONCLUSIONS
Anaphylaxis represents an important potential problem and an important cause of life threatening events.
Clinicians must be able to recognize and treat these life threatening events if they occur. Clinicians should
remember that test doses may produce anaphylaxis. There are few in vitro tests available to assess patients at high
risk for reexposure anaphylaxis. Anaphylactic reactions represent a continuing challenge, but rapid diagnosis and
treatment are important in preventing adverse clinical outcomes.
SUGGESTED WEB SITES: AnaphylaxisWeb.com, FDA.gov
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N, Zhao G, Galcheva-Gargova Z, Al-Hakim A, Bailey GS, Fraser B, Roy S, Rogers-Cotrone T, Buhse L, Whary M,
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mechanism for hypotension in man. Anesthesiology 1987; 67: 122-5
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cisatracurium in humans. Br J Anaesth 2000; 85: 844-9
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responses to opioids in humans. Anesthesiology 1989; 70: 756-60
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1991; 34: 302-8
34. Levy JH, Davis GK, Duggan J, Szlam F: Determination of the hemodynamics and histamine release of
rocuronium (Org 9426) when administered in increased doses under N2O/O2-sufentanil anesthesia. Anesth Analg
1994; 78: 318-21
35. Veien M, Szlam F, Holden JT, Yamaguchi K, Denson DD, Levy JH: Mechanisms of nonimmunological
histamine and tryptase release from human cutaneous mast cells. Anesthesiology 2000; 92: 1074-81
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claims analysis of predisposing factors. Anesthesiology 1988; 68: 5-11
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38. Tsuda A, Tanaka KA, Huraux C, Szlam F, Sato N, Yamaguchi K, Levy JH: The in vitro reversal of
histamine-induced vasodilation in the human internal mammary artery. Anesth Analg 2001; 93: 1453-9
39. Dewachter P, Jouan-Hureaux V, Franck P, Menu P, de Talance N, Zannad F, Laxenaire MC, Longrois D,
Mertes PM: Anaphylactic shock: a form of distributive shock without inhibition of oxygen consumption.
40. Dewachter P, Mouton-Faivre C, Emala CW: Anaphylaxis and anesthesia: controversies and new insights.
41. Levy JH, Zaidan JR, Faraj B: Prospective evaluation of risk of protamine reactions in patients with NPH
insulin-dependent diabetes. Anesth Analg 1986; 65: 739-42
42. Mertes PM, Laxenaire MC, Alla F: Anaphylactic and anaphylactoid reactions occurring during anesthesia
in France in 1999-2000. Anesthesiology 2003; 99: 536-45
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44. Peixinho C, Tavares-Ratado P, Tomas MR, Taborda-Barata L, Tomaz CT: Latex allergy: new insights to
explain different sensitization profiles in different risk groups. Br J Dermatol 2008; 159: 132-6
45. Cullinan P, Brown R, Field A, Hourihane J, Jones M, Kekwick R, Rycroft R, Stenz R, Williams S,
Woodhouse C: Latex allergy. A position paper of the British Society of Allergy and Clinical Immunology. Clin Exp
Allergy 2003; 33: 1484-99
46. Brown RH, Schauble JF, Hamilton RG: Prevalence of latex allergy among anesthesiologists: identification
of sensitized but asymptomatic individuals. Anesthesiology 1998; 89: 292-9
47. Blanco C, Carrillo T, Castillo R, Quiralte J, Cuevas M: Latex allergy: clinical features and cross-reactivity
with fruits. Ann Allergy 1994; 73: 309-14
48. Moneret-Vautrin DA, Morisset M, Flabbee J, Beaudouin E, Kanny G: Epidemiology of life-threatening and
lethal anaphylaxis: a review. Allergy 2005; 60: 443-51
49. Levy JH: Anaphylactic reactions to neuromuscular blocking drugs: are we making the correct diagnosis?
Anesth Analg 2004; 98: 881-2
50. Dhonneur G, Combes X, Chassard D, Merle JC: Skin sensitivity to rocuronium and vecuronium: a
randomized controlled prick-testing study in healthy volunteers. Anesth Analg 2004; 98: 986-9, table of contents
51. Levy JH, Schwieger IM, Zaidan JR, Faraj BA, Weintraub WS: Evaluation of patients at risk for protamine
reactions. J Thorac Cardiovasc Surg 1989; 98: 200-4
52. Mertes PM, Laxenaire MC: Allergic reactions occurring during anaesthesia. Eur J Anaesthesiol 2002; 19:
240-62
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Pain Medicine 2016: Emerging Issues in Policy, Coverage and Payment
Kevin E. Vorenkamp, M.D. Seattle, WA
Objectives:
1. Identify recent and upcoming policy changes and how they may impact interventional pain physicians;
2. Review current and proposed reporting measures with H.R.2 (MACRA) implementation;
3. Appraise changes in pain medicine coverage by both Medicare and other payers.
Overview of transition to MACRA

President Obama signed the Medicare Access and CHIP Reauthorization Act (MACRA) on April 16, 2015, thus
replacing the Sustainable Growth Rate (SGR). In doing so, Congress sunsets the Physician Quality Reporting
System (PQRS), Value-Based Payment Modifier (VM) and the Electronic Health Record (EHR) Incentive Program
after 2018. Although many physicians were initially excited about the avoidance of a 21% cut in Medicare
reimbursement as dictated by the SGR, the concerns regarding MACRA are becoming increasingly apparent.
Under MACRA, ASA members and other health care professionals will receive future Medicare payments by
participating (dependent upon patient population and volume) in one of two broad categories: payments through the
Merit-based Incentive Payment Systems (MIPS) or through an Alternative Payment Model (APM). The payment
system will begin in 2019 and be based in many instances upon 2017 performance. CMS released the MACRA
Proposed Rule on April 27, 2016 and has allowed comments to be submitted through June 27, 2016. ASA expects
the final rule will be posted in late 2016.
On April 27, 2016, the Department of Health and Human Services issued a Notice Executive of Proposed
Rulemaking to implement key provisions of the Medicare Access and Summary CHIP Reauthorization Act of 2015
(MACRA), bipartisan legislation that replaced the flawed Sustainable Growth Rate formula with a new approach to
paying clinicians for the value and quality of care they provide. The proposed rule would implement these changes
through the unified framework called the “Quality Payment Program,” which includes two paths: the Merit-Based
Incentive Payment System (MIPS) and the Advanced Alternative Payment Models (APMs). Like the “no child left
behind” approach to education, the goal of these systems appears to be multifold: (1) to achieve cost containment,
(2) to reward those practices that demonstrate high performance and (3) to reduce payment to those practices that
fail to adhere to standards of patient care. These last changes are incremental with the maximum adjustment factor
(positive or negative) at 4% for 2019 and rising by 1-2% annually until achieving 9% in 2022 and beyond. Of note,
these adjustments target a budget neutral endpoint. Therefore, if a lower threshold of achievement is targeted then
there will be a high percentage of practices achieving this target resulting in minimal positive adjustment with
significant penalty for those practices that do not reach this threshold. Contrarily, if a higher threshold is targeted
then higher achieving practices will see a more positive adjustment while the higher percentage of non-threshold
achieving practices may see less negative adjustment. It is unclear from the legislation what threshold will be
utilized.
Alternative payment models (APMs) are new approaches to medical care through medical care that incentivize
quality and value. MACRA provides bonus payments for participation in eligible APMs. In January 2015, Secretary
of Health and Human Services (HHS) Sylvia Burwell announced a timeline and measurable goals to shift the
Medicare program away from traditional fee-for-service payment structure toward a more outcome-based system
based on APMs tied to quality Currently, more than 20 percent of Medicare fee-for-service payments flow through
APMs, putting the Administration’s goals of 30 percent by the end of 2016 and 50 percent by 2018 within
reach. This is the first time in the history of the program that explicit goals for alternative payment models and
value-based payments have been set for Medicare. Through the CMS Innovation Center’s Transforming Clinical
Practice Initiative, CMS will invest up to $800 million in providing hands-on support to 150,000 physicians and
other clinicians for developing the skills and tools needed to improve care delivery and transition to APMs. Three
bundled payment models, Bundled Payments for Care Improvement (BPCI), Comprehensive Care for Joint
Replacement (CJR) and the Oncology Care Model (OCM), were developed in the past few years by the Innovation
Center.
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The CJR bundled payment program began April 1, 2016, and has over 750 hospitals that are mandated to participate
for five years. The CJR episode of care begins three days prior to admission to a participant hospital of a beneficiary
who is ultimately discharged under MS-DRG 469 (major joint replacement or reattachment of lower extremity with
major complications or comorbidities) or 470 (major joint replacement or reattachment of lower extremity without
major complications or comorbidities) and ends 90 days post-discharge in order to cover the complete period of
recovery for beneficiaries. These CJR mandated hospitals will be held accountable for both total Medicare spend
and for quality of care of these patients.
Merit-Based Incentive Payment System (MIPS)

Most eligible professionals will use the MIPS payment system, consisting of 4 parts: quality of care, resource use,
meaningful use of an HER (now called “Advancing Care Information”), and clinical practice improvement activities
(CPIA). Each of these components will be weighted and used to calculate a composite performance score (CPS) on
a scale from 0-100, from which a CMS will calculate and compare the composite scores for all EPs (see table).
Merit-Based Incentive Pay % Weight % Weight % Weight

System (MIPS) (2019) (2020) (2021)
Quality of Care 50 45 30
Resource Use 10 15 30
Advanced Care 25 25 25
Information
Clinical Practice 15 15 15
Improvement Activities
(CPIA)
Reporting Measures for Pain Medicine Physicians

It has been challenging to date identifying and defining measures pertinent to the MIPS reporting for pain medicine
physicians. At the time of this writing, multiple pain societies including ASA members have met to perform this task
and propose other reportable measures in all 4 categories. Comments on the proposed rule are due by June 27, 2016.
Updates will be provided at the time of presentation at the ASA Annual Meeting, although the CMS final rule is not
expected until later in the year.
Local Coverage Determinations (LCDs)

With implementation of ICD-10 on October 1, 2015, all policies required revision. With regards to spinal injection
procedures, many recent revisions incorporated the recommendations of the MPW. A prior officer of inspector
general (OIG) report identified great variation in LCD guidelines between Medicare Administrative Contractors
(MACs) and recommended more integrative policies. Although this seems in line with the efforts of the Noridian led
MPW initiative, implementation of new LCDs has not always in agreement with these guidelines. Several revised
LCDs were implemented in 2016 and will be reviewed in greater detail.
State Coverage issues

Unfortunately the Pacific Northwest again leads the charge in terms of (negative) coverage issues related to
interventional pain medicine procedures. In 2015, the Director of the Health Care), announced her desire to have the
Health Technology Clinical Committee (HTCC) re-review coverage for spinal injection procedures on the preface of
emerging issues related to the safety and efficacy of these procedures. The multisociety pain workgroup (MPW),
consisting of 15 spine and pain medicine societies, including ASA, commented at multiple stages throughout the
process. Nevertheless, the HTCC pursued re-evaluation of these codes and Spectrum was again commissioned by
WA State for this report. As background, Spectrum is a for-profit company which has received payment from WA
State of $1,006,427 and has been involved with 11 prior reviews. At the March 18, 2016 meeting, coverage was
unchanged from the 2011 decision with respect to epidural steroid injections, facet joint interventions and sacroiliac
joint injections. There was significant support from other pain societies, most notably including the spinal
intervention society (SIS) and the North American Spine Society (NASS), in addition to the American Society of
Regional Anesthesia and Pain Medicine (ASRA) and the North American Neuromodulation Society (NANS).
Washington state physicians led an effort of engagement with nearly 100 pain medicine physicians and patients
appearing at the meeting with several providing supportive comment. Maintaining access to spinal injection
therapies can provide patients with the significant benefits of pain relief and improved function and quality of life,
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reducing their need for surgery or opioids. These comments also noted that maintaining access to spinal injection
therapies may prevent patients from seeking surgery or using starting opioids or help them taper off opioids, which
is particularly important in light of the national opioid abuse epidemic. Although the overall result of the hearing
was positive, it provided a glimpse of the desperate nature of state payers to account for payment targeted at a major
cause of cost and worker disability in many states.
Despite the overall positive ruling in WA State, this served as a precursor to the negative consequences that occurred
in the adjacent state of Oregon where a negative outcome ensued. Despite a late effort from several societies, and
another letter from the MPW, the Oregon Health Authority (OHA) did not overturn its decision to eliminate
coverage of epidural steroid injections effective July 1.
Coding changes
Current Procedural Terminology (CPT®) code changes for 2016 relate primarily to the addition of new codes
related to paravertebral injections, modifications of existing neurostimulation analysis and reprogramming codes
(95970-95972) and parenthetical language related to the paravertebral (facet) joint destruction (radiofrequency
ablation) codes (64633-64636). Although primarily related to regional anesthesia and acute pain medicine, the
addition of codes 64461-64463 relate to the paravertebral space. The language here is somewhat confusing as the
traditional facet joint/medial branch injection and destruction codes, 64490-64495 and 64633-64636, although rarely
referred to as paravertebral injections do share similar terminology. Although these are distinct structures, the
language in CPT may be confusing to some practitioners and coders of these procedures. More relevant to pain
medicine practitioners is the language change in the parentheticals related to facet joint nerve destruction. In
addition to again stating that the procedure should be coded per joint rather than per facet joint nerve, the new
terminology also specifies that denervation (radiofrequency ablation) must occur at a temperature at 80C or greater
to meet criteria: “Do not report 64633, 64634, 64635, 64636 for non-thermal facet joint denervation including
chemical, low-grade thermal energy (<80 degrees Celsius), or any form of pulsed radiofrequency. To appropriately
report any of these modalities, use 64999.”
Valuation for the CPT® changes for 2017 will appear in the CMS draft final rule in the summer of 2016 and will be
presented in more detail at the ASA annual meeting. Typically, the final rule is not published until early November.
These changes are slated to take effect January 1, 2017.
Conclusions
Healthcare reform is continually evolving with the goals of increasing value and decreasing costs. Reporting the
required quality measures under MACRA; however, may prove challenging and the measures relevant to pain
medicine physicians are not yet clearly identified. With implementation of required reporting imminent, stay active
so that your practice is not the one “left behind.”
Suggested Readings:
 https://www.federalregister.gov/articles/2016/05/09/2016-10032/medicare-program-merit-based-incentive-
payment-system-mips-and-alternative-payment-model-apm
 https://www.cms.gov/Medicare/Quality-Initiatives-Patient-Assessment-Instruments/Value-Based-
Programs/MACRA-MIPS-and-APMs/MACRA-MIPS-and-APMs.html
 CPT® 2016 Professional Edition. American Medical Association.
 OR State HERC: http://www.oregon.gov/oha/herc/FactSheet/Back-policy-changes-fact-sheet.pdf
 WA State HCA: http://www.hca.wa.gov/hta/Pages/spinal_injections-rr.aspx
 Noridian LCD on Spinal cord stimulation: https://www.cms.gov/medicare-coverage-database/details/lcd-
details.aspx?LCDId=36203&ContrId=345
 ASA Timely topics: http://asahq.org/quality-and-practice-management/practice-management/timely-topics-
in-payment-and-practice-management
o MACRA Implementation: Pulse Checks along the Way (May 2016)
o Is Your ICD-10 Transition Still on Track? (May 2016)
o Are You Reporting Paravertebral Facet Joint Nerve Destruction Correctly? (December 2015)
o Why Did the Medicare Conversion Factor Go Down for 2016 When MACRA Said It Would Go
Up by 0.5%? (November 2015)
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Medical Center Adoption of a Production System: What Does it Mean

for Your Department?
Julia E. Pollock Seattle, WA
Objectives
1. Define potential benefits and challenges in a production system implementation
2. Utilize organizational implementation to realize department goals
Ted Gachowski 1 was a retired engineer diagnosed with lymphoma in 1999. He began undergoing weekly six-hour
chemotherapy infusions at Virginia Mason in 2001. Ted would arrive at the Medical Center at 8:00 am, he would
check-in at the front desk and then go to the laboratory to have his blood drawn. He would then walk to the
oncology department and wait until his lab results were available to meet with his Oncologist and review his lab
results. His oncologist would then write orders for his chemotherapy. He would then walk to the infusion Center.
Ted may also need to see additional providers in surgery or radiation oncology before receiving his chemotherapy in
the infusion center. By the time Ted was placed in a room in the infusion center and his chemotherapy began it was
12:00. At the conclusion of his infusion Ted walked to the exit. Including wait times, Ted would have been at the
Medical Center for 10 hours 25 minutes and traveled over 748 feet. If Ted needed to see the surgeon or radiation
oncologist he would have visited 8 different flours in 3 separate buildings.
Why is this Important? “Some of us are spending our last moments with each other within the walls of VMMC.
Please always remember that you are treating people, not diseases. Please don’t add to our frustration, worry and
grief by asking us to waste those last few precious moments we have with our loved ones waiting unnecessarily in
lines or waiting rooms for appointments.” Wife of a VM Patient
Introduction
In 1999 and 2001 the Institute of Medicine of the National Academies published two landmark reports To Err is
Human2 and Crossing the Quality Chasm3. These reports essentially described how American health care, thought
to be the best in the world, wasted literally billions of dollars and provided care that “too frequently harms and
routinely fails to deliver.” At approximately the same time Virginia Mason Medical Center, a 336 bed tertiary care
facility in Seattle, WA begin to lose money for the first time in its 80 year history. Questions about economic
vitality and quality and safety led leaders at Virginia-Mason to look for a management framework to help drive an
organization change to improve quality and eliminate waste throughout the Medical Center. Despite the availability
of different types of management systems no system was in widespread use in any health care delivery system at the
time. Virginia Mason decided on something call the Toyota Production System 4 which was being used locally by
The Boeing Company. VMMC decided on this system because it emphasized moving quickly to eliminate waste.
The important concept being that by eliminating waste you both improve quality and safety and reduce costs.
Alignment
Virginia Mason has been a very “patient centered” medical center. The reality in 2001 was that Virginia Mason was
that physicians were more important than patients. VM was physician led, physician centered and most of the day to
day operations (clinic schedules, OR schedules, time away, meetings) revolved around the physicians. According to
Gary Kaplan MD, CEO “We want VM to be a great place for doctors and we always want to have physicians in
leadership roles, but in order to remind ourselves that it is about the patients first, we needed a strategic plan and an
agreement with the physicians.” Thus through a long process of collaborating and meeting with physicians the VM
strategic plan and physician compact were developed.
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The use of the strategic plan and the physician compact helped ensure that everyone in the medical center was
aligned with the same commitment to quality, safety and the elimination of waste, and that the entire team believed
that doing what was best for the patient was the highest priority. These were huge cultural changes within the
organization and these changes did not come easily or without costs.5
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Promoting Change
Promoting cultural change is very difficult work. Cultural change will not be successful unless the physician leaders
and executives at the top of the organization are committed to the process. Kotter 6 describes eight steps for
successful change. Many of the necessary ingredients for driving an important change at VMMC were brought about
by external forces (increasing market competition, declining reimbursement models, patient advocacy movements)
and organizational leaders truly believed that without significant change our future as an independent medical center
was in jeopardy.
Kotter’s Eight Steps for Change

1. Increase Urgency
2. Build the Guiding Team
3. Get the Vision Right
4. Communicate for Buy-In
5. Empower Action
6. Create Short-Term Wins
7. Don’t Let up
8. Make the Change Stick
Physician Acceptance
One of the greatest selling points of production system management is that it is very data driven. Using well
described tools like Value Stream Mapping, Standard Operations, Timings, Mistake Proofing and Flow Mapping, it
becomes very easy to see where opportunities for improvement can be found. Physicians are very data driven and
accept data driven tools including Standard Work.7 Although physicians do value autonomy, they also recognize
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the value of Evidence Based Medicine. Henry Ford described standard work in 1926 as “The Best that is known
today but which is to be Improved Tomorrow.” This also how we describe evidence based medicine.
Department Implementation
There are many ways that anesthesia departments can benefit from process improvement work. For example,
pictured above is the Virginia Mason Medical Center original Department of Anesthesia standard cart set-up with a
shadow board. This set up guaranteed that any provider who came into the room at any time (breaks, relief, to assist
with an emergency) immediately knew where the important items (airway tools, vasoactive drugs, etc.) were located
because they are always in the same place in every location. There have been several subsequent version of the
shadow board as departmental and regulatory requirements have evolved.
Production system work is also extremely helpful in analysis of operations throughout entire departments. In order
to run your business, you have to really know your business. Begin your departmental improvement work by
understanding your department demand. Then select an improvement metric that reflects your departmental
objectives (orthopedic surgery length of stay, time patients spend in the recovery room, out of operating room block
utilization) or a metric that reflects the health of your departmental processes (on-time starts, case cancellation,
turnover times, block success). Then identify your supply (daily staffing) and develop and discuss your standard
work for your selected improvement. For any type of project be sure to measure and celebrate your success.
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Summary
Organization production system implementation can benefit your department—it is really about understanding your
work. Your department can utilize the principles because they are data collection and waste reduction. Using the
tools of production management, the Virginia Mason team created a better pathway for our original patient Ted.
Today Ted enters the Medical Center at 8:00 checks in at the front desk and walks to the infusion center. Then he
walks directly to the treatment room where lab draws and physician visits are conducted. The satellite pharmacy is
now located in the infusion center. Ted’s visit has been reduced from 12 hours to 7 hours and 45 minutes and the
distance walked is reduced from 748 feet to 181 feet. This is just one example of how production system
implementation can improve the patient experience. If your institution is on an improvement journey consider
yourself lucky. You can utilize the tools to improve the patient experience and make patient care less frustrating for
the entire anesthesia team.
References
1. Mr. Gachowski’s name, image and story used with permission. Information on file at the VM Floyd and
Delores Jones Cancer Center
2. Institute of Medicine. To Err is Human: Building a Safer Health System. National Academy Press 1999
3. Institute of Medicine. Crossing the Quality Chasm: A New Health Care System for the 21st Century.
National Academy Press 2001.
4. Ohno, T. Toyota Production System: Beyond Large-Scale Production. Productivity Press, 1988
5. Kenny C. Transforming Health Care: Virginia Mason’s Pursuit of the Perfect Patient Experience. Taylor
& Francis, 2011
6. Kotter JP. Leading Change: Why Transformation Efforts Fail. Harvard Business Review, March 59-67,
1995.
7. Institute for Healthcare Improvement. Going Lean in Health Care. Innovation Series 2005.
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Utility of Perioperative Transesophageal Echocardiography in Non-Cardiac
Surgery
Stanton K. Shernan, M.D. Boston / Massachusetts
Introduction
Since intraoperative echocardiography was introduced into clinical practice in the 1980s, its popularity has
steadily increased. Although not as well established as it is for cardiac surgery, the benefit of perioperative
echocardiography for noncardiac surgery is becoming increasingly more appreciated. 1-3 Selective or emergent
intraoperative transesophageal echocardiography (TEE) has been reported as beneficial in 40% to 80% of patients
respectively.4,5 In more than one-third of patients, intraoperative TEE may be associated with a change in medical
therapy including treatment of myocardial ischemia, valve disease, and right or left ventricle failure. 4,5 Furthermore,
in approximately 25% of patients, intraoperative TEE has been associated with a change in surgical procedure. 4 The
role of TEE in the perioperative management of noncardiac surgical patients is increasingly being appreciated, as
exemplified by the addition of recommendations for intraoperative echocardiography in the most recent American
College of Cardiology/American Heart Association/American Society of Echocardiography guidelines for clinical
application of echocardiography.6 Based upon findings in the literature and academic society endorsement,
intraoperative echocardiography is rapidly becoming recognized for its impact on perioperative decision-making
during noncardiac surgery.
Indications for Intraoperative Echocardiography
Indications for emergent TEE during noncardiac surgery have included hemodynamic instability,
evaluation for chest trauma, hypoxemia, and preincision cardiac evaluation prior to emergent surgery. 7 In 1996,
practice guidelines were published by the American Society of Anesthesiologists (ASA) and the Society of
Cardiovascular Anesthesiologists (SCA) Task Force on Transesophageal Echocardiography. 8 Within these
guidelines, recommendations are divided into three categories based on the strength of supporting evidence and
expert opinion that TEE improves clinical outcomes. Category I indications are supported by the strongest evidence
or expert opinion that TEE is frequently useful in improving clinical outcomes in these settings, and is often
indicated. Category II indications are supported by weaker evidence and expert consensus that TEE may be useful in
improving clinical outcomes in these settings, but absolute indications are less certain. Category III indications have
little scientific or expert support, and appropriate indications are uncertain. An update of this document was
published in 2010.9 Indications relevant to intraoperative TEE for noncardiac surgery that were identified in these
guidelines include (1) the use of TEE when the nature of the planned surgery or the patient’s known or suspected
cardiovascular disorder might result in severe hemodynamic, pulmonary, or neurological compromise and (2) the
use of TEE when unexplained life-threatening circulatory instability persists despite corrective therapy. Thus, while
practice guidelines from the ASA and SCA recognize the importance of intraoperative TEE and are perhaps most
applicable for cardiac surgery, they also have relevance for noncardiac surgery.
The role of intraoperative TEE for noncardiac surgery can be divided into two general categories. The first
is referred to as “rescue TEE” for the evaluation of acute, persistent, and life-threatening hemodynamic disturbances
in which ventricular function and its determinants are uncertain or have not responded to treatment 10 and to guide
appropriate triage and both medical and surgical intervention. In 31 adult patients undergoing noncardiac surgery,
either transthoracic echocardiography (TTE) (N = 9) or TEE (N = 22) was performed to evaluate their influence on
determining the cause of the patient’s hemodynamic instability and perioperative clinical decision-making.10 All
patients were found to have an explainable diagnosis for hemodynamic instability from the data acquired by the
echocardiographic examination. The most common diagnoses were left heart dysfunction (N = 16), right heart
dysfunction (N = 9), hypovolemia (N = 5), pulmonary embolus (N = 5) (Figure 1), and myocardial ischemia (N = 4).
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Based on echocardiography findings, 4 patients underwent and survived an emergent and initially unplanned
secondary procedure. All 31 patients recovered following their surgical procedure and 25 progressed to hospital
discharge. In another study investigating the usefulness of TEE during intraoperative cardiac arrest in noncardiac
surgery, a primary suspected diagnosis of the underlying pathological process was established with TEE in 19 of 22
patients including 9 with thromboembolic events, 6 with acute myocardial ischemia, 2 with hypovolemia, and 2 with
pericardial tamponade.11A definitive diagnosis could not be made with TEE in 3 patients. In 18 patients, TEE guided
specific management beyond implementation of Advanced Cardiac Life Support protocols, including the addition of
surgical procedures in 12 patients.
A second general category for the use of intraoperative TEE in noncardiac surgery includes its utility for
monitoring global and regional cardiac performance in patients at increased risk for hemodynamic disturbances, in
identifying emboli, and for enabling a variety of diagnoses based upon certain specific surgical procedures. In
several single-center and multicenter studies, intraoperative TEE for noncardiac surgery was shown to influence
surgical and anesthetic management in 30–40% of patients, including those who already had invasive hemodynamic
monitors (i.e., radial arterial lines and pulmonary artery catheters). 4,5,12,13 Changes in management have been based
upon confirming or invalidating a prior diagnosis, detecting new diagnoses, and acquiring pertinent information
during periods of hemodynamic instability that leads to changes in drug regimen or goal-directed fluid therapy,
unplanned reoperations, and further evaluation in the postoperative period.
While many cases in the literature would be considered indications for the utility of intraoperative TEE for
rescuing patients as described above, other reports have shown a consistent impact of intraoperative TEE on
perioperative clinical decision-making, even for nonemergent indications, among noncardiac surgical patients. In
general, rescue TEE has been shown to be useful in 60–70% of patients, and up to 0–90% when cardiopulmonary
resuscitation is ongoing. The utility of intraoperative TEE when used proactively and primarily as a monitor of
cardiac performance is 20–80% overall, including 20–60% as a guide for medical intervention and 10–30% for
surgical intervention. The lower rates in the latter category most likely reflect the more diverse populations
described in the literature for this indication and how the utility of intraoperative TEE was defined in these clinical
scenarios. Thus, in addition to earlier reports suggesting a primary benefit for intraoperative TEE as a diagnostic tool
for evaluating myocardial ischemia during noncardiac surgery,14 more recent reports also confirm its utility as a
monitor of hemodynamic status and overall cardiovascular performance.
Perioperative Ischemia Monitoring

Ischemic changes detected by two-dimensional echocardiography include new systolic wall motion
abnormalities (SWMA) and decreased systolic wall thickening. Echocardiography is also useful for evaluating
complications of myocardial ischemia including myocardial infarction (MI), congestive heart failure, valve
regurgitation, septal defects, thrombi, pericardial effusions, and ventricular free wall rupture. Controlled studies
have demonstrated a clear association between SWMA, coronary ischemia, and cardiac events. 15 Data from
perioperative TEE studies have reported specificities and negative predictive values above 90%. However,
sensitivity and positive predictive values for MI are less than 40%, possibly because not all ischemia results in MI. 14
In addition, SWMA often overestimate the area of injury and may result from causes other than ischemia including
myocardial stunning, hibernation, and tethering as well as changes in loading conditions. While monitoring,
diagnosing, and treating myocardial ischemia is important, it is not clear that routine TEE is either cost-effective or
more beneficial than echocardiographic monitoring with S-T segment analysis.16 However, TEE may be a
worthwhile monitor and a diagnostic tool of choice for the initial assessment of myocardial ischemia or MI-related
complications for high-risk patients undergoing noncardiac surgery.
Vascular Surgery
Systolic wall motion abnormalities occur frequently during vascular surgery but are less frequently
associated with perioperative MI, congestive heart failure, and cardiac death. In one study, 55% of patients
undergoing aortic reconstruction experienced new SWMA at the time of aortic clamping with a greater incidence
seen following supraceliac clamping (92%) compared with suprarenal (33%) or infrarenal (0%) clamping. 17 In this
particular series, only 1 patient (in the supraceliac group) suffered a perioperative MI.
As previously stated, SWMA may result from a variety of causes other than ischemia. Furthermore, even if
all SWMA were indicative of ischemia or ventricular dysfunction, ischemia does not always result in a major
cardiac event. Anesthetic agents, metabolic changes, blood loss, and placement of the aortic cross-clamp are known
causes of SWMA. Since these are transient processes, the occurrence of an adverse cardiac event is reduced. The
low positive predictive value of SWMA may also be attributed to rapid detection and subsequent prompt treatment.
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Nonetheless, the utilization of TEE during major vascular procedures may influence perioperative management and
outcome.
Diastolic dysfunction is commonly noted in vascular surgical patients, who often have concurrent
coronary artery disease, with or without ventricular remodeling, resulting from systemic hypertension or
valvular heart disease. Acute perioperative diastolic dysfunction may also develop in conjunction with
chronic underlying disease or independently, especially during aortic surgery. In a study of 45 patients
undergoing abdominal aortic aneurysm surgery in which intraoperative TEE was used to evaluate diastolic
dysfunction before, during, and after aortic cross-clamping, the incidence of diastolic dysfunction increased
with application of the clamp; however, it returned to baseline after removal. 18
Liver and Lung Transplantation

The anesthetic management of patients undergoing liver or lung transplantation can be challenging because
of hemodynamic volatility during surgical manipulation, cross-clamping and unclamping of the inferior vena cava,
and graft reperfusion, which can all directly impact myocardial performance.
During liver transplantation, TEE monitoring has demonstrated new findings in more than 40% of patients,
has improved hemodynamic management, and has been shown to predict major postoperative adverse cardiac events
and death.19 Despite the presence of a coagulopathy and gastroesophageal varices, TEE has been used safely in
patients undergoing liver transplantation with a reported bleeding complication rate of 1–2%.20 In a study of 116
liver transplantations, only 1 patient experienced a major complication (a significant upper gastrointestinal bleed).20
There was no statistically significant correlation between pretransplant sclerotherapy for treatment of varices and
intraoperative TEE-related gastrointestinal bleeding. The authors concluded that intraoperative TEE during liver
transplantation is associated with a reasonable risk/benefit ratio.
During lung transplantation, TEE has been used to assess the cause and severity of pulmonary
hypertension, intraoperative ventricular function (Figure 2), and the integrity of the surgical anastomosis. Diagnoses
such as pulmonary artery thrombi, patent foramen ovale, and atrial and ventricular septal defects in 25% of patients
resulted in the requirement for additional surgery in one study. 21 Furthermore, echocardiographic visualization of
pulmonary vascular anastomoses suggests that up to 30% may be abnormal, thus prompting additional surgical
procedures.22
Orthopedics
Patients undergoing total hip replacement are vulnerable to perioperative cardiac complications because of
comorbidity and hemodynamic instability occurring during certain aspects of the surgical procedure. Emboli
released during preparation of the femur are readily diagnosed with TEE and have been associated with decreases in
blood pressure, increases in pulmonary artery pressure, right and left ventricular SWMA, and occasionally
cardiovascular collapse.23 Emboli have also been diagnosed following release of the thigh tourniquet in patients
undergoing total knee replacement.24 In comparison to total hip replacement, however, the hemodynamic
consequences of these embolic events may not be as severe. 24 Although TEE may not be indicated for all patients
undergoing orthopedic procedures, elderly patients and those with significant cardiovascular and pulmonary
comorbidity may benefit from its utility as a monitor and diagnostic tool for evaluating perioperative
hemodynamics.
Neurosurgery
Hemodynamic instability during major neurological surgery is affected by a number of variables including
patient demographics, anesthetic agents, and surgical techniques. Venous air embolism, which may cause
hemodynamic and pulmonary instability, occurs in 25–50% of neurosurgical procedures and has been reported in as
many as 76% of craniotomies performed in the sitting position.25 Although precordial Doppler echocardiography or
TEE is believed to be the most sensitive monitor for venous air embolism, actual utilization varies from 25–87%.25
Patients scheduled to undergo craniotomy in the sitting position should have an echocardiographic evaluation either
preoperatively or immediately after induction of anesthesia to determine the presence of any intracardiac shunts.
Obstetrics
It is becoming more common for high-risk obstetrical patients with cardiac disease, including congenital
heart diseases, coronary artery disease, cardiomyopathies, and heart transplantation, to present for peripartum care.
In addition, a number of pregnancy-related conditions, including pregnancy-induced hypertension, pulmonary
emboli, hemorrhage, and peripartum cardiomyopathy, have a significant influence on tolerance for the normal
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hemodynamic changes associated with pregnancy. Although echocardiographic analysis during normal deliveries is
not cost-effective, its use in assessing high-risk obstetric patients may be warranted.26 Cardiac arrest in parturients
has recently been estimated at 1 in 12,000 deliveries.27 However, the Centre for Maternal and Child Enquiries report
indicates that rates for maternal collapse, defined as “an acute event involving the cardiorespiratory systems and/or
brain resulting in reduced or absent consciousness at any stage in pregnancy and up to six weeks after delivery,” are
as high as 6 in 1,000 pregnant mothers.28 Burrage et al. assessed the diagnostic benefit of TEE in guiding
resuscitation in 10 parturients through evaluation of refractory hemodynamic instability, including cardiac arrest. 29
Six patients became unstable during dilation and evacuation procedures, 1 after a forceps delivery, 1 during and 1
after cesarean delivery, and 1 during a postpartum laparotomy (Figure 3). Six patients proceeded to cardiac arrest.
However, all of the women survived their initial operation and resuscitation. TEE was instrumental in determining
the cause and guiding resuscitation in all 10 patients, including emergent cardiac surgical intervention requiring
cardiopulmonary bypass. Seven patients survived to hospital discharge; the other 3 died after experiencing
neurological complications.29 The authors concluded that emergent TEE is a valuable tool for determining the cause
and directing therapy for refractory hypotension or cardiac arrest in obstetric patients.
Lead Extraction
Removing infected or malfunctioning transvenous cardiac leads following placement of a cardiovascular
implantable electronic device has evolved markedly over the past 30 years and has developed into its own
subspecialization of cardiology and cardiac surgery. In keeping with other surgical procedures, transvenous lead
extraction (TLE) now requires a stringent, protocoled, multidisciplinary approach in anticipation of procedure-
specific potential adverse events such as pericardial effusion, pulmonary embolism, vascular or cardiac injury, or
respiratory complications. The risk of major morbidity and mortality associated with the inevitable complications
during TLE is substantially reduced by having a specially equipped emergency cart, cardiopulmonary bypass setup,
and TEE on standby for every case at the time of induction of anaesthesia. 30 In a recently published study, 26
patients who required emergent TEE to determine the cause of intractable hemodynamic instability during TLE were
evaluated.31 Pericardial effusion requiring urgent pericardiocentesis, cardiac surgical intervention, or both was
diagnosed by TEE in 10 patients and progressed to cardiac arrest in 4 (Figure 4). Hemorrhagic shock developed in 2
patients suffering from femoral vein laceration and right hemothorax respectively. One additional patient developed
acute respiratory compromise and right ventricular dysfunction, diagnosed by TEE, that necessitated prolonged
postoperative intubation and inotropic therapy. In 14 patients, TEE excluded life-threatening cardiovascular injuries
and enabled continued medical management. Two patients with reassuring TEE findings underwent intraoperative
placement of chest tubes for pneumothorax. All 26 patients were discharged from the hospital.
Trauma and Critical Care

Prompt and accurate diagnosis of traumatic cardiac injuries is crucial to improving survival. In one study of
penetrating chest injury, echocardiographic evaluation and diagnosis were achieved within 15 minutes compared
with 42 minutes in the non-echo group. Survival was 100% in the former and 57% in the latter. Compared with
TTE, TEE also significantly contributes to the diagnostic and hemodynamic evaluation of cardiac and vascular
injury, and can be performed in as little as 9–15 minutes.32,33
There is strong support for the use of echocardiography in critically ill patients. 2,3 Common indications for
postoperative echocardiography include evaluation of hypotension, ventricular function, mitral regurgitation,
prosthetic valves, aortic injury, pericardial disease, myocardial ischemia, complications following MI, cardiac
masses, and sources of emboli or infection.34-38 Echocardiographic evaluation of hemodynamic instability, trauma,
and hypoxemia are particularly common.33-37
When compared to clinical impression, echocardiography provided new information in 80% of critically ill
patients, changed medical management in 60%, and led to a surgical procedure in as many as 30% of patients. 26,34
Comparative analyses have shown that TEE improved cardiac evaluation compared with TTE in as many as 50 to
70% of patients.25,26,32-38
National Board of Echocardiography Certification in Basic Perioperative TEE

In October 2006, the ASA House of Delegates approved the development of a basic echocardiography
education training program and resolved that ASA uniquely or collaboratively explore a pathway for
anesthesiologists to obtain experience and privileges in echocardiography as a basic perioperative monitor. In 2010,
the ASA completed an agreement with the National Board of Echocardiography (NBE) to develop a basic
perioperative TEE examination and criteria for a certification pathway to achieve diplomate status in Basic
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Perioperative Echocardiography. Certification occurs within the scope of practice that includes nondiagnostic
monitoring within the customary practice of anesthesiology; with a focus on intraoperative monitoring rather than
specific diagnosis; and with the understanding that, except in emergent situations, diagnoses requiring intraoperative
cardiac surgical intervention or postoperative medical/surgical management must be confirmed by an individual
with advanced skills in TEE or by an independent diagnostic technique.
A basic perioperative TEE examination (PTEeXAM) and certification process has been available from the
NBE since 2010. Current criteria for basic certification proposed by the NBE include:
• Requirement 1. Applicants must have passed the Basic PTEeXAM or the Advanced PTEeXAM.
• Requirement 2. Applicants must hold a current and unrestricted license to practice medicine at the time of
application.
• Requirement 3. Applicants must be board certified in anesthesiology.
• Requirement 4. Applicants for Specific Training in PTEE must perform and review 150 basic PTEE
examinations with variations in requirements for supervision, CME, and time for completion, depending
upon which of the following three pathways is pursued: (1) Supervised Training Pathway, (2) Practice
Experience Pathway (available through June 2016), or (3) Extended CME Pathway (Table).
Further details pertaining to the NBE basic PTE examination and certification process can be found at
www.echoboards.org.
Conclusions
Perioperative echocardiography for noncardiac surgical patients is useful for diagnosing cardiovascular
disease and assessing hemodynamics. Integrating the information acquired from performing an intraoperative TEE
examination into the practice of medicine will influence clinical decision-making in important ways. Thus,
recognition of the importance of formal education and training in perioperative TEE, as well as appreciation of
contraindications for probe insertion, management of difficult probe insertion, and overall safety for this invasive
procedure remains critically relevant.39
A recent consensus statement by the ASE and SCA highlights the multidisciplinary recognition of the
important utility of perioperative TEE.40 Echocardiographic evaluation of cardiac performance compares favorably
with other “gold standards” and expands on the ability to obtain a comprehensive cardiovascular examination. In
recognition of the utility of intraoperative TEE for noncardiac surgery, the ASA, SCA, and NBE collaborated to
develop a pathway for certification in basic perioperative TEE (www.echoboards.org). In addition, the “ECHO-in-
ICU” group, the American College of Emergency Physicians (ACEP), and a joint effort by the ASE and ACEP have
all proposed limited-scope training guidelines for the focused use of echocardiography in the initial management of
critically ill patients in the intensive care unit41-43 and emergency room respectively.44,-45 As the popularity of
echocardiography increases and the indications for its perioperative utility evolve, appreciation for its value in the
noncardiac surgical population will continue to develop.
References
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2. Cheitlin MD, Alpert JS, Armstrong WF, Aurigemma GP, Beller GA, et al.: ACC/AHA guidelines for the
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6. Cheitlin M, Armstrong W, Aurigemma G, Beller GA, Bierman FZ, et al.: ACC/AHA/ASE 2003 guideline
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Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASE Committee to

Update the 1997 Guidelines for the Clinical Application of Echocardiography).
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echocardiography. J Am Soc Echocardiogr 1998; 11:972–7.
8. Practice guidelines for perioperative transesophageal echocardiography: a report by the American Society of
Anesthesiologists and the Society of Cardiovascular Anesthesiologists Task Force on Transesophageal
Echocardiography. Anesthesiology 1996; 84:986–1006.
9. Thys DM, Abel MD, Brooker RF, Cahalan MK, Connis RT, et al.: Practice guidelines for perioperative
transesophageal echocardiography: An updated report by the American Society of Anesthesiologists and the
Society of Cardiovascular Anesthesiologists Task Force on Transesophageal Echocardiography.
Anesthesiology 2010; 112:1084–96.
10. Shillcutt S, Markin N, Montzingo C, Brakke T: Use of rapid “rescue” perioperative echocardiography to
improve outcomes after hemodynamic instability in noncardiac surgical patients.
J Cardiothorac Vasc Anesth 2012; 26:362–70.
11. Memtsoudis S, Rosenberger P, Loffler M, Eltzschig H, Mizuguchi A, et al.: Usefulness of transesophageal
echocardiography during intraoperative cardiac arrest. Anesth Analg 2006; 102:1653–7.
12. Schmidlin D, Bettex D, Bernard E, Germann R, Tornic M, et al.: Transesophageal echocardiography in cardiac
and vascular surgery: implications and observer variability. Br J Anaesth 2001; 86:497–505.
13. Lambert A, Mazer C, Duke P: Survey of the members of the cardiovascular section of the Canadian
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Respiratory Physiology: Gas Exchange and Respiratory Mechanics
Luca M. Bigatello, MD Boston, Massachusets
Respiration provides oxygen (O2) and removes carbon dioxide (CO2) for the body. A remarkable arrangement of
functional units (the alveoli) delimited by extra-thin walls (epithelium and endothelium) creates the interface for gas
exchange between air and blood. Gas- flow in and out of the lungs (ventilation) is generated by the activity of the
respiratory muscles, or of a ventilator, and opposed by resistance within the airways and elastance (“stiffness”) of
lungs and chest wall. Knowledge of the basic physiologic events that regulate gas exchange and respiratory
mechanics provides a most useful frame to understand and treat respiratory insufficiency in the operating room (OR)
and intensive care unit (ICU).
Gas exchange
The PaO2.
How O2 gets from the atmosphere to the arterial blood: the alveolar air equation. O2 constitutes 21% of the air we
breathe. At sea level, air exerts a pressure of 760 mmHg; once fully saturated by water vapor (47 mmHg), the PO2
in the inspired air (PiO2) can be calculated as:
PiO2 = (760 - 47) mmHg x 0.21 ≈ 150 mmHg [1]
In the alveoli, one volume of O2 is exchanged for 1.2 volumes of CO2 (respiratory quotient [RQ] of 0.8): with a
normal PaCO2 of 40 mmHg, the alveolar PO2 (PAO2) will be:
PAO2 = PiO2 - PaCO2 x 1.2 ≈ 102 mmHg [2]
Past the pulmonary capillaries, arterial blood normally receives a small fraction of venous blood from a minimal
alveolar shunt (2 - 3%, increases with aging) and from blood that shunts the pulmonary circulation, such as the
bronchial veins and some diaphragmatic veins, and PaO2 decreases slightly below 102 mmHg.
Causes of hypoxemia. Understanding how O2 moves from the air to the blood (Figure 1) provides a convenient
framework to classify the various causes of hypoxemia:
Low PiO2. The most common cause of a low PiO2 is O2: From the Air to the Artery
breathing at high altitude. Breathing air at 5,300 feet in
Denver lowers PiO2 to 120 mmHg, and breathing air at
30,000 feet on the summit of Mount Everest lowers PiO2
to 40 mmHg. Although rare, causes of low PiO2 at sea PiO2 ≈ 150 mmHg
level are related to the accidental administration of a
hypoxic mixture.
O2 CO2
Low PAO2: hypoventilation. In addition to hypercapnea,
PAO2 ≈ 100 mmHg
hypoventilation may cause hypoxemia by increasing
PACO2. A PaCO2 of 80 mmHg will decrease PAO2 to
150 - 80 x 1.2 = 54 mm Hg. This scenario underlies the
importance of immediately administering O2 to a patient PaO2 ≈ 95 - 98 mmHg
that appears to be hypoventilating: supplemental O2 will
rapidly increase PiO2 and offset the effects of a high Figure 1
PACO2.
Impaired diffusion across the alveolo-capillary membrane rarely is direct cause of hypoxemia. In situation like
alveolar edema, where fluid increases the distance between alveolar air and the capillary, diffusibility of O 2 is such
that PaO2 would be only minimally affected; the hypoxemia of pulmonary edema is primarily due to ventilation /
perfusion (V/Q) mismatch. The diffusing capacity of carbon monoxide (DLCO) is a sensitive test to quantify
impairment of lung function, but DLCO is primarily affected by abnormality in V/Q rather than gas diffusion per se.
Low PaO2. The most common cause of hypoxemia is intrinsic lung disease, which alters the matching of ventilation
and perfusion. V/Q mismatch defines a continuum that ranges from no ventilation with preserved perfusion
(shunt), to no perfusion with preserved ventilation (dead space) including an infinite number of combinations.
Shunt results in venous blood (PvO2 = 40 mmHg, Fig. 2) reaching the arterial side without addition of O2, thus
decreasing PaO2 to a degree depending on the size of the shunt. The fraction of total pulmonary blood flow (Qt)
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shunted away (Qs) from unventilated alveoli can be calculated as the difference in content of O2 between the
pulmonary capillary (CcO2) and the arterial (CaO2) and venous (CvO2) blood:
Qs/ Qt = (CcO2 - CaO2) / (CcO2 - CvO2) [3]
where CcO2 is calculated using PAO2 as a surrogate of PcO2.
Content of O2 (Cont O2) is:
Cont O2 = Hb x 1.34 x O2 Sat. + PaO2 x 0.003 [4]
Shunt occurs with intracardiac defects and in diverse
pulmonary pathology such as atelectasis, pneumonia,
and acute respiratory distress syndrome (ARDS). In the Alveolo- Capillary Unit
presence of shunt, increasing FiO2 will only marginally
improve PaO2 (through an increase in PvO2); only
recruitment of collapsed alveoli will effectively treat
the hypoxemia.
Low V/Q results in arterial gas tensions PAO2 = 102 mmHg
approaching those of venous gas (Fig. 2). Despite PvO2 = 40 mmHg
PACO2 = 48 mmHg
PaO2 = 98 mmHg
multiple possible combinations of low and high V/Q PvCO2 = 46 mmHg PaCO2 = 40 mmHg
often present at the same time, hypoxemia is
predictably the main result. This is due to the shape of
the O2 dissociation curve. In a low V/Q alveolus where
Figure 2
PaO2 approximates PvO2, e.g. 50 mmHg, O2 Sat. will
be ~ 75%, which will decrease CaO2 by 25%; in an
alveolus with a correspondently high V/Q ratio, O2 Sat.
O2 Content: mls of O2 / 100 mls of blood (mls%)
cannot rise beyond the normal 100%, hence cannot
compensate for the lost 25%; an increase in PaO2 even
well beyond 100 mmHg will compensate minimally
because only 0.003 of the new PaO2 will contribute to
the CaO2. Figure 3 exemplifies this concept: the O2 Normal V/Q: High V/Q:
content leaving the alveolus with a low V/Q (16 mls / Low V/Q: 16% 19% 20%
100 mls of blood) approximates that of venous blood
(14 ml) but the O2 content leaving the alveolus with a
high V/Q (20 mls) is barely higher than that of the
normal alveolus (19 mls). Venous: 14 mls % Arterial: 17 mls %
Low PvO2 feeds venous blood into the arterial
circulation through areas of shunt. The extent of the Figure
Fig. 2 3
resulting hypoxemia depends on the magnitude of the
shunt, and is limited by local hypoxic vasoconstriction (HPV) that reduces blood flow through the shunted areas.
Through this mechanism, a low PvO2 may cause significant hypoxemia in two clinically relevant circumstances.
First, during shivering, due to an increase in O2 consumption; and second with a low cardiac output (that’s how
hypotension may cause hypoxemia!).
The PaCO2.
CO2 and H2O are end products of aerobic metabolism. CO2 is transported in blood as carbamino compounds,
bicarbonate, and dissolved. The latter determines the PaCO2, and is eliminated as a gas from the lungs. At steady
state, PaCO2 results from the equilibrium of production ( CO2) by cellular metabolism and elimination by minute
ventilation (VE):
PaCO2 = CO2 / VE [5]
PaCO2 is a potent stimulus for ventilation: for each increase of 1mmHg PaCO2, VE increases nearly instantly by 1 -
2 l/min. An alteration in this relationship is a common cause of hypercarbia (Fig. 4)
Causes of hypercarbia.
High CO2 occurs with fever, shivering, excessive caloric / carbohydrate intake, and, to its maximum extent, in
malignant hyperthermia (MH) and neuroleptic malignant syndrome (NMS). Except for MH and NMS, the increase
of CO2 is generally transient, and may be offset by an increase of VE.
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Low CO2 elimination is the most common cause of

hypercarbia and it includes two main reasons: Figure 4 ◉ Low ventilatory drive
Hypoventilation increases PaCO2 by limiting CO2 • Opiates

elimination. Common causes of hypoventilation: a) a VE • Inhalational agents
decreased central drive to breathe, as it occurs with the
administration of hypnotics and opiates (Fig. 4); b) • Hypnotics
respiratory muscle weakness, in syndromes such as • Benzo. (less)
Guillain-Barre’ and polyneuropathy of critical illness; • Butyrophenones (less)
and c) high resistive or elastic ventilatory loads
(below), as it occurs in severe asthma or abdominal
distention. Immediate treatment of hypoventilation
6 l/min
includes ventilatory support and supplemental O2 (see
hypoxemia). PaCO2
Dead space and high V/Q are a continuum of the
38 mmHg
same phenomenon, just as for shunt and low V/Q. As
perfusion decreases, venous blood fails to reach the
alveolus, and less CO2 is eliminated; exhaled PCO2 decreases and, at a constant CO2, PaCO2 rises. These
phenomena are at the basis of the measurement of the physiological dead space, as the fraction of unperfused
ventilatory space (“dead”, VD) over the tidal volume (VT):
VD/VT phys = (PaCO2 - PECO2) / PaCO2 [6]
VD/VT phys includes anatomical (proximal airways) and alveolar dead space (VD/VT alv). VD/VT phys is calculated
using mean exhaled PCO2 (PECO2), which is measured as the PCO2 averaged over several breaths. While the
anatomical dead space is for the most part fixed (25- 30% of the VE) VD/VT alv is 0 in normal lungs, and it increases
with the degree of lung disease in a number of conditions, such as ARDS and COPD / asthma. VD/VT alv can be
calculated as:
VD/VT alv = (PaCO2 - PetCO2) / PaCO2 [7]
PetCO2 is the PCO2 at end- expiration- ‘end-tidal’. In a standard a capnograph, when the expired CO2 reaches a
plateau, the PetCO2 is highly representative of the PACO2. A normal PECO2 is approximately 30 mmHg, and a
normal PetCO2 is 38 - 40 mmHg, nearly the same as PaCO2.
The linear correlation between PaCO2 (independent variable) and VE (dependent variable) gives us a clinical tool to
follow changes on a ventilator without necessarily measuring PaCO2, similarly to how we may follow O2- Sat.
without measuring PaO2. If we take note of the VE before implementing a change, and we know the PaCO2 at that
VE, no significant changes in VE will reassure us that no significant change in PaCO2 occurred. That is, with some
caveats: a) assuming the CO2 has not changed; unless we have a volumetric capnograph in use (unusual) we rely
on our judgment: fever, shivering, and agitation may increase CO2, which we need to verify; and b) assuming the
VD/VT has not changed; this can be verified following the PetCO2 from a time- based capnograph, used routinely in
the OR and frequently in the ICU.
Respiratory mechanics.
Moving air in and out of the lungs: the law of motion of the respiratory system. When we breathe spontaneously, a
negative pressure by the respiratory muscles (PMUS) causes a flow ( ) of gas through the airways that increases the
volume (V) of the lungs; exhalation occurs by passive elastic recoil. This cyclical rhythm is opposed by the
airways’ resistance to gas flow (RAW) and by the elastance (E) or ‘stiffness’ of the lung and chest wall. When a
patient is mechanically ventilated, a positive pressure (PVENT) drives the ; when a patient breathes spontaneously
and is mechanically ventilated (e.g., with pressure support ventilation) the pressure measured at the airway (PAW)
will be a combination of PMUS and PVENT. The law of motion of the respiratory system describes these phenomena:
PAW = PMUS + PVENT = x RAW = VT x E [8]
Note that we speak more commonly in terms of respiratory system compliance (CRS) than E; CRS is the reciprocal of
E, that is: a high E is a low CRS. Hence, E may be substituted in the equation by 1/CRS. The above relationship has
important corollaries:
 Ventilation works the same way whether spontaneous, mechanical, or a combination of the two.
Understanding Eq. [8] greatly facilitates understanding of mechanical ventilation.
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 The mechanical characteristics of the respiratory system, RAW and CRS (composed by compliance of the
lung [CL] and compliance of the chest wall [CCW]), are important determinants of the effects of ventilation.
 If we set a variable on a ventilator (e.g., VT) and the ventilator measures the resulting variable (PAW) we can
then calculate respiratory mechanics: RAW and CRS.
Bedside measurement of respiratory mechanics. A practical way to assess respiratory mechanics during anesthesia
and intensive care includes:
1. Setting the ventilator on volume control ventilation, constant (‘square wave’) flow.
2. Verifying that the patient is adequately relaxed and is not taking spontaneous breaths.
3. Performing an end- inspiratory pause, which separates the dynamic component of PAW, peak inspiratory
pressure (PiP), from the static component,
plateau pressure (PPLAT) and allows calculating
RAW and CRS.
pressure
PiP
4. Performing an end- expiratory pause (rarely
available in anesthesia ventilators) to measure resistance
intrinsic positive end-expiratory pressure
(PEEPi). Pplat
Figure 5 shows an airway pressure trace obtained as
described, with the respective measurements of compliance
mechanics:
CRS = VT / (PPLAT - PEEP) [9]
PEEP auto-PEEP
Raw = (PiP - PPLAT) / [10]
Normal CRS is 90 - 100 mls/cmH2O; normal RAW is 1-
3 cmH2O/l/sec. A convenient way to measure RAW Figure 5 time
includes setting the inspiratory flow at 60 l/min (1
l/sec), which allows to divide (PiP - PPLAT) by 1. At
the end of the breath, an end- expiratory pause allows to measure the expiratory PALV, provided no effort
from the patient. In the presence of expiratory flow limitation, such as in asthma and COPD, the lung does not fully
deflate at end- expiration, and PALV will be higher than 0 or PEEP, and this is PEEPi, or ‘auto- PEEP’. PEEPi has
some of the effects of externally applied PEEP: it can increase PaO 2 and can decrease cardiac output. Differently
from applied PEEP, PEEPi has to be overcome by the patient’s inspiratory effort in order to start the next breath
(increased work of breathing). This effort is wasted because it does not generate any volume, and can be taxing on
subjects with borderline respiratory function, both during spontaneous ventilation and while on the ventilator.
Compliance of an inhomogeneous lung. Figure 6 shows lungs with ARDS and severe hypoxemia, whose
mechanical characteristics, easily inferred by imaging, are vastly different. The ‘stiff’ lungs will require high
ventilating pressures that will distribute fairly similarly throughout severely diseased lung tissue, and likely will
cause damage.
The ‘small’ Figure 6
lungs will
receive pressure
mainly to those
two very limited
ventral regions,
which will
possibly
overdistend, and
do very little to
the consolidated
dorsal lung
tissue. The last set of lungs seems impossible to ventilate, which was indeed the case, and this patient was treated
with extracorporeal membrane oxygenation for three weeks. Inhomogeneous lung lesions are characteristic of
ARDS, and constitute a significant problem in providing mechanical ventilation because the positive pressure
necessary to ventilated diseased areas with very low compliance will cause pressure- and volume- damage (also
defined “stress” and “strain” respectively) of both diseased and healthier lung regions leading to ventilation-induced
lung injury (VILI) and perpetuation of lung damage.
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Lung recruitment, lung damage, and lung- protective ventilation. One can easily appreciate the complexity of
ventilating patients with inhomogeneous lung lesions and severe hypoxemia, like in ARDS. Mechanical ventilation
provides the high pressures and volumes that may normalize gas exchange, but it may also damage the lung. A low
VT (6 mls/k/IBW) limits lung damage and improves survival in ARDS. As low lung volumes may result in alveolar
de-recruitment and hypoventilation, applying PEEP helps both oxygenation by recruiting previously collapsed
alveoli, and ventilation by (through recruitment) increasing lung compliance. The precise level of PEEP that is most
beneficial is not known, and varies from patient to patient and from time to time; the general philosophy of limiting
inspiratory lung volume and pressure and adjusting PEEP to optimize compliance, constitutes lung protective
ventilation, which is the most accepted way to ventilate patients with diffuse lung injury. Data suggest that a similar
strategy may also be helpful in decreasing postoperative pulmonary complications during general anesthesia for
intra-abdominal surgery in high- risk patients.
The lung, the chest wall, and the transpulmonary pressure (PTP). What we measure under most circumstances at the
bedside is the compliance of the respiratory system (CRS) as a whole, which includes in equal parts the lung (CL) and
the chest wall (CCW). CL is what we are most interested in when ventilating patients with or at risk for lung injury,
because the lungs and not the chest wall is the structure that may require recruitment and may also be damaged. In
many cases, changes of CRS are a reasonable estimate of changes of CL. However, in situations such as morbid
obesity, abdominal distention, and large pleural effusions, the CCW is chiefly responsible for the abnormal CRS,
which in turn is no longer a good approximation of the CL. The key physiological entity to understand in order to
provide effective ventilation in these cases is the transpulmonary pressure (PTP), which is the pressure that recruits
collapsed lung tissue and that may damage normal lung tissue, depending upon the physiology of each alveolar unit.
PTP is the pressure across the lung, measured as:
PTP = PALV - PPL [11]
Unfortunately, neither PALV nor PPL can be measured directly, and are approximated by:
PTP = PPLAT - PESO [12]
Where PPLAT is the inspiratory plateau airway pressure (see Fig. 5), and PESO is esophageal pressure, measured by a
commercially available esophageal balloon. PESO allows partitioning the CRS in its two components: CL and CCW:
1/CRS = 1/CCW + 1/CL [13]
From equation [9]:
CL = VT / [(PPLAT - PESO, insp) - (PEEP - PESO, exp)] [14]
or: CL = VT / (PTP, insp - PTP, exp) [15]
CCW = VT / (PESO, insp - PESO, exp) [16]
Since in normal humans CL and CCW are of similar value, approximately half the pressure applied at one side (P ALV)
will transmit to the other side (PPL). When the lungs are “stiff”, like in ARDS, (Figure 7, left) less than half P ALV
will be transmitted to the pleural space, resulting in a
Figure 7 high PTP. When the chest wall is “stiff” (Figure 7,
30 right), more than half PALV will be transmitted to the
5 30 15
cmH2O cmH2O cmH2O pleural space, resulting in a low PTP. Hence, a low
cmH2O
CL predisposes to lung damage and a low predisposes
to de-recruitment. A loss of CCW as in morbid
obesity, pneumoperitoneum, and abdominal
compartment syndrome, requires a higher alveolar
pressure to achieve adequate lung inflation than it
30
cmH2O 30 would be predicted by just following the PPLAT. This
cmH2O phenomenon, well understood in classic respiratory
physiology, has important clinical applications.
First, in hypoxemic ARDS with abdominal distention
Low Lung Compliance: Low CW Compliance:
PTP = 30 - 5 = 25 PTP = 30 - 15 = 15 or morbid obesity, the PPLAT (surrogate of PALV)
necessary to recruit the lung is increased because of
the low CCW. Titrating the recruiting pressure to PTP
by measuring PESO has been shown to identify the
correct inflating pressure and be effective in ARDS patients with increased abdominal pressure. Second, during
laparoscopic / robotic surgery with pneumoperitoneum +/- steep head down position, a high PPLAT is largely
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determined by the high intra-abdominal pressure and consequent low CCW. Just as in ARDS, titration of the inflating
pressures to PTP rather than PPLAT allows safe delivery of larger VT and minute ventilation. Unfortunately,
esophageal balloons are seldom used in the OR. However, here we have the benefit of knowing the PAW (PPLAT can
be identified with an inspiratory pause on volume- control ventilation, or just using pressure- control ventilation) to
deliver an adequate VT before abdominal insufflation. The increase of PPLAT occurring at the same VT after
insufflation will be mostly due to the stiffening of the chest wall. A P PLAT somewhere between the pre- and post-
insufflation can be safely deliver without injuring the lung.
Suggested reading
1. JB West. Respiratory Physiology- The Essentials. Ninth edition. Lippincott Williams and Wilkins, 2012.
2. A Lumb. Nunn’s Applied Respiratory Physiology. Seventh edition. Elsevier, 2010.
3. AC Guyton, JH Hall. Textbook of Medical Physiology. Thirteen edition. Elsevier, 2016.
4. West, JB. Ventilation-perfusion relationships. Am Rev Respir Dis 1977;116:919-943.
5. Mancini M, Zavala E, Mancebo J, et al. Mechanisms of pulmonary gas exchange improvement during a
protective ventilatory strategy in acute respiratory distress syndrome. Am J Respir Crit Care Med
2001;164:1448-145.
6. Lucangelo U, Blanch L. Dead space. Intensive Care Med 2004;30:576-579.
7. Rossi A., Gottfried SB, Zocchi L, et al. Measurement of static compliance of the total respiratory system in
patients with acute respiratory failure during mechanical ventilation. Am Rev Respir Dis 1985;131:672-677
8. Gottfried SB, Reissman H, Ranieri VM. A simple method for the measurement of intrinsic positive end-
expiratory pressure during controlled and assisted modes of mechanical ventilation. Crit Care Med.
1992;20:621–629.
9. Hess D. Respiratory mechanics in mechanically ventilated patients. Resp Care 2014;59:1773-1794.
10. Hess DR, Bigatello LM. The chest wall in acute lung injury/acute respiratory distress syndrome. Curr Opin Crit
Care 2008;14:94-102.
11. Dhand R. Ventilator graphics and respiratory mechanics in the patient with obstructive lung disease. Respir
Care 2005;50:246-261.
12. Bigatello LM, Davignon KR, Stelfox HT. Respiratory mechanics and ventilator waveforms in patients with
acute lung injury. Respir Care 2005; 50:235-244
13. Grasso S, Stripoli T, Sacchi M, et al. Inhomogeneity of Lung Parenchyma during the open lung strategy. Am J
Respir Crit Care Med 2009;180:415-423
14. Gattinoni L, Protti A, Caironi P, et al. Ventilator-induced lung injury: the anatomical and physiological
framework. Crit Care Med 2010;38:S539-548.
15. Talmor D, Sarge T, Malhotra A, et al. Mechanical ventilation guided by esophageal pressure in acute lung
injury. N Engl J Med 2008;359:2095-2104.
16. Futier E, Constantin J-M, Paugam-Burtz C, et al. A trial of intraoperative low tidal volume ventilation in
abdominal surgery. N Eng J Med 2013;369:428-437
17. Pellegrino R, Gobbi A, Antonelli A, et al. Ventilation heterogeneity in obesity J Appl Phys 2014;116:1175-1181
18. Slutsky AS and Ranieri MV. N Eng J Med 2013;369:2126-2136
19. Stahl DL, North CM, Lewis A, et al. Case scenario: power of positive end-expiratory pressure. Use of
esophageal manometry to illustrate pulmonary physiology in an obese patient. Anesthesiology 2014;121:1320-
1326
20. Cinella G, Grasso S, Spadaro S, et al. Effects of recruitment maneuvers and positive end-expiratory pressure on
respiratory mechanics and transpulmonary pressure during laparoscopic surgery. Anesthesiology
2013;118:114-22
21. Amato MBP, Meade MO, Slutsky AS, et al. Driving pressure and survival in the acute respiratory distress
syndrome N Eng J Med 2015;372:747-755
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Lung Isolation: Clinical Challenges and Strategies for Success
Jerome Klafta, MD Western Springs, IL

Objectives:
1. Describe the role of lung isolation (= lung separation) in the context of successful one-lung anesthesia
2. Identify common and uncommon causes of lung separation failure and apply strategies for success
3. Recommend approaches to lung separation in patients with difficult airways
The big picture

“Success” in the context of one-lung anesthesia means that lung collapse is both complete and well tolerated
by the patient. Although the concept is simple, a number of clinical details frequently make the difference between
success and failure. Lung isolation (= functional lung separation) allows us to ventilate one lung independent of the
other (airtight seal) or to restrict passage of blood or fluids (watertight seal) from one lung to another. One-lung
anesthesia requires not only functional lung separation but also adequate one-lung ventilation (OLV) and
oxygenation. Figure 1 depicts the three clinical endpoints integral to one-lung anesthesia:
• Optimal position of double-lumen tube or

blocker
• Functional lung separation
• Adequate one-lung ventilation and oxygenation
Various overlapping subsets of these conditions can

and do occur. For example, adequate position of the
double-lumen tube (DLT) or bronchial blocker (BB)
does not ensure functional lung separation (condition
A), and adequate OLV can sometimes be achieved
with suboptimal DLT position (condition C). Table
1 lists examples of causes and solutions for each
clinical condition in Figure 1. By identifying the
exact nature of the difficulties, the anesthesiologist
can implement appropriate therapy without wasting
time on maneuvers (DLT repositioning, cuff volume
manipulations, or ventilation changes) that are not
part of the problem.
Table 1: Clinical conditions during one-lung anesthesia

Area Example Situation Typical Solution
A • No airtight cuff seal – lungs not separated • More air in cuff or larger DLT
B • Left DLT in too far occluding LUL orifice • Position DLT optimally
C • Right DLT cuff occluding RUL orifice • Position DLT optimally
• Hypoxemia • 100% oxygen/CPAP/PEEP/TLV
D
• Obstruction of the ventilating lumen of DLT • Consider alternative lung separation technique
E • No Problem!
LUL = left upper lobe; RUL = right upper lobe; TLV = two lung ventilation
Design characteristics of double lumen tubes and bronchial blockers

Common adult DLT sizes are 35, 37, 39, and 41 French (F). Some manufacturers also provide 26, 28 and 32
F sizes. The particular dimensions and design characteristics vary somewhat between manufacturers (Rusch, Portex,
Sheridan, Mallinckrodt, and Fuji Systems). The resting bronchial cuff volume (defined as the smallest cuff volume
beyond which a 0.5 cc increase results in more than a 10 Torr increase in cuff pressure) can differ between sizes (35
F = 3.7 cc; 41 F = 2.0 cc) (1). Inflation of the bronchial cuff beyond its resting volume (or even less than its resting
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volume if fitted tightly inside a bronchus) may result in dangerously high intracuff pressures and should be avoided
(1,2).
A new left-sided DLT with integrated camera (VivaSight-DLT) allows for continuous visualization of the
tracheal carina once correctly placed. In a study comparing this device to conventional DLTs placed blindly,
intubation time was faster (63 vs. 97 sec) and correct initial positioning was facilitated (3). In another study, loss of
video image quality due to secretions occurred in 30% of patients despite use of the integrated flushing mechanism
(4). It appears that this device can provide helpful continuous visual monitoring of DLT position but is unlikely to
supplant the use of the fiberoptic bronchoscope (FOB).
The Univent Torque Control Blocker (TCB) tube is shaped like a standard single lumen tube (SLT) but has 2
lumens: one housing a retractable BB and the other used for gas exchange. Typical cuff inflation volume of the
blocker balloon is 5-6 cc.
The Arndt endobronchial blocker was the first of several additions to our current armamentarium of lung
separation devices (5). This system minimizes some of the traditional difficulties associated with the use of Fogarty
embolectomy catheters as independent BBs and with Univent tubes. A patient’s lungs can be conveniently
ventilated while the blocker is fiberoptically positioned through the Arndt multiport airway adapter. The guide wire
loop that protrudes through the blocker’s tip is used to couple the blocker to the FOB which can be directed
fiberoptically to the desired location in the bronchial tree. The blocker’s 1.4 mm lumen can be used to insufflate
oxygen or suction gas from the blocked lung after the wire loop is removed. The smallest SLT for use with this
blocker coaxially (≥ 7.5 mm ID) has a corresponding outer diameter that compares favorably with that of the typical
DLTs and Univent tubes used for small adults.
Since its introduction in 1999, Cook Critical Care has made several design modifications. Characteristics of
available blockers are described in Table 2 below. A midsize 7 F catheter permits the use of a larger diameter FOB
or a smaller diameter SLT for coaxial use. “Murphy eye” side holes have been introduced into the distal end of the
9 F adult catheter to circumvent suctioning difficulty if the end hole abuts the bronchial mucosa, and the guide wire
loop of the 9F blocker can now be reinserted if needed.
Table 2: Arndt Endobronchial Blockers

Size Smallest SLT ID for Length Average cuff inflation
Cuff shape
(F) coaxial use (mm) * (cm) volume (cc)
9 7.5 78 Spherical 4–8
7 6.5 65 Spherical 2–6
5 4.5 50 Spherical 0.5 – 2.0

ID = inner diameter * with 3.4 mm FOB (data from www.cookmedical.com)
The Cohen blocker is similar to the Arndt blocker except that its distal tip is directed by way of a proximal
control mechanism instead of coupling to a bronchoscope. The Uniblocker is an independent BB controlled
similarly to the one integral to the Univent tube. The use of bronchial blockers in adults for routine cases (6) and for
selective lobar blockade (7) has been reviewed.
The Y-shaped, dual-balloon EZ-Blocker (EZB) is the newest BB design. When compared to left-DLTs in
100 patients, an SLT plus EZB performed similarly (intraoperative malposition, speed and quality of lung collapse,
gas exchange) and took only slightly longer (25 vs. 13 sec) to place (8). Importantly, the incidence of AW injury as
assessed by an independent bronchoscopist and postoperative hoarseness and sore throat were less with the EZB. A
horizontal orientation in the supine position facilitates correct initial placement of this device.
Size selection of double-lumen tubes

Assuming that the main body of a DLT will fit through the glottic opening and the trachea, an appropriately
sized DLT is the largest tube that will fit in the mainstem bronchus with only a small air leak detectable when the
cuff is deflated (2). The presence of some air leak ensures that the tube is not tightly impacted in the bronchus.
Thus, the goal is to select a DLT with an outer bronchial diameter that is 1-2 mm smaller than the diameter of the
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intubated bronchus to allow for the size of the deflated cuff (2). Although some practitioners use 35 F DLTs for all
patients (9), many select 41 F and 39 F DLTs for tall and short men, respectively, and 39 F and 37 or 35 F DLTs for
tall and short women, respectively. However, there is considerable variability in left mainstem diameters and the
relatively weak predictive value of gender and height has been repeatedly demonstrated (2,10). Since prediction is
imprecise, measurement of the left mainstem diameter is most reliable. On chest x-ray (CXR) it is discernible only
50-69% of the time (2,11) but it is reliably identified on chest CT (12). Checking the radiograph to identify
unexpectedly large or small bronchi (i.e., significant outliers) is probably most important.
One critically important assumption is that we clinicians know the dimensions of the differently sized
DLTs. Russell et al independently measured the dimensions of DLTs from 4 manufacturers and found marked
variations even within the same tube size for each manufacturer (13)! See Figure 2. Thus, any effort to predict
appropriate DLT size has this important limitation.
Figure 2 (from ref 13)
While attempting to select an appropriately sized DLT is important, it is equally important clinically to recognize
when a DLT is too large (bronchial lumen will not fit in bronchus or forms an airtight seal with no air in the cuff) or
too small (requires more than ~3 cc of air in the bronchial cuff to create a seal) and adjust accordingly.
Right-sided double-lumen tubes

The perceived or real difficulty in achieving adequate OLV with right-sided DLTs is evidenced by the fact
that they are used much less frequently than are left-sided DLTs: Currently, 96% of Bronchocath sales are left-sided
(Erich Weiss, personal communication, 2016). Use of left-sided DLTs is generally encouraged because of the
greater margin of safety in positioning them, but a retrospective analysis of 691 cases demonstrated
indistinguishable oxygenation, ventilation, and airway pressure performance between right- and left-sided DLTs
(14). Moreover, in the hands of infrequent users of DLTs, the 3 aforementioned performance criteria were less
favorable using left-sided tubes (15).
When right- and left-sided DLTs were compared for left-sided thoracic surgery in 40 patients, no right upper
lobes collapsed and the difference in the time to place the tubes was clinically insignificant (3.37 vs. 2.08 min) (16).
Although their routine use in thoracic surgery is controversial (16, ), right-sided DLTs are indicated when a patient
requires a DLT but also has an anatomic abnormality of the left mainstem bronchus such as an exophytic or stenotic
lesion or left tracheobronchial disruption. Regardless of the reasons for use, right mainstem bronchial length of at
least 23 mm best accommodates the bronchial cuff and facilitates successful use (18). This length can be
determined bronchoscopically or from a CXR or CT. Attempts to position a right-sided DLT in patients whose right
mainstem bronchi are too short are almost certainly doomed to failure.
Fiberoptic placement and positioning of double-lumen tubes

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Precise positioning of a DLT is most reliably achieved with the benefit of a FOB. In comparisons of
fiberoptic positioning of DLTs with conventional methods, over one-third of left DLTs were malpositioned after
blind intubation and the inspection and auscultatory method (19). In a study of 200 patients, the incidence of
malposition (0.5 cm deviation from ideal position) was 39.5% with 14% of them “critical” (20). Critical
malpositions were those in which the left endobronchial limb allowed no clear view of the left upper or lower lobe
bronchus, the right endobronchial limb allowed no clear view of the RUL bronchus, or there was intratracheal
dislocation of more than one-half of the endobronchial cuff. Visually unassisted placement of left DLTs may result
in initial intubation of the wrong bronchus 7-30% of the time (20,21,22,23).
Ovassapian described a reliable and reproducible method of placing left-sided tubes (and right-sided, with
slight modification) on the first attempt (22). This technique involves first inserting the DLT through the glottis
with direct laryngoscopy, rotating it 90° leftward, and advancing it only until the proximal edge of the tracheal cuff
is past the vocal cords. This limited advancement ensures that the tip of the bronchial lumen is supracarinal. After
the tracheal cuff is inflated, ventilation through both lungs is initiated. The FOB is then placed through the
bronchial lumen and advanced until the carina and mainstem bronchi are clearly identified. The posterior
membranous portion of the trachea, the 5 cm left mainstem bronchus, and the characteristic trifurcation of the RUL
bronchus are reliable anatomic landmarks to facilitate directional orientation. The FOB is then advanced into the
left mainstem bronchus to a position just proximal to the left upper and left lower lobe bronchi. After deflation of
the tracheal cuff, the entire DLT is slid over the FOB until its bronchial lumen comes into view beyond the tip of the
FOB. Confirmation of a patent left upper and left lower lobe bronchus ensures that the DLT is not in too far.
Finally, the FOB is passed through the tracheal lumen to check for a carinal or subcarinal position of the bronchial
cuff and ensure patency of the right mainstem bronchus.
Initial passage of left-sided DLTs through the glottis can sometimes be difficult using the typical 90°
counterclockwise rotation. 164 patients were randomly allocated to 90° or 180° left-sided DLT rotation once the
bronchial lumen’s tip passed the glottis. 180° rotation facilitated DLT passage through the glottis and reduced the
incidence of postoperative sore throat (20 vs. 40%) and vocal cord trauma (19 vs. 47%). All 9 of the 84 DLTs that
could not be advanced after 90° rotation were successfully placed with 180° rotation. The authors acknowledged
that attention to re-rotating 90° clockwise is important, lest the posterior membranous wall of the trachea be injured
(24).
When 50 thoracic surgical patients with left-sided DLTs were positioned from supine to lateral, the tubes
tended to move outward by an average of about 1 cm (25). Inflation of the endobronchial cuff before lateral
positioning did not decrease the incidence or the amount of overall distance change. Because of the tendency for
carinal shift and DLT movement upward with lateral positioning, there is an advantage to keeping the bronchial cuff
5-10 mm inside the left mainstem bronchus before turning laterally. In another study of 61 patients, the incidence of
proximal repositioning was reduced significantly (43% vs. 16%) after turning from supine to lateral when the left
Bronchocath was initially inserted with the proximal edge of its bronchial cuff 5 mm beyond the tracheal carina
(26). Intraoperative use of a rigid neck collar to prevent head and neck movement will minimize but still not prevent
DLT movement while positioning supine to lateral (27). Initially positioning the DLT without a headrest may
minimize this displacement (28). This same tendency toward outward movement was also recently demonstrated in
cadavers (29).
Confirming lung separation

Of the techniques described to achieve a minimum occlusive seal (30,31,32), I routinely use the positive
pressure test or bubble test depicted in Figure 3. There are a number of reasons to use a “just seal” technique to
inflate the bronchial cuff of a DLT or bronchial blocker (BB). First, a cuff that is inflated beyond a minimum
occlusive pressure may result in bronchial mucosal ischemia or even rupture (31,33). Second, an over-inflated
bronchial cuff or BB is more likely to herniate over the tracheal carina and interfere with contralateral ventilation
TBD
Page 5
Third is the ability to immediately and definitively

verify lung separation. That “moment of truth” when
the thoracoscopic port is inserted or the hemithorax is
opened is thoroughly predictable. If lung collapse is
slow or incomplete, documented lung separation
assures the anesthesiologist that manipulation of the
DLT or BB or their cuffs will not improve the
situation. Attention can be focused on other
maneuvers that will improve the surgical exposure:
manual compression, suction, additional time, or
intrahemithoracic CO2 insufflation (34).
Facilitating lung collapse

Once functional lung separation is confirmed and one-lung ventilation begins, collapse of the non-
ventilated lung occurs in 2 phases. The first phase is secondary to lung elastic recoil and commences with pleural
opening when ambient air enters the pleural space. This phase is terminated by small airways closure. The second,
slower phase is due to absorption atelectasis (35). This atelectasis was achieved most rapidly with DLTs using a
N2O/O2 mixture (FiO2=40%), then 100% O2, and then air/O2 (FiO2=40%) due to the diffusion differences of these
gases (36,37). Moreover, lung collapse will be most rapid if lung separation is initiated at end expiration (at FRC),
especially when using a BB that has a small or absent lumen (30). The use of 50% N2O prior to the initiation of
one-lung ventilation using BBs has also been shown to facilitate lung collapse without compromising oxygenation
(38). Most recently, in a study comparing BB with DLTs in patients with normal lung elastic recoil undergoing
VATS procedures, instituting 2 periods of apnea (first, prior to initiating OLV; second, coincident with pleural
opening) resulted in significantly faster and more complete lung collapse with BBs than DLTs (39). Data
supporting the use of suction to facilitate lung collapse are not compelling despite its frequent use.
Comparison of lung isolation techniques

Campos et al prospectively compared the effectiveness of lung isolation with a left Bronchocath, TCB
Univent tube, and the Arndt endobronchial blocker through a SLT in 64 elective right- and left-sided thoracic
surgical cases (40). There were no statistically significant differences among the 3 groups in frequency of tube
malpositions, number of required bronchoscopies, or overall quality of lung isolation as assessed by the surgeon
(blinded to technique) once lung isolation was achieved. The Arndt blocker took slightly longer to place (3 min, 34
sec) compared to the DLT (2 min, 8 sec) or Univent (2 min, 38 sec) groups, inclusive of time to place the SLT,
although 86- and 46-sec differences are hardly of clinical significance. Complete lung collapse took longer with the
Arndt blocker (26 min, 2 sec) than with the DLT (17 min, 54 sec) or Univent (19 min, 28 sec) and more frequently
required suction assistance.
Campos et al also studied the success with which the occasional thoracic anesthesiologist (< 2 cases per
month) correctly placed and positioned these same 3 devices in 66 patients with favorable airways (41). He found
an astonishing overall 38% failure rate with no differences between devices! When successful, placement times
averaged between 6 and 9 minutes regardless of the device used. Their observations suggested that unfamiliarity
with tracheobronchial anatomy and lack of skill in fiberoptic bronchoscopy were most responsible for the
difficulties. An excellent web-based resource for self-assessment and learning of tracheobronchial anatomy is the
Bronchoscopy Quiz and Simulator at www.thoracicanesthesia.com developed by Drs. Kanellakos, Dugas, Wong,
and Slinger.
Comparing a left Bronchocath DLT to the Arndt BB for port-access cardiac surgery, more laryngoscopy
attempts (2.3 vs. 1.1) and additional time (105 sec) to replace the DLT at the end of the case were trade offs for
slightly better right lung deflation with DLTs (42). More recently, in comparing three different BBs to left DLTs for
left-sided surgery, all four devices provided equivalent surgical exposure at 10 and 20 minutes after pleural opening
(43). Postoperative hoarseness was prospectively found to be more common with DLTs (44%) than BBs (17%) (44)
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A 2015 meta-analysis sought to determine the efficacy and adverse affects of BB and DLTs. Of 39 RCTs
published between 1996 and 2013, 13 met inclusion criteria. Overall, DLTs were quicker to place (mean difference
= 51 sec) and were less likely to be incorrectly positioned than BBs (odds ratio = 2.70). However, patients managed
with BBs had fewer sore throats (odds ratio = 0.39), less hoarseness (odds ratio = 0.43), and fewer airway injuries
(odds ratio = 0.40) than with DLTs (45).
Lung separation and the difficult airway

In the patient with a difficult airway who requires lung separation, the concern for providing lung separation
is subordinate to securing the airway. Several options exist for achieving lung separation once a SLT has been
successfully placed. BBs are especially useful in these situations, particularly when a nasal intubation is required
(46). An algorithm for airway management options is presented in Figure 4.
A. Upper and lower airway difficulties

Airway difficulties may arise from the upper airway (more common) or the lower airway. Upper airway
anatomic or pathologic features that render conventional rigid laryngoscopy difficult for placement of SLTs are even
more problematic for the placement of DLTs and Univent tubes because of their size and shape (47). Awake
fiberoptic intubation with a SLT or DLT may be the best option in cases of known or anticipated difficult intubation
and ventilation (21,48,49).
Lower airway difficulties can be encountered due to anatomical variation (e.g., aberrant or supernumerary
tracheal bronchi)(50) distortion of the tracheobronchial anatomy due to prior surgery (e.g., apically retracted LMSB
following left upper lobectomy) (51) or strictures, extraluminal compression, or intraluminal masses. These changes
may require creative solutions to lung separation and will influence the selection of the targeted bronchus and choice
of a BB or DLT. Lower airway difficulties can be detected or predicted by diagnostic bronchoscopy before
intubation or by imaging studies performed preoperatively.
B. Options for lung separation

Double-lumen tubes. The literature on videolaryngoscopy (VL) to facilitate DLT insertion has blossomed
and now contains more comparative trials rather than just case reports or series. One recent study randomly
allocated 60 patients with normal airways to intubation with a Glidescope or Macintosh direct layngoscope (DL).
Although duration of intubation was longer with DL (63 vs. 46 sec), the success of the first intubation attempt (87
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vs. 100%) was not significantly different (52). Another 2012 study allocated 170 patients to intubation with a CEL-
100 VL or Macintosh DL (this VL has a 30 degree curve whereas the Glidescope's is 60 degrees). These authors
found similar intubation times but a higher first attempt intubation success (93% vs. 79%) with the CEL-100 (53).
Critical analysis of all such studies must consider both patient characteristics (e.g., average BMIs were all <24),
design features of the particular VLs, and importantly, VL and DLT experience of the operators (54).
Oral fiberoptic intubation with a DLT is well described in both awake and asleep patients (49,55,56). A
patient’s mouth opening and oropharyngeal size must be large enough to accommodate a DLT for orotracheal
intubation. Awake placement requires good topical anesthesia, adequate conscious sedation, and assistance in
maintaining soft tissue support. Soaking a DLT in a warm water bath just before intubation and using sufficient
lubrication will minimize its rigidity and has been recently shown to decrease the incidence of postoperative sore
throat and vocal cord injuries (but not hoarseness) (57). Concurrent direct laryngoscopy may be required to elevate
the supraglottic tissues to facilitate passage of a DLT through the glottic opening after the fiberoptic scope is in the
trachea (56). Videolaryngoscopy may add further benefit (58).
Univent tubes. Some anesthesiologists consider a Univent tube easier to place and position than a DLT (59),
particularly in patients with upper airway abnormalities (60). The internal diameter of the ventilating lumen in a
size 8.5 or 9.0 Univent tube will accommodate an adult 5.0 mm bronchoscope (59), which then precludes the need to
change tubes after diagnostic bronchoscopy. Although it is also suitable for fiberoptic intubation, the Univent tube
has several limitations. First, unlike the polyvinyl chloride of the SLT and DLT, the Univent tube is constructed of a
polymeric silicone material that will not soften in a warm water bath. As such, its curved shape is fixed, and this
may be a disadvantage when sliding it over a bronchoscope. Second, the fixed concavity often makes the leading
edge of the tube impinge upon the vocal cords, impeding its passage into the trachea. A successful nasal intubation
with a 7.0 Univent tube has been described, despite its size and rigidity (61).
Endobronchial blockers. See earlier discussion.
Single-lumen endotracheal tubes. Using a SLT to intubate a mainstem bronchus is another option for
achieving lung separation and is frequently the preferred technique for children who are too small for DLTs or
coaxial BBs (62). Advantages of this approach include its simplicity and the rapidity with which lung separation
can often be achieved, particularly when the right lung must be ventilated. Blind advancement of a SLT will rarely
result in a left mainstem intubation, but rotating an in situ SLT 180° while turning the patient’s head to the right will
improve the success rate of left mainstem intubation to about 92% (63). Fiberoptic guidance of a SLT into the
appropriate mainstem bronchus is probably the easiest and most reliable technique. If significant amounts of blood
or secretions preclude fiberoptic visualization, using fluoroscopy to visualize and direct the radiopaque
bronchoscope is another option (64).
Disadvantages of the use of a SLT for lung separation include frequent exclusion of RUL ventilation when a
SLT is in the right mainstem bronchus. Left upper lobe ventilation can also be excluded when the left mainstem
bronchus is relatively short (65). Regardless of which lung is ventilated, neither independent suctioning nor
application of CPAP to the nonventilated lung is possible. Lastly, if the nasotracheal route is used, most SLTs will
not be long enough to provide a reliable mainstem intubation.
SLT to DLT exchange. Exchange of a SLT for a DLT is a strategy commonly employed to achieve lung
isolation when insertion of a DLT is difficult. In a simulator study comparing 3 different DLT designs, the Fuji-
Phycon tube was faster and easier to pass over an airway exchange catheter (AEC) than DLTs manufactured by
Rusch or Mallinckrodt when using an AEC plus Glidescope technique (66). The authors attributed this difference to
the Fuji-Phycon’s more beveled bronchial tip, softer silicon material, and more angulated bronchial limb.
Successful tube exchange is never a guarantee, especially when changing SLTs to DLT. A single center
retrospective analysis of 1177 airway exchanges found an overall 13.8% failure rate, with 43/110 (39.9%) of SLT to
DLT exchanges unable to be completed as intended (67). Cook Critical Care manufactures AECs specifically
designed for DLT exchanges. These differ from conventional AECs in that they are longer (100 cm), have
centimeter markings that extend to 50 cm, and are extra firm with a 7-cm flexible tip. 11 and 14 F sizes will fit
inside small and large DLTs, respectively.
C. The patient with a tracheostomy

Although the presence of a tracheostomy greatly simplifies airway management for most anesthetics, it presents an
interesting challenge when lung separation is required. As with orotracheal intubation, options include a DLT (21),
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Univent tube (68), or BB through the tracheostomy stoma. Depending upon the details of a patient’s anatomy such
as stomal diameter, distance between the skin and the anterior tracheal wall, and stoma-to-carinal distance, DLTs
and Univent tubes may be difficult to place and position precisely and atraumatically.
Another way to achieve lung separation in a patient with a tracheostomy is using a BB, either coaxially or
alongside a SLT or tracheostomy tube through the stoma (69) or through the mouth (70). Blind or fiberoptically
directed mainstem intubation with a SLT inserted through the stoma is yet another option, although it has the usual
limitations associated with mainstem intubations. A short DLT specially designed for use with tracheostomies is
available (71).
D. Extubation and postoperative intubation

When the decision is made to leave a patient intubated after a procedure involving lung separation, some
special considerations need to be addressed. The possibility of the recurrent need for lung separation should be
considered a reason to leave a patient intubated. Occasionally, an airway that was not difficult initially may become
difficult after a lengthy procedure involving large fluids shifts that contribute to upper airway or head and neck
edema. An anticipated need for postoperative intubation should therefore inform the preoperative choice of lung
separation technique. If a SLT with a BB was used, then all that needs to be done at the end of the procedure is to
remove the BB. If a Univent was used, then its blocker should be fully retracted, and the Univent can function as a
SLT.
If a DLT was used for lung separation, then the risks and benefits of changing to a SLT must be carefully
weighed. The main advantage to leaving the tube in place is that the hazards associated with a tube change with a
difficult airway are avoided. In this case, one can leave the tube positioned and ventilate both lungs through both
lumens. Alternatively, the tube can be withdrawn to the point at which the tip of the bronchial lumen is just above
the carina, which will position the tracheal cuff below the vocal cords (72). Increased flow resistance leading to
obstructed expiratory flow or increased work of breathing is probably not clinically significant with 37 F or larger
Rusch or Sheridan DLTs (73).
Keys to success in one-lung anesthesia
•Understand the physical details of DLTs and BBs - select them appropriately
•Use the FOB! – optimize conditions (antisialagogue, suction), learn the tracheobronchial anatomy, and practice!
•Employ a “just seal” test every time – avoid trouble and identify problems early
References
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Anesthesia for Thoracic Surgery, 2nd Ed. Philadelphia: WB Saunders, 1995: 330-389 31. Guyton DC, et al. J
Cardiothorac Vasc Anesth 1997; 11:599-603 32. Hannallah MS, et al. Anesth Analg 1993; 77:990-994 33.
Fitzmaurice BG, et al. J Cardiothorac Vasc Anesth 1999; 13:322-329 34. Brock H, et al. Anaesthesia 2000; 55:10-
16 35. Pfitzner J. Anaesth Intensive Care 2016; 44:20-27 36. Nunn JF. Nunn’s Applied Respiratory Physiology,
4th ed. Oxford: Butterworth-Heinemann, 1993:496 37. Ko R, et al. Anesth Analg 2009; 108:1092-1096 38.
Yoshimura T, et al. Anesth Analg 2014; 118:666-670 39. Bussières JS, et al. Can J Anesth 2016; 63:818-827
40. Campos JH, et al. Anesth Analg 2003; 96:283-289 41. Campos JH, et al. Anesthesiology 2006; 104:261-266
42. Grocott HP, et al. J Cardiothorac Vasc Anesth 2003; 17:725-727 43. Narayanaswamy M, et al. Anesth Analg
2009; 1097-101 44. Knoll H, et al. Anesthesiology 2006; 105:471-477 45. Clayton-Smith A, et al. J Cardiothorac
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112 61. Gozal Y, et al. Anesthesiology 1996; 84:477 62. Hammer GB, et al. Anesth Analg 1999; 89:1426-1429
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65. Lammers CR, et al. Anesth Analg 1997; 85:946-947 66. Gamez R, et al. Anesth Analg 2014; 119:449-453
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Anesthesiol 1999; 12:29-35 73. Slinger PD, et al. J Cardiothorac Vasc Anesth 1998; 12:142-14
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Anesthetic Management of the Severely Preeclamptic Patient
Joy L. Hawkins, M.D. Aurora, Colorado
Introduction
Hypertensive disorders of pregnancy are responsible for 11% of maternal deaths after a live birth in the U.S, with
death usually resulting from a cerebrovascular accident. 1 Preeclampsia occurs in 6-8% of pregnancies; 75% of cases
are mild and 25% are classified as severe. Anesthesiologists will be involved when high risk parturients deliver and
we must be an important part of the team caring for these critically ill patients.
Definitions
The American Congress of Obstetricians and Gynecologists (ACOG) classification system for hypertensive diseases
of pregnancy clarifies terminology and provides an estimate of risk for the mother and fetus. 2
 Preeclampsia / Eclampsia presents after 20 weeks’ gestation with hypertension > 140/90, proteinuria, and a
spectrum of multi-organ system dysfunction such as thrombocytopenia. HELLP syndrome is a subset of
severe preeclampsia defined by hemolysis (H), elevated liver enzymes (EL) and low platelets (LP).
 Chronic hypertension is unrelated to pregnancy, presenting before 20 weeks’ gestation or before
conception.
 Preeclampsia superimposed on chronic hypertension presents with worsening or difficult-to-control
hypertension, new onset thrombocytopenia, or other systemic manifestations of preeclampsia. This
diagnosis carries substantial increased risk for the mother and fetus.
 Transient or gestational hypertension is hypertension in late pregnancy, without other evidence of
preeclampsia that completely resolves postpartum. There is minimal risk to the mother or her fetus,
although ACOG now recommends delivery at 37 weeks.
 The terms “PIH” or “pregnancy-induced hypertension” are no longer used.
Etiology and Pathogenesis

Despite decades of research, the etiology of preeclampsia remains unknown. Preeclampsia is a syndrome that 1)
only occurs in pregnancy, 2) is characterized by maternal inflammation, and 3) is associated with the presence of a
placenta.3 Theories include placental ischemia, immunologic origin, and genetic predisposition. No theory has
withstood the test of time, and no preventive measure has proven useful. Preventive measures that have been tested
include supplementation with magnesium, zinc, fish oil, anti-oxidant vitamins (C and E) and calcium, protein or salt
restriction, antihypertensive medications in women with chronic hypertension, and exercise.4 None have reduced
the incidence of preeclampsia. Administration of unfractionated heparin, low molecular weight heparin, or low-dose
aspirin therapy have led to decreases in preeclampsia and fetal/neonatal deaths in some studies, and may be used in
high-risk pregnancies. New guidelines from the U.S. Preventive Services Task Force state that women at increased
risk of preeclampsia (e.g. preeclampsia in a previous pregnancy) derive more benefit than harm from taking low-
dose aspirin.5 They recommend 50-160 mg/day from 12 until 28 weeks’ gestation.
Although the etiology and prevention of preeclampsia remain elusive, the risk factors for developing
preeclampsia are well known. The strongest contemporary risk factor is obesity, and there is a dose-response risk
with increasing BMI such that BMI > 40 has an odds ratio (OR) of 6. 6 Other significant risk factors include pre-
gestation diabetes (OR 3.9), multiple gestation (OR 3), chronic hypertension (OR 2.7), African-American race (OR
1.9), nulliparity (OR 1.7), and infertility techniques (OR 1.7). 6
The pathophysiology of preeclampsia is different in early and late stages. The early stage involves
abnormal placentation. The spiral arteries fail to become the dilated, flaccid vessels seen in normal pregnancies, and
may even show signs of atherosis. The placenta becomes ischemic and releases vasoactive substances. Maternal
hemodynamics are hyperdynamic with elevated cardiac output. Later in gestation, the disease manifests as a
maternal systemic disorder with increased vascular sensitivity to any pressor agent, activation of the coagulation
cascade, microthrombi and intravascular fluid loss. Vasospasm, hemoconcentration, and ischemic changes in the
placenta, kidney, liver and brain are seen. Maternal hemodynamics show elevated SVR and reduced cardiac output.
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Prediction and Diagnostic Tools

A gene encoding protein sFlt1 is overactive in preeclamptic placentas. sFlt1 is known to thwart blood vessel
growth; i.e., it is anti-angiogenic. There is growing evidence that measuring elevated antiangiogenic proteins such
as soluble Flt1 and soluble endoglin can predict preeclampsia months before its clinical onset. 7 These proteins are
secreted by the placenta and increase in the maternal circulation weeks before the onset of preeclampsia, producing
systemic endothelial dysfunction such as hypertension, proteinuria and other manifestations of preeclampsia. A
systematic review of the literature on use of elevated sFlt-1 and reduced placental growth factor (PlGF – a pro-
angiogenic protein) to predict preeclampsia concluded that third-trimester increases in sFlt-1 combined with
decreases in placental growth factor levels are associated with severe preeclampsia. Measuring soluble sFlt-1 and
soluble endoglin levels in gestational hypertension, chronic hypertension, preeclampsia and normal pregnancies
demonstrated a high sensitivity and specificity in differentiating women with preeclampsia from those with other
hypertensive diseases during pregnancy.7 In the future, alterations of these proteins might be used as a screening test
for early diagnosis of preeclampsia. A pilot study of five very preterm preeclamptic women used apheresis
treatments to remove elevated circulating sFlt-1, in an attempt to prolong the pregnancy. 8 In addition to lowering
circulating sFlt-1 levels, the treatment reduced proteinuria and stabilized blood pressure without adverse effects on
the mother and with evidence of improved interim fetal growth.
Controversial Areas in the Clinical Management of the Patient with Preeclampsia

 When and by what route should delivery occur, especially when preeclampsia develops early in the 3 rd
trimester and the preterm newborn’s morbidity is high?
 When should invasive monitoring be used to optimize care of the mother? Is there a place for non-invasive
monitoring techniques?
 What are the benefits and risks of various anti-hypertensive medications? What does ACOG recommend?
 How should we manage an eclamptic seizure?
 Why administer magnesium sulfate rather than other anti-seizure medications?
 How should we optimize fluid management?
 Platelet counts – how low can we go and still safely administer neuraxial anesthesia?
 Is spinal anesthesia for cesarean delivery safe and appropriate in severe preeclampsia?
 Should α-agonists (e.g. phenylephrine) replace ephedrine as our first-line pressor to treat hypotension after
neuraxial techniques?
Current Obstetric Management Strategies

The only cure for preeclampsia is delivery, but the benefit to the mother must be weighed against the risks to the
fetus of prematurity. Women with gestational hypertension or mild preeclampsia may be managed expectantly at
home with frequent maternal monitoring and fetal surveillance. Patients with severe preeclampsia must be admitted
to L&D for continuous maternal and fetal assessment and development of a delivery plan. Those with a favorable
cervical exam should undergo induction of labor because neonates delivered vaginally have a lower incidence of
RDS. Elective cesarean delivery may be preferable in very preterm pregnancies if the cervical exam is unfavorable.
Maternal assessment must define the extent of end-organ involvement. Systems evaluated should include:
hematologic (↓ platelets, hemolysis), hepatic (epigastric pain, ↑ LFT), neurologic (headache, visual changes), renal
(oliguria, proteinuria, ↑ creatinine), pulmonary (pulmonary edema), and the placenta (growth restricted fetus,
oligohydramnios, abnormal umbilical artery Doppler studies). Fetal evaluation will include a non-stress test,
ultrasound for amniotic fluid volume, fetal growth percentile, estimate of gestational age, and a biophysical profile.
Based on these results, a decision for immediate delivery versus in-hospital expectant management will be made. If
the pregnancy is < 34 weeks, the obstetrician may delay delivery for 48 hours to administer steroids for fetal lung
maturity, but this requires daily maternal and fetal monitoring, magnesium sulfate infusion, and anti-hypertensive
drugs as needed for systolic BP > 160 or diastolic BP > 110 mmHg.9 Delivery is required for worsening maternal or
fetal condition. Patients who are not candidates for expectant management include women with eclampsia,
pulmonary edema, DIC, renal insufficiency, abruption, abnormal fetal testing, HELLP syndrome, or persistent
symptoms of severe preeclampsia.
Early-onset preeclampsia is a different and more severe disease than late-onset preeclampsia. Placental
pathology in early-onset disease is characterized by hypoplasia and vascular lesions of insufficiency, while late-
onset preeclampsia is characterized by inflammation and placental hyperplasia. 10 Early-onset preeclampsia is less
common than late-onset (0.3% versus 2.7%), but maternal mortality is higher with early-onset preeclampsia (42 per
100K deliveries with early, versus 11 per 100K with late, versus 4 per 100K with no diagnosis of preeclampsia) as is
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maternal morbidity (12.2 per 100 deliveries with early, versus 5.5 per 100 deliveries with late, versus 3 per 100
deliveries with no diagnosis of preeclampsia). 11
HELLP syndrome is a variant of severe preeclampsia. Administration of high-dose glucocorticoids
(dexamethasone 10 mg BID for example) has been reported to improve maternal and fetal outcome, but without
large multicenter trials to define the limits of benefit and any maternal or fetal risk. A review of the literature on
glucocorticoids for HELLP syndrome (including a management algorithm) concludes that the bulk of evidence to
date is positive - improved platelet count, reduced stroke and death, and less hepatorenal morbidity. The authors of
the review conclude that glucocorticoids should be considered during treatment of HELLP syndrome.12
Use of Invasive Monitoring and Treatment of Hypertension

Invasive monitoring is rarely necessary in obstetric patients. “Critically ill obstetric patients differ from those
usually encountered in medical-surgical intensive care units. They are likely to be younger, to have fewer major
organ systems involved, to have fewer chronic illnesses, and to recover fully with supportive care.” (Chest 1992)
However, arterial lines are low risk and can be useful when blood pressures are consistently greater than 160/110
mmHg and when vasodilator infusions are used. They may also be helpful for patients with coagulopathy who need
frequent blood draws, and when the patient is obese or has marked edema making venipuncture difficult. If
pulmonary edema develops, the arterial line can be used to monitor arterial blood gases. Pulse waveform analysis
(e.g., LiDCOplus™) can be used with an arterial line for hemodynamic monitoring as it correlates well with
thermodilution measurements from a pulmonary catheter.13 In contrast, central venous monitoring carries more
risks and has not been shown to affect outcome. A CVP or PA catheter may be useful if there is cardiac failure or
pulmonary edema, a large A-a oxygen gradient, or oliguria despite fluid administration and afterload reduction.
Consider your nursing resources on L&D before initiating invasive monitoring however. Can the L&D nursing staff
manage a CVP or pulmonary artery catheter on L&D, or will ICU admission be necessary?
The goal of anti-hypertensive therapy is to prevent pulmonary edema and cerebral hemorrhage by
decreasing systolic blood pressure < 160 mmHg and diastolic < 110 mmHg. At the same time, treatment should not
impair uteroplacental perfusion or cause fetal compromise. Systolic hypertension may be more important than
diastolic for preventing stroke related to severe preeclampsia.14 A review found that 93% of the strokes in their
series were hemorrhagic, 54% of women died, and almost all who lived had severe permanent disability. All had
systolic pressure >155 mmHg while only 12% had diastolic pressure >110. CVA’s that occur with hypertensive
disorders of pregnancy are associated with impaired cerebral autoregulation, which is reduced in preeclampsia and
chronic hypertension, but lowest in chronic hypertension with superimposed preeclampsia.15 Pregnancy-related
strokes have increased over the past 20 years, and strokes in women with hypertensive disorders were associated
with more frequent complications and death. 16
The ACOG Committee Opinion entitled “Emergent Therapy for Acute-Onset, Severe Hypertension with
Preeclampsia or Eclampsia” defines a hypertensive emergency as systolic pressure > 160 mmHg or diastolic
pressure > 110 mmHg lasting 15 minutes or longer.17 Previous work has shown hypertension is the most important
predictor of cerebral hemorrhage or infarction and can result in maternal death. Aggressive treatment is imperative!
Intravenous labetalol, PO nifedipine, and intravenous hydralazine are considered first-line treatments, and the
document includes order sets for administration. Importantly for anesthesiologists, the document states that if these
medications fail to control blood pressure, “emergent consultation with an anesthesiologist, maternal-fetal medicine
subspecialist, or critical-care specialist to discuss second-line intervention is recommended.”17 A national group
reported they had been able to reduce their maternal deaths from preeclampsia 5-fold by instituting a policy for
automatic, rapid anti-hypertensive therapy for defined blood pressure elevations. 18 How “tight” should blood
pressure be controlled when treating chronic hypertension during pregnancy (not preeclampsia)? An RCT of “tight”
(diastolic 85 mmHg) versus less-tight (diastolic 100 mmHg) control during pregnancy found no benefit of tight
control to the fetus and only moderate benefit to the mother.19
Many agents are effective and safe to use as anti-hypertensives. Using non-invasive hemodynamic
monitoring to determine whether the patient’s hemodynamics are hyperdynamic or characterized by elevated SVR
and compromised cardiac output can be very helpful. Trans-thoracic echocardiography, bio-impedance devices or
analysis of the arterial waveform have been described. Anti-hypertensives to consider in practice:
1. Hydralazine 5-20 mg is a popular choice in obstetrics because it is an arteriolar vasodilator that increases
uterine and renal blood flow. However, it has an unpredictable onset and duration, causes reflex
tachycardia and occasional dysrhythmias. It has also been reported to cause neonatal hypotension by
crossing the placenta.
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2. Labetalol decreases systemic vascular resistance without maternal tachycardia while preserving placental
blood flow, however its dosing and duration may be quite variable. It does not cause sympathetic blockade
in the neonate. It can be transitioned to an oral form after delivery.
3. Calcium channel blockers such as nifedipine and nimodipine cause a rapid smooth fall in blood pressure
while increasing renal perfusion and urine output. Although there has been concern about combining
magnesium therapy with nifedipine, a study found that in women already receiving magnesium sulfate
therapy, adding nifedipine did not increase muscle weakness over magnesium alone, and there was less
hypotension with nifedipine than with other anti-hypertensives. Nimodipine reverses cerebral vasospasm
as measured by trans-cranial Doppler, and is well-tolerated by mother and fetus. However, calcium
channel blockers cause uterine relaxation, making induction of labor more difficult and potentially causing
atony and hemorrhage after delivery.
4. Nitroprusside has a fast onset, short duration, and preserves uterine blood flow. However, it leads to reflex
tachycardia and has the potential for cyanide toxicity. It causes cerebral vasodilation that could increase
intracranial pressure and it decreases hypoxic pulmonary vasoconstriction potentially leading to hypoxia.
Finally, it is inconvenient to use and requires an arterial line, as does nitroglycerin.
5. ACE inhibitors and angiotensin receptor blockers are teratogenic and contraindicated in all trimesters of
pregnancy. Avoid atenolol (IUGR concerns) and chronic diuretic therapy.20
6. Magnesium sulfate is not an anti-hypertensive and has no substantial long-term effect on blood pressure,
but has other benefits. It attenuates the vascular response to pressor substances (either endogenous or
exogenous) and dilates vascular beds by increasing prostacyclin release from endothelial cells, decreasing
plasma renin activity, and decreasing ACE levels. It also provides neuroprotection for premature fetuses
less than 32 weeks.
Prevention and Management of Seizures / Eclampsia

Eclampsia has a maternal mortality rate of ~ 4% and a perinatal mortality rate of up to 30%. Seizures occur
antepartum in 50% of patients, intrapartum in 25% and postpartum in 25%. Why do we use magnesium to prevent
eclamptic seizures rather than other traditional anti-seizure medications? In large randomized clinical trials,
magnesium has been proven superior to placebo (58% lower risk of seizures), phenytoin (no seizures in the
magnesium group versus ~1% in the phenytoin group), diazepam (52% lower risk of recurrent convulsions), and
nimodipine (risk of eclampsia was 3.2 times higher in the nimodipine group). No drug is superior to magnesium at
preventing eclampsia.21,22
Magnesium therapy is not without complications however. It can cause maternal morbidity and unpleasant
side effects. It has tocolytic properties that prolong labor and increase bleeding at delivery. It decreases fetal heart
rate variability, depresses maternal and neonatal neuromuscular function, and can cause maternal respiratory
depression and cardiac toxicity at excessively high blood levels. Clearance is reduced with renal insufficiency, and
signs of toxicity are only partially reversed with calcium. Consider dialysis for life-threatening overdose.
Since major complications of preeclampsia occur in the 25% of patients with the severe form of the
disease, should mild preeclampsia even be treated with magnesium? What is the risk/benefit ratio for the mother?
A decision analytic model of magnesium therapy or no magnesium therapy found that 400 women with mild
preeclampsia need to be treated to prevent one seizure. The number needed to treat to prevent a seizure (NNT) fell
to 129 in severe preeclampsia, and to only 36 in severely preeclamptic women who had symptoms such as headache,
visual disturbances or epigastric pain.23 Women with mild preeclampsia may not require magnesium sulfate therapy.
When an eclamptic seizure occurs, the following steps should be taken:
 Administer high flow supplemental oxygen by mask and place a pulse oximeter to assure adequate
maternal oxygenation.
 Turn the patient to full left or right lateral position and have suction immediately available.
 Give a small dose of propofol or a benzodiazepine to terminate the seizure if available. Avoid poly-
pharmacy and long-lasting medications so that a neurologic exam can be done as soon as possible.
 Administer an additional 2-gram magnesium bolus to assure levels are therapeutic.
 Monitor the fetus if possible, but realize that heart rate abnormalities are common during a seizure and
usually resolve soon after the seizure is terminated. Do not intervene to deliver emergently unless
abruption or cord prolapse has occurred.
 Consider imaging with CT or MRI to rule out a cerebral hemorrhage if seizures are recurrent or focal, if
seizures occur despite therapeutic and repeated magnesium dosing, or if there is decreasing level of
consciousness after the seizure.
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 Although eclampsia is an indication for delivery, it is not an indication for cesarean delivery. When
eclamptic patients were randomized to vaginal delivery or cesarean, there was no difference in maternal or
newborn adverse events.24 Consider whether induction or augmentation of labor is feasible.
Anesthetic Management During Labor and Delivery

When the decision has been made to proceed with delivery, the anesthesiologist must have plans in mind for three
potential scenarios: 1) labor followed by a spontaneous or instrumented vaginal delivery, 2) trial of labor followed
by an urgent or emergent cesarean for fetal or maternal indications, and 3) planned cesarean for the patient who is
not a candidate for trial of labor. All plans must take into account whether neuraxial techniques are appropriate
based on platelet count or other measures of coagulopathy.
Labor Analgesia
The advantages of neuraxial analgesia for labor are numerous. It provides the best quality of pain relief, attenuates
hypertensive responses to pain, reduces circulating catecholamines, and does not require fluid preload when dilute
local anesthetic solutions with opioid are used. Two studies have compared the use of intravenous patient-controlled
opioids (IV PCA) to epidural analgesia for women with severe preeclampsia. In the first, 738 women were
randomized to IV PCA or epidural, and cesarean delivery rates were similar.25 Neonates in the IV PCA group
required more naloxone (12% versus 1%), but women in the epidural group had a longer second stage of labor, more
forceps deliveries and required ephedrine more often (11% versus 0%). Not surprisingly, epidural pain relief was
superior.25 Results were similar in the second study. 26 They found no difference in cesarean delivery rates, but
neonates were more likely to receive naloxone in the opioid group (54% versus 9%), and epidural patients had
significantly better pain relief but required more ephedrine (9% versus 0%). Perhaps most importantly, there were
no differences in preeclampsia-related complications when epidural analgesia was used.26 ACOG makes a strong
statement in their Practice Bulletin Diagnosis and Management of Preeclampsia and Eclampsia: “With improved
techniques over the past two decades, regional anesthesia has become the preferred technique for women with
severe preeclampsia and eclampsia – both for labor and delivery. A secondary analysis of women with severe
preeclampsia in the NICHD trial of low-dose aspirin reported that epidural anesthesia was not associated with an
increased rate of cesarean delivery, pulmonary edema or renal failure.”27
Fluid Management
Fluid management has been controversial, with obstetricians wanting to restrict fluids and anesthesiologists wanting
to administer fluids, however the obstetric view is probably correct. The vasculature in preeclamptic patients has
been described as contracted and porous due to endothelial damage, but not under-filled. In addition to endothelial
damage, the colloid oncotic pressure is low in pregnancy, and even lower in preeclamptic patients with proteinuria.
Crystalloids and colloids readily leak out, increasing the risk of postpartum pulmonary edema. Typical obstetric
management is to “run dry” at 80-100 ml per hour total fluid intake including magnesium and oxytocin infusions.
Anesthetic fluid management should complement theirs, using conservative preload for surgical neuraxial anesthesia
and no preload for labor analgesia. Many studies including a systematic review have shown little if any benefit of
preloading to prevent hypotension during obstetric regional anesthesia.28
Coagulopathy and Platelet Counts

What is the frequency of lab abnormalities in preeclampsia? In a large study of women with hypertension, abnormal
labs occurred in 7.3% of preeclamptic patients. 29 In mild preeclampsia only 5% of women had abnormal studies, as
compared with 9% with severe preeclampsia and 12% with severe preeclampsia plus clinical signs of end-organ
dysfunction. Women with mild disease and no signs of end-organ involvement may not require routine labs since
95% will be normal.29 Despite years of concern and study, there is still no test for platelet function and no specific
platelet count that predicts bleeding into the neuraxis after regional anesthetic techniques. For patients with
preeclampsia, many anesthesiologists are comfortable with platelet counts as low as 75,000 provided the count is
stable and not falling, and that there are no signs of clinical bleeding at venipuncture sites, gums, etc.
Thromboelastography (TEG) can add information if the test is available, but there is still no cut-off value for any
TEG variable that predicts complications. Since pregnancy is a thrombophilic state, parturients have tremendous
reserve before developing a coagulopathy. A review of 1.7 million spinal or epidural blocks found that
complications were more common after epidural than spinal anesthetics, and that obstetric patients were less likely
than surgical patients to have an injury (1: 25,000 obstetric patients versus 1:3600 after surgical epidurals in
females).30 There were two obstetric patients in their series that developed a neuraxial hematoma, for an incidence
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of 1: 200,000. One occurred after a spinal and the other after epidural catheter removal; both patients had HELLP
syndrome. This low incidence is reassuring, but balance the risk-benefit ratio for each case and each patient.
Factors that might support using a regional technique even with borderline labs would include a worrisome
airway exam, the prospect of a lengthy induction of labor, and the rarity of an epidural hematoma. Factors that
would support avoidance of regional anesthesia and use of IV opioids or general anesthesia would be clinical signs
of bleeding, a rapidly worsening platelet count, the need for an urgent cesarean and a good airway. Even if you feel
that neuraxial analgesia is not appropriate, remember that anesthesiologists are consultants in pain management.
Our obstetric colleagues may appreciate help with an IV regimen for the patient’s labor analgesia. For example,
fentanyl can be used in an IV PCA as follows: give an IV bolus loading dose of 2-3 µg/kg to initiate analgesia. Set
the PCA pump for a 50 µg incremental bolus, 10-minute lockout interval and no basal rate. As labor progresses and
titration is needed, decrease the lockout from 10 to 5 minutes, then increase the bolus dose from 50 to 75 µg.
Remifentanil has also been used successfully for patient-controlled analgesia during labor.31
Cesarean Anesthesia
The choices for cesarean anesthesia are epidural, spinal (or combined spinal-epidural) and general. In the past,
spinal anesthesia was avoided because of concerns that hypotension would be more severe and less treatable than
that seen after sympathectomy from an epidural anesthetic. However, a comparison of women with severe
preeclampsia to healthy women, all having cesarean delivery with a spinal anesthetic, found that preeclamptic
women actually had less hypotension (17% versus 53%) despite receiving less fluid preload and (by chance) a larger
dose of bupivacaine in their spinal. 32 A randomized comparison of spinal or epidural anesthesia for cesarean
delivery in women with severe preeclampsia found that although hypotension was more frequent after spinal and
required slightly more ephedrine, the duration of hypotension was short and easily managed, and neonatal outcomes
were similar in both groups.33
Regardless of the choice of neuraxial technique (spinal or epidural), pressors must be immediately available
to treat even mild hypotension since these fetuses may not tolerate any decrease in uteroplacental perfusion.
Although not studied in severe preeclampsia, clinical studies in healthy parturients have consistently shown that use
of α-agonists such as phenylephrine produce better umbilical pH values in the newborn than ephedrine.34 If
maternal heart rate is above 70, choose phenylephrine as the first-line pressor agent.
If general anesthesia is chosen, focus on attenuating hypertensive responses during laryngoscopy and
intubation, managing a potentially difficult edematous airway, and treating complications related to magnesium
therapy such as uterine atony and maternal weakness. Cerebral autoregulation is significantly reduced in women
with preeclampsia, with no correlation between the autoregulation index and blood pressure.35 A number of
adjuncts to rapid sequence induction have been described and used successfully to control hypertension associated
with laryngoscopy, e.g. small, labetalol, nicardipine, remifentanil36 and nitroglycerin. Include at least one adjunct as
part of a rapid sequence induction, or have them immediately available to treat hypertension if it occurs. 37 Airway
management may be difficult. The laryngeal mask airway (LMA) has been used in the setting of HELLP syndrome
when there was inability to intubate or ventilate.38 Postoperatively, this patient was even ventilated in the ICU using
the LMA.
Magnesium therapy has anesthetic interactions such as skeletal muscle weakness. If the mother exhibits
muscle weakness prior to induction (i.e., can she do a 5-second head lift before her anesthetic?), it may be best to
discontinue the magnesium sulfate infusion during the case and let her magnesium level decrease. However, ACOG
recommends continuing the magnesium infusion intraoperatively if possible so that the patient retains a therapeutic
level and doesn’t require re-bolus. Non-depolarizing muscle relaxants should be avoided. If she cannot meet
criteria for safe extubation at the end of the cesarean, she may require a brief period of mechanical ventilation until
she is strong enough to protect her airway. Magnesium is a uterine relaxant, and additional oxytocic medications
such as misoprostol or prostaglandin F2α should be available to treat uterine atony after delivery in addition to the
oxytocin infusion.
Postpartum Care
After delivery patients will require intense monitoring on L&D. All patients will receive 24 hours of magnesium
sulfate for seizure prevention. They should have compression stockings for thromboprophylaxis. If general
anesthesia was used, consider transversus abdominis plane (TAP) blocks to supplement analgesia.39 The mother
may need both acute and long term blood pressure control with anti-hypertensives. Fluid mobilization will begin to
occur during the first 24 hours postpartum, and this is when she is most at risk for pulmonary edema. Monitor urine
output, lung fields and pulse oximetry. Thrombocytopenia may not resolve for several days. If she has an epidural
catheter in place, decide when removal is appropriate based on her platelet count and coagulation studies. About a
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third of eclamptic seizures occur postpartum, and are associated with severe morbidity.40 Many eclamptic patients
did not have an antepartum diagnosis of preeclampsia, but most had prodromal symptoms such as headache and
visual changes. If called to evaluate a postpartum headache, consider late-presenting preeclampsia in your
differential. In a survey of pregnant women presenting to the Emergency Department with acute headache, 65% had
a primary headache diagnosis (91% migraine), but 35% had a secondary cause for the headache and preeclampsia
was the most common secondary diagnosis. 41
Prognosis After the Diagnosis of Preeclampsia

Does development of preeclampsia provide a marker for maternal disease risks later in life? A growing literature
indicates that pregnancy is a form of “stress test” that may predict later health issues in the mother. 42 A 39-year
follow-up of women who had hypertension during pregnancy (even gestational hypertension) found an elevated risk
of cardiovascular disease and chronic hypertension.43 A 22-year follow-up of formerly preeclamptic women versus
controls found hypertension was present in 55% of the formerly preeclamptic women but only 7% of the controls.44
ACOG recommends better long term follow-up of preeclamptic women by their primary care physicians. The
implications of this disease do not end at delivery. Are primary care providers aware that preeclampsia increases
later risk of cardiovascular disease? A study found gynecologists were more likely to ask women about their
pregnancy history, but didn’t get appropriate testing for cardiovascular disease. 45 Internists got the appropriate
testing, but didn’t ask about pregnancy history. Both groups need additional education.
New Guidelines from ACOG

In 2013 the ACOG Task Force on Hypertension in Pregnancy released new guidelines.2 Some highlights include:
1. There are no predictive tests or preventive measures to use, and there are no treatments except delivery.
2. Features of severe preeclampsia are BP > 160/110, platelets < 100K, elevated liver function tests or
epigastric pain, creatinine > 1.1, pulmonary edema and headache or visual changes. Proteinuria has been
eliminated because it has no effect on outcomes.
3. Deliver at 37 weeks if no severe features are present and by 34 weeks with severe features – after steroids
for fetal lung maturity.
4. During cesarean, continue magnesium infusion and use neuraxial anesthesia if possible.
5. Avoid NSAIDs if hypertension persists postpartum.
6. Discharge instructions should include warnings about signs and symptoms of postpartum preeclampsia.
In Conclusion:
 Be conservative with fluid preload before neuraxial procedures. Consider eliminating completely.
 Normalize low blood pressure with phenylephrine in preference to ephedrine.
 The goal for management of blood pressure is to keep maternal pressure near baseline to sustain
uteroplacental perfusion, but < 160 mmHg systolic to prevent cerebrovascular complications.
 Use platelet count trends and your clinical judgment. There is no absolute platelet count or TEG
value to use as a cut-off to assure the safety of neuraxial anesthetic techniques.
 Spinal anesthesia for cesarean delivery is safe. Limit fluid preload and maintain her blood pressure
close to her baseline levels.
 Actively participate as part of the L&D team caring for high risk obstetric patients. 46
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References
1
Obstet Gynecol 2015; 125: 5
2
3
Am J Obstet Gynecol 2015; 213: 268
4
Lancet 2005; 365: 785
5
JAMA 2014; 311: 2055
6
7
8
Circulation 2011; 124: 940
9
Cochrane Database Syst Rev 2013; CD003106
10
11
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Br J Anaesth 2011; 106: 77
14
15
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N Engl J Med 2015; 372: 407
20
21
Lancet 2002; 359: 1877
22
N Engl J Med 2003; 348: 304
23
24
25
26
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Obstet Gynecol 2002; 99: 159 (reaffirmed 2010)
28
Anesth Analg 2011; 113: 677
29
30
Anesthesiology 2004; 101: 950
31
Anesth Analg 2014; 109: 1925
32
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Br J Anaesth 2004; 92: 459
35
36
Int J Obstet Anesth 2013; 22: 10
37
Anesth Analg 2014; 119: 1350
38
39
Int J Obstet Anesth 2012; 21: 112
40
41
Neurology 2015; 85: 1
42
Heart 2015; 101: 442
43
Circulation 2013; 127: 681
44
45
46
Anaesthesia 2012; 67: 1009
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Occupational Infections: Risks for the Anesthesiologist
Dr. Keith Candiotti-University of Miami Miami, Florida
Introduction
The major goal of healthcare is to provide for the sick and injured. While caring for the sick, healthcare personnel
(HCP) can encounter considerable risk. Often the greatest danger to a HCP is a lack of awareness of risks and how
to minimize them. The intent of this lecture is to review some of the potential occupational risks to
anesthesiologists, as presented by infectious diseases with an emphasis on emerging infectious respiratory agents.
HCP are at increased risk of contracting infections from patients, especially emerging diseases that are often not
recognized early in an outbreak. 1 There are numerous reports of HCP contracting diseases while caring for patients
(TB, SARS, MERS-CoV, etc.). Although HCP are aware of infection control measures, they often show a low level
of compliance.2 It has been noted that HCP become less compliant under stressful situations, such as when they
work longer hours.3
Each disease outbreak has its own characteristics, and the severity of an outbreak and risk of infection to the HCP is
different in each case and depends on the agent characteristics and mode of transmission.4 How infectious agents are
transmitted can vary, and a particular disease may be transmitted via more than one route. Transmission can be
broadly divided into 2 categories, direct and indirect routes. Direct contact occurs when an infectious agent is
contracted from the carrier source, such as the patient or a body fluid (droplet transmission). Indirect contact occurs
when an infectious agent is contracted via an intermediate, like a countertop or medical instrument or from the air.
The distinction between droplet and airborne transmission is primarily one of range and timing. Droplet spread
refers to relatively large, short-range aerosols produced by sneezing, coughing, or even talking. Droplet spread
should be considered a direct form of transmission since the droplets can be encountered within a few feet from the
patient before they fall to the ground (e.g. pertussis & meningococcal).
Indirect transmission, refers to the transfer of an infectious agent from a reservoir to a host, by suspended air
particles, inanimate objects (vehicles), or animate intermediaries (vectors). Airborne transmission occurs when
infectious agents are carried by dust or droplet nuclei suspended in air. Airborne dust can include material that has
settled on surfaces and then becomes suspended by air currents. Airborne dust can also contain infectious particles
blown from the soil by the wind. Droplet nuclei are dried residue of less than 5 microns in size. In contrast to
droplets that fall to the ground within a few feet, droplet nuclei may remain suspended in the air for long periods of
time and may be blown over great distances. 5 Measles, for example, has occurred in children who came into a
physician's office after a child with measles had left. The measles virus can stay in the air for hours.6
Infectious Agents
Tuberculosis: Tuberculosis (TB) is a top infectious killer worldwide. About 1/3 of the world's population has latent
TB (LTBI), which means people have been infected by TB bacteria but are not (yet) ill with the disease and cannot
transmit the disease. In 2014, 9.6 million people fell ill with TB and 1.5 million died from the disease. Over 95% of
TB deaths occur in low- and middle-income countries. In the mid-1980s, a resurgence of outbreaks in the U.S.
brought renewed attention to TB. A total of 9,421 TB cases (a rate of 2.96 cases per 100,000 persons) were reported
in the United States in 2014, down from 2013 levels.7
HCP are 3 times as likely to contract TB as the general population. 8 The annual risk of latent TB infection in HCP,
in low incidence countries, has been reported to be around 2.9%. Of those cases, 49% appear to have been
contracted in the workplace. The median estimated annual incidence of TB among HCP was 67 cases/100,000
persons.8
Multidrug-resistant TB (MDR-TB) is resistant to isoniazid and rifampin and has become a worldwide health issue.
Globally in 2014, an estimated 480,000 people developed MDR-TB, which requires second line drugs and up to 2
years of treatment.7 The mortality from MDR-TB is around 8-21%. Extensively drug-resistant TB (XDR-TB) is a
form of multi-drug resistant tuberculosis that responds to even fewer available medicines, including the most
effective second-line anti-TB drugs. XDR-TB is resistant to isoniazid, rifampicin, quinolones, and at least 1 of 3
injectable SLDs (i.e., kanamycin, capreomycin, or amikacin).9 It is estimated that about 9.7% of MDR-TB cases are
XDR-TB. Increases in the rates of MDR-TB and XDR-TB have been noted in Eastern Europe, Asia and Southern
Africa. In the United States, 63 cases of XDR-TB were reported between 1993 and 2011. Some TB control
programs have shown that it is possible to cure an estimated 30% to 50% of people with XDR-TB.10 There is no
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proven preventive therapy for MDR-TB or XDR-TB at this time.11 Tragically, up to 33% of HCP who contract
MDR-TB die.12
Post-exposure Treatment: If a HCP is exposed to active TB, even if they have had bacille Calmette-Guerin (BCG),
they should undergo testing. A tuberculin test or interferon gamma release assay (IGRA), whichever is appropriate,
should be performed at baseline and again 8-12 weeks post-exposure. Some experts advocate a baseline chest x-ray.
If the tuberculin skin test converts to ≥ 5 mm or the IGRA is positive, the individual exposed should be treat with
isoniazid + vitamin B6 for 9 months.1
Severe Acute Respiratory Virus (SARS): Severe acute respiratory virus (SARS) is a novel coronavirus first
reported in Guangdong Province, China in 2002. The disease had a rapid course, spreading to many countries with
transmission being demonstrated in 8 countries. Between November 2002 and December 2003, there were 8096
infections and 774 deaths13 (Case fatality rate [CFR] 9.6%). A high number of HCP were infected.14 About 20% of
cases were in HCP. The disease was highly contagious and was transmitted via respiratory droplets and other
secretions. It is considered the first global occupational disease of the millennium. The last known case of SARS
was in 2004.
By the end of the outbreak 1706, HCP cases were reported to WHO. Infection risk was primarily related to
performing airway and respiratory related procedures, insufficient or inappropriate PPE, reuse of N95 respirators,
fatigue and lack of infection control training. 15 In Hong Kong, SARS HCP who wore N95 respirators or medical
masks, had lower infection rates.16 The strongest predictor of SARS transmission from a patient to a HCP was
aerosolization of secretions immediately prior to and during intubation. 15 Another important risk to HCPs was the
occurrence of “super-spreaders”. These were patients with SARS who transmitted to a large number of contacts and
had a higher attack rate.17,18 2 patients thought to have CHF and were not isolated for 12 h, and led to 10
documented infections (5 HCP) in 100 contacts.15
SARS transmission to HCP has been demonstrated via: Non-invasive positive pressure ventilation (NPPV), CPR,
Mask ventilation, Bronchoscopy, Suctioning, and Intubation (most significant risk). As an estimate, any high-risk
procedure increases the risk to healthcare personnel by a factor of 3. 19 HCP exposed should be monitored for 14
days after significant exposure.
Post-exposure Treatment: No known vaccine or specific antiviral exist. Treatment is supportive. 4
Middle East Respiratory Syndrome Coronavirus (MERS-CoV): Middle East Respiratory Syndrome
Coronavirus is a novel betacoronavirus that can cause a wide spectrum of illnesses from respiratory distress to death.
It was first isolated in September 2012, in a patient with fatal pneumonia in Saudi Arabia. The earliest human cases
occurred in March 2012, in a group of severely ill HCP in Jordan.20 Since September 2012, WHO has been notified
of 1,728 laboratory-confirmed cases of infection with MERS-CoV and 624 deaths (CFR 36%). Bats and camels
appear to be the natural reservoirs.21,22 At least 4 large outbreaks in HCP of MERS-CoV have been reported, all in
Jordan. More than 50% of the affected HCP were nurses.23
Depending on the outbreak, 1-27% of HCP developed MERS-CoV nosocomially. Higher transmission rates were
felt to be generally due to poor infection control measures.4 World wide cases have been reported after patients were
exposed in the Middle East.24 MERS-CoV can remain viable for up to 48 hours on surfaces under hospital
conditions. Spread by fecal-oral route as well as respiratory seems probable.25 In sputum and stool MERS-CoV can
be viable for 16 days and in urine 13 days.23 Monitor HCP who were exposed for 14 days for symptoms.4
Post-exposure Treatment: No known vaccine or specific antiviral exist. Treatment is supportive.
Influenza: Influenza pandemics typically occur several times each century. 26 In the 1918 influenza pandemic
(Pandemic Severity Index [PSI 5] and Case Fatality Ratio [CFR] 2%) 500 million people were infected (1/3 of the
world), and 50-100 million died. In 2009, H1N1, in the US alone, produced 57 million cases, with 257,000
hospitalized and 11,700 deaths (CFR 0.02%). In seasonal influenza, the very old and very young are typically
affected. In the 1918 and 2009 pandemic, it was mostly children and young adults.
Influenza (N1H1) 2009: N1H1, influenza was first detected in the US in April of 2009. The index case was a 10-
year-old child in California.27 It was a novel agent, never seen before. It was resistant to the antiviral drugs,
amantadine, and rimantadine, but was susceptible to the antivirals oseltamivir and zanamivir.27 One study
demonstrated an infection rate of 65% in ER staff and 35% in OR personnel, compared to a background rate of
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13%.28 It is spread by smaller particles, human-to-human. When finished 43-89 million people were infected (deaths
8,870-18,300).27
Avian Influenza (AI): Avian influenza is common in poultry and is caused by an RNA virus in the
orthomyxoviridae family. The first avian A (H5N1) outbreak occurred in Hong Kong in 1997. This variety is highly
pathogenic and causes extensive damage to poultry populations. 29
As of April 4th, 2016, 850 human cases have been reported with 449 deaths (53% mortality) in 16 countries. Most
recent cases (4) were in reported in Egypt. In March 2013, another novel avian influenza A was described in China
(H7N9). It infected 2 Shanghai residents and 1 in Anhui. No Transmission cases have been reported outside of
China.29
As of February 2015, a total of 517 human cases of AI H7N9, including 212 deaths (41% mortality) have been
reported in 4 countries. In most human cases of H5N1 and H7N9 flu, poultry or poultry market exposure are
described. 30 Rare human-to-human transmission of H5N1 has occurred via intimate contact in households where no
barrier precautions were used. Transmission has not occurred from causal, social contact. 30 There have been no
reports of AI transmissions to HCP. One study demonstrated no transmission to 25 HCP exposed to a patient with
H5N1 in a tertiary hospital in Thailand.31
However, in seasonal flu, nosocomial influenza transmission can reach 11-59%. AI is wide spread in poultry
throughout the world. The risk of genetic reassortment and pandemic potential must be considered and is monitored
by the CDC and WHO. This is especially important due to the high mortality noted (>50%). The key to preventing
spread and a pandemic outbreak is primarily based in early identification of human-to-human contact and adhering
to strict infection control practices. (Contact/droplet precautions) 30
Post-exposure Treatment: In November 2013, an H5N1 AI monovalent, adjuvant vaccine for the prevention of AI
was approved by the FDA. No H7N9 vaccine is currently available. Laboratory testing conducted so far has shown
that the H7N9 viruses are sensitive to the anti-influenza drugs known as neuraminidase inhibitors (oseltamivir and
zanamivir) but resistant to adamantanes (amantadine and rimantadine). Early information from China suggests that
when oseltamivir was given early in the course of illness, it was effective against the H7N9 virus, reducing the
severe of illness and death. HCP exposed should be monitored and excluded from work for 7 days (H5N1) and 10
days (H7N9)32
Other Emerging Viruses
Ebola: The first outbreak of Ebola occurred in 1976 in Nzara, Sudan, and Yambuku, Congo (Zaire). In December
2013, the Zaire strain emerged in a small village in Guinea, West Africa but was not identified until March 2014. It
spread rapidly, and as of May 5, 2016, a total of 28,616 Ebola cases have been reported in Guinea, Liberia and
Sierra Leone, with 11,310 deaths. Hospitalized fatalities were 31-66%. A total of 852 HCP (Nurses 35% and
Physicians 15%) were reported to WHO with 492 deaths (range 44-73%). Transmission occurred via infected body
fluids. The incubation period is 8-10 days (range 2-21 days).33
The Lagos, Nigeria index case was a symptomatic air traveler whose sister died from Ebola. The patient went to the
hospital and told them she had malaria. No protective measures were taken. 9 HCP became infected, and 4 died. In
the US there were 4 cases. The US index case was from Liberia and came to a Dallas hospital and was discharged
home with presumed sinusitis. He later returned sicker and died. 2 nurses test positive for Ebola as a result of
caring for the index case.33
In a post-acute state, some Ebola patients have demonstrated viral reservoirs in their eyes and/or testicles. Dr. Ian
Crozier thought he had recovered from an Ebola infection but developed intense eye pain with reduced vision loss.
He also noted that his eye had changed color. Eventually, after treatment, his symptoms and vision improved and
remarkably his eye color returned to its original color. He still suffers from other post-Ebola symptoms, joint pain,
fatigue etc.34
In any situation where a novel and dangerous agent is suspected, (this is usually the problem early on) protective
gear is essential. Gear consisting of a high protection respirator (N-95, N-100 or PAPR), eye goggles, gowns, shoe
covers, and gloves are mandatory when an aerosol generating procedure may be performed. Confirmed or suspected
cases require airborne isolation rooms (6-12 air changes per hour), especially for procedures. To minimize exposure,
as few HCP should be in the room during aerosol-generating procedures as possible. Close contact is considered a
minimum of 6-10 ft. from the patient or their room, if open. In outbreaks involving a very infectious or lethal agent,
the use of isolation wards should be considered. These wards can often benefit from having separate entrances and
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exits. To help prevent self-contamination while doffing gear (greatest risk) or donning gear incorrectly, observers
should be used at the entrances and exits of these areas.35
Blood Borne Agents

Every year, 600,000-800,000 sharps injuries occur in U.S. healthcare workers.36,37
Hepatitis B: A survey of 2400 unvaccinated anesthesiologists in several countries showed a mean prevalence of
HBV serologic marker of 17.8% (3.2-48.6%).38 Hepatitis B (HBV) risk from a percutaneous injury in a HCP with
no immunity is 1% to 30%. All HCP should be vaccinated for HBV with demonstrated titers. HBV PEP should be
initiated immediately when needed (24 hours is ideal but within 7 days).
Post-exposure Treatment:
HBsAg-Positive Exposure Source: Persons who have written documentation of a complete hepatitis B vaccine
series and who did not receive postvaccination testing, should receive a single vaccine booster dose. Persons who
are in the process of being vaccinated but who have not completed the vaccine series should receive the appropriate
dose of hepatitis B immune globulin (HBIG) and should complete the vaccine series. Unvaccinated persons should
receive both HBIG and hepatitis B vaccine as soon as possible after exposure (preferably within 24 hours). The
hepatitis B vaccine may be administered simultaneously with HBIG in a separate injection site. The hepatitis B
vaccine series should be completed in accordance with the age-appropriate vaccine dose and schedule. 39
Exposure Source with Unknown HBsAg Status: Persons with written documentation of a complete hepatitis B
vaccine series require no further treatment. Persons who are not fully vaccinated should complete the vaccine series.
Unvaccinated persons should receive the hepatitis B vaccine series with the first dose administered as soon as
possible. The vaccine series should be completed in accordance with the age-appropriate dose and schedule.39
Hepatitis C: HCV affects 185 million people worldwide and approximately 4 million Americans. More deaths
occur each year from HCV than HIV.40 The rate of HCV, in Anesthesiologists is about the same as the general
population, indicating a low transmission risk, although cases have been reported.38 If the source patient has active
HCV the risk is approximately 1.8% (0-7%) from a percutaneous injury. HCV can remain active on a surface for up
to16 hours. Hepatitis D-E infections have also been reported.40
Postexposure Treatment: There is no post-exposure prophylaxis for HCV. Direct viral testing with HCV RNA
PCR viral load at 6 weeks, before HCV Ab seroconversion can occur, allows for early identification of transmission
and subsequent referral for early evaluation and potential HCV treatment. The rate of spontaneous clearance of HCV
infection is about 25% in healthy persons. However, early diagnosis and treatment may increase HCV clearance to
90% or greater. HCV antibody testing should be performed at 4-6 months to rule out HCV infection. 41
Human Immunodeficiency Virus (HIV): In the U.S., there are 58 confirmed cases of HCP occupational
conversion (documented negative prior to conversion) as of 2013. In addition there are 150 possible HCP
conversions (not documented negative prior to testing positive). Actions associate with confirmed conversion (of
the 58): Percutaneous puncture or cut (49); Mucocutaneous (5); Both Percutaneous and Mucocutaneous
(2);Unknown (2).
Professions at risk (in order): Nurse, Laboratory Technician, Physician (nonsurgical), Housekeeper, and Surgery
Technician.42 Only one confirmed HCP conversion has occurred since 1999. In 2008, a laboratory technician
sustained a needle puncture while working with a live HIV culture. 43,44 HIV transmission rate is @0.3% for
percutaneous injury and 0.09% after mucous membrane exposure. The risk of non-intact skin exposure is not known
but seems to be less than mucous membrane exposure.42,43 An older study of Anesthesiologists, Greene et al.,
estimated a 0.05% conversion rate for HIV percutaneous injury.44
There is an increased risk of conversion with the following: larger quantity of agent, prolonged exposure, exposed to
a patient with a high viral load or advanced disease, deep percutaneous injury, instances where the sharp was in the
vein or artery of the infected patient, injury with a hollow bore, blood-filled needle and, limited or delayed post-
exposure prophylaxis.
Post-exposure Treatment: Post-exposure Prophylaxis (PEP) should be started as quickly as possible (placed in
Pxyis). The exact time frame is unknown however, PEP efficacy is believed to decrease with time. PEP should be
given for 28 days. If the source status is unclear then PEP should be started and reevaluated later for continuation.
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The preferred regimen is raltegravir (400 mg bid) + tenofovir (300 mg) and emtricitabine (200 mg) (Truvada is a
fixed-dose combination), which is well-tolerated with minimal drug-drug interactions. This can be used in pregnant
women as well (limited data). If the source proves to be HIV negative, then PEP can be stopped. In the presence of
drug resistance, expert consultation is recommended, however, standard prophylaxis should be started ASAP.
(Second-line agents)45
General Postexposure Prophylaxis (PEP): After a percutaneous injury with a sharp or needle, wash the area with
soap and water to clean the wound. There is no evidence that applying antiseptics or disinfectants is beneficial.
Bleach should be avoided.46 After mucosal exposure to blood or body fluids, irrigate the exposed area with water or
normal saline.47 Usually, PEP is best if given quickly. In some diseases PEP may be effective even if given long
after exposure (rabies and tetanus).47 Live vaccines should not be used in pregnant women or immunocompromised
patients. In these groups, immune globulin is preferred.46 HCP exposed to an infectious agent should be assessed at
baseline and at subsequent intervals while at risk. If exposed to blood also test for HIV, HBV, and HCV.47
Protective Measure
Personal Protective Equipment (PPE): PPE is the last line of defense. Ideally, sick and infectious patients should
be identified and isolated in advance. While wearing protective gear clearly reduces exposure risk, the removal of
gear presents its own issues. In one study of simulated exposure, 46% of participants contaminated themselves
during the doffing procedure. Contamination occurred more frequently with the removal of gloves rather than
gowns (52.9% vs. 37.8%, P=.002). Observation helped in reducing contamination (70.3% vs. 30%, P<.001).
Training was able to reduce the rate of self-contamination to around 18.9%. Training in advance of an event would
seem advisable.48
Gloves: FDA has lowered the acceptable defect rate for patient exam medical gloves and surgeons’ gloves to 2.5%
and 1.5%, respectively (Biogels have holes at half this rate 0.65%). Hot, sweaty hands are enough to eat through
latex in about 50 minutes (such that HBV and HIV can penetrate). Latex gloves need to be changed about every 30
minutes. Therefore, in an 8-hour shift, at least 32 gloves will be used and—at a 2.5% defect rate—statistically, 1 of
the gloves will be defective.
The least expensive material, vinyl, is more likely to leak and allow penetration of organisms relative to nitrile and
latex. Nitrile resists perforation better than latex and vinyl, but when it does perforate, the holes enlarge faster. 49 In
spite of a clear awareness of the risks, and implementation by the CDC of “standard precautions”, many HCP use
gloves in a sporadic pattern.37 Gloves will reduce the inoculum of blood introduced by injury, especially when
caused by a hollow bore needle.50 Glove use itself has been shown to reduce the risk of injury significantly, and
double gloving reduces injury even further. 51
Double-gloving: The CDC, AORN, OSHA and other authorities agree: wearing 2 pairs of gloves reduces infection
risks by providing backup protection if the outer glove is punctured.51 Colored under-gloves make any damage
immediately visible. Since double-gloving may reduce sensitivity and dexterity, thinness plays an important role, as
does texture. An outer glove with a smooth or lubricated inner surface may be easier to don over the first layer.
Hand Hygiene and Eye Protection: Influenza A can exist on hands for over an hour with minimal reduction. Soap
and water or alcohol-based agents can eliminate all traces.52 Hand hygiene combined with mask use has been shown
to reduce influenza transmission (35-51% reduction).53 The transocular route may be a significant route of
transmission for respiratory agents and influenza is highly efficient by this route. 54 Use of a face shield may prevent
contamination of a respirator mask as well as protect the HCP eyes.54
Masks, Respirators, and Airway Protection: The assigned protection factor (APF) is a value given or assigned to
each respirator by OSHA and NIOSH. The value indicates the factor a respirator decreases contaminating
substances in the ambient air. It is based on simulation and actual work factors. The value is derived from CO/CI
(concentration out/in) divided by 25, which gives a value of 10-10,000. The number indicates the minimum factor
by which exposure is reduced with the respirator (higher is better). N95 means the wearer will get no more than
1/10 of the hazardous particles present. PAPRs are required to have an APF of 1000+. 55
Two types of devices are commonly used to prevent transmission of airborne infectious agents, medical masks, and
respirators.56 Masks are designed to keep droplets from coming in contact with the face and mucosa of the wearer.
They are not fitted and not designed to filter small airborne infectious agents. Respirators are medical devices
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designed to protect the wearer from airborne infectious aerosols. Respirators work by filtering the airborne particles
(air-purifying respirator) or by supplying clean air (atmosphere –supplying respirator).
Air Respirators are further classified into efficiency of particle removal (95%, 99% and 100%), N-No oil resistance,
R-Oil resistance, P-Oil resistant. Type 100, is 99.97% efficient and costs around $10-$50. Type 99, are 99%
efficient and cost around $10. The 95, which are 95% efficient, cost around $0.60-$2. Controversy exists whether
there is any benefit of wearing N95 respirators in influenza or other pandemics. (N95 vs. Medical Mask for
influenza in nurses, @23% in each group).57 Many simulation studies support N95 mask use, however, cost remains
an issue. For example, in a 300-bed hospital in a pandemic @$140,000 in respirator masks would be used.
The Canadian Biosafety Standards and Guidelines note: “Using the wrong respirator or misusing one can be as
dangerous as not using one at all”.58 HCP should wear N95 respirators when performing aerosol-generating
procedures, as well as when managing patients with TB, high-risk situations in SARS cases, and in situations where
high-risk pandemic influenza exits.58 Some bodies support the use of more aggressive respiratory protective
measures, such as a powered air purifying respirators (PAPR) for very high-risk procedures (intubation and
bronchoscopy).59 In the situation of low-risk seasonal influenza, a medical mask is recommended. 60 Medical masks
reduced influenza rates in one airplane study (0% vs. 50% control).61
N95 masks have several issues. Breathing resistance can be uncomfortable, and prior fit testing does not assure
success in attaining a seal during regular use. Regular users appear to have greater success in maintaining a seal.
The reuse of N95 is discouraged but permissible if supplies are limited. (Not soiled, creased, damaged, moist or
wet). Reaerosolization of disease particles from the N95 does not occur, however, it can act as a surface for formites.
A fluid resistant N95 should be used in a surgical setting. If a respirator is going to be reused, it should be stored in a
paper bag, and not plastic to avoid condensation. 62,63,64,65
Ultimately, in the laboratory setting N95 masks appear to offer more protection than medical masks but far less than
PAPRs. Real world protection is not clear at this time. 66 An N95, combined with face/eye protection appears to be
one of the best ways to avoid viral transmission.54 2 large RCT have shown that N95 respirators can reduce
respiratory infection rates in HCP.67,68 A study of Bacterial Colonization showed a rate of 2.8% in HCP who wore
N95 respirators; 5.3% medical mask and 7.5% control. Co-infections of bacteria with viruses were also reduced.
Medical masks may actually increase the risk of respiratory co-infections (NS but trended).69 In another study on
high-risk respiratory wards, HCP were infected more often when using self-identified risks as an indication to wear
a respirator rather than continuous use of a respirator while on duty on that ward. This indicates HCP are not able to
predict when they are truly at risk.68
Powered Air Purifying Respirator (PAPR): PAPRs have a higher level of protection than N95 masks. 70 They also
provide maximum protection without a concern for fit or leak. 70 They can be used with glasses or anyone with a face
that does not fit well in a simple face respirator.71 PAPRs use a HEPA filter (99.97% efficient) and have an air-flow
greater than 170 L/min. Their cost is around $1000 per unit. They are not disposable and require proper maintenance
and cleaning.70 PAPRs can interfere with tasks and intubations, and the drape may become easily contaminated.71 In
the setting of significant risk they may provide the greatest degree of protection.
Overall Recommendations: Wearing a mask in the presence of a transmissible respiratory agent would seem to be
a basic precaution. In the presence of potentially more dangerous agents, N95 masks should be used. If high or
very high-risk procedures are to be performed a PAPR should be considered.
Prevention of transmission to HCP requires a multifaceted approach. Strong surveillance for new diseases or
diseases in an early stage can often be missed. It is the responsibility of the administrative to make sure accepted
infection controls and equipment are in place, and the structure of the hospital is conducive for the care of infectious
patients. Consistent with that same concept is the need for effective and frequent environmental cleaning.
Additionally, HCP can help protect themselves through several steps, including getting vaccinated where possible,
using the correct PPE at the right times, and following infection control protocols. Finally, while we have heard
about it over and over for many years, the importance of hand hygiene is still often overlooked. The simple task of
washing your hands may not only save the life of a patient, it may also save the life of HCP.
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Maternal Comorbidities Combined with Physiologic Changes of

Pregnancy Requiring ICU Admission
Jennifer E. Hofer, M.D. Chicago, IL
Objectives:
1. Review the role of transthoracic echocardiography in bedside diagnosis in the peripartum patient
2. Identify criteria for critical care admission of peripartum patients
3. Decipher which critical care monitoring is necessary in the critically ill parturient
4. Identify which intensive care unit is best suited to care for the critically ill parturient
5. Discuss the multidisciplinary role of the intensivist caring for the peripartum patient
Introduction:
Management of the critically ill obstetric patient provides a unique challenge to clinicians. Early
differentiation between maternal physiology versus pathology is vital to guide therapy and optimize
outcomes for both mother and fetus.
Echocardiography:
Due to dynamic physiology in pregnancy and in critical illness, bedside transthoracic echocardiography
(TTE) is increasing in usage to facilitate fast diagnoses and implement early targeted treatment. Dennis A,
et al (cited in the references) has published numerous papers on TTE in pregnancy.
Principles of the Rapid Obstetric Screen Echocardiography (ROSE) scan

1. Applicable at patient’s bedside
2. Concise examination – obtain parasternal view
3. Monitor response to therapy- ventricular contractility status/volume status
4. Evaluate for Embolism through views of the right heart
5. Assess fetal heart rate
TTE can be useful in differentiating heart failure from preeclampsia (diastolic dysfunction with preserve
ejection fraction) from peripartum cardiomyopathy (systolic dysfunction with reduced ejection fraction).
Many clinical scenarios arise that can be quickly assessed by TTE. Diagnostic questions that can routinely
be answered by TTE (in situations such as hemorrhage, heart failure, sepsis, embolism, preeclampsia,
super-obesity, respiratory emergencies, pulseless electrical activity) include:
1. Volume status
2. Wall motion abnormalities
3. Ventricular contractility/Right ventricular outflow tract obstruction
4. Presence of pericardial effusion/tamponade
ICU Admission
The decision to admit a pregnant patient to the ICU depends on multiple factors. Experts recommend
adoption of Maternal Early Warning Systems (MEWS), and call for physician assessment at the bedside
for parturients with HR < 50 or > 120, Diastolic BP > 100, Systolic BP < 90 or > 160, respiratory rate < 10
or > 30, oxygen saturation on room air < 95%, oliguria </= 35cc/hr for > 2 hrs, and maternal agitation,
confusion or unconsciousness. MEWS challenges clinicians to have a high index of suspicion to investigate
the cause of the abnormal vital sign further. Early identification and intervention has been demonstrated to
decrease maternal morbidity.
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Different pathologies have varying presentations, requiring different teams of clinicians and sometimes
invasive monitoring. Normal maternal physiology with a low systemic vascular resistance, high cardiac
output, elevated heart rate, high minute ventilation, respiratory alkalosis with compensatory metabolic
acidosis, dilutional anemia and often gestational thrombocytopenia, can confound the clinical picture when
differentiating between normal maternal physiology versus pathology.
In our ASA lecture, we will discuss different pathologies (such as preeclampsia, hemorrhage, and amniotic
fluid embolism), diagnosis and clinical team management, and maternal and fetal monitoring. A few of the
pathologies are presented below.
Preeclampsia/Eclampsia/Posterior Reversible Encephalopathy Syndrome
Preeclampsia affects 5-7% of pregnancies. New definitions of preeclampsia and preeclampsia with severe
features from ACOG in 2014 no longer require proteinuria to make the diagnosis. Posterior reversible
encephalopathy syndrome is an unwanted consequence of eclampsia, manifesting as vasogenic cerebral
edema. Management requires blood pressure control, often using high dose intravenous anti-hypertensive
medications such as esmolol, labetatalol, hydralazine, or IV nicardipine. Patients require clinical expertise
from the obstetrician, intensivist, and neurologist to optimize outcomes. Conflicting goals of care include
maintenance of intravenous magnesium for seizure prophylaxis and intravenous calcium channel blockers
for blood pressure control; the combination which may cause impaired cardiac function.
Hemorrhage/Consumptive coagulopathy
Postpartum hemorrhage (PPH) is a result of a delivery complication such as uterine atony, abnormal
placentation, retained products of conception, genital tract trauma, abnormal coagulation, or high infant
birth weight. Induced or augmented, labor, prolonged labor, chorioamnionitis, and multiple gestation are
examples of factors that increase rates of atony.
Fibrinogen has been shown to independently predict severity of PPH. Fibrinogen in pregnancy is typically
400 mg/dL or more, twice the value as in the non-pregnant population; a decrease from this baseline level
is concerning in the presence of bleeding because it signals fibrinogen consumption. When the fibrinogen
level approaches 200 mg/dL during obstetric hemorrhage, experts recommend administration of fibrinogen.
During PPH, the clinician may activate a massive transfusion protocol (MTP. The components of an MTP
may differ among institutions, but typically include fixed ratios of packed red blood cells, plasma, platelets
and cryoprecipitate. Early administration of fibrinogen in plasma, or more concentrated in cryoprecipitate,
may modify the severity of blood loss and change the course of the patient’s morbidity.
Monitoring for patients receiving massive transfusion to treat postpartum hemorrhage often includes an
arterial line to facilitate serial laboratory draws and for blood pressure monitoring, a central line for central
venous pressure measurements and central venous oxygen saturations, and for administration of a
vasopressor if needed to support the blood pressure, and large bore intravenous access for volume
resuscitation. The arterial line is also beneficial for blood gases; the patients PaO2 may decrease in a
massive transfusion, pulmonary edema and transfusion related acute lung injury may develop, and acute
lung injury ventilator management may need to be initiated.
Amniotic Fluid Embolism
Amniotic fluid embolism affects a very small population, but its sequelae is often catastrophic.
Hypotension is present in 100% of AFE cases. Other frequent signs and symptoms include pulmonary
edema/ARDS, cardiopulmonary arrest, cyanosis, and coagulopathy. AFE is considered an immunologic
phenomenon since amniotic fluid contains vasoactive and procoagulant substances that mimic the
presentation of anaphylactic shock when these substances enter maternal circulation.
A biphasic model describing the hemodynamics associated with AFE has been proposed (Gist R. et al.
Anesth Analg 2009; 108:1599-602; Clark SL, Hankins GD, Dudley DA, et al. Amniotic fluid embolism:
416
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analysis of the national registry. Am J Obstet Gynecol. 1995;172:1158-1167). Initially, there is right
ventricular failure and hypoxia from pulmonary hypertension and bronchospasm. This is followed by left
ventricular failure and pulmonary edema. Disseminated intravascular coagulation often ensues. Patients
experiencing an AFE are routinely intubated, and require continued support of hemodynamics and
correction of coagulopathy in an ICU. A central line for volume administration and vasoactive support is
often indicated, along with an arterial line for blood gases and frequent laboratory draws, and monitoring of
hemodynamics. A complication of DIC after the initial coagulopathy is corrected, is clot. The intensivist
and obstetrician need to communicate to decide when to start postpartum deep vein thrombosis prophylaxis
in this population. These patients are at high risk of clot formation due to the hypercoagulability of
pregnancy, the trauma of experiencing an AFE, and bedrest while intubated in the ICU.
Fetal Monitoring
Once a fetus is viable, the question arises whether continuous fetal monitoring is indicated. To do
continuous monitoring, it is necessary to have a nurse dedicated to watching the fetal tracing, and a team
and supplies ready to make a fast intervention (i.e. deliver the fetus surgically). Preterm fetuses often have
decelerations that are normal for their gestational age, and should not be intervened upon. To best support
maternal-fetal circulation, clinicians should optimize hemodynamics with fluids and vasoactive agents,
avoid hypoxia, and when a visibly gravid uterus is present, the patient should be placed in left uterine
displacement.
References:
Guntuappli KK, Hall N, Harnad DP, et al. Critical illness in pregnancy. Chest 2015; 148(4):1093-1104
Strek ME, O’Connor M, Hall JB, et al. Critical illness in pregnancy. In: Hall JB, Schmidt GA, Wood LD ,
eds. Principles of Critical Care. 3rd ed. New York, NY: McGraw-Hill; 2005:1593-1614
Echocardiography/PPCM/Cardiac Arrest
B elfort MA, Rokey R, Saade GR, et al. Rapid echocardiographic assessment of left and right heart
hemodynamics in critically ill obstetric patients. Am J Obstet Gynecol. 1994;171:884-892.
Fujitani S, Baldisseri MR. Hemodynamic assessment in a pregnant and peripartum patient. Crit Care Med.
2005;33:S354-S361.
Dennis A, Stenson A. The use of transthoracic echocardiography in postpartum hypotension. Anesth and
Analg 2012; 115: 1033-1037
Dennis AT. Transthroacic echocardiography in obstetric anaesthesia and obstetric critical illness. IJOA
2011; 20:160-168
Bolliger CT, Herth FJF, Mayo PH, (eds et al). Clinical chest ultrasound: from the ICU to the bronchoscopy
suite. Prog respire Res. Basel, Karger, 2009, vol 37: 60-68.
Neelankavil J, Howard-Quijano K, Hsieh TC, et al. Transthoracic echocardiography simulation is an
efficient method to train anesthesiologists in basic transthoracic echocardiography skills. Anesth and Analg
2012; 115:1042-51.
Holm JH, Frederiksen CA, Juhl-olsen P, Sloth E. Perioperative use of focus assessed transthoracic
echocardiography (FATE). Anesth and Analg 2012; 115: 1029-32.
Chalifoux LA, Sullivan JT. Applications of focused cardiac ultrasound (FoCUS) in obstetrics. Curr
Anesthesiol Rep (2015) 5:106–113
Murali S, Baldisseri MR. Peripartum cardiomyopathy. Crit Care Med. 2005;33:S340-S346
Elkayam U. Clinical characteristics of peripartum cardiomyopathy in the United States. J Amer Col Card
2011; 58: 659-670.
Harper MA, Meyer RE, Berg CJ. Peripartum cardiomyopathy: population-based birth prevalence and 7-
year mortality. Obstet & Gynecol 2012; 120: 1013-1019.
Jeejeebhoy FM, Zelop CM, Lipman S, et al. on behalf of the American Heart Association Emergency
Cardiovascular Care Committee; Council on Cardiopulmonary, Critical Care, Perioperative and
Resuscitation; Council on Cardiovascular Diseases in the Young; and Council on Clinical
Cardiology. Cardiac arrest in pregnancy: a scientific statement from the American Heart
Association. Circulation 132(18):1747-1773, 2015
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Preeclampsia/Eclampsia/PRES
The American College of Obsterticians and Gynecologists. Executive Summary: Hypertension in
Pregnancy; Report of the American College of Obstetricians and Gynecologists’ Task Force on
Hypertension in Pregnancy. Obstet and Gynecol 2013; 122:1122-1131.
Ghulmiyyah L, Sibai B. Maternal mortality from preeclampsia/eclampsia. Semin Perinatol. 2012
Feb;36(1):56-9. doi: 10.1053/j.semperi.2011.09.011
Committee Opinion no. 514: emergent therapy for acute-onset, severe hypertension with preeclampsia or
eclampsia.Obstet Gynecol. 2011 Dec;118(6):1465-8. doi: 10.1097/AOG.0b013e31823ed1ef.
Sibai BM.Diagnosis, prevention, and management of eclampsia. Obstet Gynecol. 2005 Feb;105(2):402-10.
Duley L, Henderson-Smart DJ, Walker GJ, Chou D. Magnesium sulphate versus diazepam for eclampsia.
Cochrane Database of Systematic Reviews 2010, Issue 12. Art. No.: CD000127. DOI:
10.1002/14651858.CD000127. pub2.
Thackeray EM, Tielborg MC. Posterior reversible encephalopathy syndrome in a patient with severe
preeclampsia. Anesth Analg 2007; 105:194-186
Pula J, Eggenberger E. Posterior reversible encephalopathy syndrome. Curr Opin Ophthalmol 2008;
19:479-484.
Dhar R, Dacey R, Human T, Zipfel G. Unilateral posterior reversible encephalopahty syndrome with
hypertensive therapy of contralateral vasospasm: case report. Neurosurgery 2011; 69:1176-1181.
Hemorrhage/Consumptive coagulopathy
Callaghan WM, Kuklina EV, Berg CJ. Trends in postpartum hemorrhage: United States 1994–2006. Am J
Obstet Gynecol. 2010;202:353. doi: 10.1016/j.ajog.2010.01.011.
Charbit B, Mandelbrot L, Samain E, Baron G, Haddaoui B, et al. The decrease of fibrinogen is an early
predictor of the severity of postpartum hemorrhage. J Thrombosis and Haemostasis 2007;5:266-273 World
Health Organization. “WHO/MDG 5: Improve Maternal Health.” 2011. Web 19 Mar 2011.
http://www.who.int/topics/millennium_development_goals/maternal_health/en/index.html.
Bateman BT, Berman MF, Riley LE, Leffert LR: The epidemiology of postpartum hemorrhage in a large,
nationwide sample of deliveries. Anesth Analg 2010; 110:1368-73.
ACOG Practice Bulletin Nl. 76. Postpartum hemorrhage. Obstet Gynecol 2006;
108:1039-48.
Shields LE, Smalarz K, Reffiggee L, et al. Amer J Obstet Gynecol 2011; 205:368
ATLS: http://lifeinthefastlane.com/ccc/major-haemorrhage-in-trauma/
Mhyre JM, D’Oria R, Hameed AB, et al. The maternal early warning criteria: a proposal from the national
partnership for maternal safety. Obstet Gynecol 2014; 124:782-6
Vallet B, Adamczyk S, Barreau O, Lebuffe G. Physiologic transfusion triggers. Best Practice and Res Clin
Anaesth 2007; 21:173-181.
Mercier F, Bonnet MP. Use of clotting factors and other prohemostatic drugs for obstetric hemorrhage.
Curr Opin Anaesthesiol 2010; 23:310-16.
Driessen M, Bouvier-Colle MH, Dupont C, et al. Obstet Gynecol 2011; 117:21-31.
Shields,L, Wiesner S,Fulton J,Pelletreau B. Amer J Obstet Gynecol; 2015; 272.
Bateman BT, Mhyre JM, Callaghan WM, Kuklina EV. Peripartum hysterectomy in the United States:
nationwide 14 year experience. Am J Obstet Gynecol 2012; 206:63e1-8.
Amniotic fluid embolism

Gist R. et al. Amniotic fluid embolism. Anesth Analg 2009; 108:1599-602
Knight M, Tuffnell D, Brocklehurst P, et al. Incidence and risk factors for amniotic-fluid embolism. Obstet
Gynecol. 2010;115:910-917.
Aurangzeb I, George L, Raoof S. Amniotic fluid embolism. Crit Care Clin. 2004;20:643-650.
Moore J, Baldisseri MR. Amniotic fluid embolism. Crit Care Med. 2005;33:S279-S285.
Clark SL, Hankins GD, Dudley DA, et al. Amniotic fluid embolism: analysis of the national registry. Am J
Obstet Gynecol. 1995;172:1158-1167
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Fetal monitoring
Reitman E, Flood P. Anaesthetic consideration for non-obstetric surgery during pregnancy. BJA 2011;
107(51):i72-i78
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How to Garner Support and Set Up a Pediatric Surgical Home (PSH)

Karen Thomson, MD Washington, DC
Anita Honkanen, MD Stanford, CA
Overview of the PSH concept and the differences between Pediatric and Adult models
The Perioperative Surgical Home (PSH) is a patient-centric, physician-led, team based care model that coordinates
care from the time the decision is made for surgery until the patient is safe and fully recovered at home after surgery.
With our role of frequently coordinating care and resource utilization, the anesthesiologist is positioned to be a
strong member of the team, and in some areas, may function as the physician leader.
The PSH model unites each individual patient encounter through the entire perioperative episode and may be
utilized to improve the value of health care delivered by increasing the quality while controlling or reducing the
costs. Much of the driver for value based payments has come from the Center for Medicare and Medicaid
Innovation (CMMI). Initially voluntary bundling programs for surgical repair of total joints have transitioned to the
Comprehensive Care for Joint Replacement (CCJR) which includes mandatory retrospective bundling of all charges
related to lower extremity joint replacement from day of admission until 90 days post-discharge. Pediatric hospitals
traditionally care for few Medicare patients and much of the focus on Medicaid programs may still be on adults
eligible for Medicaid due to disability or chronic disease. Thus, the drivers toward care coordination and value
based payments have somewhat lagged in pediatric hospitals, potentially slowing the growth of the PSH model.
Reducing length of stay (LOS) while preventing readmissions and limiting post-discharge care in rehabilitation or
skilled nursing facilities (SNF) have been areas of focus for adult surgical homes. In contrast, pediatric
readmissions are significantly lower than in adult populations and the reasons for readmission are drastically
different. Very few pediatric surgical patients are cared for transiently at a SNF or rehabilitation facility, and the
parents/family are already the primary caretakers.
In pediatrics, multiple suggestions have been made for potential targeted patients or surgical populations. One 2012
evaluation of the cumulative cost of surgical conditions revealed the ten most expensive pediatric inpatient
conditions to treat; the three surgical conditions include Idiopathic Scoliosis, Hypoplastic Left Heart Syndrome, and
Adenotonsillar Hypertrophy – drastically different conditions
1. Respiratory Distress Syndrome in Newborn

2. Pneumonia
3. Chemotherapy
4. Acute Respiratory Failure
5. Idiopathic Scoliosis
6. Asthma
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7. Hypoplastic Left Heart Syndrome

8. Bronchiolitis
9. Adenotonsillar Hypertrophy
10. Extreme Prematurity: BW 500-749 grams
Keren et al. Arch of Pediatric and Adolescent Medicine 2012. Prioritization of comparative effectiveness research
topics in hospital pediatrics.1
In evaluating the distribution of overall pediatric medical expenses: the most complex 0.5% of the population is
responsible for 25% of medical expenditures and the next 25% of the population with chronic disease is responsible
for 70% of pediatric medical expenses. This may support a PSH model based on a chronic medical disease. For
example, consideration has been given to use of a PSH to management a specific pediatric population with a chronic
medical condition such as Cerebral Palsy or Sickle Cell Disease while they undergo a variety of surgical procedures.
Creating an argument for support for change:

With the changes that are ongoing in healthcare today, developing an approach that focuses on improving patient
outcomes, improving the efficiency of delivering care, and improving the patients’ perception of that care is critical.
The PSH model strives to meet that triple aim (see below diagram by Vetter) while improving our understanding of
the surgical population as a whole. A comprehensive collaborative approach is the only way that all of these goals
can be achieved, eliminating redundancies in the system by clearly outlining the roles and tasks for all stakeholders,
and cleanly planning for all patients’ needs to be met. Developing a smooth financial model that enables reasonable
representation for all stakeholders will be key to ultimately achieving sustained buy-in to any model created.
Vetter et al., Anesth Analg 2014; 118(5):1131
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Identifying your key stakeholders and understanding their concerns:

There are multiple stakeholders needed to build a surgical home model: from the top of the organization leaders
invested in finding the most cost-effective solutions to providing surgical care that engages patients in a positive
way, to the front line staff, who are often caught up in trying to work-around systemic inefficiencies to manage the
expectations of the patients and their families.
The first Stakeholders often engaged are the C-suite leaders, the COO, CEO, CMO, CFO, and Chief of Staff. These
individuals will ultimately be responsible for funding any initiatives and will hear any praise or complaints from
other stakeholders in the system as changes begin to be implemented. If they are not aware of the efforts, they not
only can not contribute financial support, but may decide that the upset over changes are creating too much turmoil
and shut the effort down.
The ASA website offers multiple resources on how to engage key stakeholders to discuss the benefits of the PSH to
the institution and offers a sample business plan. Additional descriptions of case studies and relevant literature may
aid in a presentation to stakeholders to garner support. Many institutions have groups already working at care
model redesign or reducing length of stay or readmissions. Partnering with these internal projects within your
hospital may help align with corporate goals and attain access to resources to facilitate implementation of the PSH.
Alternatively, a grass roots approach, identifying pain points with individual services, and working through a care
pathway with the leaders in that area to address those issues, can lead to some clear and early wins. These pilot
studies, with metrics to support the benefits of the approach, can be presented to the hospital leadership to garner
more systemic support and resource allocation to expand the effort.
In either case, the surgeons must be engaged. These are the people most invested in seeing positive change in all the
targeted areas: patient outcomes, operational efficiencies, and patient satisfaction. As partners in the effort, a
balanced and planned approach can be taken to patient preparation, intraoperative care paradigms, and postoperative
care and follow-up. Again, finding a surgeon who has had particular pain points in any of these areas, where the
anesthesia team can be mobilized, is likely to help in encouraging participation.
Engaging the nursing team is key as well; any operational changes in clinic work, preoperative preparation,
intraoperative care, and postoperative recovery will clearly require their input and buy-in. As nurses are often the
interface with patients and families throughout surgical care, they feel the brunt most strongly when patients become
upset at delays or unexpected changes. They can be a strong force for positive change when engaged early and
given respect as key members of the team.
Finally, one cannot forget the anesthesiologists in general. If you are embarking upon creation of a surgical home
model, the Chief or Chair of the Anesthesiology Department needs to be supportive of the effort. Many PSH
champions describe resistance within their practice by anesthesiologists reluctant to adhere to care pathways. Basing
pathways on the clearest evidence (when available) and garnering support from multiple group members in creating
pathways may help. If changes in the overall processes can be implemented that keep the day moving more
smoothly for the anesthesiologists, they will be much quicker to feel positively about any changes. Metrics that
show an improvement in patient outcomes will also help in keeping the anesthesiologists and surgeons engaged and
willing to work with the team to sustain changes.
Depending on the patient population selected for an initial PSH, other stakeholders may be involved including blood
bank, laboratory medicine, pharmacy, respiratory therapy, physical therapy, ICU or floor nursing, case management
and clinic schedulers. We encourage getting everyone who has a role in the patient’s care to be involved as part of
the process in building your PSH.
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Identifying and Acquiring Potential Resources:

Pre-operative care coordination
Performance Improvement Methodologies/Project Management
Electronic Health Record (EHR) enhancement
Measurements and reports on clinical and financial metrics
Patient engagement and measurement of patient satisfaction metrics
Post-operative care coordination and handoff back to “the medical home”
Resources will be required in order to create and implement a sustainable PSH. Whether it’s additional personnel,
alterations in the EMR, new data gathering approaches and dashboards to be created by IT, or funds for specialized
equipment, there needs to be an overall gain for the system demonstrated at some point. We have listed above
resources that may be required or beneficial to the PSH. Metrics, targeted at both process improvements and patient
centered outcomes, should be chosen and tracked beginning prior to implementation. Run charts can demonstrate the
impact of the process improvements as they are made. Demonstration of value can help justify an infusion of
resources to expand or continue the PSH.
Pre-operative Care Coordination:

An active pre-operative process is very helpful and key part of a robust PSH: some institutions are able to
accomplish this without a physical clinic, using a virtual process instead. Many find that a physical Clinic is where
patients will be screened and educated, perhaps pre-optimized, and be evaluated for medical conditions that might
alter their anesthetic plan. Coordination of testing and consults, in communication with the surgical team, will
ensure adequate preparation and eliminate potential gaps and redundancies. Traditional “pre-admit” testing grids,
such as anemia management protocols from adult preoperative clinics, are not as likely to cross over for significant
benefit to pediatric PSH models. Protocols tailored to pediatric conditions and needs can be utilized well in this
phase of care for overall gains to the system.
Intraoperative Pathways:
The intraoperative care may be guided by strong evidence for inclusions or exclusions of approaches, procedures, or
medications. The decision to use a regional technique, to avoid opioid medications, to limit overall fluid infusions,
or to use antifibrinolytics during surgery are all examples of evidence based techniques that alter the immediate
outcomes and risks and ultimately the recovery profile for our patients. Some of these decisions can have long
lasting effects that manifest in patients months or years later; for example addiction/chronic pain/risk of
MI/exposure to transfusions.
Performance improvement methodologies and measurement of metrics:

Getting a system in place to track adherence to the care pathway is necessary. There will likely be a “bundle” of
elements included in the intraoperative care area, with points to follow for each of the team members: surgeons,
anesthesiologists, and nurses. Creating checklists for review on each case, and having a method for extracting
document elements that demonstrate the elements that were followed, will be helpful. Audits may be necessary in
the absence of an electronic medical record with extractable data elements. And when such system is available, it is
likely that special reports will need to be created to pull the elements from the involved cases.
Postoperative Care Coordination:

The postoperative piece of the pathway has usually been the most difficult for institutions to implement. With the
move from inpatient care to ambulatory surgery in the 80’s and 90’s, substantial recovery for most patients shifted to
the home environment. Finding a way to contact patients to be sure they follow the recommended regimens, attend
their postoperative appointments, and have questions and concerns addressed in a timely manner can make the
difference between a smooth postoperative course and readmission to the hospital. Indeed, readmission rates may
be one of the metrics found to be useful in some situations. Finding a method, whether it’s a technology based app
that allows patient feedback and instruction or a staff member who calls each patient to discuss their progress on a
regular cadence, is the key, and will inevitably involve some commitment of extra resources.
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Patient Engagement and satisfaction metrics:

As a patient centered care model, it is imperative to include patients and families in the design and implementation
of the PSH. Additionally, measuring patient satisfaction metrics will allow for ongoing assessment of patient
satisfaction and support the validity of the care model.
Demonstrating Benefits:
Finally, as mentioned above, the metrics that are chosen to track the effects of care pathway implementation are
crucial in building support for a sustained system. Targets could and should include patient satisfaction, clinical
outcomes, operational/efficiency measures, and financial measures. With staff and physician engagement becoming
an area of high concern for organizations, to minimize staff turnover and its associated costs, metrics in these areas
may be considered as well. Ideally, changes related to the surgical home pathways would not only solidify the
evidence based care given to patients to achieve improved clinical outcomes, but would also simplify workflows,
eliminate redundant steps, and create a more positive working environment for staff, physicians, and ultimately the
patients.
Implementation:
In some cases, starting with individual care pathways, working with a single surgeon and his service, will allow
demonstration of the power of the model and open the door for expansion of the approach for other services. In
other institutions, building on the 3 key areas, preoperative preparation, intraoperative care, and postoperative care,
will allow the first steps to be taken. Demonstrating the anesthesiologists’ understanding of the key factors in each
of these areas, and their ability to impact the care there is important in gaining acceptance of our involvement in
areas that may previously have been “owned” by other individuals or services. A key concept to convey is that the
anesthesiologist not only knows what is needed to optimally prepare our patients, but we also can affect the longer
term recovery and setup the patient to do well or poorly in that phase. We are positioned to understand the effects of
the intraoperative phase, and to address pain issues to ensure optimal short and long term recovery. Indeed, it’s only
by being involved in following the patients’ recovery in the postop phase that we will be able to bring feedback to
the system and adjust our intraoperative management as well.
Some institutions in the ASA PSH Learning Collaborative describe a “modular” implementation strategy: taking on
one time phase of perioperative care such as the Pre-operative phase, or the intra-operative phase. Others have taken
on the entire care episode for a patient population –such as glucose control for diabetic patients. Both can be
successful strategies. Quantifying success with metrics important to the institutions leadership can justify an infusion
of resources and buy-in that allow PSH expansion.
Implementation Strategies: Case Studies

Lucile Packard Children’s Hospital Stanford (LPCHS):
At LPCHS, we began our journey by engaging some of the key players in the hospital leadership, the Chief of the
Medical Staff, The Chief Nursing Officer, and the Chief Operative Officer. After presenting an overview of the
strategy and goals of a PSH model, the overarching aims were well accepted. Because of multiple large projects
ongoing in our hospital at that time, with a new hospital expansion due to open in one year, and a new Electronic
Medical record having just been implemented, we chose to use minimal resources to map out an overall template for
the care pathways in all surgical areas. At the same time, we began to build a couple of care pathways in diverse
areas (Spinal Fusion and T&A) to pilot the model and test the approach to implementation.
We were fortunate in having two key elements in place already: a preoperative anesthesia clinic (Pediatric
Anesthesia Resource Center), and a robust pain service, covering both acute and chronic pain patients. With these
teams in place, piecing together the whole range of the care pathways has been more straight forward, but still
highlights gaps in the overall stream of care for our patients. In particular, we have struggled to identify the ideal
approach to postoperative follow-up outside of the hospital environment.
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Children’s National Health System (CNHS):
At CNHS, we began a comprehensive PSH for patients with Idiopathic Scoliosis having posterior spinal fusion. All
4 of our spinal surgeons were eager to participate and we had full engagement with physical therapy, nursing, the
operating room, and the anesthesia pain service. We underwent a 5 month design process with help from our
Performance Improvement team with Lean Sig Sigma Mapping, project management and some prioritization of
resources to modify the EHR. We implemented a comprehensive surgical home in March 2015 with strong results
showing a decreasing length of stay (LOS). Complete data is under review for publication.
More recently we have implemented a disease specific PSH for patients with Sickle Cell Disease (SCD). The PSH
includes SCD patients undergoing any type of operative procedure. Risk stratification allows for pre-admission and
hydration for more complex, high-risk patients and for same day admission and pre-hydration in the surgical
preparation area for lower risk patients. Evidence based care pathways including multi-modal pain medications and
post-discharge planning were designed for the more common procedures of childhood such as inguinal and
umbilical hernia as well as procedures more common within the SCD population such as laparoscopic
cholecystectomy and laparoscopic splenectomy.
1. Keren R, Luan X, Localio R, et al. Prioritization of comparative effectiveness research topics in hospital
pediatrics. Archives of pediatrics & adolescent medicine 2012;166:1155-64.
2. Ferrari LR, Antonelli RC, Bader A. Beyond the Preoperative Clinic: Considerations for Pediatric Care
Redesign Aligning the Patient/Family-Centered Medical Home and the Perioperative Surgical Home. Anesthesia
and analgesia 2015;120:1167-70.
3. Berwick DM, Nolan TW, Whittington J. The triple aim: care, health, and cost. Health affairs (Project
Hope) 2008;27:759-69.
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Palliative Care and Hospice in the Perioperative Care
Allen N. Gustin, Jr., M.D., F.C.C.P. Chicago/Illinois
How many times a week does your conscience make you wonder if you should not be providing
anesthesia to a patient? How often do you ask yourself, why are we here with this particular
patient having this particular “futile” procedure? Does the patient really understand all the
risks of the procedure? Risks of transfusion, ICU admission, prolonged intubation, never leaving
the ICU, never getting home, death, etc.? If you have asked this question to yourself, you are
not alone and many of us tend to be having these thoughts more often than not, sometimes it's
a daily thought. Next, if you have concerns, is it appropriate to have a conversation with this
patient at the time the patient arrives for the surgery? A patient who found the courage to
come for surgery and who is mentally prepared for the procedure, may not take very kindly to
your questions if you start asking whether or not the patient should be having the procedure?
Is that fair to the patient? How can we potentially prevent this from ever occurring in the first
place?
On the other hand, how many patients realize that they have an option of doing nothing. Many
patients with serious conditions seek care that does not necessarily meet their overall goals of
care.(1) Surgeons, endoscopists, and bronchoscopists are all being transformed into what this
author calls “the proceduralist." The proceduralist sees a patient for a particular issue and
offers an intervention for that patient by weighing the risks and benefits of only the procedure
by itself. For example, placing a feeding tube in a 60 year old male does not sound so bad. But,
when you find out that the feeding tube is for a 60 year old male with advanced stage
dementia, then you start wondering whether we are doing the right thing for the patient.
When does someone weigh the risks and benefits of a procedure with how that procedure
aligns with the patient’s goals of care. Should this be the role of the patient’s primary care
doctor? The surgeon? The anesthesiologist? Who?
Is the perioperative surgical home the answer? The perioperative surgical home is gaining
more acceptance and has a wider range of implementation among many different physicians in
many clinical institutions. The goals of the perioperative surgical home include improving
patient satisfaction, minimizing surgical complications, and reducing per capita cost. The role
that the anesthesiologist can take in the perioperative surgical home is quite obvious. The
anesthesiologist is a well suited for keeping the patient safe throughout the continuum of
surgical care along with managing all symptoms that occur after any surgical procedure. Is a
palliative care physician appropriate anywhere in the perioperative surgical home? Do you
consider palliative care solely based on end of life care? If so, you are not alone. What do you
think about a palliative care trained anesthesiologist? Did you know that the American Board
of Anesthesiology has 153 Hospice and Palliative Medicine boarded anesthesiologists at this
time? (2)
The goal of Palliative Care/Palliative Medicine is to improve a patient's experience with

healthcare, minimize the burden of disease, and reduce cost.(1) The perioperative surgical
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home has been defined as a ”patient-centered physical led multidisciplinary and team based
system of coordinated care that guides the patient though the entire surgical experience” from
the determination of need for surgery all the way until discharge from the faculty.(1) The two
pathways of palliative medicine and the perioperative surgical home appear to be aligned with
regard to the goals for healthcare and the goals for the patient. In the preoperative setting,
palliative care's involvement in the perioperative surgical home could focus further on whether
any surgical intervention is medically appropriate and aligned with the patient’s goals of care.
Also, palliative care's involvement in the preoperative management of a patient’s symptoms
can be important for maintaining patient’s satisfaction. Intraoperatively, the goals of care focus
more on the anesthesiologist's role of getting the patient through the surgery as safely and
quickly as possible. Postoperatively, the focus changes to management of pain and other
symptoms. Palliative physicians are experts in this field of symptom management and the
palliative care anesthesiologist/ palliative care physician can facilitate all of these aspects of
patient care discussions in the perioperative setting, including whether or not the patient
should have the procedure, whether or not the procedure meets his/her goals of care, or even
whether or not the patient should be/should ever be referred to Hospice.
Palliative care and hospice are complementary but some differences do exist. Palliative care is
based on a patient’s/family’s needs while hospice care is based on the patient’s prognosis.
Palliative care can be provided with ongoing efforts related to restoring health regardless of any
life sustaining treatment (including intensive care unit care). Whereas, hospice care tends to
focus on the patient’s goals of care at the end of life without engaging in active care options.
Palliative care can be provided with no limitations to care, even with the use of
cardiopulmonary resuscitation. Hospice tends to discourage life-sustaining options that do not
support the patient’s goals of care.(3). However, patients in Hospice and present to the
operating room, patients in Hospice can be discharged from Hospice, and the demographics of
Hospice patient populations are changing. Further elaboration on this will occur during the
presentation.
Palliative medicine has been increasingly integrated into the continuance of care but for the
most part has been under used. Advances in healthcare have shifted many disease processes
that were once lethal diseases into chronic conditions. Some examples of those chronic
diseases include HIV and AIDS, heart failure, chronic obstructive pulmonary disease, end stage
renal disease, and dementia. Palliative care is offered simultaneously with all other appropriate
medical treatments and its indication is not limited to situations associated with poor prognosis
for survival. Palliative care strives to achieve more than symptom control and it should be not
be confused with non-curative treatment. (3) Despite the success of the field’s growth,
palliative medicine has been slow to be integrated into the same continuum as standard care,
especially in the perioperative areas. Palliative care can provide aggressive symptom
management, even whether or not the patient chooses curative or life prolonging therapies. (3)
The key domains of palliative care for patients (as well as by expert consensus) include the
following: effective management of distress from physical, psychological, and spiritual
symptoms; timely and sensitive communication about appropriate goals of the intensity of care
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in relation to the patient’s condition, prognosis, and values; aligning of treatment with patient
preferences; attention to family’s needs and concerns; planning of care transitions; and support
for clinicians. (4) Palliative medicine also supports physicians/healthcare team members and
attends to clinician’s suffering/pain along with any caregiver’s hardship. The National
Consensus Project to Quality Palliative Care revealed 8 domains of care. (4) Those domains
included structure and process of care; physical aspects of care; psychological and psychiatric
aspects of care; social, spiritual/religious/existential/ cultural aspects of care; care of the
imminently dying patient; and ethical legal aspects of care.
Hospice has evolved into a form of patient care designed to provide comfort and support to
both patients and their families when an illness no longer responds to treatment. A
multidisciplinary team of caregivers provides hospice care. Team members consist of
physicians, nurses, social workers, counselors, home health aids, chaplains, and volunteers. A
hospice patient’s comfort and symptom control is the central aspect of care for the patent at
the end of life. Hospice will manage pain and other symptoms, offer support with the
emotional and spiritual aspects of dying, teach families skills to help them provide care, deliver
speech and physical therapy, make short term inpatient care available when needed, and
provide support and counseling to family members and loved ones. Hospice care has been
shown to neither hasten death nor prolong life.(5) And in some chronic health conditions,
patients in hospice care tended to live longer than their non-hospice counterparts.(5)
Increasing evidence reveals that palliative care and hospice care result in higher satisfaction
ratings by families of patients when compared with standard home health care, hospital care,
and nursing home care. (3) Palliative care has been shown to improve pain and non-pain
symptom control along with family satisfaction with care in the public and Veteran’s hospital
settings. (3) Evidence also suggests that palliative medicine improves survival in some patient
populations, where several reasons are suggested: avoidance of toxic non-beneficial
treatments, improved compliance with disease directed treatments, and physiologic benefits
resulting from effective symptom relief. (3) Palliative care has reduced hospital costs, reduced
ICU stay, and it has not been shown to increase mortality or morbidity.(3)
Symptom Management:
Symptom management is the cornerstone to palliative care. Physical symptoms can be one of
the most significant causes of distress among patients at the end of life. Many symptoms are
interconnected and include symptoms in the psychological domain. Multiple symptoms can be
present at the same time with some studies reporting a mean of 9 to 11 symptoms per patient.
(3) Pain, dyspnea, nausea/vomiting, pruritus, skin lesions, diarrhea, dyspnea, fatigue,
depression, anxiety, loss of any sense of purpose (uselessness), and agitation are common
symptoms at the end of life or when dealing with chronic illness. (3)
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Cardiopulmonary Resuscitation (CPR)/DNR Orders/Operating Room Procedures:
Should DNR orders be automatically rescinded when a patient comes to the operating room or
other interventional suite? CPR is proved around 800,000 times annually in the USA and is the
only medical intervention for which no consent is required, and an explicit physician order is
necessary for it to be withheld. (3) From the 1980s to 1991, patients DNR orders were routinely
rescinded on entering the OR. (3) Many of the anesthesiologists and surgeons felt that routine
anesthesia or surgical care would be considered resuscitation on any hospital medicine ward.
The routine suspension of a DNR order in the perioperative period by policy or assumption may
be seen as consistent with the tradition of beneficence, promoting the well-being of the patient
and perhaps no exploring whether these practices violated certain patents autonomy. (3) The
Patient Self Determination Act of 1990 established the US law that a patient’s right to self-
determination was the supreme standard in medical ethics, taking precedence over
beneficence. (3) As a result of the Patient Self Determination Act of 1990, the American Society
of Anesthesiologists guidelines support the “required reconsideration” of a patient’s DNR status
before proceeding with surgery. (3) Many conversations with patients regarding goals of care
should optimally occur long before a patient arrives to the operating room. Unfortunately, this
does not occur often in personal experience. This presentation will go through the four
possible outcomes of this discussion with patients regarding advanced directives. Or the reader
can refer back to Reference 3.
Pacemakers:
Should a pacemaker be placed in a patient with advanced stage disease? Is it considered

euthanasia or physician assisted suicide to avoid a pacemaker/ICD placement in patient with
advanced stage chronic illness? If the patient is approaching the end of life? The implantation
of cardiac pacemakers has become increasingly common in recent years. (3) Those patients
who have an ICD placed may have more quality of life issues than patients who have a routine
pacemaker placement. (3) Posttraumatic stress disorders occurred in 35% in patients after
ICD/pacemaker placement. (3) This has led to some experts recommending that all patients
who receive ICDs be assessed for psychological distress after placement. The decision to
deactivate a pacemaker can raise significant ethical concerns. (3) The larger question to
consider: Is deactivating a pacemaker ever ethically appropriate? What if the pacemaker
deactivation is part of a patient’s DNR order, can it be deactivated? The lecture will discuss all
the perioperative issues associated with the management of pacemakers in the perioperative
area.
Ventricular Assist Devices (VADs)
Are ventricular assist devices (VAD) considered artificial organs or mechanical assist devices?
Can a VAD be deactivated when a patient feels that the VAD is causing too much suffering?
VADs were originally designed to be used as bridges to heart transplant or recovery of the heart
after injury. Now VADs are commonly being used as destination therapy, which means that the
VAD is intended to be the final method of managing the heart failure symptoms when the
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patient is not a candidate for heart transplantation. Are VADs without some complications or
does the patient end up with a normal recovery/activity after VAD placement? Unfortunately,
a large number of patients who receive a VAD will still experience a large burden of symptoms.
(3) Several insurance companies and CMS require palliative medicine consultation for patients
at the time of VAD consideration and evaluation. ThIs lecture will discuss all the perioperative
issues associated with both the management of VADs in the perioperative area and the
symptom management of patients after VAD implantation.
Other groups of patients that will be considered in this presentation include the elderly patient
and the delirium risk; patients with chronic cancer pain who present for surgical procedures;
patients with chronic heart and lung failure presenting for surgery; and patients who present
for tracheostomy or feeding tubes as these procedures relate to the patient's goals of care.
At the very least, anesthesiologists are quite capable of providing basic palliative care with
“skills and competencies requiring of all physicians who care for patients with serious illness.”
Specialty palliative care is provided by a physician boarded in Hospice and Palliative Medicine
and becomes appropriate when patient care requires more complicated symptom management
control or goals of care discussions.(3)
Conclusion:
Palliative care's involvement in the perioperative surgical home is expanding and can be
integral in the management of patients who present to the operating room for procedures that
you may consider futile. Palliative care and skills in palliative care allow a physician the
opportunity to meet the physical, emotional, and spiritual needs of any patient in the
perioperative areas and help address the chief concerns voiced by those patients facing any
illness. There is a subset of patients for whom conventional approaches to pain and symptom
management do not provide adequate comfort. (3) In those cases, immediate consultation with
a clinician who has expertise in the management of these complicated patients and their
symptoms would be consistent with the referral consultation paradigm following in other areas
of medical practice. (3) Anesthesiologists by virtue of their unique training can logically serve in
this capacity. (3) There is always something that can be done safely, ethically, and legally that
coincides with our duty to cure when possible and provide comfort always. (3). This
presentation will explore further the role of the anesthesiologist as a palliative care physician.
References:
(1): Website: American Board of Anesthesiology

http://monitor.pubs.asahq.org/article.aspx?articleid=2468822 Accessed June 14, 2016.
(2): American Society of Anesthesiologists. Website:

http://directory.theaba.org/SearchResults.aspx?AdvancedSearch=true&FirstName=&LastName
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=&Search=Search&City=&StateAbbreviation=&ABAID=&CertType=525 Accessed June 14,

2016.
(3): Gustin AN, Aslakson RA. Palliative Care for the Geriatric Anesthesiologist. Anesthesia Clin.
2015 Sep;33(3):591-605.
(4): National Consensus Project. Website: http://www.nationalconsensusproject.org/

Accessed June 14, 2016
(5): Connor SR, Pyenson S, Fitch K, et al. Comparing hospice and non hospice patient survival
among patients with a three year survival, Journal of Pain and Symptom Management 2007
March; 3(33):238-246.
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Patients with Congenital Heart disease for Emergent Non-cardiac Surgery: What Skills do
we Need.
Chandra Ramamoorthy Palo Alto, CA
Objectives
1. Understand the pathophysiology of common congenital heart disease
2. How does the present surgery complicate the pre-existing heart disease
3. Is Bacterial endocarditis prophylaxis indicated for this procedure
4. Getting the patient ready for the emergent surgery
Introduction
Heart disease is the most common of congenital defects with a worldwide prevalence of 9 per
1000 live births and is societally the most expensive of congenital diseases. In developed
countries, with improvements in medical and surgical care 85% survive to adulthood . These
children present for non-cardiac surgery as they are susceptible to childhood illnesses like other
children. However unlike their healthy cohorts, their perioperative outcomes depend on several
factors including the severity of the heart disease.
Several studies have confirmed that there is an increased risk of adverse outcome following
anesthesia In this population. Children with complex heart disease had a greater mortality when
compared to those who were healthy or had mild heart disease. Majority of the arrests occur
during non-cardiac surgery in younger children (<2 years of age) and 75% of arrests are
accounted for by a few lesions.
Children with single ventricle physiology, dilated cardiomyopathy with those poor ventricular
function, significant left ventricular outflow tract obstruction and moderate to severe pulmonary
hypertension are considered at a higher risk for AE. Studies confirm that surgery after hours is
associated with a higher risk for adverse events.
The word “emergent surgery” often implies after hours work with little support. Unless it is life
threatening such as hemorrhage and hypotension, there should be little reason to proceed
without a good history, physical examination, reviewing records if available and seeking help from
a cardiologist prior to making an anesthetic plan. The cardiologist can assist with the diagnosis
and pathophysiology of the disease but it’s the anesthesiologist who needs to synthesize this
information along with the surgical demands such as blood loss during spinal fusion or CO2
insufflation during laparascopic procedure. Most children with congenital heart disease have
been palliated but not cured and the anesthesiologist caring for the patient has to be the team
leader intraoperatively.
Congenital heart disease ranges from the simple such as septal defects-atrial and ventricular ,
alone or in combination, patent ductus arteriosus to the more complex where, in addition to the
aforementioned defects, patients may have transposition of great vessels or have a functional
single ventricle. Some defects may have been closed by interventional catheterization (such as
ASD, PDA, VSD) with no external evidence and others may have a surgical scar, the extent of
which is no indication of the severity of underlying disease. Following a history, presence of
clubbing, cyanosis, murmur over the precordium can guide us to seek expert help. Presence of a
syndrome can be a tip off to certain lesions. Eg: Trisomy 21 and AV canal repair and these
patients may have long standing residual PH and many have OSA or a newborn with VACTERL
association who needs to have a TE fistula repair. Over time the conseqeunces of congenital
heart disease, whether palliated or not may be due to 1) cyanosis 2) arrythmias 3) worsening
ventricular function and heart failure 4) pulmonary hypertension either alone and or a
combination of these .
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Ventricular septal defect is the most common heart disease and it may occur alone or in
association with other heart defects such as AV canal, transposition of great vessels , tetralogy of
Fallot (TOF) . TOF is the commonest of cyanotic heart disease where newborns may survive to
infancy, childhood or adulthood without surgery. This is also the lesion associated with most
survival to adulthood and represents 60% of patients seen in an adult congenital heart defect
clinic (ACHD) .
Tetralogy of Fallot
TOF makes up 10% of all congenital defects affecting more boys than girls. The constellation of
features was 1st described by a Danish anatomist, Niels Stensen. Etienne Louis Arthur Fallot, a
French Physician described the clinical course and post mortem findings in 1888 and the disease
is named after him. TOF may be associated with chromosomal abnormalities such as DiGeorge,
Alagille’s, velocardiofacial. Patients with TOF may have associated 22q 11 deletion .
The components of TOF are: right ventricular outflow tract obstruction, ventricular septal defect,
overriding aorta and right ventricular hypertrophy. These children may be palliated in infancy with
a Blalock Taussig shunt followed by a staged complete repair. This intra-cardiac repair performed
on cardiopulmonary bypass includes closure of VSD, either transannular patch or pulmonary
valve sparing surgery. Long term sequelae include arrhythmias, pulmonary insufficiency and
ventricular dysfunction. More recently instead of repeat open heart surgery, trans-catheter
placement of pulmonary valve can be performed.
Children with TOF repair can safely undergo anesthesia for non-cardiac procedures unless they
have severe ventricular dysfunction or arrhythmias or are BT shunt dependant. Important to
remember that blood pressure is often lower on the side of the Blalock -Taussig Shunt. Infants
and children with a BT shunt are susceptible to “tet spells” which is a dynamic reversible
process due to a further narrowing of the right ventricular outflow tract leading to a right to left
shunt via the ventricular septal defect. Patients who depend on a BT shunt as their sole supply of
pulmonary blood flow must be adequately hydrated to maintain preload prior to anesthesia, and
both alpha agonist such as phenylephrine and beta blocker such as esmolol may be required to
treat “a spell “. The blood flow to the lungs depends on systemic blood pressure and hypotension
at induction must be promptly treated. Older children with arrhythmias may require placement of
external cardioversion-defibrillator patches as these are easier to manage in the perioperative
setting. It is prudent t have visual aids available at hand indicating dosage for cardioversion or
defibrillation.
Based on current AHA guidelines perioperative antibiotic administration is based on surgical
needs and in those with a BT shunt ; patients with corrected lesion are not a high risk for SBE,
and prophylactic antibiotics are not indicated.
Single Ventricle Physiology
Patients with complex heart disease may have only 1 functional ventricle. This may be the result
of many defects such as tricuspid atresia-here the LV will be the systemic ventricle or mitral
atresia where the RV is the functional pumping chamber. A whole range of lesions exist where
there is effectively 1 ventricle.
Hypoplastic left heart syndrome represents about 5% of CHD, is a spectrum of left sided cardiac
malformations dominated by a hypoplastic LV, atretic or hypoplastic aortic and mitral valve and
narrow aortic arch. The right ventricle supports both pulmonary and systemic circulations at birth
via a patent ductus arteriosus . This defect is unsustainable with out surgery and the procedure
performed in the neonatal period is most often the Norwood procedure. In this procedure the
aortic arch is repaired, the ductus is ligated and a source of pulmonary blood supply is
established either via modified Blalock Taussig shunt or a ventricle to pulmonary artery conduit
(Sano modification). Some centers now perform the hybrid procedure in the catheterization
laboratory. In this the PDA is stented and both pulmonary arteries are banded to restrict blood
flow to the systemic circulation. Following either of these procedures the circulation is
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completely mixed and the infant is blue with saturation in the 80’s. This is then followed by the
second stage operation around 4-6 months of age, the bidirectional Glenn or cavo-pulmonary
anastomosis where the superior vena cava is attached to the pulmonary artery and the Sano or
BT shunt are closed via surgical clips. The sole source of blood supply now is via the Glenn.
Factors affecting cerebral blood flow will affect the peripheral arterial saturation, as the cerebral
venous return feeds the pulmonary circuit. The final stage of the procedure is called the Fontan
operation or completion of cavopulmonary anastomosis . This is undertaken roughly at 3 years of
age or 15 kgm. In this surgery the inferior vena caval blood is diverted to the pulmonary artery
thus separating the systemic venous return from the pulmonary venous return. There are different
types of Fontan operation but currently most centers perform an extra cardiac Fontan using a
goretex conduit. The Fontan may be fenestrated allowing a “pop-off “into the common atrium
should the pulmonary artery pressures increase. When this is done late in a Fontan it is more
ominous than when done early during the Fontan procedure. In the latter situation it reduces
chest tube output and shortens length of stay while in the former its often because the patient has
developed protein losing enteropathy, which is associated with a major adverse outcome.
Several studies report a higher risk of mortality and morbidity following non cardiac surgery in
infants with single ventricle physiology. This is confounded by the fact that these infants often
have oral aversion, failure to thrive and require G tubes with or without Nissen fundoplication.
More over they may also have recurrent laryngeal nerve injury during stage 1 procedure with
resulting vocal cord paresis and the risk of aspiration of liquids . The pre- glenn stage is
considered the most vulnerable and hence elective non-cardiac procedures are best avoided
until after completion of the Glenn. Nasojejunal feeds may be preferred to g-tube insertion. A
recent multi-institutional survey that included 3 major centers showed no consistency in patient
selection, timing or technique of g tube insertion in the pre Glenn stage. It also cponfirmed a
roughly 12% incidence of complications.
Following the Glenn, since the SVC is routed into the PA’s, measuring central venous pressure
via a line in the neck indicates the pulmonary artery pressure and not intra-cardiac filling
pressure. For that a femoral venous line is required. However after a Fontan there is no way to
measure true left sided preload unless a PA catheter is placed and the pulmonary capillary
wedge pressure is obtained.
The key point to remember is that flow in a Fontan circuit is passive i.e., systemic venous return
is returned to the lungs and then to the single atrium passively. The pressure difference that
drives this is called “transpulmonary gradient” and is the difference between mean pulmonary
artery pressure (glenn pressure) which is about 10-15 mmHg and the atrial pressure which is
about 5-7 mmHg. The well functioning Fontan depends on adequate venous return to the lung,
low pulmonary vascular resistance so blood flows without the benefit of a ventricle as a reservoir,
normal lung parenchyma for oxygenation and unobstructed pulmonary venous return into the
atrium which contracts and empties into a ventricle with low end-diastolic pressure which is then
ejected into the aorta with out any regurgitant valves and a low systemic vascular resistance.
Hence the development of arrhythmias (loss of atrial kick), atrio-ventricular valve or aortic valve
insufficiency spells trouble for a patient with a Fontan circuit. Similarly surgical positions such as
reverse trendelenburg, trendelenburg, lithotomy, abdominal insufflation all can reduce venous
return and thus affect cardiac output.
Spontaneous ventilation is preferable for both the Glenn and Fontan physiology as the negative
intrathoracic pressure drives flow through the lungs. However this might not be a choice during
major surgery. While permissive hypercapnia drives the Glenn flow, metabolic acidosis will
increase pulmonary vascular resistance. For a Fontan circulation whether large tidal volume with
low rate or small tidal volume with a more rapid rate should be used during IPPV is matter of
debate and institutional preference. There is universal agreement that systemic venous flow to
the pulmonary arteries is reduced or reversed during positive pressure ventilation and hence
return to spontaneous ventilation as soon as possible post-procedure is desired. Over distension
of alveoli with large tidal volume or high PEEP must be avoided and early use of Nitric oxide
might be indicated to improve oxygenation.
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The role of ECMO support before proceeding with emergent major surgery should also be
addressed both with the family and surgeon.
Due to sinus node dysfunction or ventricular dysfunction some children may have epicardial
pacemakers in place. This introduces the need for having the underlying rhythm interrogated, with
a plan on how to manage the pacemaker intraoperatively. If an AICD is in place due to ventricular
arrhythmias then the ICD function needs to be disabled.
Pulmonary Hypertension
Pulmonary arterial hypertension is defined as the presence of mean pulmonary artery pressure
greater than 25 mmHg at rest or 30 mmHg during exercise. Pulmonary hypertension may be
idiopathic or secondary. There are several causes for PH in children and congenital heart disease
is one of them. This secondary pulmonary hypertension may occur in untreated (uncorrected
VSD, PDA, Eisenmenger) treated and or untreated ( AV Canal) or palliated congenital heart
disease (single ventricle disease following Glenn or Fontan operation.
PH is associated with significant perioperative risk for complications including acute pulmonary
hypertensive crisis, which if not treated expeditiously can result in a cardiac arrest..
Retrospective studies of children undergoing cardiac catheterization and non cardiac surgery
show that they are at significantly increased risk of cardiac arrest and death when compared to
children without PH. Of over 100,000 anesthetics administered to children in a tertiary care
children’s hospital the incidence of anesthesia related deaths was 1:10,188. In all 10 cases pre-
existing medical conditions were identified as risk factors; 5 of these involved children with PH.
Risk factors for PH crisis include severity of PH, associated comorbidity such as congenital heart
or lung disease and home oxygen therapy. Patients who are already on maximal vasodilator
therapy are not immune to PH crisis.
A PH crisis is said to occur when the mean pulmonary vascular pressure exceeds mean
systemic blood pressure with associated increase in resistance. Hence it is importance to think of
an alteration in the PVR/SVR ratio. When this ratio increases the right ventricle dilates, the inter-
ventricular septum is pushed into the left ventricle affecting filling and output od the LV. This
results in impaired coronary artery perfusion, leading to arrhythmia and death.
In managing a patient with PH for emergent non-cardiac surgery, the caveat of avoiding hypoxia
and hypotension prevails. Hypoxia and hypercarbia both increase the PVR. Systemic
hypotension affects coronary perfusion and even mild hypotension can tip the scales. It is
important to think of alteration in the ratio of PVR/SVR rather than just factors lowering PVR. If
alveolar hypoxia is avoided, most gaseous anesthetics(except N2O) do not increase PVR in
children. Volatile anesthetics are non-specific pulmonary vasodilators acting via NO independent
pathways and are useful adjuncts in managing PH patients for noncardiac procedures. Propofol,
ketamine, etomidate, fentanyl , Dexmedetomidine have all been used in this population. Bolus of
propofol that reduces preload, or dexmedetomidine that slows the HR significantly can de
detrimental. Hence infusion of these agents is our preferred method of induction along with a
small bolus (0.5-1 mg/Kg) of ketamine. Positive pressure ventilation can cause significant
alterations in right sided preload and should be instituted with care using the low tidal volume
strategy. It is our preference to extubate deep when possible and avoid the hemodynamic
changes associated with awake extubation.
It is important to be prepared for PH crisis when managing this patient population. The goal of
management is to increase the SVR. This achieves 2 goals: moves the interventricular septum
rightward allowing greater left sided cardiac output ; increases coronary perfusion which might
prevent ventricular arrhythmias and right heart failure. Agents that have been tested include
phenylephrine, norepinephrine, epinephrine and arginine vasopressin. In a small pilot study of
patients with moderate to severe PH, vasopressin 0.03 units/kg IV bolus was associated with a
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consistent decrease in PVR/SVR (i.e., SVR rose more than PVR). Early use of ECMO support
should be considered if the patient continues to have arrhythmias and hypotension.
Other congenital heart diseases with residual effects include coarctation of aorta, 85% of this
lesion is associated with a bicuspid aortic valve. The child may or may not be hypertensive but
the bicuspid aortic valve increases the risk for SBE. Although the current standard for
transposition of great arteries is the arterial switch operation, it is not uncommon to encounter a
patient with the atrial switch (Mustard or Senning operation) procedure. In this since the right
ventricle is the systemic ventricle which fails over time and the patients are also susceptible to
atrial arrhythmias.
Approach to Perioperative Management for Emergent Surgery in Children with

Heart Disease : Do we need any special skills?
History and physical examination remain the cornerstone in caring for these children. Often the
parents are well informed and provide a wealth of information. Tonsillectomy is the most
common surgery that children undergo. While this may not be performed emergently, a bleeding
tonsil could be emergent. Similarly diagnostic procedures of the airway for stridor or foreign body
retrieval, abdominal emergencies, trauma occur in children with heart disease as well. A general
approach is suggested and must be tailored to individual situation.
Understanding the current anatomy and physiology is necessary and in addition the current
medications the child is on are important in the safe care of all patients we manage. Those with
poor myocardial function are likely to be on ACE inhibitors, which is associated with perioperative
hypotension. Similarly prolonged use of diuretics with low serum K+ and Mg++ may predispose to
arrhythmias under anesthesia apart from the volume depletion associated with its administration.
If a child is on PDE5 inhibitors (sildenafil), perioperative Nitric oxide might be required or the
medication may need to be restarted as soon as possible. Aspirin, Coumadin and more recently
anti-Xa inhibitors feature on the list of medications these children may be on. This could
determine the role of neuraxial blockade one might choose. For those on Coumadin
administering both a dose of Vit K and a dose of prothrombin concentrate with or without
additional fresh frozen plasma could be considered. Since these children may have been
transfused in the past some are likely to have antibodies which might make cross matching
difficult and take longer. Hence need for blood and blood product should be clearly discussed and
appropriate measures taken.
Preoperative EKG should be obtained as it could serve as a basis for comparison . Similarly an
echocardiogram might also be indicated. The key is to go to the operating room with a clear road
map of anatomy and pathophysiology. Then based on the type of surgery whether additional
monitoring is required or not can be dealt with systematically. Meticulous debubbling of all
intravenous lines to remove air is essential particularly in those with residual intracardiac defects.
Since even a single ventricle with series circulation may have fenestration it is best to assume
existence of shunts and de-bubble lines. Adopt a low threshold for arterial line and central line
placement. Trans-thoracic echo at induction is a useful tool in those with poor function or where
moderate PH is suspected. Intraoperative TEE is a valuable monitor for assessing volume status
and air.
Most anesthetic agents have been safely used in this population, including spinal and other
neuraxial blocks depending on the type of surgery and emergency. The dose and rate of
administration of anesthetics should be adjusted to the individual pathophysiology and careful
titration might be necessary. A plan needs to be in place for adequate postoperative analgesia
and where the child will be managed – floor or intensive care unit .
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Infective endocarditis prophylaxis must be discussed. Patients with cyanotic heart disease are
considered “high risk’ and antibiotics are indicated. On the other hand an ASD or VSD or PDA
that was repaired more than 6 months ago does not require IE prophylaxis. Current AHA
guidelines should be followed.
In conclusion, managing children with cardiac disease for non-cardiac surgery requires
knowledge of the lesion, the surgery, long term sequelae of the lesion, impact of current disease
and planned surgery on the pathophysiology of the disease and finally the perioperative care. As
the anesthesiologist we need not only an understanding of the medical issues but also be a good
communicator with the child and the family, cardiologist and the intraoperative team in
synthesizing and executing a plan. In addition we need to have thought through potential
complications and discussed the role and feasibility of ECMO or other forms of cardiac support
where indicated.
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References:
General articles:
1. Ramamoorthy C, Haberkern CM, Bhananker SM, Domino KB, Posner KL, Campos JS, Morray
JP. Anesthesia-related cardiac arrest in children with heart disease: data from the Pediatric
Perioperative Cardiac Arrest (POCA) registry. Anesth Analg. 2010 May 1;110(5):1376-82. doi:
2. Watkins SC, McNew BS, Donahue BS. Risks of non-cardiac operations and other
procedures in children with complex congenital heart disease.Ann Thorac Surg 2013;
95:204-11
3. Faraoni, D, Zurakowski, D, Vo, D Goobie, S M, Yuki, K , Brown ML, DiNardo JA

Post-Operative Outcomes in Children With and Without Congenital Heart Disease
Undergoing Noncardiac Surgery. J Am Coll Cardiol 2016;67:793–801
4. Wilson W, AHA recommendation: J Am Dent Assoc. 2007 Jun;138(6):739-45, 747-60. Review.
Single Ventricle:
1. Christensen RE, Gholami AS, Reynolds PI, Malviya S. Anesthetic management and outcomes
after non cardiac surgery in patients with hypoplastic left heart syndrome: a retrospective review.
Eur J Anesthesiol 2012; 29:425-430
2. Rabbitts JA, Groenewald CB, Mauermann WJ, Barbara DW, Burkhart HM, Warnes CA, Oliver
WC Jr, Flick RP. Outcomes of general anesthesia for noncardiac surgery in a series of patients
with Fontan palliation. Pediatr Anesth. 2013 Feb;23(2):180-7
3. Brown M, Dinardo J, Odegard K. Patients with single ventricle physiology undergoing

noncardiac surgery are at a high risk for adverse events. Pediatr Anesth. 2015 ; 25 (8)846-
51.
4.Jolley M, Colan SD, Rhodes R, DiNardo J. Fontan Physiology Revisited. Review Article. Anesth
Analg 2015 July :121: (1) 172-82.
Pulmonary Hypertension:
1. Williams GD, Maan H, Ramamoorthy C, Kamra K, Bratton SL, Bair E, Kuan CC, Hammer GB,
Feinstein JA. Perioperative complications in children with pulmonary hypertension undergoing
general anesthesia with ketamine. Paediatr Anaesth. 2010 Jan;20(1):28-37
2. van der Griend BF, Lister NA, McKenzie IM, Martin N, Ragg PG, Sheppard SJ, Davidson AJ.
Postoperative mortality in children after 101,885 anesthetics at a tertiary pediatric hospital.
Anesth Analg. 2011 Jun;112(6):1440-7.
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3. Friesen RH, Williams GD. Anesthetic management of children with pulmonary arterial
hypertension. Paediatr Anaesth. 2008 Mar;18(3):208-16.
4. Carmosino MJ, Friesen RH, Doran A, Ivy DD. Perioperative complications in children with
pulmonary hypertension undergoing noncardiac surgery or cardiac catheterization. Anesth Analg.
2007 Mar;104(3):521-7.
5. Taylor K, Moulton D, Zhao XY, Laussen P. The impact of targeted therapies for pulmonary
hypertension on pediatric intraoperative morbidity or mortality. Anesth Analg. 2015
Feb;120(2):420-6.
6. Siehr SS, Feinstein JA, Yang W, Peng L, Ogawa M, Ramamoorthy C.Hemodynamic

Effects of Phenylephrine, Vasopressin, and Epinephrine in Children With Pulmonary
Hypertension: A Pilot Study
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Re-evaluating Monitoring and Reversal of Neuromuscular Blockade
Roy Soto, M.D. Royal Oak, MI
Introduction
Paralysis for surgical procedures became commonplace after the introduction of a number of relatively safe
neuromuscular blocking agents in the mid-20th century. Prior to the introduction of these medications, immobility
during surgery was provided by the muscle relaxant properties of volatile agents. The high concentrations of
volatile agents needed to provide relaxation, however, was complicated with hemodynamic depression, and
paralytics allowed for the introduction of “balanced anesthetic technique”, which allowed a combination of
medications to provide ideal surgical conditions without the unwanted side effects of any one drug alone.
As new paralytics were introduced into the anesthetic armamentarium, so too were new monitoring devices which
yielded significant information regarding paralytic pharmacodynamics and the unique properties of neuromuscular
recovery. Recommendations for monitoring were well described in the literature and anesthetic texts from the 1970s
onwards described details of single twitch, train of four (TOF), double-burst suppression, post tetanic potentiation,
and sustained tetanus monitoring. Indeed, a rite of passage of any student of anesthesia included a mandatory
lecture, usually early in training, describing the percent of receptors bound at each level of train of four recovery,
and appropriate timing for administration of reversal agents (1). Despite well-established information, standardized
education, and clinical experience during training, however, many anesthesia providers (self-admittedly) do not
follow evidence-based recommendations, despite awareness of literature to the contrary (2). This refresher course
lecture will review the evidence for appropriate monitor-based medication dosing and reversal, and discuss potential
barriers to implementation of best practices.
Onset of Paralysis
Unlike many other medications, paralytics are initially dosed at supratherapeutic concentrations in order to achieve
rapid onset of clinical effect. Dosing at twice to three times the ED95 for non-depolarizing agents is the norm, and
while neuromuscular monitoring may be appropriate at the start of a case, most providers trust in the
pharmacodynamic properties of these drugs, and intubate after a set time period has elapsed. Due to these
predictable pharmacodynamics, excellent intubating conditions are generally achieved, and monitoring is felt by
many to be superfluous at this time point.
Maintenance of Paralysis
Appropriate redosing of paralytic agents should occur when patients demonstrate some spontaneous recovery of
neuromuscular function. Maintaining one to two twitches (during TOF monitoring) is the goal for providing ideal
surgical conditions, and this can generally be achieved by giving a small ED50-ED95 dose of paralytic every 20-40
minutes during the maintenance phase of anesthesia; although there is a growing body of evidence that deep
neuromuscular blockade (TOF 0-1) may indeed provide optimal surgical conditions in laparoscopic surgery (3).
Indeed many providers practice in precisely this way, using time-based dosing rather than monitor-based dosing,
despite a clear understanding that inter-patient and inter-anesthetic variability is high. Surveys of clinicians in
Germany and the United Kingdom reveal that only 28% and 10% respectively, use neuromuscular monitors of any
kind, which suggests that those that do not use monitors achieve good results nonetheless (4, 5).
Proper monitoring should involve TOF examination at the adductor pollicis muscle, and indeed the majority of data
published in basic texts (describing onset, duration, fade, and recovery characteristics) specifically cite thumb data.
At times, however, the hand may not be available or suitable for monitoring (when the arms are tucked, for
instance), and the facial nerve can be monitored instead, although we understand that certain caveats should be kept
in mind when monitoring in that location. First, inappropriate lead placement can lead to direct muscle stimulation
which can be inappropriately interpreted as neuromuscular recovery. Second, while facial nerve function closely
parallels diaphragmatic and glottic muscle function, ulnar nerve recovery more closely predicts complete recovery
from paralysis. Thus, patients undergoing facial nerve monitoring may suffer from incomplete recovery or be
incorrectly deemed “reversed” when they still have measurable paralysis in the hand. In fact, it has been
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demonstrated that patients that are monitored with facial nerve stimulation had a 5-fold increased risk of residual
paralysis when compared to those monitored at the ulnar nerve (6). Unfortunately despite these limitations, many
providers choose to monitor the facial nerve for reasons of pure convenience, despite having access to the hand.
Furthermore, clinical decisions may be based on facial nerve monitoring and extrapolated to adductor pollicis
recovery…again a situation which may lead to incomplete recovery.
Recovery from Paralysis
As previously described, introduction of paralysis is generally done without neuromuscular monitoring, and
maintenance of paralysis frequently occurs with a complete or relative lack of appropriate functional data. At the
completion of an anesthetic, appropriate reversal of neuromuscular blockade is mandatory. Reversal is typically
given at the time of some degree of spontaneous recovery, and dosing of reversal agents is either weight or time
based, or a combination thereof. Unfortunately, again, many anesthesia providers fail to monitor for recovery at the
conclusion of a case. A 2010 survey completed by Naguib and colleagues revealed that 19.3% of European and
9.4% of American respondents never use neuromuscular blockade monitors at the time of reversal (7). Most
respondents reported that neuromuscular blockade monitors should not be used as part of standard monitoring
during anesthesia despite a clear understanding of the importance of neuromuscular recovery.
Providers display a willingness to rely on clinical signs, such as respiratory pattern or measurement of oxygen
saturation to determine when patients can be safely extubated, although measurements of vital capacity, negative
inspiratory force, or minute ventilation breathing all require patient participation to be reliable and all can be normal
in the face of significant residual neuromuscular weakness. Furthermore, clinical tests of strength including head lift
and grip strength are subjective, and also have been shown to not correlate with complete recovery (5, 8).
Dosing of reversal agent also seems to be variable, with some providers considering 0.05mg/kg to be a “maximum
dose”, while others use 0.07mg/kg. Some give the maximum dose to all patients regardless of degree of paralysis at
time of reversal, while others vary their dose depending on recovery. While 0.07mg/kg is described in the literature
as a maximum dose, care must be taken when giving patients high doses of cholinesterase inhibitors in the face of
light block…the neostigmine alone can cause weakness when overwhelming doses are given (9). A more prudent
approach would be to use 0.05 to 0.07 mg/kg when patients have 3-4 twitches visible on TOF monitoring at the hand
(with fade), and 0.025mg/kg when patients have 4 strong twitches with no evidence of fade (10, 11). Note that care
should be taken when attempting to reverse patients at only 1 twitch, as recovery can take >20-30 min, even with
maximum neostigmine dosing. (12)
Clinical implications of residual paralysis
Residual paralysis, defined as having a TOF ratio less than 0.9, occurs in 30-50% of patients receiving intermediate
acting agents, and use of intraoperative monitoring decreases that risk (13). Incomplete recovery from paralysis
results in an increased risk for critical pulmonary complications in the PACU, a subjective complaint of weakness,
and a decrease in satisfaction with anesthetic recovery (14, 15). Failure to reverse neuromuscular blockade has also
been shown to increase risk of mortality or coma by 90% within 24hr of surgery (16). Yet despite these figures,
many clinicians continue to monitor and reverse casually or inappropriately.
Many clinicians point out that despite data to the contrary, they don’t see their patients having weakness-associated
adverse events, and to that point, the vast majority of our patients, despite some having residual paralysis, recover
uneventfully and are discharged with no untoward events, lending support to commonly practiced
monitoring/reversal techniques (2, 5). It must be pointed out, however, that not all patients are created equally, and
obese/elderly/pediatric/frail patients are at a uniquely increased risks of weakness-associated adverse events, and
many adverse events that have no clear causation can retrospectively be attributed to residual paralysis (17).
Sugammadex and implications for the future of paralytic management
Sugammadex is a unique cyclodextrin agent that forms a tight bond with rocuronium and vecuronium. The bond is
functionally irreversible, and the bound complex is excreted renally with no evidence of recurarization. The agent is
capable of completely reversing profound block (from 0 twitches to TOF% > 90) in less than 2 minutes, with limited
adverse effects. Its reversal properties are dose dependent, allowing for rapid reversal of shallow block (4 twitches
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on TOF monitoring), moderate block (1-3 twitches), or deep/profound block (0 twitches, with or without post-
tetanic potentiation). Although available since 2008 in Europe, this agent has only recently become available in the
United States, and pharmacoeconomic analysis will determine how large of a role this medication will play in
everyday practice. Certainly, one can predict that sugammadex should be available wherever
rocuronium/vecuronium are administered (for emergency reversal purposes), and that more predictable/complete
reversal might improve patient safety and quality of care.
Monitoring and reversal of neuromuscular blockade: evidence-based recommendations
It is therefore possible to conclude the following from the preceding discussion:
1) Evidence for appropriate dosing, monitoring, and reversal of neuromuscular blocking agents is well
established in the literature.
2) Despite this evidence, many providers do not follow evidence-based guidelines for reasons of habit or
“experience”.
3) Residual paralysis occurs frequently, but adverse events do not. Nevertheless certain high-risk patients are
clearly at a higher risk of suffering from postoperative complications when residual paralysis is present.
4) When adverse events related to weakness do occur, the results can be catastrophic, and expensive.
5) Simple evidence based guidelines should be promulgated by academic and specialty societies to improve
safety of anesthetic care, and compliance with best practices should be measured and reinforced.
Appropriate evidence-based recommendations, therefore, should include the following:
1) All patients receiving nondepolarizing neuromuscular blocking agents must be monitored for
neuromuscular function.
2) When possible, TOF monitoring should occur at the ulnar nerve. If facial nerve monitoring is necessary,
then special care must be taken to ensure complete recovery prior to extubation.
3) Patients with 1, 2, or 3 twitches (visual or tactile) at the conclusion of surgery should receive a “full dose”
of reversal agent (50-70mcg/kg), with the understanding that full reversal will not occur for 15+min.
4) Patients with 4 twitches (visual or tactile) at the conclusion of surgery should receive 30-50mcg/kg of
reversal agent, again with the understanding that full reversal will not occur for at least 7 minutes.
5) Patients with 0 twitches, or those with 0 twitches but post-tetanic potentiation should not receive
anticholinesterase reversal until spontaneous recovery has occurred.
6) Sugammadex allows for reversal at all states of paralysis, and may improve patient safety in appropriate
circumstances.
Conclusion
The etiology of weakness and weakness-related respiratory events in the PACU is multifactorial, with patient,
surgical and anesthetic factors all coming into play. Clinicians should follow time-tested and evidence-based
recommendations to prevent paralysis-related events. The Association of Anaesthetists of Great Britain and Ireland
have issued a statement mandating that peripheral nerve simulators be used whenever NMB drugs are given (8). It
would prudent (not to mention evidence-based) for the ASA to follow this lead and include peripheral nerve
stimulation/monitoring to monitoring standards when paralytics are given.
References
1. Bevan, DR, Donati, F, Kopman, AF Reversal of neuromuscular blockade. Anesthesiology. 1992; 77:785–
805
2. Todd MM, Hindman BJ, King BJ. The implementation of quantitative electromyographic neuromuscular
monitoring in an academic anesthesia department. Anesth Analg 2014; 119:323-331
3. McLean DJ, Diaz-Gil D, Farhan HN, Ladha KS, Kurth T, Eikermann M. Dose-dependent association
between intermediate-acting Neuromuscular-blocking agents and postoperative respiratory complications.
Anesthesiology. 2015; 122:1201-13
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4. Madsen MV, Staehr-Rye AK, Gatke MR, Claudis C. Neuromuscular blockade for optimising surgical
conditions during abdominal and gynaecological surgery: a systemic review. Acta Anaesthesiologica
Scandinavica. 2015: 59; 1-16
5. Fuchs-Buder T, Hofmockel R, Geldner G, Diefenbach C, Ulm K, Blobner M. The use of neuromuscular
monitoring in Germany. Anaethesitst. 2003,52-55-6.
6. Thilen SR, Hansen BE, Ramaiah R, Kent CD, Treggiari MM, Bhananker SM. Intraoperative
neuromuscular monitoring site and residual paralysis. Anesthesiology. 2012; 117:964-72
7. Grayling M, Sweeney BP. Recovery of neuromuscular blockade: a survey of practice. Anaesthesia 2007;
62:806-9.
8. Checketts MR, Alladi R, Ferguson K, et al. Recommendations for standards of monitoring during
anaesthesia and recovery 2015: Association of Anaesthestists of Great Britain and Ireland. Anaesthesia
2015
9. Sasaki N1, Meyer MJ, Malviya SA, Stanislaus AB, MacDonald T, Doran ME, Igumenshcheva A, Hoang
AH, Eikermann M. Effects of neostigmine reversal of nondepolarizing neuromuscular blocking agents on
postoperative respiratory outcomes: a prospective study. Anesthesiology. 2014; 121:959-68
10. Fuchs-Buder T, Meitelman C, Alla F, Grandjean A, Wuthrich Y, Donati F. Antagonism of low degrees of
atracurium-induced neuromuscular blockade. Dose-Effect Relationships for Neostigmine. Anesthesiology
2010; 112:34-40
11. Fuchs-Buder T, Baumann C, De Guis J, Guerci P, Meistelman C. Low-dose neostigmine to antagonize
shallow atracurium neuromuscular block during inhalational anaesthesia: A randomized controlled trial.
Eur J Anaesth 2013; 30:594-598
12. Naguib M, Kopman AF, Lien CA, Hunter JM, Lopez A, Brull SJ. A survey of current management of
neuromuscular block in the United States and Europe. Anesth Analg. 2010;111:110–9
13. Kopman AF, Eikermann M. Antagonism of non-depolarising neuromuscular block: current practice.
Anaesthesia. 2009; 64 Suppl 1:22-30
14. Murphy GS, Szokol JW, Marymont JH, et al. Intraoperative acceleromyographic monitoring reduces the
risk of residual neuromuscular blockade and adverse respiratory events in the postanesthesia care unit.
Anesthesiology 2008; 109:389-398.
15. Murphy GS, Szokol JW, Marymont JH, et al. Residual neuromuscular blokade and critical respiratory
events in the postanesthesia care unit. Anesth Analg 2008; 107:130-7.
16. Debaene B, Plaud B, Dilly M-P, Donati, F. Residual paralysis in the PACU after a single intubating dose of
nondepolorazing muscle relaxant with an intermediate duration of action. Anesthesiology 2003; 98:1042-
1048.
17. Arbous MS, Meursing AE, van Kleef JW, de Lange JJ, Spoormans HH, Touw P, Werner FM, Grobbee DE.
Impact of anesthesia management characteristics on severe morbidity and mortality. Anesthesiology. 2005;
102:257-68
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Postpartum Hemorrhage: How to Prepare for It, How to Prevent It, and
What to Do When Blood is Pooling on the Floor
Jill Mhyre, MD Little Rock, Arkansas

The learner will: 1) Identify women at risk for major postpartum hemorrhage; 2) List options available to control
and mitigate the consequences of obstetric hemorrhage; 3) Discuss how contemporary transfusion practices apply in
the obstetric setting; and 4) Draw from published guidelines and protocols to inform both individual clinical practice
and systems solutions to prepare for these emergencies.
Definitions
Postpartum hemorrhage is most commonly defined by estimated blood loss (EBL) ≥500 mL for vaginal
delivery and ≥1000 mL for cesarean delivery. The risk for adverse health outcomes accumulates with persistent
postpartum hemorrhage, when bleeding exceeds 1000 mL and persists despite the use of first-line uterotonics and
uterine massage,1 particularly if bleeding is accompanied by signs or symptoms of hypovolemia.2 The National
Partnership for Maternal Safety recently defined indicators of severe maternal morbidity as ICU admission or
transfusion with 4 or more units of blood products, and recommended that women with these indicators receive
multidisciplinary review for the purpose of identifying opportunities for systems improvement. 3 Massive blood
transfusion has been defined as >10 u blood products transfused during the hospitalization for delivery4 or as
erythrocyte transfusion >3 u/hour.5
Etiology
Primary postpartum hemorrhage develops within 24 hours of delivery and is due to uterine atony, retained
placenta, genital tract trauma, placenta accreta, increta and percreta, uterine inversion, or coagulopathy.
Coagulopathy may be inherited or result from a range of disorders in pregnancy, with amniotic fluid embolism being
the most severe.6 Secondary postpartum hemorrhage is relatively infrequent, develops over 24 hours after delivery,
and is ascribed to subinvolution of the placental site, retained products of conception, infection, or inherited
coagulation defects.
Epidemiology
Postpartum hemorrhage complicates at least 3% of all deliveries, and appears to be increasing in frequency.7,8
Approximately 3% of women receive any blood products. Hemorrhage accounts for close to half of obstetric
intensive care unit admissions,9 and 38% of cardiac arrests during the hospitalization for delivery.10
Uterine atony underlies 80% of all cases of postpartum hemorrhage.7 Population-level factors driving the
increasing frequency of uterine atony include: 1) increasing population prevalence of obesity, multiple gestation,
and advanced maternal age; 2) increasing inductions of labor;11 and 3) increasing cesarean deliveries, from 21% of
all births in 1997 to 32.7% in 2013.12 Unrelenting uterine atony leads one-third of all peripartum hysterectomies.13
Uteroplacental inflammation (e.g., chorioamnionitis, vasculitis, funisitis, endometritis, and cervicitis) appears to be a
major contributor to uterine atony that is sufficiently severe to require peripartum hysterectomy. 14
Placenta accreta with or without placenta previa is the leading cause of massive blood transfusion.4 Accreta
leads to approximately half of all peripartum hysterectomies, and rates have increased in conjunction with the
burgeoning population of pregnant women with prior cesarean deliveries.4
Historically, hemorrhage was the leading cause of maternal death in the United States, but accounts for 11% of
the total, or 1.8 maternal deaths per 100,000 live births in the United States.15 The majority of hemorrhage-related
deaths are preventable.16-19
Anticipated Postpartum Hemorrhage
Even with the physiologic anemia of pregnancy, a hematocrit less than 32% should be treated to reduce the risk
of peripartum blood transfusion (e.g., oral or intravenous iron). In addition, three groups need special antenatal
preparation: 1) women with abnormal placentation; 2) those with inherited coagulation disorders; and 3) those who
refuse blood products.
Abnormal Placentation
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With placenta accreta, the decidua basalis (i.e., the decidual basal plate) is absent, and the basal plate of the
placenta adheres to a floor of uterine myometrium. With placenta increta, chorionic villi invade into the
myometrium, and with percreta, the placenta penetrates the uterine serosa, and may even grow into other pelvic
structures, most commonly the bladder. Prior cesarean delivery, other uterine surgery, placenta previa, and maternal
age ≥35 years are important risk factors for placenta accreta. Placental location mediates the relationship between
prior cesarean and risk of accreta. Among women with a known placenta previa, the incidence of a morbidly
adherent placenta increases from 3% among primary cesarean deliveries, to 11%, 40% and >60% after one, two, and
three or more prior cesarean deliveries, respectively. 20 Given the rising incidence and prevalence of cesarean birth,
placenta accreta increased from 0.8 per 1000 deliveries in the 1980s to 3 per 1000 deliveries in the past decade.21
Intrapartum blood loss is difficult to predict, depends on the success of the surgeons in avoiding manipulation of
the placental bed, and can be rapid.22 Antenatal recognition and controlled surgical delivery improve outcomes. 23-26
Accreta is often evident on the anterior surface of the uterus, and in such cases, as long as the mother and fetus are
stable, it may be possible to close the abdomen and transfer the patient to a center of excellence for planned cesarean
hysterectomy.27 Placenta accreta remains the leading indication for unplanned peripartum hysterectomy,28 likely as a
consequence of the limitations of diagnostic accuracy.
Ultrasonography to locate the placenta and evaluate for markers of placenta accreta is recommended for every
woman who has undergone prior uterine surgery, or found to have a low-lying placenta on the routine first or second
trimester ultrasound.21,29 Magnetic resonance imaging (MRI) may help to confirm the diagnosis when ultrasound is
inconclusive, and define the extent of invasion into surrounding organs in the case of placenta percreta. 21 Women
with a diagnosis of abnormal placentation based on ultrasonography are more likely to require blood transfusion and
peripartum hysterectomy, and require more units of blood products transfused, when compared with women without
definitive ultrasound findings.22,30
In cases of extensive accreta, optimal surgical management is directed towards delivering the neonate, then
closing the uterus with the placenta left in situ, followed by planned peripartum hysterectomy.31 For women who
desire fertility preservation, prophylactic uterine artery balloon catheters, stepwise uterine devascularization, pelvic
vessel ligation or embolization, uterine compression sutures, and/or postpartum methotrexate may facilitate
hemostatic control and placental involution.32 Any of these techniques may also be appropriate for women with non-
resectable placenta percreta, in order to reduce uteroplacental vascularity in preparation for a subsequent
hysterectomy that may be scheduled 1-4 weeks postpartum.
Optimal management by the anesthesiologist ensures sufficient intravenous access and blood products to
respond to massive hemorrhage, hemodynamic and hemostatic monitoring capability (e.g., central venous and
peripheral arterial access), sequential compression stockings to prevent venous thromboembolism, padding and
positioning to prevent nerve compression injury, warming devices to ensure normothermia, standard preoperative
antibiotic prophylaxis in the hour prior to surgical incision and repeated if surgery is prolonged (i.e., ≥3 hours) or if
heavy bleeding occurs.21 Given inaccuracy of models to predict total blood loss in these cases, the total number of
recommended blood products to prepare depends on institutional capacity to maintain ongoing supply in the face of
massive hemorrhage.22,33 Aggressive uterotonic administration, cell-saver auto-transfusion, massive transfusion
management, and electrolyte and hemostatic measurement and management are discussed below.
Combined spinal epidural (or standard epidural) anesthesia allows the mother to be awake for the delivery, and
may be extended for prolonged surgery. On the other hand, general anesthesia is preferred for cases with massive
transfusion in the event of airway edema, fluid overload with pulmonary edema, or transfusion associated lung
injury (TRALI). The decision about the primary anesthetic technique will weigh the magnitude of anticipated blood
loss, the extent of the operative plan, the availability of additional anesthesia staff to assist with an unplanned
conversion to general anesthesia, and the anticipated risk of a difficult airway.
Prophylactic embolization catheters may be inserted preoperatively into the anterior internal iliac or uterine
arteries to facilitate balloon inflation or embolization immediately following delivery of the infant. 21 Efficacy has not
been verified by randomized controlled trial;34 cesarean delivery in the interventional radiology suite may improve
efficacy of intra-arterial occlusion by avoiding catheter dislodgement.35 While these catheters may be indicated for
women who desire fertility preservation, and in women with extensive or unrespectable placenta percreta, routine
use is not recommended by the Society for Maternal-Fetal-Medicine due to lack of demonstrated efficacy as well as
potential complications including insertion site hematoma, abscess, tissue infection and necrosis. 21 Epidural
anesthesia should be initiated prior to femoral sheath insertion, to facilitate optimal positioning for both procedures
and patient comfort.
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Inherited Coagulation Disorders

Von Willebrand disease, hemophilia A and B, and factor XI deficiency account for approximately 90% of
inherited bleeding disorders.1,36,37 Inherited platelet disorders (e.g., Bernard Soulier Syndrome, Glanzmann
thrombasthenia) are rare. Given the clinical heterogeneity within each diagnosis, consultation with a hematologist
and blood bank personnel will help to clarify optimal management for each patient. Sixteen percent of women who
have von Willebrand disease will experience PPH within 24 hours of delivery, and 29% will experience delayed
postpartum bleeding.38
Jehovah’s Witnesses and other women who refuse blood products

Antepartum consultation should review a comprehensive list of blood products, alternatives, and blood
conservation strategies to determine acceptability of each intervention for the patient. 39 Antepartum iron and
erythropoietin are often acceptable ways to optimize hematocrit prior to delivery, aiming for a hematocrit ≥35%, and
may be continued postpartum in the event of significant blood loss. 40,41 Neuraxial anesthesia with a catheter-based
technique may be considered for operative anesthesia because an awake patient may change her mind in the face of
impending death. Prophylactic administration of tranexamic acid may have a modest effect on cumulative blood loss
(reducing blood loss by <150 mL), but administration early in the event of hemorrhage may be beneficial. 42
Volume replacement with crystalloid or colloid can decrease viscosity of the blood and improve peripheral
perfusion while maintaining oxygen delivery (by increasing oxygen extraction in the periphery), and minimizing
cardiac work. However, excessive crystalloid resuscitation can contribute to dilutional coagulopathy and decreased
oncotic pressure. Cell-saver autotransfusion is discussed below, and a continuous circuit technique is often
acceptable for patients who would otherwise refuse blood products. 41,43 In the event of massive blood loss and
profound anemia (hgb ≤4 g/dL) prolonged postoperative sedation, intubation, thermoregulation, and paralysis may
be required to limit oxygen consumption while erythropoietin and iron are used to restore the patient’s red cell mass.
Erythropoietin requires 48-72 hours for a significant reticulocyte response in peripheral blood, and 10-14 days to
increase hemoglobin levels. Laboratory testing should be minimized using pediatric tubes and finger-stick testing
where possible.40
Risk stratified blood product preparation

Blood transfusion is rare following elective cesarean delivery (<1%), but risk is increased among women with
antenatal anemia, placenta previa, or multiple gestation pregnancy, particularly when multiple risk factors present in
combination.44 Systems to collect a blood specimen 1-3 days prior to planned Cesarean delivery may reduce
unnecessary surgical delays.45,46
Risk factors for blood transfusion may be evident before delivery (e.g., previa), on admission to the labor and
delivery unit (e.g., antenatal hemorrhage), later in labor (e.g., chorioamnionitis or prolonged labor), or on transfer to
postpartum care. Active and ongoing surveillance is recommended throughout the peripartum period.
Approximately 40% of postpartum hemorrhages occur in previously low-risk women.47
Recommendations for blood product preparation in Table 1 synthesize algorithms from the California Maternal
Quality Care Collaborative (CMQCC),48,49 Stanford University,50 and the MFMU Network.39
Table 1. Blood product preparation based on the level of risk for peripartum blood transfusion
Recommendations AND Conditions
Indication
Prepare ≥2 units PRBC  Severe anemia (antepartum Hct <25%)
Indication: Risk > 10% o Mild anemia (Hct 25.1-29.9%) + other risk factors
o Thrombocytopenia (platelets <100k) + other risk factors
o Multiple gestation + other risk factors
 Active bleeding on admission
 Coagulation disorder including HELLP
 CD for placenta previa, IUFD, or chorioamnionitis
Indication:  Positive antibodies on T&S (Anti-D is usually Rhogam†)
Prolonged Antibody Screen
 History of difficult crossmatch
 Sickle cell disease requiring extended crossmatch
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Prepare for Massive Transfusion‡  Maternal history of ≥3 Cesarean deliveries AND a placenta
 4-20 units PRBC overlying the uterine scar or placenta previa
 4-20 units FFP  Imaging indicates placenta accreta, increta, or percreta
 1-4 platelets (5-pk)
 Planned cesarean hysterectomy
CD = cesarean delivery; FFP = fresh frozen plasma; Hct = hematocrit; HELLP = hemolysis, elevated liver enzyme,
low platelet syndrome; PRBC = packed red blood cells
†
Extra time is needed to discriminate between anti-D antibiodies due to RhoGAM® and any additional antibodies
that could interfere with a type and crossmatch.51
‡
The exact number of units determined by a patient-specific assessment of risk for massive blood loss, and
institutional resources to rapidly procure additional blood products.22,33
Unanticipated Postpartum Hemorrhage
System Factors
Clear multidisciplinary guidelines and regular skills training (multidisciplinary drills) reduce the incidence of
massive PPH,52-55 and are recommended for all units by the National Partnership for Maternal Safety.47 Simulation-
based training for obstetric hemorrhage encounters can reveal specific management deficits, and thereby facilitate
targeted quality improvement and staff education.56
Accumulating evidence suggests treatment delays increase risk for severe obstetric hemorrhage and
hemorrhage-related maternal death.16,57,58,59 Bundling personnel, equipment, and drug resources ensures rapid and
reliable delivery to the bedside.47 Group paging systems can simultaneously request an entire Obstetric Medical
Emergency Team.60 Likewise, an obstetric hemorrhage cart can be used to store essential equipment. 54 An obstetric
hemorrhage drug pack containing uterotonics allows for efficient retrieval in the event of an emergency.
Hemorrhage drills may be used to measure the time interval from the request for uterotonic medication to
administration.47
Obstetric hemorrhage is noted to be a particularly traumatic birth complication, regardless of the clinical
outcome.47 Patient, family, and staff support both during and after a hemorrhagic event are increasingly recognized
as critical for restoring well-being, and mitigating complications such as post-traumatic stress disorder.47
The Staged Approach

A Unit-Wide stage-based obstetric hemorrhage emergency management plan is recommended by the
National Parternship for Maternal Safety,47 and is based on 4 stages of obstetric hemorrhage (0 through 4).
Stage 0
Stage 0 begins with all deliveries, and focuses on ongoing risk assessment and active management of the third
stage of labor. Prophylactic oxytocin decreases postpartum blood loss, and the need for additional uterotonics;61
controlled cord traction and uterine massage provide limited benefit above oxytocin alone. 62-64 The dose required to
initiate acceptable uterine tone following cesarean delivery is lower than previously assumed, 350 milliunits for
elective cesarean and 3 IU for cesarean in labor.65,66 An initial infusion of 18 IU/hour (e.g., 30 IU in 500 mL, infused
at 300 mL/hour) is effective to achieve acceptable uterine tone within 5 minutes in 90% of women undergoing
elective cesarean delivery.67-69 Alternatively, some authors recommend a 3 IU loading bolus over 15 seconds, while
supporting blood pressure with phenylephrine.70,71 In women undergoing cesarean delivery after oxytocin labor
augmentation, the combination of oxytocin and ergometrine reduces the need for additional uterotonic agents when
compared with oxytocin alone, but the addition of ergometrine increases nausea without reducing blood loss.72
No study has demonstrated that a maintenance infusion decreases postpartum blood loss, but an infusion of 10
IU/hour over 4 hours has been shown to decrease the need for additional uterotonic agents.73
The Association of Women’s Health Obstetric and Neonatal Nurses (AWHONN) recommends universal serial
assessments of cumulative blood loss, vital signs, fundal height, and uterine tone for all deliveries
(http://www.pphproject.org/resources.asp). Accurate blood loss estimation is improved by the use of calibrated
drapes, formal staff training in blood loss estimation,74,75 and gravimetric measurements.76 Blood contained in
absorbing materials (e.g., pads, sponges) can be quantified by weight, subtracting the dry weight of each item,
assuming 1 gm weight = 1 mL blood.39,76 Immediately following delivery, the team should routinely tabulate fluid
volume in suction canisters, calibrated drapes, and absorbing materials; any subsequent volume can be assumed to
be blood, not amniotic fluid.
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Because hemorrhage is often concealed or underestimated, monitoring protocols with clear triggers to escalate
care are essential.16,39 The Modified Early Obstetric Warning System is an aggregate weighted scoring system that
centers in the UK use to identify women developing critical illness. 77,78 The Maternal Early Warning System
suggests close evaluation if the heart rate exceeds 120 beats per minute; late signs of hemorrhage include
hypotension, narrow pulse pressure, pallor or mottled appearance, cold and clammy extremities, oliguria
(<0.5mL/kg/hr), anxiety, restlessness, confusion, palpitations, dizziness, diaphoresis, and dyspnea or air hunger. An
obstetric shock index (HR/SBP) >1 has been associated with postpartum hemorrhage,79,80 and a value ≥1.4 indicates
the need for urgent attention.81,82
Stage 1: Postpartum Hemorrahge

EBL>1000, brisk gush or boggy uterus, or multiple clots AND vital signs stable. At this point, both the
anesthesiologist and the obstetrician should be notified. Monitoring intensity of both vital signs and EBL should
increase. Targeted therapy includes appropriate venous access, initial fluid resuscitation, uterotonics, and analgesia
to facilitate initial obstetric interventions to investigate and control the source of bleeding. The diagnostic evaluation
should address the five Ts: (1) Tone—uterine atony; (2) Trauma—lacerations or genital tract trauma; (3) Tissue—
retained placenta; (4) Thrombin—abnormalities of coagulation; and (5) Turned inside out—uterine inversion.
Rapid intravenous infusion of oxytocin may cause peripheral vasodilation, hypotension, flushing, nausea, chest
pain, myocardial ischemia, and in the face of substantial hemorrhage, cardiovascular collapse. 66 Limiting the
infusion rate to ≤30 IU/hour appears to minimize serious hypotensive and ishemic effects.83 When bleeding persists
despite this maximal oxytocin infusion, second-line agents are indicated, including: 1) methergine 200 mcg IM if the
patient is not hypertensive, repeated once after 15 minutes; 2) misoprostol 800-1000 mcg rectally or buccally; or 3)
prostaglandin F2α 250 mcg IM every 15-20 minutes up to 8 total doses (avoided in women with asthma). Methergine
appears to be the most frequently chosen second line uterotonic, and may have superior efficacy when compared
with prostaglandin F2α, based on observational data.84,85
Stage 2: Continued bleeding despite stage 1 interventions AND <1500 mL cumulative blood loss.
With persistant postpartum hemorrhage, it becomes very important to mobilize a full team. The patient
should be moved to an operating room, large bore venous access secured, and a full panel of laboratory values sent,
hematocrit, platelets, PT, and fibrinogen. Cross-match of at least 2 units of erythrocytes is usually indicated, and
protocols for emergency release of blood products are recommended.45,47 Fibrinogen <2 g/L is an early predictor of
the severity of subsequent PPH.86-88 Ongoing uterotonics, thermoregulation, antibiotic coverage, and venous
thromboembolism prophylaxis should be addressed. Tranexamic acid and fibrinogen concentrate are being
investigated for the early treatment of postpartum hemorrhage, and are discussed below.89,90 Decisions about
transfusion, requesting additional blood products, activating a massive transfusion protocol, converting to general
anesthesia, initiating cell salvage, and establishing invasive hemodynamic monitoring depend on the ongoing state
of the patient, the rate of blood loss, and the degree to which obstetricians are effective in diagnosing and controlling
the source of bleeding.
Stage 3: EBL>1500, >2 u PRBC given, vital sign instability, evidence of coagulopathy, or ongoing
bleeding. Stage 3 qualifies as major obstetric hemorrhage. Following manual exploration and repair of
lacerations, stepwise escalation of surgical therapy includes D&C, intrauterine balloon (e.g., Bakri balloon), and
uterine compression suture (e.g., B-Lynch, O’Leary, multiple squares), selective embolization, peripartum
hysterectomy, and abdominal packing. In some cases, intraoperative manual aortic compression or cross clamping
may facilitate surgical control.91 Uterine inversion requires anesthesia and uterine relaxation to facilitate manual
replacement.
While a hemoglobin transfusion threshold of 7 g/dL is generally appropriate, laboratory results are inaccurate in
the face of ongoing hemorrhage, and transfusion should proceed empirically without waiting for laboratory results.
Failure to maintain adequate hematocrit during acute obstetric hemorrhage has been associated with end organ
dysfunction.92 Observational data suggests that hemostatic resuscitation with low transfusion ratios (FFP: PRBC and
Platelet: PRBC ratios of 1:1 to 1:2) may increase survival in massively transfused trauma victims,93 and may
decrease the need for advanced interventional procedures in postpartum hemorrhage.94 However, this evidence base
suffers from survival bias. A prospective RCT in trauma patients did not demonstrate improvements in overall
survival when early resuscitation with plasma, platelets, and erythrocytes administered in a 1:1:1 ratio was compared
with a 1:1:2 ratio.95 Caution is advised. Plasma and platelets are pro-inflammatory, and may increase risk of
pulmonary injury (e.g., TRALI) among individuals who ultimately receive ≤4-6 units of erythrocytes. 96-98 In the
absence of consumptive coagulopathy or antenatal thrombocytopenia, platelets are rarely necessary before the
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cumulative blood loss exceeds 5 litres.99 Goal-directed therapy guided by TEG or ROTEM may reduce the quantity
of plasma and platelets transfused and the risk of major complications, such as transfusion related acute circulatory
overload (TACO).100,101
Although massive transfusion protocols specifically for obstetric hemorrhage have been described, 102,103
standard institutional protocols are generally appropriate, as long as the higher transfusion threshold for fibrinogen is
noted (≥ 2 g/L). Effective protocols are activated by phone, allow for initial supply of uncross-matched products if
necessary, and supply batches of blood products that approximate the recommended 1:1:1 ratio.104 Subsequent
matched blood products are continuously prepared to maintain blood product availability, and the protocol is
automatically discontinued once additional blood products have not been requested for at least one hour.
For massive blood transfusion, laboratory specimens (i.e., hematocrit, platelets, ionized Ca, K, PT, fibrinogen,
lactate) should be sent every 30-60 minutes to establish trends. Serial coagulation tests are more helpful than single
time point measurements in assessing for development of coagulopathy. 5 Additional FFP may be needed to maintain
the PT ≤1.5 times normal, platelets to maintain the platelet count over 50 x 109/L, and cryoprecipitate or fibrinogen
concentrate 4 g to maintain the fibrinogen over 2 g/L. 86-88 Central laboratory turn-around time within 20 minutes is
possible,105 but centralized viscoelastic monitoring with point-of-care real time display is emerging as a preferred
strategy to facilitate goal directed therapy.100,101,106-109 With ROTEM, amplitude at 5 minutes (A5) on the FIBTEM
assay shows strong correlation with the Claus Fibrinogen measurement. 101
In the event of unanticipated massive hemorrhage, an interosseous needle may be rapidly inserted in the tibial
plateau or proximal humerus and used to initiate fluid resuscitation while additional intravenous access is
established.110 Temporizing maneuvers include leg elevation, manual compression of the aorta at the umbilicus, and
non-pneumatic anti-shock garments.111 Permissive hypotension (MAP 50 mmHg) may help to limit bleeding, but is
not well studied in the postpartum patient.40
Adjunctive agents: Cell salvage—Over 650 published cases of obstetric patients have described auto-transfusion
with blood salvaged and processed from the surgical field. 112,113 Newer machines in combination with leukocyte
reduction filters have demonstrated effective clearance of fetal squamous cells, phospholipid lamellar bodies, plasma
heparin, cytokines, and other coagulopathic mediators. The use of a leukocyte depletion filter has been associated
with acute hypotension at the time of transfusion of cell salvaged erythrocytes. 114 Cell-salvaged blood does contain
up to 2% fetal red blood cells; Rhesus-negative women require dose-adjusted RhoGAM® administration. Emergency
cell salvage may be most appropriate in institutions where cell saver devices are routinely used, and dedicated
technicians are available to set up the equipment.115 Some centers may elect to limit use for women with placenta
accreta or those who refuse blood products.
The anti-fibrinolytic agent tranexamic acid (1 g over 10 minutes Q 4-8 hr) improved survival in an
international randomized controlled trial of trauma patients with significant hemorrhage. 116 Although fibrinolysis
may be less important in the pathophysiology of PPH, the WHO recommends tranexamic acid when PPH continues
despite standard uterotonic agents.117 A large trial in postpartum hemorrhage patients is currently ongoing.116
Lyophylized fibrinogen concentrate 2-4 g has been reported to be helpful in coagulopathic obstetric
patients.118,119 Although derived from human serum, fibrinogen concentrate is pasteurized, available in a standard
concentration, and may be reconstituted and administered rapidly in a low volume. 120 Rigorous investigation
suggests that it is most likely to be beneficial with administered using goal-directed treatment algorithms for women
with evidence of hypofibrinogenemia.90,100,101
Registries of recombinant factor VIIa report an overall 80% success rate to control hemorrhage when other
interventions have failed, with reported doses ≤90 mcg/kg.1,121 Temperature, acidosis, calcium, platelets and
fibrinogen should be first optimized for maximal hemostatic effect. Caution is advised. Recombinant factor VIIa has
been associated with a high rate of devastating thrombotic complications. 122
Reporting and Systems Learning: Post-event debriefs are short clinical team meetings conducted immediately
after a patient safety event, designed to build teamwork and identify opportunities for improvement. In addition,
formal in-depth multidisciplinary reviews of serious hemorrhages (≥4 units of erythrocytes transfused or ICU
admission) are recommended by the Joint Commission and the National Partnership for Maternal Safety
(www.safehealthcareforeverywoman.org).47
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76. Lilley G, et al.: Int J Obstet Anesth 2015;24:8-14
77. Singh S, et al.: Anaesthesia 2012;67:12-8
78. Carle C, et al.: Anaesthesia 2013;68:354-67
79. Pacagnella RC, et al.: PloS one 2013;8:e57594
80. Le Bas A, et al.: International journal of gynaecology and obstetrics 2014;124:253-5
81. El Ayadi AM, et al.: PloS one 2016;11:e0148729
82. Nathan HL, et al.: BJOG 2015;122:268-75
83. Thomas JS, et al.: British journal of anaesthesia 2007;98:116-9
84. Butwick AJ, et al.: AJOG 2015;212:642.e1-7
85. Bateman BT, et al.: Anesthesia and analgesia 2014;119:1344-9
86. Charbit B, et al.: Journal of thrombosis and haemostasis : JTH 2007;5:266-73
87. de Lloyd L, et al.: Int J Obstet Anesth 2011;20:135-41
88. Cortet M, et al.: British journal of anaesthesia 2012;108:984-9
89. Novikova N, et al.: The Cochrane database of systematic reviews 2015:Cd007872
90. Wikkelso AJ, et al.: British journal of anaesthesia 2015;114:623-33
91. Belfort MA, et al.: Am J Perinatol Rep 2011;1:33-6
92. O'Brien D, et al.: Eur J Obstet Gynecol Reprod Biol 2010;153:165-9
93. Murad MH, et al.: Transfusion 2010;50:1370-83
94. Pasquier P, et al.: Anesthesia and analgesia 2013;116:155-61
95. Holcomb JB, et al.: Jama 2015;313:471-82
96. Inaba K, et al.: Journal of the American College of Surgeons 2010;210:957-65
97. Sambasivan CN, et al.: The Journal of trauma 2011;71:S329-36
98. Johnson JL, et al.: Archives of surgery (Chicago, Ill : 1960) 2010;145:973-7
99. Jones RM, et al.: Anaesthesia 2016;71:648-56
100. Mallaiah S, et al.: Anaesthesia 2015;70:166-75
101. Collis RE, Collins PW: Anaesthesia 2015;70 Suppl 1:78-86, e27-8
102. Burtelow M, et al.: Transfusion 2007;47:1564-72
103. Gutierrez MC, et al.: Int J Obstet Anesth 2012;21:230-5
104. Holcomb JB, Gumbert S: Current opinion in anaesthesiology 2013;26:215-20
105. Chandler WL, et al.: Transfusion 2010;50:2547-52
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109. Holcomb JB, et al.: Annals of surgery 2012;256:476-86
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115. McDonnell NJ, et al.: Anaesth Intensive Care 2010;38:492-9
116. Shakur H, et al.: Trials 2010;11:40
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TURNING OFF THE GAS: THE AGING ANESTHESIOLOGIST
Jonathan D. Katz, M.D. New Haven, Ct
How old would you be if you didn’t know how old you are?a
The learning objectives of this lecture are to:

1) Identify common physiologic changes associated with normal aging that might affect the safe
practice of anesthesiology.
2) Discuss how the aging process impacts the late- career anesthesiologist.
3) Examine some arrangements between groups and senior anesthesiologists that provide benefit
to both parties and encourage continued safe practice.
INTRODUCTION: All living creatures, including anesthesiologists, age. Aging involves a

deterioration in function of many of the biologic processes of an organism due to the sequential
and progressive physiological changes associated with getting older. The process ultimately
results in increased vulnerability to injury, illness, and death.
Aging in humans is multifaceted and includes parallel biological, psychological, spiritual and
social changes. Some abilities and skills are enhanced, such as experience and wisdom, and
others decline, such as reaction time and various aspects of memory.
We will discuss some of the changes commonly associated with aging and consider how these
changes can impact the practice of anesthesiology.
THEORIES OF AGING: Exactly how, and in what manner, an individual ages is determined
equally by genetic and environmental factors. The fundamental mechanisms underlying aging
remain to be elucidated. In part, aging is the result of the accumulation of a variety of
biochemical alterations that impair the normal functioning of nucleic acids, proteins, and lipid
membranes. These alterations involve a number of basic processes including free radical
oxidation, non-enzymatic glycosylation, DNA methylation and histone acetylation. These
changes impact an organ’s physiologic function and capacity for self- repair.
Exactly what triggers and why these cellular changes occur is unknown. Theories of aging fall
into two (overlapping) categories: programmed theories and damage or error theories.
Programmed theories posit that aging is determined by a pre- encoded biologic timetable that
begins with conception and continues through childhood, adolescence, adulthood and
senescence. Programmed longevity, the endocrine theory, and the immunologic theory each fall
into this category. Damage or error theories propose that environmental assaults cause the DNA
damage and cell injury that gradually result in degenerative changes in the structure and function
of cells and tissues. Examples of this category include the wear and tear theory, the free radical
theory, and the cross linking theory.
a
Major league pitcher Satchel Paige after repeated questioning by reporters on how he was able
to continue to pitch well into his 50’s.
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PHYSIOLOGY OF AGING: The aging process occurs throughout all stages of life. The
cellular changes described above are associated with degenerative changes in the structure and
functional reserve of tissues and in the gradual deterioration of the organism’s physiologic
systems. The accumulation over time of these changes results in the easily recognizable aging
phenotype.
Aging does not occur homogeneously. There are large intra- and inter- species differences in
how aging progresses. Even within any one individual, each organ system ages at a unique rate
and manner. One common denominator is a loss of complexity resulting in decreased variability
in an organ system’s functionality. A second common finding is a decrease in physiologic
reserves. These physiologic reserves are stretched to their limit in order to maintain homeostasis,
and are thus unable to recruit an additional response when confronted with a stressful challenge,
such as infection. This state, called “homeostenosis”, leads to increased vulnerability to disease,
a common observation seen among aging organisms.
There are a number of age related physiologic changes that, at varying times and degrees of
intensity, appear in all individuals and can impact the manner in which an anesthesiologist
practices:
1) There is a generalized decrease in muscle mass with accompanying loss of strength, fine
motor skills and stamina. Older workers are particularly sensitive to the demands imposed by
fatigue and have a decreased tolerance to shift work cycles and a greater tendency to late night
errors. 1 It is not surprising that extended work hours and night call are among the most stressful
aspects of anesthetic practice for older anesthesiologists and the most important reasons for
retirement. 2
2) Presbycusis, (hearing loss in the high frequency range) begins in early adulthood and
progressively causes deterioration of hearing. Anesthesiologists are particularly vulnerable to age
related hearing loss, especially in the higher ranges where many of the alerts and alarms of
anesthetic equipment occur.3 One or more common anesthesia alarms are below the threshold of
detectability in 39% of anesthesiologists age 65 years and older.3 The problem is exacerbated by
the high ambient noise commonly experienced in operating rooms that can exceed that found in
the hospital’s cafeteria or boiler room. 4
3) Visual impairments resulting from cataracts and other age related ailments can contribute to a
reduction of visual acuity. This can be especially problematic when an older physician is
attempting to learn new visually complex clinical skills.
4) There is a decrease in brain weight and volume as individuals age. The loss of brain tissue is
greatest in the frontal and temporal lobes and involves white matter more than grey matter. Also
observed are reductions in the total length of the brain's myelinated axons. These organic losses
may be countered by other changes such as the development of redundant neural pathways and
synaptic plasticity. Neurotransmitters and receptors also change with age‐ with some decreasing
and others increasing.
5) The anatomic changes in the central nervous system are accompanied by well-defined
functional changes. These frequently include many aspects of memory, abstraction, executive
functioning and mental flexibility. Some commonly observed changes that are particularly
significant to anesthetic practice include: difficulties with learning, which becomes slower and
requires more effort; impairment of short term memory; decreases in attention span; declines in
creative thinking and problem solving abilities; and slowing of on the spot reasoning, intellectual
quickness, and reaction time.
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6) The incidence of cognitive impairment and dementia increases along with increasing age. 5 In
addition, many of the diseases that are more frequently seen among older individuals, such as
diabetes, stroke, and cardiovascular disease can further exacerbate any age related loss of
cognitive function. As many as 15% of those over age 65 have some degree of cognitive
impairment.6 In many cases, memory and language dysfunction are among the most prominent
features. More significant for anesthesiologists, performance of stressful and complex tasks and
quick and effective decision making is frequently reduced in older individuals.
7) Several important aspects of psychology and cognition are frequently spared. For example,
optimism, resilience, compassion, long term memory, judgment, and wisdom all may be
enhanced with age. It is important to recognize that the administration of a safe and successful
anesthetic relies on a vast array of clinical skills, including technical agility, experience, and
judgment. These preserved attributes serve to augment retained clinical skills and can provide an
advantage to an older anesthesiologist.
EFFECT OF AGING ON THE PRACTICING ANESTHESIOLOGIST: Each of the age-

associated changes described above has the potential to impact the practice of anesthesiology. 7
For example, decreased visual acuity can make it more difficult to read drug labels or monitor
displays in the varying ambient light conditions found in operating rooms. Musculoskeletal
disease can hinder an older anesthesiologist’s ability to run up several flights of stairs to attend to
a non-operating room emergency. Hearing loss can interfere with the aging anesthesiologist’s
ability to hear vital conversations and alarms amid the cacophony commonly occurring in a
modern operating room.
Cognitive impairment poses the most threatening challenge to safe anesthetic practice and has
received the most attention. A high level of cognitive function is necessary for the successful
administration of a safe anesthetic. As mentioned above, advancing age is frequently
accompanied by some degree of cognitive impairment. Among physicians, this has been
observed as an age-dependent decline in their knowledge base and performance on certification
examinations.5 However, there is considerable variability, such that older physicians tend to
perform less well on average, but many score at the same or at a higher level than their younger
colleagues. As observed by Eva, “one of the more robust findings in ageing research is that the
variability across the scores individuals receive tends to increase with age.” 5
Other common shortcomings observed among older physicians is that their history taking is
often incomplete and they more frequently overlook important details and data.
A similar pattern emerges from those studies that looked at the relationship between physicians’
age and clinical outcomes- especially among preceduralists performing complex interventions. A
number of reports have identified increased complication rates in certain high risk procedures
performed by older surgeons. For example a study of carotid endarterectomy found that mortality
increased as a function of surgeons’ age. 8 A different study that examined outcomes of inguinal
hernia surgery found that the risk of recurrence after laparoscopic repair was 1.72 times higher
for surgeons older than 45 years than their younger colleagues. 9 The authors of this study
suggested that the cognitive changes associated with aging rendered the older surgeons less able
to learn and perform complex new procedures -in this case laparoscopic surgery. And in a meta-
analysis of physicians’ performance on a variety of quality measurements, 73% of the studies
demonstrated a negative association between age and length of time in practice and evidence of
good performance. 10 Most of the studies demonstrated a global decline in all of the measures.
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Participation in traditional continuing medical education activities and recertification did not
affect the results.
Not all studies have identified physicians’ age as an independent risk factor for unfavorable
procedural outcomes. Experience can play a salutary role in overcoming some of the
deficiencies that might occur due to a decreased fund of current scientific knowledge. A study of
operative mortality in a select group of high risk procedures reported that surgeons’ age was not
an important predictor in 5 of the 8 procedures studied. 11 Even in those procedures where older
surgeons did have a higher mortality rate, the effect of age was largely restricted to surgeons
with low procedure volumes.
Comparable data are sparse for anesthesiologists. In one study that employed a simulator to test
the ability of an operator to insert an emergency percutaneous cricothyroidotomy, age and years
from residency were predictors of poor performance as measured by procedural time, checklist
scores, and global rating scores. 12 Another study which was conducted among Canadian
anesthesiologists demonstrated a 50% greater risk of being found responsible for litigation
among anesthesiologists older than 65 years as compared with anesthesiologists younger than
age 51. 13 In addition, the severity of injury was 2 fold greater among the older anesthesiologists.
On the other hand, an abstract presented at the ASA Annual meeting in 2015 failed to show any
differences in clinical outcomes when comparing cases conducted by older (>age 54) vs younger
anesthesiologists. b The authors did observe a significant difference in practice patterns in which
older anesthesiologists were less likely to be involved in complex surgical procedures.
POLICIES TO ASSESS “FITNESS FOR DUTY” AMONG AGING

ANESTHESIOLOGISTS: Optimally physicians themselves or their colleagues would
recognize impairment and take action to limit the potential for patient injury. Unfortunately,
impaired physicians are often the last to know. Physicians tend to be poor analysts of their own
competence and routinely fail to identify or report failing competence in themselves or in
others.14 In fact, physicians who are the least competent are also the least able to accurately judge
their own skills and often give the appearance of being the most self- confident. 15
In the absence of adequate self- policing as a safeguard for public safety, health care
organizations, medical boards, and many certifying bodies and specialty societies are developing
policies and procedures to address concerns about patient safety. These span the spectrum from
benign neglect to imposition of a mandatory retirement age. Most are somewhere in the middle
and act by requiring a physical, cognitive and psychological assessment, as well as focused case
reviews on a regular basis once the clinician has achieved a predetermined age (most commonly
65 or 70 years). To be equitable, the comprehensive evaluation must be specific to the clinician’s
specialty and desired privileges. Done properly, these policies will avoid discrimination or
imposition of unnecessary restrictions on older physicians. Optimally, these policies will serve
the dual function of identifying impaired physicians and encouraging those with no impairment
to practice longer.
b
http://www.asaabstracts.com/strands/asaabstracts/searchArticle.htm;jsessionid=8DBCAA9AE2
987399C71771E0C907E032?index=0&highlight=true&highlightcolor=0&bold=true&italic=fals
e. Accessed 5/25/2016
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The ASA is relatively silent on the subject of how age might affect the practice of their members,
stating only that, “The practice of quality anesthesia care requires that anesthesiologists maintain
their physical and mental health and special sensory capabilities.” c
LEGAL CONSIDERATIONS: Many industries in which public safety is at risk impose age –
related work restrictions. For example, commercial airline pilots must undergo regular health
screenings starting at age 40 and must retire at age 65 (increased from age 60 in 2007) The
mandatory retirement age for air traffic controllers is age 55years and for FBI agents age 57. In
contrast, there are no laws or regulations in the United States that mandate health screening or
retirement age for health care providers (or Supreme Court Justices).
The practice of medicine is a privilege granted by the state in which one practices and is
accompanied by many responsibilities, including the obligation to remain physically, mentally
and emotionally competent in one’s profession. Historically, neither state licensure nor hospital
privileges have been specifically limited by the chronologic age of the practitioner. However,
most states and hospital bylaws do require that a physician and/ or their colleagues report when
there is substantial suspicion that their professional skills may be compromised by any potential
source of impairment, including age.
Several federal laws, including the Age Discrimination in Employment Act of 1967 and the
Americans with Disabilities Act of 1990 protect any worker from discrimination in employment
due to age alone and outlaw compulsory retirement on the basis of age. Title II of the Americans
with Disabilities Act pertains specifically to medical licensure and prohibits state and local
governments from excluding qualified individuals from any government program, such as
medical licensure or renewal.
However, there are important exceptions to protections afforded by these laws. A significant
limitation to the applicability of these laws is whether or not the worker is an “employee” with a
written agreement or understanding with their employer. An anesthesiologist who is a
contracting agent with a health care institution might not be eligible for protection according to
that requirement. Also important is the condition that any individual who poses a direct threat to
the health and safety of others is not considered a “qualified person” under the Americans with
Disabilities Act. A case recently decided by the U.S. Court of Appeals for the Fifth Circuit
(EEOC v. Exxon Mobil Corp), affirmed Exxon’s right to consider age as a “bona fide
occupational qualification,” and provides some additional guidance for those considering such
actions for other workers in safety sensitive areas such as anesthesiology.d
EMPLOYMENT ARRANGEMENTS FOR LATE CAREER ANESTHESIOLOGISTS:

The physician workforce in general, and the specialty of anesthesiology specifically, is aging. In
the year 1990 the largest age group among members of the American Society of
Anesthesiologists (ASA) was in the 35-44 year range (35%). e Only 13% were in the 55-64 year
group and 10% were older than 65 years of age. There has been a significant shift in these
demographics-such that by 2010 the 45- 54 group became the largest. The 65 + age group has
c
American Society of Anesthesiologists. Guidelines for the ethical practice of anesthesiology.
Available at https://www.asahq.org. . Accessed 5/25/2016
d
http://www.bakerbotts.com/news/2014/03/fifth-circuit-rules-for-exxonmobil-ending-eighty_
Accessed 5/25/2016
e
American Society of Anesthesiologists. Personal communication
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grown from 10% in 1990 to 17% currently. For comparison, approximately 40% of the nation’s
1 million physicians are older than 55 and 21% are older than 65 years, up from 35% and 18%,
respectively, in 2006.
The aging of the workforce and an impending shortage of anesthesiologists (according to many
predictions) has added to the necessity of developing arrangements to enable competent senior
clinicians to continue working. A number of factors play a role in any plan to continue to employ
senior associates. The size and business structure of a group and the collective philosophy of its
members are major considerations. Polices for distributing call and vacation, dividing income,
providing benefits and governing the group all are important factors. Because administrative
costs and malpractice premiums are associated with each employee whether they are full or part
time, the assignment of overhead expenses can be particularly problematic.
“Winding down” employment arrangements fall into 3 general categories:1) a shared position
where 2 or 3 anesthesiologists agree to carry all of the clinical, administrative, and financial
responsibilities of one partner; 2) a part time position in which 1 individual continues to perform
all of the functions of a full time clinician but at a reduced rate- for example 2/3 call, 2/3 clinical
time, etc.; 3) a part time position that completely eliminates some aspects of practice (for
example night call) and limits exposure to the most complex procedures and other stressful
elements of practice. Additional details on how these arrangements might work can be found in a
review by Baxter. 16 The most challenging aspect of any of these arrangements is how to value
these tradeoffs, which is specific to each situation and can only be made on a practice by practice
basis.
RETIREMENT: As previously discussed, there are no mandated retirement ages for

physicians. The decision to retire frequently remains solely at the discretion of the individual
anesthesiologist. Age is inevitably one of the leading factors in decisions concerning retirement.
The median age of retirement for anesthesiologists as of 2012 was approximately 64 years.2
Commonly cited reasons for retirement among older anesthesiologists include on-call
responsibilities, financial considerations including diminishing reimbursement, lack of
professional satisfaction, health concerns, and changes in governmental policies and the health
care operating environment.2 On the other hand, those older anesthesiologists who decide to
postpone retirement cite career satisfaction, financial obligations, and the need to maintain health
insurance for family members as the primary reason to remain in the workforce.
MORTALITY AMONG ANESTHESIOLOGISTS: As observed by the great Hank Williams

Sr. "I'll Never Get Out of This World Alive"f. Death is an expected consequence of normal
aging. There is a wide range of lifespans both within and between species and populations.
American life expectancies have increased substantially in recent years. A male who is age 65 in
2016 can expect to live until age 84.3. g A woman who is age 65 can expect to live until age
86.6. Just 25 years ago, comparable life expectancies were age 71.8 years for men and 78.8 for
women. About 25% of 65-year olds today will live past age 90.
f
Williams, Hank. Song Lyrics from “ I'll Never Get Out of This World Alive “ Available at
www.youtube.com/watch?v=w7FQeFOBtBk Accessed 5/15/2016
g
U.S. Social Security Agency. Available at http://www.ssa.gov/planners/lifeexpectancy.html
Accessed 5/29/2016
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Anesthesiologists are also living longer. Early reports expressed concern that the stressful nature
of the job and the consequence of excessive exposure to potentially toxic substances such as
anesthetic gases and radiation resulted in premature deaths among anesthesiologists. A more
recent study has challenged that assumption and concluded that the age adjusted mortality rate
among anesthesiologists is not different than among other physicians. 17 The commonest cause of
death among anesthesiologists has also changed over the past 50 years. Early reports cited a
concern about an excess risk of cancer related mortality. More recent reports cite a
disproportionate number of drug related deaths and suicide. 18
CONCLUSION: Aging is a universal process that affects every clinician. Aspects of aging
impart both advantages and disadvantages to the late- career anesthesiologist. A working
arrangement can frequently be forged that benefits the anesthesiologist, the group, and their
patients.
REFERENCES
1. Howard SK, Rosekind MR, Katz JD, Berry AJ: Fatigue in anesthesia: implications and
strategies for patient and provider safety. Anesthesiology 2002; 97: 1281-94
2. Orkin FK, McGinnis SL, Forte GJ, Peterson MD, Schubert A, Katz JD, Berry AJ, Cohen
NA, Holzman RS, Jackson SH, Martin DE, Garfield JM: United States Anesthesiologists over
50: Retirement Decision Making and Workforce Implications. Anesthesiology 2012; 117: 953-
963
3. Wallace MS, Ashman MN, Matjasko MJ: Hearing acuity of anesthesiologists and alarm
detection. Anesthesiology 1994; 81: 13-28
4. Katz JD: Noise in the operating room. Anesthesiology 2014; 121: 894-8
5. Eva KW: The aging physician: changes in cognitive processing and their impact on
medical practice. Acad Med 2002; 77: S1-6
6. Schonknecht P, Pantel J, Kruse A, Schroder J: Prevalence and natural course of aging-
associated cognitive decline in a population-based sample of young-old subjects. Am J
Psychiatry 2005; 162: 2071-7
7. Katz JD: The aging anesthesiologist. Curr Opin Anaesthesiol 2016; 29: 206-11
8. O'Neill L, Lanska DJ, Hartz A: Surgeon characteristics associated with mortality and
morbidity following carotid endarterectomy. Neurology 2000; 55: 773-81
9. Neumayer LA, Gawande AA, Wang J, Giobbie-Hurder A, Itani KM, Fitzgibbons RJ, Jr.,
Reda D, Jonasson O, Investigators CSP: Proficiency of surgeons in inguinal hernia repair: effect
of experience and age. Ann Surg 2005; 242: 344-8; discussion 348-52
10. Choudhry NK, Fletcher RH, Soumerai SB: Systematic review: the relationship between
clinical experience and quality of health care. Annals of Internal Medicine 2005; 142: 260-73
11. Waljee JF, Greenfield LJ, Dimick JB, Birkmeyer JD: Surgeon age and operative
mortality in the United States. Ann Surg 2006; 244: 353-62
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12. Siu LW, Boet S, Borges BC, Bruppacher HR, LeBlanc V, Naik VN, Riem N, Chandra
DB, Joo HS: High-fidelity simulation demonstrates the influence of anesthesiologists' age and
years from residency on emergency cricothyroidotomy skills. Anesth Analg 2010; 111: 955-60
13. Tessler MJ, Shrier I, Steele RJ: Association between Anesthesiologist Age and Litigation.
Anesthesiology; 116: 574-579
14. DesRoches CM, Rao SR, Fromson JA, Birnbaum RJ, Iezzoni L, Vogeli C, Campbell EG:
Physicians' perceptions, preparedness for reporting, and experiences related to impaired and
incompetent colleagues. JAMA 2010; 304: 187-93
15. Davis DA, Mazmanian PE, Fordis M, Van Harrison R, Thorpe KE, Perrier L: Accuracy
of physician self-assessment compared with observed measures of competence: a systematic
review. JAMA 2006; 296: 1094-102
16. Baxter AD, Boet S, Reid D, Skidmore G: The aging anesthesiologist: a narrative review
and suggested strategies. Can J Anaesth 2014; 61: 865-75
17. Katz JD: Do anesthesiologists die at a younger age than other physicians? Age-adjusted
death rates. Anesth Analg 2004; 98: 1111-3
18. Alexander BH, Checkoway H, Nagahama SI, Domino KB: Cause-specific mortality risks
of anesthesiologists. Anesthesiology 2000; 93: 922-30
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Anatomy and Physiology of Commonly Encountered

Congenital Heart Lesions in Adults
James A. DiNardo, M.D., FAAP Boston/MA
This lecture is intended to review the frequency, anatomy and pathophysiology of commonly
encountered lesions in adults with congenital heart disease (ACHD). It can be useful to categorize ACHD
lesions based on broad categories such as cyanotic, non-cyanotic, shunt lesions, single ventricle lesions and
the like. However, optimization of hemodynamic status ultimately depends on an individualized assessment
of functional status and identification of the specific physiologic liabilities most likely to lead to
decompensation during the perioperative period. Assessment of functional status is best approached by
evaluation of patients for symptoms of heart failure (HF). The manifestations of HF in the ACHD
population can be very different than those seen in patients with structurally normal hearts and systolic and
diastolic LV dysfunction.
Introduction
Tremendous advances in cardiac surgery, anesthesia, intensive care unit management,

diagnostic/interventional cardiac catheterization, and non-invasive diagnostic techniques have marked the
last 50 years. As a result of these advances and continued refinements there has been explosive growth in
the number of ACHD patients. At present approximately 85% of babies born with CHD can be expected to
reach adulthood with this percentage likely to increase over the next 10-20 years 1 2. As a consequence, the
ACHD population now exceeds that of children with congenital heart disease. A conservative estimate of
the number of adult patients with congenital heart disease in the United States was 787,800 in the year
2000; approximately 400,000 of which require specialized care due the presence of complex (117,000) or
moderate disease (300,000) 1. Data from Quebec indicates that 60% of those alive in 2010 with severe
congenital heart disease were adults3. Data from the Nationwide Inpatient Sample indicates that the number
of hospital admissions for CHD patients ≥ 18 years of age increased 101.9% from 1998 to 2005 4. There
were similar increases in admissions for both simple and complex defects. The leading indications for
hospitalization are treatment of arrhythmias, chest pain/coronary artery disease, and HF 4,5. Within this time
span the percentage of admissions during which cardiac surgery was performed remained steady at 18%.
Average patient age increased from 52.3 to 53.8 years and the percentage of patients with ≥ 2 medical co-
morbidities increased from 23 to 33%. The estimated national cost of these hospitalizations increased 357%
to $3.16 billion 4.
ACHD patients may be repaired, palliated, or unrepaired. Virtually all ACHD patients, except those
with coiled or ligated patent ductus arteriosus, and closed atrial or ventricular septal defects, will have
residua (lesions for the most part intentionally left behind at the time of reparative surgery) or sequalae
(necessary consequences of reparative operations or the natural history of the lesions) 2. As a consequence,
ACHD patients can be categorized as those with simple CHD, those with CHD of moderate complexity,
and those with CHD of great complexity 6. All ACHD patients should therefore initially be classified as
ACC/AHA Stage B patients based on the presence of structural heart disease 7.
Heart Failure Incidence
The incidence and natural history of progression of HF in ACHD patients varies by diagnosis. The
incidence of HF in a cohort of 345 ACHD patients with simple, moderate, and complex congenital heart
disease was recently undertaken 8. HF, defined as a peak oxygen consumption (VO2) < 25 ml/kg/min in
combination with a NT-pro-brain natriuretic peptide (BNP) plasma level > 100 pg/ml, was present in 26%
of this mixed cohort 8. These HF patients are surprisingly young with most in the third decade of life. The
probability of developing HF over time varies in relation to both the anatomy and more importantly to the
complexity of the underlying CHD. The incidence is highest in patients with single ventricle physiology
palliated with a Fontan procedure, repaired tetralogy of Fallot (TOF), and two groups of patients with a
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series, two-ventricle circulation in which the right ventricle (RV) is the systemic ventricle;
dextro-transposition of the great arteries (D-TGA) palliated with a Mustard or Senning atrial level switch
procedure and congenitally corrected TGA (C-TGA). It is lowest in those with repaired coarctation of the
aorta.
In addition, the rate of development of HF over time in these subsets of patients is very different 8.
Patients with single ventricles, particularly those with right ventricular morphology 9, patients with a
systemic right ventricle, and those with TOF have the highest rate of development. HF in patients with
repaired coarctation is rare. This is true despite the fact that these patients, even in the absence of re-
stenosis, have altered aortic compliance characteristics leading to hypertension at rest and during exercise
and subsequent development of left ventricular hypertrophy 10 11.
Commonly Encountered Lesions and the Etiology of Functional Limitation
The etiology of functional limitation in the current ACHD population is multi-factorial and lesion
specific. It is likely that the incidence of ischemic ventricular dysfunction will increase as the ACHD
population ages and the incidence of coronary artery disease increases in parallel with the general
population 12. In addition, there is growing concern for the long-term patency and vasomotor reactivity of
the coronary arteries in patients who have undergone the arterial switch operation for D-TGA, long felt to
one of the truly completely reparative operations for patients with complex CHD 13 14.
TOF
The current adult cohort of TOF patients represents the 30-40 year natural history of residual
pulmonary regurgitation (PR) following TOF repair. At the time of these patients’ original operation PR
was felt to be a benign lesion and the portion of the operations performed to relieve pulmonary and
subpulmonary stenosis commonly involved pulmonary valvectomy and large infundibular incisions. It is
now well appreciated that long standing PR produces HF in TOF patients as the result of RV dilatation.
This dilatation results in RV dysfunction, left ventricular (LV) dysfunction due to abnormal septal
configuration and LV myofibrils shared with the dysfunctional RV, and electromechanical dyssynchrony 15
16 17
.
C-TGA
C-TGV refers specifically to the anatomic circumstance wherein there is discordance of the
atrioventicular connections associated with discordance of the ventriculoarterial connections. The most
common manifestation (94%) of this physiology occurs in patients with [S,L,L] segmental anatomy. That
is, there is atrial situs solitus, L-loop ventricles, and L-loop great arteries. A right sided right atrium
connects via a right sided mitral valve and LV to a right sided pulmonary artery. A left sided left atrium
connects via a left sided tricuspid valve and RV to a left sided aorta. Although these patients have a series
circulation there is a high incidence of associated cardiac abnormalities of clinical importance. In addition,
the morphologic RV functions as the systemic ventricle.
A ventricular septal defect (VSD) is present in 70 % of patients. The VSD is typically a large
subpulmonary perimembranous defect. Left ventricular outflow tract obstruction (pulmonary atresia,
pulmonary and subpulmonary stenosis) occurs in 56 % of patients is always associated with a VSD.
Subpulmonary obstruction may be the result of posterior deviation of the conal septal portion of the VSD
toward the left ventricular free wall or atrioventricular (AV) valve tissue located in the outflow tract.
Isolated pulmonary valve stenosis is rare. Abnormalities of the left sided systemic valve (tricuspid valve)
are intrinsic to this lesion although functional consequences are limited to about 50 % of patients. The
valve is said to be Ebstein-like with tethering of the septal and posterior leaflets to the posterior wall of the
RV by short, thickened chordae. Unlike Ebstein’s anomaly there is rarely apical displacement of the valve
leaflets with subsequent atrialization of the RV nor is there associated tricuspid stenosis. Fibrous of the
abnormally positioned AV conduction bundle is responsible for an approximately 2% incidence per year of
spontaneous complete heart block.
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The natural history of C-TGA in the rare patient without significant associated
lesions is generally normal functional status into the fifth decade of life. Approximately 1/3 of these of
these patients will have clinical HF secondary to RV dysfunction by the age of 45. In contrast 2/3 of
patients with significant lesions having required operative intervention will have HF by the same age 18. By
age 45 only 20% of patients with poor RV function will be alive while 80% of those with normal RV
function will be alive 19. RV function may be further compromised by the presence of impaired coronary
blood flow reserve in patients with C-TGA 20.
The etiology of poor RV function is multifactorial with tricuspid regurgitation (TR), heart block,
systemic afterload, and RV systolic dysfunction all playing a role. The question as to whether the
development of systemic AV valve (tricuspid valve) insufficiency and RV volume overload leads to
systemic ventricular (RV) failure or RV failure and dilation leads to TR remains unanswered 19 21.
However, there is some suggestion that while primary RV dysfunction is uncommon it is a frequent
consequence of an abnormal tricuspid valve and TR 22. Although the precise role of previous operative
interventions and the role of arrhythmias and heart block in the development of CHF are unclear complete
heart block tends to exacerbate the hemodynamic consequences of RV dysfunction and TR.
Atrial Switch Procedures for D-TGA
Both the Mustard and the Senning procedures are atrial switch procedures that surgically create
discordant AV connections in TGA. Systemic venous blood is baffled to the LV, which is connected to the
pulmonary artery. Likewise pulmonary venous blood is baffled to the RV, which is connected to the aorta.
This arrangement results in physiologic but not anatomic correction of TGA, as the morphologic RV
becomes the systemic ventricle. Given the current success with and the almost universal application of the
more definitive arterial switch operation these intra-atrial switch procedures are rarely currently performed
in patients with D-TGA.
As with patients with C-TGA a major concern in patients having undergoing atrial switch
procedures is that the RV and tricuspid valve may not be physiologically adapted to support the systemic
circulation. The systemic (RV) ventricular ejection fraction is mildly to severely impaired in the majority of
atrial switch patients, and RV end diastolic volume is elevated 23 24. HF in the presence of preserved
systolic function is frequently the result of significant TR 25.
Fontan
Figures 1 and 2 provide a schematic representation of a normal, two-ventricle series circulation,

single ventricle parallel circulation, and a Fontan series circulation. In the normal circulation the left
ventricle supplies only the energy to overcome the resistance of the systemic circulation. In the single
ventricle circulation the systemic ventricle is presented with a large volume load and supplies the energy to
overcome the resistance of both the systemic and pulmonary circulations arranged in parallel. Parallel
arrangement of 2 resistances requires ¼ the energy necessary to provide the same flow as in a circuit where
2 resistances are arranged in series. In the Fontan circulation the systemic ventricle faces both the systemic
and pulmonary resistances arranged in series with the systemic venous circulation and the total
cavopulmonary connection (TCPC) pathway interposed between the two 26 27.
Afterload is elevated in the Fontan circulation because three resistance beds: the systemic vascular
bed, the TCPC pathway, and the pulmonary vascular bed are arranged in series. As a consequence, even
Fontan patients with normal ventricular function have contractility afterload mismatch at rest and during
exercise 28. Elevated systemic venous pressure is a necessity in Fontan physiology because the interposition
of the TCPC pathway and pulmonary vascular bed between the systemic venous system and the pulmonary
venous atrium results in an increase in the resistance to venous return 29. As resistance to venous return
increases due to increases in TCPC resistance, pulmonary vascular resistance, or both, true preload
(pulmonary venous atrial pressure or ventricular end-diastolic pressure) will fall unless systemic venous
pressure and subsequently systemic ventricular afterload increase sufficiently. As a result, despite elevated
systemic venous pressure, ventricular preload and preload reserve are reduced in the Fontan circulation 30.
Incremental increases in systemic venous pressure while necessary to provide adequate preload to
the systemic ventricle have the unfortunate consequence of simultaneously increasing systemic ventricular
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afterload 29. This situation does not exist in a normal two-ventricle circulation because in
addition to providing a pulsatile source of pulmonary blood flow the right ventricle serves as a compliant
reservoir system for the systemic venous circulation (Figure 2) 31. Thus, the ‘failing Fontan’ cycle whether
initiated by increased afterload, depressed systolic function of the single ventricle, or both is self
perpetuating as systemic venous pressure rises.
Heart Failure Symptoms
The overwhelming majority of ACHD patients with rigorously defined HF are asymptomatic and
are NYHA class I or II 8 32. Nonetheless, it is worthwhile to review the unique aspects of HF
symptomatology present in the ACHD population.
Ischemic systemic ventricular dysfunction leading to pulmonary venous hypertension and
congestion is the most common manifestation of HF in the general population but is much less common in
the current ACHD population. When pulmonary venous hypertension and congestion exist they are most
commonly the result of systemic right ventricular dysfunction and associated tricuspid valve (systemic
atrioventicular valve) insufficiency in either a single ventricle (Fontan procedure) or two-ventricle
circulation (D-TGA with atrial switch procedure and C-TGA) 9 33.
Symptoms of systemic venous hypertension, uncommon in the adult acquired HF population, are the
most common HF finding in TOF and Fontan patients. RV diastolic dysfunction, RV systolic dysfunction,
and tricuspid valve insufficiency can all contribute to elevated systemic venous pressure in TOF patients.
As previously discussed, in Fontan physiology elevated systemic venous pressure is a necessity.
An additional, oft overlooked cause of both pulmonary and systemic venous hypertension and
congestion in the ACHD population, in the absence of ventricular dysfunction and/or atrioventricular valve
dysfunction, is mechanical obstruction of baffled pulmonary venous pathways following an atrial level
switch procedure. The most severe cases of pulmonary and systemic venous obstruction require
intervention. Reoperation is an option; however pulmonary and systemic venous obstruction following both
the Mustard and the Senning repairs are generally treated now by interventional cardiologists utilizing
percutaneous balloon dilation and stent placement.
Exercise Capacity
Cardiopulmonary exercise testing (CPX) has emerged as a valuable tool in predicting morbidity and
mortality in the ACHD population in patients with specific lesions such as TOF 34, atrial switch procedures
for D-TGA 24, and Fontan circulation 35 36 as well as in the entire ACHD cohort 32 37 38. Exercise capacity is
reduced in the vast majority of ACHD patients, including those who are asymptomatic and HF
classification underestimates the severity of objective exercise intolerance 32. Virtually the entire cohort of
ACHD patients has a functional capacity, defined as peak oxygen consumption (VO2) well below the age
matched control mean value of 45 mL/kg/min 32. This is true for both symptomatic (mean peak VO2 21
mL/kg/min) and asymptomatic (mean peak VO2 26 mL/kg/min) patients. Many of the patients have a peak
VO2 < 14 mL/kg/min, which is a major objective criteria, used to determine eligibility for cardiac
transplantation 39. In fact, the entire cohort of ACHD patients with a mean age of 33 years has a
distribution of HF symptoms and functional capacity identical to that of the conventional adult heart failure
population with a mean age of 59 years 32. As would be expected, the subgroups with the highest incidence
of HF tended to have the lowest peak VO2.
The minute ventilation (VE) to carbon dioxide production (VCO2) slope (VE/VCO2) derived during
CPX is elevated as ventilatory efficiency decreases. Elevations in slope are seen in patients with TOF, HF,
and pulmonary hypertension secondary to pulmonary blood flow maldistribution and ventilation/perfusion
mismatch; this elevation is associated with increased risk of mortality 40 41. In Fontan patients, elevations in
slope are intrinsic to the physiology of non-pulsatile pulmonary blood flow and not predictive of mortality
in this population 35. This contention is supported by the fact that fenestration Fontan closure, with
elimination of intracardiac right to left shunting and chemoreceptor driven increases in VE from delivery of
blood high in CO2 to the arterial circuit, improves but does not normalize V E/VCO2 slope 42.
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The etiology of impaired exercise capacity is multifactorial and to some extent lesion
specific. Chronotrophic incompetence, as defined by the chronotrophic index is common in ACHD patients
and is associated with increased mortality 37. Oxygen pulse, defined as VO2/HR, is a surrogate measure of
stroke volume and is depressed in patients with impaired ventricular function and in Fontan patients even in
the absence of ventricular dysfunction 40 43. This is a reflection of the inability of the Fontan circulation to
deliver adequate increases in preload to the systemic ventricle during exercise 44. Finally, ACHD patients
systematically severely overestimate their actual measured exercise capacity 45. This may be a consequence
of a lifetime of diminished capacity perceived of as normal.
Figure 1. Schematic representations of normal two-ventricle circulation (top), and Fontan physiology
(bottom). See text for description. SV=single ventricle; LV = left ventricle; RV=right ventricle;
RS=systemic vascular resistance; RP=pulmonary vascular resistance; Ao=aorta; LA=left atrium; RA=right
atrium; PA=pulmonary artery. Adapted with permission from: Rodefeld MD, Boyd JH, Myers CD, Presson
RG, Jr., Wagner WW, Jr., Brown JW: Cavopulmonary assist in the neonate: an alternative strategy for
single-ventricle palliation. J Thorac Cardiovasc Surg 2004; 127: 705-11
Figure 2. A hydraulic schematic of the Fontan circulation in which the systemic and pulmonary resistance
beds are arranged in series. The single ventricle is represented as a pump that moves blood from a high-
compliance, low-pressure venous reservoir into a low compliance, high pressure arterial reservoir. Blood
return to the venous reservoir is gradient driven across a single resistance, the systemic vascular resistance
(SVR). Unlike a 2-ventricle circulation, blood return to pump (ventricular preload) is gradient driven from
the venous reservoir across 2 interposed resistances: the pulmonary vascular resistance (PVR) and the
resistance across the cavopulmonary connection (not shown separately here but incorporated in PVR). Two
means exist whereby the driving pressure in the venous reservoir can be increased to increase ventricular
preload: increase the volume of the venous reservoir by expanding the blood volume or reduce venous
capacitance. Unique to the Fontan circulation is the fact that increases in venous reservoir pressure
simultaneously increase preload and afterload to the single ventricle because all resistances and pressures
are in series. All the energy necessary to provide sufficient gradients for flow in the presence of elevated
venous pressure is supplied by the single ventricle (Adapted from Tyberg 46 by Katherine Black).
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Figure 2
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Congenital Heart Disease and Pregnancy

Susan Eagle, M.D. Nashville, TN
The increasing survival of patients with congenital heart disease (CHD) into adulthood can be
attributed to advances in surgical and medical management in this patient population. As such,
more women with CHD are living into childbearing age. [Between 2000 and 2010, deliveries
increased from 6.4 to 9 per 10,0000.[1] These deliveries had a increased incidence of
complications, both medical and obstetric. Each parturient with CHD should be considered at risk
for developing heart failure during her pregnancy and postpartum course. Given the differences
in severity of cardiac lesions and functional class, an individualized approach with a
multidisciplinary medical team is recommended for each parturient. This lecture serves as a
guide for the anesthesiologist for managing the parturient with CHD.
Risk Stratification
The World Health Organization (WHO) risk stratification for parturients with CHD is outlined in
Talbe 1.[2, 3] Lesions that place parturients at very high maternal risk where pregnancy is
discouraged include severe symptomatic left-sided valve stenosis, ejection fraction <30%,
pulmonary hypertension, and Marfan syndrome/biscuspid aortic valve with ascending aortic
diameter>45mm. Patients considered at high risk for maternal mortality include transposition of
great arteries with systemic right ventricle, Fontan palliation, ejection fraction 30-40%, and
asymptomatic left ventricular outflow track obstruction.
Hemodynamic changes with pregnancy

During the course of pregnancy, cardiac output increases steadily to ~45% above baseline until
the end of the second trimester when it plateaus. Cardiac output increases ~80% above baseline
during labor until delivery. Similarly, stroke volume increases ~30% above baseline and plateaus
toward the end of the second trimester. Following delivery, stroke volume increases to ~60%
above baseline values. These increases in cardiac output and stroke volume may account for the
highest incidence of heart failure during the latter part of the second trimester and in the
immediate postpartum periods. Depending on the type of defect and severity of the cardiac lesion,
adaptive responses to pregnancy may be altered. Preeclampsia and multiple gestational births
pose further risk for the parturient with CHD. According to the ROPAC registry, women with
CHD have a 30% risk of heart failure.[4] This lecture is intended to cover the risk stratification of
parturients with CHD and common CHD lesions encountered in the obstetrical arena.
Obstetrical Drugs
Pharmacologic agents used in the obstetrical arena can have unwarranted side effects for the
parturient with CHD.[5] Beta-mimetics (terbutaline, e.g.) used for tocolysis can result in
tachycardia and are therefore contraindicated in patients with left-sided outflow track obstruction,
left sided valve stenosis (aortic or mitral), and those with a propensity for tachyarrhythmias.
Drugs used for the induction of labor such as oxytocin should be administered as low, continuous
infusions to prevent hypotension. Prostoglandin E1 (Misoprostol, e.g.) can cause coronary
vasospasm and arrhythmias. However, Prostoglandin E is a pulmonary vasodilator and has been
used successfully in patients with pulmonary hypertension.[6] For control of postpartum
bleeding, Prostaglandin F analogs (Carboprost, e.g.) may cause severe pulmonary hypertension
and is therefore contraindicated in patients with pulmonary hypertension or right heart failure.
PGF should be used with extreme caution if at all in patients with Fontan physiology. Ergot
derivatives (methylergonovine, e.g.) may cause severe hypertension and should be used with
caution in patients with severe heart failure.
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Cesarean section vs. vaginal delivery

With few exceptions, most parturients with CHD can have a safe vaginal delivery with epidural
anesthesia. However, cesarean section is recommended for women with Marfan syndrome (or
bicuspid aortic valve) with ascending aortic diameter >45mm, symptomatic aortic stenosis, and
severe symptomatic heart failure.[5]
Select CHD lesions in pregnancy

Left to right shunts & pulmonary hypertension: Typically, small atrial septal defects (ASD)
and ventricular septal defects (VSD) without evidence of pulmonary hypertension are well
tolerated in pregnancy. There is risk for paradoxical embolism and air filtering intravenous
catheters is acceptable. Parturients with large unrepaired shunts with pulmonary hypertension or
Eisenmenger syndrome are at high risk for maternal and fetal (40-50%) mortality.[6, 7] Maternal
mortality occurs secondary to acute right heart failure and pulmonary thrombosis and most
commonly occur during the last trimester and up to a few weeks postpartum.[7]Pregnancy is
therefore not recommended in patients with pulmonary hypertension. The anesthetic
management of presenting with pulmonary hypertension is to maintain or increase the systemic
vascular resistance (SVR).[8] Thus, spinal anesthesia is not recommended and epidural dosing
should commence slowly to avoid a sudden decrease in SVR.
Congenital aortic valve disorders: Parturients with severe symptomatic congenital aortic
stenosis are at a high risk for maternal mortality. Even patients who are asymptomatic have a
10% incidence of heart failure and up to a 35% incidence of arrhythmias.[3] Supravalvular
obstructive lesions may occur in patients with William syndrome. In patients with obstructive
lesions, whether in the left ventricular outflow track, aortic valve, or supravalvular, the key
management is to maintain or increase systemic vascular resistance and maintain normal sinus
rhythm and rate. This author discourages spinal anesthesia. Epidural anesthesia may be used
with cautious boluses of local anesthetics. Symptomatic patients may need cessarian section
under general anesthesia.
Parturients with bicuspid aortic valve are at risk for aortic dissection, particularly for ascending
aortic diameters >45mm.[9, 10]
Right-sided lesion: Ebstein abnomaly, or ventricular displacement of the tricuspid valve into the
right ventricle, results in right ventricular failure and is associated with superventricular
tachyarrthythmias and a patent foramen ovale. This lesion is tolerated well in pregnancy, but is
associated with increased fetal loss.[11] Patients with cyanosis are at high risk for maternal
mortality.
Repaired Tetralogy of Fallot is generally well tolerated in pregnancy, assuming there are no
significant residual lesions.[12] One of the most common complications of TOF repair is
pulmonic insufficiency resulting in right ventricular dilatation and failure. Pulmonic valve
replacement is recommended prior to pregnancy in these cases.[13] Ventricular arrhythmias are
also common due to the right ventriculotomy scar from surgical repair. This complication should
be elicited in the parturient’s history. Patients with a QRS complex >180ms on
electrocardiogram are at an increased risk for malignant ventricular arrhythmias.[7]
Transposition of Great Arteries (TGA): d-TGA is the most common cyanotic congenital heart
disorder. Historically, surgical repair consisted of an atrial switch procedure. However, the
arterial switch procedure is the most common surgical approach in modern times for TGA.
Regardless of the approach, the right ventricle acts as the systemic ventricle. Parturients with
adequate repair have a good outcome overall.[14] However, there remains a risk of neo-aortic
root dilatation, failure of the systemic RV, chronotropic failure, and insufficient coronary blood
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flow with the arterial switch. Patients with congenitally corrected TGA have a lifetime risk for
systemic RV failure, AV node block (2% per patient per year), and reentrant arrhythmias.[15]
Fontan palliation: Parturients with Fontan palliation are at increased risk for decreased systemic
(single) ventricular failure, thromboembolic events, and supraventricular arrthythmias,
particularly intraatrial reentrant tachycardia (IART) or slow atrial flutter.[16, 17] Vaginal
deliveries can be performed, though assist is common due to decreased cardiac output with
Valsalva maneuver. Epidural analgesia is warranted for vaginal delivery or cesarean section.
However, slow epidural dosing is recommended in order to avoid sudden decreases in venous
return that can significantly impair cardiac output. Spinal anesthesia is not recommended.[16]
1. Thompson, J.L., et al., Medical and Obstetric Outcomes Among Pregnant

Women With Congenital Heart Disease. Obstet Gynecol, 2015. 126(2): p. 346-
54.
2. Brickner, M.E., Cardiovascular management in pregnancy: congenital heart
disease. Circulation, 2014. 130(3): p. 273-82.
3. European Society of, G., et al., ESC Guidelines on the management of
cardiovascular diseases during pregnancy: the Task Force on the Management
of Cardiovascular Diseases during Pregnancy of the European Society of
Cardiology (ESC). Eur Heart J, 2011. 32(24): p. 3147-97.
4. Ruys, T.P., et al., Heart failure in pregnant women with cardiac disease: data
from the ROPAC. Heart, 2014. 100(3): p. 231-8.
5. Greutmann, M. and P.G. Pieper, Pregnancy in women with congenital heart
disease. Eur Heart J, 2015. 36(37): p. 2491-9.
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6. Bonnin, M., et al., Severe pulmonary hypertension during pregnancy: mode of

delivery and anesthetic management of 15 consecutive cases. Anesthesiology,
2005. 102(6): p. 1133-7; discussion 5A-6A.
7. Naguib, M.A., D.P. Dob, and M.A. Gatzoulis, A functional understanding of
moderate to complex congenital heart disease and the impact of pregnancy.
Part II: tetralogy of Fallot, Eisenmenger's syndrome and the Fontan operation.
Int J Obstet Anesth, 2010. 19(3): p. 306-12.
8. Bennett, J.M., et al., Anesthetic management and outcomes for patients with
pulmonary hypertension and intracardiac shunts and Eisenmenger syndrome:
a review of institutional experience. J Clin Anesth, 2014. 26(4): p. 286-93.
9. Hiratzka, L.F., et al., 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM
guidelines for the diagnosis and management of patients with Thoracic Aortic
Disease: a report of the American College of Cardiology Foundation/American
Heart Association Task Force on Practice Guidelines, American Association for
Thoracic Surgery, American College of Radiology, American Stroke Association,
Society of Cardiovascular Anesthesiologists, Society for Cardiovascular
Angiography and Interventions, Society of Interventional Radiology, Society of
Thoracic Surgeons, and Society for Vascular Medicine. Circulation, 2010.
121(13): p. e266-369.
10. Etz, C.D., et al., Current indications for surgical repair in patients with bicuspid
aortic valve and ascending aortic ectasia. Cardiol Res Pract, 2012. 2012: p.
313879.
11. Donnelly, J.E., J.M. Brown, and D.J. Radford, Pregnancy outcome and Ebstein's
anomaly. Br Heart J, 1991. 66(5): p. 368-71.
12. Veldtman, G.R., et al., Outcomes of pregnancy in women with tetralogy of
Fallot. J Am Coll Cardiol, 2004. 44(1): p. 174-80.
13. Gelson, E., et al., Tetralogy of Fallot: maternal and neonatal outcomes. BJOG,
2008. 115(3): p. 398-402.
14. Canobbio, M.M., et al., Pregnancy outcomes after atrial repair for transposition
of the great arteries. Am J Cardiol, 2006. 98(5): p. 668-72.
15. Hornung, T.S. and L. Calder, Congenitally corrected transposition of the great
arteries. Heart, 2010. 96(14): p. 1154-61.
16. Eagle, S.S. and S.M. Daves, The adult with Fontan physiology: systematic
approach to perioperative management for noncardiac surgery. J Cardiothorac
Vasc Anesth, 2011. 25(2): p. 320-34.
17. Khairy, P., et al., Long-term survival, modes of death, and predictors of
mortality in patients with Fontan surgery. Circulation, 2008. 117(1): p. 85-92.
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Outcomes of Adults With Congenital Heart Disease

Presenting for Outpatient and Moderate to Complex Non-Cardiac Surgery
Bryan G. Maxwell, MD, MPH Portland, OR
The problem
Over the past four decades, increasing success in the management of pediatric congenital heart disease (CHD) has
resulted in dramatic increases in the number who survive to adulthood1 and adults now outnumber children with
CHD2, accounting for approximately 66% of the overall CHD population.3 Since 2000, the prevalence of CHD has
increased most dramatically in patients age 26-40 years old.3 But many CHD lesions are treated with long-term
palliative strategies that are not truly curative, and many adult congenital heart disease (ACHD) patients require
cardiac reintervention and eventually develop progressive heart failure as a late sequela of their initial CHD.
These patients are at high risk of morbidity and mortality when they present for cardiac reoperations,
electrophysiology interventions, noncardiac surgery, 4 and obstetric care.5 Anesthesiologists will encounter these
patients with increasing frequency, and provider survey data suggest that anesthesiologists have limited knowledge
of and comfort with this patient subgroup. 6
The setting: who, what, and where?
The typical survival pattern from CHD shows a small initial dropoff in infancy, a long plateau phase, and then a late
epoch of mortality that results from long-term sequelae of good palliation techniques that are nonetheless not true
cures. For instance, the atrial switch technique for repairing transposition of the great arteries left the right ventricle
in a systemic position, which eventually fails in many patients.
Because CHD survivors typically enjoy a long plateau phase of generally good health, they often transition out of
the concentrated and highly specialized centers of pediatric cardiac care where they received care as children and
spread across a wide range of community settings. A loss to followup for years is common.
Single-center data suggest that only a small fraction of ACHD patients return to their original CHD center for adult,
noncardiac care. Investigators at the Mayo Clinic reviewed noncardiac surgery in all patients who previously
had undergone a Fontan operation (n = 1,133), and identified only 39 general anesthetics in 31 patients. 7
American College of Cardiology/American Heart Association consensus guidelines recommend that ACHD patients
should receive perioperative care in specialized ACHD centers. ACHD patients are addressed both as a special
population at risk in the guidelines for evaluation of cardiovascular disease for all patients undergoing noncardiac
surgery8 and by a more focused set of guidelines for the care of ACHD patients (in which noncardiac
surgery is discussed as a potentially high-risk event)9. These guidelines specifically establish the standard that
preoperative evaluation, risk assessment, and surgery for ACHD patients should occur in regional centers because of
access to congenital cardiology care, experienced surgeons and cardiac anesthesiologists. However, there is
evidence that ACHD care remains decentralized, despite these guidelines, with perioperative care occurring
primarily in the community setting.
An analysis based on administrative data from California identifying ACHD patients by home zip code and mapping
their location of care for noncardiac surgery shows that while the majority of pediatric CHD patients (57%) had
surgery in a CHD center of expertise (n=14 in California), the majority of ACHD patients (74%) had surgery in a
non-specialty center (other hospitals and surgery centers). This difference largely was driven by distance: ACHD
patients who had surgery at a non-specialty center lived farther from the nearest CHD center (37.9 miles) than adult
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CHD patients who had surgery at a CHD center (23.2 miles, p<0.0001). These patients, on average, traveled only
11.9 miles to their (nonspecialty) surgical facility – i.e. an average of 26 miles closer than the nearest CHD center. 10
It seems plausible that anesthesiologists across a wide range of clinical settings outside of CHD centers may
continue to see ACHD patients with substantially increasing frequency, and should be prepared to manage them.
Outcome studies
Robust and highly granular outcome data are limited, but there are a few studies that help demonstrate that ACHD
patients have less favorable outcomes of noncardiac interventions.
A retrospective analysis of National Surgical Quality Improvement Program data from the American College of
Surgeons suggest that compared with a matched control cohort, young adults with congenital or early acquired heart
disease experienced significantly greater perioperative morbidity (4.2 vs 1.6%, p<0.001) and mortality (2.9 vs 1.1%,
p<0.001) after noncardiac surgery. 11
A national analysis of administrative data from the Nationwide Inpatient Sample produced similar results, that a
cohort of over 10,000 ACHD patients, compared to matched controls, had higher inpatient mortality (4.1 vs 3.6%,
p<0.001) and major morbidity (21.4% vs 16.0%, p<0.001). ACHD remained an independent predictor of mortality
after multivariable logistic regression.4
Similar findings are evident from analyses of outcomes from other procedural categories. For instance, during
catheter-based electrophysiologic interventions, ACHD patients have worse outcomes compared to non-ACHD
patients.12
Further registry efforts are underway to better delineate subgroups of ACHD patients who are at risk for poor
outcomes at the time of noncardiac operations and to investigate possible outcome differences when care occurs in
CHD centers of excellence compared to in the community.
How to approach ACHD patients: the paradigm of limited reserve
Cardiac dysfunction and end-organ compromise often are under-recognized in ACHD patients, in part because of a
self-conception that they have no functional limitations, which may result from their youth, tendency to regard
themselves as normal and healthy, and their lack of any comparative life experiences with normal cardiac
physiology. While substantial functional impairments exist in the ACHD population, 13 patients underappreciate and
underreport them.14 For instance, ACHD patients underreport exercise limitation, and substantial impairment is
often apparent if assessed with exercise testing. A cohort of 335 ACHD patients followed at the Royal Brompton in
London (average age 33 years, with the majority describing themselves as “asymptomatic”) demonstrated an
average peak oxygen consumption only 48% of that seen in age-matched controls without ACHD. This impairment
was on par with that demonstrated by a comparison cohort of acquired heart failure patients (average age 58
years).15 Likewise, end-organ compromise is common: for instance, restrictive lung disease 16 and renal
insufficiency17 each have been demonstrated in approximately 50% of a broad panel of young ACHD patients, the
majority of which described themselves as fit and healthy.
The core challenge for such high-risk patients is to devise an anesthetic strategy that minimizes the chances of
destabilizing a patient with minimal reserve. With few exceptions (i.e. patients presenting in extremis for an
emergent intervention), even the sickest patients with the most severely depressed ventricular function present for an
anesthetic having achieved some homeostatic equilibrium of adequate circulatory function. The key difference
between such a patient and a patient without cardiac disease is the physiologic reserve he or she has to tolerate
additional insults during the perioperative period: hypoxia, hypercarbia, hypotension, pain, sympathetic surges,
abnormal pressure conditions (e.g. positive pressure ventilation, pneumoperitoneum, etc.), blood loss, arrhythmias,
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and fluid shifts. In caring for these high-risk patients, we are tasked not with fixing their tenuous – though, at the
moment, adequate – circulation, but with putting them in the best possible position to enable that circulation to
withstand those perioperative stressors.
A general perspective on improving outcomes
A subsequent lecture will address perioperative management in more detail. Let me offer here a more general
perspective on how we can improve outcomes in the ACHD population.
Because ACHD patients may have limited reserve with little margin of error during the perioperative period, even
small details matter a great deal. The best single-line encapsulation of the approach to these patients is this: “Be
meticulous.”
In our practice, the applicable model is that the anesthesiologist leads a multidisciplinary effort to prepare the team
for and execute a perioperative plan that is detail-oriented and builds in contingencies for as comprehensive as
possible a range of perioperative insults. One must anticipate and try to prevent or immediately reverse all of the
adverse occurrences that, in another patient, would be transient and inconsequential but that might be enough to tip a
precarious patient over the edge. Logistical and operational considerations play a large role.
References
1
Moons P, Bovijn L, Budts W, Belmans A, Gewillig M. Temporal trends in survival to adulthood among patients
born with congenital heart disease from 1970 to 1992 in Belgium. Circulation 2010;122(22):2264–72.
2
Marelli AJ, Mackie AS, Ionescu-Ittu R, Rahme E, Pilote L. Congenital heart disease in the general population:
changing prevalence and age distribution. Circulation 2007;115(2):163–72.
3
Marelli AJ, Ionescu-Ittu R, Mackie AS, Guo L, Dendukuri N, Kaouache M. Lifetime Prevalence of Congenital
Heart Disease in the General Population from 2000 to 2010. Circulation 2014.
4
Maxwell BG, Wong JK, Kin C, Lobato RL. Perioperative outcomes of major noncardiac surgery in adults with
congenital heart disease. Anesthesiology 2013;119(4):762–9.
5
Maxwell BG, El-Sayed YY, Riley ET, Carvalho B. Peripartum outcomes and anaesthetic management of
parturients with moderate to complex congenital heart disease or pulmonary hypertension. Anaesthesia
2013;68(1):52–9.
6
Maxwell BG, Williams GD, Ramamoorthy C. Knowledge and attitudes of anesthesia providers about noncardiac
surgery in adults with congenital heart disease. Congenit Heart Dis 2013;9(1):45–53.
7
Rabbitts JA, Groenewald CB, Mauermann WJ, Barbara DW, Burkhart HM, Warnes CA, Oliver WC Jr, Flick RP:
Outcomes of general anesthesia for noncardiac surgery in a series of patients with Fontan palliation. Paediatr
Anaesth 2013; 23:180–7
8
Fleisher LA, Beckman JA, Brown KA, Calkins H, Chaikof EL, et al. (2007) ACC/AHA 2007 guidelines on
perioperative cardiovascular evaluation and care for noncardiac surgery: a report of the American College of
Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 50: e159–241.
doi:10.1016/j.jacc.2007.09.003.
9
Warnes CA, Williams RG, Bashore TM, Child JS, Connolly HM, et al. ACC/AHA 2008 guidelines for the
management of adults with congenital heart disease: a report of the American College of Cardiology/American
Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 52: e143–263.
doi:10.1016/j.jacc.2008.10.001.
10
Maxwell BG, Maxwell TG, Wong JK (2014) Decentralization of Care for Adults with Congenital Heart Disease
in the United States: A Geographic Analysis of Outpatient Surgery. PLoS ONE 9(9): e106730.
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11
Maxwell BG, Wong JK, Lobato RL. Perioperative morbidity and mortality after noncardiac surgery in young
adults with congenital or early acquired heart disease: a retrospective cohort analysis of the NSQIP database. Am
Surgeon 2014; 80: 321-6.
12
Maxwell BG, Steppan J, Cheng A. Complications of catheter-based electrophysiology procedures in adults with
congenital heart disease: a national analysis. J Cardiothorac Vasc Anesth 2015; 29: 258-264.
13
Tobler D, Williams WG, Jegatheeswaran A, et al. Cardiac outcomes in young adult survivors of the arterial switch
operation for transposition of the great arteries. J Am Coll Cardiol 2010;56(1):58–64.
14
Gratz A, Hess J, Hager A. Self-estimated physical functioning poorly predicts actual exercise capacity in
adolescents and adults with congenital heart disease. Eur Heart J 2009;30(4):497–504.
15
Diller G-P, Dimopoulos K, Okonko D, et al. Exercise intolerance in adult congenital heart disease: comparative
severity, correlates, and prognostic implication. Circulation 2005;112(6):828–35.
16
Alonso-Gonzalez R, Borgia F, Diller G-P, et al. Abnormal lung function in adults with congenital heart disease:
prevalence, relation to cardiac anatomy, and association with survival. Circulation 2013;127(8):882–90.
17
Dimopoulos K, Diller G-P, Koltsida E, et al. Prevalence, predictors, and prognostic value of renal dysfunction in
adults with congenital heart disease. Circulation 2008;117(18):2320–8.
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Perioperative Management Strategies for Adults with Congenital Heart

Disease Presenting for Non-cardiac Surgery
Jochen Steppan, MD, DESA Baltimore/Maryland
Congenital heart disease (CHD) includes a wide spectrum of conditions encompassing relatively simple lesions,
such as atrial and ventricular septal defects, to more complex lesions, such as hypoplastic right heart. Moreover
CHD can be part of a syndrome that also has non-cardiac manifestations (e.g. VACTERL association). An
exhaustive and complete discussion of every lesion and combination thereof is beyond the scope of this review, and
the reader is referred to the excellent textbooks on this topic 1. The goal of this review is to provide an overview of
key perioperative management strategies that are applicable to patients with a wide range of congenital heart lesions.
Introduction
Despite an unchanged CHD incidence of about 8/1,000 live births, the last few decades have seen a steady increase
in the number of adults with congenital heart disease2. It is estimated that more adults than children are currently
living with CHD in the USA3. This dramatic increase can be attributed not only to new surgical techniques, but also
to profound improvements and coordination of care provided by pediatricians, cardiologists, anesthesiologists, and
critical care physicians. Therefore adults with CHD, including patients in their 60s and above, increasingly present
for non-cardiac surgeries and diagnostic or interventional procedures that are independent of their underlying
congenital heart defect4,5. They not only suffer from the same comorbidities as their age-matched non-CHD
counterparts, but also have a higher incidence of certain conditions. These include, but are not limited to: heart
failure (especially right heart failure), arrhythmias/conduction abnormalities, pulmonary hypertension, cyanosis,
altered lung mechanics, renal insufficiency, hepatic congestion, paradoxical emboli, coagulopathies, and
erythrocytosis6-9. It is not surprising that adults with CHD are at higher risk for perioperative mortality and
morbidity4,10.
Preoperative Management
Adults with CHD do not represent a homogenous patient population, and ideally a multidisciplinary team of experts
should provide care for these patients3. It is important to discuss these patients with colleagues from cardiology and
surgery to determine 1) if the patient is optimized for surgery, 2) if the surgical approach needs to be modified, 3) if
the provider has the expertise to take care of this specific patient, and 4) the ideal location for the procedure and
postoperative disposition. Patients at high risk for perioperative complications, such as those with single-ventricle
physiology, severe pulmonary hypertension, cyanotic lesions, etc., should be cared for in a regional center of
excellence for adult congenital heart disease (ACHD)3.
The preoperative evaluation includes the routine assessment, such as airway, medications, and past medical
history, as well as invasive and noninvasive testing. Providers should be cognizant of coexisting syndromes that
occur in almost 20% of patients with CHD11. They might have further implications for their management (e.g. a
difficult airway in a patient with Down’s syndrome). The latest guidelines recommend obtaining a systemic arterial
oxygen saturation, an ECG, a chest x-ray, and laboratory tests3. However, many patients will also require an
echocardiogram and potentially more complex studies such as a cardiac MRI if there is any uncertainty about the
current anatomy.
Special attention should be paid to assess the potential difficulty of gaining vascular access, both venous and
arterial. Patients who underwent heart surgery at a very young age frequently will have had multiple attempts to gain
venous access, and may have had an arterial cut-down. Furthermore, prior surgery, such as a Blalock-Taussig shunt
or a subclavian flap, can render blood pressure measurements on the affected side unreliable.
Endocarditis prophylaxis in high-risk patients is reasonable for dental procedures that involve manipulation of
gingival tissue, the periapical region of teeth, or perforation of the oral mucosa, and for vaginal delivery at the time
of membrane rupture12. It is no longer recommended that infective endocarditis prophylaxis be used for non-dental
procedures such as colonoscopies12. Patients with CHD at high risk for adverse outcomes from infective
endocarditis include those with:
(1) Prosthetic cardiac valve or prosthetic material used for cardiac valve repair
(2) Previous infective endocarditis
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(3) Unrepaired and palliated cyanotic CHD, including surgically constructed palliative shunts and conduits
(4) CHD completely repaired with prosthetic materials, whether placed by surgery or by catheter intervention,
during the first 6 months after the procedure
(5) Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic
device that inhibits endothelialization
Lastly, the type of surgery or procedure confers its own unique risks. For example, in a patient with a single
ventricle who is dependent on passive pulmonary blood flow, high ventilatory pressures and steep Trendelenburg
during a laparoscopic case might be poorly tolerated 13. Using a team-based approach, a consensus might be reached
to either perform an open procedure or to trial a laparoscopic approach with low inflation pressures, to minimize
Trendelenburg position, and to have a low threshold for converting to an open approach. As stated above, it is
important to involve all parties early in the preoperative process to ensure a mutual understanding of the risk and
potential complications that might alter the perioperative course.
Intraoperative management
Given the multitude of different lesions, the different types of CHD can be divided with different schemes into
groups based on the severity of the lesion, the status of the repair, or the dominant physiology and can provide a
basis for management strategies. One especially useful approach is to determine pathophysiology as primarily a
result of: 1) Obstructive lesions, 2) Shunting lesions, 3) Pulmonary hypertension and right heart failure, or 4) a
single-ventricle physiology.
Obstructive lesions
Congenital heart lesions that include some obstruction to blood flow are relatively common at birth. Those
obstructions can be at the level of 1) the venous inflow (e.g. pulmonary vein stenosis), 2) the atrioventricular
connections (e.g. tricuspid atresia), 3) ventriculoarterial connection (e.g. pulmonary atresia), or 4) the great arteries
(e.g. aortic coarctation). The majority of obstructive lesions will be either mild at birth and become symptomatic
later in life (e.g. bicuspid aortic valve) or be so severe that they require surgery for survival (e.g. tricuspid atresia
necessitating a Fontan palliation). The most prominent exception to that rule is aortic coarctation. The adult
anesthesiologist will therefore encounter only a few congenitally originated obstructive lesions. The management of
the remaining lesions either will be very familiar (e.g. aortic stenosis) or will fall into the category of single-
ventricle repair (see section below).
One true obstructive lesion that can be encountered in adulthood (either corrected or uncorrected) is aortic
coarctation. The obstruction in those patients can be either preductal, which usually manifests in childhood with
lower extremity cyanosis, or postductal, which can persist undetected into adulthood with upper body hypertension
and faint or absent pulses in the lower half of the body. Consequently, the latter is the one most likely encountered in
adults (repaired, unrepaired, or repaired but with recurring coarctation). Management is somewhat similar to that of
patients with aortic valve stenosis (though coronary perfusion is usually not as severely compromised). Patients
frequently present with left ventricular hypertrophy and signs of congestive heart failure. Care must be taken not to
raise blood pressure excessively and to avoid spikes in blood pressure and heart rate, given an increased incidence of
cerebral aneurysms in those patients.
Shunting lesions
Most CHD lesions encountered by the adult anesthesiologist will likely involve some degree of shunting. Common
examples include atrial septal defects (ASD), ventricular septal defects (VSD), and rarely Tetralogy of Fallot (either
unrepaired or with a residual VSD). The intraoperative management of these patients depends on the direction of
blood flow (right to left, left to right, or bidirectional) and the severity of the shunt (restrictive or unrestrictive). The
ratio of pulmonary-to-systemic blood flow (Qp:Qs) is commonly used to determine the direction of blood flow, as
well as the severity.
Most patients with only a minor left-to-right shunt (Qp:Qs ratio of less than 1.5:1, e.g. small ASD) will only
require minor anesthetic adjustments, such as avoiding air bubbles in the intravenous line and the risk of paradoxical
air emboli. However, patients with large or unrestrictive left-to-right shunts (e.g. unrestricted VSD) are at
increasingly high risk of heart failure owing to the increased volume load of the heart. For these patients it is
important to limit the amount of pulmonary blood flow by maintaining or slightly increasing pulmonary pressures,
while keeping the systemic vascular resistance low (see table 1). Patients with a significant left-to-right shunt
usually tolerate a balanced anesthetic with positive pressure ventilation, mild permissive hypercapnia, a low inspired
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concentration of oxygen, and the use of vapor anesthetics to decrease the systemic vascular resistance, all of which
will limit the amount of left-to-right shunting. The use of drugs or interventions that increase systemic vascular
resistance or decrease pulmonary vascular resistance should be avoided (see table 1).
The opposite goals apply for patients with a primary right-to-left shunt (e.g. patients with unrepaired Tetralogy
of Fallot, patients with a Glenn shunt, or patients with severe pulmonary hypertension and a VSD). Those patients
not only have a Qp:Qs ratio less than 1.0, but also varying degrees of cyanosis. Drugs and maneuvers that increase
systemic vascular resistance are used to decrease right-to-left shunting and include sympathetic stimulation or
vasoconstrictive medications. Pulmonary vascular resistance can be lowered either pharmacologically (e.g., nitric
oxide or milrinone) or with non-pharmacologic measures such as hyperventilation with a high inspired oxygen
concentration, alkalosis, minimizing positive pressure ventilation or positive end-expiratory pressure, maintaining
normothermia, and lowering catecholamine levels (deep anesthesia, avoiding pain and anxiety). These measures
increase pulmonary blood flow (improve oxygen saturation) but also have the potential to exacerbate preexisting
heart failure symptoms (table 1). It is therefore not recommended to increase oxygen saturation to 100% in every
patient, especially if they are cyanotic at baseline, but rather to maintain their oxygen saturation at baseline. Pulse
oximetry can be used as a simple tool to assess changes in the magnitude and direction of shunting.
To achieve the above-mentioned hemodynamics, many providers use ketamine for induction or as an infusion
for maintenance. Although ketamine carries a potential risk of increasing pulmonary vascular resistance, it routinely
leads to an improvement in pulmonary blood flow, which is most likely due to the increased inotropy of the right
ventricle and the proportionally increased systemic vascular resistance that offsets the increase in pulmonary
vascular resistance. A balanced anesthetic technique that includes vapor anesthetic in combination with an
intravenous opioid and a benzodiazepine, however, is used most frequently. This approach allows a high inspired
oxygen concentration, ideally combined with low mean airway pressures, and can be compensated with inhaled
nitric oxide or milrinone. Regardless of the technique used, a primarily systemic vasopressor (e.g. vasopressin)
should be readily available to counteract decreases in systemic vascular resistance.
Patients with a large right-to-left shunting lesion tend to have a more rapid induction with intravenous agents
because a significant amount of drug bypasses the lungs and therefore reaches its target (the brain) both faster and
relatively less diluted than in a patients without a shunting lesion. The reverse is true for inhaled anesthetics, which
exhibit a slower induction, as blood concentrations rise more slowly; however, very few adults will require an
inhaled induction. There is no clinically significant change in the induction speed with either inhaled or intravenous
induction agents in patients with left-to-right shunting lesions, as long as cardiac output is maintained.
Pulmonary hypertension and/or right ventricular failure

An in-depth review of pulmonary hypertension (PHT) and its treatment is beyond the scope of this review lecture.
Briefly, PHT is classified by the World Health Organization (WHO) according to the underlying disease14. In
patients with CHD, PHT is usually a result of volume and/or pressure overload (WHO class II), or is related to
chronic hypoxia (WHO class III). Despite the often vastly different underlying pathologies, for the purpose of this
review, the management of PHT and right heart failure are grouped together, given that their management strategies
are very similar. Also, encountering PHT or right heart failure is very common for the adult anesthesiologist taking
care of CHD patients, as it can result from a broad spectrum of congenital lesions.
Examples of patients with PHT and right heart failure in the absence of shunts include those status post-
Tetralogy of Fallot repair presenting with pulmonary insufficiency; a patient status post-Mustard procedure for
transposition of the great arteries; or a patient status post-repair of Ebstein anomaly. The most common scenarios
with a shunt (right to left) are patients with Eisenmenger, for example after a longstanding, uncorrected, and
unrestricted VSD.
Similar to patients with right-to-left shunts, the central element in managing these patients is to lower
pulmonary vascular resistance and maintain system vascular resistance (table 1). One must avoid factors that
increase pulmonary vascular resistance such as hypercarbia, hypoxemia, hypothermia, acidosis, stress, pain,
increased mean airway pressures, certain medications, and left-sided heart failure. In the case of right heart failure,
inotropic support is also required (e.g. milrinone). In addition to supporting contractility and lowering afterload, it is
necessary to optimize right ventricular preload, as well as rate and rhythm. Extensive fluid boluses (especially of
cold fluids) and medications that increase pulmonary vascular resistance (e.g. phenylephrine) are very poorly
tolerated. The goals for these patients are to maintain euvolemia; to support contractility while lowering afterload;
and to treat acidosis, hypothermia, and low calcium levels. One potential option is to use vasopressin or
norepinephrine to increase systemic vascular resistance and milrinone or inhaled nitric oxide to lower pulmonary
vascular resistance.
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Single ventricle
The Fontan palliation in its modern form is the common endpoint for many diverse lesions that ultimately are
unsuitable for a two-ventricle repair (e.g. tricuspid atresia, hypoplastic left heart, double outlet right ventricle, or
unbalanced AV-canal)13. The surgical repair to achieve the final Fontan palliation takes many years and is carried
out in stages during childhood. Very briefly, it consists of an initial operation to establish and/or balance pulmonary
blood flow (e.g. Norwood procedure), followed by the first unloading of the single ventricle (Glenn shunt), before
completely separating the circulations (Fontan completion). The adult anesthesiologist will mainly encounter
patients who have already undergone a complete Fontan palliation and who will present either fully compensated or
at different stages of ventricular failure. In all of those patients, blood flows passively from both the superior and
inferior vena cava into the right pulmonary artery, through the pulmonary vasculature into a common atrium, across
an atrioventricular valve into the single ventricle, and finally out of the aorta into the systemic circulation.
Therefore, irrespective of the underlying constellation of lesions that led to the Fontan palliation, the adult anatomy
differs in only three essential features: 1) the location of the inferior vena cava connection to the right pulmonary
artery, 2) the presence or absence of a fenestration between the inferior vena cava to pulmonary artery conduit and
the right atrium, and 3) if the single ventricle is an embryologically derived left or right ventricle (table 2).
(1) Initially the inferior vena cava was kept in continuity with the right atrium and the right atrial appendage
connected to the right pulmonary artery. However, this resulted in severe right atrial dilation, which was a
nidus for clot formation and arrhythmias. The next innovation was to create a tunnel inside the right atrium
that connected the inferior vena cava to the right pulmonary artery. This lowered the amount of right atrial
dilation, but the long suture lines remained a culprit for arrhythmias. The latest development is the creation
of an extracardiac Fontan, in which a conduit is placed between the inferior vena cava and the right
pulmonary artery, eliminating most of the previous problems.
(2) To guarantee adequate ventricular preload in times of increased pulmonary pressures, a fenestration is
sometimes created in the conduit that connects the inferior vena cava to the right pulmonary artery
(especially in patients with only a small transpulmonary pressure gradient). This allows for a small and
restricted left-to-right shunt, which is largely inconsequential at baseline. However if pulmonary pressures
spike, blood can now shunt from right to left, resulting in a minor drop in oxygen saturation, while
maintaining preload of the single ventricle and consequently systemic cardiac output.
(3) The presence of either a congenital left or right ventricle is important for the long-term prognosis, with a
left ventricle being more durable in the long term and probably more robust in terms of its ability to tolerate
acute changes in the perioperative period.
Blood flow to the single ventricle is passive and occurs along a pressure gradient from the Glenn anastomosis
(connection between the inferior and superior vena cava to the right pulmonary artery) across the lung, to the
common atrium. However, only a small pressure gradient is needed for passive pulmonary blood flow and barring
any ventricular failure or atriovalvular regurgitations (both of which increase atrial pressures), central venous
pressure should be either normal or only mildly elevated. It is therefore important to maintain euvolemia, balancing
adequate ventricular preload with the risk of volume overloading the single ventricle. Arterial oxygen saturations
should be normal in patients with a Fontan, and cyanosis should prompt an evaluation for bridging veins that bypass
the lungs and drain directly into the left-sided circulation, i.e. shunting. Other long-term complications in these
patients include venous congestion and pleural effusions, liver congestion, and protein-losing enteropathy.
Management of anesthesia depends on the type and magnitude of surgery, and on the presence and absence of
heart failure. Standard ASA monitors with little change in anesthetic care are sufficient for well-functioning Fontan
patients, especially in cases where minimal hemodynamic changes or fluid shifts are expected. Blood pressure
should be measured on the side contralateral to the previous Blalock Taussig shunt. For more complex procedures or
patients with more severe comorbidities, invasive blood pressure monitoring or central venous access might be
warranted. Central venous pressure (CVP) monitoring obtained via the jugular or subclavian vein will reflect mean
pulmonary artery pressures, rather than CVP. However, central venous lines placed close to a Glenn anastomosis
can potentially cause a clot or disrupt the anastomosis, thereby obstructing blood flow to the lungs and significantly
decreasing preload. Alternatively, CVP can be estimated from a femoral line or a large-bore intravenous catheter
placed peripherally. Lastly, if close cardiopulmonary monitoring is required, and if appropriate equipment and
personnel are available, transesophageal echocardiography can be used to provide direct visualization of cardiac
filling and function, and as a method to calculate cardiac output (table 2).
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Postoperative Management
The postoperative care of adults with CHD is as important as the pre- and intraoperative management. However, a
discussion of the area is beyond the scope of this lecture and is discussed in excellent reviews15. The first decision in
the postoperative care of ACHD patients is to determine appropriate disposition. The choices range from discharge
home for an outpatient procedure, to admission to the floor, to a range of monitored settings including intensive care
units. In our practice, we have a low threshold for admission to a relatively higher level of care. Sometimes it might
be warranted to admit a postsurgical patient undergoing a low-risk procedure to a medical cardiac intensive care,
where there is a higher level of familiarity and expertise with CHD. Unfortunately, there is no easy algorithm to
determine postoperative disposition. As with most patients, it is important to take into account the patient's specific
ACHD history, his/her current cardiac status, comorbidities, and the surgery undertaken. As alluded to, rates of
postoperative complications in this patient cohort are high, and effective handoffs are critical for the effective
continuation of care16. Effective handoffs may even utilize anatomic and physiologic figures to facilitate optimum
management.
Tables:
Table 1: Factors affecting Qp:Qs
Favoring systemic blood flow Favoring pulmonary blood flow

Increase pulmonary vascular resistance Lower pulmonary vascular resistance
 Low inspired oxygen concentration  High inspired oxygen concentration
 Permissive hypercapnia  Mild hyperventilation
 Acidosis  Alkalosis
 Hypothermia  Normothermia
 Elevated mean airway pressures  Low mean airway pressures
(e.g. positive pressure ventilation) (e.g. spontaneous ventilation)
 Catecholamine release  Avoid catecholamine release
(e.g. pain or anxiety) (e.g. pain control)
 Medications  Medications
(e.g. alpha agonists or nitrous oxide) (e.g. iNO or milrinone)
Increase systemic vascular resistance
Lower systemic vascular resistance  Vasopressin
 Vasodilators  Hypothermia
 Neuraxial anesthesia
 General anesthesia
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Table 2: Cheat sheet for single-ventricle patients
Key questions regarding the patient’s anatomy:

 Location of the vena cava to right pulmonary artery anastomosis (lateral tunnel versus extracardiac)
 Presence of a fenestration between the inferior vena cava connection and the right atrium
 Congenital origin of the single ventricle (left or right)
Cautious with:
 Central lines, as they can advance into the right pulmonary artery and clot off the Glenn anastomosis
 Blood pressure measurements on the side of a prior Blalock-Taussig shunt
Hemodynamic goals
 Maintain the transpulmonary gradient with an adequate central venous pressure and low pulmonary
pressure; avoid or minimize:
o Positive pressure ventilation, hypoxia, and hypercarbia
o Pneumoperitoneum
o Non-sinus rhythm
o Air in IVs (increase pulmonary pressures by blocking capillary blood flow)
 Strive for euvolemia; avoid or minimize:
o Prolonged fasting
o Large fluid boluses and volume overload (especially of cold fluids)
 Support the systemic ventricle, low threshold for inotropic support
(especially in the congenital right ventricle)
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Massive Transfusion Protocol in Trauma Anesthesia
Charles E. Smith, MD Cleveland, Ohio
Principle:
A massive transfusion protocol (MTP) is activated in response to a patient in hemorrhagic shock. Once a
patient is in the protocol, the blood bank is able to insure rapid and timely availability of blood components to
facilitate resuscitation. When the protocol is activated, a team approach is required and appropriate support staff are
necessary. Source control of hemorrhage (surgery, interventional radiology) and timely volume resuscitation with
warmed fluids and blood components remains the cornerstone of treatment for civilian trauma. Whole blood is
sometimes available (e.g., military trauma, special ops, and some civilian centers). Once definitive control of
bleeding has been achieved, a restrictive approach to transfusion is done, because of the well-known risks of
transfusion such as multiple organ failure, systemic inflammatory response syndrome, TACO (transfusion
associated circulatory overload), TRALI (transfusion related acute lung injury), increased infection and mortality.
The protocol at MetroHealth Medical Center has been in use since 2008 and also addresses MTP for pediatrics
(Table 1). Since last year, point-of-care viscoelastic coagulation testing has been employed at the authors’ institution
to help guide MTP.
Rationale:
Transfusion of packed red cells (RBCs), plasma, and platelets in a similar proportion as whole blood (e.g.,
1:1:1) minimizes the effects of dilutional coagulopathy and hypovolemia. Retrospective studies in trauma patients
demonstrate a survival advantage of increased plasma: red cell ratio on mortality in massive transfusion after trauma.
Some studies have demonstrated a survival advantage with increased platelet: red cell transfusion ratio. Because these
studies were retrospective, survivor bias may have occurred, in which surviving patients had more opportunity to receive
increased volumes of plasma and/or platelet transfusions, thus potentially leading to higher calculated ratios. Ho et al
examined 26 such studies and found that only 10 of the studies did not have a survival bias for or against 1:1 transfusion
ratios. The American Association of Blood Banks (AABB) and the European Task Force recommend early intervention
with plasma but do not endorse a specific plasma to RBC ratio. More recently, the PROPPR study has been published.
This prospective randomized study was designed to determine the effectiveness and safety of transfusing severely
bleeding trauma patients with plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio. Primary
outcomes were 24-hour and 30-day all-cause mortality. 680 patients were studied at 12 trauma centers. There were no
significant differences in mortality at 24 hours (12.7% in 1:1:1 group vs 17.0% in 1:1:2 group; or at 30 days (22.4% vs
26.1%, respectively). Exsanguination, which was the predominant cause of death within the first 24 hours, was decreased
in the 1:1:1 group (9.2%vs 14.6% in 1:1:2 group); More patients in the 1:1:1 group achieved hemostasis than in the 1:1:2
group (86% vs 78%). There were no between group differences in the frequency of complications such as ARDS,
multiple organ failure, venous thromboembolism, sepsis, and transfusion-related complications. Limitations of the study
were that both groups had a low occurrence of massive transfusion (45% of the 1:1:1 group vs. 47% of the 1:1:2 group),
use of cryoprecipitate was not controlled, and many patients in both groups died of traumatic brain injury, not
hemorrhagic shock. It is important to note that the important question of goal-directed vs ratio-driven blood product
resuscitation was not addressed in the PROPPR trial.
Definitions:
The traditional definition of massive transfusion in trauma is 1 blood volume transfusion in a 24 hr period. A
commonly used definition in the scientific literature is > 10 units RBCs in 24 hours. Both of these definitions are
reasonable, but are not practical in an ongoing resuscitation. Other definitions include: loss of 0.5 blood volume within 3
hours; use of at least 5 units RBCs in 4 h; use of 6 units RBCs in 12 hours. From a practical standpoint, requirement for >
4 RBC units in 1 hour with ongoing need for transfusion, or blood loss > 150 ml/min with hemodynamic instability and
need for transfusion are reasonable definitions in the setting of a MTP situation. The variability in defining massive
bleeding results in variability initiating a MTP.
Predicting Need for MTP in Trauma

3-5% of civilian adult trauma patients receive massive transfusion. Early identification of patients requiring
MTP has been evaluated by assigning a value of 0 or 1 to the following four parameters: penetrating mechanism,
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positive FAST for fluid (focused assessment sonography in trauma), arrival systolic BP <90 mm Hg, and arrival
pulse >120 bpm. A score of 2 or more is considered positive. The score is 75% sensitive and 85% specific. Patients
receiving uncross-matched RBCs in the emergency department are three times more likely to receive massive
transfusion. In military trauma, casualties presenting with any two of four possible variables (heart rate >110 bpm,
systolic blood pressure <110 mm Hg, base deficit < -6, and hemoglobin <11 g/dl) had a 54% incidence of massive
transfusion. More recently, the massive transfusion score (MTS), traumatic bleeding severity score (TBSS), and
trauma associated severe hemorrhage scores (TASH), have been employed. The MTS is calculated at initial
presentation using the following parameters: systolic BP < 90 mmHg, base deficit < -6, temperature < 35.5 C, INR >
1.5, hemoglobin < 11 g/dL. The TBBS assigns points based on age, systolic BP after rapid infusion of 1 L of
crystalloid, FAST scan findings, pelvic fracture type, and lactate. TBBS > 15 had high sensitivity and specificity for
predicting massive transfusion (97% sensitive and 96% specific). The TASH score is based on clinical and lab data
including gender, hemoglobin, base deficit, systolic BP, heart rate, positive FAST, unstable pelvic fracture, and open
or dislocated femur fracture.
Pathophysiology of Hemorrhagic Shock in Trauma:

Major trauma causes tissue injury and hemorrhage. Shock occurs due to decreased circulating volume, cardiac
output and oxygen delivery which is compounded by inflammation, acidosis, and tissue hypoperfusion. Hypothermia is
aggravated by altered thermoregulation, environmental exposure, and initial resuscitation with unwarmed fluids.
Aggressive crystalloid fluid resuscitation leads to hemodilution with decreased oxygen carrying capacity and dilution of
coagulation factors. Progressive coagulopathy leads to further hemorrhage and shock. Refractory coagulopathy,
progressive hypothermia and persistent metabolic acidosis lead to end stage shock and death. Circulatory derangements
on CT scans such as flat inferior vena cava (marker of hypovolemia) and the presence of shock bowel (marker of
hypoperfusion) show strong correlation with injury severity, resuscitation needs, and clinical outcomes.
Mechanism(s) of Trauma-Induced Coagulopathy:

The coagulation disturbance in trauma is more than just the result of consumption of clotting factors at sites
of injury and dilution from the infusion of fluids and RBCs. In 2003, Brohi et al analyzed a cohort of 1088 trauma
patients and found that 24% had a coagulopathy on arrival. Patients presenting abnormal laboratory test results had a
higher rate of death (46% vs 11%). The incidence of coagulopathy was strongly associated with the injury severity
score, suggesting that the degree of tissue injury and/or hypoperfusion was a causative factor. Acute coagulopathy
appears to be due to activation of anticoagulant and fibrinolytic pathways. The thrombomodulin–protein C pathway
has been implicated. Shock and hypoperfusion are key drivers of the trauma-induced coagulopathy of trauma.
According to Frith and Brohi, hypoperfusion increases the expression of thrombomodulin on endothelium which
then complexes with thrombin. This reduces the amount of thrombin available to produce fibrin and increases
circulating concentrations of anticoagulant activated protein C.
In trauma, hypothermia and acidosis play a key role by reducing thrombin generation due to altered enzyme
kinetics. Both coagulation factors and platelets are reduced by hemodilution. Platelet count is higher than predicted
due to release of platelets sequestered in the spleen and lungs. Antithrombin activity decreases to less than 30% of
normal with extensive hemodilution. A threshold level of fibrinogen 1g/L (100 mg/dL) is reached after losing 150%
of circulating blood volume as opposed to 200% for clotting enzymes. Systemic hyperfibrinolytic states may be seen
in up to 20% of trauma patients. Fibrinolysis is significantly increased due to dilution of FXIII and α2 –antiplasmin
which reduces fibrin cross-linking, decreases resistance to fibrinolysis and prolongs plasmin half-life. Plasminogen
activator inhibitor is decreased, prolonging tissue plasminogen activator (tPA) activity. Stress, thrombin,
epinephrine, vasopressin, desmopressin, and bradykinin trigger tPA release. Excessive fibrinolysis contributes to
coagulopathy and is associated with increased mortality.
Recommendations for Resuscitation during MTP:

In addition to a MTP, all efforts must be directed towards damage control resuscitation including control of
bleeding and correction of hypothermia, acidosis, shock, and coagulopathy. Before reaching the hospital, hemostatic
dressings and tourniquets are liberally used to minimize and prevent ongoing blood loss. Limiting the use of isotonic
crystalloid will help prevent dilutional coagulopathy. Permissive hypotension (systolic BP pressure 80-100 mmHg)
until bleeding is controlled is generally recommended, unless there is concern for brain or spinal cord injury. Early
use of plasma, platelets as well as RBCs is necessary. Use of O positive RBCs (instead of O negative) and group A
plasma (instead of AB) may be necessary due to limited availability of “universal donor” components. Liquid
plasma (never frozen plasma) can be used instead of thawed FFP. Fibrinogen levels above 1.5 g/L (150 mg/dL) are
targeted, using cryoprecipitate 50 mg/kg or fibrinogen concentrate doses of 3-4 g. Base deficit and lactate are
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monitored to assess adequacy of resuscitation. Electrolyte abnormalities are corrected (e.g., hypocalcemia from
citrated anticoagulants). Early administration of tranexamic acid to adult trauma patients results in reduced all-cause
mortality, reduced mortality from bleeding and a safe side effect profile in bleeding trauma patients. The use of
coagulation factors (4 factor prothrombin complex concentrates- PCCs and fibrinogen concentrates) has been
adopted in some centers, especially Europe in conjunction with point of care coagulation testing (see below). Use of
rFVIIa merits consideration in trauma patients undergoing massive transfusion who continue to exsanguinate, with
an understanding of the limitations of its effect (see section below). Massive transfusion in pediatric patients remains
poorly defined, although a threshold of 40 mL/kg of all blood products given at any time in the first 24 hours
reliably identified pediatric massive transfusion in a military setting.
Coagulation Testing in Trauma:

Standard coagulation tests such as PT, PTT, INR, platelet count, and fibrinogen usually require 30–60
minutes for results to be available. For patients requiring acute interventions, results may not be an accurate
reflection of coagulation function. The use of point of care viscoelastic testing [thromboelastography (TEG) and
thromboelastomety (ROTEM)] is becoming an integral part of the evaluation of trauma-induced coagulopathy.
Protocols and transfusion algorithms can direct a focused approach to appropriately resuscitate trauma patients while
reducing exposure of trauma patients to allogeneic blood products. For example, by using ROTEM-guided
hemostatic therapy with fibrinogen concentrate and prothrombin complex concentrate, Schochl et al were able to
reduce exposure of bleeding trauma patients to allogeneic blood products without any increase in morbidity and
mortality. Moore et al and Cotton et al have shown that parameters derived from viscoelastic tests have been shown
to predict transfusion requirements in patients with trauma
These point of care hemostatic assays provide a graph of the displacement caused by viscoelastic changes in
whole blood as clotting progresses and fibrin strands form between the cup and pin. Clot strength is decreased by
hypofibrinogenemia, thrombocytopenia, low FXIII level, or reduced thrombin generation. Rapid TEG (coagulation
is initiated by the addition of tissue factor) gives faster results compared to kaolin TEG. ROTEM, EXTEM (uses
recombinant tissue factor to activate coagulation) and FIBTEM (measures contribution of fibrinogen to clot
strength) allow differential diagnosis of thrombocytopenia and hypofibrinogenemia. The key parameter obtained
from TEG/ROTEM is Maximum Amplitude/Maximum Clot Firmness (MA/MCF), which reflect the extent of
thrombin-mediated platelet activation and fibrin polymerization. Plasma fibrinogen levels can be estimated by
fibrin-specific tests on TEG (functional fibrinogen) and ROTEM (FIBTEM).
Use of TEG/ROTEM does not exclude the need to evaluate PT/INR and platelets. Neither TEG nor ROTEM
have particularly good sensitivity for vitamin K factor deficiency. Dynamic hematocrit changes can also affect the
MA/MCF; Disorders of primary hemostasis such as von Willebrand’s disease cannot be determined with
ROTEM/TEG, nor do the effects of aspirin and clopidogrel on platelets influence the results. Platelet aggregation
inhibitors which affect the glycoprotein IIb/IIIa receptors may reduce clot strength at high doses. Despites these
caveats, transfusion algorithms incorporating viscoelastic testing are employed in major bleeding trauma patients
across European level 1 trauma centers and are increasingly being employed in the USA and other countries.
Factor Concentrates and MTP in Trauma:

Factor concentrate therapy offers the advantage of smaller volumes of resuscitative fluids directed at specific
phases of coagulation as identified by hemostatic assays. Fibrinogen plays a major role in hemostasis and is now
commercially available as fibrinogen concentrate made from human pooled plasma. The fibrinogen content of
fibrinogen concentrate is 15-20 mg/mL per 50-100mL vials. To increase fibrinogen concentration by 100mg%, one
can administer 3-4 g F 1 (approximately 50 mg/kg). Three factor PCC (prothrombin complex concentrate) contains
Factor II, IX and X. Four factor PCC contains F II,VII, IX and X. PCCs are utilized to acutely reverse
anticoagulation therapy, especially warfarin and targets the early phase of clot formation. 4F-PCC is well suited to
the treatment of trauma induced coagulopathy as it contains factors from the extrinsic pathway which is activated
during tissue damage after trauma. Bothe 3F and 4F-PCCs are available in the United States. PCC has an established
record of reversing coagulopathy in brain injured patients on warfarin. FVIIa can reverse coagulation abnormalities
and decrease blood loss. However, a well-defined outcome benefit is less clear. Although fibrinogen and PCC can
correct coagulation abnormalities and reduce blood product usage, their outcome benefit has not yet been
demonstrated in well powered prospective trials and there is a risk of thromboembolism.
Complications of MTP in Trauma:

Blood transfusion is an independent predictor of multi-organ failure in a retrospective and prospective
study of trauma patients with injury severity score > 15 and survival greater than 24 hours. There is a 2-6 fold
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increase in SIRS, 4 fold increase in ICU admission and mortality in transfused patients. One study showed that
transfusion was an independent predictor of death in non-operative blunt trauma and the risk of death increased with
each additional RBC unit. In a retrospective review of 1312 patients, the mean transfusion volume for elderly
survivors vs young was 4.6 units vs 6.7 units; No patient over age 75 who was transfused > 12 units RBCs survived.
In a meta-analysis of 20 studies, the odds ratio for bacterial infection in transfused vs non-transfused patients was
3.45. The odds ratio increased to 5.26 in the subgroup analysis for trauma patients. TRALI is likely under-diagnosed
after trauma since it is difficult to differentiate from other causes of lung injury in trauma. In transfusion associated
micro-chimerism, a small population of donor hematopoetic stem cells may engraft into the recipient, persisting
sometimes for years.
MTP after the Bleeding has Stopped:

A restrictive approach to blood product utilization is advocated once hemorrhage is controlled and the
patient is stable. The MTP is discontinued (requires a phone call to Blood Bank). Prompt return of blood products to
the blood bank may help minimize RBC, plasma and platelet wastage associated with fixed ratio transfusion
protocols. Signs and symptoms of impaired oxygen delivery and decreased tissue perfusion are closely monitored.
RBC transfusion is generally required for anemia in the setting of persistent base deficit, lactic acidosis, and signs of
end organ ischemia.
Summary:
The use of a MTP facilitates rapid availability of components in an increased ratio of plasma and platelets to
RBCs. Increased ratios of plasma and platelets to RBCs and their early administration are associated with improved
outcome in trauma, decreased coagulopathy and decreased overall transfusion requirements. MTPs have also been
developed for pediatrics, although a recent survey of hospitals in the USA and Canada showed wide variation with
regard to both activation criteria and blood products administered. A restrictive transfusion strategy should be
adopted once hemorrhage is controlled to minimize unnecessary exposure to blood. There are many unresolved
issues with MTP including use of fibrinogen concentrates, PCCs, optimal timing and ratios of product, transfusion
algorithms, and point-of care testing. Prospective randomized trials are underway to determine optimal timing of
blood component administration (e.g.,PAMPer study- Prehospital Air Medical Plasma). Another trial aims to
compare goal-directed hemostatic resuscitation using viscoelastic tests vs a fixed ratio transfusion protocol (e.g.,
Targeted Action For Curing Trauma Induced Coagulopathy). Better understanding of trauma-induced coagulopathy
is clearly needed (e.g., Secondary outcomes analysis of PROPPR database; The Trans-Agency Research Consortium
for Trauma-Induced Coagulopathy- TACTIC; Traumatic Coagulopathy & Massive Transfusion - Improving
Outcomes & Saving Blood).
Table 1. Massive Transfusion Protocol @ MetroHealth Medical Center, Cleveland, Ohio
The clinician contacts the Blood Bank and activates the MTP. There are 3 types of patients (Adult, Large Child or
Small Child). Once a particular patient is identified as being entered into the Massive Transfusion Protocol, the
following procedure is followed. This situation is encountered in surgical or medical emergencies as well as in
trauma.
SPECIMEN:
Pre- or post-transfusion blood sample (signed, 7mL pink top tube) from massively transfused patient .
QUALITY CONTROL:
See procedure: DAILY REAGENT QUALITY CONTROL
MATERIALS/REAGENTS:
See procedure ABO GROUPING, D ANTIGEN TESTING, ANITBODY SCREENING TEST, COMPATIBILITY
TESTING
PROCEDURE
Section I – MTP General Procedure:
1. When clinician contacts Blood Bank on the distinct-ring, MTP Hot-line phone and gives a verbal order to
begin the MTP on a patient, complete a pink verbal PHONE ORDER form. Record two patient identifiers,
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the date, location, the physician’s name/PIN #, and the person calling and initiating the MTP. Assume that
the patient is an adult unless the order is stated for a Small Child or Large Child.
2. A properly labeled blood sample should be submitted to the Blood Bank as soon as possible.
3. A runner will be provided by the area in which the patient is residing to obtain the products from the Blood
Bank. On the off-shifts and weekends, a call should be placed, by the Trauma Team or their designee in the
Trauma Bay, to the nursing supervisor for assistance with runner resource identification. If a runner cannot
be provided, the Blood Bank will tube the blood to the appropriate area providing the area is approved to
receive tubed blood products.
4. FIRST MTP PACK (ADULT) - Collect the 4 O Negative RBCs and 2 AB plasma units already set-up for
Emergency Release. Pack in a Blood Bank Insulated Cooler. Complete the pink ALERT label for the
insulated cooler [BLOOD STORAGE TRACKING SHEET +INSULATED COOLER SIGN-OUT
SHEET. See procedure BB1 65.0 – Transportation of Blood in an Insulated Cooler.
5. As soon as the 1st MTP pack is issued, begin preparing the 2nd MTP pack.
6. If a sample has not yet been submitted contact the Blood Bank Medical Director and inquire as to whether
the patient should be switched to O Rh Positive.
7. SECOND ADULT AND ALL SUBSEQUENT ADULT MTP PACKS CONSIST OF THE
FOLLOWING–
-6 units of RBCs (O Neg/Pos or type specific if sample has been submitted)
-4 units of Plasma (AB or type specific if sample has been submitted)
-A/AB platelets (one 5-day pool or 1 apheresis platelet product) as available
-Second Insulated Cooler
-Necessary Emergency Release/Insulated Cooler paperwork
8. As soon as the 2nd MTP pack is issued, begin preparing the 3rd MTP pack.
9. Third and subsequent packs should have the RBCs crossmatched using the BB1 43.0 -Massive Transfusion
Abbreviated Crossmatch Procedure since 10 RBCS will at that point be issued in less than a 24 hour
period.
10. Continue with preparing an MTP PACK after an MTP pack has been issued until the Blood Bank has been
notified by a clinician to discontinue the MTP. Record on a verbal Phone Order the two patient
identifiers,the date, location, the physician’s name/PIN #, and the person calling to inactivate the MTP
order.
11. The Small and Large Child MTP Protocol is as follows:
Small Children (< 30kg)
MTP Pack 1 MTP Pack 2 MTP Pack 3 MTP Pack 4

2 units of PRBCs 2 units of PRBCs 2 units of PRBCs 2 units of PRBCs
2 units of FFP 2 units of FFP 2 units of FFP 2 units of FFP
(½) 6 pack plts (½) 6 pack plts (½) 6 pack plts
6 units, pooled cryo 6 units, pooled cryo
Large Children (30kg- 50kg)
MTP Pack 1 MTP Pack 2 MTP Pack 3 MPT Pack 4

4 units of PRBCs 4 units of PRBCs 4 units of PRBCs 4 units of PRBCs
2 units of FFP 4 units of FFP 4 units of FFP 4 units of FFP
(1) 6 pack ptls (1) 6 pack ptls (1) 6 pack ptls
6 units, pooled cryo 6 units, pooled cryo
.
PROCEDURAL NOTES:
1. Once the second MTP PACK has been issued, the BB1 43.0 - Massive Transfusion Abbreviated
Crossmatch Procedure may be initiated since 10 units of RBCs will have been issued.
2. If no sample has been received after a patient has received 10 RBCs, the Blood Bank Medical Director has
approved switching to O POS RBCs under the following circumstances:
a. The patient is male. One must obtain the person’s name and division, PIN number or
b. employee number and document this under the C button in Safetrace.
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c. The patient has received 10 RBCs in 24 hours or less.

d. No sample has been received for testing.
3. Clinician should send a blood sample to the Blood Bank as soon as possible (signed, 7mL pink top tube via
pneumatic tube station 122 or via a runner.
4. Since there are only 4 Insulated Coolers, remind runners to bring back the empty Insulated Cooler, with the
completed paperwork, each time they come back for another MTP pack of blood so that Blood Bank tech
can pack the next MTP pack in it. Remind runner to also bring any completed Emergency Release forms
and INSULATED COOLER – BLOOD STORAGE TRACKING SHEETs.
5. As long as RBCs and Plasma remain in properly packed insulated cooler, their storage is good for up to 8
hours and may be returned to inventory if not used and otherwise acceptable.
6. Keep ahead as much as possible with the platelet orders. Order two 6-packs of platelets from the blood
supplier each time a courier run of platelets is needed during an MTP.
7. If it is discovered that the patient has a history of clinically significant alloantibodies, all RBC units
prepared for the patient MUST be screened antigen negative for the patient's antibody(ies) if possible. It is
important to remember that the patient's antibody(ies) may not be demonstrating due to dilution with large
volumes of donor blood and components, but if antigen positive units were infused they would have
shortened survival.
8. In the above situation, antigen positive blood may be issued upon written or verbal approval of the Blood
Bank Medical Director. Document approval on the Emergency Blood Product Release Request Form. If the
request is at a time when the Blood Bank Medical Director is unavailable, the ER physician may sign for
the antigen positive blood and the Blood Bank Medical Director and/or Blood Bank Supervisor should be
notified that day. Record this event in the deviation book for Blood Bank Medical Director to review and
sign. Notify clinician or nurse of the situation. Document who you spoke to in Patient Comments in LIS.
As soon as possible, units should be tested for the antigen and the test results conveyed to the
Supervisor/Medical Director for guidance.
9. Patients involved in a Massive Transfusion Protocol (see procedure) will only receive RBCs crossmatched
via the abbreviated method once the Blood Bank has issued 10 units of RBCs and not before.
10. Paperclip the start and stop verbal PHONE ORDERs to the Emergency Release forms for the Medical
Director review.
11. The Trauma Team must sign all blood products in and out of the coolers and complete all Emergency
Release of Blood Products forms and return them to the Blood Bank.
REFERENCES:
AABB Technical Manual, Current Edition.
AABB Standards, Current Edition
MHMC Policy, 2008, Revised- 7/2010
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Hemorrhagic and Infectious Complications of Neuraxial Anesthesia

Terese T. Horlocker, M.D. Rochester, Minnesota
Spinal Hematoma
The actual incidence of neurologic dysfunction resulting from hemorrhagic complications associated with neuraxial blockade
is unknown; however, recent epidemiologic studies suggest the incidence is increasing (1). In a review of the literature between 1906
and 1994, Vandermeulen et al. (2) reported 61 cases of spinal hematoma associated with epidural or spinal anesthesia. In 87% of
patients, a hemostatic abnormality or traumatic/difficult needle placement was present. More than one risk factor was present in 20
of 61 cases. Importantly, although only 38% of patients had partial or good neurologic recovery, spinal cord ischemia tended to be
reversible in patients who underwent laminectomy within eight hours of onset of neurologic dysfunction.
It is impossible to conclusively determine risk factors for the development of spinal hematoma in patients undergoing
neuraxial blockade solely through review of the case series, which represent only patients with the complication and do not define
those who underwent uneventful neuraxial analgesia. However, large inclusive surveys that evaluate the frequencies of
complications (including spinal hematoma), as well as identify subgroups of patients with higher or lower risk, enhance risk
stratification. In the series by Moen et al. (3) involving nearly 2 million neuraxial blocks, there were 33 spinal hematomas. The
methodology allowed for calculation of frequency of spinal hematoma among patient populations. For example, the risk associated
with epidural analgesia in women undergoing childbirth was significantly less (1 in 200,000) than that in elderly women undergoing
knee arthroplasty (1 in 3600, p<0.0001). Likewise, women undergoing hip fracture surgery under spinal anesthesia had an increased
risk of spinal hematoma (1 in 22,000) compared to all patients undergoing spinal anesthesia (1 in 480,000).
Overall, these series suggest that the risk of clinically significant bleeding varies with age (and associated abnormalities of the
spinal cord or vertebral column), the presence of an underlying coagulopathy, difficulty during needle placement, and an indwelling
neuraxial catheter during sustained anticoagulation (particularly with standard heparin or LMWH). They also consistently demonstrate
the need for prompt diagnosis and intervention. Practice guidelines or recommendations summarize evidence-based reviews. However,
the rarity of spinal hematoma defies a prospective-randomized study, and there is no current laboratory model. As a result, the
consensus statements developed by the American Society of Regional Anesthesia and Pain Medicine represent the collective
experience of recognized experts in the field of neuraxial anesthesia and anticoagulation (4). They are based on case reports, clinical
series, pharmacology, hematology, and risk factors for surgical bleeding. An understanding of the complexity of this issue is essential to
patient management.
Oral Anticoagulants
Clinical experience with patients who, congenitally, are deficient in factors II, IX, or X suggests that a factor activity level
of 40% for each factor is adequate for normal or near-normal hemostasis. Bleeding may occur if the level of any clotting factor is
decreased to 20% to 40% of baseline. The PT is most sensitive to the activities of factors VII and X and is relatively insensitive to
factor II. During the first few days of therapy, the PT reflects primarily a reduction of factor VII, the half-life of which is
approximately 6 hrs. After a single dose, marked prolongation of the INR may occur, although adequate factor levels are still
present. However, with additional doses, an INR greater than 1.4 is typically associated with factor VII activity less that 40% (and
the potential for inadequate clotting) (5).
Few data exist regarding the risk of spinal hematoma in patients with indwelling epidural catheters who are anticoagulated
with warfarin. The optimal duration of an indwelling catheter and the timing of its removal also remain controversial. Odoom and Sih
(6) performed 1000 continuous lumbar epidural anesthetics in vascular surgical patients who were receiving oral anticoagulants
preoperatively. The thrombotest (a test measuring factor IX activity) was decreased (but not below 10% activity) in all patients prior to
needle placement. Heparin was also administered intraoperatively. Epidural catheters remained in place for 48 hours postoperatively.
There were no neurologic complications. While these results are reassuring, the obsolescence of the thrombotest as a measure of
anticoagulation combined with the unknown coagulation status of the patients at the time of catheter removal limit the usefulness of
these results. Therefore, except in extraordinary circumstances, spinal or epidural needle/catheter placement and removal should not be
performed in fully anticoagulated patients.
There were no symptomatic spinal hematomas in two smaller series with a total of nearly 700 patients undergoing
neuraxial block in combination with warfarin anticoagulation perioperatively (6-8). In both studies, epidural catheters were left
indwelling approximately two days. The mean international normalized ratio (INR) at the time of catheter removal was 1.4,
although in a small number of patients the INR was therapeutic (2.0-3.0). A large variability in patient response to warfarin was also
noted, demonstrating the need for close monitoring of the coagulation status. There were no spinal hematomas in a series of 11,235
patients receiving epidural analgesia after total knee replacement (9). Patients received warfarin (5-10 mg) starting the night of
surgery. Epidural catheters were removed within 48 hrs. The mean INR in a subset of 1030 patients at the time of catheter removal
was 1.5 (range, 0.9-4.3); the INR was less than 1.5 in nearly 40% of patients. These series suggest that not only the INR but also the
duration of warfarin therapy must be considered and that prolongation within the first 48 hrs may represent a significant increase in
risk.
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Intravenous and Subcutaneous Standard Heparin

The safety of neuraxial techniques in combination with intraoperative heparinization is well documented, providing no other
coagulopathy is present. In a study involving over 4000 patients, Rao and El-Etr (10) demonstrated the safety of indwelling spinal and
epidural catheters during systemic heparinization during vascular surgery. However, the heparin was administered at least 60 minutes
after catheter placement, level of anticoagulation was closely monitored, and the indwelling catheters were removed at a time when
circulating heparin levels were relatively low. A subsequent study in the neurologic literature by Ruff and Dougherty (11) reported
spinal hematomas in 7 of 342 patients (2%) who underwent a diagnostic lumbar puncture and subsequent heparinization. Traumatic
needle placement, initiation of anticoagulation within one hour of lumbar puncture and concomitant aspirin therapy were identified as
risk factors in the development of spinal hematoma in anticoagulated patients. Subsequent studies using similar methodology have
verified the safety of this practice, provided the monitoring of anticoagulant effect and the time intervals between heparinization and
catheter placement/removal are maintained.
Low-dose subcutaneous standard (unfractionated) heparin is administered for thromboprophylaxis in patients undergoing
major thoracoabdominal surgery and in patients at increased risk of hemorrhage with oral anticoagulant or low molecular weight
heparin (LMWH) therapy. There are nine published series totaling over 9,000 patients who have received this therapy without
complications(12), as well as extensive experience in both Europe and United States without a significant frequency of
complications. There are only five case reports of neuraxial hematomas, four epidural (2,13) and one subarachnoid,(14) during
neuraxial block with the use of subcutaneous heparin.
The largest study of thrice daily unfractionated heparin involved 768 epidural catheter placements. Sixteen patients from this
group had a positive match for hemorrhage codes on their discharge records, with none of the episodes being identified within a
major hemorrhage category. Laboratory value analysis failed to reveal changes in the aPTT values of significance (4). The safety of
neuraxial blockade in patients receiving doses greater than 10,000 U of UFH daily or more than twice-daily dosing of UFH has not
been established. Although the use of thrice-daily UFH may lead to an increased risk of surgical-related bleeding, it is unclear
whether there is an increased risk of spinal hematoma. If thrice-daily unfractionated heparin is administered, techniques to facilitate
detection of new/progressive neurodeficits (eg, enhanced neurologic monitoring occur and neuraxial solutions to minimize sensory
and motor block) should be applied.
Low Molecular Weight Heparin

Extensive clinical testing and utilization of LMWH in Europe over the last ten years suggested that there was not an increased risk of
spinal hematoma in patients undergoing neuraxial anesthesia while receiving LMWH thromboprophylaxis perioperatively (2,15).
However, in the five years since the release of LMWH for general use in the United States in May 1993, over 60 cases of spinal
hematoma associated with neuraxial anesthesia administered in the presence of perioperative LMWH prophylaxis were reported to the
manufacturer (16,17). Many of these events occurred when LMWH was administered intraoperatively or early postoperatively to
patients undergoing continuous epidural anesthesia and analgesia. Concomitant antiplatelet therapy was present in several cases. The
apparent difference in incidence in Europe compared to the United States may be a result of a difference in dose and dosage schedule.
For example, in Europe the recommended dose of enoxaparin is 40 mg once daily (with LMWH therapy initiated 12 hours
preoperatively), rather than 30 mg every twelve hours. However, timing of catheter removal may also have an impact. It is likely that
the lack of a trough in anticoagulant activity associated with twice daily dosing resulted in catheter removal occurring during significant
anticoagulant activity. Importantly, there are no data to suggest that the risk of spinal hematoma is increased with specific LMWH
formulations (16). The incidence of spinal hematoma in patients undergoing neuraxial block in combination with LMWH has been
estimated at 1 in 40,800 spinal anesthetics and 1 in 3100 continuous epidural anesthetics (18). It is interesting in that the frequency of
spinal hematoma in this series is similar to that reported by Moen et al (3) for women undergoing total knee replacement with epidural
analgesia.
Indications for thromboprophylaxis as well as treatment of thromboembolism or MI have been introduced. These new
applications and corresponding regional anesthetic management warrant discussion (19). Several off-label applications of LMWH are
of special interest to the anesthesiologist. LMWH has been demonstrated to be efficacious as a “bridge therapy” for patients
chronically anticoagulated with warfarin, including parturients, patients with prosthetic cardiac valves, a history of atrial fibrillation,
or preexisting hypercoagulable condition. The doses of LMWH are those associated with DVT treatment, not prophylaxis, and are
much higher. An interval of at least 24 hours is required for the anticoagulant activity to resolve.
Dabigatran
Dabigatran etexilate is a prodrug that specifically and reversibly inhibits both free and clot-bound thrombin. The drug is absorbed
from the gastrointestinal tract with a bioavailability of 5%(20). Once absorbed it is converted by esterases into its active
metabolite, dabigatran. Plasma levels peak at two hours. The half-life is eight hours after a single dose and up to 17 hours after
multiple doses. It is likely that once daily dosing will be possible for some indications because of the prolonged half-life. Because
80% of the drug is excreted unchanged by the kidneys, it is contraindicated in patients with renal failure(21). Dabigatran prolongs
the aPTT, but its effect is not linear and reaches a plateau at higher doses. However, the ecarin clotting time (ECT) and thrombin
time (TT) are particularly sensitive and display a linear dose response at therapeutic concentrations. Reversal of anticoagulant
effect is theoretically possible through administration of recombinant factor VIIa, although this has not been attempted
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clinically(21). Indeed, product labeling suggests that dialysis may be considered for patients with significant bleeding due to
dabigatran.
Rivaroxaban
Rivaroxaban is a potent selective and reversible oral activated factor Xa inhibitor, with an oral bioavailability of 80%. After
administration, the maximum inhibitory effect occurs one to four hours, however, inhibition is maintained for 12 hours. The
antithrombotic effect can be monitored with the PT, aPTT and Heptest, all of which demonstrate linear dose effects. Rivaroxaban
is cleared by the kidneys and gut. The terminal elimination half-life is nine hours in healthy volunteers and may be prolonged to
13 hours in the elderly due to a decline in renal function (hence a need for dose adjustment in patients with renal insufficiency
and contraindicated in patients with severe liver disease).
Rivaroxaban was approved in the United States for thromboprophylaxis following total hip or knee replacement in
2011. Overall, clinical trials comparing rivaroxaban (5- 40mg mg daily, with the first dose six to eight hours after surgery) with
enoxaparin (40 mg, beginning 12 hours before surgery) demonstrate similar rates of bleeding and comparable efficacy. While a
“regional anesthetic” was performed in over half of the patients included in the clinical trials, no information regarding needle
placement or catheter management was included. Although there have been no reported spinal hematomas, the lack of
information regarding the specifics of block performance and the prolonged half-life warrants a cautious approach.
A minimum of three days should elapse between discontinuation of rivaroxaban and neuraxial block. Indwelling
neuraxial catheters are contraindicated due to the “boxed warning”. Likewise, indwelling neuraxial catheters should be removed
six hours prior to initiation of rivaroxaban therapy postoperatively.
Apixaban
Apixaban inhibits platelet activation and fibrin clot formation via direct, selective and reversible inhibition of free and clot-bound
factor Xa. , The oral bioavailability is 50%. After administration, the maximum inhibitory effect occurs in three to four hours,
however, inhibition is maintained for 12 hours. Apixaban is cleared by the liver and kidneys. The terminal elimination half-life is
12 hours in healthy volunteers and may be prolonged in patients with renal impairment.
A minimum of three days should elapse between discontinuation of apixaban and neuraxial block. Indwelling neuraxial catheters
are contraindicated and should be removed six hours prior to initiation of rivaroxaban therapy postoperatively.
Table 1 Recommendations for Management of Patients Receiving Neuraxial Blockade and Anticoagulant Drugs
Warfarin Discontinue chronic warfarin therapy 4–5 days before spinal procedure and evaluate INR. INR should be within
the normal range at time of procedure to ensure adequate levels of all vitamin K-dependent factors.
Postoperatively, daily INR assessment with catheter removal ideallyoccurring with INR< 1.5; monitor carefully
for 1.5 < INR < 3.0
Antiplatelet medications No contraindications with aspirin or other NSAIDs. Thienopyridine derivatives should be discontinued to allow
complete recovery of platelet function (clopidogrel 5-7 days, ticlodipine 10 days, prasugrel 7-10 days, and
ticagrelor 5-7 days) prior to procedure. GP IIb/IIIa inhibitors should be discontinued to allow recovery of platelet
function prior to procedure (8 hours for tirofiban and eptifibatide, 24–48 hours for abciximab).
Thrombolytics/ There are no available data to suggest a safe interval between procedure and initiation or discontinuation of these
fibrinolytics medications. Follow fibrinogen level and observe for signs of neural compression.
LMWH Delay procedure at least 12 hours from the last dose of thromboprophylaxis LMWH dose. For "treatment" dosing
of LMWH, at least 24 hours should elapse prior to procedure. LMWH should not be administered within 24 hours
after the procedure. Indwelling epidural catheters should be maintained only with once daily dosing of LMWH
and strict avoidance of additional haemostasis altering medications, including NSAIDs. Post catheter removal,
wait 4 hrs for subsequent LMWH dose.
Unfractionated SQ heparin There are no contraindications to a neuraxial procedure if dose is ≤ 5000 units and total daily dose is ≤ 15,000
units. For higher dosing regimens, increase neurologic monitoring and cautiously co-administer antiplatelet
medications.
Unfractionated IV heparin Delay needle/catheter placement 2–4 hours after last dose, document normal aPTT. Heparin may be restarted 1
hour following procedure. Sustained heparinization with an indwelling neuraxial catheter associated with
increased risk; monitor neurologic status aggressively.
Dabigatran Discontinue 5 days prior to procedure; for shorter time periods, document normal TT. First postoperative dose 24
h after needle placement and 6 hours post catheter removal (whichever is later).
Rivaroxaban, Apixaban, and Discontinue 3 days prior to procedure. First postoperative dose 24 h after needle placement and 6 hours post
Edoxaban catheter removal (whichever is later).
Antiplatelet Medications
Antiplatelet medications are seldom used as primary agents of thromboprophylaxis. However, many orthopedic patients report
chronic use of one or more antiplatelet drugs. Although Vandermeulen et al (2) implicated antiplatelet therapy in 3 of the 61
cases of spinal hematoma occurring after spinal or epidural anesthesia, several large studies have demonstrated the relative safety
of neuraxial blockade in both obstetric, surgical and pain clinic patients receiving these medications (22-24). In a prospective
study involving 1000 patients, Horlocker et al (24) reported that preoperative antiplatelet therapy did not increase the incidence
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of blood present at the time of needle/catheter placement or removal, suggesting that trauma incurred during needle or catheter
placement is neither increased nor sustained by these medications. The clinician should be aware of the possible increased risk of
spinal hematoma in patients receiving antiplatelet medications who undergo subsequent heparinization (11). Ticlopidine and
clopidogrel are also platelet aggregation inhibitors. These agents interfere with platelet-fibrinogen binding and subsequent platelet-
platelet interactions. The effect is irreversible for the life of the platelet. Platelet dysfunction is present for 5-7 days after
discontinuation of clopidogrel and 10-14 days with ticlopidine.
Prasugrel is a new thienopyridine that inhibits platelets more rapidly, more consistently, and to a greater extent than do
standard and higher doses of clopidogrel. In the United States, the only labeled indication is for acute coronary syndrome in
patients intended to undergo percutaneous coronary intervention. After a single oral dose, 50% of platelets are irreversibly
inhibited, with maximum effect two hours after administration. Platelet aggregation normalizes in 7-9 days after discontinuation
of therapy. The labeling recommends that the drug “be discontinued at least 7 days prior to any surgery”.Platelet glycoprotein
IIb/IIIa receptor antagonists, including abciximab (Reopro ), eptifibatide (Integrilin ) and tirofiban (Aggrastat ), inhibit platelet
aggregation by interfering with platelet-fibrinogen binding and subsequent platelet-platelet interactions. Time to normal platelet
aggregation following discontinuation of therapy ranges from eight hours (eptifibatide, tirofiban) to 48 hours (abciximab). Increased
perioperative bleeding in patients undergoing cardiac and vascular surgery after receiving ticlopidine, clopidogrel and glycoprotein
IIb/IIIa antagonists warrants concern regarding the risk of anesthesia-related hemorrhagic complications.
Anesthetic Management of the Anticoagulated Patient

The decision to perform spinal or epidural anesthesia/analgesia and the timing of catheter removal in a patient receiving
thromboprophylaxis should be made on an individual basis, weighing the small, though definite risk of spinal hematoma with the
benefits of regional anesthesia for a specific patient. Alternative anesthetic and analgesic techniques exist for patients considered to
be at an unacceptable risk. The patient’s coagulation status should be optimized at the time of spinal or epidural needle/catheter
placement, and the level of anticoagulation must be carefully monitored during the period of epidural catheterization (Table 1). It is
important to note that patients respond with variable sensitivities to anticoagulant medications. Indwelling catheters should not be
removed in the presence of a significant coagulopathy, as this appears to significantly increase the risk of spinal hematoma (2,3). In
addition, communication between clinicians involved in the perioperative management of patients receiving anticoagulants for
thromboprophylaxis is essential in order to decrease the risk of serious hemorrhagic complications. The patient should be closely
monitored in the perioperative period for signs of cord ischemia. If spinal hematoma is suspected, the treatment of choice is
immediate decompressive laminectomy. Recovery is unlikely if surgery is postponed for more than 10-12 hours; less than 40% of
the patients in the series by Vandermeulen et al. (2) had partial or good recovery of neurologic function.
Meningitis and Epidural Abscess

Bacterial infection of the central neuraxis may present as meningitis or cord compression secondary to abscess formation. Possible
risk factors include underlying sepsis, diabetes, depressed immune status, steroid therapy, localized bacterial colonization or
infection, and chronic catheter maintenance. Bacterial infection of the central neural axis may present as meningitis or cord
compression secondary to abscess formation. The infectious source for meningitis and epidural abscess may result from distant
colonization or localized infection with subsequent hematogenous spread and CNS invasion. The anesthetist may also transmit
microorganisms directly into the CNS by needle/catheter contamination through a break in aseptic technique or passage through a
contiguous infection. An indwelling neuraxial catheter, though aseptically sited, may be colonized with skin flora and consequently
serve as a source for ascending infection to the epidural or intrathecal space.
Historically, the frequency of serious CNS infections such as arachnoiditis, meningitis, and abscess following spinal or
epidural anesthesia was considered to be extremely low- cases were reported as individual cases or small series (25,26). However,
recent epidemiologic series from Europe suggest that the frequency of infectious complications associated with neuraxial
techniques is increasing (3,27). In a national study conducted from 1997 to 1998 in Denmark, Wang et al (28) reported the
incidence of epidural abscess after epidural analgesia was 1:1930 catheters. Patients with epidural abscess had an extended duration
of epidural catheterization (median 6 days, range 3-31 days). In addition, the majority of the patients with epidural abscess were
immunocompromised. Often the diagnosis was delayed; the time to first symptom to confirmation of the diagnosis was a median of
five days. S. aureus was isolated in 67% of patients. Patients without neurologic deficits were successfully treated with antibiotics,
while those with deficits underwent surgical decompression, typically with only moderate neurologic recovery. It is difficult to
determine why the frequency of symptomatic epidural abscess was so high in this series. Since perioperative antithrombotic therapy
was involved in most cases, it is possible that the epidural abscesses were infected “micro” epidural hematomas, but this is not
strongly supported by the diagnostic imaging studies and neurosurgical findings.
In the series by Moen et al (3) there were 42 serious infectious complications. Epidural abscess occurred in 13 patients;
nine (70%) were considered immunocompromised as a result of diabetes, steroid therapy, cancer or alcoholism. Six patients
underwent epidural block for analgesia following trauma. The time from placement of the epidural catheter to first symptoms
ranged from 2 days to 5 weeks (median 5 days). Although prevailing symptoms were fever and sever backache, five developed
neurologic deficits. All seven positive cultures isolated S. aureus. Overall neurologic recovery was complete in 7 of 12 patients.
However, four of the five patients with neurologic symptoms did not recover. Meningitis was reported in 29 patients for an overall
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incidence of 1:53,000. A documented perforation of the dura (intentional or accidental) occurred in 25 of 29 cases. In the 12
patients in whom positive cultures were obtained, alpha-hemolytic streptococci were isolated in 11 patients and S. aureus in one.
These large epidemiologic studies represent new and unexpected findings regarding the demographics, frequency,
etiology and prognosis of infectious complications following neuraxial anesthesia. Epidural abscess is most likely to occur in
immunocompromised patients with prolonged durations of epidural catheterization. The most common causative organism is S.
aureus, which suggests the colonization and subsequent infection from normal skin flora as the pathogenesis. Delays in diagnosis
and treatment result in poor neurologic recovery, despite surgical decompression. Conversely, patients who develop meningitis
following neuraxial blockade typically are healthy and have undergone uneventful spinal anesthesia. Furthermore, the series by
Moen et al (3) validates the findings of individual case reports of meningitis after spinal anesthesia- the source of the pathogen is
mostly likely to be the upper airway of the proceduralist. While the frequency of serious infectious complications is much higher
than reported previously, the results may be due to differences in reporting and/or clinical practice (asepsis, perioperative antibiotic
therapy, duration of epidural catheterization)
Meningitis after Dural Puncture and Neuraxial Anesthesia

Dural puncture has long been considered a risk factor in the pathogenesis of meningitis. Exactly how bacteria cross from the blood
stream into the spinal fluid is unknown. The presumed mechanisms include introduction of blood into the intrathecal space during needle
placement and disruption of the protection provided by the blood-brain barrier. Initial investigations were performed over 80 years ago
(29). Subsequent clinical studies reported conflicting results regarding the causal relationship between dural puncture during
bacteremia and meningitis However, the protective effect of antibiotic administration prior to lumbar puncture was suggested
(30,31).
Epidural Abscess after Epidural Anesthesia

Several relevant studies have specifically examined the risk of epidural abscess in patients receiving epidural anesthesia and/or analgesia.
Bader et al. (32) investigated the use of regional anesthesia in women with chorioamnionitis. Three hundred nineteen women were
identified from a total of 10,047 deliveries. Of the 319 women, 100 had blood cultures taken on the day of delivery. Eight of these had
blood cultures consistent with bacteremia. Two hundred ninety-three of the 319 patients received a regional anesthetic, in 43 patients
antibiotics were administered prior to needle or catheter placement. No patient in the study, including those with documented
bacteremias, had infectious complications. In addition, mean temperatures and leukocyte counts in patients who received blood cultures
showed no significant differences between bacteremic and nonbacteremic groups. These authors continue to administer spinal and
epidural anesthesia in patients with suspected chorioamnionitis because the potential benefits of regional anesthesia outweigh the
theoretical risk of infectious complications.
The safety of epidural analgesia in 75 patients admitted to the intensive care unit was prospectively evaluated by Darchy et al
(33). There were no epidural abscesses. However, five of nine patients with positive cultures of the catheter insertion site also had
positive catheter tip cultures (epidural catheter infection); Staphylococcus epidermidis was the most commonly cultured microorganism.
Local infection of the catheter site was treated with catheter removal, but antibiotic therapy was not specifically prescribed. Concomitant
infection at other sites, antibiotic prophylaxis, and duration of epidural analgesia were not risk factors for epidural-analgesia related
infections. The authors noted that the presence of both erythema and local discharge is a strong predictor of local and epidural catheter
infection.
Epidural anesthesia and analgesia in a patient with a known systemic or localized infection remains controversial. Jakobsen et
al (34) retrospectively reviewed the records of 69 patients with abscesses or wound infections who underwent epidural catheter placement
for surgical debridement over a seven year-period. Several patients had more than one catheter inserted. Catheters were left indwelling
for a mean of nine days. On 12 occasions (eight patients) the catheter was removed because of local infection. None of the patients
demonstrated signs or symptoms of neuraxial infection. The authors concluded that epidural anesthesia is relatively safe for patients
requiring repeated surgical treatment of localized infection. In contrast, Bengtsson et al. (35) reported three epidural catheter-related
infections in patients with cutaneous wounds over a four year-period. All patients were treated with antibiotic therapy; one patient
underwent transcutaneous drainage of an epidural abscess. However, there were no neurologic deficits. It is difficult to determine the
actual risk of epidural abscess in patients with chronic localized infections who undergo epidural catheter placement due to the small
number of patients studied and the rarity of this complication. Therefore, the clinician must maintain vigilance in neurologic monitoring
to assure early recognition and treatment.
Neuraxial Blockade in the Immunocompromised Patient

Large series have demonstrated that patients with immunodeficiencies are at increased risk for infectious complications compared to
those with intact immune function. However, there are few investigations which have evaluated the frequency of meningitis or
epidural abscess within a specific immunodeficient population (3,27,36).
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Table 2. Infectious Complications following Neuraxial Anesthesia in the Immunocompromised Patient

 The attenuated inflammatory response within the immunocompromised patient may diminish the clinical signs and symptoms often
associated with infection and result in a delay in diagnosis and treatment.
 The range of microorganisms causing invasive infection in the immunocompromised host is much broader than that affecting the general
population and includes atypical and opportunistic pathogens.
 Early and effective therapy is paramount in optimizing neurologic outcome- consultation with an infectious disease specialist is advised.
 Prolonged antibiotic therapy (weeks-months) is often required because of persistent and immunologic deficiencies.
 Since eradication of infection is difficult once established, prevention of infection is paramount in caring for immunocompromised patients.
From: Horlocker, et al 2006, with permission
Herpes Simplex Virus

Herpes simplex virus type 2 (HSV-2) infection is an incurable, recurrent disease characterized by asymptomatic periods alternating with
recrudescence of genital lesions. The primary infection is associated with viremia and can be accompanied by a variety of symptoms,
including fever, headache, and rarely aseptic meningitis. In contrast, recurrent or secondary infections present as genital lesions without
evidence of viremia. When obstetric patients present for delivery with evidence of active HSV-2 infection, cesarean section is
recommended to avoid exposing the neonate to the virus during vaginal delivery. Neuraxial block in these patients is controversial
because of the theoretical potential of introducing the virus into the CNS. However, there are little data to support these concerns.
Human Immunodeficiency Virus

The risk of performing neuraxial block in patients infected with human immunodeficiency virus (HIV) is largely undetermined.
Approximately 40% of patients with the diagnosis of acquired immune deficiency syndrome (AIDS) have clinical signs of neuropathy,
and 70% to 80% have neuropathic changes present at autopsy. Since the virus infects the CNS early in the disease, it is unlikely that
neuraxial block would result in new CNS transmission. However, the neurologic symptoms associated with HIV infection such as
aseptic meningitis, headache, and polyneuropathy would be indistinguishable from those related to regional technique. Hughes et al.
(37) reported safe administration of neuraxial block to 18 HIV-infected parturients. The patients studied showed no postpartum
change in immune, infectious or neurologic status. Avidan et al. (38) and Bremerich et al.(39) also reported a low complication
rate for parturients with HIV infection on antiretroviral therapy who underwent spinal anesthesia. However, in all three series
(with a combined total of 117 patients), the patients were relatively healthy and in the early stage of their disease. The effects of
anesthesia on patients with more advanced disease are unreported.
Aseptic Technique
Although previous publications have repeatedly recommended meticulous aseptic technique, only recently have standards for
asepsis during the performance of regional anesthetic procedures been defined (40) (Table 3). Handwashing remains the most
crucial component of asepsis; gloves should be regarded as a supplement to- not a replacement of- handwashing (41). The use of
an antimicrobial soap reduces bacterial growth and reduces the risk of bacteria being released into the operative field should
gloves become torn or punctured during the procedure. An alcohol-based antiseptic provides the maximum degree of
antimicrobial activity and duration. Prior to washing, all jewelry (rings, watches, etc) should be removed; higher microbial counts
have been noted in health care workers who do not routinely remove these items before handwashing. Sterile gloves protect not
only patients from contamination, but also health care workers from blood-borne pathogens and are required by the Occupational
Safety and Health Administration (40). Glove leaks are more likely to occur with vinyl compared to latex gloves (24% vs. 2),
with contamination of the health care workers’ hands noted following the leaks in 23% of cases (42). Conversely, the use of
gowns does not further reduce the likelihood of cross contamination in an intensive care unit setting compared to gloves alone. At
this time, there are insufficient data to make recommendations regarding routine use for single injection or temporary
neuraxial/peripheral catheter placement. However, placement of an indwelling permanent device, such as a spinal cord
stimulator, warrants the same asepsis as a surgical procedure, including gowns, hats, and antibiotic pretreatment (40,43).
Surgical masks, initially considered a barrier to protect the proceduralist from patient secretions and blood, are now
required by the Center for Disease Control due to the increasing number of cases of post spinal meningitis, many of which result
from contamination of the epidural or intrathecal space with pathogens from the operator's buccal mucosa (3,44-47). A recent
ASA Practice Advisory also recommends the wearing of masks (48).
Antiseptic Solutions
Controversy still exists regarding the most appropriate and safe antiseptic solution for patients undergoing neuraxial and
peripheral techniques. Povidone iodine and chlorhexidine gluconate (with or without the addition of isopropyl alcohol) have been
most extensively studied (49,50). In nearly all clinical investigations, the bactericidal effect of chlorhexidine was more rapid and
more effective (extending its effect hours following its application) than povidone iodine. The addition of isopropyl alcohol
accelerates these effects. Chlorhexidine is effective against nearly all nosocomial yeasts, and bacteria (gram-positive and gram-
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negative); resistance is extremely rare. It also remains effective in the presence of organic compounds, such as blood. It must be
noted that chlorhexidine-alcohol labeling contains a warning against use as a skin preparation prior to lumbar puncture. The FDA
has not formally approved chlorhexidine for skin preparation prior to lumbar puncture because of the lack of animal and clinical
studies examining the neurotoxic potential of chlorhexidine, not due to a number of reported cases of nerve injury. Indeed, it is
important to note that there are no cases of neurotoxicity with either chlorhexidine or alcohol (40). Therefore, as a result of its
superior effect, alcohol-based chlorhexidine solutions are considered the antiseptic of choice for skin preparation before any
regional anesthetic procedure (40).
Anesthetic Management of the Infected or Febrile Patient

In summary, several clinical and laboratory studies have suggested an association between dural puncture during bacteremia and
meningitis. The data are not equivocal, however. The clinical studies are limited to pediatric patients who are historically at high-
risk for meningitis. Many of the original animal studies utilized bacterial counts that were far in excess of those noted in humans in
early sepsis, making CNS contamination more likely. Despite these conflicting results, it is generally recommended that except in
the most extraordinary circumstances, central neuronal block should not be performed in patients with untreated bacteremia. Patients
with evidence of systemic infection may safely undergo spinal anesthesia, if antibiotic therapy is initiated prior to dural puncture, and the
patient has demonstrated a response to therapy, such as a decrease in fever. Placement of an indwelling epidural (or intrathecal) catheter
in this group of patients remains controversial; patients should be carefully selected and monitored for evidence of epidural infection (51).
The attenuated inflammatory response within the
immunocompromised patient, including patients with HSV
and HIV, may diminish the clinical signs and symptoms
often associated with infection. Likewise, the range of
microorganisms causing invasive infection in the
immunocompromised host is much broader than that
affecting the general population and includes atypical and
opportunistic pathogens. Consultation with an infectious
disease specialist is advised to facilitate initiation of early
and effective therapy (36). Meticulous aseptic technique,
including hand-washing with chlorhexidine, wearing of
mask and sterile gloves by the proceduralist, skin asepsis
with chlorhexidine and antibiotic pretreatment for the placement of permanent devices, is critical to the prevention of infectious
complications related to regional anesthesia (40).
All patients with an established local or systemic infection should be considered at risk for developing infection of the CNS.
A delay in diagnosis and treatment of even a few hours significantly worsens neurologic outcome. Bacterial meningitis is a medical
emergency. Mortality is approximately 30%, even with antibiotic therapy. The clinical course of epidural abscess progresses from spinal
ache and root pain, to weakness (including bowel and bladder symptoms) and eventually paralysis. The initial back pain and radicular
symptoms may remain stable for hours to weeks. However, the onset of weakness often progresses to complete paralysis within 24
hours. Although the diagnosis was historically made with myelogram, radiologic examination such as CT scan, or more preferably MRI,
is currently recommended. A combination of antibiotics and surgical drainage remains the treatment of choice. As with spinal
hematoma, neurologic recovery is dependent on the duration of the deficit and the severity of neurologic impairment before treatment.
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1999;91:1928-36.
29. Weed LH, Wegeforth P, Ayer JB, Felton LD. The production of meningitis by release of cerebrospinal fluid during an experimental
septicemia. JAMA 1919;72:190-3.
30. Carp H, Bailey S. The association between meningitis and dural puncture in bacteremic rats. Anesthesiology 1992;76:739-42.
31. Teele DW, Dashefsky B, Rakusan T, Klein JO. Meningitis after lumbar puncture in children with bacteremia. N Engl J Med
1981;305:1079-81.
32. Bader AM, Gilbertson L, Kirz L, Datta S. Regional anesthesia in women with chorioamnionitis. Reg Anesth 1992;17:84-6.
33. Darchy B, Forceville X, Bavoux E, Soriot F, Domart Y. Clinical and bacteriologic survey of epidural analgesia in patients in the intensive
care unit. Anesthesiology 1996;85:988-98.
34. Jakobsen KB, Christensen MK, Carlsson PS. Extradural anaesthesia for repeated surgical treatment in the presence of infection. Br J
Anaesth 1995;75:536-40.
35. Bengtsson M, Nettelblad H, Sjoberg F. Extradural catheter-related infections in patients with infected cutaneous wounds. Br J Anaesth
1997;79:668-70.
36. Horlocker TT, Wedel DJ. Regional anesthesia in the immunocompromised patient. Reg Anesth Pain Med 2006;31:334-45.
37. Hughes SC, Dailey PA, Landers D, et al. Parturients infected with human immunodeficiency virus and regional anesthesia. Clinical and
immunologic response. Anesthesiology 1995;82:32-7.
38. Avidan MS, Groves P, Blott M, et al. Low complication rate associated with cesarean section under spinal anesthesia for HIV-1-infected
women on antiretroviral therapy. Anesthesiology 2002;97:320-4.
39. Bremerich DH, Ahr A, Buchner S, et al. [Anesthetic regimen for HIV positive parturients undergoing elective cesarean section].
Anaesthesist 2003;52:1124-31.
40. Hebl JR. The importance and implications of aseptic techniques during regional anesthesia. Reg Anesth Pain Med 2006;31:311-23.
41. Saloojee H, Steenhoff A. The health professional's role in preventing nosocomial infections. Postgrad Med J 2001;77:16-9.
42. Olsen RJ, Lynch P, Coyle MB, et al. Examination gloves as barriers to hand contamination in clinical practice. Jama 1993;270:350-3.
43. Rathmell JP, Lake T, Ramundo MB. Infectious risks of chronic pain treatments: injection therapy, surgical implants, and intradiscal
techniques. Reg Anesth Pain Med 2006;31:346-52.
44. Couzigou C, Vuong TK, Botherel AH, et al. Iatrogenic Streptococcus salivarius meningitis after spinal anaesthesia: need for strict
application of standard precautions. J Hosp Infect 2003;53:313-4.
45. Molinier S, Paris JF, Brisou P, et al. [2 cases of iatrogenic oral streptococcal infection: meningitis and spondylodiscitis]. Rev Med Interne
1998;19:568-70.
46. Schneeberger PM, Janssen M, Voss A. Alpha-hemolytic streptococci: a major pathogen of iatrogenic meningitis following lumbar puncture.
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47. Trautmann M, Lepper PM, Schmitz FJ. Three cases of bacterial meningitis after spinal and epidural anesthesia. Eur J Clin Microbiol Infect
Dis 2002;21:43-5.
48. Horlocker TT, Birnbach DJ, Connis RT, et al. Practice advisory for the prevention, diagnosis, and management of infectious complications
associated with neuraxial techniques: a report by the American Society of Anesthesiologists Task Force on infectious complications
associated with neuraxial techniques. Anesthesiology 2010;112:530-45.
49. Birnbach DJ, Stein DJ, Murray O, et al. Povidone iodine and skin disinfection before initiation of epidural anesthesia. Anesthesiology
1998;88:668-72.
50. Kinirons B, Mimoz O, Lafendi L, et al. Chlorhexidine versus povidone iodine in preventing colonization of continuous epidural catheters in
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51. Wedel DJ, Horlocker TT. Regional anesthesia in the febrile or infected patient. Reg Anesth Pain Med 2006;31:324-33.
427
Page 1
Update on Cardiocerebral Resuscitation: What is New in the 2015 ACLS

Guidelines?
Part I: Epidemiology of Cardiac Arrest and Update on 2015 Adult Cardiac Life Support
Guidelines
Tom P. Aufderheide, MD, MS Milwaukee, WI
According to the Institute of Medicine (IOM) Report titled, “Strategies to Improve Cardiac Arrest Survival: A Time
to Act”,1 the estimated incidence of total cardiac arrests in the United States occurring outside the hospital (i.e., out-
of-hospital cardiac arrests [OHCAs]) is approximately 395,000.2 The most recent estimates document an additional
200,000 cardiac arrests occurring in hospitals (i.e., in-hospital cardiac arrests [IHCAs]).3 Nationally, less than 6
percent of people who experience an OHCA and 24 percent of patients who experience an IHCA survive to hospital
discharge.2,4
2015 Basic Life Support Update5
 Compression rate is modified to a range of 100 to 120/min. 6

 Compression depth for adults is modified to at least 2 inches (5 cm) but should not exceed 2.4 inches (6 cm). 7
 To allow full chest wall recoil after each compression, rescuers must avoid leaning on the chest between
compressions.8,9
 Criteria for minimizing interruptions (< 10 seconds) is clarified with a goal of chest compression fraction as
high as possible.10
 For patients with ongoing CPR and an advanced airway in place, a simplified ventilation rate of 1 breath every
6 seconds (10 breaths per minute) is recommended. 11
 In adult cardiac arrest, total preshock and postshock pauses in chest compressions should be as short as
possible. (Class I)12
 Resuscitation systems should establish ongoing CPR monitoring and continuous quality improvement of
systems of care.13
2015 Advanced Life Support Update14
 The combined use of vasopressin and epinephrine offers no advantage to using standard-dose epinephrine in
cardiac arrest. Also, vasopressin does not offer an advantage over the use of epinephrine alone. Therefore, to
simplify the algorithm, vasopressin has been removed from the Adult Cardiac Arrest Algorithm-2015 Update.15
 Low end-tidal carbon dioxide (ETCO2) in intubated patients after 20 minutes of CPR is associated with a very
low likelihood of resuscitation. While this parameter should not be used in isolation for decision making,
providers may consider low ETCO2 after 20 minutes of CPR in combination with other factors to help
determine when to terminate resuscitation.16
 When rapidly implemented, extra-corporeal membrane oxygenation (ECMO) CPR can prolong viability, as it
may provide time to treat potentially reversible conditions or arrange for cardiac transplantation for patients
who are not resuscitated by conventional CPR.17
 In cardiac arrest patients with nonshockable rhythm and who are otherwise receiving epinephrine, the early
provision of epinephrine is suggested.18
 Emergency coronary angiography is recommended for all patients with ST elevation and for hemodynamically
or electrically unstable patients without ST elevation for whom a cardiovascular lesion is suspected.19
 Targeted Temperature Management (TTM) recommendations have been updated with new evidence suggesting
that a range of temperatures may be acceptable to target in the post-cardiac arrest period. 20
 After TTM is complete, fever may develop. While there are conflicting observational data about the harm of
fever after TTM, the prevention of fever is considered benign and therefore is reasonable to pursue. 20
 Prognostication is now recommended no sooner than 72 hours after the completion of TTM; for those who do
not have TTM, prognostication is not recommended any sooner than 72 hours after ROSC.
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Page 2
References
1. Strategies to improve cardiac arrest survival: a time to act. http://wwwiom.edu /CardiacArrestsurvival.

Accessed June 30, 2015.
2. Daya, M., R. Schmicker, S. May, and L. Morrison. 2015. Current burden of cardiac arrest in the United States:
Report from the Resuscitation Outcomes Consortium. Paper commissioned by the Committee on the Treatment
of Cardiac Arrest: Current Status and Future Directions. http://www.iom.edu/ ~/media/Files/Report
Files/2015/ROC.pdf (accessed June 30, 2015).
3. Merchant RM, Yang L, Becker LB, Berg RA, Nadkarni V, Nichol G, Carr BG, Mitra N, Bradley SM, Abella
BS, Groeneveld PW; American Heart Association Get With The Guidelines-Resuscitation Investigators.
Incidence of treated cardiac arrest in hospitalized patients in the United States. Crit Care Med. 2011
Nov;39(11):2401-6.
4. Chan, P. S. 2015. Public health burden of in-hospital cardiac arrest. Paper commissioned by the Committee on
the Treatment of Cardiac Arrest: Current Status and Future Directions. http://www.iom.edu/~/media/Files/
Report Files/2015/GWTG.pdf (accessed June 30, 2015).
5. Perkins GD, Travers AH, Berg RA, Castren M, Considine J, Escalante R, Gazmuri RJ, Koster RW, Lim SH,
Nation KJ, Olasveengen TM, Sakamoto T, Sayre MR, Sierra A, Smyth MA, Stanton D, Vaillancourt C; on
behalf of the Basic Life Support Chapter Collaborators. Part 3: adult basic life support and automated external
defibrillation: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular
Care Science With Treatment Recommendations. Circulation. 2015;132(suppl 1):S51–S83.
6. Idris AH, Guffey D, Aufderheide TP, Brown S, Morrison LJ, Nichols P, Powell J, Daya M, Bigham BL, Atkins
DL, Berg R, Davis D, Stiell I, Sopko G, Nichol G; Resuscitation Outcomes Consortium (ROC) Investigators.
Relationship between chest compression rates and outcomes from cardiac arrest. Circulation. 2012;125:3004–
3012.
7. Stiell IG, Brown SP, Nichol G, Cheskes S, Vaillancourt C, Callaway CW, Morrison LJ, Christenson J,
Aufderheide TP, Davis DP, Free C, Hostler D, Stouffer JA, Idris AH; Resuscitation Outcomes Consortium
Investigators. What is the optimal chest compression depth during out-of-hospital cardiac arrest resuscitation
of adult patients? Circulation. 2014;130:1962–1970.
8. Aufderheide TP, Pirrallo RG, Yannopoulos D, Klein JP, von Briesen C, Sparks CW, Deja KA, Conrad CJ,
Kitscha DJ, Provo TA, Lurie KG. Incomplete chest wall decompression: a clinical evaluation of CPR
performance by EMS personnel and assessment of alternative manual chest compression-decompression
techniques. Resuscitation. 2005 Mar;64(3):353-62.
9. Yannopoulos D, McKnite S, Aufderheide TP, Sigurdsson G, Pirrallo RG, Benditt D, Lurie KG. Effects of
incomplete chest wall decompression during cardiopulmonary resuscitation on coronary and cerebral perfusion
pressures in a porcine model of cardiac arrest. Resuscitation. 2005;64:363–372.
10. Vaillancourt C, Everson-Stewart S, Christenson J, Andrusiek D, Powell J, Nichol G, Cheskes S, Aufderheide
TP, Berg R, Stiell IG; Resuscitation Outcomes Consortium Investigators. The impact of increased chest com-
pression fraction on return of spontaneous circulation for out-of-hospital cardiac arrest patients not in
ventricular fibrillation. Resuscitation. 2011;82:1501–1507.
11. Aufderheide TP, Sigurdsson G, Pirrallo RG, Yannopoulos D, McKnite S, von Briesen C, Sparks CW, Conrad
CJ, Provo TA, Lurie KG. Hyperventilation-induced hypotension during cardiopulmonary resuscitation.
Circulation. 2004;109:1960–1965.
12. Cheskes S, Schmicker RH, Verbeek PR, Salcido DD, Brown SP, Brooks S, Menegazzi JJ, Vaillancourt C,
Powell J, May S, Berg RA, Sell R, Idris A, Kampp M, Schmidt T, Christenson J; Resuscitation Outcomes
Consortium (ROC) investigators. The impact of peri-shock pause on survival from out- of-hospital shockable
cardiac arrest during the Resuscitation Outcomes Consortium PRIMED trial. Resuscitation. 2014;85:336–342.
13. Meaney PA, Bobrow BJ, Mancini ME, Christenson J, de Caen AR, Bhanji F, Abella BS, Kleinman ME,
Edelson DP, Berg RA, Aufderheide TP, Menon V, Leary M; CPR Quality Summit Investigators, the American
Heart Association Emergency Cardiovascular Care Committee, and the Council on Cardiopulmonary, Critical
Care, Perioperative and Resuscitation. Cardiopulmonary resuscitation quality: [corrected] improving cardiac
resuscitation outcomes both inside and outside the hospital: a consensus statement from the American Heart
Association. Circulation. 2013;128:417–435.
14. Callaway CW, Soar J, Aibiki M, Böttiger BW, Brooks SC, Deakin CD, Donnino MW, Drajer S, Kloeck W,
Morley PT, Morrison LJ, Neumar RW, Nicholson TC, Nolan JP, Okada K, O’Neil BJ, Paiva EF, Parr MJ,
Wang TL, Witt J; on behalf of the Advanced Life Support Chapter Collaborators. Part 4: advanced life support:
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2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science
With Treatment Recommendations. Circulation. 2015;132(suppl 1):S84–S145.
15. Mukoyama T, Kinoshita K, Nagao K, Tanjoh K. Reduced effectiveness of vasopressin in repeated doses for
patients undergoing prolonged cardiopulmonary resuscitation. Resuscitation. 2009;80:755–761.
16. Wayne MA, Levine RL, Miller CC. Use of end-tidal carbon dioxide to predict outcome in prehospital cardiac
arrest. Ann Emerg Med. 1995;25:762–767.
17. Stub D, Bernard S, Pellegrino V, Smith K, Walker T, Sheldrake J, Hockings L, Shaw J, Duffy SJ, Burrell A,
Cameron P, Smit de V and Kaye DM. Refractory cardiac arrest treated with mechanical CPR, hypothermia,
ECMO and early reperfusion (the CHEER trial). Resuscitation. 2015;86:88-94.
18. Andersen LW, Kurth T, Chase M, Berg KM, Cocchi MN, Callaway C, Donnino MW; American Heart
Association’s Get With The Guidelines-Resuscitation Investigators. Early administration of epinephrine
(adrenaline) in patients with cardiac arrest with initial shockable rhythm in hospital: propensity score matched
analysis. BMJ. 2016 Apr 6;353:i1577.
19. Dumas F, Bougouin W, Geri G, Lamhaut L, Rosencher J, Pene F, Chiche JD, Varenne O, Carli P, Jouven X,
Mira JP, Spaulding C and Cariou A. Emergency Percutaneous Coronary Intervention in Post-Cardiac Arrest
Patients Without ST-Segment Elevation Pattern: Insights From the PROCAT II Registry. JACC Cardiovascular
interventions. 2016;9:1011-8.
20. Nielsen N, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, Horn J, Hovdenes J, Kjaergaard J,
Kuiper M, Pellis T, Stammet P, Wanscher M, Wise MP, Åneman A, Al-Subaie N, Boesgaard S, Bro-Jeppesen J,
Brunetti I, Bugge JF, Hingston CD, Juffermans NP, Koopmans M, Køber L, Langørgen J, Lilja G, Møller JE,
Rundgren M, Rylander C, Smid O, Werer C, Winkel P, Friberg H; TTM Trial Investigators. Targeted
temperature management at 33°C versus 36°C after cardiac arrest. N Engl J Med. 2013 Dec 5;369(23):2197-
206.
21. Zellner T, Gärtner R, Schopohl J, Angstwurm M. NSE and S-100B are not sufficiently predictive of neurologic
outcome after therapeutic hypothermia for cardiac arrest. Resuscitation. 2013;84:1382–1386.
Part II: Update on Adjunct Mechanical Devices and Translational Research

Matthias L. Riess, MD, PhD Nashville, TN
Adjunct Devices
Even under optimal conditions, external chest compressions can only produce about 20 to 30% of the normal
cardiac output. Due to limited endurance of the rescuer, the quality of manual chest compressions also decreases
over time. A more efficient utilization of the heart and chest to pump blood during CPR and to increase critical
cerebral blood flow by lowering intracranial pressure are the mechanism by which two recently developed adjunct
devices work synergistically to improve CPR by lowering intrathoracic pressure during chest compressions.1
Active Compression-Decompression
Inspired by the case of a son rescuing his father after cardiac arrest by using a toilet plunger, 2 Lurie et al.3 have
significantly contributed to the development of Active Compression-Decompression (ACD), where a suction cup is
used to actively decompress the chest after a preceding compression, thus lowering intrathoracic pressure faster,
and improving cardiac output and generated systolic pressure when used alone. A commercially available device
has a gauge meter to guide compression and decompression forces and a metronome to guide duty cycle and chest
compression rate. Marketed in different countries, it recently received approval by the Food and Drug
Administration in the United States.
Automated Chest Compression
Automated chest compressors are also available in the United States. LUCAS-2® (Lund University
Cardiopulmonary Assist System), a newer version of the original LUCAS®, is a battery-powered mechanical piston
device that offers active compression and decompression programmed to not exceed normal sternum levels. It runs
with a constant rate of 100 min-1, a force of 600 N, a compression depth of 2 inches, and 1:1 duty cycle. In contrast,
load-distributing band devices use a circumferential band to actively squeeze the entire chest and rely on passive
elastic recoil during decompression. They deliver an even distribution of the compression across the entire chest,
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while the compression depth can be adjusted to the individual patient’s chest diameter. More technical details on
mechanical devices from different manufacturers are available in recent review articles.4,5 Although earlier reports
have suggested a higher incidence of rib and sternal fractures after manual ACD vs conventional manual CPR,6 and
some case reports have described rare complications such as tension pneumothorax, 7 liver8 or splenic laceration,9
neither of these are thought unique to automated vs conventional manual chest compressions.10 There may be,
however, subtle differences among devices whose significance still needs to be determined.
Taken together, automated mechanical CPR devices enable reliable compressions of a

 constant rate,
 depth and
 location,
and avoid
 provider fatigue11 with subsequent
 inconsistencies of manual compressions,
 provider injury,12 and additionally
 free up personnel.13
The 2015 AHA guideline update considers mechanical piston devices as a reasonable alternative for use by properly
trained personnel (Class IIb) to be considered in specific settings where high-quality manual chest compressions
may be difficult or impossible; clearly, interruptions in CPR during device deployment and removal need to be
limited to an absolute minimum.14 Recommendations for load-distributing band devices are similar.
Impedance Threshold Device
More importantly, ACD works best in tandem with the so-called Impedance Threshold Device (ITD).15 The ITD
is placed between a tight sitting face mask or the endotracheal tube and the ventilation bag or ventilator as early as
possible during ongoing CPR. It opens for spontaneous or positive pressure ventilation and/or for negative
intrathoracic pressures of minus 10 mmHg or lower. ACD and ITD synergistically result in largely improved
systemic blood pressures and cerebral perfusion during CPR in animal models 15 and patients16 by enhancing venous
return to the right heart. Aufderheide et al.17 have shown the combination of ACD with ITD to improve
neurologically intact survival in cardiac arrest patients by 50% on hospital discharge with modified Rankin
Scale scores comparable to the control group one year later.
When the ITD is used in conjunction with conventional manual CPR alone,18-20 the generation of negative
intrathoracic pressure largely depends on the intrinsic elastic recoil of the chest and the quality of CPR; fractured
ribs, for example, or a rigid, non-compliant chest reduce elastic recoil. Moreover, limited recoil through leaning has
detrimental physiological effects on venous return and intracranial pressure as described above. Interestingly, a trial
with 8718 patients randomly assigned to conventional manual CPR with a sham or an active ITD 20 could not show a
benefit of the ITD alone across all-comers which largely contributed to a neutral (Class III) recommendation in the
2015 AHA guidelines update.14 This was before, however, a recent post-hoc analysis of the data21 demonstrated a
clear benefit of the ITD in those patients treated with high quality manual CPR with regards to compression
rate, depth and time spent with chest compressions as opposed to those who did receive CPR outside of the current
recommendations.
If continuous negative intrathoracic pressure through an intrathoracic pressure regulator by combining an ITD with a
vacuum suction to maintain a constant intrathoracic vacuum between minus 5 and 10 mmHg except during
intermittent positive pressure ventilations is an improvement over the ITD during CPR or other models of increased
intracerebral pressure, remains the subject of ongoing animal studies.22 First promising results in humans, however,
have been achieved during coronary bypass graft surgery23 and hemorrhagic shock.24
Experimental Postconditioning to Ameliorate Global Ischemia-Reperfusion Injury
Ideally, most patients would receive CPR immediately after cardiac arrest. Unfortunately, in most emergency
systems only a minority of patients receives CPR before the arrival of first responders. This translates cardiac arrest
into an absent circulation and whole body ischemia for an average of 8-10 min. In a recent multicenter
randomized CPR trial,17 no patient was discharged from the hospital with favorable neurological outcome when the
time from the emergency call to CPR exceeded 10 min.17 Paradoxically, reperfusion, i.e., the reintroduction of
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blood flow after prolonged untreated ischemia, is thought to add significantly to overall ischemia-reperfusion
(IR) injury, with mitochondrial dysfunction and reactive oxygen species production contributing to cell death. 25
Therefore, recent research has focused on ways to improve outcomes by mitigating IR injury after cardiac arrest
beyond what was previously thought possible. While preconditioning would require prior knowledge of an ischemic
event, postconditioning strategies can be employed upon reperfusion.26 In the context of cardiac arrest, actual
reperfusion starts early with the first onset of CPR, and not later with ROSC. Postconditioning can be achieved by
early targeting of some of the known intracellular signaling pathways that lead to cellular dysfunction and
eventually cell death. Although the exact mechanisms are still unclear, postconditioning likely includes activation
of the Reperfusion Injury Salvage Kinase and Survival Activating Factor Enhancement pathways, resulting in
reduced apoptosis and improved cardiac and neurological function and increased survival in different animal models
of cardiac arrest.27 For example, the introduction of several well-defined pauses limited to only the very beginning
of CPR,28 or the very early administration of pharmacological agents29-31 to trigger postconditioning pathways shows
highly promising results in animal experiments. Before their translation into clinical practice, however, conclusive
clinical trials are necessary to understand their role in humans.
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patients treated with manual chest compressions compared with mechanical compressions with the LUCAS
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compressions. Resuscitation 1998; 37: 149-52.
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15. Lurie KG, Voelckel WG, Zielinski T, McKnite S, Lindstrom P, Peterson C, Wenzel V, Lindner KH, Samniah
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Dorian P, Callaway CW, Idris AH, Andrusiek D, Stephens SW, Hostler D, Davis DP, Dunford JV, Pirrallo RG,
Stiell IG, Clement CM, Craig A, Van Ottingham L, Schmidt TA, Wang HE, Weisfeldt ML, Ornato JP, Sopko
G, Resuscitation Outcomes Consortium I: A trial of an impedance threshold device in out-of-hospital cardiac
arrest. The New England journal of medicine 2011; 365: 798-806.
21. Yannopoulos D, Aufderheide TP, Abella BS, Duval S, Frascone RJ, Goodloe JM, Mahoney BD, Nadkarni VM,
Halperin HR, O'Connor R, Idris AH, Becker LB, Pepe PE: Quality of CPR: An important effect modifier in
cardiac arrest clinical outcomes and intervention effectiveness trials. Resuscitation 2015; 94: 106-13.
22. Metzger A, Rees J, Kwon Y, Matsuura T, McKnite S, Lurie KG: Intrathoracic Pressure Regulation Improves
Cerebral Perfusion and Cerebral Blood Flow in a Porcine Model of Brain Injury. Shock 2015; 44 Suppl 1: 96-
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the intrathoracic pressure regulator on hemodynamics and cardiac output. Shock 2011; 35: 114-6.
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ischemia/reperfusion vs preconditioning. Redox biology 2014; 2: 702-14.
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28. Segal N, Matsuura T, Caldwell E, Sarraf M, McKnite S, Zviman M, Aufderheide TP, Halperin HR, Lurie KG,
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Myocardial and Mitochondrial Function in a Pig Model of Prolonged Untreated Ventricular Fibrillation.
30. Bartos JA, Matsuura TR, Sarraf M, Youngquist ST, McKnite SH, Rees JN, Sloper DT, Bates FS, Segal N,
Debaty G, Lurie KG, Neumar RW, Metzger JM, Riess ML, Yannopoulos D: Bundled postconditioning
therapies improve hemodynamics and neurologic recovery after 17 min of untreated cardiac arrest.
31. Derwall M, Ebeling A, Nolte KW, Weis J, Rossaint R, Ichinose F, Nix C, Fries M, Brücken A: Inhaled nitric
oxide improves transpulmonary blood flow and clinical outcomes after prolonged cardiac arrest: a large animal
study. Crit Care 2015; 19: 328.
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Anesthetic Implications of Pharmacogenetics

Itay Bentov Seattle/WA
Anesthetic Implications of Pharmacogenetics

In a recent editorial in Anesthesiology,1 the authors stated that “education in genomics will be essential for
practitioners to translate genomic discoveries into clinical practice.” The Refresher Course lecture on which this
chapter is based is designed to be part of that effort. First, basic concepts and nomenclature of genetics are reviewed.
We will then discuss examples of the influence of genetic information and genetic research strategies upon patient
care in anesthesia.
Envision that you are reviewing the laboratory results for your next patient and you find that the blood counts and
serum chemistries are all within normal limits. However, you notice that your patient has had genetic testing and is
carrying allele A290G (*1b) for the gene CYP3A4, homozygous for the butyrylcholinesterase Asp70Gly
polymorphism and has an alarming single nucleotide polymorphism (SNP) analysis of natriuretic peptide receptor
C/guanylate cyclase C (atrionatriuretic peptide receptor C), also known as NPR3, and natriuretic peptide precursor A
As she comes into your office, you see that she has flaming red hair. During the interview she claims that she
requires large doses of local anesthetics when she visits the dentist.
Would this information alter your anesthetic plan?
TERMINOLOGY
Define: Pharmacogenetics (Pharmacogenomics)

Pharmacogenetics refers to genetic differences in metabolic pathways that can affect individual responses to drugs
(their therapeutic effect as well as adverse effects). Pharmacogenetics is not a new concept; it has been used since
the mid-1950s to explain primaquine sensitivity in malaria and isoniazid response in tuberculosis as well as, in the
field of anesthesia, to explain prolonged effect of succinylcholine in the setting of butyrylcholinesterase deficiency.
Define: Transcription, Promoter, mRNA, Intron, Exon, Translation

Deoxyribonucleic acid (DNA) is the nucleic acid that is the genetic material determining the makeup of all living
cells and many viruses. It consists of two long strands of nucleotides linked together in a structure resembling a
ladder twisted into a spiral. DNA can replicate itself. DNA also serves as a template for the synthesis of ribonucleic
acid (RNA).
Transcription is the process of transcribing or making a copy of genetic information stored in a DNA strand into a
complementary strand of RNA (messenger RNA, or mRNA) with the aid of RNA polymerases.
Promoter is a site on DNA to which the enzyme RNA polymerase can bind and initiate the transcription of DNA
into RNA.
Messenger RNA (mRNA) is synthesized from a DNA template during transcription; it mediates the transfer of
genetic information from the cell nucleus to ribosomes in the cytoplasm, where it serves as a template for protein
synthesis.
Exon is a segment of a gene that contains information used in coding for protein synthesis.
Intron is a segment of a gene situated between exons that is removed before translation of mRNA and does not
function in coding for protein synthesis.
Translation is the process by which the genetic code carried by mRNA directs the production of proteins from amino
acids.
Define: Gene, Locus, Allele, Mutation, Single Nucleotide Polymorphism

Gene is the basic physical unit of heredity; a linear sequence of nucleotides along a segment of DNA that provides
the coded instructions for synthesis of RNA, which, when translated into protein, leads to the expression of
hereditary character.
Locus is the chromosomal position of a gene as determined by its linear order relative to the other genes on that
chromosome.
Allele is an alternative form of a gene. An allele determines distinct traits that can be passed on from parents to
offspring. The process by which alleles are transmitted was reported by Mendel.
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Mutation is a permanent, heritable change in the nucleotide sequence in a gene or a chromosome.

Single nucleotide polymorphism (SNP) is DNA sequence variations that occur when a single nucleotide (A,T,C or
G) in the genome sequence is altered. Each individual has many single nucleotide polymorphisms that together
create a unique DNA pattern.
Define: Phenotype, Genotype, Homozygous, Heterozygous

Phenotype is the “outward, physical manifestation” of the organism. These are the physical parts, structures,
metabolism, energy utilization, organs, and so on (for example, tall or short stature).
Genotype is the “internally coded, inheritable information” carried by all living organisms. For example, mutation in
locus 16q24.3 (which is found on chromosome 16 in the long arm region 2, band 4, sub-band 3; bands are visible
under a microscope) in the gene encoding the melanocortin 1 receptor (genotype) leads to red hair (phenotype).
Homozygous refers to having identical alleles for a single trait.
Heterozygous refers to having two different alleles for a single trait.
CLINICAL IMPLICATIONS
What is Gene Polymorphism and what is the Nomenclature Used to Label It?
Genetic polymorphism occurs when, at a specific locus, several forms of DNA sequences exist within the
population. It also implies a discontinuous genetic variation that results in different forms or types of individuals
among the members of a single species (for example, the ABO blood type).
Gene polymorphisms are labeled using three different naming systems:
1. A118G SNP of the µ-opioid receptor gene codes for the replacement of the nucleotide adenine (A) at base
pair 118 with guanine (G). The number signifies the gene locus (118). The letter before the number signifies the
nucleotide most commonly found at the gene locus (i.e., the “wild-type” or major allele), whereas the letter after the
number represents the nucleotide found in the mutant or minor allele.
2. Asp70Gly polymorphism of the butyrylcholinesterase gene describes a glycine substitution for aspartate at
the 70th amino acid of the protein (in a similar fashion as the previous example, though describing protein instead of
DNA).
3. Numbering the different alleles (e.g., *1). For example, the CYP2D6*5 allele is the fourth identified variant
in the cytochrome P-450 (CYP) enzyme 2D6. This system is the least descriptive but most flexible.
What are the Potential Anesthetic Implications for Medicating This Patient?
Recall that our patient carries the allele A290G (*1b) for the gene CYP3A4 and is homozygous for
butyrylcholinesterase Asp70Gly polymorphism. In a study performed in young healthy men (our patient is female),
hepatic CYP3A activity and the systemic clearance of midazolam were about 30% lower in G/G homozygotes than
in A/A homozygotes.2 In addition, there is considerable inter-individual variability, and body size appears to be an
important determinant. Furthermore, it is not known whether the patient carries a single allele with the substitution
(heterozygote) or two alleles (homozygote). For these reasons, the information concerning CYP3A4 is not very
helpful in managing this patient.
Being homozygous for the butyrylcholinesterase Asp70Gly polymorphism, however, is very informative: after a
single dose of succinylcholine, the normal population usually recovers within ten minutes. Heterozygous (single
allele) expression of the butyrylcholinesterase Asp70Gly polymorphism results in production of a less effective form
of plasma butyrylcholinesterase. These patients typically take three to eight times longer to recover neuromuscular
function after succinylcholine administration. Homozygous expression (both alleles) of the butyrylcholinesterase
Asp70Gly polymorphism prolongs the recovery of neuromuscular function even further, resulting in a recovery
period up to 60 times longer than that associated with the normal allele.
Can a Genetic Polymorphism of a Single Locus Affect the Use of Different Agents from Multiple Drug
Groups?
The cytochrome P450 2D6 (CYP2D6) genetic polymorphism is an outstanding example of the potential implications
of applying pharmacogenetic principles to anesthetic care. CYP2D6 is responsible for the metabolism and
elimination of numerous drugs used in clinical care: antipsychotics, selective serotonin reuptake inhibitors (SSRIs),
beta-blockers, antiarrhythmics, and many others. For example, CYP2D6 metabolizes codeine and tramadol from
prodrugs to the active forms (activation) but metabolizes ondansetron to inactive metabolites (clearance). As
different alleles of CYP2D6 determine activity, patients show a spectrum of CYP2D6 activity: ranging from poor
metabolizers (little or no CYP2D6 function), in whom codeine and tramadol will not convert from prodrugs to
active metabolites and will be clinically ineffective, to ultra-rapid metabolizers in whom ondansetron is quickly
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metabolized to inactive metabolites and therefore is less effective. Side effects are likewise augmented. A striking
example comes from a case report of the death of a child two days following surgery. The child was prescribed a
commonly recommended dose of codeine but developed respiratory arrest due to toxic accumulation of morphine
because he was a CYP2D6 ultra-rapid metabolizer.3
What Are Genetic Linkage and Gene Association Studies?

Genetic linkage is the tendency of certain loci or alleles to be inherited together. Assume that we observe individuals
of an experimental population by looking at the relationships among phenotypes. Some phenotypes or traits can
occur randomly with respect to one another (independent assortment) or with some correlation with respect to one
another. Independent assortment occurs when the genes affecting the phenotypes are found on different
chromosomes or are separated by a great enough distance on the same chromosome. The exception to independent
assortment occurs when genes appear in close proximity on the same chromosome. This phenomenon usually causes
the genes to be inherited as a single unit. Genes inherited in this way are said to be linked. A haplotype is a
combination of alleles at closely linked loci on a single chromosome that tend to be inherited together.
“Classic” linkage studies typically examine families with a high prevalence of an anomalous phenotype, comparing
thousands of genes between family members with and without the anomaly. Gene association studies are used to
determine the influence of human genetic variation on the pathogenesis of disease, variability in disease expression,
and response to treatment. SNPs have been shown to be a powerful tool for identifying disease genes by association
analysis of patients and controls. However, association analyses must have adequate statistical power and they must
also include adequate genetic variation within each of the groups (cases or controls). Lastly, the assumption that
trait-influencing genes are inherited by descent may not identify influential genes, because the association will be
divided between multiple loci in the sample of affected individuals.
Can an SNP Profile Predict Postoperative Complications?

Gene association studies have addressed the linkage between ventricular dysfunction and specific gene variants.
From 10–20% of patients suffer from ventricular dysfunction after cardiac surgery. In a study, blood samples were
collected from more than 1,000 patients undergoing coronary artery bypass graft operations and genotyped for 139
different SNPs within seven genes (genes that belong to the natriuretic peptide system).4 Results showed that seven
NPPA/NPPB SNPs were associated with decreased risk of postoperative ventricular dysfunction, defined by the
need for two or more inotropes, intraaortic balloon pump or ventricular assist device, and dyspnea score (OR 0.44–
0.55), while four NPR3 SNPs were associated with increased risk of postoperative dysfunction (OR 3.89–4.28).
Similar association between genotypes within the natriuretic peptide system and cardiovascular outcomes were
found when patients with known coronary heart disease were followed for a median of 2.8 years.5 The SNPs do not
have to be part of a known gene—they can be just a marker. For example, noncoding (within an intron and hence
cannot be translated to a biologically significant protein) SNPs within the chromosome 4q25 region are
independently associated with postoperative atrial fibrillation after coronary artery bypass graft surgery.6
What is the Genetic Basis for the Difference in Pain Sensitivity in Redheads?
Red hair is a classic phenotype. The genetic basis for red hair is two copies of a recessive gene for melanocortin-1
receptor on chromosome 16. Dysfunctional melanocortin-1 receptor on the surface of melanocytes produces low
levels of the dark pigment eumelanin and high levels of reddish pigment pheomelanin. Women with red hair require
almost 20% more anesthetic (desflurane) than women with dark hair7 and are more resistant to the effect of
subcutaneous lidocaine8 (Supplemental Digital Content 3, http://links.lww.com/ASA/A461). The melanocortin-1
receptor gene mediates not only mechanisms of analgesia in a mouse model in which the gene is mutated and
rendered dysfunctional (interestingly, for females only), but had the same effect in healthy redheaded women as
well.9 The cause of this phenomenon is not thoroughly understood; although the melanocortin-1 receptor is
expressed in glial cells and the pituitary, the central nervous system is not a major site of expression.
Is DNA Extraction, Storage, and SNP Analysis a Complicated and Costly Process?
DNA can be extracted from every nucleated cell in the body; a saliva sample is sufficient. Extraction is so simple
that it can be performed with equipment and ingredients found in almost every kitchen (liquid soap detergent, salt,
meat tenderizers, and some rubbing alcohol) and is safe enough to do with elementary school children. DNA is very
resilient and can easily be stored for a long time in the kitchen refrigerator. (The premise behind the film “Jurassic
Park,” that dinosaur DNA will be maintained intact for 70 million years, is probably a bit far-fetched, but for the
duration of our lifetime, or over several hundred years, DNA degradation should not be an issue.)
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The economics of DNA analysis (sequencing) have changed considerably in the past decade. In April 2003, the
International Human Genome Sequencing Consortium announced that a project begun in 1990 had essentially been
completed. A version of the human genome sequence (about three billion base pairs) was made publicly available.
The cost of the project to American taxpayers was close to three billion dollars. In 2007, a complete sequence of a
single person’s DNA cost approximately one million dollars, while in 2013 it costs about $4,000 for a full sequence.
In addition, SNP analysis is now available to the general public by commercial companies for less than $100 for
analysis of over 20,000 SNPs (Supplemental Digital Content 4, http://links.lww.com/ASA/A462). Free public online
resources (SNPedia and others) are allowing the public to learn about 50,000 known SNP polymorphisms that are
associated with the risk of disease as well as athletic ability, alcohol craving, and baldness.
A novel technique to selectively sequence the coding regions of the genome (exons; see Figure 1) is called exome
sequencing. The human genome contains about 180,000 exons which constitute about 1% of the human genome, or
about 30 million base pairs. It is an effective and cheaper alternative to whole genome sequencing and is now
commercially available for approximately $500–$1,000).
CONCLUSION
Should DNA testing be conducted for every patient? The answer is clearly no at the present time. Our clinical care
should uphold the most rigorous standards in ensuring privacy and confidentiality of our patients, and we should be
mindful of the costs, risks, and benefits of every clinical procedure. Privacy relates to persons: the control over the
extent, timing, and circumstances of sharing oneself with others. Confidentiality relates to information: treatment of
information that an individual has disclosed with trust and with the expectation that it will not be divulged to others
in ways that are inconsistent with the understanding of the original disclosure. Genetic investigation has the tools to
discover, but may not have sufficient tools to protect. Potential breaches of both privacy and confidentiality can arise
in numerous ways. For example, by analyzing several family members, the genetic characteristics of other family
members can be fairly accurately presumed even if they have not consented to undergo genetic testing. Bias,
discrimination, and stigma can easily flourish. The Genetic Information Nondiscrimination Act of 2008 (GINA)
protects Americans from discrimination in health insurance and employment decisions on the basis of genetic
information, but the act does not cover life insurance or disability insurance providers.
The Genomics and Personalized Medicine Act of 2010 (Bill 5440 in the House of Representatives) has a
commendable goal: “To secure the promise of personalized medicine for all Americans by expanding and
accelerating genomics research and initiatives to improve the accuracy of disease diagnosis, increase the safety of
drugs, and identify novel treatments.…” Regrettably, it has not been enacted.
References
1. Eisenach JH, Schroeder DR: Genomic discoveries in perioperative medicine: educating the audience.
2. Wandel C, Witte JS, Hall JM, Stein CM, Wood AJ, Wilkinson GR: CYP3A activity in African American
and European American men: population differences and functional effect of the CYP3A4*1B5'-promoter region
polymorphism. Clin Pharmacol Ther 2000; 68: 82-91
3. Ciszkowski C, Madadi P, Phillips MS, Lauwers AE, Koren G: Codeine, Ultrarapid-Metabolism Genotype,
and Postoperative Death. New England Journal of Medicine 2009; 361: 827-828
4. Fox AA, Collard CD, Shernan SK, Seidman CE, Seidman JG, Liu KY, Muehlschlegel JD, Perry TE,
Aranki SF, Lange C, Herman DS, Meitinger T, Lichtner P, Body SC: Natriuretic peptide system gene variants are
associated with ventricular dysfunction after coronary artery bypass grafting. Anesthesiology 2009; 110: 738-47
5. Ellis KL, Newton-Cheh C, Wang TJ, Frampton CM, Doughty RN, Whalley GA, Ellis CJ, Skelton L, Davis
N, Yandle TG, Troughton RW, Richards AM, Cameron VA: Association of genetic variation in the natriuretic
peptide system with cardiovascular outcomes. J Mol Cell Cardiol 2011; 50: 695-701
6. Body SC, Collard CD, Shernan SK, Fox AA, Liu KY, Ritchie MD, Perry TE, Muehlschlegel JD, Aranki S,
Donahue BS, Pretorius M, Estrada JC, Ellinor PT, Newton-Cheh C, Seidman CE, Seidman JG, Herman DS,
Lichtner P, Meitinger T, Pfeufer A, Kaab S, Brown NJ, Roden DM, Darbar D: Variation in the 4q25 chromosomal
locus predicts atrial fibrillation after coronary artery bypass graft surgery. Circ Cardiovasc Genet 2009; 2: 499-506
7. Liem EB, Lin CM, Suleman MI, Doufas AG, Gregg RG, Veauthier JM, Loyd G, Sessler DI: Anesthetic
requirement is increased in redheads. Anesthesiology 2004; 101: 279-83
8. Liem EB, Joiner TV, Tsueda K, Sessler DI: Increased sensitivity to thermal pain and reduced subcutaneous
lidocaine efficacy in redheads. Anesthesiology 2005; 102: 509-14
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9. Mogil JS, Wilson SG, Chesler EJ, Rankin AL, Nemmani KV, Lariviere WR, Groce MK, Wallace MR,
Kaplan L, Staud R, Ness TJ, Glover TL, Stankova M, Mayorov A, Hruby VJ, Grisel JE, Fillingim RB: The
melanocortin-1 receptor gene mediates female-specific mechanisms of analgesia in mice and humans. Proc Natl
Acad Sci USA 2003; 100: 4867-72
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Perioperative Management of Patients Undergoing Spine Surgery
Susan Black, MD Birmingham, AL
Patients undergoing surgical procedures of the spine represent a diverse group of patients with varying severities of
pathology, undergoing a wide range of procedures from minimally invasive to high risk multilevel procedures.
Developing a perioperative management strategy to optimize outcome for these patients requires understanding of
the disease processes, surgical procedures, and options for management.
Airway Management
Patients with cervical spine pathology require special consideration for airway management. Patients with cervical
spine disease have a higher incidence of difficult intubation, in particular those with rheumatoid disease, cervical
fractures or tumors, disease involving the upper cervical spine, and with internal or external fixation. In patients
with cervical spine disease conventional airway assessment remains the best predictor of encountering a difficult
airway. Cervical spine pathology in patients with a concerning airway exam further increases the potential for
difficulty.1 Endotracheal intubation in the presence of cervical spine disease may be associated with risk of
neurologic injury. In patients with an unstable cervical spine, intubation is not associated with an increased risk of
neurologic deterioration compared to those not requiring intubation (1-2%) if the instability is recognized.2 In
patients with unrecognized cervical spine instability, risk of neurologic deterioration with intubation is significantly
increased to approximately 10%.3
Studies have attempted to identify optimal techniques for intubation in patients at risk for cervical spine injury.4
During airway maneuvers, the greatest motion of the cervical spine has been shown to occur at the atlanto-occipital
junction followed by the junction of the first two cervical vertebrae.5 In patients with known or suspected cervical
spine instability it is important to limit motion of the cervical spine during airway management. Use of manual in
line stabilization remains the most accepted technique to limit motion, but is associated with increased difficulty in
obtaining an optimal view of the glottic opening. A wide variety of intubation techniques have been evaluated for
use in these patients. Direct laryngoscopy is the tool with the longest history of documented safe use. A number of
devices including indirect laryngoscopes, laryngeal mask airways, and fiberoptic scopes have been shown to be
effective in limiting motion of the cervical spine while managing the airway. Depending on the clinical situation
including airway examination, patient’s mental status and other comorbidities, and experience of provider, one of
these techniques may be advantageous. In planning airway management of patients undergoing cervical spine
surgery awareness of the risk of spinal cord injury with intubation, recognition of the increased risk of encountering
a difficult airway, and attention to minimizing motion of the cervical spine are more important to success than
choice of a particular technique. There is no single best approach.
Certain patient groups may also have risk of postoperative airway problems – the difficult extubation patient.
Patients undergoing multiple level anterior cervical spine procedures may be at risk for postoperative neck and
airway edema causing airway compromise with airway complications occurring in up to 6%, requiring reintubation
in approximately 2%, and leading to mortality in 0.3%. Identified risk factors are operative time > 10 hours,
requirement for > 4 units transfusion, obesity, reoperations, and operations of 4 or more cervical spine levels or
involving the second cervical vertebrae.6 Authors of a recent review article divided risk factors into primary or
surgical factors, and secondary either patient or anesthetic factors. Based on their review they recommended that
patients be classified as high risk (>1 surgical risk factor), intermediate risk (1 surgical risk factor) and low risk (0
surgical risk factors). High risk patients should be left intubated until surgical edema resolved. Intermediate risk
patients require assessment of secondary factors. Intermediate risk patients with one or more secondary factors may
warrant delayed extubation while intermediate risk patients without secondary factors could be extubated
immediately postoperatively but have more intensive monitoring in the first 12 to 24 hours postoperatively. Low
risk patients require no special consideration for extubation.7
Table 1: Risk Factors for Delayed or Failed Extubation
Primary factors Secondary factors
Surgical Patient Anesthetic
Duration > 5 hours Morbid obesity Grade 3-4 view
> 3 levels Pulmonary disease Multiple intubation attempts
C2-C4 Cervical myelopathy Fluids
> 300 EBL Prior c-spine surgery
Anterior + posterior
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Hemodynamic Management
In some circumstances induced hypertension is utilized in spine procedures, particularly in cervical spine procedures
in patients with significant cord compression. It is a common practice to maintain very strict control of blood
pressure intraoperatively utilizing direct arterial pressure monitoring and attempting to maintain systemic perfusion
pressure at or very near awake levels. While this has not been studied in a prospective fashion, it is believed by
many neurosurgeons and neuroanesthesiologists to be important in minimizing risk for new neurologic injury in this
patient population. 8 On the other hand, induced hypotension continues to be utilized in some centers for patients
undergoing procedures associated with high perioperative blood loss, in particular multilevel thoracic and lumbar
reconstructive procedures. There is little evidence to indicate that mild degrees of induced hypotension as is most
commonly utilized in these procedures is effective to significantly decrease perioperative estimated blood loss or
perioperative transfusion requirement. However, less bleeding in the operative field, may improve surgical
exposure. This may be an appropriate and effective strategy in patients that are not placed at increased risk of
perioperative morbidity by the use of mild degrees of induced hypotension.9
Transfusion Management
While many surgical procedures of the spine are not associated with large blood loss, procedures involving
significant bone work at multiple levels may be associated with large intraoperative blood loss and a high incidence
of transfusion. A number of factors have been found to predict requirement for transfusion allowing us to identify
patients at risk for high blood loss who would benefit by interventions that decrease need for transfusion. 9-13
Table 2: Factors Predicting Need for Perioperative Transfusion during Spine Surgery
Patient factors Procedure factors
ASA Classification >3 associate with higher loss Location Lumbar & thoracic > cervical
Gender Female > male Number levels
Age Fusion
Weight loss Complexity
Preoperative Hg Surgeon specialty Orthopedics > neurosurgery
Coagulopathy
Coumadin use Even if lab normal
Several techniques to decrease intraoperative blood loss have been investigated. Induced hypotension is applied
most commonly to multiple level thoracic or lumbar spine procedures in healthy patients without neurologic deficits.
Efficacy in decreasing blood loss and transfusion has not been consistently demonstrated.14 Operative positions
which prevent abdominal compression (such as the Jackson table) have been reported to result in less blood loss as
compared to positions in which some degree of abdominal compression may occur (prone on bolsters or Wilson
frame). Antifibrinolytic agents, tranexamic acid and aminocaproic acid, have been shown in many studies to
decrease intraoperative and total perioperative blood loss with some studies demonstrating a decrease in transfusion
of blood products and others revealing no difference in transfusion requirements. Use of these agents has not been
associated with complications related to hypercoagulation.10,14,15 In a small series, recombinant activated factor
VII was shown to be effective at decreasing intraoperative blood loss and transfusion in patients undergoing
multiple level spinal fusion procedures when given after loss of 10% of estimated blood volume.16 However this
practice has not been studied in a large population.
Numerous approaches to decrease requirement for homologous blood transfusion have also been investigated.
Epoetin alfa administration preoperatively has been shown to decrease requirement for homologous transfusion in
some studies, either alone or in combination with preoperative autologous donation, but has been was associated
with a higher incidence of deep venous thrombosis when pharmacologic antithrombotic prophylaxis was not
used.17,18 Preoperative donation of autologous blood, immediate preoperative hemodilution and collection of
autologous blood, and perioperative blood salvage have all been utilized in spine surgery to decrease requirement for
intraoperative homologous transfusion. Each has been shown to be similarly effective used alone, but in most
circumstances combination of more than one of these techniques does not further decrease requirement for
homologous blood products.19-21 In addition, numerous recent studies have pointed out the high rate of wasting of
autologous units collected prior to spine surgery with wasting of at least one unit in up to 50% of patients
undergoing scoliosis correction.22 A meta analysis reviewing available maneuvers to decrease transfusion found
that there was good evidence to support the use of antifibrinolytic agents, while there was little of no evidence to
support recombinant factor VII, induced hypotension, staging of long procedures, normovolemic hemodilution, or
intraoperative cell salvage. To decrease requirement for transfusion during spine surgery and the associated
complications, it is important to first identify the subset of patients at risk for large blood loss and then selectively
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utilize one of the available techniques with potential to decrease need for homologous transfusion. Patients expected
to loose less than 10% of their estimated blood volume will likely not benefit from utilization of the techniques
described above, those anticipated to loose 10-30% of estimated blood volume will see benefit from use of one
technique, and combination of multiple techniques is only indicated when a very high blood loss is anticipated. In
all patients optimal preoperative preparation (i.e. anemia management) and optimal positioning to lessen
requirement for transfusion is appropriate. Over the last decade rates of transfusion of blood products during spine
surgery have not decreased as they have in other procedure types. Rates of transfusion of allogeneic blood have
increased and the use of autologous products has decreased. The reason for this in the face of increasing emphasis
on decreasing transfusion of banked blood is unclear.23
Postoperative Pain Management
Spine procedures may be associated with significant postoperative pain. Neuraxial techniques including intrathecal
narcotics and postoperative epidural analgesia have been shown to be effective techniques in lumbar and thoracic
procedures and are not associated with increased incidence or delayed diagnosis of neurologic injury if the dosing
regimen is planned to allow early neurologic assessment. Benefits include earlier return of bowel function, earlier
mobilization, shorter hospital stay, improved pain control at rest and with movement, less nausea and vomiting, and
less puritis.24,25 Wound catheters with infiltration of local anesthetic have also been effective in pain relief and to
decrease the incidence of chronic dysesthesias.26 Multimodal medication regimens including pre and post operative
oral controlled release narcotics, perioperative ketamine, preoperative methadone, perioperative oral pregabalin or
gabapentin, and scheduled perioperative acetaminophen or nonsteroidal anti-inflammatory agents have been shown
to improve pain management and decrease systemic narcotic side effects.27-29 In a prospective study utilizing
patient survey postoperatively, a variety of multimodal regimens were compared. There was no difference between
medication combinations, however when multimodal regimens were instituted preoperatively they were more
effective, resulting in better pain control postoperatively and improved patient perception of function after discharge
compared to similar regimens initiated postoperatively.30 Multimodal techniques in particular when instituted
preoperatively appear to offer advantages over single medication regimens after spine surgery as has been seen in
many other procedure types.
Neurologic Monitoring and Injury Prevention
Neurologic monitoring may be utilized in a number of spine procedures. During repair of scoliosis, continuous
neurologic monitoring is considered an indicated technique by the Scoliosis Research Society and is felt to result in
a lower risk of intraoperative neurologic injury.31 Neurologic monitoring of other spine procedures in patients felt
to be at high risk for neurologic injury is felt by some to decrease risk of neurologic injury, but is not utilized
consistently in all centers. Somatosensory evoked potential (SSEP) and transcranial motor evoked potential
(TcMEP) monitoring are utilized in patients felt to be at risk for spinal cord injury either from surgical trauma,
operative position, or impairment of blood supply. Electromyography (EMG) is utilized when it is felt that nerve
roots may be at risk during the procedure, most commonly with lumbar stabilization procedures. Conclusions from
a recent literature review were that there is good evidence that neurologic monitoring effectively detects
intraoperative neurologic injury, but little evidence that use of monitoring decreases the risk of developing a new
neurologic deficit. The authors recommend consideration of intraoperative neurologic monitoring during spine
surgery.32 SSEP monitoring places some limitation on anesthetic management, most notably limiting the dose of
volatile agents and benzodiazepines. Likewise TcMEP monitoring impacts anesthetic management. Most
commonly intravenous techniques are utilized (propofol and/or narcotic infusion supplemented with nitrous,
benzodiazepines, ketamine, or lose dose volatile agents). Patients’ disease states influence ability to successfully
monitor their neurologic function intraoperatively. Patients with preexisting neurologic deficits, diabetes mellitus,
and hypertension have an increased rate of inability to monitor TcMEP’s intraoperatively. Having more than one
disease or use of volatile anesthetic agents increased the risk of failure to monitor further.33 EMG requires
avoidance of muscle relaxants.
Postoperative Vision Loss
Postoperative vision loss is a rare complication of spine surgery occurring in 0 – 0.1% of cases.34-37 While
awareness of this complication has increased over the last decade, the incidence nationally appears to be
decreasing.38 Postoperative vision loss is most often due to posterior ischemic optic neuropathy (PION), less
commonly anterior ischemic optic neuropathy (AION), and rarely due to the +other reported causes of postoperative
vision loss; central retinal artery or vein occlusion and occipital lobe infracts. Reported risk factors for
postoperative ION include patient factors such as risk factors for atherosclerotic disease and intraoperative factors.
While occasional cases of vision loss due to positioning errors with pressure on the eye are reported, this rarely
appears to be a factor. The prone position is associated with significant increases in intraocular pressure and
potentially, retrobulbar pressure. Some have postulated that acute venous congestion and a compartment-like
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syndrome develops in the retrobulbar space predisposing these patients to ischemia of the optic nerve. Both head
dependent positioning and vigorous fluid resuscitation could contribute to this phenomenon.39 In a recent case
control study the Postoperative Visual Loss Study Group investigated factors reported to be with PION.40 Results
are shown in Table 3.
Table 3: Proposed Risk Factors Postoperative ION
Risk factors associated ION Risk factors not associated with ION
Male sex Age
Obesity Comorbid conditions (diabetes, hypertension, smoking)
Use of Wilson frame Number levels
Anesthetic duration Head positioning device
Estimated blood loss Hypotension
Lower colloid use (as % of nonblood infusions) Lowest HCT
Vasopressor use
Total volume, total nonblood volume replacement
Because neither the mechanisms nor definitive risk factors have been identified, methods to prevent this
complication are unknown. In fact, the patient profile for those suffering this complication after spine surgery is
males aged 45 to 55 with risk factors for vascular disease present in only about 50%. The ASA published a practice
advisory in 2006, which was revised in 2012. A summary of the recommendations follows.
 There is a subset of patients undergoing prone spine procedures and receiving general anesthesia that has an
increased risk for development of perioperative visual loss, including patients who are anticipated to undergo
procedures that are prolonged, have substantial blood loss, or both.
 Consider informing high risk patients that there is a small, unpredictable risk of perioperative visual loss.
 Blood pressure should be monitored continuously in high risk patients. Use of deliberate hypotension should be
determined on a case by case basis.
 Use of central venous pressure monitoring should be considered in high risk patients. Colloids should be used
along with crystalloids to maintain intravascular volume in patients who have substantial blood loss.
 At this time, there is no apparent transfusion threshold that would eliminate the risk of perioperative visual loss
related to anemia.
 Use of alpha adrenergic agonists should be determined on a case by case basis.
 High risk patients should be positioned so that their heads are level with or higher than the heart when possible.
In addition, their heads should be maintained in a neutral forward position when possible.
 Consideration should be given to the use of staged spine procedures in high risk patients.41
Outpatient Spine Surgery
Increasingly, spine procedures are being performed as outpatient procedures. Not only are lumbar procedures
commonly outpatient procedures, but increasingly cervical spine procedures are being considered as outpatient
procedures. Available literature suggests this can be done successfully provided careful patient and procedure
selection is carried out. Unplanned admission or readmission is uncommon (2-5%), with no reported complications
specifically related to the outpatient status. The most common causes of admission are dural tear, anesthetic
complications, poor pain control, new neurologic symptoms, and urinary retention. In centers with successful
outpatient spine surgery practices, common exclusion criteria for outpatient procedures include significant co-
morbidities, difficult airway, living a long distance away or living alone, and procedures finishing late in the day. In
general postoperative stay is at least 4 to 6 hours to allow detection of the majority of complications. Outpatient
spine surgery can be performed safely offering our patients the benefits associated with outpatient procedures
including lower cost and lower risk for hospital associated complications.42-44 It will be imperative for
anesthesiologists to be involved in the development of protocols for safe outpatient spine surgery, as there is a rapid
evolution in practice over recent years. The proportion of more involved cervical spine procedures such as
decompressions done as outpatients has doubled in just over a decade, while the number of outpatient lumbar disc
procedures has increased 5 fold and outpatient procedures for lumbar stenosis by nine fold over the same time
frame.45
Optimizing Outcome
A number of factors, which can be managed by anesthesiologists in the perioperative period, have been associated
with increased risk of complications in retrospective studies. These include presence of anemia preoperatively,
operating room delays of greater than 60 minutes, and use of FiO2 less than 50%. 46-48 Postoperative surgical site
infections (SSI) after spine surgery cause significant increases in morbidity, hospital length of stay and health care
cost. SSI’s occur at rate of 0.7 to 4.0 per 100 cases. A number of risk factors have been identified, many of which
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are not amenable to perioperative intervention and are reflections of the patients disease or co-morbid conditions.
These include ASA physical classification, prior spine surgery, operative duration, obesity, and age. However a
number of factors can be modified and are under the purview of the anesthesiologist. These include perioperative
glucose management, temperature control, and administered FiO2. Patients with nasal colonization by methicillin
resistant staphylococcal aureus have been shown to be at a higher risk for SSI, which can be reduced by preoperative
treatment with either mupirocin or providone-iodine.49
Patients undergoing spine surgery present diverse challenges to the anesthesiologist. Optimal management depends
on the anesthesiologist understanding the pathologic process and the risk and needs of the operative procedure. This
group of patients is one in which anesthesiologists have the opportunity to significantly improve patient safety and
quality of care when we are engaged in the entire perioperative period.
References
1. Calder I, Calder J, Crockard HA: Difficult direct laryngoscopy in patients with cervical spine disease.
Anaesthesia 50:756-763, 1995
2. Suderman VS, Crosby ET: Elective oral tracheal intubation in cervical spine-injured adults. Can J Anaesth
38:785-789, 1991
3. Hastings RH, Kelley SD: Neurologic deterioration associated with airway management in a cervical spine-
injured patient. Anesthesiology 78:580-583, 1993
4. Crosby ET: Airway management in adults after cervical spine trauma. Anesthesiology 104:1293-1318,
2006
5. Lennarson PJ, Smith DW, Sawin PD: Cervical spinal motion during intubation: efficacy of stabilization
maneuvers in the setting of complete segmental instability. J Neurosurg (Spine 2) 94:265-270, 2001
6. Epstein NE, Hollingsworth R, Nardi D, Singer J: Can airway complications following multilevel anterior
cervical spine surgery be avoided: J Neurosurg 94(2 Suppl):185-188, 2001
7. Palumbo MA, Aidlen JP, Daniels AH, Bianco A, and Caiati JM: Airway compromise due to
laryngopharyngeal edema after anterior cervical spine surgery: J Clinical Anesthesia 25: 66-72, 2013.
8. Kim KA, Wang MY: Anesthetic considerations in the treatment of cervical myelopathy. Spine J6:207S-
211S, 2006
9. Elgafy H, Bransford RJ, McGuire RA, Dettori JR, Fischer D: Blood loss in major spine surgery: are there
effective measures to decrease massive hemorrhage in major spine fusion surgery? Spine 20;35(9 Suppl):S47-56,
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10. Lenoir B, Merckx P, Paugam-Burtz C, et al: Individual probability of allogeneic erythrocyte transfusion in
elective spine surgery. The predictive model of transfusion in spine surgery.
11. Torres-Claramunt R, Ramı´rez, M, Lo´pez-Soques M, et al: Arch Orthop Predictors of blood transfusion in
patients undergoing elective surgery for degenerative conditions of the spine. Arch of Orthop Trauma Surg E Pub
June 2012.
12. Hiroyuki: Predictors of allogeneic blood transfusion in spinal fusion in the United States, 2004-2009.
Spine 39:304-310, 2014
13. Seicean: Surgeon specialty and outcome after elective spine surgery. Spine 39: 1605-1613
14. Bess RS, Lenke LG: Blood loss minimization and blood salvage techniques for complex spine surgery.
Neursurg Clin N Am 17:227-234, 2006
15. Shapiro F, Zurakowski D, Sethna NF: Tranexamic acid diminishes intraoperative blood loss and
transfusion in spinal fusions for Duchene muscular dystrophy scoliosis. Spine 32:2278-2283, 2007
16. Sachs B, Delacy D, Green J, et al: Recombinant activated factor VII in spinal surgery. Spine 32:2285-
2293, 2007
17. Vitlae MG, Privitera DM, Matsumoto H, et al: Efficacy of preoperative erythropoietin administration in
pediatric neuromuscular scoliosis. Spine 32:2662-2667, 2007
18. Stowell CP, Jones SC, Enny C, et al: An Open-label, randomized, parallel-group study of perioperative
epoetin alfa versus standard of care for blood conservation in major elective spine surgery. Spine 34:2479-2485,
2009.
19. Blais RE, Hadjipavlou AG, Shulman G: Efficacy of autotransfusion in spine surgery: comparison of
autotransfusion alone and with hemodilution and apheresis. Spine 21(23):2795-2800, 1996
20. Cavallieri S, Riou B, Roche S, et al: Intraoperative autologous transfusion in emergency surgery for spine
trauma. J of Trauma 36(5):639-643,1994
21. Cha CW, Deible C, Muzzonigro T, et al: Allogeneic transfusion requirements after autologous donations
in posterior lumbar surgeries. Spine 27:99-104, 2002
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22. Bess RS, Lenke LG, Bridwell KH, et al: Wasting of preoperatively donated autologous blood in surgical
treatment of adolescent idiopathic scoliosis. Spine 31:2375-2380
23. Yoshihara H, Yoneoka D: Trends in the Utilization of Blood Transfusions in Spinal Fusion in the United
States From 2000 to 2009. Spine 39: 297-303, 2014
24. Tobias JD. A review of intrathecal and epidural analgesia after spine surgery in children. Anesth Analg
98;956-965, 2004.
25. Van Boerum DH, Smith JT, Curtin MJ: A comparison of the effects of patient controlled analgesia with
intravenous opioids versus epidural analgesia on recover after surgery for idiopathic scoliosis. Spine 25:2355-2357,
2000
26. Singh K, Phillips FM, Kuo E, et al: A prospective randomized, double blinded study of the efficacy f
postoperative continuous local anesthetic infusion at the iliac crest bone graft site after posterior spinal arthrodesis: a
minimum 4-year followup: Spine 32:2790-2706, 2007.
27. Gottschalk A, Durieux ME, Nermergut EC: Intraoperative methadone improves postoperative pain
control in patients undergoing complex spine surgery. Anesth Analg 112:218-223, 2011
28. Kim JC, Choi YS, Kim KN, et al: Effective dose of peri-operative oral pregablin as an adjunct to
multimodal analgesic regimen in lumbar spinal fusion surgery. Spine 36:428-433, 2011
29. Loftus RW, Yeager MP, Clark JA, et al: Intraoperative ketamine reduces perioperative opiate
consumption in opiate-dependent patients with chronic pain undergoing back surgery. Anesthesiology 113:639-646,
2010
30. Lee BH, Park JO, Suk KS, et al: Pre-emptive and multi-modal perioperative pain management may
improve quality of live in patients undergoing spinal surgery. Pain Physician 16:E217-E226, 2013.
31. Nuwer MR, Dawson EG, Carlson LG, Kanim LE, Sherman JE: Somatosensory evoked potential spinal
cord monitoring reduces neurologic deficits after scoliosis surgery: results of a large multicenter survey.
Electroencephalography Clin Neurophysiology 96:6-11, 1995
32. Fehlings MG, Brodke DS, Norvell DC, Dettori JR: The evidence for intraoperative neurophysiological
monitoring in spine surgery. Does it make a difference: Spine 37:S37-S46, 2010
33. Stacie G. Deiner, MD,* Shawn G. Kwatra, BS, Lin H, Weisz DJ: Patient characteristics and anesthetic
technique are additive but not synergistic predictors of successful
motor evoked potential monitoring. Anesth Analg 111:421, 2010.
34. Stevens WR, Glazer PA, Kelley SD, Lietman TM, Bradford DS: Ophthalmic complications after spine
surgery. Spine 22:1319-1324, 1997
35. Myers MA, Hamilton SR, Bogosian AJ, Smith CH, Wagner TA: Visual loss as a complication of spine
surgery. A review of 37 cases. Spine 22:1329, 1997
36. Cheng MA, Sigurdson W, Tempelhoff R, Lauryssen C: Visual loss after spine surgery: a survey.
Neurosurgery 46(3):625-631, 2000.
37. Lee LL, Newman NJ, Wagner TA, Dettoir JR, Dettori NJ: Perioperative Ischemic Optic Neuropathy.
Spine 35:S105-S116, 2010
38. Shen Y, Drumm M, Roth S: The prevalence of perioperative visual loss in the United States: A 10-year
study from 1996-2005 of spinal, orthopedic, cardiac, and general surgery. Anesth Analg 109:1534-1545, 2009
39. Cheng MA, Tempelhoff R, et al: The effect of prone positioning on intraocular pressure in anesthetized
patients. Anesthesiology 95:1351-1355, 2001.
40. The Postoperative Visual Loss Study Group: Risk factors associated with ischemic optic neuropathy after
spinal fusion surgery. Anesthesiology 116:15-24, 2012.
41. Practice Advisory for Perioperative Visual Loss Associated with Spine Surgery. Anesthesiology 116:274 –
285, 20012.
42. Wohns R: Safety and cost-effectiveness of outpatient cervical disc arthroplasty: Surg Neurol Int13;1:77,
2010.
43. Walid MS, Robinson JS 3rd, Robinson ER, Brannick BB, et al: Comparison of outpatient and inpatient
spine surgery patients with regards to obesity, comorbidities and readmission for infection. J Clin
Neurosci17(12):1497-8, 2010.
44. Purzner T, Purzner J, Massicotte EM, et al: Outpatient brain tumor surgery and spinal decompression: a
prospective study of 1003 patients. Neurosurgery. 69(1):119-26, 2011.
45. Best MJ, Buller LT, Eismont FJ: National trends in ambulatory surgery for intervertebral disc disorders
and spinal stenosis: A 12-year analysis of the national surveys of ambulatory surgery.
Spine 40: 1703-11, 2015.
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46. Maragakis LL, Cosgrove SE, Martinez EA, et al: Intraoperative fraction of inspired oxygen is a modifiable
risk factor for surgical site infection after spinal surgery. Anesthesiology 110:556 – 62, 2009.
47. Seicean A. Seicean S, Alan N, et al: Preoperative anemia and perioperative outcome in patients who
undergo elective spine surgery. Spine 38:1331-1341, 2013.
48. Radcliff KE, Rasouli MR, Neusner A, et al: Perioperative delay of more than 1 hour increases risk for
surgical site infection. Spine 38:1318-1323, 2013.
49. Thakkar V, Ghobrial GM, Maulucci CM et al: Nasal MRSA colonization: impact on surgical site infection
following spine surgery. Clinical Neurology and Neurosurgery 125:94-97, 2014
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NORA: Complexity, Safety, Efficiency and Leadership
Basem Abdelmalak, MD Cleveland/OH

Alan Marco, MD Dayton,/OH
Donald Mathews, MD Burlington/ VT
Introduction:
Anesthesia providers are being increasingly asked to provide care outside of the traditional operating room setting.
This has led to the recognition of a distinct type of anesthesia service known as Non-Operating Room Anesthesia
(NORA). NORA (table 1) has been on a steady rise, in distinct contrast to the numbers of patients served in
standard main operating rooms. (1) this is for the most part attributed to new advances in the procedures either not
requiring the full capabilities of an operating room (such as endoscopic procedures) or requiring complex and
immobile technology (such as interventional radiology). In these settings the tradition of the proceduralist providing
sedation while simultaneously performing the procedure has been found to be inadequate.
NORA Challenges:
In addition to the introduction of more advanced and complex procedures, higher risk patients who were not
previously considered candidates for intervention are now included as the advances in technology have made
available an alternative option for those very high risk patients for whom traditional invasive surgeries are too risky
to undertake. With the complexity and technological advancement of these procedures rising, the proceduralist
needs to focus and thus, the need for anesthesia services became inevitable, adding personnel and equipment to these
already tight rooms. As these services are added to an already existing endoscopy suite or a procedural areas such as
interventional radiology that were built and designed to meet the needs of the procedures and the proceduralists, the
anesthesia team often works in sub-optimal settings which may hinder the provision of high quality care as
anesthesiologists try to minimize the equipment used to fit the very limited (and often dimly lit) space available.
Further complicating care is often poor access to the patient, and lack of availability of needed medications,
supplies, and rescue equipment commonly accessible in the traditional OR environment. Moreover, NORA differs
from traditional anesthesia in that the anesthesia practitioner is frequently a “stranger in a strange land”. Working in
strange environments can impede teamwork, which may result in negative impacts on patient care.(2) There is an
inherent difference in team dynamics between performing an anesthetic for a pediatric MRI with only the radiology
technician available for assistance versus performing an anesthetic for craniotomy with intra-operative MRI in the
MRI suite with the standard OR nursing and surgical team. Another challenge stems from the fact that the pre-
procedure evaluations can be less thorough or complete than those performed for OR patients; often the patients
have been referred to the proceduralist who is unfamiliar with them and may only know the patient from his
transferred records. Finally, our procedural colleagues have high (and perhaps unrealistic) expectations; they
expect a quiescent, immobile patient with near-instantaneous turnovers.
No wonder the provision of anesthesia services in such locations became an undesirable activity. Many groups
decided to evenly divide this "stressful burden" amongst their members in an attempt to avoid professional burnout.
However this does not have to be the case. As these advances in patient care are being introduced to our practices it
is incumbent upon the anesthesiologist to participate in the planning of such locations starting with the initial
meetings for exploring new construction or expansion or remodeling of already existing and functioning locations to
ensure that patient and provider needs are met. Such involvement not only strengthens and helps establish “the
team” that will be functioning together when clinical service ensues, but will also facilitate communications and set
ground rules, and expectations, critical elements that will help such services to grow, and provide the highest level
of service possible. Table 2 lists some of these challenges and suggested solutions.
Table1: Locations for Non-Operating Room Anesthesia (NORA) Services

Gastroenterology Endoscopy Suite
Interventional Radiology areas including CT
Bronchoscopy Suite
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Cardiac Catheterization Lab

Electrophysiology Lab
MRI ( Diagnostic, and surgical)
Nuclear Medicine
PACU (Electroconvulsive therapy)
Pain Management procedure rooms
Minimal Requirements for Safe Anesthesia in NORA Locations

To assist its members with such a challenging task, the American Society of Anesthesiologists (ASA) has issued a
statement,(3) listing the minimal requirements in such locations in terms of space , equipment, and personnel as a
starting points in the discussions with fellow proceduralists, hospital architects, and administrators to build and
design safe environment for delivering high quality and safe patient care .
TABLE 2: Sources of Complexity in Nora and Proposed Solutions
Challenge Description Solution
Space Anesthesia is an afterthought, insufficient Be part of the plan from inception to ensure these areas
room for anesthesia machine or supplies are designed with dedicated anesthesia space
Equipment Not enough and old equipment are used Ensure the same equipment standards as in the main
operating rooms initial planning involvement to set
capital budget for startup
Staff Proceduralists and their teams are not used Effective communication, team building, clear
to working with anesthesia teams expectations
Patients High risk patients are served Establish and optimize the pre-op evaluation process. ,
maintain monitoring standards, develop a formal
system for summoning help and designate a well-
trained recovery staff and location
Procedures New , complex , more invasive and risky Effective communications, pre-operative time out,
procedures including discussion of procedure and anesthetic
concerns
■Space Allocation and Equipment Needs

•Availability of a reliable oxygen source and delivery method (nasal cannulas, face masks), along with
backup supply of oxygen in the form of a full E cylinder
•Availability of adequate suction
•Ability to scavenge waste gases when inhaled anesthetic agents are required
•Presence of a self-inflating resuscitator bag that can administer at least 90% oxygen and deliver positive-
pressure ventilation in the event of respiratory distress
•Adequate anesthetic drugs, monitoring equipment, and supplies for the duration of the case
•Adequate lighting and electrical outlets for proper visualization and operation of anesthesia equipment
•Availability of sufficient space for the anesthesia provider and any other necessary personnel, as well as
unobstructed access to the patient, anesthesia equipment, and emergency supplies
•Emergency cart with a defibrillator and emergency drugs for cardiopulmonary resuscitation
•Observance of all applicable building codes and facility standards
•Availability of adequately trained staff for immediate assistance of the anesthesia provider, as well as
reliable two-way communication with which to request additional assistance
•Provision of adequate postanesthesia care, which should include appropriately trained staff and equipment
that ensures safe transport of the patient to the designated recovery area
After these conditions have been met, the anesthesia caregiver can focus on the actual care of patients
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Patient Monitoring:
It should be emphasized that the same monitoring standards applied in traditional operating room settings should
also be applied to patients served in NORA locations. The importance of patient monitoring during anesthesia has
been emphasized by a statement from ASA.(4) The first and most important standard highlighted in that statement
is: “Standard 1: Qualified anesthesia personnel shall be present in the room throughout the conduct of all general
anesthetics, regional anesthetics and monitored anesthesia care”. Accordingly, patients are monitored both by
clinical observation (“look, listen, feel”) as well as by using specialized monitoring equipment (see Table 3).
Table 3: Monitoring equipment typically employed during an anesthetic.

Electrocardiogram
Blood pressure (manual, automatic, arterial catheter)
Pulse oximeter
Capnograph
Oxygen analyzer
Anesthetic agent concentration analyzer
Temperature (when indicated)
Gas flows/spirometry (part of anesthesia machine)
Airway pressure monitor (part of anesthesia machine)
Airway disconnect alarm
Nerve Stimulator (where non-depolarizing muscle relaxants have been used)
Urometer (measure urine output - where appropriate)
Depth of hypnosis monitor ( optional, more so preferred for TIVA)
Recovery and Discharge Criteria After Monitored Anesthesia Care
Anesthetics used in NORA areas should permit rapid recovery because these patients are often outpatients and have
minimally invasive procedures. At the same time, each location should develop recovery and discharge protocols
that are appropriate for its specific patients and procedures. Recovery and discharge criteria should be no different
from those used in the main Post Anesthesia Care Unit (PACU).(5)
Physicians should be able to assess home readiness in a simple, clear, reproducible manner. Medicolegal
considerations mandate that physicians have documented objective evidence that the patient’s discharge criteria
were met and that all discharge instructions have been signed by the patient and documented in the medical record.
Patients should be duly informed that home readiness does not confer the ability to drive a car or immediately return
to work
.MAC in NORA
One of the commonly provided anesthesia service in NORA is monitored anesthesia care (MAC) , inducing varying
degrees of sedation, with the option to convert to general anesthesia when needed. The process of delivering
sedation can be complicated: constant vigilance is required as patients can easily descend into deeper planes of
sedation than intended. It is not surprising that concerns about patient safety during NORA have arisen given the
issues listed above. The ASA Closed Claims database has revealed interesting information: in a review of MAC
cases, respiratory depression due to an absolute or relative overdose of sedating agents was responsible for 21% of
MAC-related claims and over half of these adverse events were felt to be preventable with better monitoring.(6)
Compared with OR claims, those in the NORA locations are more often associated with patient death, issues with
ventilation and higher payout.(7) Until recently data about incidence of complications in NORA procedures has
been incomplete; we knew there were cases with bad outcomes, but we did not have a denominator to know the
incidence of morbidity and mortality in the NORA areas. From a recent quality assurance database of
approximately 143,000 cases, a large academic medical center reported that there were 52 patients cared for with
moderate sedation that had an adverse safety outcome.(8) The authors reported that oversedation leading to apnea
(30/52 patients) and the use of reversal agents (29/52 patients) were the most frequently reported adverse outcomes.
The National Anesthesia Clinical Outcomes Registry (NACOR) is also beginning to provide information about
NORA safety with data about incidence of complications. (1) Overall mortality was greater in OR patients compared
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to NORA patients, 0.4 vs 0.2 %, respectively, however the cardiology and radiology areas had a mortality rate
significantly greater than the OR of 0.5%. Hemodynamic instability was reported in 0.1% of NORA patients and
respiratory complications in 0.09%, both significantly lower than rates reported in the OR data.
It is clear from the above information that respiratory inadequacy in the NORA patient is a significant concern.
Medications administered for sedation can suppress central respiratory drive and lead to airway obstruction,
aspiration, and respiration depression. Hypoventilation, apnea and hypoxemia are the principal causes of sedation-
related morbidity. (9)At a level of moderate sedation, these risks are less significant, however, moderately sedated
patients can progress to levels of deep sedation with an increased likelihood of respiratory compromise. Moreover,
doses of sedating medications that are sub-hypnotic can result in significant pharyngeal dysfunction.(10) When
patients move from states of consciousness to states of unconsciousness their genioglossus nerve shows a significant
decrease in EMG activity potentially causing airway obstruction.(11) Detecting inadequate ventilatory function is
very important and may allow for interventions that could prevent sedation-related complications. Ventilatory
monitoring is therefore an essential component in assuring that the sedated patient receives quality care. Clinical
observation of ventilation has shown to be unreliable in assessing respiratory status.(12) Monitoring methods
beyond routine observation and pulse oximetry are therefore advisable. These include capnography, chest wall
impedance techniques and monitoring of acoustic signals.
Pulse oximetry is inadequate as a monitor of ventilation. It can detect arterial oxygen desaturation ( as a
consequence to hypoventilation) but does not reflect alveolar ventilation with sufficient sensitivity. With the
provision of supplemental oxygen, pulse oximetry will be slow to detect alveolar hypoventilation during respiratory
depression.(13) Some people, therefore, withhold supplemental oxygen so that a decrease in oxygenation will
herald inadequate ventilation.(14) Withholding oxygen may help detect inadequate ventilation early, however can
be harmful and quite dangerous. Inadequate ventilation in the setting of hypoxemia is likely to be more harmful
than inadequate ventilation alone.
The use of capnography has been shown to be associated with earlier detection of ventilatory depression compared
to pulse oximetry in patients receiving sedation and should be used whenever technically possible.(15) In addition,
interventions based on capnography compared to care with a pulse oximeter are associated with decreased episodes
of hypoxemia and apnea.(16) A meta-analysis concluded that utilization of capnography is associated with a
significantly greater (17.6x) chance of detected episodes of ventilatory depression compared to routine monitoring.
(17) In 2011 the ASA amended its Standards for Basic Anesthetic Monitoring to recommend end-tidal carbon
dioxide monitoring during moderate and deep sedation . (4)However, not all studies demonstrate a benefit of using
capnography. Patients undergoing minor gynecologic procedures who did not receive supplemental oxygen showed
no difference in the incidence of hypoxemia when capnography was utilized vs. no capnography. (18) In a small
study of gastroenterologist-administered moderate sedation for colonoscopy without supplemental oxygen, no
difference in the incidence of hypoxemia was seen when comparing patients with and without capnography.(19) It
thus seems that some of our non-anesthesiologist colleagues who administer moderate sedation are not convinced of
the utility of capnography in these patients.
Other respiratory monitoring modalities have been described. It is possible to analyze breath sounds as monitored at
the larynx. While low-technology devices such as a precordial stethoscope placed at the sternal notch may be used,
one commercial monitor has been described: the rainbow Acoustic Monitor™ (Masimo Inc., Irvine, California,
United States). During sedation, when compared to capnography this technology demonstrated a similar ability to
detect respiratory pauses with a decreased frequency of false alarms.(20) In the post anaesthesia care unit acoustic
monitoring had improved sensitivity in detecting respiratory pauses compared to capnography.(21) However, using
respiratory rate alone may miss a significant number of situations of decreased minute ventilation.(22) Another
approach is to monitor impedance changes in the chest wall during ventilation. A monitor has been described that
largely eliminates the issue of false positive during respiratory attempts with a closed glottis, the Respiratory
Volume Monitor (RVM, Respiratory Motion Inc., Waltham, Massachusetts, United States).(23) During
colonoscopy the RVM detected hypoventilation in a greater percentage of patients than did capnography.(24)
Ultimately, more research is required to determine the best method to assure adequate ventilation during NORA
sedation.
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Emerging Issues with Anesthesiologist-Administered Propofol Sedation

Anesthesiologists believe that when they provide sedation for NORA procedures, they are augmenting patient safety
and contributing to improved clinical outcomes, especially compared to sedation care without their involvement.
There have been some recent reports that challenge this assumption. A study that reviewed a 5% sample of a
Medicare database for patients undergoing diagnostic colonoscopy from 2000-2009 compared complications
between patients with and without anesthesiology service codes. They found a significantly higher incidence of
patients who had diagnosis code for aspiration pneumonia in the anesthesia care group .(25) From a larger
administrative claims database from 2008 through 2011 investigators examined outcome codes for 30 days
following colonoscopy in 3,168,228 patients in aged 40-64 years. They found that use of anesthesia service was
associated with a 13% increase in the risk of any complication within 30 days and was associated specifically with
an increased risk of perforation, hemorrhage, abdominal pain, complications secondary to anesthesia and stroke.
Another study utilized the Clinical Outcomes Research Initiative National Endoscopic Database, a network of 84
sites in the United States, and examined the incidence of serious adverse events (SAE) associated with colonoscopy
comparing sedation care delivered by anesthesiology personnel to that delivered by gastroenterologists.(26) They
found no difference in SAE in the colonoscopy patients, but a significantly greater incidence in the upper endoscopy
patients when anesthesia personnel were involved, particularly in ASA I and II patients. These studies suffer from
the problems of using billing data to reflect clinical outcomes, lack of risk adjustment (e.g. were the cases with
anesthesia services involved selected for their complex co-morbidities?), and lack of randomization; still, editorials
in the GI literature are sharply questioning the value of anesthesiology involvement in the GI NORA sedation area .
(27)
It is an interesting moment in the evolution of NORA care. With the recent decision by Johnson and Johnson (New
Brunswick, New Jersey)to discontinue sales of the Sedasys® system, it is entirely possible that another “disruptive
technology” might emerge. The limited data published about Sedasys® demonstrated very high patient and
provider satisfaction from a system that claimed to deliver mild to moderate sedation. (28) Head-to-head
comparison of automated sedation to anesthesiology-administered sedation has not been published. In addition, the
assumption that anesthesiologist-provided care (often deep sedation or general anesthesia with a natural airway) is
safer is being challenged by studies such as those presented above. At the moment, what we believe to be true- that
anesthesiologist-delivered sedation for NORA is a safe practice and beneficial to patients- is yet to be documented
through a rigorous prospective trial.
The situation is reminiscent in many ways to the controversy in the 1990’s when studies in the OB/GYN literature
that linked epidural analgesia to increased Cesarean section rates. This was ultimately addressed by well-designed
and conducted studies that identified the true effects of epidural analgesia on labor and delivery. In the meantime,
however, labor epidural practiced changed from relatively deep blocks to today’s minimalist approaches; the
controversy had some effect on fostering change. We need a similar effort to identify the best methods of
providing care for NORA procedures. We need to know the ideal agents or combination of agents and the
appropriate depth of sedation or anesthesia to provide the safest care with the highest satisfaction. The “best”
approach in the GI suite may not be so for other NORA sites.
Economic Efficiency and Regulatory Compliance

NORA can have significant impact on resource utilization, especially of “human capital”. In physician
anesthesiologist only practices, staff assignments for NORA can be considered much like any other location, but
when working in the anesthesia care team mode or when supervising resident physicians, billing and accreditation
rules can make scheduling more complex. Because of billing rules for medical direction, having scattered remote
sites causes economic inefficiency. For example, a hospital-based endoscopy suite with one room is suitable for a
physician anesthesiologist providing care solo but if practicing in the Anesthesia Care Team model ( with nurse
anesthetists, or anesthesiologist assistants, for simplicity will refer to them both as anesthetists), the anesthesiologist
needs to be directing at least three concurrent locations to be economically feasible. An attending anesthesiologist
can medically direct up to two locations with a combination of resident physicians and anesthetists (a residency
accreditation standard) or up to four anesthetists (or combination of anesthetists and residents) if they are co-located
within a procedure suite (a billing compliance standard). However, interventional radiology suites are often single
settings and with the complexity of procedures being performed in them, the anesthesia team often becomes
inefficient by having a single physician and either an anesthetist or resident on the anesthesia team. Typically, these
suites are geographically remote from the operating rooms, often on separate floors or wings, making it a challenge
to meet the “remain immediately available” criterion for medical direction. If the interventional radiology suite has
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multiple procedure rooms that can be shared by several services such as radiology, neurology, and cardiology, it is
possible to have more efficient use of anesthesia services by having the physician anesthesiologist direct the care for
simultaneous cases in interventional suite. For smaller facilities, designing a multiservice suite will likely improve
its overall utilization and for large quaternary referral centers, each specialty might have enough case volume to
justify a dedicated suite with the ability to conduct multiple concurrent procedures. Encouraging a facility to
construct procedure suites that can be utilized by several specialties improves the operational and economic
efficiencies for both the providers and the facility. Horizontal expansion into more simultaneous anesthetizing sites,
while appearing to be a satisfier for proceduralists, can lead to apparent decreases in anesthesia productivity when
measured as encounters per site per year yet burden the anesthesiology group with the need to hire additional
providers.(29) This may result in the anesthesiology group looking to the facility to share some of their profit from
such procedures to support these economically inefficient (from the anesthesia service stand point) programs.
Scheduling of Anesthesia Services

For services that have sufficient volume, scheduling dedicated time (block time) may improve utilization and ensure
that unassigned time (open time) is filled sequentially will improve financial productivity.(30) Scheduling full days,
whether 8, 10 , or 12 hours long, rather than partial days of coverage should improve efficiency; for lower volume
services this may mean having a long day every other week rather than shorter blocks every week. An economic
goal is to reduce overutilized time, which is more expensive (due to both the cost of paying overtime and the effects
on morale) than underutilized time.(31) If the case volume supports a longer block, it is better to schedule a long day
of ten or twelve hours and be transparent on expectations than to schedule anesthesia services for eight hours and
routinely run over which is a major staff dissatisfier. Scheduling of patients requiring anesthesia services outside of
the operating room can often be cumbersome (not including patients cared for in a hospital setting requiring minimal
or moderate sedation administered by the proceduralist).Scheduling should be integrated into the electronic system
used for the operating rooms to ensure appropriate assignments and enterprise-wide scheduling is more convenient
for the proceduralist and patient, and can improve coordination of appointments and instructions.(32)
Provider Issues
Other aspects of human capital need to be considered. Do the personnel assigned to NORA enjoy working in those
environments? If not, and NORA is seen as a chore, the reduction in job satisfaction caused by such an assignment
can lead to increased staff turnover with its significant inherent costs of recruitment and training.(33, 34)
It has been estimated that recruitment and training costs average 1.5 times the annual salary of highly skilled
employees, so increased turnover has a significant economic impact even beyond the ability to provide patient care.
Non-technical skills (task management, team working, situation awareness, and decision making) while important to
all anesthesiologists, are particularly important in NORA and selection and potential assessment of staff involved in
NORA for these skills can be accomplished.(35)
NORA Leadership
Leadership in developing a NORA program does not end with identifying sites and settling on staffing models. One
of the biggest causes of medical harm is problems with communication.(36) Communication issues in the NORA
environment potentially lie in three major domains: between the anesthesia care team and procedure suite staff;
between the anesthesia care team and the proceduralists; between the anesthesia care team and other anesthesia
providers. Communication between the anesthesia team and the procedure suite team in NORA locations can be
critical. This may be because of hazards of the local setting such as ionizing radiation exposure or the impact of
magnetic fields that produce a direct hazard to the providers or patient, or it may concern support for the anesthesia
providers themselves. However, NORA presents a setting where many of the factors impeding effective information
transfer are rampant, including high-acuity settings such as the Operating Room and information sharing across
professional boundaries.(37) A request to the circulating nurse in an operating room to apply cricoid pressure or
hand a mask is reasonably expected to be fulfilled as required. However, asking the procedural technician to “hand
me the mask” might be met with a blank stare or the wrong item (facemask for ventilation, personal protective
equipment, or even masking tape) because of the lack of knowledge about anesthesia needs in that group. The
educational level of nurses has increased over time with the majority now holding at least a bachelor’s degree in
nursing;(38) however, the technical staff in a specific area, such as radiology my not be nurses and may have limited
general medical training.
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Communication between the physician anesthesiologist and the proceduralist is also crucial. Clearly understanding
the proposed procedure and likely events is important in all anesthetics. In NORA, patient selection and preoperative
discussions of special issues is crucial. While the proceduralist might be more comfortable performing the case in,
say, the endoscopy suite, patient factors might influence whether or not the case should be done in a remote setting
without the support available in a standard operating theater. For example, a critically ill patient with the need for
specialized invasive monitors might be better supported in the operating room; it is up to the anesthesiologist to
negotiate with the proceduralist to balance whose specialized equipment and support structures are most portable in
those cases. If the procedure must be done in the remote site (such as interventional neurology requiring specific
imaging equipment with specialized software packages), careful planning beforehand can offset many of the risks of
working in the remote environment.
Lastly, in developing a NORA program or site, the physician anesthesiologist leaders should develop plans for
assistance when needed. In traditional operating rooms it is common to have an overhead paging system with which
one can call for “any anesthesiologist” to assist and have a reasonable expectation that those not personally
providing anesthesia care would respond. In remote locations, how does the anesthesia team call for help? This can
range from needing more labels for medications to a critical event. Activating a “code blue” may get people there,
but the “code team” is unlikely to be familiar with the needs and issues of a patient under anesthesia. And, what if
something more specific is needed, such as help with an unexpected difficult intubation? Having a radio, mobile
phone, or other system in place and having educated the non-OR staff on how to activate the help system can be life-
saving for the patient and certainly would reduce stress and difficulties for the anesthesiologist. Setting in advance
how to summon help and who will respond is an important leadership function.
Customer satisfaction is always an important issue. As anesthesiologists providing NORA services, identifying the
customer is key. The patient, first and foremost, is our customer and ensuring a safe, effective, and timely anesthetic
should be our primary goal. Appropriate pre-procedure evaluation and addressing the concerns of the
patient/patient’s surrogates and family will go a long way toward satisfying this customer. Another customer is the
proceduralist. While the proceduralist has many drivers such as competing duties, consults, clinic patients to see,
etc., ultimately s/he has the same goal in mind- caring for the patient. Communication with these other physicians
will go a long way towards not only improving care, but achieving high levels of satisfaction. Lastly, the third
customer is the hospital administration. They want timely and efficient provision of services resulting in improved
patient outcomes. Anesthesiologists should take the lead in designing processes for NORA that help satisfy all
customers. One option for improving patient, proceduralist, and hospital administrator satisfaction is to have a
“service guarantee” such as agreeing that NORA cases will be accommodated within a two-week window of the
request. This differs from block time in that the anesthesiology group is committing to offering a time, not a specific
time within that window.
Another major leadership entity in NORA concerns the anesthesiologist oversight over procedural sedation provided
by the proceduralists as mandated by CMS as a condition of participation. Anesthesiologists’ presence in NORA
would facilitate such service, and strengthen their relationship with the procedural sedation teams with the goal of
enhancing patient safety and outcomes. Moreover, the anesthesiologists practicing in NORA will need to be in
charge or at least playing a major role in crafting the policies and procedures that govern NORA services.
NORA and Changes in the US Health Care System
A looming issue is how do we as anesthesiologists adapt NORA in the move towards value-based purchasing of
health care and population health. Publically reported performance measures are more frequently including cost as a
measure and with more patients having health care coverage under high-deductible plans, the out-of-pocket coast
can be a significant driver of where patients receive care. Under current fee for service payment systems, NORA
cases may not decrease the charges from hospitals because of their reliance on Diagnosis Related Codes (DRG) and
Ambulatory Procedure Codes (APC) for billing, but increased use of NORA might expand capacity and reduce
length of stay, helping health care systems meet the triple aim of improving the health of their patients through faster
service, enhancing patients’ experience and outcomes when receiving care, and reducing the total cost of care. Since
some procedures (dental, endoscopy) do not need the sterile environment of an operating room, facilities may be
able to provide these services in facilities that cost less to build and maintain. How empty hospitals are (by reducing
length of stay and need for admission) is an indicator of how successful the health care system is at achieving the
triple aim.(39) Under population health, proceduralists become cost centers rather than revenue centers to the
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facility. That is, the facility would no longer look to the proceduralist as one who brings in dollars but rather
someone who is spending health care premium dollars that would otherwise flow to the facility’s bottom line.
Anesthesiologists need to position themselves as leaders in how to meet that triple aim of health care.
Conclusion:
1The future of NORA is bright and as more minimally invasive procedures replace conventional surgeries, the
demand for the anesthesiologist’s role outside the operating room will expand.(40) As a result, we must leave the
familiar environment of the operating rooms and venture into the unfamiliar territory of hospital policy and
procedures to ensure that our non-operating room patients receive the same high standard of care that is available to
them in the operating room. Successful safe delivery of NORA would require well thought out plan and organization
(table 4). Patient safety in the NORA area is of paramount importance, more efforts are necessary if we are to
maximize safety through better training and better use of technology and pharmacology. Enhanced knowledge from
new research findings will enable us to strengthen our efficiency in this arena and accommodate the growing
number of patients and specialists requiring our services. Anesthesiologists must continue to provide safe care and
develop the evidence-based medicine to demonstrate value and to improve practice.
Table 4. The 8 effective habits for successful NORA
1 Improvement in pre-procedure evaluation
2 Improvement in NORAPACUs
3 Adequate anesthesia equipment and reliable support
4 Development of database for clinical outcomes
5 Improved billing for anesthesia services
6 Identification and formalization of leadership (anesthesiologists, proceduralists, nurses)
7 Involvement of anesthesia in procedural ( moderate) sedation
8 Improvements in scheduling
Adopted with permission from Dr. Walter Maurer, MD, Emeritus President of the Society for Ambulatory
Anesthesia (SAMBA);
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Table1: Locations for Non-Operating Room Anesthesia (NORA) Services
Gastroenterology Endoscopy Suite
Interventional Radiology areas including CT
Bronchoscopy Suite
Cardiac Catheterization Lab
Electrophysiology Lab
MRI ( Diagnostic, and surgical)
Nuclear Medicine
PACU (Electroconvulsive therapy)
Pain Management procedure rooms
TABLE 2: Sources of Complexity in Nora And Proposed Solutions
Challenge Description Solution
Space Anesthesia is an afterthought, insufficient Be part of the plan from inception to ensure these areas
room for anesthesia machine or supplies are designed wirh dedicated anesthesia space
Equipment Not enough and old equipment are used Ensure the same equipment standards as in the main
operating rooms initial planning involvement to set
capital budget for startup
Staff Proceduralists and their teams are not used Effective communication, team building, clear
to working with anesthesia teams expectations
Patients High risk patients are served Establish and optimize the pre-op evaluation process. ,
maintain monitoring standards, develop a formal
system for summoning help and designate a well-
trained recovery staff and location
Procedures New , complex , more invasive and risky Effective communications, pre-operative time
procedures out,including discussion of procedure and anesthetic
concerns
Table 3: Monitoring equipment typically employed during an anesthetic.

Electrocardiogram
Blood pressure (manual, automatic, arterial catheter)
Pulse oximeter
Capnograph
Oxygen analyzer
Anesthetic agent concentration analyzer
Temperature (when indicated)
Gas flows/spirometry (part of anesthesia machine)
Airway pressure monitor (part of anesthesia machine)
Airway disconnect alarm
Muscle twitch monitor (where muscle relaxants have been used)
Urometer (measure urine output - where appropriate)
Depth of hypnosis monitor ( optional, more so preferred for TIVA)
Table 4. The 8 effective habits for successful remote location anesthesia
1 Improvement in pre-procedure evaluation
2 Improvement in remote location PACUs
3 Adequate anesthesia equipment and reliable support
4 Development of database for clinical outcomes
5 Improved billing for anesthesia services
6 Identification and formalization of leadership (anesthesiologists, proceduralists, nurses)
7 Involvement of anesthesia in moderate sedation
8 Improvements in scheduling
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Virtual Cadaver Lab –

Anatomy Pearls in Regional Anesthesia to Improve Clinical Success
David B. Auyong, MD Seattle, WA
Key Words:
Regional Anesthesia
Anatomy
Nerve Blocks
Learning objectives:
1) Compare highlighted anatomical structures in photos of fresh tissue dissections to anatomical

structures on ultrasound images and videos;
2) Summarize the anatomical relationships of nerves to surrounding structures that facilitate
placement of nerve blocks and improve clinical efficacy of regional anesthesia;
3) Examine, at a gross anatomy level, why some nerve blocks are more appropriate than others for
specific surgeries of the upper and lower extremity;
4) Recognize anatomic variations in ultrasound images and cadaver dissections and correlate how
these variations affect regional anesthesia
Description:
This lecture covers the anatomical relationships of nerves, vessels, muscle, bone, and skin that form the
foundation of regional anesthesia. Images will be presented from multiple dissections in many different
fresh tissue cadavers. Unique and clinically relevant correlations will be made between classic anatomical
textbook images, the cadaver anatomy and ultrasound images. Anatomical pearls will be reviewed and
highlighted for many nerve block approaches to the upper and lower extremity including interscalene,
supraclavicular, suprascapular, infraclavicular, axillary, femoral, fascia iliaca, adductor canal, and the
sciatic nerve in the subgluteal and popliteal regions. The interplay of gross anatomy and ultrasound images
will cement important anatomical relationships, improving clinical success in regional anesthesia. Many oft
repeated teachings in regional anesthesia will be explored and then confirmed or refuted by revisiting the
gross anatomy of the human body.
Summary:
Interscalene Nerve Block
The interscalene nerve block is performed to supply analgesia to the shoulder and clavicle. Anatomical
landmarks that can be identified are sternocleidomastoid muscle, anterior/middle scalene, pre-vertebral
fascia, roots and trunks of the brachial plexus, vascular landmarks, and specific nerve roots (primarily C5 -
monofasicular and C6 – bifasicular). C7 is much deeper. Ultrasound resolution is good enough allowing us
to image some of the fascicles that make up the microscopic anatomy of these nerve roots and trunks. It is
not good enough to image all fascicles. Other nerves that can be identified include dorsal scapular, long
thoracic, suprascapular, and phrenic.
Supraclavicular Nerve Block
Evaluation of the classic image of the supraclavicular nerve block compared to cadaver dissections and
microscopic anatomy results in most concluding that this block is usually performed at the level of the
trunks. There are three trunks of the brachial with differing emphasis on injection depending on location of
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the surgery. At this level the suprascapular nerve is usually quite identifiable and presents a good location
for local anesthetic deposition for shoulder surgery. The suprascapular nerve can often be located at the
most lateral point of the supraclavicular ultrasound image. For more distal surgery (elbow or lower) the
injection at the lower trunk is likely more appropriate.
Cervical Plexus Nerve Block
Although previously divided into a deep (muscular) and superficial (skin) nerve block without ultrasound
guidance, a complete cervical plexus block can now be easily performed with an injection between the
sternocleidomastoid (superficial) and scalene muscles (deep). In subjects that image well, small nerve
roots of C2, C3, and C4 can be readily visualized traveling in this plane above the prevertebral fascia.
Infraclavicular Nerve Block
The infraclavicular nerve block is significantly facilitated by the Houdini Clavicle maneuver (abducting the
arm). This moves the clavicle posterior and allows for a more posterior needle insertion. This posterior
needle insertion allows a needle trajectory that is perpendicular to the ultrasound wave propagation and
therefore results in a brighter needle image during advancement. This advancement also ensures injection
deep to the clavipectoral fascia, a primary barrier to success. Dissections will show significant anatomic
variation and the clinical correlate is to place local anesthetic deep to the artery for good success, peri-
arterial for optimal success. For safety, needle trajectory should be aimed laterally. A variation is the
RAPTIR approach behind the clavicle that can be useful when arm abduction is not possible.
Axillary Nerve Block
The axillary nerve block is similar to the infraclavicular block in that the nerves, though often described in
a classic sense are almost randomly arranged around the axillary artery. In the same patient, nerves can be
mobile and found in different places depending on arm, probe position, or probe compression. Most
importantly, the “conjoint tendon” is not a tendon but rather a fascial covering. Tendons are terminations
of muscles, not covering of muscles. Whatever you want to call it, the fascial covering of the teres major is
the perfect anatomic structure to make axillary block reliable. Usually this blocks takes two or three
injections: One below, one above, and the musculocutaneous.
Femoral Nerve Block:
The femoral nerve block is dependent on placement of the local anesthetic under the fascia iliaca. The
“triangle” next to the artery is not the femoral nerve. The branch of the femoral nerve that exits to innervate
the sartorius muscle exits superficially and therefore is often stimulated with classic stimulator or out-of-
plane femoral nerve block approaches. The “fascia iliaca” block is not much different than a properly
executed femoral nerve block and likely provides the same clinical effect. A good ultrasound sign of proper
injection deep to the fascia iliaca is the spread of local anesthetic underneath the artery. Innervation of the
hip joint from the femoral nerve is significant and the branches to the hip capsule exit after the classic area
a femoral nerve block is performed. The arteries of the femoral regional provide a perfect road map to
identifying the femoral nerve.
Selective Femoral (Adductor Canal) Nerve Block:
The adductor canal nerve block is performed by identifying the superficial femoral artery in the medial
mid-leg. At this level, the sartorius muscle presents an important landmark for placement of the adductor
canal block. The sartorius muscle crosses over the artery so the placement of the artery directly under the
sartorius muscle is a reliable landmark to ensure the block is not performed too proximal or too distal. The
nerves of the adductor canal are reliably found with the artery at this level and are covered with a vasto-
adductor membrane. This membrane must be traversed in order to place reliable nerve blocks at this level.
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Sciatic, Popliteal
The anatomic relationship of the tibial nerve, artery, and vein at the crease of the knee (snowman) allows
the tibial nerve to be easily identified. At this level, the nerves are surrounded in adipose tissue give two
clinical correlates: a bayonet artifact may be present with in-plane needle approaches and prolonged nerve
blocks may be possible. Clinically, the tibial component (medial and larger) of the sciatic nerve deserves
the majority of the local anesthetic resulting in higher quality nerve blocks. Most of the innervation to the
knee, leg and foot from the sciatic nerve can be blocked with this approach.
Paravertebral Nerve Block (PVB)
There are many approaches to the paravertebral block and each technique can work in the right hands. The
reason we do PVB blocks is to get mutli-level spread and sympathetic fibers, which can theoretically
improve analgesia over intercostal blocks. Some keys are to recognize the PVB space as related to the
intercostal space. Whether in-plane or out-of-plane, error on safety as pneumothorax in this setting would
be detrimental to a block program. The nerve exits and is found reliably about 1cm deep to the transverse
process. The lung should not be readily visible when imaging the paravertebral space. The superior
costotransverse ligament forms the dorsal (posterior) portion of the paravertebral space and needs to be
accurately described in the medical literature as it is often mislabeled. It is a ligament that courses from the
transverse process superiorly to the rib inferiorly. It does not join with the pleura.
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Local Anesthetics in 2016: Mechanisms, Toxicities and Controversies From a Clinical

Perspective
John F. Butterworth, IV, M.D. Richmond, Virginia
General Considerations
Local anesthetics (LAs) and regional anesthesia were introduced to western medicine in 1884 when Köller and
Gartner reported topical cocaine anesthesia of the corneas of a frog, rabbit, dog and of each other and when Halsted
reported brachial plexus and mandibular nerve blocks in patients.1 Notable subsequent advances in LAs and regional
anesthesia have included: better understanding of LA mechanisms; safer LAs; LAs compounded with novel drugs,
microspheres, liposomes, toxins, or other LAs; better needles and infusion devices; more reliable techniques for nerve
localization and LA injection; safer techniques for conscious sedation; and more effective resuscitation techniques for
LA systemic toxicity (LAST). This review will review the current state of knowledge while focusing on the scientific
and clinical implications of studies performed in the past few years.
LA Structures and Chirality

LAs share many structural features. All LAs save for articaine, an agent used
almost exclusively in dentistry, have a substituted benzene ring at one end of the
molecule and a tertiary amine nitrogen at the opposite end (Figure 1).2-5 Articaine has
as a thiophene (sulfur containing) ring in the place of the benzene ring. LAs are
designated either as an ester or an amide based on a chemical linkage in the middle
portion of the molecule. Assymetrically substituted (chiral) carbon atoms in
compounds that are commercially available as single S(-) enantiomers are designated
with an asterix (*) on Figure 1. Mepivacaine has a chiral carbon atom but no asterix
because it is only supplied as a racemic mixture. Bupivacaine is either a racemic
mixture or a single enantiomer (levobupivacaine) as indicated on the figure. Other
compounds that produce local or regional anesthesia have widely varying structures
and include: general anesthetics, α2 agonists, tricyclic antidepressants, alcohols, nerve
toxins, cannabinoids, and even 2-heptanone, a honey bee secretion!2,7-15 Some of these
compounds inhibit voltage-gated Nav channels, confirming that their mechanism of
clinical action could be the same as “classical” LAs. Perhaps one of these “non-
traditional” antagonists will prove safer or more effective than traditional LAs.16
Voltage-gated Na (Nav) Channels

A sufficient number of Na v channels must activate and “open” to initiate and/or
propagate Na currents and action potentials in an axon.3-5 After being applied near a
peripheral nerve LAs may migrate into the axonal plasma membranes, where they bind
Nav channels and prevent them from “opening.” Nav channels are large, integral
membrane proteins containing 1 larger α-subunit and 1 or 2 smaller β-subunits. The α-subunit, the site of ion
conduction and drug binding, includes roughly 2000 amino acids and 4 “domains,” each with 6 α-helical, membrane-
spanning segments. β-subunits regulate multiple channel activities, including channel insertion into the plasma
membrane and the voltage-dependence and kinetics of α-subunit gating.3-5,17,18
Humans have 7 genes that code for neuronal Nav channel α-subunits, 1 gene that code for Nav α-subunit isoforms
in skeletal and and another gene for cardiac muscle, and 1 “silent” nonfunctional Nav channel α-subunit gene.19,20
Specific Nav isoforms (gene products) predominate on unmyelinated axons, nodes of Ranvier, and small dorsal root
ganglion nociceptors. Genetic variants of Nav 1.5 (the isoform found only in cardiac muscle) require differing
therapeutic drug concentrations.21 Similarly, Nav isoforms may have differing drug affinities.19 Alternative splicing
of gene products can yield additional variation, as was demonstrated for Nav 1.7 channels in human dorsal root ganglia
(DRG).22 Some isoforms may be particularly important in the pathophysiology of chronic pain syndromes or in small-
fiber neuropathy.23 Nav 1.7 accumulates in painful human neuromas.23 Nav 1.8 increases in DRG in animal models of
inflammatory pain and increases in peripheral afferent nerves when there is persisting pain after a spinal cord injury.24
Increased prevalence of Nav 1.9 associates with painful diabetic neuropathy. Na v 1.3 expression in DRG increases
after peripheral nerve injury and in human neuromas formed after injury. Na v 1.6 may underlie repetitive firing in
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lumbar DRG neurons with inflammation and knockdown of this channel eliminates abnormal spontaneous DRG
electrical activity and pain behavior in animals.25
Nav channels exist in at least 3 functional states in vivo: “resting,” “open,” and “inactivated,” as was first described
by Hodgkin and Huxley.2-4 During action potentials Nav channels “open” briefly, allowing Na ions to flow into the
cell, depolarizing the plasma membrane. After a few milliseconds, Nav channels “inactivate” and Na flux ceases.
Mammalian myelinated fibers require no contribution from K currents for membrane repolarization, and Nav channels
return to the “resting” conformation with repolarization. 2-4 Such “voltage gating” of channel states likely results from
small movements of paddle-shaped, voltage-sensing amino acid sequences.26 Patients with genetic Nav variants in
which “resurgent” Na currents appear during repolarization, presumably from a lack of conventional inactivation, may
present with a paroxysmal extreme pain disorder (Nav 1.7), paramyotonia congenital (Na v 1.4), and long-QT3/sudden
infant death (Nav 1.5), depending on which isoform is abnormal.20
Mechanisms of Local Anesthesia by “Classical” and Quaternary LAs

In 1959 Taylor demonstrated that LAs inhibit Na currents yet standard anesthesia textbooks continued to discuss
other discredited mechanisms of LA action for more than 30 years! Our knowledge of LA electropharmacolgy is now
much more refined. LA binding has been associated with specific regions of the Nav α-subunit.3 Some Nav isoforms
are less sensitive to LA or tetrodotoxin (TTX) than others.13,27 LA inhibition of Na currents increases with repetitive
depolarizations, often called “use-dependent” block, a phenomenon believed to underlie antiarrhythmic actions of
LAs.2 What is the mechanism of “use-dependent” block? One possibility: repetitive depolarizations increase the
fraction of Nav channels that are “open" or “inactivated” relative to “resting” channels with less LA affinity.2,19
Alternatively, LAs may preferentially modulate Na v channel movements associated with opening events.
Compare lidocaine with its quaternary derivative QX-314 in Figure 2. Note QX-314’s positively-charged nitrogen
(see the “+”) as a consequence of QX-314’s extra ethyl moiety. When QX-314 is applied intracellularly, this relatively
membrane-impermeant agent powerfully inhibits Na currents.4,5 But does this have
relevance to clinical use of LAs where there is no opportunity to deliver agents
intracellularly? Recent studies strongly suggest that QX-314 and other drugs may gain
entrance to the cytoplasm through vanilloid TRPV1 channels when these channels are
activated by pain, lidocaine or capsaicin.28-32 TRPV1 channel activation underlies
nociception in primary sensory afferent fibers.33 After a greater delay of onset than with
lidocaine, quaternary local anesthetics produce prolonged analgesia (perhaps by transit
through TRPV1 channels).34 Recently, infused QX-314 has been shown to relieve cancer
induced bone pain in animals by selective inhibition of TRPV1 channels in primary
afferent neurons.35
LA Actions at Sites Unrelated to Nav Channels or Nerve Block

LAs have limited potency and are relatively nonselective. LAs solubilize and disrupt
membranes. LAs bind and inhibit channels (including KATP, Ca release, voltage-gated K,
Ca, and HERG), enzymes (including mitogen activated kinases, adenylyl cyclase, and
phosphorylases), receptors (nicotinic acetylcholine, NMDA, β-adrenergic, TRPV1, bradykinin B2, 5-HT3), and
signaling mechanisms (G-protein-mediated signaling).2,36 LA binding to these sites could contribute to spinal or
epidural anesthesia, useful or toxic effects of systemically absorbed LAs, or (despite being described in myriad
publications) have no importance whatsoever!36 Circulating LAs have effects on coagulation, inflammation,
microcirculation; immune responses to infection and malignancy, postoperative gastrointestinal function, and
analgesia.37 Infused LAs relieve neuropathic pain and improve perioperative analgesia.38 Infused LAs shorten hospital
lengths of stay as effectively as epidural analgesia. Lidocaine inhibits cardiac ischemia and reperfusion injury in mice
by an antiapoptotic effect.39 Conversely, LAs promote apoptosis and may promote chondrolysis after prolonged
intraarticular infusion.40,41 LAs inhibit kinesis theoretically inhibiting cancer metastasis. Should we conclude that LAs
are the new wonder drugs? Probably not! Other studies suggest that any beneficial effect of LAs or regional anesthesia
on cancer progression likely is the result of reduced opioid consumption and not from a direct effect of the LA on
cancer cells.42 Finally, a recent study confirmed that reduced opioid requirements after intraperitoneal LA were the
results of local, not systemic, LA actions.43
LA Pharmacodynamics
LA Volumes and Concentrations during Nerve Block
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During clinical regional blocks, only a vanishingly small fraction of the injected LA molecules will be bound by
neuronal Nav channels specifically or even by neurons generally.44 Most drug molecules will be bound by other tissues
and/or be removed by the blood stream. As noted earlier, clinical regional anesthesia will not arise unless conduction
is blocked over a sufficient length of nerve. This “critical length” exceeds 2 cm (far longer than the 3 Ranvier nodes
specified in textbooks) except at very increased LA concentrations.45 Extent and duration of LA effects can be loosely
correlated with LA content of nerves in animal experiments. 44,46-48 There is debate as to whether injectate volume,
injectate concentration, or mass (volume x concentration) of drug is paramount in determining the success of blocks.
In rat sciatic nerve blocks, lower volumes of more concentrated lidocaine produce shorter latencies and longer
durations.48 Nevertheless, human studies often conclude that anesthesia quality improves with increasing mass of drug,
whether achieved by increasing volume or concentration.49.50
Maximum doses
It is foolish to speak of one, universal, “safe” maximal dose of a LA compound, yet lecturers, textbooks and
regulatory agencies perpetuate this nonsense.51 The maximal tolerable dose depends on many factors, including the
site, rate, and duration of LA administration, additives, patient weight and body habitus, and the presence of pregnancy
or disease. A LA dose given for intercostal blocks produces greater peak LA concentrations than if given for plexus
or epidural blocks.3,52 A LA concentration in blood produced by a sudden, accidental bolus iv injection may produce
CNS toxicity; the same concentration approached gradually over time as a consequence of LA absorption during a
perineural infusion may have no discernible adverse effects. Despite the use of ultrasound during nerve blocks
complete with direct visualization of nerves and reduced LA doses, accidental intravenous injection and LA systemic
toxicity remain a risk.53
LA Potency and Duration
Nerve-blocking potency of LAs increases with increasing molecular weight and increasing lipid solubility. 52,54,55
Larger, more lipid-soluble LAs bind Nav channels with greater affinity and are less readily “washed out” from nerves
than smaller, less lipid-soluble LAs. Increased lipid solubility also associates with increased protein binding, longer
duration of action, and an increased potency at CV toxicity. Think of the profound reduction in potency, onset delay,
and duration of block that result from a methyl for butyl substitution (compare mepivacaine to bupivacaine in Figure
1, with mepivacaine being the smaller, less potent, less lipid soluble agent).
LA Speed of Onset
Generally, the onset of clinical regional anesthesia slows with increasing LA lipid solubility (compare
mepivacaine to bupivacaine or chloroprocaine to tetracaine). Curiously, many textbooks describe pKa as inversely
related to delay of onset despite contradictory data!52 Chloroprocaine, the agent with the largest pKa, has the shortest
delay of onset of all.56
Differential Sensory Nerve Block
A LA nerve block that is sufficient to block incisional pain will impair motor function. 2 Smaller fibers can be
blocked at lower concentrations of LA than larger fibers of the same type. 2 But, greater LA concentrations are required
to block impulses in C fibers than in Aδ or Aβ fibers.46,57 Bupivacaine and ropivacaine are relatively selective for
sensory fibers.58 As previously noted, differing Nav channel forms have distinct affinities for LAs and other
compounds, and specific Nav channel gene products are found in unmyelinated nerves, motor nerves, and dorsal root
ganglia, offering the tantalizing, as yet unrealized, possibility of selective drugs.26,559,60
Other Factors Influencing LA Activity
Many factors influence the quality of local and regional anesthesia, including the dose, site of administration,
temperature, pregnancy, diabetes, and additives. In general, the fastest onset and shortest duration of anesthesia occur
with intrathecal or subcutaneous injections; a slower onset and longer duration are obtained with plexus and peripheral
nerve blocks.2,52 Pain on injection of warmed LA solutions is less than with room temperature solutions, which hurt
less than cold solutions.61 Pregnancy increases both spread of neuraxial anesthesia and neuronal susceptibility to
LAs.62,63 Diabetic patients and diabetic animals appear to have delayed recovery from peripheral nerve blocks. It is
unclear that this results from increased susceptibility to LAs of diabetic nerves because there is no obvious effect of
diabetes upon onset of anesthesia.64
Is There Convincing Evidence for Preemptive or Persisting Effects of Local Anesthetics?
Many studies show the need for opioids and other analgesics is greatly reduced following peripheral nerve blocks
or local anesthetic infusions and this effect persists for multiples of the local anesthetic elimination half-life. It is likely
that absorbed local anesthetic may contribute to analgesia following nerve blocks; however, most studies indicate that
actual nerve blocks provide better analgesia than local anesthetic infusions. Whether nerve blocks are administered
before or after the surgical procedure does not appear to be of major importance for postoperative pain control or long
term outcomes.38
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LA Formulations for Prolonged Analgesia

After a single injection, with or without additives, LA effects generally will not persist longer than 24 hours. This
limitation has led investigators to explore ways to prolong LA actions. Continuous (catheter infusion) blocks and
wound infusion catheters represent one approach to prolong the clinical effects of LAs. Lidoderm™ patches provide
sustained 24-hour release of topical lidocaine for relief of postherpetic neuralgia. Exparel™ a liposomal suspension
of bupivacaine has a licensed indication for administration into the surgical site to produce postsurgical analgesia.
After bunionectomy or hemorrhoidectomy (the two procedures that were studied prior to regulatory approval), when
combined with opioids this agent produced better pain scores than opioids alone. Nevertheless, there was no difference
in pain scores after 24 hrs despite Exparel™ patients requesting less opioid dosing than placebo patients. This agent
is being studied for some peripheral nerve blocks with mixed success.64 It could ultimately form part of the “local
infiltration analgesia” mixture of dilute local anesthetic and ketorolac that has become the mainstay of analgesia after
total knee arthroplasty in Scandinavian countries.65
LA Additives and LA Mixtures

The most popular LA additives in anesthesia practice (epinephrine, clonidine, opioids, NaHCO3, dextrose, and
steroids) are variously added to increase the safety, quality, distribution, duration, and speed of onset of anesthesia,
and to reduce blood loss.2,52,66 Clonidine and dexmedetomidine have LA properties and prolong the duration of nerve
blocks produced by lidocaine and mepivacaine.11 NaHCO3 increases the fraction of LA molecules that are uncharged,
increases the apparent LA potency, and speeds the onset of some nerve blocks.2,67 NaHCO3 is particularly useful in
speeding the onset of anesthesia produced by more “acidic” LA formulations, such as those that are prepared with
epinephrine by the manufacturers. Bicarbonate also reduces the pain of local infiltration. Opioids are commonly added
to spinal or epidural LAs. Recent preclinical studies have explored combinations of LA with nerve toxins and have
measured prolonged analgesia relative to the LA alone.68
Mixing of LAs has long been popular. In current practice mepivacaine is often mixed with bupivacaine or
ropivacaine in the hope of decreasing the onset delay. Data generally indicate that mixtures yield onset delays and
durations approximating the mean of the component LAs. The toxicity of mixed LAs appears to be no more and no
less than additive.69
There are persisting misconceptions about epinephrine. One is that LA-epinephrine solutions are unsafe in
patients at risk for coronary artery disease. However, in high-risk patients, epinephrine reduces LA concentrations in
blood without producing tachycardia, arrhythmias, or myocardial ischemia. 70 Another misconception is that
epinephrine is unsafe in digital nerve blocks. Review of the published medical literature shows no amide LA-
epinephrine combination ever having been linked to gangrene after digital block. LA solutions containing epinephrine
are now widely used by dermatologists and hand surgeons for digital nerve blocks.71
LA Blood Concentrations, Protein Binding, Metabolism, and Pharmacokinetics

In blood, all LAs are partially protein-bound, primarily to α1-acid glycoprotein (AAGP) and secondarily to
albumin. 52 LA affinity for AAGP increases with hydrophobicity and decreases with protonation.72 Extent of protein
binding increases with increasing concentrations of AAGP. Protein binding and AAGP concentrations decline during
pregnancy.73 During longer infusions of LA, concentrations of serum binding proteins progressively increase. 74 There
is considerable first-pass uptake of LAs by lung.75 Ester LAs undergo rapid hydrolysis in blood, catalyzed by
pseudocholinesterase.52 Procaine and benzocaine are metabolized to p-aminobenzoic acid (PABA). Amide LAs
undergo oxidative N-dealkylation in the liver (by cytochrome P450).52 Amide LA clearance depends on hepatic blood
flow, hepatic extraction, and enzyme function; clearance is reduced by drugs and conditions that decrease hepatic
blood flow such as β-adrenergic or H2-receptor blockers, and heart or liver failure.52
Toxic Side Effects of LAs

LAs can produce a long list of toxic side effects of which the following types seem most often to be associated
with misconceptions, confusion, and examination questions!
Methemoglobinemia
Generations of textbooks have described the unique and predictable production of methemogloblinemia at
prilocaine doses >600 mg in adults.52 In fact, lower doses given to healthy patients produce toxic
methemoglobinemia.76 Nevertheless, perioperative methemogloblinemia in North America more commonly results
from benzocaine, dehydration, or drugs other than prilocaine!77 Thus, topical benzocaine (formerly ubiquitous in
endoscopy suites) has been removed from the formularies of many hospitals.
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Allergy
Textbooks state (usually without providing data) that there is greater risk of allergy to ester than amide LAs,
particularly to those LAs (procaine and benzocaine) metabolized to p-aminobenzoic acid.52 True LA allergy is rare.
Despite an apparent “allergic” or even anaphylactoid reaction, only a rare tested patient will have a IgE immune
responses to preservative-free LAs.78-80 Allergy to LAs must be distinguished from allergy to other agents (e.g. latex,
antibiotics, paralytics, blood products) and also from other conditions that mimic allergic reactions.81
Cardiovascular (CV) Toxicity
LA-associated death (after cocaine or tetracaine topical anesthesia) first was formally studied by a national
commission in the 1930s. After >80 years many important, fundamental issues remain unsettled including: 1. What is
the mechanism(s) of LA CV toxicity? 2. Do all LAs produce CV toxicity by a common mechanism(s)? 3. Which
animal model best mimics clinical LA systemic toxicity (LAST)?82,83 4. Has the introduction of ultrasound reduced
the risk of LAST?
As previously mentioned, the specific Nav channel forms and LA binding are different in the heart than in
peripheral nerves.84,85 “State” specific binding may explain how relatively low blood concentrations of LAs that have
no effect on nerve conduction can have major positive or negative effects on the heart. “Slow” LA binding to Nav
channels in the inactivated state occurs at relatively low LA concentrations and is likely of greater importance when
LAs serve as class I antiarrhythmics or produce LAST than as an explanation for how LAs produce conduction block
of peripheral nerves.85 The greater concentrations typically used for regional anesthesia are sufficient even for LA
binding and inhibition of “resting” Nav channels.
Laboratory studies provide insight into why bupivacaine appears to have a greater propensity to produce severe
LAST than most other LAs. Bupivacaine binds cardiac Nav channels more avidly and longer than lidocaine. 3-5 R(+)
isomers bind cardiac Nav channels more avidly than S(-) isomers (levobupivacaine and ropivacaine).86 When applied
to isolated cardiac Nav1.5 channels bupivacaine produces concentration- and voltage-dependent inhibition. It
promoted inactivation and impaired activation of Nav1.5. 87 LAs inhibit cardiac conduction with the same rank order
of potency as for nerve block.88 LAs produce myocardial depression. As noted earlier, LAs bind and inhibit cardiac
Ca and K channels, but at concentrations greater than needed to inhibit Nav channels.2,89 LAs bind β-adrenergic
receptors and antagonize epinephrine stimulation of adenylyl cyclase. 90,91 LAs produce CNS excitation, tachycardia,
and hypertension at lower doses and concentrations than those associated with cardiac depression. 52
Different LAs have differing patterns of CV toxicity. In whole animal experiments, most LAs will only produce
CV toxicity at blood concentrations greatly exceeding those producing seizures; however, experimental and clinical
reports suggest a reduced margin of safety for bupivacaine compared to other agents.52,92 In dogs, supraconvulsant
doses of bupivacaine more commonly produce arrhythmias than supraconvulsant doses of ropivacaine or lidocaine.92
Animals premedicated with midazolam or diazepam (or receiving general anesthesia) may manifest bupivacaine
LAST as CV collapse without convulsions.93 In animals, the rank order of potency for cardiac toxicity appears to be
the same as for nerve block.94,95 Both programmed electrical stimulation and epinephrine elicit more arrhythmias with
bupivacaine than with lidocaine or ropivacaine.96-98 When given LAs to the point of extreme hypotension, dogs given
lidocaine could be resuscitated, but required continuing infusion of epinephrine to counteract LA-induced myocardial
depression. When extreme hypotension was produced by bupivacaine or ropivacaine, some dogs required only
electrical defibrillation; others could not be resuscitated using the full ACLS armamentarium.96-98 Studies in pigs also
show that bupivacaine (compared to lidocaine) may have a greater relative potency for producing both arrhythmias
and myocardial depression, but that the potency ratio for producing arrhythmias is much greater (16:1) as compared
to their relative potency at producing nerve block .99
Chondrotoxicity
In recent years there has been increasing use of LA infusions into surgical wounds for postoperative pain control. As
previously mentioned, some patients who received LA infusions into joint spaces have developed chondromalacia,
and this has resulted in litigation against physicians and suppliers of LAs and wound infusion devices. Increasing
evidence documents adverse effects of LA infusions on articular cartilage leading to a growing consensus that
prolonged exposure (days) of articular cartilage to LAs is ill-advised.41,100,101
Treatment of LA Toxicity
Serious degrees of methemoglobinemia are treated with oxygen and methylene blue 1 mg/kg IV. Anaphylactoid
reactions may require epinephrine, fluid resuscitation, and steroids. Minor LA reactions usually will terminate
spontaneously. Severe LAST requires active treatment in which adherence to a check-list protocol will likely increase
patient safety.102 LA-induced seizures require maintenance of adequate ventilation and oxygenation and protection of
the patient from injury. Seizures may be terminated with IV midazolam (0.05-0.10 mg/kg), propofol (0.5-1 mg/kg), or
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perhaps intravenous lipid.3,83,103,104 If LA intoxication produces hypotension without cardiac arrest it may be treated
by infusion of vasopressors (phenylephrine 0.5-5 µg/kg/min, norepinephrine 0.02-0.2 µg/kg/min, or vasopressin 2-20
units IV). A survey of academic anesthesia departments in the USA confirmed inadequate understanding and no
consensus regarding resuscitation drugs for LAST.106 I hope that the situation has improved. In any case I recommend
that LAST be treated per the ASRA guidelines104 Epinephrine may be required, but it should be administered in
incremental, just sufficient doses to avoid toxic side effects.105 With unresponsive LA CV toxicity, IV lipid should be
administered and cardiopulmonary bypass (or other forms of mechanical cardiopulmonary support) should be
considered.107-109 Animal experiments and human case reports describe the ability of lipid infusion to resuscitate
animals from bupivacaine LAST, even after "conventional" resuscitative efforts (including ventilation with oxygen,
chest compressions, and ACLS drugs) have proven unsuccessful.107,108 The prevailing explanation for lipid’s
mechanism of action is that LA diffuses from the CV system and is absorbed into a “lipid sink.” There is also evidence
that certain lipids may antagonize the binding of LAs to the Na v channel.110 Experimental evidence is conflicting
whether long-chain lipids (e.g. IntralipidTM) are preferable to mixed long- and medium-chain lipid emulsion.111,112
Lipid can treat overdoses of lipophilic compounds other than LAs such as bupropion and lamotrigine, and has also
been used for lidocaine overdose in the critical care unit.113 Lipid resuscitation is advocated for treatment of poisoning
by other xenobiotics including tricyclic antidepressants and verapamil.114 Some now speculate that lipid therapy
should be initiated for incipient LA toxicity (e.g. for CNS symptoms) before conventional drug treatments. Toxic side
effects of lipid resuscitation have been reported only rarely.
Summary
After >125 years the place of both LAs and regional blocks in medical practice remain secure. Some features of
LAs and regional anesthesia are well understood. Peripheral nerve blocks almost certainly result from LA inhibition
of Nav channels in axonal membranes. On the other hand, the relative clinical potency of the various LAs remains
poorly defined,115 and the mechanisms of spinal and epidural anesthesia remain unclear. The clinical importance of
LA binding to TRPV1 channels remains speculative. The precise mechanism by which LAs produce CV toxicity is
not clear and there may be more than 1 mechanism: more potent agents (bupivacaine) have greater propensity for
arrhythmias and conduction disturbances than less potent agents (lidocaine); all LAs at increased concentrations will
produce myocardial depression. Avoiding LAST is clearly preferable to treating it, however effective lipid
resuscitation may be. Finally, ultrasound guidance and good technique have likely reduced (but not removed) the risk
of LAST during regional nerve blocks.116
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Difficult Airway Management in Pediatrics: Approaches for Success

Narasimhan Jagannathan, MD ` Chicago, IL
GENERAL CONSIDERATIONS
Management of the pediatric airway poses its own unique challenges compared to the adult airway. Anatomically, small children
(infants) have a more cephalad larynx, floppier epiglottis, larger tongues, smaller mouth opening, and are more prone to rapid
oxygen desaturation due to their higher rates of oxygen consumption.
The management of the pediatric airway has experienced a number of changes in the past decade. Equipment advancements in
pediatric sizes and pediatric-specific algorithms have improved the options available to the clinician.
Current and ongoing clinical trials have helped define the role of these newer devices and their effectiveness in the pediatric
population.
Fundamentally, oxygenation is the most critical function of airway management. Methods to ensure gas exchange should be
governed by the patient’s medical condition, the clinical scenario, and the resources available. A recent multicenter study of over
a thousand children with difficult airways found that the most common severe complication was cardiac arrest, occurring in 2%
of these children from persistent hypoxemia. The most common complication overall was hypoxemia (SPO2 < 85%).
The child with a difficult airway may manifest as the inability to mask ventilate, perform direct laryngoscopy, or both. Multiple
factors, including disease processes involving the airway, can impair access to the airway and ventilation.
Independent risk factors associated with complications during management of the pediatric difficult airway:
a. Short thyromental distance (micrognathia)
b. Weight less than 10 kg
c. Greater than two tracheal intubation attempts
d. Three direct laryngoscopy attempts before an indirect technique (e.g. videolaryngoscopy, fiberoptic bronchoscopy)
INCIDENCE OF DIFFICULT AIRWAY
The unanticipated difficult airway occurs less frequently in children than in adults
The overall incidence of the difficult airway in children is less than in adults, is especially rare in healthy children. Some studies
have found that the incidence of difficult mask ventilation in children was 0.2% (vs. 1.4% in adults); and incidence of difficult
laryngoscopy was 0.06%-4.7% (vs. 1.5%-8.5% in adults). Most notably, children less than 1 year of age are more likely to have
an increased incidence of difficult laryngoscopy (4.7%; Cormack & Lehane Grade III or higher). There exists an 80% rate of
anticipated difficult airways in children. There appears to be a 20% unanticipated difficult airway rate, which is greater than what
has been traditionally taught to anesthesia practitioners.
THE ANTICIPATED DIFFICULT AIRWAY
Pediatric difficult airways are often anticipated, as they are typically associated with dysmorphic features, which are usually
recognized during the preoperative assessment.
Craniofacial syndromes are the most common reason for difficult airways in the pediatric population
Micrognathia is the most common physical finding associated with difficult laryngoscopy in an infant
A meticulous history and physical examination can reveal important findings that are predictive of a difficult airway
and may help localize the site of airway obstruction.
Detecting potential abnormalities pre-operatively will allow the clinician to formulate an adequate plan for airway management
prior to the induction of anesthesia.
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A practical approach is to classify the child according to the functional abnormality and associated condition (Table 1). It is also
critical to determine if there is enough of a mouth opening to allow for the insertion of the airway device one plans to use (i.e.
Supraglottic airway (SGA) or videolaryngoscope).
Depending on the age of the child and the type of syndrome, anatomic changes related to the growth of the child can either
improve or worsen as the patient ages (Table 1)
THE UNANTICIPATED DIFFICULT AIRWAY
The unanticipated difficult airway, is likely to occur after induction of general anesthesia, and should prompt early recruitment of
additional resources (call for help, ENT surgeon)
Iatrogenic injures of the airway can occur from multiple intubation attempts that can lead to bleeding and supraglottic edema,
even with gentle instrumentation.
No single method has been proven to be effective in all patients; the airway management plan in these situations should be
tailored to the specific patient’s condition and the availability resources.
Limiting the number of direct laryngoscopy attempts to avoid airway trauma, and use of alternative devices, including
videolaryngoscopy, use of supraglottic airways (SGAs) for rescue, and/or as a conduit for fiberoptic guided tracheal intubation
are potential options.
MANAGEMENT STRATEGIES
A true ‘awake’ intubation is often impractical in children and seldom utilized. Exceptions may be considered when difficult mask
ventilation is predicted, there is severe upper airway obstruction at rest (i.e. mucopolysaccaradosis and Treacher Collins
syndrome), or ‘full stomach’ precautions are needed. The following scenarios may warrant consideration of an awake intubation
in a child: a patient that is predicted to be a potential difficult laryngoscopy AND has any of the following: 1) high aspiration
risk; 2) severe upper airway obstruction at rest; 3) predicted difficult mask ventilation. The awake patient has the ability to
maintain their own oxygenation and ventilation, avoid worsening airway obstruction, and can better protect their airway from
aspiration of gastric contents.
In clinical practice, the majority of anticipated difficult airways are managed after induction of general anesthesia, while
maintaining spontaneous ventilation. Pharmacologic agents such as sevoflurane, ketamine, dexmedetomidine, and topicalization
of the airway with local anesthetics may provide adequate conditions for airway manipulation while minimizing reflex activation
of the airway and respiratory depression.
The use of NMBDs in the management of children with difficult airways vs. maintenance of spontaneous ventilation remains a
controversial topic. The use of NMBDs after sevoflurane inhalational induction has been associated with fewer adverse
respiratory events in children with normal airway anatomy when compared with sevoflurane without NMBDs. In contrast, there
is little evidence on the effects of NMBDs in children with abnormal airway anatomy.
Consideration should be given to whether native muscle tone is needed to maintain airway patency when making the decision to
use NMBDs (i.e. anterior mediastinal mass). In such cases, avoidance of NMBDs may be warranted.
The use of an awake SGA or modified nasal trumpet (a nasopharyngeal airway is inserted into the patient, and then fitted with an
endotracheal tube adapter that is connected to an oxygen source) will allow the clinician to provide oxygen, continuous positive
airway pressure, bypass airway obstruction, and allows the option of delivering inhaled agents (sevoflurane), if a spontaneous
breathing technique under anesthesia is needed.
Figure 1 is proposed algorithm for the management of the unanticipated difficult airway in children. (Adapted From the 2013
ASA Guidelines)
DEVICES USED IN THE MANAGEMENT OF DIFFICULT AIRWAYS
Flexible Fiberoptic bronchoscope
The flexible fiberoptic bronchoscope remains the “gold standard” for securing the airway in the face of a difficult tracheal
intubation, despite the availability of newer videolaryngoscopes.
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The major advantage is its versatility of use, allowing for intubation of the trachea via the oral route, nasal route, or through an
SGA. It can also be used to evaluate the lower airways as well as assist in the positioning of bronchial blockers and double lumen
tubes. Table 2 summarizes the advantages and limitations with various routes used for fiberoptic intubation,
The fiberoptic bronchoscope is available in sizes appropriate even for neonates. The smallest fiberoptic scope is 2.2 mm in
diameter (ultra-thin). A limitation of the ultra-thin bronchoscope is the lack of a suction channel. A disadvantage of fibreoptic
bronchoscopes is the vulnerability of the image quality to secretions and blood in the airway. Maneuvering of the bronchoscope
can be challenging (especially with the ultra-thin bronchoscopes). The learning curve is steep and requires practice and regular
use to acquire and maintain one’s skill.
Videolaryngoscopes
The use of video or optical laryngoscopes has gained popularity as an alternative to flexible fiberoptic bronchoscopy guided
tracheal intubation. These devices combine a fiberoptic bundle or video camera on an intubating blade that may be fixed or
malleable, and displays the laryngeal view on a screen or eyepiece. The ASA difficult airway algorithm strongly suggests using a
videolaryngoscope as the initial approach in a patient with suspected difficult airway.
These devices require less head and neck mobilization compared with direct laryngoscopy (DL), and may be useful in patients
with cervical instability.
Some studies suggest videolaryngoscopes can improve the glottic view when compared with traditional DL, but at the expense of
increased time for tracheal intubation. However, the greater time to intubation may be acceptable, if the improved laryngeal grade
of view allows for successful tracheal intubation, particularly in situations where DL has failed. Common advantages and
disadvantages of videolaryngoscopes vs direct laryngoscopes are presented in Table 3.
Pediatric sizes are available for the GlideScope Video Laryngoscope (Verathon, Bothell, Washington, USA), Airtrach Disposable
Optical Laryngoscope (Prodol Meditec, Vizcaya, Spain), Pentax AWSTM (Pentax Corporation, Tokyo, Japan), Stortz DCITM
Video Laryngoscope (Karl Storz, Tuttlingen, Germany), Truview PCD Infant (Truphatek, Netanya, Israel), McGrath airway
scope (Teleflex, Triangle Park, NC.), and Bonfils optical stylet (Karl Storz, Tuttlingen, Germany)
Supraglottic airway devices (SGA):
The effectiveness of SGAs has helped establish their role in the management of children with difficult airways. An SGA may be
able to bypass obstructions at the supraglottic level, and be a useful rescue device by improving airway patency. This is
particularly true in children with airway obstruction at birth (e.g. Pierre Robin Syndrome) where SGAs can be placed in the
awake state.
These devices may also be helpful in patients that may otherwise be difficult to mask ventilate, and can be used as a temporary or
primary means to maintain ventilation if difficult or failed intubation is encountered. Additionally, they can also be used as a
conduit for fiberoptic tracheal intubation. It is important to use specifically designed SGAs as a conduit for fiberoptic guided
tracheal intubation (e.g. air-Q, Ambu Aura), as these devices a shorter and wider bored to accommodate cuffed tracheal tubes.
It is important to note that with the placement of an SGA, the anatomic position does not necessarily correlate to the functional
quality of the airway: varying degrees of epiglottic downfolding may be present, even with adequate ventilation through the
SGA. Epiglottic downfolding is a common finding in SGAs, especially in small children
(<10kg). Therefore, visualization techniques (e.g. fiberoptic assisted) may have increased success compared with blind
techniques when tracheal intubation is attempted.
There are several different SGAs on the market; each of them has advantages and disadvantages as determined by their specific
features Table 4 presents the SGAs that have been studied and used in children.
CANNOT INTUBATE, CANNOT OXYGENATE:
The “cannot oxygenate, cannot intubate” (CICO) scenario is a rare event in children, and represents a very challenging and
resource limited situation.
The best way to approach this situation in small children is still unclear. A specific anatomic feature in the pediatric airway, such
as the proportionally smaller cricothyroid membrane, especially in infants and neonates, significantly reduces the success of
trantracheal catheter placement.
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Data suggests that success rates of needle cricothyrotomy can be as low as 65.8%, and information is lacking regarding the
adequacy of ventilation using these methods in small children.
Needle/cannula cricothyrotomy has been proposed as the most expeditious approach for invasive tracheal access, when ENT
surgical intervention is not immediately available. Even in skilled hands, a high rate of complication, including posterior tracheal
wall puncture can occur.
When a cricothyrotomy is necessary, a device designed specifically for this purpose should be used, such as a Ravussin jet
ventilation catheter (Cook Medical; Bloomington, IN USA).
A makeshift device consisting of an angiocatheter (at least 18 G), a 3 ml syringe, and 3.0 mm ID tracheal tube adapter may be an
alternative if commercial kits are not available. If possible, a kink-resistant angiocatheter may be preferable when using this
technique.
An Enk Oxygen Flow ModulatorTM (Cook Medical, Bloomington, IN, USA) may be used for oxygenation, at 1 L per year of age
flow rate, and providing enough time to allow expiration.
The use of jet ventilation through transtracheal catheters is associated with an increased rate of complications and barotrauma,
even in a controlled setting. Adequate oxygenation has shown to be possible through transtracheal catheters without the use of jet
ventilation in animal and bench studies.
It is important to remember that needle cricothyrotomy only provides a temporary means for oxygen insufflation and that
effective ventilation may not be possible.
Future studies on scalpel techniques are needed to determine if this may be a more effective option in the CICO situation.
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FIGURE 1. PROPOSED ALGORITHM FOR THE MANAGEMENT OF THE UNANTICIPATED

DIFFICULT AIRWAY IN CHILDREN. (Adapted from the 2013 ASA Guidelines)
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TABLE 1. FUNCTIONAL CLASSIFICATION OF CONDITIONS ASSOCIATED WITH DIFFICULT

AIRWAY
Functional Classification
Supraglottic Abnormalities Maxillary hypoplasia:
Apert syndrome
Crouzon syndrome
Pfeiffer syndrome
Saethre-Chotzen syndrome
DiGeorge syndrome
Mandibular hypoplasia:
Pierre Robin sequence
Treacher Collins
Goldenhar syndrome
Sticklers syndrome
Mobius syndrome
Micrognathia
CHARGE association
Abnormalities of the whole airway Mucopolysaccharidoses:
including the glottis Hurler syndrome
Hunter syndrome
Sanfilipo syndrome
Morquio síndrome
Maroteaux-Lamy syndrome
Vascular lymphatic malformations:
Beckwith-Wiedemann syndrome
Chronic Subglottic Subglottic stenosis
Abnormalities Laryngeal stenosis
Tracheal stenosis
Laryngo/tracheomalacia
Masses (neck/parapharyngeal)
Poor mouth opening or mobility of Freeman-Sheldon
jaw, neck Noonan syndrome
Spinal fusion
Cervical stenosis
Cervical Instability
Other abnormalities Infections
Burns
Miscellaneous
Sturge-Weber syndrome
Robinow syndrome
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TABLE 2. A COMPARISON BETWEEN DIFFERENT FIBEROPTIC INTUBATION (FOI)

APPROACHES
Route for FOI Advantages Limitations
 Shorter path to the larynx vs. nasal  Patient can bite bronchoscope
route  Greater skill required to maneuver
Oral
 Avoids shearing of adenoidal tissue the scope
and epistaxis
 Simpler midline placement  Potential risk for epistaxis and/or
 Relatively straightforward path to adenoidal tissue shearing
larynx  Sinusitis
 Easier to acquire skills
Nasal  Useful in children with extremely
limited mouth opening
 Avoids the risk of the child biting
the scope
 Provides a hands free airway  Modifications of equipment needed

 Relatively straightforward path to for some SGAs (ie. LMA Classic),
the larynx especially when using a cuffed TT
 Ability to overcome upper airway
obstruction
 Can oxygenate and provide inhaled
Supraglottic airway assisted anesthetic during intubation
 Specific SGAs designed for
intubation are available (ie. air-Q,
Ambu Aura-i)
TABLE 3 ADVANTAGES AND LIMITATIONS OF VIDEOLARYNGOSCOPY AND DIRECT

LARYNGOSCOPY IN CHILDREN
Videolaryngoscopy Direct laryngoscopy
Advantages -Improved glottic views in known difficult airways -Long history of efficacy in
-Less force needed to displace soft tissue to obtain an management of the pediatric airway
adequate glottic view -Faster times for tracheal intubation in
-Provides a more anterior view of the glottis the normal airway
-Port for oxygen delivery (in certain models) -Several sizes of blades available
-Allows glottic view to be displayed onto an external
monitor
-Less levering of the maxillary teeth
-No need to sweep & displace the tongue
Disadvantages -Longer times for tracheal intubation in the normal airway -Poorer glottic views in known difficult
-Increased hand-eye coordination required airways poor technique in the
-Impractical for patients with small mouth opening difficult airway
-More expensive -Requires direct line of site to glottis for
-Soiled airway (blood, vomit) will obscure the lenses an adequate view
-Complications: perforation of the palatopharyngeal arch -Greater work force required
and soft palate have been reported -Large tongues may be difficult to
displace
-Impractical for patients with small
mouth opening
-Complications: airway edema; greater
complications such as hypoxemia,
dental trauma
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TABLE 4. SUPRAGLOTTIC AIRWAY DEVICES AVAILABLE FOR CHILDREN

Device Advantages Disadvantages
Classic LMA/ LMA UniqueTM  Long history of safety and  In infants: delayed airway
(Teleflex, Triangle Park, NC) efficacy obstruction (<10kg)
 Large evidence base  Have to modify when using it for
fiberoptic intubation
 No gastric drain provision
ProSeal LMATM  Long history of safety and  No single-use version
(Teleflex, Triangle Park, NC) efficacy  Narrower lumen of airway tube
 Large evidence base makes tracheal intubation through
 Gastric drain tube this device more challenging
 Higher leak pressure than LMA
classic
 Stable In small children
air-QTM  Designed for tracheal intubation  No gastric drain provision
(Mercury Medical Clearwater, FL)  Large evidence base for difficult
airway management
 Can accommodate cuffed tracheal
tubes
 Stable In small children
Supreme LMATM  Single-use  Not suitable for fiberoptic-guided
(Teleflex, Triangle Park, NC)  Gastric drain tube intubation secondary to narrow
 Higher leak pressure than LMA airway tube
classic
i-GelTM  Higher leak pressures  Tendency to spontaneously dislodge
(Intersurgical, Wockingham, UK)  Gastric drain tube after placement in small children
 Favorable fiberoptic views  Laryngeal bulging observed in small
children
 Small sizes (1, 1.5) cannot
accommodate cuffed tracheal tubes
References/ Suggested reading

 Fiadjoe JE, Nishisaki A, Jagannathan N et al. Airway management complications in children with difficult tracheal intubation from
the Pediatric Difficult Intubation (PeDI) registry: a prospective cohort analysis. Lancet Respir Med; 2016. 4: 37-48.
 Jagannathan N, Sohn L, Fiadjoe JE. Paediatric difficult airway management: what every anaesthetist should know! Br J Anaesth. 2016
 Heinrich S, Birkholz T, Ihmsen H, et al. Incidence and predictors of difficult laryngoscopy in 11,219 pediatric anesthesia procedures.
Pediatr Anesth. 2012;22:729-36.
 Lee J-H, Park Y-H, Byon H-J, et al. A comparative trial of the GlideScope video laryngoscope to direct laryngoscope in children with
difficult direct laryngoscopy and an evaluation of the effect of blade size. Anesth Analg. 2013;117:176-181
 Asai, T., A. Nagata, K. Shingu, Awake tracheal intubation through the laryngeal mask in neonates with upper airway obstruction.
Pediatr Anaesth, 2008. 18: 77-80.
 Huang AS, Hajduk J, Jagannathan N. Advances in supraglottic airway devices for the management of difficult airways in children.
Expert Rev Med Devices. 2016;13:157-69
 Jagannathan, N., Sequera-Ramos L, Sohn L et al., Elective use of supraglottic airway devices for primary airway management in
children with difficult airways. Br J Anaesth, 2014. 112: 742-8.
 Holm-Knudsen R, Eriksen K, Rasmussen LS. Using a nasopharyngeal airway during fiberoptic intubation in small children with a
difficult airway. Pediatr Anesth. 2005;15: 839-4
 Stacey J, Heard AMB, Chapman G, et al. The “Can’t Intubate Can’t Oxygenate’ scenario in Pediatric Anesthesia: a comparison of
different devices for needle cricothyroidotomy. Paediatr Anaesth. 2012; 22:1155-1158.
 Wong CF, Yuen VM, Wong GT, et al. Time to adequate oxygenation following ventilation using the Enk oxygen flow modulator
versus a jet ventilator via needle cricothyrotomy in rabbits. Pediatr Anesth. 2014;24:208-13
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Incomes are Based on Outcomes:

Evidence-based Approach to Assimilating Large Data in Children
Santhanam Suresh, MD Chicago, Illinois
Infrequent adverse events within peri-operative period in pediatric anesthesia can result in adverse events
for patients and providers. The scarcity of these events has traditionally limited the ability of researchers to identify
associated and modifiable predictors and risk factors. A recent rapid growth in large database research in
anesthesiology has begun reshaping the landscape of improved peri-operative clinical care, long-term outcomes, and
helping draft
evidence-based guidelines, however many limitations still exist primarily in the field of pediatric
anesthesiology. This Refresher Course will give an overview of strengths and limitations of large data, describe
large databases and their contributions to pediatric anesthesia, and give an overview of evidence-based approaches
to utilizing this data for every day practice.
Overview of large data

Multiple unique ethical, study design, time- and cost-prohibitive barriers in the field of anesthesiology
further complicate the conduct randomized, and single-center prospective trials. Overcoming these barriers requires
utilization of large databases with administrative, automated perioperative (anesthesia information management
systems), and registry data.1 The majority of large pediatric data comes from registry data.
There is no single unified definition of ‘big data’ or ‘large data, as it varies across professional fields
between medical subspecialties2. Even within subspecialties such as anesthesiology, ‘big data’ will have a different
connotation between that collected in adults and pediatrics.3 Perhaps the most comprehensive definition comes from
the NIH, which describes Big Data as “more than just very large data or a large number of data sources. Big Data
refers to the complexity, challenges, and new opportunities presented by the combined analysis of data. In
biomedical research, these data sources include the diverse, complex, disorganized, massive, and multimodal data
being generated by researchers, hospitals, and mobile devices around the world.” 4 Similarly, the NIH acknowledges
challenges associated with “unwieldy amount of information, lack of organization and access to data and tools, and
insufficient training in data science methods” which, “make it difficult for Big Data’s full power to be harnessed.” 4
Although some would argue pediatric anesthesia has a long way to go before true ‘big data’ is available, there are
definite examples of ‘large data’ in the field.
Example of strengths and limitations of large data

A prime example of the new insight, and challenges, which accompany larger data in pediatrics, can be
represented by the study by Mathis et. al. which retrospectively reviewed 11,910 anesthesia cases with the Laryngeal
Mask Airway Unique and Classic and identified risk factors for device failure in 102 of these cases.5 These included
ear/nose/throat surgery, nonoutpatient admission status, prolonged surgical duration, and congenital/acquired airway
abnormality, and patient transport. Of editorial note6, although sensitive enough to detect subtle differences, the
results must be interpreted with caution and in context. Although congenital/acquired airway abnormalities are a risk
factor for failure, it is well established that the LMA may still by-pass these abnormalities to provide lifesaving gas
exchange7, and emphasizes approaching every child on a case-by-case basis.
Litman3 most succinctly states the study is “only the tip of the iceberg with regard to improving safety in
pediatric anesthesia and other practices with relatively low error rates. The information learned from big data
analyses will help us plan clinically relevant prospective studies, and when the numbers are large enough, may even
help us plan the safest anesthetic.” As described further in this refresher course, multiple large prospective studies,
databases, and registries are currently amassing data to achieve the goal of safer anesthesia for pediatric patients.
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Future of Large Data Research and Reporting

Recently, the journal Anesthesiology, in a similar fashion as the Journal of the American Medical
Association (JAMA) and Public Library of Science (PLoS), has adapted a new requirement that all observational
studies (including existing database analyses, post-hoc analyses of prospectively collected data in most any design
where measurements are collected on a process of interest that is left free to vary) transparently report whether an
analysis plan was developed and documented before accessing data. This is in addition to already established
Strengthening and reporting of Observational Studies in Epidemiology (STROBE) guidelines.8 The journal
recognizes observational studies are sometimes the only practical study design due to ethical or practical constraints
on anesthesia related research, however this limitation does not absolve the research from the many well-known
threats to interpretation of results. 9
Anesthesia Quality Institute

Chartered in 2008 by the American Society of Anesthesiologists, the Anesthesia Quality Institute (AQI)
developed the National anesthesia Clinical Outcomes Registry (NACOR). In contrast to many of the other databases
described with predefined data elements targeting subspecialty areas and hypotheses, AQI collects more
heterogeneous data based on any readily available digitized information for the purposes of quality information. 10
Several high impact articles related to patient care11,12 and the general practice of anesthesia13–15 have come from the
database, however none specifically related to pediatric anesthesia.
Pediatric Regional Anesthesia Network

The Pediatric Regional Anesthesia Network (PRAN) is a longitudinal North American consortium project
with the goal of accruing data on practice patterns, safety, complications, and risks associated with regional
anesthesia in children16,17. The project mirrors the efforts of The French Language Society of Pediatric
Anesthesiology” (ADARPEF) prospective reporting studies of regional anesthesia in 1996 and 2010 and the national
pediatric epidural audit from Britain in 2008. Organized in 2006 with 6 member sites and collecting data since April
2007, the database now contains data on approximately 100,000 nerve blocks from 22 active sites. Organized with
an elected steering and research committee which oversees data mining requests and publications, the group has
produced a string of peer reviewed manuscripts that can provide evidenced based approach to pediatric regional
anesthesia worldwide. These include demonstrating the safety of placement of blocks in children under anesthesia
(52,564 cases)18, transversus abdominis plane blocks, TAP (1,994 cases)19, intrascalene brachial plexus blocks (518
cases)20, and caudal blocks (18,650) 21 as well as the complication rates of peripheral nerve catheters in children
(2,074 cases)22 and neuraxial catheters in neonates (307 cases)23.
A very notable contribution of the PRAN database has been its input to the formation of a practice advisory
and recommendations on controversial topics in pediatric regional anesthesiology through collaboration between
European and American societies of regional anesthesia (ASRA/ESRA).24 Findings from the PRAN database
contributed evidence toward recommendations about awake versus asleep regional anesthesia and test dose
performance in children, loss of resistance with air or saline and compartment syndrome. Although only
recommendations and not guidelines, this example of the evaluation of multiple large databases to generate
evidence-based decision making in an evolving and controversial field is a quintessential example of clinical care
influenced by large data. This is in contrast to well-established guidelines, such as the difficult airway algorithm,
which based primarily on existing and ‘accepted’ clinical practice patterns.
National Surgical Quality Improvement Program - Pediatric

Perhaps the most widely known perioperative registry is the American College of Surgeons’ National
Surgical Quality Improvement Program (ACS-NSCIP). Founded in the 1990’s, it now collects over 300 variables
from more than 400 hospitals on over 650,000 cases. Cases data is abstracted from rigorously trained reviewers with
inter-reviewer reliability above 98% and exclusion of data from hospitals with less than 95% are excluded from
analysis. However the low number of anesthesia related variables has limited it’s impact on the anesthesia
literature25. The overall success of the program has led efforts to development and expansion of the NSQIP Pediatric
Program (NSQIP-P) in conjunction with the American Pediatric Surgical Association (APSA). The program
includes 94 data points on children up to 30 days following a given procedure. Analysis of 1,059 cranial vault
reconstructions found transfusions in excess of 60 ml/kg significantly increased risk of complications and length of
stay26. The findings purported a previous body of evidence for thresholds and reducing transfusions in these cases,
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and provided valuable population-specific data27. One other anesthesia specific publication has resulted from the
database, describing risk factors for unexpected reintubation (personal correspondence SS).
Pediatric Difficult Intubation Registry

The Pediatric Difficult Intubation (PeDI) registry is a database of prospectively collected tracheal
intubation data from 13 children’s hospitals. Utilizing ReThe collaborative group was formed as part of the Society
for Pediatric Anesthesia in 2010, with 10 key stakeholders formulating the registry over four consensus development
meetings over a year. Utilizing standardized data definitions and data collection methods, the group collected and
analyzed 1,018 difficult pediatric tracheal intubation encounters over 3 years. The significant findings demonstrated
more than two direct laryngoscopy attempts to be associated with a high rate of failure and increased incidence of
severe complications, suggesting that quick transitioning to an indirect technique when direct laryngoscopy fails
would enhance patient safety.28
Of note, the study also reports a 3% first attempt success rate of intubation with direct laryngoscopy, even
in the hands of pediatric anesthesiologists. This evidence is in stark contrast to the difficult airway algorithm which
recommends first attempts with direct laryngoscopy, followed by possible repeated direct laryngoscopy with
adjustments; guidelines which were made by expert opinion through a Delphi method, in light of a paucity of an
evidence base. Limitations of the study included four centers contributing the majority of data, limiting
generalizability, and possible inaccuracy of incidence reporting. Nevertheless, the database is a prime example of a
large database possibly setting a precedent for evidence based recommendations in an understudied area of pediatric
anesthesia.
Pediatric Craniofacial Surgery Perioperative Registry

The Pediatric Craniofacial Surgery Perioperative Registry (PCSPR) collects data on perioperative care
from children undergoing procedures including anterior/posterior/total vaults, fronto-orbital advancement, LeFort,
open/endoscopic strip craniectomy, and cranioplasty procedures. Data is collected on preoperative history,
intraoperative anesthetic management (notably including fluid, blood product, and drug administration) as well as
complications, lab values, and through the first two postoperative days.
Currently, 31 institutions contribute data with information on over 2,500 enrolled in the registry. As of
spring 2016, there were three projects currently in the final data analysis and manuscript phases regarding
antifibrinolytic safety, benchmarking and outcomes, as well as endoscopic versus open repairs in infants29. The lead
investigators have utilized the database in conjunction with their own prospectively collected institutional data to
demonstrate epsilon-aminocapricoic acid reduces blood loss, fewer intraoperative blood donor exposures, and lower
drain output.30 The group has identified the potential to be a leading voice in writing consensus statements or
creating quality improvement interventions.
Multicenter Perioperative Outcomes Group

The Multicenter Perioperative Outcomes Group (MPOG), started by the University of Michigan in 2008
collects electronic health record, administrative, and outcome data from academic and private practices. Data is
cleaned, scrutinized, and validated at the user and group levels. The group has 25 actively contributing members in
the United States and Netherlands and an additional 34 in the process of membership. A yearly contribution of
10,000 cases is required for full membership. Data is available to participating and contributing members and the
group has since made significant contributions to the field of anesthesia with reports on lung-protective measures31,
predictors of difficult mask ventilation32, as well as risks and outcomes of epidural hematomas33. Currently, no
pediatric specific reports have come from the group, however many from the group leadership were involved with
the large data study reporting on failure of laryngeal mask airways in children 5, as previously noted.
Wake Up Safe
Launched in 2008 by the Society for Pediatric Anesthesia, the ‘Wake up Safe’ (WUS) quality improvement
initiative is a database project focused on serious adverse events, occurring within 24 hours of the end of anesthesia
in pediatrics.34 Its aim is to not only provide insight into the incidence and trends of events, but to provide an
interpretation of causes to allow for institutional implementation of changes in processes of care, quality, and safety.
Events are those which required significant escalations in case, prolonged hospitalization, were life threatening, or
resulted in death; as well as ‘never events’ such as wrong-side procedures or patient awareness. Other events
hospital-wide incident reporting systems also contribute to identifying events. Root-cause analyses of these events
identify causation and trends. Member site are able to access and query the database. Sites also contribute total case
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volume information to report an overall incidence of these events occurring. Currently, there are no published
research findings from the group; however it has issued multiple advisories and reports.
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References
1. Freundlich RE, Kheterpal S. Perioperative effectiveness research using large databases. Best Pract Res Clin
Anaesthesiol. 2011;25(4):489-498.
2. Fisher DM. “Big data” has not come to pediatric anesthesia. Anesthesiology. 2014;121(1):204.
3. Litman RS. In reply. Anesthesiology. 2014;121(1):204-205.
4. What is Big Data? | Data Science at NIH.
5. Mathis MR, Haydar B, Taylor EL, et al. Failure of the Laryngeal Mask Airway Unique TM and ClassicTM in the
pediatric surgical patient: a study of clinical predictors and outcomes. Anesthesiology. 2013;119(6):1284-
1295.
6. Litman RS. Complications of laryngeal masks in children: big data comes to pediatric anesthesia.
Anesthesiology. 2013;119(6):1239-1240.
7. Jagannathan N, Sequera-Ramos L, Sohn L, Wallis B, Shertzer A, Schaldenbrand K. Elective use of

supraglottic airway devices for primary airway management in children with difficult airways. Br J Anaesth.
2014;112(4):742-748.
8. von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in
Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet Lond Engl.
2007;370(9596):1453-1457.
9. Eisenach JC, Kheterpal S, Houle TT. Reporting of Observational Research in ANESTHESIOLOGY: The
Importance of the Analysis Plan. Anesthesiology. 2016;124(5):998-1000.
10. Liau A, Havidich JE, Onega T, Dutton RP. The National Anesthesia Clinical Outcomes Registry. Anesth
Analg. 2015;121(6):1604-1610.
11. Heinrich S, Birkholz T, Ihmsen H, Irouschek A, Ackermann A, Schmidt J. Incidence and predictors of
difficult laryngoscopy in 11,219 pediatric anesthesia procedures. Paediatr Anaesth. 2012;22(8):729-736.
12. Whitlock EL, Feiner JR, Chen L-L. Perioperative Mortality, 2010 to 2014: A Retrospective Cohort Study
Using the National Anesthesia Clinical Outcomes Registry. Anesthesiology. 2015;123(6):1312-1321.
13. Dexter F, Dutton RP, Kordylewski H, Epstein RH. Anesthesia Workload Nationally During Regular
Workdays and Weekends. Anesth Analg. 2015;121(6):1600-1603.
14. Pollak KA, Stephens LS, Posner KL, et al. Trends in Pain Medicine Liability. Anesthesiology.
2015;123(5):1133-1141.
15. Schonberger RB, Dutton RP, Dai F. Is There Evidence for Systematic Upcoding of ASA Physical Status
Coincident with Payer Incentives? A Regression Discontinuity Analysis of the National Anesthesia Clinical
Outcomes Registry. Anesth Analg. 2016;122(1):243-250.
16. Polaner DM, Taenzer AH, Walker BJ, et al. Pediatric Regional Anesthesia Network (PRAN): a multi-
institutional study of the use and incidence of complications of pediatric regional anesthesia. Anesth Analg.
2012;115(6):1353-1364.
17. Polaner DM, Martin LD, PRAN Investigators. Quality assurance and improvement: the Pediatric Regional
Anesthesia Network. Paediatr Anaesth. 2012;22(1):115-119.
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18. Taenzer AH, Walker BJ, Bosenberg AT, et al. Asleep versus awake: does it matter?: Pediatric regional block
complications by patient state: a report from the Pediatric Regional Anesthesia Network. Reg Anesth Pain
Med. 2014;39(4):279-283.
19. Long JB, Birmingham PK, De Oliveira GS, Schaldenbrand KM, Suresh S. Transversus abdominis plane block
in children: a multicenter safety analysis of 1994 cases from the PRAN (Pediatric Regional Anesthesia
Network) database. Anesth Analg. 2014;119(2):395-399.
20. Taenzer A, Walker BJ, Bosenberg AT, et al. Interscalene brachial plexus blocks under general anesthesia in
children: is this safe practice?: A report from the Pediatric Regional Anesthesia Network (PRAN). Reg Anesth
Pain Med. 2014;39(6):502-505.
21. Suresh S, Long J, Birmingham PK, De Oliveira GS. Are caudal blocks for pain control safe in children? an
analysis of 18,650 caudal blocks from the Pediatric Regional Anesthesia Network (PRAN) database. Anesth
Analg. 2015;120(1):151-156.
22. Walker BJ, Long JB, De Oliveira GS, et al. Peripheral nerve catheters in children: an analysis of safety and
practice patterns from the pediatric regional anesthesia network (PRAN). Br J Anaesth. 2015;115(3):457-462.
23. Long JB, Joselyn AS, Bhalla T, et al. The Use of Neuraxial Catheters for Postoperative Analgesia in
Neonates: A Multicenter Safety Analysis from the Pediatric Regional Anesthesia Network. Anesth Analg.
2016;122(6):1965-1970.
24. Ivani G, Suresh S, Ecoffey C, et al. The European Society of Regional Anaesthesia and Pain Therapy and the
American Society of Regional Anesthesia and Pain Medicine Joint Committee Practice Advisory on
Controversial Topics in Pediatric Regional Anesthesia. Reg Anesth Pain Med. 2015;40(5):526-532.
25. Hua M, Brady J, Li G. The epidemiology of upper airway injury in patients undergoing major surgical
procedures. Anesth Analg. 2012;114(1):148-151.
26. Chow I, Purnell CA, Gosain AK. Assessing the Impact of Blood Loss in Cranial Vault Remodeling: A Risk
Assessment Model Using the 2012 to 2013 Pediatric National Surgical Quality Improvement Program Data
Sets. Plast Reconstr Surg. 2015;136(6):1249-1260.
27. Stricker PA, Hsu G. Discussion: Assessing the Impact of Blood Loss in Cranial Vault Remodeling: A Risk
Assessment Model Using the 2012 to 2013 Pediatric National Surgical Quality Improvement Program Data
Sets. Plast Reconstr Surg. 2015;136(6):1261-1263.
28. Fiadjoe JE, Nishisaki A, Jagannathan N, et al. Airway management complications in children with difficult
tracheal intubation from the Pediatric Difficult Intubation (PeDI) registry: a prospective cohort analysis.
Lancet Respir Med. 2016;4(1):37-48.
29. Society for Pediatric Anesthesia. Pediatric Craniofacial Surgery Perioperative Registry Meeting Minutes.
April 2016.
30. Hsu G, Taylor JA, Fiadjoe JE, et al. Aminocaproic acid administration is associated with reduced
perioperative blood loss and transfusion in pediatric craniofacial surgery. Acta Anaesthesiol Scand.
2016;60(2):158-165.
31. Bender SP, Paganelli WC, Gerety LP, et al. Intraoperative Lung-Protective Ventilation Trends and Practice
Patterns: A Report from the Multicenter Perioperative Outcomes Group. Anesth Analg. 2015;121(5):1231-
1239.
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32. Kheterpal S, Healy D, Aziz MF, et al. Incidence, predictors, and outcome of difficult mask ventilation
combined with difficult laryngoscopy: a report from the multicenter perioperative outcomes group.
Anesthesiology. 2013;119(6):1360-1369.
33. Bateman BT, Mhyre JM, Ehrenfeld J, et al. The risk and outcomes of epidural hematomas after perioperative
and obstetric epidural catheterization: a report from the Multicenter Perioperative Outcomes Group Research
Consortium. Anesth Analg. 2013;116(6):1380-1385.
34. Tjia I, Rampersad S, Varughese A, et al. Wake Up Safe and root cause analysis: quality improvement in
pediatric anesthesia. Anesth Analg. 2014;119(1):122-136.
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Head and Neck Pain:

Recent Advances in Medical and Interventional Management
Samer Narouze, MD, PhD Cuyahoga Falls, OH
Head pain stemming from the neck or neck pain radiating up to the head is usually referred to as
“cervicogenic headache”. Cervicogenic headache was initially defined as unilateral headache that is
provoked by neck movement or pressure over tender points in the neck with associated reduced range of
movement of the cervical spine. The headache occurs in non-clustering episodes and is usually non-
throbbing in nature, originating from the neck, and spreading over the occipital, temporal, and frontal
regions.1-3 These clinical criteria are not enough to make a definite diagnosis of cervicogenic headache, as it
is sometimes difficult to differentiate clinically between cervicogenic headache, migraine, and tension-type
headache. 4-6 Response to diagnostic block of the nerve supply of these cervical structures or intraarticular
injection of local anesthetic into the affected joint is now considered the major criterion in the diagnosis of
cervicogenic headache.7 Also, cervicogenic headache can be unilateral or bilateral. 7 These clinical findings
prompted the development of new diagnostic criteria for the diagnosis of cervicogenic headache by the
International Headache Society (IHS) in 2004 (ICHD-2nd edition) More recently, the ICHD-3rd edition was
released .8
Diagnostic criteria of cervicogenic headache by the International Classifications of Headache

Disorders. 3rd edition (ICHD-3)8:
A. Any headache fulfilling criterion C

B. Clinical, laboratory and/or imaging evidence of a disorder or lesion within the cervical spine or soft
tissues of the neck, known to be able to cause headache
C. Evidence of causation demonstrated by at least two of the following:
1. Headache has developed in temporal relation to the onset of the cervical disorder or appearance of the
lesion
2. Headache has significantly improved or resolved in parallel with improvement in or resolution of the
cervical disorder or lesion
3. Cervical range of motion is reduced and headache is made significantly worse by provocative maneuvers
4. Headache is abolished following diagnostic blockade of a cervical structure or its nerve supply
D. Not better accounted for by another ICHD-3 diagnosis.
Etiology:
Cervicogenic headache is referred pain from cervical structures innervated by the upper three
cervical spinal nerves. Thus possible sources of cervicogenic headache are: atlanto-occipital joint, median
and lateral atlanto-axial joints, C2-3 intervertebral disc, C2-3 zygapophysial joint, upper posterior neck, and
paravertebral muscles. Other sources include the trapezius and the sternocleidomastoid muscles, spinal and
posterior cranial fossa dura matter, cervical spinal nerves, and roots and the vertebral artery. 9
Neuroanatomy and Neurophysiology:

The spinal nucleus of the trigeminal nerve extends caudally to the outer lamina of the dorsal horn
of the upper three to four cervical spinal segments. This is known as the trigeminocervical nucleus, which
receives afferents from the trigeminal nerve as well as the upper three cervical spinal nerves. Convergence
between these afferents accounts for the cervical-trigeminal pain referral. Therefore, pain originating from
cervical structures supplied by the upper cervical spinal nerves could be perceived in areas innervated by
the trigeminal nerves such as the orbit and the frontotemporoparietal region (Figure 1).
Bartsch and Goadsby10 showed that noxious stimulation of the greater occipital nerve induces increased
central excitability of supratentorial afferents and vice versa, stimulation of the dura mater increases
trigeminocervical neurons responsiveness to cervical input.11
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Figure 1: The trigemino-cervical complex
Differential Diagnosis of Cervicogenic Headache

Atlanto-occipital joint
Atlanto-axial (C1-2) joints
C2-3 zygapophysial joint
C2-3 intervertebral disc
Occipital, suboccipital, and upper cervical paravertebral muscles
Posterior cranial fossa lesions
Cervical spinal nerves lesions
Vertebral artery disorders
Common Sources of Cervicogenic Headache:

We will discuss here the clinical presentations of the common causes of cervicogenic headache and how to
come up with an accurate diagnosis, and a plan of care (Table 1).
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Table 1:
Algorithm for the diagnosis and management of cervicogenic headache. (Reprinted with permission from
Narouze S, ed. Interventional management of head and face pain)
Atlanto-axial Joint
The lateral atlanto-axial joint, which is innervated by the C2 ventral ramus, is not an uncommon
cause of cervicogenic headache. It may account for 16% of patients with occipital headache. 12 In human
volunteers, distending the lateral atlanto-axial joint with a contrast agent produces occipital pain and
injection of local anesthetic into the joint relieves the headache. 12, 13 Clinical presentations suggestive of
pain originating from the lateral atlanto-axial joint include occipital or suboccipital pain, focal tenderness
over the suboccipital area or over the transverse process of C1, restricted painful rotation of C1 on C2, and
pain provocation by passive rotation of C1. These clinical presentations merely indicate that the lateral
atlanto-axial joint could be a possible source of occipital headache, however they are not specific and
therefore cannot be used alone to establish the diagnosis.9
The pathology of lateral atlantoaxial joint pain is usually osteoarthritis or post-traumatic in nature.
14,15
However, the presence of osteoarthritic changes on imaging studies doesn’t mean than the joint is
necessary painful, also the absence of abnormal findings doesn’t preclude the joint from being painful. The
only means of establishing a likely diagnosis is a diagnostic block with intra-articular injection of local
anesthetic.12
There is no conservative treatment for lateral atlanto-axial joint pain. However intra-articular steroids are
effective in short-term relief of pain originating from the lateral atlanto-axial joint. 16,17 Long-lasting pain
relief may require arthrodesis of the lateral atlanto-axial joint. 18, 19
Atlanto-axial joint intra-articular injection has the potential for serious complications, so it is
imperative that the interventional pain physician is familiar with the anatomy of the joint in relation to the
surrounding vascular and neural structures (Fig 2). The vertebral artery lies lateral to the atlanto-axial joint
as it courses through the C2 and C1 foramina. Then it curves medially to go through the foramen magnum
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crossing the medial posterior aspect of the atlanto-occipital joint (Fig 2). The C2 dorsal root ganglion and
nerve root with its surrounding dural sleeve crosses the posterior aspect of the middle of the joint.
Therefore, during atlanto-axial joint injection, the needle should be directed toward the posterolateral
aspect of the joint. This will avoid injury to the C2 nerve root medially or the vertebral artery laterally (Fig
3-4).12, 17 Meticulous attention should be paid to avoid intravascular injection as the anatomy may be
variable. Injection of a contrast agent should be performed under real-time fluoroscopy, preferably with
digital subtraction, prior to the injection of the local anesthetic, as negative aspiration is of low sensitivity.
Inadvertent puncture of the C2 dural sleeve with CSF leak or high spinal spread of the local anesthetic may
occur with atlanto-axial joint injection if the needle is directed a few millimeters medially. Spinal cord
injury and syringomyelia are potential serious complications if the needle is directed further medially.
Figure 2: Illustration showing the relationship of the atlantoaxial and atlantoccipital joints to the vertebral
artery
Figure 3: A. The lateral atlanto-axial joint, B. The tip of the needle and the contrast agent within the
lateral AA joint
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Figure 4: Lateral view showing the tip of the needle and the contrast agent within the lateral AA
joint
C2-3 zygapophysial joint and third occipital headache

The C2-3 zygapophyseal joint is innervated by the third occipital nerve, which is the superficial
medial branch of the dorsal ramus of C3.20 Pain stemming from this joint (named third occipital headache)
is seen in 27% of patients presenting with cervicogenic headache after whiplash injury.21 Tenderness over
the C2-3 joint is the only suggestive physical examination finding and a diagnostic third occipital nerve
block is mandatory to confirm the diagnosis. Earlier reports showed that radiofrequency neurotomy of the
third occipital nerve were not effective. 22 With improved radiofrequency technique, complete relief was
obtained in 88% of patients with third occipital headache (Fig 5).23
C2-3 zygapophyseal joint intra-articular steroid injection was effective in one study. 24 On the other hand;
Barnsley et al25 reported the lack of efficacy of intra-articular steroids for chronic pain stemming from the
cervical zygapophyseal joints.
Third occipital nerve neurolysis:
The third occipital nerve is the superficial medial branch of C3 dorsal ramus. It supplies the C2-3
zygapophysial joint while crossing the joint laterally. Also it supplies part of the semispinalis capitis
muscle and its cutaneous branch supplies a small area of skin below the occiput. 20 Third occipital
radiofrequency neurolysis was shown to be effective in the treatment of headache stemming from the C2-3
joint. There is usually incomplete lesioning of the third occipital nerve because of its variable anatomy. 22
The use of the three needles technique to accommodate all variations in the anatomy of the third occipital
nerve from just lateral to the joint line to above or below the joint, and creating consecutive lesions no more
than one electrode width from adjacent lesion markedly improves the results. 23 (Fig 5)
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Figure 5: Lateral view showing three radiofrequency needles appropriately placed just lateral to the
C2-3 joint, above and below the joint line
Anesthesia dolorosa has not been reported with neurolysis of the third occipital nerve. However
numbness in the cutaneous distribution of the nerve is very common, whereas dysesthesia and
hypersensitivity typically at the border of the area of numbness occur in up to 50% of cases. These are
temporary complications that usually persist for only a few days to weeks.22, 23 Temporary ataxia has been
reported in most patients as third occipital neurotomy partially denervates the semispinalis capitis muscles
with the resultant interference of the tonic neck reflexes. Most patients can overcome this sensation by
relying on visual cues.22, 23
Occipital neuralgia
According to the 2nd edition of the International Classification of Headache Disorders (ICHD),
occipital neuralgia is coded separately under cranial neuralgias.8 It is discussed because of its relevance to
cervicogenic headaches. The diagnostic criteria include the following:
A. Paroxysmal stabbing pain, with or without persistent aching between paroxysms, in the distribution(s) of
the greater, lesser and/or third occipital nerves
B. Tenderness over the affected nerve
C. Pain is eased temporarily by local anaesthetic block of the nerve
Occipital neuralgia was long thought to be the result of entrapment of the greater occipital nerve as
it emerges from the trapezius muscle. However, surgical nerve release gives only short-term relief in about
80% of cases, while nerve excision provides short-term relief in about 70% of patients.26, 27 Occipital
neuralgia must be distinguished from occipital referral of pain from the atlantoaxial or upper
zygapophyseal joints or from tender trigger points in neck muscles or their insertions. 8
The greater occipital nerve is the terminal branch of the dorsal ramus of C2 with contribution from
C3 while the lesser occipital nerve is a branch of the dorsal ramus of C3 with contributions from C2.
Segmental nerve blocks at C2 and C3 may be necessary to make the diagnosis in some cases. 28
Cryoneurolysis, radiofrequency ablation, and more permanent neuroablative approaches as dorsal
rhizotomy at C1-3 and partial posterior rhizotomy at C1-3 showed variable responses. 29-32
Occipital neurostimulation
Percutaneous occipital nerve stimulation, unlike neuroablative techniques, offer the potential for a
minimally invasive, low risk, and reversible approach to managing occipital neuralgia, chronic migraine,
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cluster headaches, and other types of intractable primary headaches.33-35 PET scan studies showed
increased regional cerebral blood flow in areas involved in central neuromodulation in chronic migraine
patients treated with occipital nerve electrical stimulation.36 A percutaneous trial of peripheral nerve
stimulation is performed using subcutaneous electrodes placed superficial to the cervical muscular fascia at
the level of the C1 or the nuchal line. If effective, a permanent implant may be carried out using the same
electrode lead type or paddle-type surgical lead and attached to a pulse generator implanted in the
infraclavicular area, abdomen, flank, or upper buttock (Fig 6,7).
The ONSTIM (occipital nerve stimulation for the treatment of intractable migraine) trial, examined the
safety and efficacy of ONS. 37 It is a multi-center prospective randomized single-blind controlled feasibility
study. Patients who responded favorably to occipital nerve block (ONB) were randomized (2:1:1) into 3
groups: adjustable stimulation (AS), preset stimulation (PS), or medical management (MM). Those who did
not respond to ONB formed an ancillary group (AG). One hundred and ten patients were enrolled from 9
centers. Sixty sex subjects completed diary data during 3-month follow-up. At 3 months, percent reduction
in headache days/month was 27.0% (AS), 8.8% (PS) (p = 0.132), 4.4% (MM) (p = 0.058), 39.9% (AG) (p =
0.566). Responder rate was 39% (AS), 6% (PS) (p =0.032), 0% (MM) (p = 0.003), and 40% (AG) (p =
1.000).
More recently, another prospective, multi-center, double-blind, controlled study of ONS in patients with
CM. 38 One hundred and fifty-seven patients from 15 centers were enrolled and randomized (2:1) to either a
stimulation trial followed by device implantation and active stimulation for 12 weeks (n = 105) or a
stimulation trial followed by device implantation but sham stimulation for 12 weeks (n = 52). After 12
weeks, subjects were un-blinded but patients were followed for one year. There was a significant difference
in the percentage of patients that achieved a 30% reduction in daily visual analog scale scores (p = 0.01).
There were significant group differences for all assessments at 12 weeks (p< 0.01).
The most frequent complication of the ONS is lead migration. Various anchoring techniques were
described to improve lead stability, however the problem persists. 35
In one review, lead migration was found to be 33% and 60% 6 months and one year post-implant
respectively. 39 The ONSTIM study reported lead migration in 24% of subjects.37 The use of self-anchoring
leads (e.g. tined leads) looks promising. 37 In a series of 12 patients, only one patient had a few mm lead
migration with little change in the stimulation pattern, there was no loss of efficacy.40 None of 12 patients
required a surgical revision for lead migration during a mean follow up period of 13 months (Fig 9). Unlike
spinal cord stimulation, wound dehiscence and infection carry a lower morbidity risk although this usually
requires total system explant.
Figure 6: AP view showing bilateral occipital surgical leads

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Figure 7: AP view showing right occipital percutaneous lead
Figure 8: AP view showing bilateral occipital self anchoring leads.
C2 Neuralgia
C2 neuralgia is a distinctive type of occipital neuralgia and it is caused by lesions affecting the C2
nerve root or dorsal ganglion such as neuroma, meningioma, or anomalous vessels. 41,42 The C2 root lies
posterior to the lateral atlanto-axial joint, thus disorders or inflammation of this joint may lead to irritation
or entrapment of the nerve root.43 C2 neuralgia manifests as intermittent lancinating occipital pain that is
associated with lacrimation, ciliary injection, and rhinorrhea. Abolition of pain by selective C2 nerve root
block is essential to make the diagnosis. C2 neuralgia that responds poorly to pharmacotherapy and
thermocoagulation, decompression, or C2 ganglionectomy may be indicated. 9
Cervical Myofascial Pain

Trigger points in the posterior neck muscles specially the trapezius, sternocleidomastoid, and the
splenius capitis have been proposed as a cause of headache. 44,45 According to the 2nd edition of the
International Classification of Headache Disorders (ICHD), Headache causally associated with cervical
myofascial tender spots is coded as episodic or chronic tension-type headache associated with pericranial
tenderness. 8
Moreover these tender points usually overlie the zygapophyseal joints, so it is difficult to be distinguished
from underlying painful joints. 9 Needling therapies in the management of myofascial pain showed no
efficacy beyond that of placebo. 46 The use of botulinum toxin is controversial. It might be effective in the
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management of migraine and chronic daily headaches, however its efficacy in myofascial pain and
cervicogenic headaches still debatable. 47-49
Cervical discogenic pain
C2-C3 provocative discography, but not at the lower levels, can reproduce cervicogenic
headache.50 Radiofrequency lesioning was shown to be effective in obtaining some pain relief for a few
months in one study. 51 However, cervical disc interventions are not commonly performed because of the
potential for serious complications.
In summary, cervicogenic headache is one of the most debatable and challenging area in headache
medicine. Patients usually benefit the most from a multidisciplinary approach incorporating physical
therapy, pharmacotherapy, psychotherapy (biofeedback and relaxation therapy), alternative medicine
(acupuncture), and the judicious utilization of interventional pain management modalities.
References
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2- Fredriksen TA, Hovdal H, Sjaastad O. Cervicogenic headache: clinical manifestation. Cephalalgia 1987; 7: 147-
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3- Sjaastad O. Fredriksen TA, Pfaffenrath V. Cervicogenic headache: diagnostic criteria. Headache 1990; 30: 725-
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4- Leone M, D’Amico D, Moschiano F, et al. Possible identification of cervicogenic headache among patients with
migraine: an analysis of 374 headaches. Headache 1995; 35: 461-464.
5- Leone M, D’Amico D, Grazzi L, et al. Cervicogenic headache: a critical review of the current diagnostic criteria.
Pain 1998; 78: 1-5.
6- Suijlekom JA, de Vet HCW, van den Berg SGM, Weber WEJ. Interobserver reliability of diagnostic criteria for
cervicogenic headache. Cephalgia 1999; 19: 817-823.
7- Sjaastad O. Fredriksen TA, Pfaffenrath V. Cervicogenic headache: diagnostic criteria. Headache 1998; 38: 442-
445
8- Headache Classification Subcommittee of the International Headache Society. The international classification of
headache disorders (3rd edn.). Cephalalgia 2013 in press
9- Bogduk N. The neck and headache. Neurologic clinics 2004;22(1): 151-171
10- Bartsch T, Goadsby PJ. Stimulation of the greater occipital nerve induces increased central excitability of dural
afferent input. Brain 2002; 125:1496-1509
11- Bartsch T, Goadsby PJ. Increased responses in trigeminocervical nociceptive neurons to cervical input after
stimulation of the dura mater. Brain 2003; 126:1801-1813
12- Aprill C, Axinn MJ, Bogduk N. Occipital headaches stemming from the lateral atlanto-axial (C1-2) joint.
Cephalalgia 2002; 22(1):15-22.
13- Busch E, Wilson PR. Atlanto-occipital and atlanto-axial injections in the treatment of headache and neck pain.
Reg Anesth 1989; 14(Suppl 2):45.
14- Ehni G, Benner B. occipital neuralgia and the C1-2 arthrosis syndrome. J Neurosurg 1984; 61: 961-965.
15- Schonstorm N, Twomey L, taylor J. The lateral atlanto-axial joints and their synovial folds: an in vitro study of
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16- Narouze SN, Casanova J. The efficacy of lateral atlanto-axial intra-articular steroid injection in the management of
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17- Narouze SN, Casanova J, Mekhail N. The longitudinal effectiveness of lateral atlanto-axial intra-articular steroid
injection in the management of cervicogenic headache. Pain Med 2007;8:184-188
18- Joseph B, Kumar B. Gallie’s fusion for atlantoaxial arthrosis with occipital neuralgia. Spine 1994; 19: 454-455.
19- Ghanayem AJ, Leventhal M, Bohlman HH. Osteoarthrosis of the atlantoaxial joints- long term follow up after
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20- Bogduk N. The clinical anatomy of cervical dorsal rami. Spine 1982; 7: 319-30.
21- Lord S, Barnsley L, Wallis B, Bogduk N. Third occipital headache: a prevalence study. J Neurol Neurosurg
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22- Lord SM, Barnsley L, Bogduk N. Percutaneous radiofrequency neurotomy in the treatment of cervical
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23- Govind J, King W, Baily B. Bogduk N. Radiofrequency neurotomy for the treatment of third occipital headache. J
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24- Slipman CW, Lipetz JS, Plastara CT, et al. Therapeutic zygapophyseal joint injections for headache emanating
from the C2-3 joint. Am J Phys Med Rehabil 2001; 80: 182-88.
25- Barnsley L, Lord SM, Wallis BJ et al. Lack of effect of intraarticular corticosteroids for chronic pain in the
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headache. A follow up study. Headache 1992; 32: 175-9.
27- Anthony M. Headache and the greater occipital nerve. Clin Neurol Neurosurg 1992; 94: 297-301.
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29- Silverman SB. Cervicogenic headache: interventional, anesthetic, and ablative treatment. Curr Pain Headache
Rep 2002; 6: 308-314.
30- Sjaastad O, Stolt-Nielsen A, Blume H et al. Cervicogenic headache. Long-term results of radiofrequency treatment
of the planum nuchale. Funct Neurol 1995; 10: 265-271.
31- Horowitz MB, Yonas H. Occipital neuralgia treated by intradural dorsal nerve root sectioning. Cephalalgia 1993;
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32- Dubuisson D. Treatment of occipital neuralgia by partial posterior rhizotomy at C1-3. J Neurosurg 1995; 82: 591-
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33- Weiner RL, Reed KL. Peripheral neurostimulation for control of intractable occipital neuralgia. Neuromodulation
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34- Kapural L, Mekhail N, Hayek SM, et al. Occipital nerve electrical stimulation via the midline approach and
subcutaneous surgical leads for treatment of severe occipital neuralgia: a pilot study. Anesth Analg 2005; 101:171-
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35- Weiner RL. Occipital neurostimulation (ONS) for treatment of intractable headache disorders. Pain Med
2006;7:S137-S139
36- Matharu MS, Bartsch T, Ward N, et al. Central neuromodulation in chronic migraine patients with suboccipital
stimulation: A PET study. Brain 2004; 127:120-130
37- Saper JR, Dodick DW, Silberstein SD, McCarville S, Sun M, Goadsby PJ. Occipital nerve stimulation for the
treatment of intractable chronic migraine headache: ONSTIM feasibility study. Cephalalgia. 2011;31(3):271-285.
38- Silberstein SD, Dodick DW, Saper J, et al. Safety and efficacy of peripheral nerve stimulation of the occipital
nerves for the management of chronic migraine: results from a randomized, multicenter, double blinded,
controlled study. Cephalalgia. 2012;32:1165-1179.
39- Schwedt TJ, Dodick DW, Hentz J, Trentman TL, Zimmerman RS. Occipital nerve stimulation for chronic
headache- Long term safety and efficacy: Cephalalgia 2007;27:153-157.
40- Narouze SN, Saad R, Nagem H, Kapural L. Occipital Nerve Stimulation with self-anchoring leads for the
management of refractory chronic migraine headache (abstract). Pain Med 2009;10:221
41- Kuritzky A. Cluster headache-like pain caused by an upper cervical meningioma. Cephalalgia 1984; 4: 185-6.
42- Sharma RR, Parekh HC, Prabhu S, et al. Compression of the C2 root by a rare anomalous ectatic vertebral artery. J
Neurosurg 1993; 78: 669-72.
43- Poletti CE, Sweet WH. Entrapment of the C2 root and ganglion by the atlantoepistrophic ligament: clinical
syndrome and surgical anatomy. Neurosurgery 1990; 27: 288-91.
44- Travell J, Rinzler SH. The myofascial genesis of pain. Postgrad Med 1952; 11: 425-34.
45- Freund B, Schwartz M. Post-traumatic myofascial pain of the head and neck. Curr Pain Headache Rep 2002; 6:
361-369.
46- Cummings TM, White AR. Needling therapy in the management of myofascial trigger point pain: a systemic
review. Arch Phys Med Rehabil 2001; 82: 986-92.
47- Cheshire WP, Abashian SW, Mann JD. Botulinum toxin in the treatment of myofascial pain syndrome. Pain 1994;
59: 65-69.
48- Freund BJ, Schwartz M. Treatment of whiplash associated neck pain [corrected] with botulinum toxin-A: a pilot
study. J Rheumatol. 2000; 27: 481-484.
49- Wheeler AH, Goolkasian P, Gretz SS. A randomized, double-blind, prospective pilot study of botulinum toxin
injection for refractory, unilateral, cervicothoracic, paraspinal, myofascial pain syndrome. Spine 1998; 23: 1662-
1666.
50- Grubb SA, Kelly CK. Cervical discography: clinical implications from 12 years of experience. Spine 2000; 25:
1382-1389.
51- Blume HG. Cervicogenic headaches: radiofrequency neurotomy and the cervical disc and fusion. Clin Exp
Rheumatol. 2000; 18: S53-S58.
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Fluid Management as Adjunct to Enhanced Recovery After Surgery
Ehab Farag Cleveland/OH
Enhanced recovery after surgery (ERAS) or Fast Track programs is a bundle of best
evidence based practices of perioperative interventions to maintain physiological
function and facilitate postoperative recovery after major surgery. The goals of
ERAS pathways are to decrease postoperative complications and to facilitate
recovery after major surgery. Perioperative fluid management is at the heart of
ERAS. Of note, a change in fluid management alone on the day of surgery has been
shown to reduce postoperative complications by 50%.
Fluid overload has deleterious effects on the patients’ outcomes. Patients received
excessive fluid after colonic surgeries had prolonged the gastric emptying, increased
postoperative complications and longer hospital stay compared to those patients
who received zero-balance fluid (input fluid=output fluid with almost no increase
body weight). Moreover, intraoperative fluid overload impaired the healing of the
ileo-ileal anastomosis in rat model. Fluid overload can result in increased the intra
abdominal pressure, impaired the organ perfusion and even induced abdominal
compartment syndrome. Fluid overload will increase the secretion of atrial naturitic
peptide (ANP) that degrades the endothelial glycocalyx and the integrity of vascular
barrier.
The use of excessive amounts of normal saline could result in hyperchloremic
acidosis that reduces gastric blood flow and decreases gastric intramucosal pH. In
addition the fluid overload could produce tissue edema in an encapsulated organ
such as the kidney that results in increased in interstitial pressure. The increased in
interstitial pressure could comprise the renal blood flow, which results in acute
kidney injury (AKI).
Perioperative fluid management according to ERAS protocol
Maintain good preoperative hydration
- ASA guidelines recommend intake of clear fluids up to two hours before

induction.
- Give carbohydrates drink containing high concentration of complex
carbohydrates will result in reducing thirst, hunger, anxiety and
postoperative insulin resistance.
- Avoid routine bowel preparation, as routine bowel preparation will result in
increasing dehydration, unpleasant sensation for the patient and increasing
fluid overload during the intraoperative period. Routine bowel preparation
does not reduce anastomotic leakage, wound infection or mortality.
However, it increases incidence of spillage of bowel contents due to liquid
bowel contents.
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Intraoperative fluid management

- Maintenance fluid should not exceed 1-2 ml/kg/hr. infusion of a balanced
crystalloid solution.
- Restrictive fluid term should be replaced by zero-balance fluid therapy to
maintain central euvolemia while minimizing excess salt and water to
maintain preoperative body weight.
- Volume therapy is used to replace blood loss or fluid / protein shifts from the
circulation especially in major surgeries.
- Volume therapy is preferably being given with colloid as small fluid boluses
over ten minutes.
- It is worth mentioning that only 50% of hemodynamically unstable patients
in the intraoperative period are volume responders. Moreover, volume
responsiveness does not always mean fluid is needed.
- If there is no reason to suspect a volume deficit and the blood pressure is
low a judicious use of vasopressor is indicated.
- Heart rate and mean arterial pressure are rough indicators of patients’ fluid
status as healthy volunteers could tolerate the loss up to 25% of their blood
volume without change in their heart rate and mean arterial blood pressure.
- CVP measurement for fluid management should be discontinued in the ICU
and the intraoperative settings.
- The urine output (UOP) is a crude marker of renal function and/or volume
status. Moreover, perioperative oliguria (UOP <0.5 ml/kg/hr) is extremely
common and occurs as a neurohormonal response to surgical stress.
The use of goal –directed fluid therapy (GDFT) for fluid management
The stroke volume (SV) optimization is preferably to be used to guide the fluid
management throughout the perioperative period. An increase in SV by more than
10% by fluid challenge means the patient is fluid responder and in the steep part of
Frank-Starling curve and would benefit of further fluid challenge. Once the patient is
euvolaemic and on the plateau of the Frank-Starling curve, there will be no benefit
of further fluid boluses. However, there might be harmful as they may induce fluid
overload.
Dynamic indices such as stroke volume variation (SVV), pulse pressure variation
(PPV), and systolic pressure variation (SPV) are commonly used to predict the fluid
responsiveness. A PPV or SVV of > 13% is highly predictive of fluid responsiveness.
However, 9-13 % is considered as a grey zone.
Systemic vascular resistance does not affect the SVV. Therefore, PPV/SVV ratio is
defined as dynamic arterial elastance (Eadyn) and can be used to predict the arterial
pressure response after volume loading in hypotensive, preload –dependent
patients. Patients with Eadyn value < 0.89 will not have an increase MAP with
volume administration, which means that vasopressors should be added with fluids
to raise the MAP. Nonetheless, an Eadyn value > 0.89 indicates that fluid loading alone
will raise blood pressure and the use of vasopressors can be delayed.
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The use of dynamic parameters has its own limitations. PPV and SVV require NSR
and normal pressures in abdomen and chest; otherwise their predictive value is
reduced. They depend on heart /lung interactions during controlled ventilation.
Therefore, the tidal volume (TV) less than 8 ml/kg decreases this interaction and
results in low values of PVV and /or SVV.
Dynamic parameters neither provide a measure of fluid bolus effectiveness nor
should they to be used as an indication to give fluids. The final decision to
administer fluids must be supported by the apparent need for hemodynamic
improvement, the presence of fluid responsiveness and the lack of associated risk.
Therefore, the GDFT should be individualized according to the patient. GDFT is
unlikely to cause harm or to add benefit in healthy patients undergoing uneventful
surgery within an ERAS pathway. However, patients with preoperative bowel
preparation and have significant comorbidities and prolonged surgery with blood
loss will benefit from GDFT.
Postoperative Period
Early oral intake reduces the risk of infection and length of hospital stay with no
increased risk of anastomotic dehiscence. The intravenous fluid therapy in the
postoperative period should provide low-sodium, low –volume and enable patients
to return their zero fluid and sodium balance over the postoperative period. GDFT
should be continued into the postoperative period in high-risk patients. It is worth
mentioning that hypotension in normovolemic patients with thoracic epidural
should not be treated by excess fluid but with either reducing and/ or modifying the
epidural infusion and the use of vasopressors.
What fluid should be used?
Intraoperative fluid maintenance fluid should be balanced crystalloid solution like

LR, Plasma-Lyte or Normosol-R. Colloid solution preferably albumin is the
preferred choice for fluid replacement in cases of blood loss and objective
hypovolemia. Normal saline can be used in specific condition like hypochloremic
metabolic alkalosis as result of high GI losses. While in the postoperative period
reduced salt solution like dextrose saline is the preferred one.
References
1- Lobo DN et al Lancet 2002; 359:1812-1818.

2- Nisanevich V et al Anesthesiology 2005; 103:25-32.
3- Marjianovic G et al Ann Surg 2009;249: 181-185.
4- Navarro L H C et al Perioperative Medicine 2015;4:3.
5- Miller T E et al Can J Anesth 2015;62:158-168.
6- Pearse R et al JAMA 2014;311:2181-90.
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Perioperative Analgesia and Effect on Patient Outcomes
Spencer S. Liu, M.D. New York/NY
Introduction
Provision of high quality perioperative analgesia has become recognized as an important goal. However,
ability of analgesia to improve outcomes remains controversial. 1 A key component of this continuing controversy
is that individual clinical trials need large patient sample sizes due to the current relatively low incidences of major
postoperative morbidity. Thus, this lecture will focus on studies with large subject samples to evaluate effects of
postoperative analgesia on major postoperative outcomes. Most discussed evidence involves epidural analgesia, as
this is the most studied regional anesthesia/analgesia technique for major postoperative outcomes. Furthermore, the
lecture will discuss effects of regional analgesia on patient oriented outcomes. As anesthesia and perioperative care
become increasingly safe, these patient oriented outcomes may assume greater importance.
Effect of regional analgesia on major morbidity

Epidural analgesia
Mortality
Meta-analyses: The largest meta-analysis of RCTs was published in 2000 (CORTRA) and included 141 RCTs
(through Jan 1, 1997) with 9,559 patients undergoing a variety of surgical procedures 2. This meta-analysis
examined effects of neuraxial block (spinal anesthesia, epidural anesthesia, and epidural analgesia) vs general
anesthesia, but results from this meta-analysis likely apply to perioperative epidural analgesia as 66 of the RCTs
with 4,498 of the patients utilized epidural anesthesia and analgesia. This meta-analysis observed a reduction in
mortality with neuraxial blockade (1.9% vs 2.8%, OR 0.7 with 95% CI 0.54 to 0.9) and specifically for thoracic
epidural blocks (1.5% vs 2.9%) and orthopedic procedures. A recent (2014) meta-analysis of only Cochrane
systematic reviews did not report an effect on mortality with use of neuraxial anesthesia vs general anesthesia . 3
Several procedure specific meta-analyses have been conducted, and all report inconclusive effects on
mortality with epidural analgesia for open abdominal aortic surgery 4, coronary artery bypass grafting 5, abdominal
surgery 6, and hip and knee replacement surgery 7.
Randomized Controlled Trials: The most recent large RCT was conducted in 2011 in 654 patients undergoing
cardiac surgery that were randomized to combined general/thoracic vs general anesthesia. 8 This RCT did not note
any differences between groups in mortality (0.6 vs 0.3%). 2 large RCTs have been performed in non-cardiac
surgery patients. In 2001, the Veterans Affairs Cooperative Studies Program (VACS) randomized 984 patients (all
or mostly men) undergoing 4 types of surgery (aortic, gastric, biliary, or colon) to combined general/epidural
anesthesia followed by epidural morphine vs general anesthesia followed by systemic opioid treatment 9.
Approximately 85% of the epidurals were placed at the thoracic level. Overall mortality rates were similar between
groups (4 vs 3.4%). In 2002, the Multicentre Australian Study of Epidural Anesthesia (MASTER) trial 10 enrolled
915 high risk patients (prospectively defined in the protocol) who had undergone mixed abdominal surgical
procedures and were randomized to combined general/epidural anesthesia followed by 72 hours of postoperative
epidural analgesia (low thoracic or high lumbar placement) with local anesthetic and opioids vs general anesthesia
followed by systemic opioid treatment. This RCT was limited by poor protocol compliance, as only 225/447
patients fully adhered to the epidural analgesia protocol. Overall mortality rates were again similar between groups
(5.1 vs 4.3%).
Clinical registries: In 2008, a propensity score analysis of a single institution electronic registry of 259,037 patients
undergoing mixed surgery reported a significant reduction in 30 day mortality in patients selected for epidural
anesthesia/analgesia (n=56,556) of 1.7% vs 2%. 11 In 2004, a 5% random sample of the Medicare claims database.
Patients undergoing a variety of surgical procedures were stratified to the presence (n=12,780 subjects) or absence
(n=55,943) of coding for postoperative epidural analgesia. 12 After adjusting for comorbidities, age, gender, and
hospital size, regression analysis revealed that the presence of postoperative epidural analgesia was associated with a
significantly lower incidence for both 7-day (0.5 vs 0.8%, OR = 0.52 with 95% CI 0.38 to 0.73) and 30-day (2.1 vs
2.5%, OR = 0.74 with 95% CI 0.63 to 0.89) mortality 12. There was a significantly lower mortality in patients who
received postoperative epidural analgesia for higher-risk procedures (e.g., lung resection, colectomy) but not lower-
risk procedures (e.g., total knee replacement, hysterectomy) or in patients with lower comorbidity indices. Although
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the number of patients from these registry analyses is impressive, these data are limited by retrospective nature,
accuracy of coding for complications, and degree of association between epidural analgesia and outcomes.
Summary statement: There is modest evidence for reduction of mortality with epidural analgesia for non-cardiac
procedures. The largest meta-analysis observed a reduction with neuraxial block. Procedure specific meta-analyses
and individual RCTs have not noted an effect from epidural analgesia but lack sufficient sample size due to the
relatively low incidence of mortality (0.2-5%). Analysis of clinical registries offers large patient numbers and a
modest association between epidural analgesia and reduced mortality.
Cardiovascular
Perioperative cardiac complications remain common, and recent evidence suggests that even subclinical
myocardial injury (e.g., TnT of 0.03 ng/ml) is associated with a 4 fold greater risk of death 13. Uncontrolled
postoperative pain may contribute to cardiac morbidity through activation of the sympathetic nervous system,
surgical stress response and coagulation cascade. Experimental data suggest that thoracic epidural anesthesia with
local anesthetics can reduce sympathetic activation and provide a favorable balance of myocardial oxygen, but
lumbar epidural anesthesia may not provide the same physiologic benefits as thoracic epidural anesthesia 14,15.
Meta-analyses: Six meta-analyses were identified that examined efficacy of epidural analgesia on cardiovascular
events 2,3,16-18. The largest was the previously described CORTRA meta-analysis that reported a non-significant
decrease in the risk of myocardial infarction (0.9% vs 1.3%). It should be noted that the majority of patients
received lumbar epidural or spinal anesthesia, which may not provide the physiologic benefit of TEA.
Three smaller but more specific meta-analyses examining the efficacy of postoperative epidural analgesia
and cardiovascular events suggest a benefit for epidural analgesia and TEA in particular for open major vascular
procedures. The meta-analysis by Popping in 2008 in abdominal and thoracic procedures noted a significant
reduction in myocardial infarction with primarily thoracic epidural analgesia (2.6 vs 4.6%). Beattie et al noted a
significantly lower incidence of myocardial infarction in those who received epidural analgesia (rate difference = -
3.8% with 95% confidence interval of -7.4% to -0.2%; p = 0.049) primarily in vascular surgery patients (579 out of
632 patients), and analgesic subgroup analysis revealed that TEA but not LEA provided a significant reduction in
the rate of myocardial infarction (3.6% vs 8.5%, rate difference = -5.3% with 95% CI of -9.9% to -0.7%). A similar
but more procedure specific meta-analysis of open abdominal aortic surgery with 1,224 patients (through June 2004)
noted significant reduction in risk of cardiovascular complications (RR 0.74 with 95% CI 0.56-0.97) and myocardial
infarction (RR 0.52 with 95% CI 0.29 to 0.93) with epidural vs systemic analgesia 4. Subgroup analysis again
indicated that only TEA and not lumbar epidural analgesia was associated with reduced risk of myocardial
infarction. These findings would support the experimental data demonstrating physiologic cardiac benefits of
thoracic but not necessarily lumbar epidural analgesia. Another procedure specific meta-analysis examined 28
RCTs with 2731 patients undergoing coronary artery bypass surgery with or without TEA. 5 Myocardial infarction
was not reduced with an odds ratio of 0.81, but significant reduction in risk of dysrhythmias was noted with TEA
(RR 0.68 with 95% CI 0.5-0.93). Other procedure specific meta-analyses examining effects of epidural analgesia on
abdominal, and hip and knee replacement surgery concluded that there was insufficient evidence to analyze
cardiovascular complications. 6,7,17
Randomized Controlled Trials: The large RCT of 654 patients undergoing cardiac surgery did not note any
differences between groups in myocardial infarction (4.9% in both groups). 8 The VACS trial did not note a
significant reduction in cardiovascular complications (myocardial infarction, heart failure, dysrhythmias, severe
hypotension) with use of epidural morphine (8.6 vs 11.2%) for all patients 9. However, the abdominal aortic surgery
subgroup (n=374) had significantly lower incidences of cardiovascular complications (9.8 vs 17.9%, p=0.03)
primarily due to reduction in myocardial infarction (2.7 vs 7.9%, p=0.05). The MASTER trial did not note
significant differences between groups.
Summary statement: There is consistent evidence that thoracic epidural analgesia may reduce the risk of
cardiovascular complications, especially myocardial infarction, in patients undergoing open major vascular surgery
and dysrhythmias in patients undergoing cardiac surgery. This is likely due to a higher underlying rate of
cardiovascular complications for this surgical population (4-37%).
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Pulmonary
Postoperative pulmonary complications (PPCs) are as common as cardiac complications for patients
undergoing non-cardiac procedures, and may carry the same risk of increased mortality and length of hospital stay
19
. The pathophysiology of postoperative pulmonary complications (PPC) after surgery is multifactorial and may
include disruption of normal respiratory muscle activity from either surgery or anesthesia, a reflex inhibition of
phrenic nerve activity with subsequent decrease in diaphragmatic function, and uncontrolled postoperative pain 20.
Epidural analgesia will confer superior analgesia thus improving voluntary pulmonary function 21. Segmental block
from thoracic epidural anesthesia may result in increased tidal volume and vital capacity related in part to improved
pain control and also to interruption of the reflex inhibition of phrenic nerve activity, thus improving diaphragmatic
activity.
Meta-analysis: In the CORTRA study, neuraxial block in mixed surgical procedures was associated with
significantly decreased risk of pneumonia (3.1% vs 6%, OR 0.61 with 95% CI 0.48-0.76) especially with TEA (OR
0.48 with 95% CI 0.35 to 0.67) vs spinal anesthesia or lumbar epidural anesthesia (OR 0.76 with 95% CI 0.55-1.04)
2
. This finding would support the underlying potential physiologic benefit for TEA for reducing PPCs. This finding
was confirmed in the 2008 meta-analysis (n=5,904) by Popping et al that noted a significant reduction in pneumonia
with primarily thoracic epidural analgesia (8 vs 12%) in patients undergoing abdominal or thoracic surgery. 18 The
2014 systematic review of Cochrane systematic reviews also reported a reduction (OR 0.46) in postoperative
pneumonia with use of neuraxial anesthesia. 3
More procedure specific meta-analyses were also identified. Use of TEA in coronary artery bypass surgery
(n=2,731) was associated with significantly decreased risk of PPC (RR 0.53 with 95% CI 0.4 to 0.69). 5 Use of TEA
in open abdominal aortic surgery (N= 861) was associated with significantly decreased risk of respiratory failure
(RR 0.63 with 95% CI 0.51-0.79) 4.
Randomized Controlled Trials: The large RCT of 654 patients undergoing cardiac surgery did not note any
differences between groups in pulmonary complications (9.2 vs 5.8%). 8The VACS study observed a non-significant
reduction in respiratory failure for all patients in the epidural group (9.9% vs 14%) 9. However, subgroup analysis
of the abdominal aortic surgery subgroup (n=374) noted a significant reduction in respiratory failure with use of
epidural analgesia (14% vs 28%, p<0.01). The MASTER study (N=915) found observed similar findings with a
lower incidence of respiratory failure in the epidural analgesia group for high risk patients undergoing mixed
abdominal surgical procedures (23 vs 30%, p=0.02) 10. As described above, most epidurals were placed at the
thoracic level for both RCTs.
Summary statement: There is consistent evidence from meta-analyses and large RCTs that thoracic epidural
analgesia reduces risk of postoperative pulmonary complications, especially in high risk surgery.
Gastrointestinal
Postoperative ileus is very common after abdominal surgery (>90% in many series) and may increase
resource utilization by prolonging hospital stay 22. Although the pathophysiology of postoperative ileus is
multifactorial, primary mechanisms include neurogenic (spinal, supraspinal adrenergic pathways), inflammatory
(i.e., local inflammatory responses initiate neurogenic inhibitory pathways), and pharmacologic (e.g., opioids)
mechanisms 23. Epidural analgesia provides superior pain control and marked sparing of opioid consumption 21.
Sympathetic block from epidural local anesthetics may attenuate postoperative reflex inhibition of GI motility.
Suppression of the surgical stress response and systemic absorption of epidural local anesthetics may reduce the
inflammatory response to attenuate postoperative ileus 22,23. Consistent with these mechanisms, experimental data
consistently indicate that epidural analgesia with local anesthetics shortens time of intestinal paralysis, increases the
strength of colonic contractions, and does not impair anastomotic healing or increase risk of anastomotic leakage 24.
Meta-analysis: A Cochrane Library meta-analysis that included 22 RCTs with 1,023 patients undergoing
abdominal surgery 25 and a meta-analysis from 2007 (n=806) both noted consistent reduction in postoperative ileus
with epidural analgesia with local anesthetics.
Summary statement: There is consistent evidence from meta-analysis that epidural analgesia with local
anesthetics hastens return of postoperative GI function after abdominal surgery by 24 to 37 hours.
Cancer recurrence
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The immune system is critical for ability to detect and eliminate cancer cells. Current evidence suggests a
primary role for NK cells for “elimination, equilibrium, escape” process. The immune system is initially able to
eliminate cancer cells. However, natural selection over time results in resistant cancer cells that are contained in an
equilibrium state. Disruption to the immune system, such as surgical stress, may tip the equilibrium into an escape
phase that allows metastases. Multiple perioperative factors may be involved in the equilibrium/escape phase, and
regional anesthesia/analgesia may play a protective role. 26 Laboratory evidence indicates that acute pain suppresses
NK cell activity, increase adrenergic activity, and is associated with tumor development in animals. Conversely,
relief of postoperative pain reduces postoperative metastasis in rats. Proposed mechanisms for beneficial effects of
regional anesthesia/analgesia include attenuation of perioperative immunosuppression, decreased use of volatile and
opioid agents, and improved tissue oxygenation. There are currently no prospective large scale RCTs specifically
designed to support or refute this theoretical benefit. Most current evidence is either observational or post-hoc re-
analysis of a RCT designed for a different hypothesis. Initial data were very favorable for the ability of regional
anesthesia/analgesia to reduce risk of cancer metastasis, however subsequent data, including minimally invasive
surgery patients, were more equivocal. 27,28
Summary statement: There is a lack of evidence from well designed prospective studies to support or refute a role
for regional anesthesia/analgesia and cancer recurrence.
Effect of regional analgesic technique on patient oriented outcomes

As risk of major perioperative complications decrease, patient oriented outcomes are increasingly being
viewed as valuable. Indeed, patient oriented outcomes such as postoperative pain or nausea are consistently rated as
top priorities in patient surveys. Unfortunately, there are few validated tools for measuring patient evaluation of
such outcomes, as most tools are uni-dimensional and do not recognize patient preferences for different
combinations of outcomes and linked side effects. 29
Epidural Analgesia
Analgesia: Two meta-analyses have compared epidural analgesia to systemic analgesia for mixed surgical
procedures.9,10 For both meta-analyses, epidural analgesia (compared to systemic opioids including intravenous
patient-controlled analgesia [IV PCA]) provided statistically superior analgesia at rest and with activity for all types
of surgery through postoperative day (POD) 4. Greater improvements were noted when the regimen included local
anesthetics and when level of epidural catheter matched site of surgery (e.g., thoracic catheter for thoracic surgery).
Multiple procedure specific meta-analyses have also been published13-16, and all consistently note statistically
significantly lower pain scores with epidural techniques.
Side effects: The meta-analyses from 2003 and 2005 also reported on incidences of side effects. As expected
epidural and IV PCA analgesia offered different profiles of side effects with epidural analgesia associated with
significantly reduced risk of nausea and sedation but significantly higher incidences of pruritus, urinary retention,
and motor block. When continuous epidural analgesia was compared to patient controlled epidural analgesia,
patient controlled epidural analgesia offered a reduced risk of side effects with significantly lower incidences of
nausea and motor block but greater incidence of pruritus.
Summary statement: Epidural analgesia provides superior analgesia to any form of systemic opioid including IV
PCA delivery for at least the first 3 POD for a variety of surgical procedures. Use of local anesthetics can maximize
this efficacy. Side effect profiles differ between regimens
Continuous peri-neural analgesia

Analgesia and side effects
A meta analysis published in 2006 (19 RCTs with 603 patients) compared continuous peri-neural analgesia
vs. mixed systemic opioids (13 of 19 RCTs used IV PCA). 25 Peri-neural analgesia, which can be used on an
ambulatory basis27, provided statistically superior analgesia at rest and with activity for 48-72 hours with a reduction
in risk of nausea, sedation, pruritus but increased risk of motor block.
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Functional outcomes
Several recent RCTs suggest that use of perineural analgesia can be used to shorten length of stay of major
orthopedic procedures such as total shoulder, knee, and hip replacement by nearly 30 %. 30-32 After total shoulder
replacement, patients were randomized to saline or ropivacaine via an interscalene catheter. Patients receiving
ropivacaine achieved prospectively defined discharge criteria in 21 vs 51 hrs (p<0.001). After total knee
replacement surgery, patients were randomized to saline or ropivacaine via a femoral nerve catheter. Patients
receiving ropivacaine achieved prospectively defined discharge criteria in 25 vs 71 hrs (p<0.001). After total hip
replacement surgery, patients were randomized to saline or ropivacaine via a lumbasr plexus catheter. Patients
receiving ropivacaine achieved prospectively defined discharge criteria in 29 vs 51 hrs (p<0.001). Long term
investigations have also followed these same patients out for a year after surgery to determine if early superiority in
functional outcomes with regional analgesia is preserved. However, no differences in health related quality of life
were noted between groups. 33 A RCT randomizing patients to TEA/GA vs GA for off-pump CABG noted that
TEA resulted in better analgesia, less sedation, faster time to tracheal extubation, and shorter length of ICU and
hospital stay. 34
Ambulatory surgery now comprises 60-70% of surgical volume. Regional analgesia also appears to have
similar salutatory effects for ambulatory surgery. Patients undergoing shoulder or foot/ankle ambulatory surgery
were randomized to receive either patient controlled regional analgesia with ropivacaine (via interscalene or
popliteal catheter) versus patient controlled intravenous analgesia with morphine. Patients receiving regional
analgesia had statistically superior pain control, less side effects, and greater degrees of independent activity for the
first 3 days after surgery. 35 Indeed, recent case series suggest that use of perineural analgesia can convert total
shoulder, hip, and knee replacement from fully hospitalized to ambulatory surgery stays. 36,37
Finally, a recent narrative review noted that use of peripheral regional anesthesia was strongly associated
with reduction in pain scores and/or opioid use and improved patient satisfaction. 38
Summary statement: Meta analysis indicates that continuous peri-neural analgesia provides superior analgesia for
up to 48 hours after surgery with reduced side effects when compared to systemic opioids. Recent clinical trials
suggest use of perineural analgesia may decrease hospital stay for major orthopedic procedures and improve
functional status at home after ambulatory surgery.
Summary and Future Directions

Regional analgesia has modest beneficial effect on mortality. Epidural analgesia reduces cardiopulmonary
complications in major open procedures such as open aortic repair. Epidural analgesia with local anesthetic
containing solutions consistently reduces duration of ileus after open abdominal procedures. Beneficial effects have
been reduced by current low rates of postoperative complications and increased use of minimally invasive surgery
such as laparoscopic colectomy. 39 Effects of regional anesthesia/analgesia on cancer recurrence are of great interest
but await high quality prospective data. Patient oriented outcomes have become an increasingly important field for
investigation. Epidural analgesia consistently provides superior analgesia to systemic opioids and a different
package of side effects. Perineural analgesia consistently provides superior analgesia and reduced side effects
compared to systemic analgesia and may reduce length of stay after major orthopedic procedures.
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References
1. Liu SS, Wu CL: Effect of postoperative analgesia on major postoperative complications: a

systematic update of the evidence. Anesth Analg 2007; 104: 689-702
2. Rodgers A, Walker N, Schug S, McKee A, Kehlet H, van Zundert A, Sage D, Futter M, Saville G,
Clark T, MacMahon S: Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia:
results from overview of randomised trials. BMJ 2000; 321: 1493
3. Guay J, et al. Neuraxial anesthesia for the prevention of major postoperative mortality and
morbidity. An overview of Cochrane systematic reviews
4. Nishimori M, Ballantnye JC, Low JHS: Epidural pain relief versus systemic opioid based pain
relief for abdominal aortic surgery. Cochrane Database Syst Rev In Press
5. Svircevic V, van Dijk D, Nierich AP, Passier MP, Kalkman CJ, van der Heijden GJ, Bax L: Meta-
analysis of thoracic epidural anesthesia versus general anesthesia for cardiac surgery. Anesthesiology 2011; 114:
271-82
6. Werawatganon T, Charuluxanun S: Patient controlled intravenous opioid analgesia versus
continuous epidural analgesia for pain after intra-abdominal surgery. Cochrane Database Syst Rev 2005: CD004088
7. Choi PT, Bhandari M, Scott J, Douketis J: Epidural analgesia for pain relief following hip or knee
replacement. Cochrane Database Syst Rev 2003: CD003071
8. Svircevic V, Nierich AP, Moons KG, Diephuis JC, Ennema JJ, Brandon Bravo Bruinsma GJ,
Kalkman CJ, van Dijk D: Thoracic epidural anesthesia for cardiac surgery: a randomized trial. Anesthesiology 2011;
114: 262-70
9. Park WY, Thompson JS, Lee KK: Effect of epidural anesthesia and analgesia on perioperative
outcome: a randomized, controlled Veterans Affairs cooperative study. Ann Surg 2001; 234: 560-9
10. Rigg JR, Jamrozik K, Myles PS, Silbert BS, Peyton PJ, Parsons RW, Collins KS: Epidural
anaesthesia and analgesia and outcome of major surgery: a randomised trial. Lancet 2002; 359: 1276-82
11. Wijeysundera DN, Beattie WS, Austin PC, Hux JE, Laupacis A: Epidural anaesthesia and survival
after intermediate-to-high risk non-cardiac surgery: a population-based cohort study. Lancet 2008; 372: 562-9
12. Wu CL, Hurley RW, Anderson GF, Herbert R, Rowlingson AJ, Fleisher LA: Effect of
postoperative epidural analgesia on morbidity and mortality following surgery in medicare patients. Reg Anesth
Pain Med 2004; 29: 525-33
13. Bartels K, Sullivan BL, Eitzschig HK. Blowing the cover from perioperative myocardial injury.
Anesthesiology 2014:129:533-5
14. Taniguchi M, Kasaba T, Takasaki M: Epidural anesthesia enhances sympathetic nerve activity in
the unanesthetized segments in cats. Anesth Analg 1997; 84: 391-7
15. Meissner A, Rolf N, Van Aken H: Thoracic epidural anesthesia and the patient with heart disease:
benefits, risks, and controversies. Anesth Analg 1997; 85: 517-28
16. Liu SS, Block BM, Wu CL: Effects of perioperative central neuraxial analgesia on outcome after
coronary artery bypass surgery: a meta-analysis. Anesthesiology 2004; 101: 153-61
17. Marret E, Remy C, Bonnet F: Meta-analysis of epidural analgesia versus parenteral opioid
analgesia after colorectal surgery. Br J Surg 2007; 94: 665-73
18. Popping DM, Elia N, Marret E, Remy C, Tramer MR: Protective effects of epidural analgesia on
pulmonary complications after abdominal and thoracic surgery: a meta-analysis. Arch Surg 2008; 143: 990-9;
discussion 1000
19. Qaseem A, Snow V, Fitterman N, Hornbake ER, Lawrence VA, Smetana GW, Weiss K, Owens
DK, Aronson M, Barry P, Casey DE, Jr., Cross JT, Jr., Sherif KD, Weiss KB: Risk assessment for and strategies to
reduce perioperative pulmonary complications for patients undergoing noncardiothoracic surgery: a guideline from
the American College of Physicians. Ann Intern Med 2006; 144: 575-80
20. Warner DO: Preventing postoperative pulmonary complications: the role of the anesthesiologist.
21. Wu CL, Cohen SR, Richman JM, Rowlingson AJ, Courpas GE, Cheung K, Lin EE, Liu SS:
Efficacy of postoperative patient-controlled and continuous infusion epidural analgesia versus intravenous patient-
controlled analgesia with opioids: a meta-analysis. Anesthesiology 2005; 103: 1079-88; quiz 1109-10
22. Mythen MG: Postoperative gastrointestinal tract dysfunction. Anesth Analg 2005; 100: 196-204
23. Bauer AJ, Boeckxstaens GE: Mechanisms of postoperative ileus. Neurogastroenterol Motil 2004;
16 Suppl 2: 54-60
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24. Fotiadis RJ, Badvie S, Weston MD, Allen-Mersh TG: Epidural analgesia in gastrointestinal
surgery. Br J Surg 2004; 91: 828-41
25. Jorgensen H, Wetterslev J, Moiniche S, Dahl JB: Epidural local anaesthetics versus opioid-based
analgesic regimens on postoperative gastrointestinal paralysis, PONV and pain after abdominal surgery. Cochrane
Database Syst Rev 2000: CD001893
26. Gottschalk A, Sharma S, Ford J, Durieux ME, Tiouririne M: Review article: the role of the
perioperative period in recurrence after cancer surgery. Anesth Analg 2010; 110: 1636-43
27. Day A, Smith R, Jourdan I. Retrospective analysis of the effect of postoperative analgesia on
survival in patients after laparoscopic resection of colorectal cancer. BJA 2012:109:185-90
28. Myles PS, Peyton P, Silbert B, Hunt J, Rigg JR, Sessler DI: Perioperative epidural analgesia for
major abdominal surgery for cancer and recurrence-free survival: randomised trial. BMJ 2011; 342: d1491
29. Liu SS, Wu CL: The effect of analgesic technique on postoperative patient-reported outcomes
including analgesia: a systematic review. Anesth Analg 2007; 105: 789-808
30. Ilfeld BM, Le LT, Meyer RS, Mariano ER, Vandenborne K, Duncan PW, Sessler DI, Enneking
FK, Shuster JJ, Theriaque DW, Berry LF, Spadoni EH, Gearen PF: Ambulatory continuous femoral nerve blocks
decrease time to discharge readiness after tricompartment total knee arthroplasty: a randomized, triple-masked,
placebo-controlled study. Anesthesiology 2008; 108: 703-13
31. Ilfeld BM, Vandenborne K, Duncan PW, Sessler DI, Enneking FK, Shuster JJ, Theriaque DW,
Chmielewski TL, Spadoni EH, Wright TW: Ambulatory continuous interscalene nerve blocks decrease the time to
discharge readiness after total shoulder arthroplasty: a randomized, triple-masked, placebo-controlled study.
32. Ilfeld BM, Ball ST, Gearen PF, Le LT, Mariano ER, Vandenborne K, Duncan PW, Sessler DI,
Enneking FK, Shuster JJ, Theriaque DW, Meyer RS: Ambulatory continuous posterior lumbar plexus nerve blocks
after hip arthroplasty: a dual-center, randomized, triple-masked, placebo-controlled trial. Anesthesiology 2008; 109:
491-501
33. Ilfeld BM, Shuster JJ, Theriaque DW, Mariano ER, Girard PJ, Loland VJ, Meyer S, Donovan JF,
Pugh GA, Le LT, Sessler DI, Ball ST: Long-term pain, stiffness, and functional disability after total knee
arthroplasty with and without an extended ambulatory continuous femoral nerve block: a prospective, 1-year follow-
up of a multicenter, randomized, triple-masked, placebo-controlled trial. Reg Anesth Pain Med 2011; 36: 116-20
34. Caputo M, Alwair H, Rogers CA, Pike K, Cohen A, Monk C, Tomkins S, Ryder I, Moscariello C,
Lucchetti V, Angelini GD: Thoracic epidural anesthesia improves early outcomes in patients undergoing off-pump
coronary artery bypass surgery: a prospective, randomized, controlled trial. Anesthesiology 2011; 114: 380-90
35. Capdevila X, Dadure C, Bringuier S, Bernard N, Biboulet P, Gaertner E, Macaire P: Effect of
patient-controlled perineural analgesia on rehabilitation and pain after ambulatory orthopedic surgery: a multicenter
randomized trial. Anesthesiology 2006; 105: 566-73
36. Ilfeld BM, Wright TW, Enneking FK, Mace JA, Shuster JJ, Spadoni EH, Chmielewski TL,
Vandenborne K: Total shoulder arthroplasty as an outpatient procedure using ambulatory perineural local anesthetic
infusion: a pilot feasibility study. Anesth Analg 2005; 101: 1319-22
37. Ilfeld BM, Gearen PF, Enneking FK, Berry LF, Spadoni EH, George SZ, Vandenborne K: Total
hip arthroplasty as an overnight-stay procedure using an ambulatory continuous psoas compartment nerve block: a
prospective feasibility study. Reg Anesth Pain Med 2006; 31: 113-8
38. Kessler J et al. Peripheral regional anaesthesia and outcomes. Lessons learned from the past 10
years. BJA. 2015:114: 728-45
39. Levy BF, Scott MJ, Fawcett W, Fry C, Rockall TA: Randomized clinical trial of epidural, spinal
or patient-controlled analgesia for patients undergoing laparoscopic colorectal surgery. Br J Surg 2011; 98: 1068-78
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Radiation Safety for the Anesthesiologist and Pain Physician

Carlos A. Pino, M.D. Burlington, VT
Introduction
Everyone on Earth is exposed to back ground radiation and it is estimated that if you combine
cosmic radiation with medical, industrial and commercial sources, the average American is
exposed to 6.2 mSv/year. Over the last two decades, pain physicians have increasingly used
imaging to aid in performing procedures and anesthesiologists are progressively called to care
for patients, in and out of the operating room, where radiation exposure is a hazard. The majority
of the published studies focus on the exposure to surgeon or proceduralist, but very few
publications address the exposure of the anesthesiologist. It has been estimated that pilots and
flight attendants on ordinary aircrafts can receive annual doses around 10 mSv/year.
Definitions
Absorbed dose is the amount of energy deposited in the tissues at a specific point. It is measured
in Gray (Gy) or Rads (1 Gy=100 rads).
Equivalent dose is a dosimetry metric that attempts to quantify biologic damage by different
types of radiation. It is primarily used for radiation protection purposes and are only
“approximate indicators” of potential harm. Equivalent dose is expressed in Sievert (Sv) (1 Sv =
100 rem). For example, alpha particles emitted in radiation therapy can do more damage than
electrons emitted by x-ray imaging.
Effective dose is used to deal with the non-uniform dose distribution in the body and whether
radiation is absorbed by a specific tissue. You need to take into account the type of radiation and
the variable sensitivity of the organ (tissue weighting factors). Effective dose is expressed in
Sieverts(Sv). The tissue weighting factor is the fractional contribution of each organ to the total
whole-body radiation. (Tables 1 and 2)
Absorbed Dose -----------------> Equivalent Dose ----------------> Effective Dose
Radiation Tissue
weighting weighting
factor factor
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Table 1: Organ relative radiosensitivity (Tissue weighting factors) used by ICRP.
Tissue Weighting Factor Organs Detriment
0.12 Bone marrow; colon; lung; Cancer

stomach; breast; adrenals, etc
0.08 Gonads Hereditary
0.04 Bladder, liver; esophagus, Cancer

thyroid
0.01 Skin; bone; brain Cancer
Table 2: Organ dose (mGy) or Equivalent dose (mSv) for radiographic examinations.
Organ Lateral Skull PA Chest AP Abdomen
Bone marrow 0.05 0.02 0.2
Lungs <0.01 0.06 0.02
Stomach <0.01 0.01 1.3
Colon <0.01 <0.01 1.3
Breast <0.01 0.01 0.01
Gonads <0.01 <0.01 0.60
Effective Dose (mSv) 0.03 0.015 0.5
Radiation Biology - Interactions of radiations with tissue
Biologic effect of radiation depends on the total energy deposited in the cell (absorbed dose).
The primary variable is that inherent to the cells at the time of irradiation, but there are other
variables related to the radiation itself (type of radiation, absorbed dose, etc.). Damage to
biologic systems always occurs first at the molecular level. Loss of molecular function will
ultimately lead to cellular dysfunction and organ damage.
Direct vs. Indirect Ionizing Radiation
Direct action occurs when Compton electrons and photoelectrons ionize DNA molecules. It is
responsible for less than 1/3 of the biological damage by ionizing radiation.
Indirect action occurs when Compton and photoelectrons interact with water in the cell to
produce free hydroxyl radicals. These radicals can diffuse and damage target molecules, such as
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DNA. About 2/3 of the biologic damage by x-rays is caused by indirect action.
Deterministic vs. Stochastic Effects
Deterministic effects are harmful tissue reactions that occur above a threshold dose (D
threshold). For doses above the threshold dose, deterministic effects are expected to occur in all
exposed individuals and are generally a direct result of cell destruction. Severity of of these
effects may increase with increasing dose. Examples of deterministic effects include skin burns,
epilation, eye cataracts, and sterility.
Skin: High skin doses generally occur at the point where an x-ray beam enters the patient.
Below skin doses of 2 Gy, no effects are observed. Between 2 and 5 Gy erythema may occur,
and above 5 Gy erythema will occur, so patients should be advised to perform self-exam in the
following 2-10 weeks.
Epilation: The loss of hair can occur following irradiation of the scalp in high risk procedures.
Below 3 Gy no loss of hair is expected. For scalp doses 3 to 6 Gy, temporary epilation may
occur, with an onset at 2-3 weeks and complete regrowth at 6-12 months. At scalp doses of 7 Gy
or above, epilation is likely to be permanent.
Cataract: As of 2011, the International Commission of Radiological Protection (ICRP)

considers the threshold dose for cataract induction at 0.5 Gy. The latency period for the
development of cataracts may be of several years and as the doses increase, the latency period
may get shorter.
Sterility: Doses as low as 0.2 Gy can result in low sperm count and doses above 0.5 Gy can
result in azoospermia. Permanent sterility in men requires a single dose of 6 Gy, and fractionated
exposure to the gonads produce more damage than acute exposure. In females, doses for sterility
(permanent ovarian failure) are dependent on age. Whereas 10 Gy can result in permanent
sterility in prepuberty, only 2 Gy will do so in in premenopausal females.
Stochastic effects are random tissue reaction that have no threshold dose and the severity of these
reactions are also independent of the radiation dose. In stochastic effects, the radiation dose only
affects the probability of the event occurring. Examples of stochastic effects are carcinogenesis
and hereditary effects.
Carcinogenesis: It is generally accepted that at higher (therapeutic) doses, radiation may result
in cancer (i.e. radiation therapy for breast cancer and Hodgkin’s lymphoma). Although there is
still some uncertainty, growing evidence suggest that lower dose, such as those encountered in
diagnostic applications, may result in increased carcinogenic risk (i.e. increased in leukemia and
brain tumors in children who underwent CT in the UK).
Hereditary effects: these are based on animal data. Studies of children born to the A-bomb
survivors have not shown any significant increased effects. In a population that excludes
children, the hereditary risk is about 0.1% and in the entire population, the ICRP hereditary risk
estimate is 0.2% per Gy. For conceptus deterministic risks, please see the ACR Practice
Guidelines for Imaging Pregnant Women.
Radiation Safety for patients and staff

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Approximately 400 million diagnostic exams are performed in the United State each year (table
3). Average exposure of the US population has increased from 0.6 mSv in the 1980s to 3 mSv in
2006. CT scans now account for 17% of all diagnostic x-ray examinations and half the
population medical dose. Practitioners need to understand the magnitude of risk to benefit ratio
of x-ray exam or x-ray guided procedure.
Table 3: Radiology exams performed in the United States in 2006
Type of exam # performed Average effective Per Capita dose (mSv)

(millions) dose/patient exam
(mSv)
Radiography & 290 0.3 0.3

Fluoroscopy
Interventional 20 8 0.4
Radiology
Computed 70 7 1.5
Tomography
Nuclear Medicine 20 13 0.8
Total 400 2.5 3.0
Radiation protection is aimed at preventing deterministic effects and minimizing risk of

stochastic effects. As a general rule, the scatter dose at 1 meter is about 0.1% of the entrance skin
dose. Methods to control radiation dose are decreasing exposure time, increasing distance from
the source and shielding.
Exposure time should always be minimized. Fluoroscopy units have a 5-minute alarm that
reminds operators of increasing exposure. Pulsed fluoroscopy should be used rather than
continuous fluoroscopy whenever possible. Table 4 shows how using pulse fluoroscopy can
reduce radiation dose.
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Table 4: Pulse fluoroscopy and effect on radiation dose
Distance: Radiation intensity is inversely proportional to the square of the distance from the
source, such that doubling the distance reduces the doses fourfold. Increasing the distance from a
source is more effective at reducing operator doses than reducing the exposure time.
Shielding: x-ray attenuation by lead is high due to its high density and atomic number. Lead
aprons should have 0.25 – 0.5 mm of lead and should be worn at all times. Lead aprons are
expected to attenuate at least 90% of an incident x-ray beam. Lead aprons can crack when folded
improperly so they should be tested annually. Lead neck shield should be worn to reduce thyroid
exposure and leaded glasses reduce eye lens exposure. (Figure 1) The table should have a lead
curtain to protect the staff in the room. Leaded gloves may be used to minimize extremity doses
Figure 1: Devices available for operator and staff protection.
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References:
1) Henderson KH, Lu JK, Strauss KJ, Treves ST, Rockoff MA. Radiation exposure of
anesthesiologists. Journal of Clinical Anaesthesia 1994; 6: 37–41.
2) Ismail S, Khan FA, Sultan N, Naqvi M. Radiation exposure of trainee anaesthetists.
Anaesthesia 2006; 61: 9–14.
3) McGowan C, Heaton B, Stephenson RN. Occupational x-ray exposure of anaesthetists.
British Journal of Anaesthesia 1996; 76: 868–9.
4) Huda W. Review of Radiologic Physics. 4th Ed. Wolters Kluwer. Philadelphia 2016.
5) Mehlman CT, DiPasquale TG. Radiation exposure to the orthopaedic surgical team
during fluoroscopy: ‘‘How far away is far enough?” Journal of Orthopaedic Trauma
1997; 11: 392–8.
6) Sass-Kortsak AM, Purdham JT, Bozek PR, Murphy JH. Exposure of hospital operating
room personnel to potentially harmful environmental agents. American Industrial
Hygiene Associa- tion Journal 1992; 53: 203–9.
7) Semelka RC, Armao DM, Elias J Jr, Huda W. Imaging strategies to reduce the risk of
radiation in CT studies, including selective substitution with MRI. Journal of Magnetic
Resonance Imaging 2007; 25: 900–9.
8) Theocharopoulos N, Perisinakis K, Damilakis J, Papadokostakis G, Hadjipavlou A,
Gourtsoyiannis N. Occupational exposure from common fluoroscopic projections used in
orthopaedic surgery. American Journal of Bone and Joint Surgery 2003; 85: 1698–703.
9) Rhea EB, Rogers TH, Riehl JT. Radiation safety for anaesthesia providers in the
orthopaedic operating room. Anaesthesia 2016, 71, 455–461 doi:10.1111/anae.13400.
10) Semelka RC, Armao DM, Elias J Jr, Huda W. Imaging strategies to reduce the risk of
radiation in CT studies, including selective substitution with MRI. Journal of Magnetic
Resonance Imaging 2007; 25: 900–9.
11) Barish RJ. Health physics concerns in commercial aviation. Health Physics 1990; 59:
199–204.
12) ACR-AAPM Technical Standard for Management of the Use of Radiation in
Fluoroscopic Procedures.
http://www.acr.org/~/media/ACR/Documents/PGTS/standards/MgmtFluoroProcedures.p
df viewed June 14, 2016.
13) ACR-SPR Practice Paramenter for Imaging Pregnant or Potentially Pregnant Adolescents
and Women with Ionizing Radiation.
http://www.acr.org/~/media/ACR/Documents/PGTS/guidelines/Pregnant_Patients.pdf
viewed June 14, 2016.
14) Rathmell JP. Ch 2. Radiation Safety. In: Atlas of Image-Guided Intervention in Regional
Anesthesia and Pain Medicine. Lippincott Williams & Wilkins. 2012:8-15
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Perioperative Stroke for the General Anesthesiologist and Specialist
Laurel E. Moore, M.D. Ann Arbor, MI
Introduction
Perioperative stroke is a known complication of high risk procedures such as open heart and carotid endarterectomy
(CEA) but it is increasingly recognized as a major cause of morbidity and mortality following noncardiac and
nonneurosurgical procedures as well. Perioperative stroke is difficult to study in these low-risk surgical populations
for several reasons: its relatively low incidence, difficulty in recognizing stroke in post-surgical patients, varying
definitions of “perioperative” between studies, and the lack of available biomarkers such as troponins to assist in the
diagnosis of stroke. Our understanding of perioperative stroke is improving, however, and this trend has been
helped by recent developments in our understanding of the pathology of stroke, improved treatment options for
acute ischemic stroke (AIS) and the improved accessibility of “big data” to study this low-incidence complication.
My goals for this refresher course include updating attendees on the recent science surrounding stroke in general and
to discuss those areas of clinical practice that are relevant to patient care but remain controversial.
Significance of Perioperative Stroke
While the incidence of perioperative stroke in the noncardiac nonneurologic surgical populations is seemingly low
(0.1%), (1) this number may be overly reassuring. This figure is true for patients without significant medical co-
morbidities but the incidence increases 20-fold for patients with significant medical illness, even when undergoing
“low risk” surgical procedures. (1) Furthermore, we may be missing a significant proportion of strokes which
remain unrecognized clinically but are evident radiographically. In the nonoperative setting silent brain infarction
(“SBI”) is associated with a 2-fold increased risk of subsequent symptomatic stroke (2) as well as long-term
complications such as cognitive dysfunction(3), dementia (3) and early mortality. (4) There is an approximately 20%
incidence of SBI by magnetic resonance imaging (MRI) in older adults overall and in postoperative noncardiac
surgery patients over 65 the incidence of new clinically unrecognized defects on MRI is as high as 11%.(5)
Perioperative stroke has numerous implications, some of which are not immediately apparent. Clearly the
neurologic sequelae of perioperative stroke can be both physically and emotionally devastating for an individual
patient. Furthermore, 30-d mortality is markedly increased for patients suffering perioperative stroke. For the
noncardiac nonneurologic surgical population mortality can be increased 8-20 fold in patients suffering
stroke.(1,6,7) Mortality for perioperative stroke is roughly 30% (8) and half of survivors recover with major
disabilities (8,9), outcomes far worse than stroke in the nonoperative setting. What is becoming apparent over time
is that stroke may be a marker for patients at risk for other complications associated with surgery. For example, in
cardiac surgery patients those individuals suffering late stroke (following uneventful emergence from anesthesia,
presumably nonprocedural) had a higher mortality rate over years compared to patients suffering early (procedural)
stroke or those without stroke.(10) In patients with a history of stroke undergoing elective noncardiac procedures
there is a close temporal relationship between the interval since stroke and the risk of recurrent stroke and major
adverse cardiac events (MACE: myocardial infarction, ischemic stroke or cardiovascular death) and 30-day
mortality.(11) Even patients with a remote history of stroke (> 12 months prior to surgery) have a 2.5-fold increased
risk of MACE.(11) Thus not only is perioperative stroke an independent risk factor for perioperative mortality but it
may also be a marker for those patients at risk for related perioperative cardiovascular complications and poor long-
term neurologic outcomes.
Difficulties in reducing the risk of perioperative stroke
Given the above concerns regarding perioperative stroke it would seem reasonable to work to reduce the risk of
stroke for our patients preoperatively. Unfortunately, many of the associations with perioperative stroke are not
modifiable. In terms of procedural risks, there may be minor differences in the incidence of perioperative stroke
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between two surgical options, for example between open and endovascular abdominal aortic repair.(6) However,
surgical decision making does not frequently allow for such options and more importantly, for any individual patient
the relative risk reduction is minor. There are clearly surgical procedures at increased risk for stroke such as open
heart procedures and CEA, but as a general statement surgical associations with stroke are relatively fixed and not
an opportunity to reduce stroke incidence.
As regards medical co-morbidities associated with perioperative stroke, unfortunately there is also little opportunity
to optimize patients perioperatively. Known patient risk factors include a prior history of stroke or transient
ischemic attack, advanced age, chronic renal disease and female gender,(1,6) none of which is modifiable in the
perioperative setting. Other known patient factors such as a history of atrial fibrillation (8) or hypertension (1) have
the potential for modification but there are currently no data to support that preoperative clinical optimization of
these risk factors may reduce the risk of perioperative stroke.
Clinically relevant management decisions which may affect the incidence of perioperative stroke
While the risks associated with perioperative stroke are relatively fixed for patient and surgical factors, there may be
opportunity to reduce the risk of stroke based on perioperative clinical management, although hard evidence for
improved outcomes is lacking.
Timing of elective surgery following ischemic stroke

The timing of elective surgery following ischemic stroke deserves consideration based on the findings of one large
study utilizing the Danish nationwide cohort.(11) Prior recommendations for patients suffering ischemic stroke
were to delay elective surgery for 4-6 weeks(12) in order to allow some return of cerebral autoregulatory
mechanisms. Jorgensen et al, however, have demonstrated a strong temporal relationship between ischemic stroke
and the risk of complications following elective noncardiac surgery.(11) For example, when elective surgery is
scheduled within 3 months of stroke the adjusted odds of recurrent stroke is increased 67-fold. The risks of 30-day
mortality and MACE within this time frame were similarly increased 3- and 14-fold respectively. This window for
increased risk extends as far out as 9 months following ischemic stroke. One criticism of this retrospective study
was its absence of nonoperative control patients and the possibility that the temporal relationship of recurrent stroke
and other complications may be identical to what is seen for nonoperative ischemic stroke. In response, Jorgensen’s
group reanalyzed the data comparing complications in the original postoperative population to a nonoperative
population of patients suffering stroke.(13) The group found that for nonoperative stroke patients the risk of
recurrent stroke followed a similar temporal trend but that the relative risks were far below those for surgical
patients. This further supports that the perioperative period places stroke patients at particular risk for recurrent
stroke and other cardiovascular complications and should be regarded as a high risk period for this patient
population.
Perioperative β-blocker therapy

The original POISE trial(14) demonstrated for the first time a relationship between the use of acutely administered
perioperative β-blockers and postoperative stroke and death. Subsequent work has supported that β-blockers and
particularly nonselective β-blockers such as metoprolol may be uniquely associated with perioperative
stroke.(15,16) The reasons for this relationship are at least 2-fold. Acute metoprolol administration reduces the
compensatory cardiac output response to hemodilution.(17) It has also been demonstrated in animals(18) and
humans (16) that nonselective β-blockers such as metoprolol and atenolol may be associated with a greater risk of
stroke via inhibition of β2-mediated cerebral vasodilation to stimulants such as anemia. It is important to note that
acute withdrawal of β-blocker therapy in the perioperative setting has its own set of risks and complications and
should not be considered without further study. However, it seems reasonable while we wait for further clinical
study to choose β1-selective agents when possible perioperatively, and to consider a higher transfusion trigger for
those patients on chronic β-blocker therapy, particularly when other risk factors for perioperative stroke are present.
Perioperative antiplatelet therapy

The continuation of antiplatelet therapy throughout the perioperative period is accepted as standard practice for
patients who have undergone recent percutaneous coronary intervention (PCI).(19) The management of patients on
chronic aspirin (ASA) therapy for other indications, however, is less clear. In 2014 Devereaux et al published the
results of the POISE-2 trial(20) evaluating the use of perioperative ASA therapy on the primary outcomes of death
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and nonfatal myocardial infarction. Half of the 10,000 patients were randomized to ASA (either continuation or
initiation groups based on whether they were on ASA at entry) and half were in the placebo group. Those patients
randomized to placebo who were on ASA at entry discontinued their antiplatelet therapy at least 3 days prior to
surgery. Eligible patients met defined criteria as evidence for existing cardiovascular disease but patients who had
undergone bare-metal stent within 6 weeks or drug-eluting stent within 1 year and patients undergoing CEA were
specifically excluded from participation. They found no difference between groups for either death or myocardial
infarction but there was an increased risk of well-defined major bleeding for those patient randomized to ASA. The
authors and the accompanying editorial(21) conclude that the increased risk of bleeding with perioperative ASA
outweighs the potential benefits of continued antiplatelet therapy. Concerns regarding POISE-2 include several
points: 1. A minority of study patients were on antiplatelet therapy for American Heart Association supported 1° or
2° preventive therapy indications, possibly obscuring any detrimental effect of ASA withdrawal for those patients on
antiplatelet therapy for guideline-supported indications. 2. Only 4.9% of patients underwent vascular surgery
procedures and CEA patients were excluded from participating, diluting any potential benefit for those patients who
might benefit most from ASA continuation. 3. A large proportion of subjects received some combination of
antiplatelet or anticoagulant therapy within 3 days following surgery, thus confounding results. POISE-2 is
considered to be the definitive study on the topic of perioperative ASA administration and the conclusions are
relevant to the majority of our patients. Two considerations to make, however, include that we routinely continue
perioperative ASA for patients s/p PCI without pause and it is possible that POISE-2 excluded those subjects who
had the most to gain by continuing ASA in the perioperative period. It seems reasonable to consider each patient
individually based on their indications for ASA therapy and the risk of hemorrhage associated with their operative
procedure.
Perioperative hypotension and stroke in noncardiac patients

In the recent literature, hypotension is increasingly associated with poor perioperative outcomes including acute
kidney injury, myocardial injury and an increased mortality.(22-24) Surprisingly, the relationship between
intraoperative hypotension and perioperative stroke in noncardiac and nonneurosurgical procedures is less clear.(25)
While intraoperative hypotension is common, patients emerging from anesthesia with new neurologic deficits are
seen infrequently and stroke onset is frequently delayed 2-3 days postoperatively(6,25,26) Still, there is evidence
that intraoperative hypotension is associated with perioperative stroke .(15,27) It has been suggested that patients
suffering intraoperative hypotension may be more likely to also have hemodynamic instability postoperatively when
they are not as closely monitored, and this could contribute to the association between intraoperative hypotension
and perioperative stroke.(27) Given that the mechanisms of perioperative stroke are generally felt to be thrombotic
or embolic in origin,(25) current studies support that perioperative hypotension may be contributory to ischemic
injury rather than the primary causative insult. More research is required on this important clinical association.
Recent practice changes for Acute Ischemic Stroke (AIS)
In the past two years 5 randomized controlled trials in support of endovascular intervention for anterior large vessel
occlusion have been published, optimally in combination with systemic thrombolysis [MR CLEAN (28), ESCAPE
(29), EXTEND-IA (30), SWIFT PRIME (31), REVASCAT (32)]. As a result many stroke centers are seeing an
increasing volume of patients presenting with AIS. The implications of these nonoperative stroke studies on the
care of patients suffering perioperative stroke is unclear. While there are reports of postoperative patients receiving
systemic thrombolysis, (33,34) this therapy clearly presents risks for surgical patients. Endovascular mechanical
thrombolysis, however, would seem to be an ideal treatment option for patients with perioperative stroke because
systemic thrombolysis is not required. The challenge becomes early recognition and rapid referral of perioperative
stroke so that endovascular therapy can be offered as a treatment option.
Recognition and management of stroke in postoperative patients
Recognition of stroke in the postoperative setting is difficult for many reasons including residual anesthetic effect,
pain and pain therapy and delirium from other causes. Patients with a prior history of stroke without apparent
sequelae may have unmasking of their prior deficit via “differential awakening”(35), further complicating diagnosis.
As previously mentioned, the onset of stroke may be delayed beyond the immediate (and closely monitored)
perioperative period and thus recognition of stroke may occur beyond the window of eligibility for endovascular
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therapy.(26) There are currently no evidence-based screening tools specifically for perioperative patients, although
a recent excellent review recommends a variation of the directed FAST test which includes consideration of
residual anesthetic effects (FAAST: Face, Arm, Anesthesia, Speech and Time).(9) Given the recent evidence
supporting the therapeutic benefits of endovascular therapy, postoperative patients with evidence of stroke should be
immediately evaluated including referral to the hospital stroke team and emergent non-contrast head CT to rule out
intracranial hemorrhage. Systemic thrombolysis may be considered on a case-by-case basis in conjunction with the
surgical team, but for clinically significant stroke symptoms endovascular therapy should be immediately considered
and if these resources are not available, emergent transfer to a regional stroke center should be discussed. While the
window of eligibility for systemic thrombolysis is 4.5 hours,(36) eligibility for endovascular therapy extends to 6
hours (36) and studies are underway to investigate extending this temporal window further.
Conclusion
Perioperative stroke in the noncardiac and nonneurologic surgical settings is fortunately rare, but it may not be as
infrequent as we think. As options for management of perioperative stroke continue to improve we need to work to
rapidly recognize this potentially devastating complication of surgery in order to optimize care for these high risk
patients.
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Page 5
References
1. Mashour GA, Shanks AM, Kheterpal S. Perioperative stroke and associated mortality after noncardiac,
nonneurologic surgery. Anesthesiology. 2011;114(6):1289-96.
2. Gupta A, Giambrone AE, Gialdini G, et al. Silent Brain Infarction and Risk of Future Stroke: A Systematic
Review and Meta-Analysis. Stroke. 2016;47(3):719-25.
3. Vermeer SE, Prins ND, den Heijer T, et al. Silent brain infarcts and the risk of dementia and cognitive
decline. N Engl J Med. 2003;348(13):1215-22.
4. Bokura H, Kobayashi S, Yamaguchi S, et al. Silent brain infarction and subcortical white matter lesions
increase the risk of stroke and mortality: a prospective cohort study. J Stroke Cerebrovasc Dis. 2006;15(2):57-63.
5. Mrkobrada M, Hill M, Chan MT, et al. Abstract TMP9: The Neurovision Pilot Study: Non-cardiac Surgery
Carries A Significant Risk Of Acute Covert Stroke. Stroke. 2013:ATMP9.
6. Sharifpour M, Moore LE, Shanks AM, et al. Incidence, predictors, and outcomes of perioperative stroke in
noncarotid major vascular surgery. Anesth Analg. 2013;116(2):424-34.
7. Axelrod DA, Stanley JC, Upchurch GR, Jr., et al. Risk for stroke after elective noncarotid vascular surgery.
J Vasc Surg. 2004;39(1):67-72.
8. Bateman BT, Schumacher HC, Wang S, Shaefi S, Berman MF. Perioperative acute ischemic stroke in
noncardiac and nonvascular surgery: incidence, risk factors, and outcomes. Anesthesiology. 2009;110(2):231-8.
9. Sun Z, Yue Y, Leung CC, Chan MT, Gelb AW. Clinical diagnostic tools for screening of perioperative
stroke in general surgery: a systematic review. Br J Anaesth. 2016;116(3):328-38.
10. Hedberg M, Boivie P, Engstrom KG. Early and delayed stroke after coronary surgery - an analysis of risk
factors and the impact on short- and long-term survival. Eur J Cardiothorac Surg. 2011;40(2):379-87.
11. Jorgensen ME, Torp-Pedersen C, Gislason GH, et al. Time elapsed after ischemic stroke and risk of
adverse cardiovascular events and mortality following elective noncardiac surgery. JAMA. 2014;312(3):269-77.
12. Mashour GA, Moore LE, Lele AV, Robicsek SA, Gelb AW. Perioperative care of patients at high risk for
stroke during or after non-cardiac, non-neurologic surgery: consensus statement from the Society for Neuroscience
in Anesthesiology and Critical Care*. J Neurosurg Anesthesiol. 2014;26(4):273-85.
13. Jorgensen ME, Gislason GH, Andersson C. Time since stroke and risk of adverse outcomes after surgery--
reply. JAMA. 2014;312(18):1930-1.
14. Devereaux PJ, Yang H, Yusuf S, et al. Effects of extended-release metoprolol succinate in patients
undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. Lancet. 2008;371(9627):1839-47.
15. Mashour GA, Sharifpour M, Freundlich RE, et al. Perioperative metoprolol and risk of stroke after
noncardiac surgery. Anesthesiology. 2013;119(6):1340-6.
16. Ashes C, Judelman S, Wijeysundera DN, et al. Selective beta1-antagonism with bisoprolol is associated
with fewer postoperative strokes than atenolol or metoprolol: a single-center cohort study of 44,092 consecutive
patients. Anesthesiology. 2013;119(4):777-87.
17. Ragoonanan TE, Beattie WS, Mazer CD, et al. Metoprolol reduces cerebral tissue oxygen tension after
acute hemodilution in rats. Anesthesiology. 2009;111(5):988-1000.
18. El Beheiry MH, Heximer SP, Voigtlaender-Bolz J, et al. Metoprolol impairs resistance artery function in
mice. J Appl Physiol (1985). 2011;111(4):1125-33.
19. Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA Guideline Focused Update on Duration of Dual
Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of
Cardiology/American Heart Association Task Force on Clinical Practice Guidelines: An Update of the 2011
ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention, 2011 ACCF/AHA Guideline for Coronary
Artery Bypass Graft Surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and
Management of Patients With Stable Ischemic Heart Disease, 2013 ACCF/AHA Guideline for the Management of
ST-Elevation Myocardial Infarction, 2014 AHA/ACC Guideline for the Management of Patients With Non-ST-
Elevation Acute Coronary Syndromes, and 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation
and Management of Patients Undergoing Noncardiac Surgery. Circulation. 2016: In Press
20. Devereaux PJ, Mrkobrada M, Sessler DI, et al. Aspirin in patients undergoing noncardiac surgery. N Engl J
Med. 2014;370(16):1494-503.
21. Vaishnava P, Eagle KA. The yin and yang of perioperative medicine. N Engl J Med. 2014;370(16):1554-5.
22. Willingham MD, Karren E, Shanks AM, et al. Concurrence of Intraoperative Hypotension, Low Minimum
Alveolar Concentration, and Low Bispectral Index Is Associated with Postoperative Death. Anesthesiology.
2015;123(4):775-85.
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23. Monk TG, Bronsert MR, Henderson WG, et al. Association between Intraoperative Hypotension and
Hypertension and 30-day Postoperative Mortality in Noncardiac Surgery. Anesthesiology. 2015;123(2):307-19.
24. Walsh M, Devereaux PJ, Garg AX, et al. Relationship between intraoperative mean arterial pressure and
clinical outcomes after noncardiac surgery: toward an empirical definition of hypotension. Anesthesiology.
2013;119(3):507-15.
25. Bijker JB, Gelb AW. Review article: the role of hypotension in perioperative stroke. Can J Anaesth.
2013;60(2):159-67.
26. Vlisides PE, Mashour GA, Didier TJ, et al. Recognition and Management of Perioperative Stroke in
Hospitalized Patients. A and A Case Reports. In Press
27. Bijker JB, Persoon S, Peelen LM, et al. Intraoperative hypotension and perioperative ischemic stroke after
general surgery: a nested case-control study. Anesthesiology. 2012;116(3):658-64.
28. Berkhemer OA, Fransen PS, Beumer D, et al. A randomized trial of intraarterial treatment for acute
ischemic stroke. N Engl J Med. 2015;372(1):11-20.
29. Goyal M, Demchuk AM, Menon BK, et al. Randomized assessment of rapid endovascular treatment of
ischemic stroke. N Engl J Med. 2015;372(11):1019-30.
30. Campbell BC, Mitchell PJ, Kleinig TJ, et al. Endovascular therapy for ischemic stroke with perfusion-
imaging selection. N Engl J Med. 2015;372(11):1009-18.
31. Saver JL, Goyal M, Bonafe A, et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in
stroke. N Engl J Med. 2015;372(24):2285-95.
32. Jovin TG, Chamorro A, Cobo E, et al. Thrombectomy within 8 hours after symptom onset in ischemic
stroke. N Engl J Med. 2015;372(24):2296-306.
33. Ezzet KA. Reversal of acute ischemic stroke after THA using tissue plasminogen activator. Orthopedics.
2013;36(5):e676-8.
34. Seifert CL, Sprenger T, Mucke T, et al. Systemic thrombolysis in ischemic stroke after recent oral surgery
and management of oral cavity bleeding. Ann Emerg Med. 2011;57(5):517-9.
35. Lin N, Han R, Zhou J, Gelb AW. Mild Sedation Exacerbates or Unmasks Focal Neurologic Dysfunction in
Neurosurgical Patients with Supratentorial Brain Mass Lesions in a Drug-specific Manner. Anesthesiology.
2016;124(3):598-607.
36. Powers WJ, Derdeyn CP, Biller J, et al. 2015 American Heart Association/American Stroke Association
Focused Update of the 2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke
Regarding Endovascular Treatment: A Guideline for Healthcare Professionals From the American Heart
Association/American Stroke Association. Stroke. 2015;46(10):3020-35.
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Page 1
The Myths of Plasma and Synthetic Colloid Use During Cardiac Surgery
Roman M. Sniecinski, MD Atlanta, GA
Introduction
In the early days of cardiac surgery, large priming volumes were required for cardiopulmonary bypass (CPB)
circuits and, as a result, blood was almost universally used. As the circuits became more refined and the perfusion
benefits of hemodilution became embraced, [1] crystalloid solutions began to replace blood for priming purposes.[2]
Myocardial edema, however, became recognized as a problem with crystalloid CPB primes.[3] Around the same
time, following the Vietnam War, there was an interest in decreasing the amount of crystalloid administered to
trauma patients in order to decrease tissue edema resulting from large volume resuscitations.[4] It was demonstrated
that colloids were able to produce a greater plasma volume expansion with less volume administered, thus more
rapidly restoring plasma volume and potentially leading to less fluid accumulation in the lung and interstitial
space.[5] These observations have guided the resulting search for the ideal fluid for CPB priming, as well as for
resuscitation commonly required in cardiac surgical patients.
Traditional Startling Principles

The Starling Equation summarizes the exchange of fluid across the capillary wall (Figure 1).[6] Hydrostatic
forces fall across the
capillary from about 30
mmHg at the arterial end to
about 15 mmHg at the
venous end. It becomes
obvious from the Starling
Equation, that the higher the
capillary (i.e. intravascular)
osmotic pressure, the less
fluid will migrate into the
interstitium. The colloid
osmotic pressure (COP) is a
function of the number of
molecules exerting an effect,
so colloids are additive. The
COP of blood is essentially
that of plasma, since large
molecules such as platelets
and red blood cells are
relatively few in number
Figure 1: Starling Equation describing the movement of fluid across a capillary compared to other protein
molecules such as albumin.
The initial volume effect of colloids will be greater than an equal volume of administered crystalloid since more of
the fluid will be retained in the intravascular space. It is important to keep in mind, however, that different capillary
beds will allow the movement of colloid molecules into the interstitium to varying degrees. The typical reflection
coefficient (σ) for systemic capillaries is about 0.95, while it is about 0.7 in the pulmonary beds.[7] Inflammation
and trauma will further decrease these reflection values.
Rationale for Colloids in Cardiac Surgery

Early studies in cardiac surgical patients demonstrated a decrease in COP of about 50% upon initiation of CPB
with a crystalloid prime.[8] As a result, some experts advocated the use of colloids in the pump prime to lessen this
dilution.[9] There have been numerous studies published over the past 2 decades comparing the synthetic colloids
to both crystalloid and albumin for purposes of priming the CPB circuit without a clear-cut winner. It is not
surprising that surveys have shown a wide variety of practice patterns in this regard.[10] In truth, the CPB prime
fluid is likely much less important in modern systems since the volume required is now more on the order of 1 – 1.5
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liters versus 2 – 2.5 L. Additionally, with the technique of retrograde autologous priming, the patient may
experience an initial volume load of <500 ml upon CPB institution.
Fluid resuscitation is also a major issue in cardiac surgery, consisting of not only volume expansion, but
treatment of post-CPB coagulopathy as well. The agent of choice for fluid resuscitation varies widely among
centers and countries.[11] The crystalloid versus colloid debate in critical care medicine has raged on for decades
and has been the subject of numerous large multi-center randomized controlled trials. These are summarized in
Table 1. In general, no mortality benefits have been demonstrated with the use of colloids. It is noteworthy that
although most randomized trials on this subject include a varying numbers of surgical patients, those undergoing
cardiac surgery are almost always specifically excluded. A recent systematic review of 59 trials involving 16,889
patients included only 695 cardiac surgical patients (4.1%).[12] Thus, the application of most critical care trial
results to patients exposed to CPB remains somewhat in question.
Table 1: Major ICU Colloid Vs Crystalloid Trials

Clinical Trial Study Population* Major Finding
SAFE trial[13] 6997 ICU patients No difference in 28 day mortality, but ↑
4% albumin vs NS (42% surgical) death with albumin in TBI sub-analysis
CRISTAL trial[14] 2857 ICU patients No difference in 28 day mortality
Gelatin/Dextran/HES/Albumin vs (7% surgical) between colloid & crystalloid groups
NS/LR
6S trial[15] 798 ICU patients ↑ risk of death at 90 days and ↑ need for
6% HES 130/0.42 vs LR (29% surgical) RRT in HES group
CHEST trial[16] 6742 ICU patients No difference in 90 day mortality, but ↑
6% HES 130/0.4 vs NS (42% surgical) use of RRT in HES group
ALBIOS trial[17] 1818 ICU patients Albumin supplementation did not
20% albumin + crystalloids vs (43% surgical) improve 28 day survival
crystalloids alone
* surgical patients do NOT include post-cardiac srugery; NS=normal saline; TBI=traumatic brain injury;
HES=hydroxyethyl starch;LR=lactated Ringer’s; RRT=renal replacement therapy
The Glycocalyx and Revision of Starling

One of the interesting findings of the major colloid versus crystalloid randomized trials is the lack of realized
volume advantage of the colloid. Traditional teaching is that colloids are three times more effective than
crystalloids at restoring intravascular volume.[18] Even in states of shock, with a presumed altered reflection
coefficient (σ), the 1:3 ratio (3 cc’s of crystalloid for every cc blood loss) is often practiced. However, in the studies
mentioned in table 1, the difference in colloid administered compared to crystalloid given is more in the range of
1:1.3. There are a variety of reasons why colloid use does not result in the expected fluid “savings,” but perhaps the
most important one is that the traditional view of fluid movement between the intravascular and interstitial
compartments is not completely accurate. The traditional transcapillary osmotic gradient (i.e. πcap – πint) has much
less of an effect on fluid exchange than predicted. In situations with reduced hydrostatic pressure (i.e.
hypovolemia), there is a transient fluid flux into the vascular space, but it is limited to about 500 ml. In a steady
state, reabsorption of fluid at the capillary venous end does not actually occur.[19]
The endothelial glycocalyx consists of glycoproteins and proteoglycans bound to the luminal side of endothelial
cells. Electron micrographic studies have shown this thin (around 500 nanometers) layer to have a fragile, brush-
like structure which likely acts as a mechanotransducer of fluid sheer stress to the endothelial cells.[20] The osmotic
pressure within the glycocalyx, not the interstitium, accounts for the transcapillary gradient promoting fluid
movement through the small pores in the endothelium. The protein concentration within the glycocalyx is kept
lower than the interstitial protein concentration by active protein transport. Proteins from the interstitium are
generally prevented from diffusing into the glycocalyx layer by the force of the fluid moving through the
intracellular junction. Filtration of fluid out of the capillary can approach zero, but does not turn negative since a
diminished filtration will allow more proteins to enter the glycocalyx layer and decrease the osmotic gradient. This
has been referred to as “the no absorption rule.”[21] Clinically, this means the notion of “pulling” fluid out of the
interstitium by raising intravascular oncotic pressure is fundamentally flawed.
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Synthetic Colloids
Despite the improved understanding of fluid movement in the microcirculation, there remains many proponents
of colloid use. Given the expense of albumin, along with theoretical risks of disease transmission, the search for a
synthetic colloid continues. There are three major classes: gelatins, dextrans, and hydroxyethyl starches. While all
will raise COP, they vary in their molecular weight and pharmacological profiles. Unlike human albumin, which is
considered a monodisperse colloid, the synthetic colloids are polydisperse. This means that the molecules within
any given solution will range significantly in size. Lower molecular weight molecules will exert a greater oncotic
effect with lower viscosity since there will be a greater number of them. However, the larger molecular weight
molecules will persist longer before being filtered at the glomerulus or lost to the interstitium. A comparison of
synthetic colloid solutions is summarized in Table 2.
Gelatins are prepared from bovine collagen by first submersing it in alkali and boiling water, then cross-linking
the subunits with either hexamethyl di-isocyanate (urea-linked gelatin) or succinyl anhydride (succinylated
gelatin).[22] Of the synthetic colloids, gelatins have the smallest molecular weight, about 30 – 35 kiloDaltons (kD),
and are readily filtered at the glomerulus, providing only 2-3 hours of volume expansion.[23] All synthetic colloids
share the property of decreasing von Willebrand Factor levels, and can thus impair coagulation.[24] Gelatins may
also affect fibrin polymerization, resulting in decreased clot strength.[25] Although intravenous gelatins have been
used for more than 100 years, a recent review concluded that there is a relative paucity of data concerning their
safety.[26]
Dextran is a branched polysaccharide derived from the action of Leuconostic mesenteroides bacteria on sucrose.
The major derivations in clinical use are Dextran-40 and Dextran-70, having molecular weights of 40 kD and 70 kD
respectively. Both dextrans have the propensity to coat blood cells and the endothelium, reducing their interactions
and promoting peripheral blood flow. The duration of volume expansion for Dextran-40 is about 3-4 hours, and
about 5 hours for the larger Dextran-70.[27] Deserved or not, dextrans had the reputation for causing more
anaphylactic reactions compared to the other synthetic colloids. This has largely been overcome by the current
practice of pre-treatment with Dextran-1, which acts as a hapten inhibitor to existing antibodies.[28] Dextrans, often
used in vascular or plastic surgery for their anti-thrombotic effects, additionally enhance fibrinolysis.[29]
Hydroxyethyl starches (HES) are derived from amylopectin that has hydroxyethyl residues attached to the
anhydrous glucose molecules within the polymer. The degree of substitution determines how easily amylase can
break down the starch.[30] “Hetastarch” refers to a degree of substitution of about 0.7, and is less easily
metabolized than “pentastarch” (degree of substitution of 0.5) or “tetrastarch” (degree of substitution of 0.4). The
duration of plasma expansion varies significantly among HES solutions and is more dependent on the degree of
substitution and where the hydroxyethyl groups are located than on the molecular weight.[31] Difficulty in clearing
highly substituted HES can lead to persistence in the tissues resulting in prolonged pruritis.[32] Of the synthetic
colloids, HES has undergone the most scrutiny recently. A recent meta-analysis including more than 8700 patients
reported an increased risk of acute kidney failure for all types of HES administration.[33] The FDA released a
safety communication in June 2013 with recommendations for healthcare professionals against using HES solutions
in patients admitted to the ICU and avoiding them in patients undergoing open heart surgery in association with
CPB.[34]
Table2: Summary of Various Colloid Solutions

Agent Duration of Volume Effect Comments
(adapted from [23],[30])
Gelatin 2-3 hours Oldest colloid with limited safety
3.5% urea or 4% succinylated data available
3.5% Dextran-40 3-4 hours Antifibrinolytic properties
6% Dextran-70 5 hours
HES 6% 450/0.7 6-12 hours* Increased risk of kidney injury
HES 6% 200/0.5 3.5 – 9 hours*
HES 6% 130/0.4 4-6 hours*
* HES pharmacokinetics are complex and will vary depending upon where hydroxyethyl groups are located
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Conclusions
The overall role of colloids in cardiac surgery still remains unclear. Until large scale clinical trials specifically
aimed at this patient population are undertaken, their use will likely remain a matter of preference. With that said,
there appears to be significant disadvantages of the synthetic colloids, including potential for renal failure and
bleeding issues, both of which are major concerns in the cardiac surgical patients. Whether albumin, a natural
colloid, provides benefits without these disadvantages is another question yet to be adequately answered. While the
ALBIOS trial did not demonstrate a mortality benefit with replacing albumin levels, a recent study in off-CPB
coronary surgery showed a reduced incidence of acute kidney injury in hypo-albuminemic patients when 20%
albumin was administered prior to grafting.[35]
What is probably more important than administering colloids, however, is avoiding the general over-use of fluid
therapy. It has been shown that a 10% fluid overload in cardiac surgical patients is independently associated with
mortality.[36] So rather than debate the proposed benefits or colloids or crystalloids, the bigger challenge is likely
finding out how to judiciously use both of them.
References
1. Greer, A.E., J.M. Carey, and N. Zuhdi, Hemodilution principle of hypothermic perfusion. A concept
obviating blood priming. J Thorac Cardiovasc Surg, 1962. 43: p. 640-8.
2. Verska, J.J., L.G. Ludington, and L.A. Brewer, 3rd, A comparative study of cardiopulmonary bypass with
nonblood and blood prime. Ann Thorac Surg, 1974. 18(1): p. 72-80.
3. Foglia, R.P., et al., Iatrogenic myocardial edema with crystalloid primes: effects on left ventricular
compliance, performance, and perfusion. Surg Forum, 1978. 29: p. 312-5.
4. Santry, H.P. and H.B. Alam, Fluid resuscitation: past, present, and the future. Shock, 2010. 33(3): p. 229-
41.
5. Haupt, M.T. and E.C. Rackow, Colloid osmotic pressure and fluid resuscitation with hetastarch, albumin,
and saline solutions. Crit Care Med, 1982. 10(3): p. 159-62.
6. Salmon, J.B. and M.G. Mythen, Pharmacology and physiology of colloids. Blood Rev, 1993. 7(2): p. 114-
20.
7. Taylor, A.E., Capillary fluid filtration. Starling forces and lymph flow. Circ Res, 1981. 49(3): p. 557-75.
8. Yeoman, P.M., D.E. Vence-Pastor, and S.V. Rithalia, Changes in colloid osmotic pressure in patients
undergoing cardiothoracic surgery. Resuscitation, 1981. 9(4): p. 307-13.
9. London, M.J., Pro: colloids should be added to the pump prime. J Cardiothorac Anesth, 1990. 4(3): p. 401-
5.
10. Lilley, A., The selection of priming fluids for cardiopulmonary bypass in the UK and Ireland. Perfusion,
2002. 17(5): p. 315-9.
11. Finfer, S., et al., Resuscitation fluid use in critically ill adults: an international cross-sectional study in 391
intensive care units. Crit Care, 2010. 14(5): p. R185.
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patients. Br J Surg, 2016. 103(1): p. 14-26.
13. Finfer, S., et al., A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N
Engl J Med, 2004. 350(22): p. 2247-56.
14. Annane, D., et al., Effects of fluid resuscitation with colloids vs crystalloids on mortality in critically ill
patients presenting with hypovolemic shock: the CRISTAL randomized trial. JAMA, 2013. 310(17): p.
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2012. 367(20): p. 1901-11.
17. Caironi, P., et al., Albumin replacement in patients with severe sepsis or septic shock. N Engl J Med, 2014.
370(15): p. 1412-21.
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18. Falk, J.L., E.C. Rackow, and M.H. Weil, Colloid and crystalloid fluid resuscitation. Acute Care, 1983.
10(2): p. 59-94.
19. Levick, J.R. and C.C. Michel, Microvascular fluid exchange and the revised Starling principle. Cardiovasc
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20. Weinbaum, S., J.M. Tarbell, and E.R. Damiano, The structure and function of the endothelial glycocalyx
layer. Annu Rev Biomed Eng, 2007. 9: p. 121-67.
21. Woodcock, T.E. and T.M. Woodcock, Revised Starling equation and the glycocalyx model of transvascular
fluid exchange: an improved paradigm for prescribing intravenous fluid therapy. Br J Anaesth, 2012.
108(3): p. 384-94.
22. Saddler, J.M. and P.J. Horsey, The new generation gelatins. A review of their history, manufacture and
properties. Anaesthesia, 1987. 42(9): p. 998-1004.
23. Lange, M., et al., Intravascular volume therapy with colloids in cardiac surgery. J Cardiothorac Vasc
Anesth, 2011. 25(5): p. 847-55.
24. de Jonge, E. and M. Levi, Effects of different plasma substitutes on blood coagulation: a comparative
review. Crit Care Med, 2001. 29(6): p. 1261-7.
25. Mardel, S.N., et al., Reduced quality of clot formation with gelatin-based plasma substitutes. Br J Anaesth,
1998. 80(2): p. 204-7.
26. Thomas-Rueddel, D.O., et al., Safety of gelatin for volume resuscitation--a systematic review and meta-
analysis. Intensive Care Med, 2012. 38(7): p. 1134-42.
27. Niemi, T.T., R. Miyashita, and M. Yamakage, Colloid solutions: a clinical update. J Anesth, 2010. 24(6):
p. 913-25.
28. Ljungstrom, K.G., Dextran 40 therapy made safer by pretreatment with dextran 1. Plast Reconstr Surg,
2007. 120(1): p. 337-40.
29. Eriksson, M. and T. Saldeen, Effect of dextran on plasma tissue plasminogen activator (t-PA) and
plasminogen activator inhibitor-1 (PAI-1) during surgery. Acta Anaesthesiol Scand, 1995. 39(2): p. 163-6.
30. Jungheinrich, C. and T.A. Neff, Pharmacokinetics of hydroxyethyl starch. Clin Pharmacokinet, 2005.
44(7): p. 681-99.
31. Westphal, M., et al., Hydroxyethyl starches: different products--different effects. Anesthesiology, 2009.
111(1): p. 187-202.
32. Bork, K., Pruritus precipitated by hydroxyethyl starch: a review. Br J Dermatol, 2005. 152(1): p. 3-12.
33. Zarychanski, R., et al., Association of hydroxyethyl starch administration with mortality and acute kidney
injury in critically ill patients requiring volume resuscitation: a systematic review and meta-analysis.
JAMA, 2013. 309(7): p. 678-88.
34. FDA, Safety Communication: Boxed warning on increased mortality and severe renal injury, and
additional warning on risk of bleeding, for use of hydroxyethyl starch solutions in some settings.
http://www.fda.gov/biologicsbloodvaccines/safetyavailability/ucm358271.htm, 2013.
35. Lee, E.H., et al., Effect of Exogenous Albumin on the Incidence of Postoperative Acute Kidney Injury in
Patients Undergoing Off-pump Coronary Artery Bypass Surgery with a Preoperative Albumin Level of Less
Than 4.0 g/dl. Anesthesiology, 2016. 124(5): p. 1001-11.
36. Stein, A., et al., Fluid overload and changes in serum creatinine after cardiac surgery: predictors of
mortality and longer intensive care stay. A prospective cohort study. Crit Care, 2012. 16(3): p. R99.
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The Myths of Plasma and Synthetic Colloid Use During Cardiac Surgery
Jonathan H. Waters, MD Pittsburgh, PA
1. Categorize the variety of plasma preparations

2. Identify the limitations of transfusing plasma
3. Assess the indications for plasma by clotting activity
Plasma can be derived via two sources, either from a whole blood donation or through apheresis. The
volume of the unit varies dependent upon how it is collected. Generally, 500 mL of blood is collected
during a whole blood donation so the volume of plasma is dictated by the hematocrit of the donor. In
other words, if the patient has a hematocrit of 40%, then 40% of the 500 mL is red cells suspended in
300 mL of plasma. The volume of the donation is also dictated by the donor size. AABB standards allow
for collection of 10.5 mL of blood per kg of donor weight. So, variability can be introduced by donation
from a small patient. Another method of collection is through apheresis. With apheresis, blood is
removed from the donor, fractionated and the targeted blood component is saved whereas the other
components are returned to the donor. Apheresis plasma volume varies between 500 mL and 800 mL.
The naming of the plasma product will reflect how the product has been handled after donation. For
instance, fresh frozen plasma (FFP) is used for a product that is frozen within 8 hours of collection.
Plasma Frozen within 24 Hours (PF24) is used when the product is frozen within 24 hours. Studies have
shown that the activity of the labile coagulation components is well maintained with both time frames
of freezing. As such, many institutions use FFP and PF24 interchangeably.
Once thawed, FFP and PF24 must be transfused within 24 hours. If the product is not used, but is
maintained at 1 to 6°C, the plasma may be relabeled as “thawed plasma” and stored for up to 4 more
days at 1 to 6°C. This thawed plasma is what many institutions use for the management of unexpected
hemorrhage such as that associated with trauma. Other types of plasma products include
cryoprecipitate-reduced plasma which is generally used in patients with thrombotic thrombocytopenic
purpura undergoing therapeutic apheresis.
Normal plasma would be expected to have procoagulant concentrations of most coagulation factors
approaching 100% of baseline activity or 1 U/mL. However, the preservative solution and citrate
anticoagulant in the plasma will dilute the plasma. Anticoagulant solutions (CPD, CPDA-1, ACD, CP2D)
make up about 10% of the volume of all plasma units. Thus the procoagulant concentration of the
product is approximately 0.9 U/mL. In addition to this dilution, some procoagulant activity can be lost
during processing. This most prominently affects Factors V and VIII where levels can be reduced to 40-
60% of baseline activity. With these effects, a 250 mL unit of plasma might be expected to provide
approximately 200 units of procoagulant activity, on average. Thus, in a 70 kg patient, transfusion of one
250 mL unit of plasma might be expected to increase most factors by about 2.5% (or 0.025 U/mL).
Transfusion of four units would raise the level by about 10%.
While most practitioners give plasma in two unit doses, all of the variables that have been discussed
make the therapeutic response unpredictable with the two unit approach. Two unit doses in many
instances may result in under-dosing. Therefore, optimal patient care requires tailoring the dosage to
the patient on a mL per kg basis. As such, a standard dosage to begin should be 10 to 20 mL/kg. For
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instance, a 70 kg patient should receive approximately 1400 mL of plasma to correct an elevated INR.
This sizable volume highlights one of the most common complications associated with plasma which is
volume overload, otherwise known as transfusion associated circulatory overload. The upper end of this
volume range would be appropriate in the setting of severe coagulation deficits.
Commonly used coagulation tests, such as the PT/INR or the activated partial thromboplastin time
(aPTT) were developed as screening tests for coagulation factor deficiency. Both tests are routinely
ordered in preparation of a surgical procedure; however, neither test is predictive of who is going to
bleed. When considering the clinical indications for transfusing plasma, it is important to remember
that the mere presence of a moderately abnormal coagulation test result does not equate with
excessive bleeding nor imply a benefit from plasma transfusion. For most procoagulants, only a small
fraction of the normal concentration is necessary in order to maintain normal function of the
coagulation system. Even in situations where procoagulants are being activated and some are being
consumed, there may be adequate concentrations to provide normal kinetics of hemostasis in vivo.
Timing of plasma transfusion is important, particularly if the effects of coumadin is being counteracted
in anticipation of a surgical procedure. Factor VII has a 5-6 hour half-life so the effect of a prophylactic
transfusion the night before a procedure might largely be gone the following day. Correction of the
coagulation abnormalities associated with hepatic failure are similarly complicated by the short half-life
of some procoagulants and the increase in plasma volume attributable to the colloid that comes with
each unit of plasma. “Normalization” of coagulation tests cannot be expected in such circumstances.
Finally, it is critically important to understand that hypothermia and acidosis need to be corrected when
managing a bleeding patient. In a study by Cosgriff and colleagues, a predictive model for predicting
life-threatening coagulopathy was developed. The risk factors that they found were a combination of
high injury severity scores, low blood pressure, hypothermia and acidosis. When all four were
abnormal, the patients stood close to a 100% probability of developing a coagulopathy. They concluded
that healthy doses of plasma would not stop the bleeding if the patient’s temperature and acid-base
status were not normalized. With this in mind, plasma should be administered in conjunction with
temperature and acid-base correction.
References:
1. Roback JD, Combs MR, Grossman BJ, Hillyer CD, Editors. Technical Manual. 16th Ed. AABB
Press. Bethesda, MD.
2. Dzik WH, in Mintz PC ed. Transfusion therapy: principles and practice, 2nd edition.
AABB Press, 2005
3. Meng ZH, Wolberg AS, Monroe DM, Hoffman M. The Effect of Temperature and pH on the
Activity of Factor VIIa: Implications for the Efficacy of High-Dose Factor VIIa in Hypothermic and
Acidotic Patients. Journal of Trauma-Injury Infection & Critical Care. 2003;55:886-91.
4. Roback JD, Caldwell S, Carson J, Davenport R, Drew MJ, Eder A, Fung M, Hamilton M, Hess JR,
Luban N, Perkins JG, Sachais BS, Shander A, Silverman T, Snyder E, Tormey C, Waters JH,
Djulbegovic B. Evidence-based practice guidelines for plasma transfusion. Transfusion
2010;50:1227-39.
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Emergent intubation: tips, tricks, and evidence
Aaron M. Joffe, DO Seattle, WA
Learning Objectives
At the end of this lecture, the reader should be able to:
1. Describe what everyone in attendance at an intubation should know regardless of the role they are playing
2. To discuss aspects of optimizing first attempt intubation success
3. To describe a risk stratification scheme for tracheal extubation
Introduction:
Emergency tracheal intubation outside of the OR is required in patients requiring immediate assistance with
oxygenation. Compared to elective intubation in the OR for general anesthesia the occurrence of difficult intubation
outside of the OR is several-fold higher. In addition, airway-related complications such as hypoxemia, hypotension,
esophageal intubation, and aspiration are far more common as is cardiac arrest. The Fourth National Audit Project
by the Royal College of Anaesthetists (NAP4) has most recently and comprehensively highlighted this. Of the 184
reported airway events, nearly 20% occurred in either the ICU or emergency department (ED) of which nearly two-
thirds directly resulted in death or permanent neurologic injury. Furthermore, factors considered to be contributory
or causal were often related to communication failures or the judgment and training of the operators. In over 1/3 of
events in the ICU, the quality of airway management was judged to be poor.
Patient Positioning
Appropriate positioning of the patient in preparation for airway instrumentation is an important, but often
neglected aspect of airway management. Over 40 years ago, Stept and Safar reported on “Rapid
Induction/Intubation for Prevention of Gastric-Content Aspiration.” As part of a multi-step process, practitioners are
instructed by step 6 to “place patient in semisitting, V-position, with trunk elevated about 30 degrees…” Positioning
patients in this manner may improve the efficacy of preoxygenation, maintain the airway in a more anatomic
position, improve laryngeal exposure, and, of course, decrease the chances of passive regurgitation. This can be
accomplished quite readily with most modern hospital beds by first putting the bed in trendelenburg position and
pulling the patient up until their occiput rests on the edge of the mattress. Next the head of the bed is elevated to 30
degrees. And, lastly, if necessary to ensure that the external auditory meatus is aligned with the sternal notch, an
additional headrest can be placed under the occiput. This position has reported to decrease complication rates in
emergent out-of-operating room intubations. An extreme version of this, which has been recently reported, called
“face-to-face” intubation, involves providing all airway management with the patient in a nearly fully seated
position. Airway instrumentation is accomplished with a video laryngoscope.
Direct versus Indirect Laryngoscopy
The use of newer rigid video laryngoscopes to increase patient safety by increasing first attempt intubation
success and/or decreasing time to successful intubation remains contentious. A recent meta-analysis evaluated a
number of prospective randomized trials comparing direct laryngoscopy (DL) with the Glidescope (GS). The
proportion of intubations taking place with a full view of the glottis (Cormack-Lehane grade 1) was significantly
higher with the GS than DL. This was true for all intubations as a whole, although the effect was greater among
intubations labeled as difficult. However, neither the first attempt success rate nor the time to intubation was
different between techniques. This was due to, in large part, a small number of studies including novice or
inexperienced operators, which did show the GS to be beneficial, having been balanced by a larger number of
studies of expert operators where no benefit was reported. In addition, a recently published pilot prospective
randomized trial of DL versus GS for intubation in the intensive care unit also failed to show a difference in any
important outcome. It is also notable that while this study was small with 40 patients, it included what many would
consider inexperienced operators, the very group that had been previously reported to benefit for the GS. At this
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time, there is little high quality data to support the widespread preferential use of a GS over DL by experienced
personnel for initial intubation attempts. Nonetheless, based on this same data after examining the upper and lower
limits of the 95% Cis, it does appear that “the worst you would expect” regarding failed first attempt success is
better with video rather than direct laryngoscopy. Furthermore and in contrast to traditional teaching, not attempting
to obtain the “best” view of the glottis may actually enhance, not hinder, first attempt intubation rates. It should be
noted that the most current version of the ASA guidelines states that “consideration of the relative clinical merits
and feasibility of four basic management choices” should be made. Choice number 3 is “video-assisted
laryngoscopy as an initial approach to intubation.”
Extubation of the difficult airway
Extubation has traditionally been considered a routine part of the emergence from anesthesia. Anecdotally,
the need to keep a patient who presented for elective non-major surgery has been considered a failure on the part of
the anesthesiologist to perform their duties adequately. However, it is now recognized that some patients are at risk
for extubation failure post-procedure and that failure to acknowledge this phenomena may lead to serious morbidity
or death. For example, multilevel anterior cervical spine surgery with a duration > 5 hours and > 300 ml blood loss
have been reported to increase the risk of upper airway obstruction post-procedure. In a retrospective review of over
2000 patients who were extubated while in the ICU of a large urban tertiary care referral hospital, nearly 1 in 5
(19%) required reintubation at some point during their hospitalization. The median time to reintubation was <24
hours with 1 in 10 of those patients needing to be reintubated within 1 hour of extubation. Additionally, the need for
reintubation was associated with higher ICU length of stay, in-hospital mortality, and greater cost of care. Further,
the NAP4 Investigators recently reported that more than 1 in 4 airway related events occurred at extubation or in the
recovery area post procedure. The root cause of 100% of these events was judged to be due to some form of airway
obstruction. Highlighting that these events are not innocuous, death or permanent brain damage occurred in 3
instances with all of the remaining patients requiring ICU level care. In response, the Difficult Airway Society of
the United Kingdom has recently published extubation guidelines. As there is a dearth of literature support for any
particular risk stratification or algorithm, what these types of guidelines chiefly offer is a prompt to actually consider
the likelihood of extubation failure in any given patient. Underscoring the paucity of data with which to guide
specific recommendations is the use of airway exchange catheters over which extubation takes place. In adults, only
430 patients contained in 3 case series have been reported, all of which were considered at high risk for extubation
failure. However, extubation failure was reported to occur in only 13.4% of these patients overall (58/430)
indicating that even in well selected patients, the use of the exchange catheter was unnecessary more than 85% of
the time. The data for use of a SAD to bridge patients from tracheal tube to spontaneous respiration without an
artificial airway is sparser still with a total of 41 patients reported to date with a 0% extubation failure rate.
Conclusion
Practitioners are likely to encounter difficulty in airway management far more often than they are
accustomed to when performing these tasks outside the operating room. In addition, the incidence of serious
complications is also higher. These complications are not simply a brief blip on the monitor screen, but rather are
associated with a several fold risk of death or permanent disability. In order to optimize pre-oxygenation, laryngeal
exposure, and to decrease the risk of gastric-content regurgitation, patients should be positioned in a 30 degree head
up position. Currently, no new airway technology has been shown to be superior to direct laryngoscopy for initial
attempts at instrumenting the airway among expert operators for critically ill patients overall. Of course, no airway
management technology will be successful 100% of the time. Practitioners should familiarize themselves with
alternative techniques. While literature estimates of extubation failure vary depending on the population studied and
the time frame within which extubation was not considered to be a success, it occurs with some regularity in
critically ill hospitalized patients. Additionally, perhaps one-in-ten of these events will occur in the first hour after
extubation. Given that the consequences of a lost airway may be catastrophic, a well articulated reintubation plan
should be developed for patients who possess high-risk features for extubation failure.
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References:
1. Schwartz DE, Matthay MA, Cohen NH. Death and other complications of emergency
airway management in critically ill adults. A prospective investigation of 297 tracheal
intubations. Anesthesiology 1995;82:367-76.
2. Jaber S, Amraoui J, Levering JY, et al. Clinical practice and risk factors for immediate
complications of endotracheal intubation in the intensive care unit: a prospective,
multiple-center study. Crit Care Med 2006;34:2355-61.
3. Griesdale DE, Bosma TL, Kurth T, et al. Complications of endotracheal intubation in the
critically ill. Intensive Care Med 2008;34:1835-42.
4. Mort TC. Emergency tracheal intubation: complications associated with repeated
laryngoscopic attempts. Anesth Analg 2004;99:607-13.
5. Cook TM, Woodall N, Harper J, Benger J; Fourth National Audit Project.Major
complications of airway management in the UK: results of the Fourth National Audit
Project of the Royal College of Anaesthetists and the Difficult Airway Society. Part 2:
intensive care and emergency departments. Br J Anaesth 2011;106:632-42.
6. Cook TM, Woodall N, Frerk C. Major complications of airway management in the UK:
results of the Fourth National Audit Project of the Royal College of Anaesthetists and the
Difficult Airway Society. Part 1: Anaesthesia. Br J Anaesth 2011;106:617-31.
7. Stept WJ, Safar P. Rapid induction-intubation for prevention of gastric-content
aspiration. Anesth Analg 1970;49:633-6.
8. Khandelwal N, Khorsand S, Mitchell SH, Joffe AM. Head-Elevated Patient Positioning
Decreases Complications of Emergent Tracheal Intubation in the Ward and
Intensive Care Unit. Anesth Analg. 2016 Apr;122(4):1101-7.
9. Griesdale DE, Liu D, McKinney J, Choi PT. Glidescope® video-laryngoscopy versus
direct laryngoscopy for endotracheal intubation: a systematic review and meta-analysis.
Can J Anaesth 2012;59:41-52.
10. Griesdale DE, Chau A, Isac G, Ayas N, Foster D, Irwin C, Choi P; for the Canadian
Critical Care Trials Group. Video-laryngoscopy versus direct laryngoscopy in critically
ill patients: a pilot randomized trial. Can J Anaesth 2012;59:1032-1039.
11. Gu Y, Robert J, Kovacs G, Milne AD, Morris I, Hung O, MacQuarrie K, Mackinnon S,
Adam Law J. A deliberately restricted laryngeal view with the GlideScope® video
laryngoscope is associated with faster and easier tracheal intubation when
compared with a full glottic view: a randomized clinical trial. Can J Anaesth. 2016
Apr 18. [Epub ahead of print]
12. Joffe AM, Liew EC, Matioc AA, Willmann K. Unanticipated difficult intubation in the
medical-surgical intensive care unit: its effect on outcome of critically-ill adults. The
Internet Journal of Anesthesiology 2010:24(1).
13. Schmidt UH, Kumwilaisak K, Bittner E, George E, Hess D. Effects of supervision by
attending anesthesiologists on complications of emergency tracheal intubation.
14. Lecky F, Bryden D, Little R, Tong N, Moulton C. Emergency intubation for acutely ill
and injured patients. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD001429
15. Albert SG, Ariyan S, Rather A. The effect of etomidate on adrenal function in critical
illness: a systematic review. Intensive Care Med 2011;37:901-10.
16. Chan CM, Mitchell AL, Shorr AF. Etomidate is associated with mortality and adrenal
insufficiency in sepsis: A meta-analysis. Crit Care Med 2012;40:2945-53.
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17. Cuthbertson BH, Sprung CL, Annane D, Chevret S, Garfield M, Goodman S, Laterre PF,
Vincent JL, Freivogel K, Reinhart K, Singer M, Payen D, Weiss YG. The effects of
etomidate on adrenal responsiveness and mortality in patients with septic shock.
Intensive Care Med 2009;35:1868-76.
18. Cherfan AJ, Arabi YM, Al-Dorzi HM, Kenny LP. Advantages and disadvantages of
etomidate use for intubation of patients with sepsis. Pharmacotherapy 2012;32:475-82.
19. Payen JF, Clement D, Thibaut TB, et al. Corticosteroid after etomidate in critically ill
patients: A randomized controlled trial. Crit Care Med 2012;40:29-35.
20. Jaber S, Jung B, Corne P, Sebbane M, Muller L, Chanques G, Verzilli D, Jonquet O,
Eledjam JJ, Lefrant JY. An intervention to decrease complications related to
endotracheal intubation in the intensive care unit: a prospective, multiple-center study.
Intensive Care Med 2010;36:248-55.
21. Wilcox SR, Bittner EA, Elmer J, Seigel TA, Nguyen NT, Dhillon A, Eikermann M,
Schmidt U.Neuromuscular blocking agent administration for emergent tracheal
intubation is associated with decreased prevalence of procedure-related
complications.Crit Care Med 2012;40:1808-13.
22. Ferson DZ, Rosenblatt WH, Johansen MJ, et al. Use of the intubating LMA-FastrachTM
in 254 patients with difficult-to-manage airways. Anesthesiology 2001;95:1175-81.
23. Wong DT, Yang JJ, Mak HY, Jagannathan N. Use of intubation introducers through a
supraglottic airway to facilitate tracheal intubation: a brief review. Can J Anaesth
2012;59:704-15.
24. Atherton D, O’Sullivan E, Lowe D, et al. A ventilation-exchange bougie for fiberoptic
intubations with the laryngeal mask airway. Anaesthesia 1996;51:1123-6.
25. Arndt GA, Topp J, Hannah J, et al. Intubation via the LMA using a Cook retrograde
intubation kit. Can J Anaesth 1998;45:257-60.
26. Sagi HC, Beutler W, Carroll E, Connolly PJ. Airway complications associated with
surgery on the anterior cervical spine. Spine (Phila Pa 1976). 2002;27:949-53.
27. Menon N, Joffe AM, Deem S, Yanez ND, Grabinsky A, Dagal AH, Daniel S, Treggiari
MM.Occurrence and Complications of Tracheal Reintubation in Critically Ill Adults.
Respir Care 2012;57:1555-63.
28. http://www.das.uk.com/content/das-extubation-guidelines. Accessed October 10, 2012
29. Loudermilk EP, Hartmannsgruber M, Stoltzfus DP, Langevin PB. A prospective study of
the safety of tracheal extubation using a pediatric airway exchange catheter for patients
with a known difficult airway. Chest 1997;111:1660-5.
30. Mort TC. Continuous airway access for the difficult extubation: the efficacy of the
airway exchange catheter. Anesth Analg 2007;105:1357-62.
31. Dosemeci L, Yilmaz M, Yegin A, Cengiz M, Ramazanoglu A. The routine use of
pediatric airway exchange catheter after extubation of adult patients who have undergone
maxillofacial or major neck surgery: a clinical observational study. Crit Care
2004;8:R385-90.
32. Russo SG, Goetze B, Troche S, Barwing J, Quintel M, Timmermann A. LMA-ProSeal
for elective postoperative care on the intensive care unit: a prospective, randomized trial.
33. Patel P, Verghese C.Delayed extubation facilitated with the use of a laryngeal mask
airway (LMA) on the intensive care unit (ICU). Anaesthesia 2000;55:396.
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CME Questions
1. All of the following are correct regarding etomidate except?

a. Glucocorticod production may be inhibited for up to 72 hours after a single dose
b. Hemodynamic stability is maintained better during induction of anesthesia than with
other agents
c. All-cause mortality in patients with sepsis may be negatively effected by its use
d. None of the above
Answer: b
2. The final outcome of critical airway management can be conceptualized as being determined
by the interaction of which of the following variables?
a. Patient
b. Personnel and equipment
c. Time
d. All of the above
Answer: d
3. Which of the following patients is most at risk of extubation failure?

a. 25 year-old polytrauma with cervical spine fractures, intubated pre-hospital, in ICU. He
is in a hard cervical immobilization collar and has a BMI of 41 kg/m2. He is awake,
follows commands, and has passed his spontaneous breathing trial. A cuff leak is present.
b. 45 year-old man who has undergone a 2-level lumbar decompression and posterior spinal
fusion in prone position. Blood loss was minimal and the surgery was 2.5 hours in
duration.
c. 65 year-old female who has had a large left middle cerebral artery territory stroke with
right sided motor deficits. She requires frequent oral suctioning.
d. 75 year-old man who has undergone a carotid endarterectomy
Answer: b
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Continuous Peripheral Nerve Blocks, Liposome Bupivacaine, and (or?)

Percutaneous Peripheral Nerve Stimulation in 2016
Brian M. Ilfeld, MD, MS (Clinical Investigation) San Diego, California
Continuous Peripheral Nerve Blocks

Introduction. Continuous peripheral nerve blocks (CPNB) consist of a catheter that is percutaneously
inserted adjacent to a peripheral nerve, followed by local anesthetic administration via the catheter.
Therefore, the terms “perineural local anesthetic infusion” and CPNB are often used synonymously. The
maximum duration of a single-injection peripheral nerve block is currently 8-24 hours. Therefore, when a
prolonged neural blockade is desired, CPNB provides an option.
Indications. CPNB is used to prolong intraoperative surgical anesthesia; treat intractable hiccups; induce
sympathectomy and vasodilation to increase blood flow following a vascular accident, digit
transfer/replantation or limb salvage; alleviate the vasospasm of Raynaud's disease; and treat peripheral
embolism. CPNB can provide analgesia during transportation following trauma, or waiting for surgical
treatment. Reports describe CPNB to treat chronic pain, such as intractable phantom limb pain, pain from
terminal cancer and trigeminal neuralgia, and complex regional pain syndrome. However, the most
common indication is providing postoperative analgesia (the only indication validated with randomized,
controlled clinical trials [RCT]).
Most providers use CPNB exclusively for surgical procedures that are expected to result in pain not easily
controlled with less-invasive analgesic techniques because there are intrinsic risks with the techniques,1 or
in patients with an intolerance to alternative analgesics (e.g., opioid-induced nausea). Although
recommendations for the use of various catheter locations for specific surgical procedures exist, there is
little published data specifically illuminating this issue. In general, axillary, cervical paravertebral (CPVB),
infraclavicular, or supraclavicular infusions are used for surgical procedures involving the hand, wrist,
forearm, and elbow (infraclavicular the most effective); interscalene, CPVB and intersternocleidomastoid
catheters are used for surgical procedures involving the shoulder or proximal humerus (interscalene optimal
risk-benefit ratio); thoracic paravertebral catheters are used for breast or thorax procedures; psoas
compartment catheters are used for hip surgery; fascia iliaca, femoral, and psoas compartment catheters are
used for knee or procedures thigh (occasionally hip surgery, although this is somewhat controversial); and
popliteal or subgluteal catheters are used for surgical procedures of the leg, ankle, and foot (popliteal
optimal risk-benefit ratio). CPNB has been described in hundreds of pediatric patients, although it is not as
thoroughly validated as in adults.
Patient Selection. Little published data is available regarding the balancing of potential perineural
infusion risks and benefits for patients with significant comorbidities. Investigators often exclude patients
with known hepatic or renal insufficiency, in an effort to avoid local anesthetic toxicity. For infusions that
may effect the phrenic nerve and ipsilateral diaphragm function (e.g. interscalene or cervical paravertebral
catheters), patients with heart or lung disease are often excluded since continuous interscalene local
anesthetic infusions have been shown to cause frequent ipsilateral diaphragm paralysis. Although the effect
on overall pulmonary function may be minimal for relatively healthy patients,2 practitioners must be aware
of the possible related risks and be prepared to manage complications.
Catheter Insertion (Nerve Stimulation). Various catheter insertion techniques have been used, inducing
paresthesias, eliciting a facial “click”, and fluoroscopic guidance. However, most reports involve electrical
stimulation. One common technique involves giving a bolus of local anesthetic via an insulated needle to
provide a surgical block, followed by the introduction of a “nonstimulating” catheter. Many studies report a
high success rate using this procedure,3-6 but the catheter tip may be unknowingly misplaced during
insertion.7,8 To help counter this risk, the perineural catheter may be first inserted, followed by a local
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anesthetic bolus via the catheter itself.9-12 Unfortunately, this technique requires waiting at least 15 minutes
for block onset/failure, followed by removal of the catheter/dressing, re-preparation, and catheter
reinsertion for failed a failed insertion.13 In addition, a partial block is possible suggesting the catheter tip
is not optimally located, but often precluding replacement using electrical current.
Alternatively, catheters which deliver current to their tips have been developed in an attempt to improve
initial placement success rates.14 These catheters provide feedback on the positional relationship of the
catheter tip to the target nerve prior to local anesthetic dosing. There is data to suggest that in the area of
the popliteal fossa, using stimulation during catheter advancement results in the catheter tip being placed
closer to sciatic nerve.15-18 The clinical relevance is questionable femoral and interscalene catheters. 19-27
Regrettably, stimulating catheters guarantee neither a complete surgical block nor an effective
postoperative infusion.21,28-30 Furthermore, an acceptable muscle contraction may not always be obtained
during catheter insertion;21,31-34 and, stimulating catheters often require an increased insertion time and cost
more than their non-stimulating counterparts,18 resulting in many questioning their cost-benefit ratio.
Finally, the minimal acceptable current resulting in a muscle contraction remains unknown.
Also remaining unknown is the optimal distance to insert the catheter past the needle tip. However,
increasing the insertion distance is correlated with an increased the risk of catheter coiling, and perhaps the
ultimate distance between the catheter and target nerve.35 With catheter insertion over 5 cm, numerous
catheter knots have been reported;36 and, a maximum insertion of 5 cm appears warranted. Likewise,
remaining unknown is the optimal minimum insertion distance; but, studies suggests that 0-1 cm results in
a minimal risk of secondary block failure,6 but possibly an increased risk of subsequent dislodgement.
Catheter Insertion (Ultrasound). The limited length of this article precludes an in-depth discussion of
ultrasound-guided perineural catheter insertion; but, the information is available elsewhere.37 While
ultrasound guidance would intuitively seem to increase the accuracy of catheter tip location, identifying the
catheter tip is often challenging. Multiple practitioners observe the location of injected fluid,38 an agitated
fluid/air mixture,39 or simply air.40,41 For most anatomic locations, ultrasound-guided insertion decreases
insertion time and associated discomfort compared with an electrical technique (and provide at least similar
analgesia). 31,32,34,42-45 The majority of reports of combining ultrasound and nerve stimulation suggest little
benefit,39,46-50 Currently, insufficient data are available to determine either the optimal
techniques/equipment for these insertion modalities, as well as their associated risks and benefits.37
Infusates. The majority of perineural infusion publications have involved bupivacaine or ropivacaine,
although levobupivacaine and shorter acting agents have been reported. While the available data suggests
bupivacaine and levobupivacaine are more potent than ropivacaine, 51 all three provide similar analgesia
within human trials, although the ropivacaine concentration is often increased up to 50% to compensate for
decreased potency.51,52 When a bupivacaine perineural infusion is paused, the motor and sensory effects
greatly outlast those of ropivacaine.52 This is often important when titrating dose to limit undesired CPNB
effects. Also unknown is whether the primary determinant of CPNB effects is only local anesthetic
dose/mass, or if volume (rate) and/or concentration have an influence.53-55 Currently, additional research is
warranted, and no optimal concentration/rate combination may be recommended for all anatomic
locations.56 For bupivacaine/levobupivacaine and ropivacaine, the most-commonly-cited concentrations
are between 0.1-0.125% and 0.1-0.2%, respectively. Unfortunately, no adjuvants—such as clonidine,
epinephrine, and opioids—have been found to improve analgesia and/or decrease undesirable CPNB-
related side effects; and infusing solely long-acting local anesthetic appears warranted.
Local Anesthetic Delivery Regimens. Currently available data suggest that following procedures
producing moderate-to-severe pain, providing patients with the ability to self-administer local anesthetic
doses increases perioperative benefits and/or decreases local anesthetic consumption. Unfortunately,
insufficient information is available to base recommendations on the optimal basal rate, bolus volume, or
lockout period accounting for the many variables that my effect these values (e.g. catheter type, location,
surgical procedure). Until recommendations based on prospectively-collected data are published,
practitioners should be aware that investigators have reported successful analgesia using the following with
ropivacaine (0.2%) or bupivacaine (0.125%): a basal rate of 5 (lower extremity) or 8 (upper extremity)
mL/h; a bolus volume of 2 – 5 mL; and a lockout duration of 20 – 60 min. Additionally, the maximum safe
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dose remains unknown. However, multiple investigations involving patients free of renal or hepatic
disease have reported blood concentrations within acceptable limits—and an absence of toxicity
symptoms/signs—following multiple weeks of perineural infusion with similar dosing schedules. 57,58
Infusion Pumps. There is no single optimal infusion pump for every clinical scenario; and, therefore,
pump preference is usually dictated by desired device characteristics.59 Although elastomeric infusion
pumps cannot match their electronic counterparts in delivering a basal infusion rate within ±5% expected
for the entire infusion duration, whether the increased variability is clinical significant—or in which clinical
situations it is relevant—remains unknown.59 Providing an adjustable basal infusion rate permits titration
of local anesthetic dose for inadequate analgesia, an insensate extremity, undesired side effects (e.g.,
muscle weakness),60 or maximizing infusion duration (e.g., ambulatory patients with a set reservoir
volume). Furthermore, multiple clinical benefits are provided with a patient-controlled bolus option, such
as increasing analgesia and decreasing opioid consumption. Electronic pumps provide an adjustable basal
rate, patient-controlled bolus doses, and a variable bolus lock-out period.59 And, while most elastomeric
devices include a fixed basal infusion rate, a few provide similar flexibility to electronic pumps.
Elastomeric pumps are often preferred for their smaller size and lighter weight; lack of audible alarms;
disposability; and silent operation (electronic pumps may disturb patient sleep). In addition, elastomeric
devices with no bolus dose capability and a manufacturer-fixed basal rate are usually less costly. However,
inexpensive disposable “cassettes” provide sterile infusion for individual patients utilizing reusable
electronic pumps. A few disposable electronic pumps are available. At least within the United States, the
infusion pump/reservoir must now be filled under a laminar flow workbench.61 Of note, at least within the
United States, there are no national guidelines regarding the maximum safe CPNB duration. 61
Ambulatory Perineural Infusion. While length limitations of this article preclude an extensive discussion
of ambulatory CPNB, this information is available elsewhere.59 Ambulatory perineural infusion may be
provided to outpatients using a portable pump. Perineural infusion is often provided for ambulatory surgery
without an overnight hospital stay;59 but may also shorten hospitalization duration,62,63 and/or bestow
benefits following discharge to either a rehabilitation facility or home.6,58 Ultrasound guidance—with its
demonstrated decreased insertion time—is often beneficial in high-turnover ambulatory centers where time
constraints are often severe.31,34,45,64 Patient selection criteria are often more stringent for ambulatory
CPNB since outpatients are rarely directly monitored; and not all patients desire or are capable of accepting
the additional responsibility of caring for the catheter and pump system. Patients with hepatic or renal
insufficiency are often excluded from ambulatory CPNB to decrease the risk of local anesthetic toxicity.
Caution is warranted during interscalene and cervical paravertebral infusion (frequently induce diaphragm
weakness) for obese individuals and those with heart/lung disease who may not be able to compensate for
mild hypoxia and/or hypercarbia.
Ambulatory perineural infusion may reduced time until discharge readiness;6,29,62,65 and, in select cases,
actual discharge.62,63 Early discharge after total knee arthroplasty may decrease hospitalization-related
costs.66 However, caution is warranted prior to allowing discharge with a continuous posterior lumbar
plexus and femoral nerve block given that these catheters are associated with an increased risk of falling.67
Nonetheless, relatively small published series document the feasibility of total joint arthroplasty with only a
single-night hospital stay—or even on an outpatient basis—when patients are provided CPNB at home.68-72
Benefits. The most-common indication for CPNB is to provide postoperative pain control, and it appears
that most CPNB benefits are dependent upon successfully improving analgesia.56 RCT-documented
benefits include decreased postoperative pain, supplemental analgesic requirements, opioid-related side
effects, sleep disturbances, dissatisfaction, discharge readiness, actual discharge, and inflammatory
markers. In addition, an accelerated resumption of passive joint range-of-motion is documented following
total knee arthroplasty procedures with 48-72 hours of continuous femoral perineural infusion. Analgesia
is most impressive when the perineural infusion effects the entire innervation of the surgical site; as is often
the case for shoulder and foot procedures (interscalene and sciatic perineural catheters, respectively). 4,7,62
Unfortunately, even though brachial plexus infusions (theoretically) cover the entire surgical site for
procedures at or distal to the elbow, they provide less impressive analgesia.73. Severely lacking are RCT-
documented benefits of continuous axillary,74 supraclavicular,75 and transversus abdominus plane blocks.56
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And, while the benefits of infraclavicular infusion are validated, 73 analgesia is often less-than-optimal
unless a high enough dose of local anesthetic is administered, frequently rendering the extremity insensate.
Similarly, for surgical sites innervated by multiple nerves (such as the knee, hip and ankle), a single
perineural usually provide less-than-optimal analgesia without the concurrent use of additional
analgesics.6,29,55 While a lumbar epidural provides roughly equivalent analgesia to femoral perineural
infusion for hip and knee arthroplasty, CPNB results in a more-favorable side-effect profile without the risk
of epidural hematoma during concomitant anticoagulant administration. 76-78
While the evidence for CPNB benefits during the infusion is vast,56 there are few studies documenting
benefits following catheter removal. Exceptions include increased health-related quality-of-life in one
study79 (but not five others);80-84 improved analgesia after a few days5,85,86 or six months;87 faster tolerance
of passive knee flexion resulting in earlier discharge from rehabilitation centers;77,78,85 and more-rapid
resumption of lavatory use and unassisted standing.85 Noticeably absent is evidence of medium- or long-
term improvements in measures of health-related quality-of-life.80-84,88 See below for additional
information.
Complications. Relatively minor CPNB-related complications occur at a frequency similar to single-

injection peripheral nerve blocks.89 In contrast, severe and permanent infusion-related injuries are
uncommon. Unfortunately, generalizations are difficult given the multiple anatomic locations for perineural
infusion as well as diverse equipment and techniques. For example, the incidence of secondary block
(infusion) failure reported by three different trials includes 1%,90 20%,7 and 50%.9 Catheter insertion-
related complications include inaccurate catheter tip placement; and—in extremely rare cases—intraneural,
intrathecal, epidural, intravascular, and even interpleural catheter insertion. Complications during the
perineural infusion include catheter obstruction or dislodgement; catheter site fluid leakage; infusion pump
disconnection, malfunction, or undesired pause; allergic reaction or simply skin irritation to the catheter
dressing and/or liquid adhesive; and, catheter-induced brachial plexus irritation. One of the most common
complications is an insensate extremity that may be unnerving to patients, hinders rehabilitation, and often
believed to be a risk factor for injury.54,55 In such cases, pause the infusion until sensory perception returns,
and then restarted the infusion at a lower basal rate. Conversely, breakthrough pain or persistent inadequate
analgesia may be treated with patient-controlled bolus doses and increasing the basal infusion, respectively.
More serious—and remarkably uncommon—complications include systemic local anesthetic toxicity;

myonecrosis with repeated large boluses of bupivacaine; retroperitoneal and peri-catheter hematoma
formation; catheter knotting, retention, shearing, or breakage; a prolonged Horner’s syndrome; and lower
lobe collapse during infusions affecting the phrenic nerve. In patients with preexisting neuropathy and/or
diabetes, limited evidence suggests that prolonged local anesthetic exposure may increase the risk of nerve
injury. Infusions affecting the femoral nerve is associated with an increased risk of falling following knee
and hip arthroplasty.67 Catheter site infection and abscess are rare (infection incidence 0-3%;91,92 but most
reports <1%),11,89,93 although inflammation (3-4%)1,90,94 and bacterial colonization (6%-57%) are more
common. Risk factors include the absence of perioperative antibiotic prophylaxis, male sex,
axillary/femoral catheter insertion, and presence in an intensive care unit.1 The infection risk is also
correlated with infusion duration;1 but, nevertheless, a minimal incidence of infection has been reported for
CPNB during inter-continental transportation for up to 34 days95 and provided at home for up to 83 days.58
Because all surgical procedures are associated with a variable incidence of nerve injury—regardless of the
application of a regional anesthetic/analgesic—it is often problematic to determine what percentage (if any)
of a new-onset neurologic deficit is attributable to CPNB. Keeping this limitation in mind, the incidence of
transient adverse neurologic symptoms associated with CPNB is 0-1.4% for interscalene,1,11,89,90 0.4-0.5%
for femoral,1,96 and 0-1.0% for sciatic catheters.1,90,96,97 Another study reported a 0.2% incidence of
neurologic deficits lasting longer than 6 weeks in nearly 3,500 catheters from multiple anatomic locations. 90
In this latter study, it remains unknown if the deficits resolved after the 6-week study period; but multiple
prospective investigations report that the overwhelming majority of neurologic symptoms present at 4-6
weeks resolve spontaneously within three months of surgery. 1,11,89 Long-term and/or permanent nerve
injury has occurred.98 Five large,1,11,89,96,97 prospective series that followed patients for at least three months
reported 3 cases of unresolved adverse neurologic events.89,96,97 These investigations combined (4,148 total
subjects) suggests the risk of neurologic injury lasting longer than nine months associated with CPNB is
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0.07% (all of the risk may not be conclusively attributed to the perineural infusion).1,11,89,96,97 While
ultrasound-guidance may decrease the incidence of many/most of these reported complications, 99 to date
there are few data supporting this proposition;100,101 and case reports suggest that completely abolishing
such events is unlikely.102-104
There has been a significant amount of data published in the last few years involving neurologic risk in the
presence of a CPNB.105 In most cases of postoperative neurologic symptoms, it is problematic assigning
causality to the surgical procedure, CPNB, or simply general anesthetic (e.g., positioning injuries on an
unrelated part of the body). Interpreting the available data is further complicated due to a lack of controls
and/or randomization, which lead to multiple types of bias. An excellent example is a prospective,
uncontrolled cohort study of patients with continuous popliteal-sciatic nerve blocks (n=151) following foot
and ankle surgery reporting an alarming 41% incidence of postoperative neurologic symptoms (PONS)
within 2 weeks, 24% at 34 weeks, and 4% following 48 weeks. 106 A similar retrospective study (n=157)
found a 1.9% incidence of unresolved PONS at 11 months. 107 These risks are an order of magnitude higher
than previous estimates for popliteal infusions (0-0.4%),108,109 and are most-likely due to numerous biases,
beginning with selection bias.
Another relatively new retrospective investigation of 1,182 continuous interscalene and femoral nerve
blocks identified 4 (0.3%) patients with PONS at any time point, with one of these cases resolving by 6
months.110 Of note, these investigators reported an increased incidence of PONS lasting more than 6
months among patients with continuous versus single-injection peripheral nerve blocks (0.24% vs. 0.07%,
P=0.08).110 It is important to be aware of the very high risk of selection bias from this retrospective,
nonrandomized cohort (e.g., larger surgical procedures—with inherently higher neurologic risk—more
represented in the catheter group). The most reliable, recently-published data is derived from two
prospective investigations of over 2500 interscalene and femoral catheters, reporting a PONS incidence of
4.9-5.3% resolving by 6 months, with all but 0.3-0.7% of these resolving by 11 months.111,112 To
emphasize, it is critical that practitioners are cognizant of the fact that these values approximate association
and not necessarily causation: an unknown percentage of subjects with PONS would have experienced
them without any regional analgesic due to the surgery or other factors. Unfortunately, the available data
does not suggests that ultrasound guidance has a “meaningful impact on the incidence of PONS,” so
switching from a different insertion technique is not expected to decrease the rate of PONS. 113
The risk of falling following knee and hip arthroplasty have become better appreciated within the previous
decade.114,115 Single-injection femoral nerve blocks do not appear to increase this risk;116 but data from
randomized, controlled trials suggest that a continuous femoral or psoas compartment block is associated
with a 4-5 time increased risk of falling,117-119 although some investigators have questioned this
correlation.120,121 Regardless of the relationship between CPNB and falls, this complication continues to
occur even with the implementation of specific, intensive fall-prevention programs.122-125 While replacing
continuous femoral nerve blocks with adductor canal infusions have been proposed as a method to decrease
the risk of falling due to decreases induced quadriceps weakness, 126,127 such an association has yet to be
demonstrated.127,128
Benefits (Update). Novel indications for CPNB have been published within the past few years, suggesting
benefits for an even wider array of morbidities.129-150 New RCTs have provided evidence that adding a
perineural infusion following a single-injection peripheral nerve block improves postoperative analgesia
(and in most cases decreases supplemental analgesic requirements) using interscalene, 151-153
paravertebral,154 adductor canal,143-148 femoral,155-158 and sciatic catheters (Table 3).159-162 Compared with
epidural infusions,163 CPNB provides similar analgesia164 but improves hemodynamic stability (presumably
by inducing less sympathectomy),165-167 and following knee arthroplasty shortens the time to achieve
flexion goals, improves analgesia, and lowers supplemental analgesic requirements. 157 Compared with
intrathecal morphine, continuous posterior lumbar plexus blocks provide similar analgesia with lower
supplemental opioid requirements and incidence of pruritis. 168 And, data continues to accumulate
demonstrating that CPNB provides superior analgesia compared with continuous wound infusions.169,170
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Due to the association between continuous femoral nerve blocks and falling after knee arthroplasty, 117,118,125
the last five years have seen a plethora of research validating adductor canal catheter effectiveness
following major knee surgery,143-148 based on the theory that any risk of falling will be decreased due to less
induced quadriceps weakness compared with femoral infusion (Table 3). 126,127 Of the 6 RCTs directly
comparing continuous adductor canal and femoral nerve blocks,126,127,171-174 3 demonstrated dramatic
improvements for subjects with adductor catheters in the ability to stand, sit, ambulate, and climb
stairs.126,171-173 One study did not investigate ambulation;174 but, the 2 remaining RCTs failed to detect
mobilization improvements using an adductor infusion—although they did document and quantify
improved quadriceps femoris strength (52% vs. 18% of baseline in one). 126,127 It is noteworthy that these
two latter studies provided solely a fixed basal infusion (8 mL/h) without either patient-controlled or
repeated provider-administered bolus doses,126,127 which may have decreased adductor infusion
effectiveness. In addition, two of the RCTs detected improved analgesia for subjects with femoral
infusions at either rest (unicompartment arthroplasty)173 or with movement (tricompartment
arthroplasty),172 while the others failed to detect differences between the two catheter locations. Lastly, one
of the investigations reported a decreased time until discharge favoring the adductor catheters (3.1 vs. 3.9
days),171 although there were issues raised regarding its protocol/findings175-177 and a similar RCT detected
no decrease in time until discharge readiness or actual discharge, 172 albeit with slightly different criteria.
What does appear likely is that continuous adductor canal blocks are associated with greater mobilization
ability while providing at least similar analgesia compared with their femoral counterparts. 178 What
remains unclear is the ideal catheter insertion location/protocol,179,180 optimal method of local anesthetic
delivery (e.g., basal infusion vs. repeated bolus doses, basal rate, bolus volume, etc.) and if an optimized
delivery regimen can shorten hospitalization duration.181-183
In an effort to further improve analgesia following total knee arthroplasty, 184,185 three recent RCTs have
investigated the effects of adding a continuous sciatic nerve block to a continuous femoral or posterior
lumbar plexus (psoas compartment) block.160-162 All demonstrated lower pain scores and decreased
supplemental analgesic consumption,160-162 and one detected a lower incidence of nausea and vomiting as
well as improved knee flexion and ambulation.161 As has been previously opined, there are potential
drawbacks to providing a continuous sciatic nerve block such as the extra time required to place a second
catheter, an inability to fully evaluate sciatic nerve function postoperatively, 186 and interference with
physical therapy goals (e.g., foot drop, leg weakness).187
While there are relatively few demonstrated benefits of CPNB following catheter removal, 188 there are
significant additions to our knowledge base within recently-published data. Two RCTs found that a 2-3
day postoperative continuous interscalene or femoral nerve block resulted in less pain,152,189 opioid
requirements,152,189 and sleep disturbances152 on postoperative day 7 compared with a control group
following shoulder and knee procedures, respectively. Similarly, two RCTs add to the previous evidence
that a continuous femoral nerve block following total knee arthroplasty improves joint flexion for up to 6
months.157,189
However, it is the possibility of decreasing persistent post-surgical pain that has perhaps garnered the most
attention and optimism.190,191 Four new RCTs add data to the single previous positive study that involved
the addition of a femoral catheter to a popliteal infusion for major ankle surgery. 192 One study reported that
providing a continuous femoral nerve block following total knee arthroplasty reduced chronic pain at 3 and
6 months;189 and, another involving the same surgical procedure found that providing a continuous sciatic
nerve block in addition to a femoral infusion resulted in a reduction of dynamic pain at 3 months (no
difference at 12 months for either trial).193 Finally, two RCTs investigating continuous paravertebral blocks
following mastectomy detected improvements in analgesia up to a full year following surgery,194,195
including superior physical and mental health-related quality-of-life194 and decreased pain-related physical
and emotional dysfunction.195
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Liposome Bupivacaine
Liposomes consist of two hydrophobic tails and a hydrophilic head,196 and can form vesicles to act as a
medication “depot” (Figure 1).197,198 Following administration, the liposomes gradually break down,
resulting in an extended release of medication.199,200 Combining liposomes and a local anesthetic
(lidocaine) was first proposed in 1979,201 initially used in humans in 1988,202 and first reported for
postoperative analgesia in 1994.201,203 Although multiple subsequent reports were published,204-212 a
liposome local anesthetic was not approved by the United States FDA until 2011 (Exparel liposome
bupivacaine, Pacira Pharmaceuticals, Parsippany, New Jersey) for administration at the surgical site to
provide postoperative analgesia in adults.198
Two multicenter RCTs demonstrated superior postoperative analgesia of this approved medication
compared with placebo wound infiltration following hemorrhoidectomy213 and bunionectomy.214 In
contrast, when compared with bupivacaine HCl (“standard” bupivacaine), 10 of the 12 currently-published
RCTs were negative for their primary (and most secondary) analgesic end points. 215-221 Of the two positive
RCTs versus bupivacaine HCl, one involved hemorrhoidectomy, 222 although another similar trial had
negative results.215 The second positive RCT involved submuscular augmentation mammoplasty in which
mean pain scores were reduced by less than 1 on the 0-10 numeric rating scale and the investigators
concluded, “…it is our assertion that the additional cost of liposomal bupivacaine is unjustified for this
particular use.”223 Some of these 14 RCTs were dose-response studies, not powered to be a conclusive test
of efficacy; and, when combined with the placebo-controlled trials, there were some detected positive
associations for secondary end points such as pain scores at individual time points,224 opioid use (although
differences were minimal),224 and duration until first use of opioid analgesics.215,224 However, considering
the new medication costs an estimated 100 times that of bupivacaine HCl, it is incumbent upon those
proposing the conversion to produce data conclusively demonstrating superiority. 221 Various large RCTs
currently ongoing should provide much-needed data to help practitioners make evidence-based decisions
involving this analgesic modality (ClinicalTrials.gov NCT02713490, NCT02111746, NCT02197273).
There are no RCTs directly comparing CPNB with liposome bupivacaine wound infiltration. 225 The only
direct comparison to a single-injection femoral nerve block following total knee arthroplasty suggests that
liposome bupivacaine infiltration provides inferior analgesia during the duration of the peripheral nerve
block without subsequent differences between the two treatments.226 Considering there are now four
negative published RCTs comparing liposome bupivacaine with bupivacaine HCl following total knee
arthroplasty,215,217-219 and the literature is replete with positive studies involving CPNB,188 the evidence
certainly does not suggest even equivalence between these two modalities.
In contrast to wound infiltration, recently-published data from one RCT strongly suggests that liposome
bupivacaine within a single-injection subcostal TAP block provides statistically and clinically superior
analgesia to bupivacaine HCl up to 3 days following robotic assisted hysterectomy. 227 In a separate RCT,
few differences were detected between a continuous subcostal TAP block and epidural infusion following
open renal or hepatobiliary surgery,142 although this investigation was designed as a superiority study and
the negative findings should be viewed as inconclusive and not equivalence. Therefore, a randomized
comparison of a TAP with liposome bupivacaine bolus compared with either a epidural infusion or
perineural local anesthetic TAP infusion appears warranted.228,229 Of note, the United States FDA recently
revised the label for the single approved liposome bupivacaine formulation explicitly including,
“infiltration into the transversus abdominis plane (TAP) which is a field block technique [is] covered by the
approved indication for EXPAREL.”
Although no liposome local anesthetic is currently approved for use within the epidural space 230 or
peripheral nerve blocks, a great deal of related research has been completed (if not all published). 198 Both
preclinical toxicology and clinical data indicate that liposome bupivacaine has at least as favorable safety
profile as bupivacaine HCl.231-241 Though phase 1-3 clinical trials involving the use of liposome
bupivacaine have been reported for intercostal and ankle blocks, 197,198,231 the most published data may be
found for femoral nerve blocks.242,243 No direct comparisons with CPNB are available, but liposome
bupivacaine in a femoral nerve block produced over 72 hours of analgesia with an incomplete motor block
in healthy volunteers,242 and demonstrated analgesic activity for up to 72 hours versus placebo in subjects
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following total knee arthroplasty (albeit extraordinarily minimal analgesic differences following 24
hours).243 Further sizable RCTs involving adductor canal, brachial plexus, and femoral nerve blocks with
liposome bupivacaine are ongoing (ClinicalTrials.gov NCT02607579, NCT02713230, NCT02713178).
Theoretical benefits over CPNB include the avoidance of catheter insertion (e.g. less procedure time, no
catheter management/removal), the lack of an infusion pump and anesthetic reservoir to purchase/carry, a
lower risk of infection, and no risk of catheter dislodgement or leakage. It is emphasized that at the time of
this writing, there are no liposome bupivacaine local anesthetics approved for use in the epidural space 230 or
peripheral nerve blocks (other than the possible exception of TAP blocks, depending on how this block is
categorized).
Percutaneous Peripheral Nerve Stimulation

Electric current applied in both the central and peripheral nervous systems induces analgesia. There are
numerous theories regarding the mechanism of action,244 but most are usually based on Melzack and Wall’s
“gate control theory”:245 current activates large-diameter myelinated afferent peripheral nerves which
then—within the spinal cord— impede pain signal transmission from small-diameter pain fibers to the
central nervous system.246,247 Implanted spinal cord and peripheral nerve stimulators have since been used
to treat multiple chronic pain states.248-252 In contrast, the use of peripheral nerve stimulation to treat
acute/postoperative pain is extraordinarily rare,253-255 in no small part due to cutaneous pain fiber activation
with transcutaneous electrical nerve stimulation246 and the invasive requirement of surgically
implanting/removing peripheral nerve electrodes/leads.256,257
Electrical leads are now available with a diameter small enough to allow passage through a needle,
allowing percutaneous insertion (Figure 3a).258-260 Perineural placement is possible using ultrasound
guidance,261,262 and has been reported to treat chronic pain.263-266 More recently, postoperative pain was
treated using ultrasound-guided percutaneous peripheral nerve stimulation.267 Femoral—and in 2 cases
sciatic—leads were inserted in subjects (n=5) 8-58 days following total knee arthroplasty.267 Percutaneous
peripheral nerve stimulation decreased pain an average of 93% at rest (reduced from a mean of 5.0 to 0.2
on a 0-10 numeric rating scale), with 4 of 5 subjects experiencing complete resolution of pain. During
passive and active knee motion pain decreased an average of 27% and 30%, respectively. Neither
maximum passive nor active knee range-of-motion was consistently affected in this small cohort of
subjects.
There are no direct comparisons with CPNB, but theoretical benefits of percutaneous peripheral nerve
stimulation are numerous.267 Leads function optimally when inserted 0.5-3.0 cm from a target peripheral
nerve, negating the importance of location within a particular facial plane. Electrical generators are now so
minute that their footprint is smaller than a business card and may be literally adhered to a patient’s limb—
so, there is no large portable infusion pump or local anesthetic reservoir to carry (Figure 3b). Helically
coiled leads are designed to minimize the risks of migration and fracture, and decrease the infection risk to
approximately 0.05 per 1000 indwelling days.267 These characteristics permit a dramatically-long duration
of lead retention—well-over a year in some cases268-270—raising the possibility of preoperative insertion
and continued postoperative stimulation for the entire interval of surgically-related pain.268-272 There are
theoretically no induced sensory, proprioception, or motor deficits, enabling full engagement in physical
therapy and likely lacking any association with an increased falling risk. Obviously, there is no risk of
local anesthetic toxicity or leakage. Conversely, practical implementation of percutaneous peripheral nerve
stimulation to treat acute pain states is dependent upon multiple factors that are currently undetermined:
the time required for lead insertion, the cost of leads and electrical generators, the maximum provided
analgesia, and the future availability of a United States FDA-approved lead and generator.273
References (273) may be found at:
https://drive.google.com/file/d/0Bym_j5sEGX0xd19HREViWW94N2s/view?usp=sharing
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Radiofrequency Ablation for the Treatment of Spine and Musculoskeletal

Pain: Understanding the Basic Principles and Clinical Application
David Provenzano, MD Pittsburgh, Pennsylvania
As a result of completing this activity, the participant will be able to

 Explain the role of radiofrequency ablation (RFA) for spine and musculoskeletal pain
 Define the electrophysiological principles of radiofrequency lesioning
 Discuss the evidence for the safety and efficacy for radiofrequency treatment of pain
 Define the technical limitations of radiofrequency and methods to modulate lesion size
 Analyze the current level of evidence for radiofrequency treatment of knee pain
Radiofrequency ablation (RFA) is an interventional technique frequently employed for the treatment of specific pain
conditions that originate from the axial spine and musculoskeletal system. These common conditions include lumbar
and cervical facet syndrome, sacroiliac (SI) joint dysfunction and osteoarthritic knee pain.
To utilize RFA effectively, practitioners must understand the electrophysiological principles and technical aspects to
successfully treat the targeted structure and limit the risk of complications. In addition, practitioners should have an
in-depth understanding of relevant anatomy and appropriate patient selection to improve procedural outcomes. The
purpose of this refresher course is to provide an overview of the utilization of RFA for the treatment of spine
conditions. Particular areas to be discussed include the current level of efficacy and safety data and
electrophysiological principles of thermal, pulsed, and cooled RFA. The technical limitations of RFA and methods
to optimize and modulate lesion size are also described.
General Principles
The ability to ablate specific tissues while limiting destruction to nontargeted tissues is dependent on factors that
influence energy delivery and local physiological tissue characteristics. The bioheat equation describes coagulation
necrosis.1
Bioheat equation
Coagulation necrosis = (heat generated × local tissue interactions) – heat lost
In a simplified thermal RFA system, three primary factors determine heat generation and the size of the lesion:
distance from the active tip, radiofrequency current density, and duration of application of the radiofrequency
current.2 Heat losses that influence RFA include conduction, convection, and low-resistance shunting.
Monopolar and Bipolar Thermal RFA

Thermal RFA involves the use of high-frequency alternating current and results in irreversible cellular damage from
focal high temperature tissue heating.3 Temperature-controlled RFA systems are primarily employed in
interventional pain medicine. For monopolar RFA, the high-frequency alternating current flows from the uninsulated
active tip into the tissue. The alternating current produces frictional heating in the tissue surrounding the electrode. 2
In RFA, heat flows from the tissue to the cannula.
For conventional RFA, the time of lesioning, tip size, and set temperature all influence the final lesion size. With
monopolar RFA, lesions are in the shape of a prolate spheroid with coagulation occurring primarily in the radial
direction perpendicular to the long axis of the electrode. Minimal lesioning occurs distal to the tip. Therefore, for
monopolar RFA, the cannula should be placed with its shaft parallel to the target nerve.4,5 When performing
monopolar thermal RFA, it is important to understand the maximum tolerable margin of error for placement that is
allowed with a specific cannula as well as the radiofrequency settings that will still allow for a lesion to incorporate
the full diameter of the targeted nerve (Figure 1). The monopolar lesion size for interventional pain medicine is
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small at present, and the radius of the lesion is approximately 1 to 2 times the width of the electrode for a no fluid
preinjection set up.5,6
Figure 1. Diagram demonstrating monopolar RF lesioning of a nerve (yellow structure) with an RF cannula. The
cannula’s active tip is white. The red circle highlights the zone of lesioning. d: diameter of the nerve, e: maximum
tolerable margin of error, r: effective radius of lesioning, L: length of nerve lesioned. Figure adapted. 6
In bipolar RFA, a passive electrode replaces the grounding pad with the goal of focusing the electrical current
between the electrodes. A 3-dimensional Cartesian coordinate system describes a bipolar lesion (Figure 2). Bipolar
RFA is employed when a larger lesion is required and has been used for SI RFA of the lateral branches.7-12 When
performing bipolar RFA, it is important to understand specific configuration parameters that will influence lesion
development including: 1) active tip size and length, 2) fluid preinjection composition, technique and volume, 3)
interelectrode distance, 4) lesion time, 5) tip configuration, and 6) tip temperature.8,10 One parameter that is of
crucial importance is the set interelectrode distance (IED). The goal should be to choose an IED that will allow for
the ablation of the desired area and minimize destruction to nontargeted structures. In addition, the IED should be
set to limit hourglass lesioning. The maximum allowed IED will depend on multiple configuration parameters
including the size of the active tip, lesioning time, and composition of the preinjected fluid.7,8,10
Figure 2. A schematic diagram demonstrating important lesion parameters for a bipolar configuration. x: maximum
lesion length, ymax: maximum height, ymin: minimum height, z: maximum depth, IED: set interelectrode distance.
The yellow dot represents a nerve that is not being treated secondary to incomplete (hourglass) lesioning in the
middle of the lesion in the y-axis. Reprinted with permission.49
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Cooled RFA
Recently, cooled RFA has been used for the treatment of SI joint dysfunction.11-13 Compared with traditional thermal
RFA, cooled RFA results in significant lesion development distal to the tip of the RFA cannula. Lesioning distal to
the tip is advantageous in certain anatomical areas, such as the SI joint, where perpendicular placement of the
cannula is often required. In cooled RFA, an electrode is utilized that allows for continuous internal cooling of the
tip with a perfusate.14 The coolant flow rate can be adjusted to modulate lesion size. The internal perfusate serves as
a heat sink and removes heat closest to the electrode. The internal cooling allows for greater current deposition
which may result in in larger lesions.
Methods to Modulate the Local Tissue Environment to Increase Lesion Size

In the quest to enlarge the coagulation zone, methods to modulate the local tissue environment surrounding the RFA
cannula to allow for greater energy deposition have been investigated.10,14-16 The nerves innervating the facet joints
have a diameter of less than 2 mm and anatomical variability is common.6,17,18 Therefore, the development of
controlled and defined larger lesions may assist with lesioning structures that are small and have variable courses,
with the goal of limiting technical failures. The chemical composition of the preinjected fluid has been shown to
alter lesion size and development in both monopolar and bipolar RFA setups. Increasing the sodium chloride
concentration of the preinjected fluid has been shown to significantly increase power output and lesion size. 16,19
Studies to date have been in ex vivo models and further research is warranted. Unlike, monopolar and bipolar RFA,
the volume of lesion associated with cooled RFA with interventional pain medicine equipment does not appear to be
influenced by the preinjection of small volumes (0.5 ml) of specific fluids.20
Pulsed RFA
Pulsed RFA uses brief bursts of radiofrequency energy separated by longer time periods when radiofrequency
energy is not applied. The pauses between bursts allow for heat to dissipate within the surrounding tissue. Since the
tip temperature does not rise above 42°C, neurodestructive temperatures are not achieved.21 Although the exact
mechanism of pulsed RF is unknown, multiple mechanisms have been proposed. Pulsed RF seems to preferentially
target small diameter C and A fibers. In addition, pulsed RF has been shown to alter gene expression in the dorsal
horn of the spinal cord, suppress the release of excitatory amino acids in the DRG, attenuate microglial activation in
the dorsal horn and enhance the noradrenergic and serotonergic descending pain inhibitory.22-27 The theoretical
appeal of pulsed RFA is the ability to modulate pain without causing the extensive tissue injury seen with thermal
RFA.28 For the treatment of lumbar facet pain, thermal RFA has been shown to be superior to pulsed RFA.29,30
Lumbar Medial Branch RFA for Facet Joint Mediated Pain

When performing RFA, it is important to understand the anatomy of the lumbar medial branch and the technical
specifications of a radiofrequency lesion.4,31 As mentioned, the medial branches targeted are small, often less than 2
mm in diameter. Therefore, incorrect needle technique will result in inability to lesion the targeted nerve. Electrodes
should be placed parallel to the target nerve.5
The therapeutic efficacy of lumbar medial branch RFA has been evaluated in observational and randomized
controlled trials (RCTs). Of the six RCTs, three had technical flaws in both patient selection and surgical technique,
which hinders interpretation of the results.32-34 The other three studies had definitively positive results for
RFA.29,35,36 The study by Nath et al.36 demonstrated that the active treatment groups had statistically significant
improvement in back/leg pain and back/hip movement at six months. Improvement was also seen in quality-of-life
scores and in reduced use of analgesics. No significant complications were reported. Two observational studies also
demonstrated that RFA is effective.37,38 Dreyfuss et al.,38 in a study of 15 patients with a diagnosis of lumbar facet
syndrome made with diagnostic controlled medial branch blocks, demonstrated 90% pain relief in 60% of treated
individuals at 12 months. At least 60% pain reduction was seen in 87% of the patients at 12 months. Gofeld et al.37,
in a large clinical audit of 209 patients (179 of whom completed the study; 35 were lost to follow-up), reported that
68.4% had good (>50% pain relief) to excellent (>80% pain relief) results lasting from 6 to 24 months.
Cervical Medial Branch RFA for Facet Joint Mediated Pain

A systematic review evaluating a randomized controlled trial and four observational studies provides strong
evidence that cervical medial branch RFA is a successful treatment for chronic neck pain.39 Lord et al.,40 in a
randomized double-blind trial, compared RFA to sham denervation in patients with cervical facet pain confirmed
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with double-blind, placebo-controlled local anesthetic blocks. RFA denervation was found to be superior to the
sham procedure, and the median time that elapsed before pain returned to at least 50% of the preoperative level in
the RFA group was 263 days.
SI Joint RFA
Several RFA techniques that target the posterior innervation of the joint have been developed to treat SI joint pain.
One of the associated challenges with SI joint RFA includes an incomplete understanding of the innervation of the
joint. Furthermore, the innervation of the SI joint consists of small nerves with diameters ranging from 0.292 to
0.997 mm that are difficult to locate with sensory stimulation and have variable anatomic courses in relation to bony
anatomy.41 RFA techniques utilized include bipolar intraarticular RFA, bipolar lateral branch RFA, cooled RFA of
the lateral branches, and sensory stimulation guided SI joint RFA.8,9,11,12,42,43 Recently the employment of cooled
RFA has shown promise in the treatment of SI pain. In a randomized placebo-controlled study examining lateral
branch radiofrequency denervation with cooled RFA, Cohen et al.11 reported that 57% of patients obtained 50% or
greater pain relief at 6 months. Cooled RFA creates wide diameter lesions that may increase the ability to target
areas of nociceptive input. The study by Cohen also demonstrated functional improvements. In individuals with
successful pain relief, the median duration of relief was 7.9 ± 4.7 months. Patel et al.12 studied the efficacy of lateral
branch cooled RFA in a randomized placebo-controlled study. Significant improvements in pain, disability, physical
function, and quality of life at 3-month follow-up were demonstrated with cooled RFA compared with placebo.
Knee RFA
In a double-blind randomized controlled trial RFA applied to the articular nerves of the knee was examined for the
treatment of chronic osteoarthritis knee joint pain in comparison to sham treatment over a 12 week time course. 44
Compared to control, RFA led to significant pain reduction and functional improvement. Following the publication,
an editorial questioned the anatomical basis of the described genicular nerves in the manuscript.45 In an effort to
further define the innervation of the anterior capsule of the human knee, dissections of the 8human knees were
performed.46 The dissections revealed 6 nerves: superolateral branch from the vastus lateralis, superomedial branch
from the vastus medialis, middle branch from the vastus intermedius, inferolateral branch from the common
peroneal nerve, inferior medial branch from the saphenous nerve, and a lateral articular nerve branch from the
common peroneal nerve. At least 3 of the nerves were assessable to RFA ablation.
Complications
Although radiofrequency treatment can be associated with both minor and major complications, there are limited
data documenting the occurrence of these events.47,48 Following RFA, a temporary exacerbation of pain secondary to
an inflammatory response will often occur and can last several days to two weeks. Lord et al.6 audited 83 cervical
medial branch RFA procedures and recorded procedural side effects and complications. Following cervical medial
branch RFA, increasing postoperative pain occurred in 97% of cases with a median duration of 10 days. Some
patients may also experience transient dysesthesias of the skin over the operative area, arising from partial
denervation of the lateral branch of the posterior primary ramus. These transient dysesthesias occur more frequently
with cervical medial branch RFA.
Another concern with RFA is the morphological changes that may occur in the spine after lesioning the medial
branches. In the lumbar spine, in addition to providing sensory innervation to the lumbar facet joint, the medial
branch also provides innervation to the multifidus muscle. The multifidus muscle plays an important role in
segmental spine stabilization and postural stability. Following RFA, electromyography has demonstrated
denervation of the multifidus muscle.49 A recent single cohort retrospective study, suggested that RFA may
influence the rate of disc degeneration at treated levels.50 Validation of this finding is needed in a prospective
controlled study.
Other complications that may occur following cervical medial branch and third occipital nerve RFA include ataxia
and spatial disorientation.51 These complications are more common with cervical medial branch RFA of the upper
cervical levels, especially the third occipital nerve, and are usually mild and self-limiting.
One of the most feared complications is damage to surrounding nontargeted spinal nerves. Methods to prevent this
complication include precise anatomical placement of the RFA cannula through fluoroscopic guidance,
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physiological testing, and a detailed understanding of lesion dimensions. The RFA active tips should be positioned
safely away from the neuroforamen to avoid thermal lesioning of the spinal nerves. This is especially relevant when
methods are used to enhance lesion size, including cooled RFA and fluid preinjection. In addition, the risk of
toxicity to nontargeted tissues, including central and peripheral nervous system structures, should be considered
prior to injecting specific fluids (i.e., high saline concentrations).16
CONCLUSION
RFA is an effective therapeutic treatment for spinal pain originating from cervical and lumbar facet joints and SI
joints. In addition, recent research suggests that it may be a promising treatment for osteoarthritic knee joint.
Additional work is needed to improve patient selection, extend the duration of relief, and limit technical failures.
Furthermore, optimal lesioning algorithms need to be developed which incorporate multiple factors into decision-
making.
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8. Cosman ER, Jr., Gonzalez CD: Bipolar radiofrequency lesion geometry: implications for palisade treatment
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9. Burnham RS, Yasui Y: An alternate method of radiofrequency neurotomy of the sacroiliac joint: a pilot
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10. Provenzano DA, Lutton EM, Somers DL: The effects of fluid injection on lesion size during bipolar
radiofrequency treatment. Regional anesthesia and pain medicine 2012; 37: 267-276
11. Cohen SP, Hurley RW, Buckenmaier CC, 3rd, Kurihara C, Morlando B, Dragovich A: Randomized
placebo-controlled study evaluating lateral branch radiofrequency denervation for sacroiliac joint pain.
12. Patel N, Gross A, Brown L, Gekht G: A randomized, placebo-controlled study to assess the efficacy of
lateral branch neurotomy for chronic sacroiliac joint pain. Pain medicine (Malden, Mass.) 2012; 13: 383-398
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16. Provenzano DA, Liebert MA, Somers DL: Increasing the NaCl concentration of the preinjected solution
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17. Cohen SP, Rathmell JP: Tackling the technical challenges that hinder the success of facet joint
radiofrequency treatment for spinal pain. Regional anesthesia and pain medicine 2010; 35: 327-328
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Radio-frequency thermal ablation with NaCl solution injection: effect of electrical conductivity on tissue heating
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32. Gallagher J, Petriccione dVPL, Wedley JR, Hamman W, Ryan P, Chikanza I, Kirkman B, Price R, Watson
MS, Grahame R, Wood S: Radiofrequency facet joint denervation in the treatment of low back pain: A prospective-
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44. Choi WJ, Hwang SJ, Song JG, Leem JG, Kang YU, Park PH, Shin JW: Radiofrequency treatment relieves
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45. Gofeld M: Letter to the editor. Pain 2014; 155: 836-7
46. Franco CD, Buvanendran A, Petersohn JD, Menzies RD, Menzies LP: Innervation of the Anterior Capsule
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48. Kornick C, Kramarich SS, Lamer TJ, Todd Sitzman B: Complications of lumbar facet radiofrequency
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49. Dreyfuss P, Stout A, Aprill C, Pollei S, Johnson B, Bogduk N: The significance of multifidus atrophy after
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50. Smuck M, Crisostomo RA, Demirjian R, Fitch DS, Kennedy DJ, Geisser ME: Morphologic changes in the
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“A Pioneer’s Perspective on Point-of-Care Ultrasound (POCUS) and on State

of the Art POCUS Practice for the Anesthesiologist”
Erik Sloth, MD, PhD, DMSc Aarhus, Denmark

Stephen Haskins, MD New York, NY, USA
Introduction (Stephen Haskins, MD)

Learn from a true pioneer in anesthesiology that helped lead the way in the development of clinical applications,
educational guidelines, materials and training courses for Point-of-Care Ultrasound (POCUS) over the course of a 25-
year career. POCUS involves using ultrasound at the bedside to obtain and interpret images simultaneously, thereby
using ultrasound like the “21st Century Stethoscope” where instead of just listening to the patient, the clinician can
now look inside to evaluate for and manage major pathology including shock and cardiac arrest. POCUS has only
recently become one of most exciting topics in anesthesiology with publications frequently coming out in major
journals on it’s expanding educational role and it’s many clinical uses in the perioperative setting (1,2). Professor
Sloth will provide the anesthesia provider with insight into the very beginnings of this clinical movement, the
incredible inertia it once experienced and the now ever growing enthusiasm and seemingly endless applications for
for POCUS within our profession.
My Story – How, When and Why Focus Assessed Transthoracic Echo (FATE)?
One year after graduating from Medical School in 1987 I was employed for a year as an anesthesiologist. In Denmark
this meant practicing intraoperative anesthesia, critical care, emergency airway management, and emergency
assessment in the field! Although I enjoyed all aspects, I was most drawn to the cardiac and circulatory systems and
applied for an opportunity to work in cardiology. Because cardiology was highly competitive and prestigious, it was
almost impossible for an upcoming anesthesiologist to be hired; however, after being offered one month of
employment “without any possibility for extension” I managed to stay on for a full year.
From day one echocardiography fascinated me and the newest literature showed an increasing use of transesophageal
echocardiography (TEE) among cardiothoracic anesthesiologists in USA (3). Cardiologists in Denmark had just
bought their first TEE probe so I eagerly learned TEE, but I also focused on the surface approach, transthoracic
echocardiography (TTE) (4,5). The hemodynamic monitoring potential for these tools were obvious to me, but it
became clear that TTE was a more universal clinical tool in the perioperative setting. As an anesthesiologist, I began
wondering if TTE would change outcomes when dealing with hemodynamic unstable patients? I could recall several
cases where we would have completely changed our approach if we could use TTE to see what we were facing! I
decided to spend my time learning TTE and within 6 months I was advanced enough to achieve all 2D views, and
apply calculations with m-mode and Doppler.
permission. Reprinting or using individual refresher course lectures contained herein is strictly prohibited without permission from
the authors/copyright holders.
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I began to use bedside TTE on a daily basis to manage

cardiac arrests (6) (Fig. 1) and assess patients admitted to
the cardiac ICU while on call. I used TTE as a goal
directed means to improve diagnosis and continuously
manage evolving pathology. I also learned to evaluate the
lungs and use ultrasound to find significant pleural
effusions (7,8). Another major issue I discovered was the
frequent mismanagement of patients with hypovolemia
and normal myocardial function with inotropes (4,9). I
termed this inappropriate treatment “Iatrogenic Inotropic
Intoxication Syndrome” (IIIS).
After a year in cardiology I returned to anesthesiology in

November 1990; however, I knew cardio-pulmonary
ultrasound would continue to be a part of my clinical
practice and I believed that all other anesthesiologist
Figure 1. FATE during cardiac arrest. I have used this should learn this skill as well. Unfortunately, at the time
since 1990 with great success (6)!! few agreed and my colleagues felt we should leave
cardiac ultrasound to the cardiologists. For years I could not publish my research on focused cardiac ultrasound and
the original Focus Assessed Transthoracic Echocardiography (FATE) paper with outstanding data on more than 200
mixed ICU patients was repetitively rejected in Europe and USA. Fortunately, over the next decades enthusiasm for
Point-of-Care (POC) cardiothoracic ultrasound has grown as a result of persistence, enthusiasm, effort, and education
by innovators – and, of course, the increasing availability of ultrasound technology.
The first FATE hands-on course held in 1996 was a great success, and by 2000 FATE became part of the
Scandinavian Intensive Care training program and in 2002 it was taught at the first annual EACTA echocardiography
course.
Please note that we do not teach FATE as a substitute for a comprehensive TTE performed by the cardiologists, but,
like all point-of-care techniques, it should be considered a supplement to the clinical evaluation. FATE allows for
bedside imaging via a non-invasive, safe and affordable technology that provides new and important information in
most cases (4,5,10,11,12). Today perioperative physicians are finally embracing focused cardio-thoracic ultrasound
and it is recommended by many societies and associations (13,14) 25 years after I began this journey.
Why PoCUS for Every Anesthesiologist?

To fully understand the importance of POC ultrasound (POCUS) it is necessary to recall the basic physiology and to
acknowledge the challenges of diagnosing serious pathology without imaging, e.g. pericardial and pleural effusion
(overload) that are easily diagnosed by means of POCUS.
Physiology and pathology

Physicians involved in the management of patients with potential or manifest critical illnesses are obliged to assess
the circulatory state and screen for heart disease as part of the patient assessment. A conventional hemodynamic
assessment typically consists of a clinical examination, ECG, measurement of heart rate and peripheral blood
pressure, and some times invasive pressures and surrogate markers of cardiac output. These parameters may be useful
in detecting overall change in the patient’s condition. However, they reveal little about the underlying and
determining hemodynamic parameters. Full disclosure of hemodynamic status requires information about preload,
afterload, and myocardial function. The myocardial function is predominantly determined by four parameters: systolic
and diastolic function on the right and left sides of the heart. In order to avoid the unnecessary risks associated with
invasive measurements, imaging of the heart is the best way to assess these fundamental parameters.
•Preload is the end volumetric pressure that stretches the right or left ventricle of the heart to its greatest geometric
dimensions under variable physiological demands. Clinically, preload is often described as the left ventricular end-
diastolic volume.
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•Afterload is the tension developed in the myocardial wall of the left ventricle (LV) during the ejection period.
According to the modified Laplace's law, the tension on the muscle fibers in the myocardial wall is the product of the
pressure within the ventricle, multiplied by the volume of the chamber, divided by the thickness of the myocardial
wall.
•Myocardial contractility is the intrinsic ability of the myocardium to contract. Thus, direct measurement of
myocardial contractility in vivo in not clinically feasible. However, there are many surrogate parameters of
myocardial contractility, and in order to avoid confusion of terms, they are often expressed as myocardial function. A
number of methods for the assessment of myocardial function are available and can be learned from textbooks.
It follows from the facts above that the chamber dimensions of the heart and the thickness of the myocardial walls are
key parameters for a complete hemodynamic evaluation. FATE is a perfect tool for that (5).
The protocol is based on TTE and developed to detect obvious and dangerous pathological heart conditions and to
assess basic hemodynamic determinants. In order to address the respiratory and circulatory consequences of eventual
pleural effusion, the protocol was supplemented with imaging of the lower part of the thoracic cavity on both sides.
During the 1990s, the protocol was optimized and the first original paper on this subject came out in 2004 and
evaluated the feasibility of FATE in a mixed intensive care population (4). Since then the protocol has been part of a
modern hemodynamic approach to circulatory evaluation – NOT manipulating pressure and flow without
acknowledging the underlining physiological determinants and present significant pathology.
The FATE protocol follows a simple focused approach:
• Look for obvious pathology

• Assess wall thickness and chamber dimensions
• Assess biventricular function
• Image pleura on both sides
• Relate the information to the clinical context
• Apply additional ultrasonography
Four scanning positions are of particular interest in the FATE protocol (Fig. 2). It is recommended to begin the
examination without altering patient positioning with the option of changing position in the case of suboptimal image
quality.
1. Subcostal 4-chamber view (Fig. 2). The transducer is placed inferior to the right costal curvature pointing toward
the patient’s left shoulder. The orientation marker (OM) on the transducer is orientated toward the patient’s left side
and caudally until all four cardiac chambers appear on the screen. This subcostal 4-chamber view will display any
pericardial effusion, severe LV failure, and severe right ventricular dilation. Pointing the OM cranially the IVC can be
displayed in a long axis view.
2. Apical 4-chamber view (Fig. 2). The transducer is placed over the cardiac apex beat. The OM is aimed to the
patient’s left, and the ultrasound beam is directed parallel to the long axis of the heart. Small adjustments are made
until the 4 chambers are presented on the screen. The apical 4-chamber view allows evaluation of LV systolic
function, left atrial size, and right ventricular size.
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The latter should be two-thirds of the LV, provided that

the LV is normal.
3. Parasternal views (Fig. 2). The transducer is placed on

a line connecting the apex beat with the middle of the
right clavicle, adjacent to the left lateral margin of the
sternum. By pointing the OM toward the patient’s right
shoulder, the parasternal long-axis view is displayed.
Rotation of the transducer 90° clockwise will display a
short-axis view. The parasternal views may reveal
pathological states such as hypovolemia, LV failure, LV
hypertrophy, or dilation of the right ventricle suggestive
of right ventricular failure or pulmonary embolism.
4. Pleural views (Fig. 2). The transducer is placed on the

lateral thoracic wall. By orienting the OM cranially,
caudal structures will be presented to the left side of the
screen and vice versa. The diaphragm is a mandatory
landmark seen as a white curved line. The patient should
be placed in a semi-recumbent position, because pleural
fluid obeys the law of gravity.
Interpretation of POC echocardiography examinations

should provide rapid assessment of the hemodynamic
state and disclose important pathology. The results of the
examination are related to the clinical context
immediately and should never have to stand alone. This
limits the need for precise measurements to a large
degree. Outcomes from a POC echocardiography
Figure 2. The very famous FATE card (Page 1 of 4) examination should be dichotomous or categorical and
where you can find all essential information for rely on simple pattern recognition or distance
learning focused cardiac ultrasound. measurements. In contrast to this is the full standard TTE
with imaging from multiple views including the use of Doppler. In figure 3 six of the most important pathological
entities are shown.
Pericardial effusion
Pericardial effusion (PE) is a relatively common condition with a large number of different etiologies. It is essential to
recognize this particular condition since it may progress to severe hemodynamic compromise, defined as the clinical
condition of cardiac tamponade.
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Left ventricular dilatation

LV dilatation is a severe condition, regardless of the
underlying cause. The detection of a dilated LV is of
great importance in any patient regardless of
circumstances and co-morbidity.
In the clinical setting, experienced examiners in
echocardiography will most often qualify the degree of
LV dilatation with linguistic terms as “mild”,
“moderate”, or “severe”. However, many experts agree
that a LV end diastolic diameter ≥ 62mm is significant.
Right ventricular dilatation

The RV is essential to the heart, and failure or severe
pathology will severely compromise circulation.
However, the shape and function of the RV is complex
and incompletely visualized during echocardiography.
Thus, detailed assessment of RV dimensions and
function is a complex challenge requiring substantial
skills and training.
Left ventricular hypertrophy

LV hypertrophy is very common, and severe cases
Figure 3. Six cases of severe pathology detected by have impact on systolic and diastolic function. There
POC ultrasonography at the bedside. Upper left panel: are many specific underlying conditions that can cause
Pericardial effusion. Upper right panel: Left ventricular LV hypertrophy; among these are various
dilation. Middle left panel: Right ventricular dilation. cardiomyopathies, aortic stenosis, and other valvular
Middle right: Left ventricular hypertrophy. Lower left: lesions. LV hypertrophy can be defined as wall
Impaired ejection fraction. Lower right: Aortic stenosis. thickness ≥ 13mm. LV hypertrophy is extremely
dangerous in relation to general anesthesia.
Left ventricular failure

LV systolic failure is responsible for many cases of heart failure. The diagnosis has a poor prognosis and is associated
with poor quality of life. Hence, evaluation of any patient with POC echocardiography should always include an
assessment of LV function most often as ejection fraction (EF) where 60% is normal.
Aortic stenosis
Aortic stenosis (AS) is the most common valvular heart disease, accounting for a significant contribution to overall
cardiovascular mortality. A significant AS can be defined as a maximum flow velocity across the valve ≥ 3m/s.
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Feasibility of FATE
When used as a preoperative evaluation tool, a full FATE examination can be made in approximately 70 seconds, and
4-chamber views can be achieved in only 10 seconds (15). Whether such limited time consumption is applicable to
perioperative settings and to the ICU remains to be proven. Ultrasonography in the postoperative period in patients
recovering from thoracic surgery can be challenging because of issues with air in the mediastinum, bandages, and
dressings that cover imaging windows. However, it has been shown that images suitable for interpretation can be
obtained in 88% of this particular patient population on the first postoperative day. Successful use of focused
ultrasonography in the sitting patient has been published, making FATE even more feasible, also as a part of the
preoperative assessment. As for feasibility and clinical impact, a recent study on the use of focused echocardiography
in the preoperative clinic, including patients older than 65 years or patients with suspected heart disease, showed
convincing results.
The Expansion of PoCUS

Over the years, POCUS has emerged and has been adapted into the ABC context, extremely relevant to the
anesthetist.
Lung ultrasound (LUS)

Pleural effusion is easily diagnosed with a cardiac transducer. Also the so-called B-lines, giving information on the
content of lung water can be evaluated using a cardiac probe (4). The presence of B-lines excludes pneumothorax and
changing to a linear or curved transducer US can be used to diagnose and monitor the size of a pneumothorax by
demonstrating the lung-point (16). The lung-point arises where the two pleural blades separate in case of
pneumothorax.
Focused Assessment with Sonography in Trauma (FAST)

These 4 abdominal views (fig 4) serves to diagnose free
fluid en the pericardium and abdomen and can also be very
beneficial to the anesthetist. Position 1, the subcostal view
is already introduced as this is part of the FATE-protocol.
The other 3 views are position 2 RUQ - perihepatic
morrison’s pouch, position 3 LUQ - perisplenic and
position 3 Pelvic longitudinal and transverse planes –
retrovesicular and pouch of douglas. It is becoming more
and more common, also to scan the abdominal aorta, for the
evaluation of the size and/or calcification. Optimal
abdominal scanning requires a curved abdominal
transducer. (17)
Vascular access
Because US guided vascular access applies to all health
care workers as almost no patient in the healthcare system
gets through without a minimum of IV access, I predict that
this will emerge into the most important utilization of US of
all! US is considered mandatory for central venous access,
but still only used as a rescue technique for peripheral
venous and arterial cannulation. This will change over the
next few years. With the goals of achieving radial artery
cannulation as quick as possible with minimal attempts,
ultrasound should not be a rescue technique but the “first
Figure 4. FAST views choice!” (18). The same will prove to be true for pediatric
vascular access.
Future Directions
There is a growing evidence that POCUS works and can be learned quickly by novices. To make POCUS a universal
tool for the anesthesiologist, education and certification is required. Although the learning curve is steep, there is still
a need for effective educational programs that include hands-on training. Many societies offer courses of differing
quality, but e-learning together with very structured hands-on training is the key. US simulation is also important to
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reinforce skills and clinical relevance. Competency with certification and maintenance should be based on testing and
adherence to cases logged as endorsed by the societies taking a lead in POCUS .
Finally, technological advances are important for a routine use of POCUS. Pocket and tablets ultrasound devices are
already widely available, but we will need US quality to go up while simultaneously have size and price go down for
these devices to become mainstream.
POCUS is a new and exciting paradigm in anesthesia. It will change the way future anesthetists work in the
perioperative setting and it’s importance will become increasingly obvious as our patients continue to get older and
sicker with increasingly severe CO-morbidities.
References
1. Mahmood et al. Perioperative Ultrasound Training in Anesthesiology: A Call to Action. Anesthesia and Analgesia
2016 Jun;122(6):1794-1804.
2. Zhang et al. Inferior Vena Cava Ultrasono before General Anes Can Predict Hypotension after Induction.
Anesthesiology. 2016 Mar;124(3):580-9
3. Cahalan MK, Lurz FC, Schiller NB. Transoesophageal two-dimensional echocardiographic evaluation of
anaesthetic effects on left ventricular function. Br J Anaesth. 1988;60 (8 Suppl 1):99S-106S.
4. Jensen MB, Sloth E, Larsen KM, Schmidt MB. Transthoracic echocardiography for cardiopulmonary monitoring in
intensive care. Eur J Anaesthesiol. 2004;21(9):700-7.
5. Holm JH, Frederiksen CA, Juhl-Olsen P, Sloth E. Perioperative use of focus assessed transthoracic
echocardiography (FATE). Anesth Analg. 2012;115(5):1029-32.
6. Sloth E, Jakobsen CJ, Melsen NC, Ravn HB. The resuscitation guidelines in force--time for improvement towards
causal therapy? Resuscitation. 2007;74(1):198-9.
7. Oveland NP, Bogale N, Waldron B, Bech K, Sloth E. Case Reports in Clinical Medicine 2 (2013) 133-137.
8. Hermansen JF, Juhl-Olsen P, Frederiksen CA, Christiansen LK, Hørlyck A, Sloth E. Drainage of large pleural
effusions increases left ventricular preload. J Cardiothorac Vasc Anesth. 2014;28(4):885-9.
9. Sloth E. Inotropic support with little physiological rationale. Acta Anaesthesiol Scand. 2004;48(2):255.
10. Christiansen LK, Frederiksen CA, Juhl-Olsen P, Jakobsen CJ, Sloth E. Point-of-care ultrasonography changes
patient management following open heart surgery. Scand Cardiovasc J. 2013;47(6):335-43.
11. Bøtker MT, Vang ML, Grøfte T, Sloth E, Frederiksen CA. Routine pre-operative focused ultrasonography by
anesthesiologists in patients undergoing urgent surgical procedures. Acta Anaesthesiol Scand. 2014;58(7):807-14.
12. Laursen CB, Sloth E, Lassen AT, Christensen Rd, Lambrechtsen J, Madsen PH, Henriksen DP, Davidsen JR,
Rasmussen F. Point-of-care ultrasonography in patients admitted with respiratory symptoms: a single-blind,
randomised controlled trial. Lancet Respir Med. 2014;2(8):638-46.
13. Via G, Hussain A, Wells M, Reardon R, ElBarbary M, et al; International Liaison Committee on Focused Cardiac
UltraSound (ILC-FoCUS); International Conference on Focused Cardiac UltraSound (IC-FoCUS). International
evidence-based recommendations for focused cardiac ultrasound. J Am Soc Echocardiogr. 2014;27(7):683.e1-
683.e33.
14. Fagley RE(1), Haney MF, Beraud AS, Comfere T, Kohl BA, Merkel MJ, Pustavoitau A, von Homeyer P, Wagner
CE, Wall MH. Critical Care Basic Ultrasound Learning Goals for American Anesthesiology Critical Care Trainees:
Recommendations from an Expert Group. Anesth Analg. 2015;120(5):1041-53.
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15. Frederiksen CA, Juhl-Olsen P, Larsen UT, Nielsen DG, Eika B, Sloth E. New pocket echocardiography device is
interchangeable with high-end portable system when performed by experienced examiners. Acta Anaesthesiol Scand.
2010;54(10):1217-23.
16. Oveland NP, Søreide E, Lossius HM, Johannessen F, Wemmelund KB, Aagaard R, Sloth E. The intrapleural
volume threshold for ultrasound detection of pneumothoraces: an experimental study on porcine models. Scand J
Trauma Resusc Emerg Med. 2013; 1;21:11.
17. Scalea TM(1), Rodriguez A, Chiu WC, et. al. Focused Assessment with Sonography for Trauma (FAST): results
from an international consensus conference J Trauma. 1999 46(3):466-72.
18. Hansen MA, Juhl-Olsen P, Thorn S, Frederiksen CA, Sloth E. Ultrasonography-guided radial artery
catheterization is superior compared with the traditional palpation technique: a prospective, randomized, blinded,
crossover study. Acta Anaesthesiol Scand. 2014;58(4):446-52.
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Anesthesia for Non-obstetric Surgery During Pregnancy

Yaakov Beilin, M.D. New York, New York
The incidence of surgery for non-obstetric procedures during pregnancy is between 0.3%-2%.1,2 As there are
approximately 4,000,000 deliveries per year in the United States this translates to 80,000 anesthetics to pregnant women
per year, and most likely more due to surgery performed prior to clinical recognition of the pregnancy. Studies have
demonstrated that many women presenting for surgery are unaware that they are pregnant. Unknown pregnancies in
women presenting for surgery occurs in roughly 0.3%-1.3%3,4 of adults and 2.4% of adolescents between the age of 15
and 20.5 For this reason a urinary pregnancy test should be considered in women of child-bearing age prior to surgery,
unless an emergency clinical situation precludes this.
Surgery may be required at any time during pregnancy, though a large Swedish study of 720,000 found it was
most common during the first trimester (42%), followed by the second (35%) and third (24%).2 Appendectomy is the
most frequently performed nonobstetric operation during pregnancy.6 However, almost every type of surgical procedure
has been successfully performed on the pregnant patient, including open heart procedures with cardiopulmonary bypass,7
neurosurgical procedures requiring hypotension and hypothermia,8 and liver transplantation.9
Anesthesia for the pregnant woman is one of the rare situations where the anesthesiologists must be concerned
about two patients, the mother and the unborn fetus. Provision of a safe anesthetic requires an understanding of the
physiologic changes of pregnancy and the impact of anesthesia and surgery on the developing fetus. Maternal
considerations result from the physiology that affects almost every organ system. Fetal concerns include the possible
teratogenic effects of anesthetic agents, avoidance of intrauterine fetal asphyxia and prevention of premature labor.
Physiologic changes of pregnancy
The pregnant woman undergoes significant physiologic changes to allow adaptation for the developing fetus.
Respiratory System
Due to increased progesterone levels during the first trimester, minute ventilation is increased by almost 50%
and remains so for the remainder of the pregnancy. Because anatomic dead space does not change significantly during
pregnancy, at term, alveolar ventilation is increased by 70%. From 20 weeks’ gestation, the functional residual capacity
(FRC), expiratory reserve volume and residual volume begin to decrease as a result of upwards displacement of the
diaphragm by the gravid uterus; this reaches its maximum reduction of 20% by term Vital capacity is not appreciably
changed from pre-pregnancy levels. The increase in minute ventilation leads to a decrease in PaCO2 to approximately 30
mm Hg. Arterial pH remains unchanged because of a compensatory increase in renal excretion of bicarbonate ions. The
increased alveolar ventilation and reduced FRC lead to a more rapid uptake and excretion of inhaled anesthetics. The
decrease in FRC in conjunction with increases in cardiac output, metabolic rate, and oxygen consumption lead to a much
greater risk of arterial hypoxemia during periods of apnea or airway obstruction.
Anatomic changes to the airway include laryngeal and pharyngeal edema that can make ventilation and tracheal
intubation more difficult. In addition, mucosal capillary engorgement can cause bleeding during airway manipulation.
Mallampati scores have been found to increase during pregnancy - Pilkington et al.,10 found the incidence of grade 4
airways increased by 38% from the 12th to the 38th week of pregnancy. Together with inherent weight gain and
enlargement of breasts, these changes make tracheal intubation more difficult, as evidenced by failed intubation as a well
recognized cause of maternal mortality.11
Cardiovascular System
Cardiac output is increased by 30-40% during the first trimester and 50% at term. This is primarily due to an
increase in stroke volume (30-40%), and secondarily to an increase in heart rate (15%).12 Further rises in cardiac output
occur during labor and immediately postpartum. Blood pressure normally decreases during pregnancy because of a fall
in systemic vascular resistance due to the vasodilatory effects of estrogen and progesterone. Diastolic pressure is
decreased to a greater extent (10-20%) than the systolic (0-15%). Near term, 10-15% of patients have a dramatic
reduction in blood pressure in the supine position, often associated with diaphoresis, nausea, vomiting, pallor and
changes in cerebration. This is known as the supine hypotensive syndrome and is caused by compression of the inferior
vena cava and aorta by the gravid uterus.13 This can begin as early as the second trimester and may lead to a reduction in
renal and uteroplacental blood flow. Symptoms can be alleviated by tilting the patient on her left side.
Increases in cardiac output will hasten the speed of intravenous anesthesia induction. Compression of the
inferior vena cava by the gravid uterus leads to dilatation of the azygos system and the epidural veins. Epidural venous
engorgement decreases the volume of the epidural and intrathecal spaces - drugs used in neuraxial blockade should
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therefore be decreased. Additionally, progesterone may increase the sensitivity of nerves to local anesthetics since
neuraxial drug requirements decrease prior to uterine enlargement.14
Gastrointestinal System
Traditionally, gastric emptying was considered prolonged in the pregnant woman by the end of the first
trimester.15,16 This was thought to be related to progesterone and mechanical changes as the stomach is displaced upward
by the enlarging uterus. However, recent studies using acetaminophen absorption have not found a difference in gastric
emptying in pregnant women. Wong et al., found no difference in gastric emptying between term women who ingested
50 mL vs. 300 mL of water in both non-obese17 and obese women.18 This is in contrast to active labor when gastric
emptying is delayed.19 Although gastric emptying per se may not be delayed until the onset of labor, when the gravid
uterus enters the abdominal cavity at 20 weeks’ gestation bariatric pressure is increased. In addition there is an increase
in the acidity of gastric secretions and a reduction in lower esophageal sphincter tone due to the influence of hormones.20
Hematologic system
Intravascular volume is increased by 45% during pregnancy due to an increase in plasma volume. Since this
increases by a greater proportion than the red blood cell volume (55% and 30% respectively) there is a relative anemia
during pregnancy. Nevertheless a hemoglobin concentration of less than 11 g/dL is considered abnormal. Most of the
coagulation factors are elevated during pregnancy and consequently pregnancy is considered a hypercoagulable state,
with an increased risk of thromboembolic events.21 Platelet counts generally decrease by approximately 20% during
a normal pregnancy; approximately 7% of all parturients will present with a platelet count < 150,000·mm-3, and
0.5-1% will present with a platelet count < 100,000·mm-3.22
Hepatic Changes
Tests of liver function are commonly increased during pregnancy, though this does not necessarily indicate
abnormal liver function. Pseudocholinesterase activity declines by as much as 20% during the first trimester and remains
at this level for the remainder of the pregnancy.
.23 Accordingly, the doses of inhalational agents should be reduced. Also, doses of local anesthetics in the neuraxis
should be reduced.14 This is related to progesterone and to mechanical effects from the gravid uterus pressing on the
spinal and epidural space enhancing spread of local anestheticHowever, prolonged apnea is rarely a problem following a
standard dose of succinylcholine and the duration of ester-linked local anesthetics are not prolonged.
Nervous System
The minimum alveolar concentration (MAC) for inhaled anesthetics is decreased by up to 40% during
pregnancy due to progesterone and endorphins and begins in the 1st trimester.
Fetal Considerations
Drug teratogenicity
A teratogen is a substance that produces an increase in the incidence of a particular defect that cannot be
attributed to chance. In order to produce a defect, the teratogen must be administered in a sufficient dose at a critical
point in development. In humans this critical point is during organogenesis, which extends from 15 days to
approximately 60 days gestational age. Each organ system has its own unique period of susceptibility, e.g., the heart
develops between days 18 and 40 and limbs between days 24-34. However, the central nervous system does not fully
develop until after birth, hence the critical time for this may extend beyond gestation.
Well controlled randomized human studies are essentially impossible to perform due to ethical limitations and
the large number of patients required to study these rare defects.24 Four approaches have been utilized to study the effects
of anesthesia in the pregnant patient: 1) animal studies, 2) limited retrospective human studies, 3) studies of chronic
exposure of operating room personnel to trace concentrations of inhaled anesthetics, and 4) outcome studies of women
who underwent surgery while pregnant.
Almost all anesthetic agents have been found to be teratogenic in some animal models. However, the results of
animal studies are of limited value because of species variation and the doses of anesthetic agents in animal studies were
generally in greater concentrations than those used clinically. In addition other known teratogenic factors such as
hypercarbia, hypothermia and hypoxemia were either not measured or not controlled. Species variation is particularly
important. Thalidomide has no known teratogenic effects on rats and was approved by the United States FDA for use in
humans. However it later became apparent that thalidomide is teratogenic in humans.25
The United States FDA has established a risk classification system to assist physicians weigh the risks and
benefits when choosing therapeutic agents for the pregnant woman.26 To date there are only five drugs known to be
teratogens, thalidomide, isotrentinoin, coumarin (Warfarin), valproic acid, and folate antagonists, and none of them are
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anesthetic agents.27 Most anesthetic agents, have been assigned a Category B or C classification. Only the
benzodiazepines have been assigned as category D (Positive evidence of risk. Investigational or post-marketing data
show risk to the fetus. Nevertheless, potential benefits may outweigh the potential risk). Cocaine is in category X, or
contraindicated.
Nitrous Oxide
Nitrous oxide is a known teratogen in mammals and rapidly crosses the human placenta.28,29 It had been
presumed that the teratogenicity of nitrous oxide in animals is related to its oxidation of vitamin B12, which then cannot
function as a cofactor for the enzyme methionine synthetase - essential for the formation of thymidine, a subunit of
DNA. There is some evidence that the effects in animals of nitrous oxide are not related to these proposed effects on
DNA synthesis. Pretreatment of rats exposed to nitrous oxide with folinic acid, which bypasses the methionine
synthetase step in DNA synthesis, does not prevent congenital abnormalities,30 and suppression of methionine synthetase
occurs at low concentrations of nitrous oxide31 - concentrations found safe in animal studies.32 Despite these theoretical
concerns, nitrous oxide has not been found to be associated with congenital abnormalities in humans.1, 2, 33, 34
Benzodiazepines
The use of sedatives, in particular benzodiazepines, in the first trimester of pregnancy is controversial.
Benzodiazepines exert their action through the inhibition of gamma-aminobutyric acid (GABA) receptors in the
central nervous system. GABA has been shown to inhibit palate shelf reorientation leading to cleft palate
formation.35 Some investigators in human retrospective studies noted an association between diazepam ingestion in the
first six weeks of pregnancy and cleft palate.36,37 These findings have been questioned by the results of two prospective
studies that did not demonstrate an association.38,39 It is important to note that in the studies that found an association, the
assessment was in women chronically exposed to benzodiazepines and not in women with a one-time low dose exposure
as typically occurs during surgery. The FDA has assigned benzodiazepines a Class D designation and although
controversial,40 this author prefers not to use benzodiazepines during nonobstetric surgery unless there is a compelling
reason to do so.
Human studies:
There have been two approaches to assess the effects of anesthetic agents on pregnancy outcome: large
retrospective epidemiologic surveys of women chronically exposed to anesthetic gases, and retrospective database
studies comparing women who underwent surgery while pregnant to those who were not.
Epidemiologic studies
A number of epidemiologic studies were performed in the 1970’s to determine the health hazards,- of chronic
exposure to anesthetic gases, including birth defects and spontaneous abortions.4142 All the studies found similar results
and the most consistent finding was that the rate of miscarriage among exposed women is approximately 25-30% greater
than non-exposed women. However, all these studies were later criticized for their lack of a control group, low response
rate to questionnaires, recall bias, and statistical inaccuracies.43,44
Outcome studies of women who had surgery while pregnant
There have also been a number of retrospective studies of pregnant women who had undergone surgery to seek
an association between anesthesia and surgery and congenital defects, spontaneous abortions or fetal demise. The largest
study to date was performed by Mazze and Kallen.2 They linked the data from three Swedish health registries - the
Medical Birth Registry, the Registry of Congenital malformations, and the Hospital Discharge registry for the 9 year
period 1973-1981. They examined the data for four adverse outcomes; congenital defects, stillborn infants, infants born
alive but who died within 7 days, and infants with a birth weight < 1,500 grams and < 2,500 grams. They found 5,405
women had undergone surgery during their pregnancy from a total of 720,000 pregnancies. In their data set, most
procedures were performed during the first trimester (41.6%), and the incidence decreased during the second (34.8%)
and third (23.5%) trimesters. Most of the cases (54%) were done with general anesthesia, almost all of them (>98%)
with nitrous oxide. They were not able to find an increase in congenital abnormalities or stillborn births among those
who underwent surgery while pregnant during any trimester. However, the number of babies born with a birth weight <
1,500 and 2,500 grams, and the number of babies who died within 7 days of the operation was greater in those who
underwent surgery while pregnant. This was true during all three trimesters. These risks could not be linked to either the
specific anesthetic agents or the anesthetic technique. The increased risk to the fetus may be due to the condition that
necessitated surgery in the first place, with the highest rate in gynecologic procedures. These data are important because
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they clearly demonstrate that anesthetic agents are not teratogenic and that the greatest risk is premature labor with the
delivery of a low birth weight baby.
Behavioral teratology and Apoptosis in the newborn brain

In 1963 Werboff and Kesner 45 used the term behavioral teratology to describe the adverse action of a drug
on the behavior of the offspring to its environment. It is well known that the halogenated agents particularly
halothane and enflurane cause learning deficits in rodents.46,47 Most anesthetic agents act by either blocking N-
methyl-d-aspartate (NMDA) receptors or by enhancing GABA. Studies have demonstrated that when agents that act
by either of these mechanisms (e.g., ketamine, nitrous oxide, midazolam, barbiturates and volatile agents) are
administered to the rodent during the period of synaptogenesis, they induce widespread neuronal apoptosis in the
developing brain.48,49 Learning deficits have been described in the offspring of female rats exposed to commonly
used anesthetic agents and widespread neurodegeneration was seen on histological examination.50 The concern in
the animal model extends beyond directly anesthetizing the animal but also anesthetizing the mother while she is
pregnant. There are animal studies that demonstrate widespread apoptosis in the developing fetus and behavioral
issues once born,51,52 and one study suggested that environmental enrichment mitigated the effects on the offspring.
Although an association between anesthetic agents and neuronal apoptosis has been demonstrated in the
animal model, extrapolation from animal studies to humans is problematic at best.53 While most organ systems have
completed development by the end of the first trimester or earlier, the brain continues to develop until after delivery.
The time of greatest concern is during synaptogenesis or rapid growth spurt which is from the third trimester until
three years of age. Randomized trials to confirm apoptosis in the human brain obviously cannot be done and
evaluating effect of anasthesia on the brain is complicated. Recently two separate authors assessed the effect of
anesthesia and surgery on human behavior later in life. One looked at learning disabilities 54 and the other deviant
behavior.55 Both found an association between surgery and anesthesia and their outcome measures. The studies are
far from conclusive as they were not randomized, and one was only a survey,55 but they certainly highlight the need
for well controlled studies. At this point it is premature to make any changes in anesthesia practice based on the
data to date and the FDA at an advisory committee meeting came to the same conclusion.56
Avoidance of intrauterine fetal asphyxia

The most important consideration for the fetus during non-obstetric surgery is the maintenance of a normal
intrauterine physiologic milieu and avoidance of intrauterine fetal asphyxia. Fetal oxygenation is directly dependent on
maternal arterial oxygen tension, oxygen carrying capacity, oxygen affinity, and uteroplacental perfusion. It is therefore
critical to maintain a normal maternal PaO2, PaCO2 and uterine blood flow.
Mild to moderate maternal hypoxemia is generally well tolerated by the fetus because fetal hemoglobin has a
high affinity for oxygen. However, severe hypoxia will lead to fetal death. General anesthesia is a particular risk to the
pregnant woman because management of the airway can be difficult, and the rate of hemoglobin oxygen desaturation is
increased due to the decreased functional residual capacity and increased oxygen consumption. Care must also be taken
during a neuraxial anesthetic because a high dermatomal level of anesthesia, a toxic local anesthetic reaction, or
oversedation can also lead to a hypoxic event. Elevated maternal oxygen tension commonly occurs during general
anesthesia. Some have expressed concern that increasing the inspired oxygen level to the mother could be detrimental to
the fetus by causing premature closure of the ductus arteriosus or retrolental fibroplasias. However, due to placental
shunting of blood, fetal PaO2 never rises above 60 mmHg even if maternal PaO2 is 600 mmHg. Therefore, maternal
inspired oxygen concentration should not be limited.
Both maternal hypercapnia and hypocapnia can be detrimental to the fetus. Severe hypocapnia produced by
excessive positive pressure ventilation may increase mean intrathoracic pressure, decrease venous return and lead to a
decrease in uterine blood flow. In addition, maternal alkalosis, as produced by hyperventilation, will decrease uterine
blood flow by direct vasoconstriction, and it will decrease oxygen delivery by shifting the maternal oxyhemoglobin
dissociation curve to the left. Severe hypercapnia is detrimental because carbon dioxide readily crosses the placenta and
is associated with fetal acidosis and myocardial depression.
Uterine blood flow is affected by both drugs and anesthetic procedures. Placental blood flow is directly
proportional to the net perfusion pressure across the intervillous space and inversely proportional to the resistance.
Perfusion pressure will be decreased by hypotension which may be due to the sympathectomy from local anesthetics
administered as part of an epidural or spinal anesthetic, from aorto-caval compression in the supine position, or from
hemorrhage.
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Prevention of premature Labor

Spontaneous abortions, premature labor and preterm delivery are the most significant risks to the fetus during
maternal surgery,1,2,36,37 It is unclear if this is due to the surgery, anesthetic or underlying medical condition, but the
greatest risk is during gynecologic or pelvic procedures when there is uterine manipulation and the lowest risk
occurs during the second trimester. The potent inhaled anesthetic agents decrease uterine tone and inhibit uterine
contractions so from this perspective they may be beneficial. Also, medications that increase uterine tone such as
ketamine at doses > 2 mg/kg should theoretically be avoided. No study, however, has ever documented that any
particular anesthetic agent or technique is associated with a greater or smaller incidence of abortion or preterm labor.
Laparoscopic surgery
Once considered an absolute contraindication during pregnancy, laparoscopic surgery is now routinely
performed.57,58 Reedy et al.59 compared five fetal outcome variables among pregnant women who had a laparotomy
(n=2,181) versus those who had laparoscopy (n=1,522) between the fourth and twentieth week gestation, and the general
pregnant population who did not undergo surgery. They found that there was an increased risk of preterm delivery and
low birth weight (<2,500 grams) in both surgical groups as compared to the general population. But there was no
difference in any of the other outcome variables between the two surgical groups.
Specific anesthetic considerations during laparoscopy include maintaining normocarbia because carbon dioxide
is commonly used to maintain a pneumoperitoneum. Adjusting maternal ventilation to maintain end tidal carbon dioxide
between 30 and 35 mmHg should avoid hypercarbia and fetal acidosis. The Society of American Gastrointestinal and
endoscopic surgeons proposed guidelines for laparoscopic surgery during pregnancy. Surgical concerns include caution
during placement of the trochars which can be accomplished as an open technique and maintaining low
pneumoperitoneum pressures (< 15 mm Hg) to maintain uterine perfusion.60
Fetal heart rate monitoring

Fetal heart rate (FHR) monitoring becomes feasible around 16-18 weeks with an external tocodynamometer,
but the indication for its use intraoperatively is less well defined, and it obviously cannot be used in every case such as
abdominal procedures. One issue is how to act on the information? If the fetus is not viable and the FHR tracing is
concerning, all that can be done is normalize the physiologic milieu. Is this sufficient reason to use the monitor when
this should be done anyway? Katz et al.61 reported a case in which they were able to correct an abnormal fetal heart rate
in a woman who was undergoing eye surgery, by increasing the percentage of inspired oxygen given to the mother.
Another issue is who should interpret the tracing. Anesthetic agents will change the FHR baseline and decrease
variability and these changes need to be distinguished from fetal compromise. Furthermore, if a change is noted and the
fetus is viable will the obstetrician intervene with immediate delivery?
The American College of Obstetricians and Gynecologists issued a joint statement with the American Society
of Anesthesiologists on this issue.62 General guidelines from the statement include:
1. A qualified individual should be readily available to interpret the FHR.
2. If the fetus is below a viable gestation, it is generally sufficient to ascertain the FHR before and after the
procedure, but that in “select circumstances” intraoperative monitoring may be considered to facilitate
positioning or oxygenation interventions”
3. If the fetus is viable then simultaneous FHR and contraction monitoring should be performed before and
after the procedure and an obstetric provider should be available and willing to intervene for fetal
indications
The statement concludes by stating, “the decision to use fetal monitoring should be individualized”… and “ultimately,
each case warrants a team approach for optimal safety of the woman and fetus”.
General Recommendations for anesthetic management
Whenever possible, anesthesia and surgery should be avoided during the first trimester. Although no anesthetic
drug has been proven teratogenic in humans it is prudent to minimize or eliminate fetal exposure during this period of
organogenesis if at all possible.
Prior to initiating any anesthetic an obstetrician should be consulted and fetal heart rate tones should be
documented. Precautions against aspiration should be taken from as early as the 12th week and a clear nonparticulate
oral antacid, H2 receptor blocker and metoclopramide should be considered.
Apprehension should be allayed by reassurance from the anesthesiologist rather than with premedication, if
possible. The patient should be informed that there is no known risk to the baby regarding congenital malformations but
that there is an increased risk of abortion or premature labor. This is a good opportunity to educate the patient as to the
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signs of premature labor, e.g., back pain in someone prior to term, which can occur up to one week after the procedure.
The patient should be transported to the operating room with left uterine displacement to avoid aorto-caval compression
after 16-18 weeks gestation.
In addition to the standard ASA intraoperative monitors, the fetal heart rate and uterine tone should be
monitored, if at all possible. It is the best way to assure maintenance of a normal physiologic milieu for the baby.
Monitoring and interpretation should be performed by an obstetrician or someone other than the anesthesiologist with
expertise in FHR interpretation. Regardless of the decision to perform intraoperative FHR monitoring, the FHR and
uterine contractions should be monitored before and after the surgery.
The type of anesthesia should be based on maternal indications, the site and nature of the surgery, and the
anesthesiologist’s experience. Because MAC is decreased, the dose of all anesthetic agents for regional or general
anesthesia should be reduced. Although no study has found any difference in neonatal outcome in terms of congenital
defects or preterm delivery, regional anesthesia may be preferable to general anesthesia to avoid the risk of pulmonary
aspiration and decrease fetal drug exposure.
The largest risk of neuraxial anesthesia is hypotension, which reduces uteroplacental perfusion. Prevention of
hypotension is difficult since prehydration does not reliably reduce the incidence of hypotension. If hypotension occurs
ephedrine or phenylephrine can be used and there may be a benefit to phenylephrine. The key is not which drug is
chosen but that hypotension should be treated quickly.
General anesthesia should be preceded by careful evaluation of the airway, denitrogenation, and a rapid
sequence induction with the application of cricoid pressure. Edema, weight gain and increase in breast size may make
tracheal intubation technically difficult. An array of laryngoscope blades and handles, and other emergency airway
management equipment should be available. Capillary engorgement of the mucosal lining of the upper airway
accompanies pregnancy. This mandates extreme care during manipulation of the airway and the use of a smaller-than-
normal tracheal tube. The use of a nasal airway and naso-tracheal intubation should be avoided. A high inspired
concentration of oxygen should be used (at-least 50%) and arterial pCO2 should be maintained at normal pregnancy
levels (30-35 mmHg). End-tidal CO2 is an excellent approximation of paCO2 in the pregnant patient because the
arterial-to-end-tidal CO2 gradient decreases during pregnancy.
Fetal heart rate and uterine activity monitoring should continue postoperatively. Epidural or subarachnoid
opioids are an excellent choice for pain management because they cause minimal sedation and smaller doses can be
utilized compared to the intramuscular or intravenous routes. Non-steroidal anti-inflammatory drugs should be avoided
because they may cause premature closure of the ductus arteriosus.
Regardless of the technique, attention to detail and maintenance of a normal intra-uterine physiologic milieu
throughout the perioperative period, including the avoidance of hypotension, hypoxemia, hypercarbia, hypocarbia,
hypothermia and acidosis, is the key to a successful outcome.
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32. Mazze RI, Fujinaga M, Rice SA, et al. Reproductive and teratogenic effects of nitrous oxide, halothane, isoflurane and enflurane in Sprague-Dawley rats.
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45. Werboff J, Kesner R. Learning deficits of offspring after administration of tranquilizing drugs to the mothers. Nature. 1963;197:106-7.
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59. Reedy MB, Kallen B, Kuehl TJ: Laparoscopy during pregnancy: a study of five fetal outcome parameters with use of the Swedish Health Registry. Am J Obstet
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Extubation of the Difficult Airway with a Focus on Patient Outcomes
Maged Argalious, MD, MSc, MBA, MEd Cleveland, OH
Data from the American Society of Anesthesiologists (ASA) Closed Claims Project showed that 17 % of brain
injuries and deaths occurred after extubation in the operating room or postanesthesia care unit (PACU). (1-2) After
the introduction of guidelines for the management of difficult intubation, claims of airway-related injury at the
induction of anesthesia significantly decreased, while the claims arising from airway injury at extubation remain
unchanged. Among claims for failed extubation reported since 2000, death and permanent brain damage occurred in
15 of 16 claims (94%), and there were 8 claims with difficult airway management that occurred postextubation in
the recovery period, all (100%) resulting in death/brain damage. (3)
Learning Objective 1: Formulate a stepwise approach to the safe extubation of patients with a difficult
airway
Tracheal extubation is an elective process and should follow a stepwise approach. Before extubation of patients the
following steps need to be followed:
1- Adherence to evidence based extubation criteria( table 1)
2- Identification of potential causes for extubation failure (table 2)
3- Decision on whether the patient will be extubated awake or deep. Patients with a difficult airway ( difficult
intubation and or ventilation), patients at risk of aspiration, patients with questionable baseline conscious
level and obese patients may not be candidates for deep extubation
4- A preformulated plan for reintubation in case of extubation failure including access to all the required
equipment and medications
5- Established institutional protocols that guide extubation timing after complex surgery with close
communication of the perioperative team (surgical, anesthesia, respiratory therapist, nursing).
Examples include anteroposterior cervical spine surgeries, maxillomandibular advancement surgery for
OSA
6- Consideration for routine fiberoptic evaluation prior to extubation for evidence of resolution of laryngo-
pharyngeal edema in select surgeries (4)
Table 1: Extubation criteria (5):

a- General criteria
Awake, cooperative patient
Hemodynamic stability on no or minimal vasopressors
Absence of surgical bleeding or coagulopathy
Temperature ≥ 36 °C
b- Mechanical criteria:
Tidal volume ≥ 6 ml/kg
Vital capacity ≥ 15 ml/kg
Negative inspiratory force ≥ 30 cm H 2 O
Rapid shallow breathing index (Respiratory Rate/Tidal Volume) <100
c- Chemical criteria:
PH ≥ 7.25
PaO 2 /FIO 2 ratio >300
PaO 2 ≥ 65 mmHg on FiO 2 ≥ 0.4
Minimal PEEP of 5–8 cm H 2 O
Acceptable PaCO2 (PaCO 2 ≤ 50 mmHg)
Stable metabolic status (serum HCO 3 ≥ 20 mmHg)
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Table 2: Risk factors for extubation failure (6):

a- Pharyngeal obstruction
Glossoptosis, low tidal volumes, reduced cough strength, accumulation of airway secretions, or retropharyngeal
hematoma (anterior cervical spine surgery)
b- Laryngo-tracheal obstruction
Edema of the larynx, laryngospasm, vocal cord paralysis, tracheomalacia
c- Pulmonary etiology
Pulmonary edema (cardiogenic, noncardiogenic negative pressure), atelectasis, pneumothorax, pneumonia, ARDS,
d- Bleeding or mass lesions
External or internal hematoma/ bleeding compressing or obstructing the airway or presence of an airway, substernal
or mediastinal mass
Learning objective 2: Correct performance and interpretation of the cuff leak test
Post-extubation stridor and upper-airway obstruction are multifactorial in etiology and can occur as a result of
laryngotracheal edema, intubation trauma, excessive cuff pressure with mucosal ulceration, and prolonged
intubation with secondary inflammation and granuloma formation.(7)
Cuff leak tests (CLTs) were introduced in an attempt to predict post-extubation upper-airway obstruction and reduce
the incidence of extubation failure. Qualitative CLTs were performed by deflating the endotracheal tube (ETT) cuff,
blocking the ETT opening, and listening for an audible leak around the ETT while patients were spontaneously
breathing.(8) In an effort to increase the accuracy of CLTs in detecting post-extubation stridor, methods of
quantifying a cuff leak were introduced. Miller and Cole (9) described the cuff-leak test with the
ventilator set in assist-control mode at a tidal volume (VT) of 10–12 mL/kg. An inspiratory VT and 6 subsequent
expiratory VT values were recorded after oropharyngeal suctioning and ETT cuff deflation. The cuff leak was
measured as the difference between the preset inspiratory VT and the average of the 3 lowest of the subsequent 6
expiratory VT values. The threshold cuff-leak volume was determined by visual inspection of the receiver-operating
characteristic plot. A leak of <110 mL was considered a positive result of the CLT and indicated that patients were
at risk for post-extubation stridor secondary to laryngeal edema. (9)
This quantitative cuff leak has been expressed as an absolute volume or as a percentage of the inspired VT.
When the cuff leak volume is < 110–130 mL (9, 10) or <10– 15.5% (11, 12) of the delivered VT, the risk for post-
extubation stridor is significantly elevated. Other attempts have focused on quantifying a cuff leak volume in
spontaneously breathing patients receiving CPAP. (13) The leak volume was calculated as the difference between
the expiratory VT with inflated cuff and the expiratory VT with deflated cuff.
Even with quantifiable cuff leak volumes, studies reported a low sensitivity and a low positive predictive value of
cuff leak volumes in detecting post-extubation stridor.(9,10,11,14) This was attributed to several factors, including
the lack of standardization of the ratio of ETT size to the laryngeal diameter (a large ETT will result in a smaller
cuff leak volume for the same laryngeal diameter), and the possible contribution of the exhaled limb of the breathing
circuit and the ventilator to an increased airway resistance and therefore an increase in cuff leak volume.
Most studies on cuff leak volume document a high specificity and a high negative predictive
Value, which means that patients with a cuff leak volume above a certain threshold (cuff
leak volume >15% of VT or > 140 mL) have a low probability of developing post-extubation stridor. Incorporating
the CLT into the clinical decision making tree may avoid unnecessary delays in extubating patients for fear of
post-extubation stridor, once other extubation criteria are met. (15) While there is currently no evidence that
delaying extubation of patients with a positive CLT improves outcomes, a positive cuff leak test should be
considered a risk factor for extubation failure and should trigger the formulation of the stepwise approach to patient
extubation outlined above under objective.
Learning objective 3: Identify the correct and safe use of airway exchange catheters in the extubation of the
difficult airway
Although the presence of an airway exchange catheter does not guarantee success at subsequent reintubation, a high
success rate of reintubation has been reported with their use. 16, 17 In addition, oxygen insufflation through an
airway exchange catheter (AEC) can maintain oxygenation until definitive measures are taken to secure the airway
(e.g., tracheal intubation, cricothyroidotomy, and tracheostomy).
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Numerous AECs are available, but these devices must be used correctly because airway complications can develop
(e.g., perforation of the tracheobronchial tree, failure to pass the ETT over the AEC, barotrauma) when the wrong
size, type, or technique is used. (18—24)
Suggestions for success include the following:
 AECs with a very small outer diameter should be avoided because they are prone to kinking, making
railroading of the new ETT difficult
 Match the marking of the AEC with the centimeter markings on the ETT to avoid excessive advancement
of the AEC, which can irritate the carina and cause bronchial trauma and bleeding
 Use an AEC with an inner hollow lumen that allows oxygen insufflation, whether by jet ventilation or a bag
valve device.
 If resistance is encountered during the advancement of the ETT over the AEC, oral laryngoscopy (if
feasible) can aid tube advancement. Rotation of the ETT in 90-degree increments also helps to pass the
ETT tip past the arytenoids. ETTs with flexible tips serve the same purpose in that the tube tip is prevented
from becoming caught against the arytenoids
 Avoid using force in advancing the AEC and the ETT because it may traumatize airway structures (21)
 Applying a silicone-based spray or a lubricant gel on the outside of the AEC can facilitate tube
advancement
 The position of the new ETT should be confirmed before the AEC is withdrawn. This can be done by end-
tidal capnography through a flexible bronchoscope adapter. (18)
 Longer AECs are available for double-lumen tubes and can be used with the same precautions
Learning Objective 4: Organize the steps required for management of the airway in patients with failed
extubation, including patients with expanding neck hematoma
A preformulated plan for resecuring the airway in cases of extubation failure is an essential step in planning for
extubation and involves (3):
1- A multidisciplinary approach that ensures immediate availability of experienced personnel (anesthesia and
surgical teams, respiratory therapists)
2- Airway management equipment ( oxygen source, suction, AEC, oral and nasopharyngeal airways,
supraglottic ventilation devices, endotracheal tubes of different sizes, variety of laryngoscopes and
fiberoptic scope, jet ventilation, cricothyroidotomy kit).
3- Resuscitation and induction medications
4- ASA monitoring including capnography
5- Extubation setting: OR, PACU, ICU, with bed controls that allow easy access to the patient’s airway
6- Additional surgery specific strategies: (airway surgeries, neck surgeries, maxillofacial surgeries)
Table 3 outlines the steps in management of patients with an expanding neck hematoma (25)
Table 3: Management of Postoperative Neck Hematoma (25)

1- Apply pressure to bleeding site
2- Notify surgery and anesthesia team (call for help)
3- Consider reversal of residual anticoagulation
4- Tight blood pressure control
Outcome:
A- No further hematoma expansion
 Communication with surgical team
 Mark the boundaries of the hematoma for early identification of further expansion
 Close observation and extended (8-12 hours) monitoring in a critical care environment
B- Continuous expansion of hematoma with no airway compromise
 Awake (fiberoptic) intubation either in the PACU or after immediate transfer to the operating room after
topical anesthesia to the airway followed by general anesthesia for exploration of wound and drainage of
neck hematoma.
 Assess neurologic status at the end of the case.
 Consider maintaining the patient intubated postoperatively until resolution of reactionary airway edema
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C-Expansion of neck hematoma with rapidly progressive airway compromise

Emergent intubation (ASA algorithm):
 Cannot intubate Can Ventilate: using face mask, oral or nasal airways, laryngeal mask airway:
o Consider immediate surgical drainage of the neck hematoma followed by further attempts to
secure the airway
 Cannot intubate Cannot ventilate:
o Surgical airway (Emergent cricothyroidotomy, percutaneous or surgical tracheostomy)
o Evacuation of hematoma and wound exploration
o Neurologic assessment
o Maintain airway secured postoperatively
Learning objective 5: Recognize how safe extubation of patients with a difficult airway can impact patient
outcomes using Kirkpatrick’s 4th level of evaluation model
Most of the data on airway related complications occurring during extubation (including death and neurologic
injury) arise from the ASA closed claims project database. (1) While this continues to be an important source of
data, there are several limitations to the exclusive use of closed claims data for identifying trends in complications
including:
1- On average, it takes 5 years between the dates of an injury to the entry of a claim into the closed claims
project database, creating a very long feedback loop.
2- Closed claims are biased towards more severe injuries, meaning that routine cases of extubation failure as
well as near misses are not included in the database
3- Not all cases of severe airway related injuries result in a claim, meaning that the numbers in the data are an
under-representation.
So how can we enhance patient outcome and reduce the number of extubation failures and extubation related
complications:
1- Adopting evidence based extubation protocols (surgery specific in special situations)

2- A robust, accurate mechanism for identifying and reporting cases of extubation failure at the local (
departmental) level with quality committee oversight that conduct peer review, and provide
recommendations with a short feedback cycle
3- Adopting a universal definition for extubation failure that allows reporting of its incidence to national
organizations concerned with quality and performance improvement including Aspire ( Anesthesiology
Performance Improvement and Reporting Exchange and AQI (the Anesthesia Quality Institute)
4- Sharing best practices and evidence based extubation protocols among anesthesiology departments and
through peer reviewed publications
5- Avoiding unintended consequences of the use of extubation failure alone as a quality metric since this may
result in a paradoxical increase in the incidence of patients being kept intubated at the end of surgery.
Tracking other related quality metrics (e.g.: prolonged mechanical ventilation) should be considered.
6- Use of collected data on patterns of airway injury to update airway management algorithms
By addressing practice variations and tracking protocol adherence, identifying best practices, and providing a shorter
ongoing feedback loop to departments, patient outcomes can be improved
Linking Kirkpatrick’s Evaluation Model to Patient Outcomes
Level Definition Method of evaluation

1- Reaction participants react favorably to the Participant survey
learning event
2- Learning participants acquire the Pre and posttest questionnaires
knowledge, skills and attitudes
based on their participation
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3- Behavior participants apply what they Simulation activities, OSCEs, quality metrics, peer
learned during the session when morbidity and mortality reviews, root cause analysis
they are back on the job
4- Results Patient outcome Rate of extubation failure, rate of reintubation in
PACU, rate of reintubation within 24 hours, rate of
postoperative medical emergency team activation
due to airway related issues
References:
1- Peterson GN, Domino KB, Caplan RA, Posner KL, Lee LA, Cheney FW. Management of the Difficult
Airway. A Closed Claims Analysis. The Journal of the American Society of Anesthesiologists. 2005 Jul
1;103(1):33-9.
2- Apfelbaum JL, Hagberg CA, Caplan RA, Blitt CD, Connis RT, Nickinovich DG, Benumof JL, Berry FA,
Bode RH, Cheney FW, Guidry OF. Practice Guidelines for Management of the Difficult AirwayAn
Updated Report by the American Society of Anesthesiologists Task Force on Management of the Difficult
Airway. The Journal of the American Society of Anesthesiologists. 2013 Feb 1;118(2):251-70.
3- Cavallone LF, Vannucci A. Extubation of the difficult airway and extubation failure. Anesthesia &
Analgesia. 2013 Feb 1;116(2):368-83.
4- Li KK, Riley RW, Powell NB, et al. Postoperative airway findings after maxillomandibular advancement
for obstructive sleep apnea syndrome. Laryngoscope 2000;110:325–7.
5- Argalious M. Postoperative Anesthesia Care. In Basic Clinical Anesthesia 2015 (pp. 575-584). Springer
New York.
6- Argalious M. Management of Postanesthesia Care Unit Emergencies. ASA Refresher Courses in
Anesthesiology. 2009 Jan 1;37(1):1-2.
7- Epstein SK. Preventing postextubation respiratory failure. Crit Care Med 2006;34(5):1547-1548.
8- Potgieter PD, Hammond JM. “Cuff” test for safe extubation following laryngeal edema. Crit Care Med
1988;16(8):818.
9- Miller RL, Cole RP. Association between reduced cuff leak volume and postextubation stridor. Chest
1996;110(4):1035-1040.
10- Jaber S, Chanques G, Matecki S, Ramonatxo M, Vergne C, Souche B, et al. Postextubation stridor in
intensive care unit patients. Risk factors evaluation and importance of the cuff-leak test. Intensive Care
Med 2003;29(1):69-74.
11- De Bast Y, De Backer D, Moraine JJ, Lemaire M, Vandenborght C, Vincent JL. The cuff leak test to
predict failure of tracheal extubation for laryngeal edema. Intensive Care Med 2002;28(9):1267-1272.
12- Sandhu RS, Pasquale MD, Miller K, Wasser TE. Measurement of endotracheal tube cuff leak to predict
postextubation stridor and need for reintubation. J Am Coll Surg 2000;190(6):682-687.
13- Antonaglia V, Vergolini A, Pascotto S, Bonini P, Renco M, Peratoner A, et al. Cuff-leak test predicts the
severity of postextubation acute laryngeal lesions: a preliminary study. Eur J Anaesthesiol 2010;27(6):534-
541.
14- Engoren M. Evaluation of the cuff-leak test in a cardiac surgery population. Chest 1999;116(4):1029-31.
15- Argalious MY. The Cuff Leak Test: Does It “Leak” Any Information?. Respiratory care. 2012 Dec
1;57(12):2136-7.
16- Mort TC: Continuous airway access for the difficult extubation: The efficacy of the airway exchange
catheter. Anesth Analg 2007; 105:1357--62.
17- Loudermilk EP, Hartmannsgruber M, Stoltzfus DP, Langevin PB: A prospective study of the
safety of tracheal extubation using a pediatric airway exchange catheter for patients with a known difficult
airway. Chest 1997; 111:1660--5.
18. Takata M, Benumof JL, Ozaki GT: Confirmation of endotracheal intubation over a jet stylet: In vitro
studies. Anesth Analg 1995; 80:800--5.
19. Benumof JL: Airway exchange catheters: Simple concept, potentially great danger.Anesthesiology 1999;
91:342--4.
20. Cooper RM: The use of an endotracheal ventilation catheter in the management of difficult extubations. Can
J Anaesth 1996; 43:90—3.
21. Benumof JL: Airway exchange catheters for safe extubation: The clinical and scientific details that make
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the concept work. Chest 1997; 111:1483--6.

22. Argalious M, Ritchey M, deUngria M, Doyle DJ: An airway exchange catheter contributing to airway
obstruction. Can J Anaesth 2008; 55:128--9.
23. Argalious M, Doyle DJ: Questioning the length of airway exchange catheters. Anesthesiology 2007;
106:404.
24. Argalious M: Airway challenges in PACU/ICU. Anesthesiol News 2005; 31:57--61.
25.Argalious M: Postoperative hematoma and airway compromise after carotid endarterectomy . In
Case Studies in Neuroanesthesia and Neurocritical Care, edited by George A. Mashour and Ehab Farag,
Cambridge University Press, 2011.
26. Kirkpatrick DL. Evaluating training programs: The four levels Berrett-Koehler. San Francisco. 1994.
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Perioperative Management of Pulmonary Arterial Hypertnsion and RV

Dysfunction.
Eric Jacobsohn, MBChB, MHPE, FRCPC Winnipeg, CANADA
Key points:
 The physiology of patients with PAH involves complex cardiopulmonary interactions.
 PAH patients are at high risk for complications and ideally should be managed in specialty centers.
 Complications, including death, can often be prevented by understanding the conditions causing
perioperative deterioration.
 Many monitoring modalities are important in at risk patients. The choice is patient/ situation specific. The
CVP is a very useful monitor, as a low CVP generally means that the RV is coping, while a high CVP
portends trouble. In high risk patients, continuous monitoring of RV function with echocardiography and
PA pressures with a PA catheter may be helpful.
 Systemic hypotension, from any cause, is disastrous in patients with PH. It causes further displacement of
the intraventricular septum towards LV, globular dilation of RV, further RV dysfunction of the already
compromised RV, and reduced coronary artery perfusion. This leads to a rapid and lethal spiral.
 Emergency vasopressors must be must be in-line and “ready to go” when caring for these patients, and
should start while searching for the cause of the hypotension. Use incremental boluses of vasopressin,
starting with boluses of 0.2 to 0.4 U (20U vasopressin in 100ml diluent = 0.2U/ml), rapidly escalating if
needed, and start an infusion of 2.4U/hr. (12ml/hr. of aforementioned solution). Also start a norepinephrine
infusion at 0.05mcg/kg/min, and titrate as required.
 The cause of acute RV failure in the setting of PH is often multifactorial and includes: factors that
exacerbate the existing PAH (increased PVR), change in RV function due to changes in volume, rate,
rhythm, septal position, and contractility. The causes must be immediately treated.
 PVR is dependent on many factors that can be manipulated in the perioperative period. Most acute
increases in PVR can be remedied by the non-pharmacological methods, especially those factors that
affecting functional residual capacity and PVR. An inhaled pulmonary vasodilator must be immediately
available if these measures are not successful.
 Delay in treating acute RV failure causes rapid multiple organ system failure (MOSF) due to “the double
hit” phenomenon.
 Institution of acute mechanical circulatory assist (peripheral VA ECMO) must be available in very high
risk cases. It must be started early in the cycle of RV deterioration, before the onset of organ injury.
Introduction
Pulmonary hypertension (PH) and the associated right ventricular (RV) dysfunction are increasingly being
encountered in the perioperative period. Managing these patients is challenging as they have a high morbidity and
potentially high mortality. A thorough understanding of the pathophysiology of PH and the related RV dysfunction
allows the practitioner to anticipate, prevent, and successfully manage these patients. Normal systolic, diastolic, and
mean PA pressures are 25, 10, and 15 mmHg, respectively; the normal range for pulmonary vascular resistance
(PVR) is 0.9–1.4 Wood units or 90–120 dynes • s • cm–5. PVR = (ΔP)/flow, where ΔP represents the mean
pulmonary artery pressure (mPAP) minus the left atrial pressure (LAP), and flow is the cardiac output (CO). The
gradient between mPAP and LAP is the transpulmonary gradient (TPG). If the TPG is elevated, there is an increase
in PVR; on the contrary, if the TPG is not elevated, the increase in mPAP is caused by an elevation in LAP resulting
from left heart pathology. Thus, PVR = (mPAP – LAP) ÷ CO, or mPAP = LAP + (CO × PVR). Therefore, only
three physiological factors could cause a rise in mPAP: (1) increased LAP, (2) increased pulmonary flow
(congenital heart disease with L to R shunt), and (3)increased PVR (caused by pulmonary parenchymal/airway
disease, hypoxia, interstitial lung disease, thromboembolic disease, or idiopathic pulmonary artery hypertension
(PAH).1 Because of pulmonary vascular remodeling in the long run, even factors 1 and 2 could eventually lead to an
increased PVR, and the associated rise in mPAP will reflect both an increase in LAP as well as an eventual elevation
in PVR. For example, patients with mitral stenosis who have an increased mPAP solely because of elevated LAP
(without increased PVR, i.e., early or “reversible” PH) usually have an uncomplicated mitral valve replacement with
little risk of RV failure after surgery. In comparison, patients with mitral valve stenosis associated with a
preoperative increase in LAP, mPAP, and PVR (secondary to pulmonary vascular remodeling, i.e., “fixed” PH) may
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have severe RV failure after mitral valve replacement, which could lead to difficulty in weaning from bypass.
Acute-on-chronic increases in PVR are common in the perioperative period and can lead to acute decompensation in
RV function. Some of the factors responsible for acute exacerbations in PVR are hypoxia, hypercapnia, acidosis,
hypothermia (shivering), increased sympathetic tone (pain, anxiety), and exogenous or endogenous pulmonary
vasoconstrictors such as catecholamines, serotonin, thromboxane, and endothelin. Early recognition and reversal of
these causes of acute deterioration could be lifesaving. The majority of this educational session will be dealing with
the perioperative management of those patients with PAH, the factors that cause deterioration and how to recognize
and treat the acute deterioration. It will not focus on the patient with acute PH due to heart failure – the focus there is
treating the left heart, although some of the principles of supporting the acutely failing RV may also apply.
Definition and classification of pulmonary hypertension
The diagnosis, assessment and

management of patients with
PAH is largely based on
guidelines developed during the
World Symposia on Pulmonary
Hypertension (WSPH). The
guidelines are largely based on
the 4th WSPH held 2008, with
some clarifications to this at the
5th WSPH, in 2013. Normal
resting mPAP is 14 ± 3 mmHg,
with an upper limit of 20
mmHg. The significance of
mPAP between 21–24 mmHg is
unclear. The European Society
of Cardiology and Respiratory
Society define precapillary PH
as a persistent increase in mPAP
≥ 25 mmHg at rest as assessed
by right heart catheterization in
the setting of a normal pulmonary capillary wedge pressure (PCWP) of ≤15 mmHg, PVR ≥3 Wood units, and
normal or reduced cardiac output. They define postcapillary PH as a persistent increase in mPAP ≥25 mmHg at rest
as assessed by right heart catheterization (RHC) in
Fig. 2
the setting of an increased PCWP ≥15 mmHg, PVR
≥3 Wood units, and normal or reduced CO.2 The
definition of PH according to the American College
of Cardiology/American Heart Association 2009
Expert Consensus Document on Pulmonary
Hypertension is a measurement, by RHC, of a resting
mPAP ≥25 mmHg, PCWP/LAP ≤15 mmHg, and
PVR ≥3 Wood units.3 PH has undergone several
reclassifications over the past 20 years (Figure 1).4
There are 5 major categories: (1) pulmonary arterial
disease (PAH), (2) left heart disease, (3) lung disease
with hypoxemia (4) chronic thromboembolic PH
(CTEPH), (5) unclear and/or multifactorial causes.
Because this classification is not based on a
physiological approach, classification into
precapillary, postcapillary, and mixed PH may more
useful in the perioperative period (Figure 2).
Pathogenesis
PH is a syndrome resulting from a pathological increase in PVR that leads to restricted flow through the PA
circulation and, ultimately, RV failure. The loss of vascular cross-section due to remodeling is the predominant
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reason for the rise in PVR; however, excessive vasoconstriction may be a significant contributing factor in about
20% of patients.5 The vasculopathy, which predominantly affects small resistance pulmonary arteries, consists of
intimal hyperplasia, medial hypertrophy, adventitial proliferation, thrombus in situ, and varying degrees of
inflammation. There is an associated genetic proclivity, with several mutations having being identified. The lack of
penetrance in families with PAH suggests that some form of second “insult” is required, in addition to the mutation,
for PH to be manifested. Environmental factors associated with the development of PAH include hypoxia,
anorexigenics, and central nervous system stimulants. Hypoxia causes vasodilatation of systemic vessels but
vasoconstriction of the pulmonary vasculature, in part through the action of endothelin and serotonin. Acute hypoxia
further inhibits the function of voltage-gated K+-ATP channels of the pulmonary artery smooth muscle cells,
resulting in membrane depolarization, an increase in cytoplasmic calcium concentration, vasoconstriction, and
eventually PH. Endothelial dysfunction contributing to PAH involves increased production of vasoconstrictor and
mitogenic compounds such as endothelin-1, angiotensin II, serotonin, thromboxane A2, VIP, and deficient
production of vasodilators including prostacyclin and N.6 Prostacyclin, normally a potent local vasodilator, inhibits
platelet activation and has antiproliferative properties. These mechanisms are thought to be associated with PAH
that complicates the use of appetite suppressants and, in PAH of the newborn, the use of SSRIs in pregnancy.
Diagnosis and investigations

Most of the patients presenting for in the perioperative period will have had a full diagnostic workup and will be on
the appropriate therapy. The most common presenting symptoms in patients with PAH are related to
cardiopulmonary limitation: fatigue, dyspnea, chest pain, syncope, palpitations, and lower extremity edema.
Syncope is an ominous sign that predicts a poor prognosis. Signs of PH and RV failure include tachypnea,
tachycardia, distended neck veins, RV parasternal lift, audible TR murmur, RV S3 gallop, hepatomegaly, ascites,
and lower extremity edema. ECG, chest x-ray, and transthoracic echocardiogram (TTE) may display signs
suggestive of PH. A TTE should be done as soon as PH is suspected. Possible causes of PH that can be excluded or
confirmed by TTE are congenital and other heart disease, pulmonary emboli, and it assesses the severity of the
associated RV dysfunction. CTEPH must be excluded; 50% of patients with CTEPH have no prior history of
pulmonary embolism. The screening test of choice is radionuclide perfusion scanning. Spiral CT, although excellent
in ruling out acute PE, is less sensitive than perfusion scanning in excluding CTEPH. A right heart cath will
delineate the hemodynamic profile and assess the response to vasodilator therapy. Targeted serology is done to
delineate possible systemic disease. Liver and kidney functions assess the severity of chronic RV failure.
Polysomnography is done sleep apnea when suspected.
Long term therapy

Treatment goals include improvement and improving functional capacity (6-minute walk test, cardiopulmonary
exercise testing), lowering mPAP, normalizing CO, slowing progression of the disease, and improvement in
survival.3 Low-level aerobic exercise (walking) is
encouraged. Avoidance of high altitudes and oxygen
supplementation on commercial aircraft for patients
with room air saturations <92% is advised. Oxygen
therapy is indicated if RA saturations are < 90%.
Ideally, pregnancy should be avoided.
Anticoagulation with warfarin may improve survival.
Judicious use of diuretics and a sodium-restricted diet
are indicated in RV dysfunction. Calcium channel
blockers are indicated in only a very small group of
patients with idiopathic PAH who show vasodilator
responsiveness on RHC. BIPAP may improve PVR
and RV function in patients with OSA. There are 5
classes of drugs: prostanoids (IV, SC, inhaled, and
oral), phosphodiesterase inhibitors (PO), endothelin
antagonists (PO), guanylate cyclase stimulants (PO),
Fig. 3 and calcium channel blockers (PO) (Figure 3). The
choice of agent is largely dependent of the disease
severity, the availability of the drug in a particular
country, cost, medical support in a particular
community (ability to deliver home IV infusions), patient preference and other factors. Severely ill patients with
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functional class IV symptoms are still stabilized with IV prostanoid therapy (prostacyclin, treprostinil). However,
due to the significant invasiveness and cost associated with this delivery method, less invasive therapies have
evolved. Treprostinil can be given subcutaneously, and iloprost can be given by inhalation. Oral prostanoid therapy
is now a reality, with selexipag (selective agonist of the prostacyclin IP receptor) and oral treprostinil. Several
studies have shown improvement in symptoms, exercise tolerance, hemodynamics, quality of life, and survival.
Many patients eligible for prostanoid therapy do not receive it due to the very high cost. Although tachyphylaxis
occurs, the beneficial effects of prostanoids are sustained for years and many patients have been removed from
heart-lung transplantation lists as a result of these drugs. Activation of endothelin receptors causes pulmonary
vasoconstriction; the oral endothelin receptor antagonists (bosentan, ambrisentan, macitentan) are also used as first-
line oral therapy in less severely symptomatic patients. Oral phosphodiesterases(PDE) inhibitors (sildenafil,
tadalafil) are also first line agents in less severely symptomatic patients. PDE-3 and -5 are the enzymes that
metabolize cAMP and cGMP respectively, the second messengers of prostacyclins and NO. PDE augment cAMP-
and cGMP levels, causing vasodilation and decreased PVR. A new class of oral agent called the soluble guanylate
cyclase stimulators (riocuguat) increases the production of and sensitivity to cGMP. Depending of the response to
the initial oral first line agents, some patients may end up on combinations of the various agents.
Patients whose PH is associated with Eisenmenger syndrome (R to L shunt) generally have superior survival rates
compared to patients with idiopathic PAH, mainly because of decompression of a pressure-overloaded RV,
improved LV filling, and a resulting increase in CO. 8 Atrial septostomy is considered a palliative procedure and may
be a bridge to lung or heart-lung transplantation in patients with intractable RV failure.8 The shunt causes a decrease
in systemic arterial oxygen saturation that is compensated for by increases in CO and systemic oxygen delivery.
Pulmonary endarterectomy is an important therapy for some patients with CTEPH, notably those with a proximal
mechanical component amenable to surgery and a variable degree of distal arteriopathy amenable to medical
therapy. Identification of these patients is important, since CTEPH is underdiagnosed has a poor prognosis if
untreated.9 these procedures should only be done in high-volume centers. Bilateral lung transplantation (and
occasionally heart-lung transplantation) is the final option for a minority of patients in whom medical therapy has
failed or present in such an advanced stage that medical therapy is not an option. Although effective medical therapy
has reduced the rate of transplantation, death rates on waiting lists are high because of a global shortage of donor
organs. Only approximately 4% of lung and combined heart/lung transplants performed annually worldwide are for
patients with PH.10 Extracorporeal support is an important rescue option for acute RV failure caused by reversible
causes of increased PVR e.g. massive PE and others. VA ECMO has also been used as a bridge to lung
transplantation, support after lung transplant, treatment of severe reperfusion pulmonary edema after pulmonary
endarterectomy, and for RV failure unresponsive to medical therapy. 11,12 Patients with end-stage RV failure due to
idiopathic PAH have generally done poorly with RV assist devices, as the increased flow in a high resistance circuit
damages the pulmonary microcirculation, causing hemorrhage.
Long term prognosis

Predictors of poor prognosis include advanced NYHA Functional Class 3 or 4, rapid symptom progression, poor
exercise capacity, significant RV dysfunction, low CO, elevated brain natriuretic peptide, and an associated
diagnosis of scleroderma. The best survival rates are seen in patients with congenital heart disease associated with
PH. The natural history of idiopathic PAH reveals a median survival of 2.8 years with 1-, 3-, and 5-year survival
rates of 68%, 48%, and 34% respectively.13
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Perioperative RV failure in patients with PAH

Although often preventable, acute decompensation of patients with PAH during the perioperative period is common,
may be fatal, and results in acute RV cardiogenic shock. As recent as 2002, patients with Eisenmenger syndrome
undergoing cesarean section had a mortality of 70%. 14 In
2005, patients with PAH undergoing liver transplantation had
Fig. 4
Fig. 5
a reported mortality of 80%.15 It is noteworthy that

the perioperative risks associated with PAH have improved over the past decade, likely as a result of better chronic
medical management, risk stratification and perioperative management (Figures 4 and 5).
Emergency procedures, ASA class >2, intermediate- or high-risk surgery, longer duration of surgery (>3 hours),
coronary artery disease, chronic renal insufficiency,
history of PE poor functional class have been
identified as predictors of morbidity and mortality
after non-cardiac surgery. High-risk surgical
procedures are: significant perioperative systemic
inflammatory response, blood loss, high possibility of
venous or CO2 emboli (laparoscopic), fat or cement
Fig. 6A, 6B emboli, and lung resection. Surgery should be delayed
if possible if PVR is largely fixed on vasodilator
testing with inhaled NO, if moderate to severe PAH
with significant RV dysfunction is present. Some of
the important factors that impact these decisions are
also shown in figure 4. All attempts must be made to
optimize PVR before surgery, including maximizing
medical therapy and preventing conditions that may
cause acute deterioration. Patients on chronic PAH
therapy should continue their regimen throughout the
perioperative period, as discontinuation can precipitate
an acute PAH hypertensive crisis. Intravenous
prostacyclin has potent antiplatelet properties and
changing to inhaled therapy preoperatively should be
considered, especially if increased blood loss is
anticipated. In patients not on PAH-specific therapies, a preoperative RHC, vasodilator trial and PAH-specific
therapy should be started. Acute perioperative decompensation and the subsequent potentially lethal RV failure are
often under-recognized or misdiagnosed.
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Shock caused by acute RV failure is schematically presented in Figure 6 A, B and has a poorer prognosis as
compared to LV. RV failure (low end-organ inflow pressure due to reduced LV stroke volume and high end-organ
outflow pressure due to elevated RA pressure) has a worse prognosis than shock due to acute LV failure (only low
end-organ inflow pressure) because of the “double-hit” on end-organs, leading to rapid multiorgan failure. In
addition, elevation in RA may cause hypoxemia by R to L shunting across a PFO. It is important to note that TR is
common in acute and chronic RV failure; hence, thermodilution CO are not reliable at all. However, PA pressure
measurements are useful to monitor in selected patients to assess response to vasodilators, inotropes,vasopressors
and to assess the very helpful RV pressure curves (see below). Many issues in the perioperative period, some of
them “minor” by themselves, can critically affect the outcome of these patients. These include, among others, the
timing of extubation, meticulous management of mechanical ventilation, the surgical acumen, fluid and electrolyte
shifts, balancing the positive vs. negative effects of transfusion, intravascular volume optimization, acid-base
optimization (pH >7.4, PaCO2 30–35 mmHg, PaO2 >100 mmHg), avoiding hyperchloremia, temperature control,
optimized analgesia, and early restarting of noninvasive ventilation.
Prevention and treatment of perioperative complications

1. Optimize heart rate, rhythm: Restoring and maintaining SR is critical for optimal filling of a hypertrophied/dilated
RV. Because of the association of RV failure with TR, higher heart rates (80–100 bpm) may be desirable to reduce
end-diastolic volume. Furthermore, because an increase in RV stroke volume is limited by the increase in RV
afterload, it is best to avoid bradycardia as the RV CO becomes rate dependent. Early cardioversion should be
considered; the loss of SR may lead to acute RV shock. If pacing is possible, atrial or AV pacing may improve RV
diastolic filling. Electrolytes must be optimized to prevent arrhythmias. Efforts made to mitigate mechanical
irritation of the cardiac chambers by central lines (e.g. make certain the distal end of the central venous catheter does
not enter the RA).
2. Optimize RV filling : Perioperative CVP monitoring is crucial. In general, if the CVP is low, the RV must be
“coping” even if the PA pressure and PVR are elevated i.e. the RV has been “primed” (hypertrophied) as a result of
being exposed to high PA pressure and PVR over time, or it is truly under filled. On the other hand, an elevated
CVP may imply a failing RV, especially when accompanied by increasing size of V waves (worsening TR) and
decrease in PA pressure and CO (by clinical signs, pulse pressure, but no thermodilution). The compromised RV
will tolerate neither hypovolemia nor overfilling; therefore, an optimal position has to be determined and maintained
on the (compromised) RV Frank-Starling curve. Because the RV is mainly a “volume chamber,” it is less dependent
on preload than the LV. Thus, for a given increase in preload, a smaller increase in SV is expected. However,
because the normal RV it is thin walled, the RV is much more afterload dependent than the LV, and RV cardiac
output decreases significantly with an acute increase in mPAP. Past teachings have often suggested that the RV be
filled aggressively to passively increase pulmonary blood flow and CO. This may hold true when the PVR is normal
(Fontan physiology), but not when it is high i.e. the case of patients with PH. Excess volume loading in these
circumstances will result in acute RV distention, increased TR, further R to L shift of the interventricular septum,
and impaired LV filling, leading to a decrease in LV SV and CO . The resultant drop in systemic blood pressure
causes decreased right coronary artery perfusion as well as a decline in the transeptal gradient (TSG), and eventually
hemodynamic collapse. This is especially true once the CVP reaches values of 15–20 mmHg. Assessment of optimal
RV filling can be very difficult. Options include a fluid bolus (500 mL of Lactated Ringer’s solution) or
autotransfusion (by elevation of the patient’s legs). Ongoing fluid boluses are indicated if leg elevation causes a
modest (2–5 mmHg) increase in CVP and corresponding increase in PCWP, cardiac output, and/or blood pressure;
an increase in only the CVP (with minimal or no change in PCWP, cardiac output, or mean arterial pressure) likely
indicates RV distention and precludes further fluid boluses. A relatively underfilled RV is likely the lesser of the two
evils. Bedside TTE is invaluable. If TTE is not possible, TEE should be considered if intubation was to be part of
the perioperative plan. In patients with a PAC, monitoring RV filling pressures through continuous transducing of
the RV pressure tracing is an underused but invaluable tool (see below).16 The assessment of volume is therefore a
multimodal approach; no one approach is superior.
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3. Maintain RV myocardial performance: (Figure 7). This includes maintenance of RV coronary perfusion pressure
and RV inotropy. Normally, RV coronary perfusion occurs during systole and diastole. However, as the PVR and
RV systolic pressure rise, flow through the R coronary artery occurs mainly in diastole, similar to left. RV
subendocardial ischemia caused by myocardial oxygen supply-demand imbalance is common in PAH. Therefore,
systemic
Fig. 7
hypotension and
excessive increases
in RV systolic
pressure,
contractility, and
heart rate must be
avoided. When
acute RV failure is
suspected, the
systemic blood
pressure must be
increased
immediately to
ensure adequate
RCA perfusion
pressure and
restoration of TSG.
This can be
achieved by
optimizing volume
status and with early
use of
norepinephrine with
or without
vasopressin.
Accumulating clinical experience, as well as animal data, suggests that vasopressin causes little or no increase in
PVR, whereas norepinephrine through its alpha agonism, does increase PVR. Vasopressin binds to peripheral V1
receptors and causes systemic vasoconstriction while
Fig. 8 stimulating NO release and vasodilation in the pulmonary
circulation. The choice of anesthetic technique (GA versus
regional) and the anesthetic agents used are much less
important than understanding the possible physiological
perturbations that may result from either. All anesthetic
agents and techniques cause varying degrees of myocardial
and autonomic nervous system depression. In this regard,
volatile agents, propofol, thiopental, narcotics, ketamine,
and etomidate can all be used in the appropriate manner.
Contractility may need to be enhanced in the acutely failing
RV with either a β-adrenoreceptor agonist (dobutamine) or
PDE-3 inhibitor (milrinone). If the increase in RV CO not
offset the reduction in SVR, blood pressure will decrease
with resultant decline in RCA perfusion and a reduced TSG.
The combination of low-dose dobutamine and low-dose
milrinone is synergistic in inotropy and has fewer negative
effects on SVR. Monitoring overall RV function with continuous RV pressure transduction through the RV port of
the PAC is invaluable (Figure 8), which shows progression form a flat (A) diastolic pressure relationship (i.e. a
normal, compliant RV), to the non-compliant square-root type waveform in the failing, pressure-overloaded RV.
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4. Maintain the TSG and RV geometry (Fig 9A, 9B): At normal systolic pressure (RV 25 mmHg, LV 125 mmHg),
there is a large TSG (TSG = 100 mmHg) which is responsible for bulging of septum towards the RV (i.e. the normal
configuration of the IV septum); this provides a “base:
Fig. 9A
PASP 75 LVSP 100

TSG 25 (N >100)
Fig. 9B
for the free wall to contract against. The septal component accounts for more than 50% of RV systolic function.
Therefore, conditions that reduce LV systolic pressure (systemic hypotension) or increase RV systolic pressure will
reverse the TSG and severely compromise RV function. The normal helical nature of myocardial fibres and bands
will unfold and lead to a globular, dysfunctional RV (Figure 9B). Septal function be compromised because of
misalignment of the obliquely oriented septal myofibrils to a transverse configuration, resulting in less contractile
force, but the free wall loses its sturdy “base” as the distance between the free wall and the septum increases (the
result of leftward septal bowing). In order to restore the TSG, the PVR needs to be reduced and LV systolic pressure
needs to be aggressively maintained or increased. This is critical!
5. Reduce PVR: Perioperative hypoxemia, hypercapnia, atelectasis, pleural effusions, hypothermia, fluid overload,
pain, and anxiety all cause acute rises in PVR
with resultant RV decompensation. Patients on
Fig. 10 chronic therapy for PAH should continue
established treatment. Functional residual
capacity (FRC) must be carefully maintained,
as both hyperinflation and atelectasis cause an
increase in PVR. The important relationship
between lung volume and FRC during
mechanical ventilation is U -shaped with PVR
the lowest at FRC (Figure 10). At low lung
volumes, hypoxia and hypercapnia cause
hypoxic pulmonary vasoconstriction; on the
other hand, hyperinflation causes compression
of intraalveolar vessels with a resultant increase
in PVR in both circumstances. PEEP >15
mmHg also leads to an increase in PVR. In
contrast to systemic arteries, PAs constrict with
hypoxia (Euler-Liljestrand reflex) and dilate
with hyperoxia. Therefore, perioperative
ventilation strategies for patients with PH
should incorporate high concentrations of
oxygen, low TV (6 mL/kg of predicted weight),
a respiratory rate sufficient to achieve mild hypocapnia, and optimum PEEP (5–10 cmH2O). Early drainage of
pleural effusions and recruitment maneuvers should be considered. Intravenous air or particulate material
(precipitated drugs) should be meticulously avoided as R to L embolization through an open PFO may occur. In
addition to the aforementioned physiological considerations, the PVR can be reduced by selective PA vasodilators.
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Unfortunately, none of common the IV vasodilators (NTG, SNP, CCB) are selective to not cause accompanying
catastrophic systemic vasodilation; these agents could also potentially worsen hypoxia by inhibiting HPV. They
should not be used. Similarly, IV prostacyclin should not be started during a crisis. Inhaled PA vasodilators are a
crucial part of the management of the PAH/RV failure crisis when non-pharmacological methods have not corrected
the increased
PVR. Inhaled
PA
vasodilators
improve V/Q
matching and
arterial
saturation,
which in itself
Fig. 11 decreases PVR
and reduce
PVR with
much less
systemic
effects.
Unfortunately,
there are few
outcome
studies and
most of their
use is based on
case reports,
institutional
experience and protocols. It is advisable that all centers that that deal with perioperative PH develop a plan for what
inhaled pulmonary vasodilator they will use. One such proposed algorithm for their use is shown in Figure 11.
Unlike the IV PA vasodilators, these agents have little effect on SVR. Inhaled nitric oxide (iNO) is a selective PA
vasodilator (increases cGMP production) that is almost immediately inactivated by binding to Hb and is easy to use.
Other agents that have been given by inhalation include sodium nitroprusside, nitroglycerine, prostacyclin,
milrinone, iloprost, sildenafil, treprostinil and others. Rapid weaning of any inhaled agent can lead to rebound PAH.
The powerful inhaled prostanoids treprostinil and iloprost are ideally suited to use in the perioperative period,
although there is little published. No one inhaled agent has been shown to have better outcomes. A combination of
these agents, working at different receptor sites, may give have added benefit on PVR reduction. What is crucial is
that the medical center has an algorithm for inhaled PA vasodilator use, that the practioners are familiar with it, and
that the inhaled agents are immediately accessible. The PDE-5 inhibitor sildenafil has been used to manage acute
RV dysfunction in heart transplant recipients, wean patients from iNO, reduce the duration of mechanical
ventilation, and prevent pulmonary endothelial cell dysfunction after prolonged CPB. It also extends and potentiates
the effects of iNO. Sildenafil has a significant first-pass metabolism, so the sublingual route (25-50 mg dissolves
readily 1ml of sterile water) is an easy way to augment the inhaled agent.
6. Mechanical circulatory assist: The initiation of peripheral VA ECMO is an option for acute RV failure that is not
responsive to medical therapy and if the overall patient condition is conducive to this intervention. In the appropriate
patient this should not be a “late” event but should rather be instituted before the onset of multiple organ system
dysfunction. VA ECMO will serve as a bridge to recovery of RV function due to reversing the precipitating event
and optimizing medical therapy, and some situations, as a bridge to a heart-lung transplantation. Pure RV assist
devices have little or no role in acute RV cardiogenic shock due to a PH crisis as the high flows through a high
resistance lung causes pulmonary bleeding. RV assist devices may of course have a significant role in RV
cardiogenic shock due to mainly RV contractile dysfunction in the absence of severely abnormal pulmonary
vascular resistance.
Conclusions
The perioperative management of patients with PAH and associated RV dysfunction is complex and requires a
thorough understanding of the pathophysiology. Failure to make an early diagnosis of RV shock and institute the
correct therapy will lead to high perioperative morbidity/mortality. The anesthesiologist must be aware of the
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potential treatment strategies including optimizing physiological parameters, use of selective PA vasodilators,
inotropic support, and systemic blood pressure maintenance. Wherever possible, these patients should be cared for
in specialty centers.
Key references
This Refresher course is similar in content to previous ASA Refresher courses delivered by the author in 2012-2014.
1. Strumpher J, Jacobsohn E: Pulmonary hypertension and Right Ventricular Dysfunction: Physiology and
perioperative management; J Cardiovasc Thorac Anesth, 2011
2. Thunberg A, et al. PHT in patients undergoing cardiac surgery. J Cardiothor Vasc Anesth, 2013
3. Ventetuolo C, Klinger J. Management of RV failure in ICU. Annals ATS, 2014
4. McLaughlin V, Palevsky H. Parenteral and inhaled protsanoid therapy in treatment of PAH. Clin Chest
Med, 2013
5. Galie N, et al. Guidelines for the diagnosis and treatment of pulmonary hypertension: ESC/ERS
GUIDELINES. Eur Heart J, 2009
6. McLaughlin V, et al. et al for the Writing Committee: CCF/AHA 2009 Expert Consensus Document on
Pulmonary Hypertension: A Report of the American College of Cardiology Foundation Task Force on
Expert Consensus Documents and the American Heart Association Developed in Collaboration with the
American College of Chest Physicians; American Thoracic Society, and the Pulmonary Hypertension
Association. J Am Coll Cardiol, 2009
7. Simonneau G, et al. Updated clinical classification of PH. J Am Coll Cardiol, 2009
8. Herget J, et al. Role of the oxidant tissue injury in the development of HPV. Physiol Res, 2000
9. Christman BW, et al. An imbalance between the excretion of thromboxane and prostacyclin metabolites in
pulmonary hypertension. N Engl J Med, 1992
10. Pullamsetti S, et al Novel, Emerging Therapies for PH. American J Resp Crit Care Med, 2014
11. Doyle RL, et al. Surgical treatments/Interventions for pulmonary arterial hypertension: ACCP evidence
based clinical practice guidelines. Chest, 2004
12. Lewczuk J, et al. Prognostic factors in medically treated patients with chronic PE. Chest 119:818-823, 2001
13. Toyoda Y, et al. Long-term outcome of lung and heart-lung transplantation for idiopathic pulmonary
arterial hypertension. Ann Thorac Surg , 2008
14. Vlasselaers D, et al. Femoral venoarterial extracorporeal membrane oxygenation for severe reimplantation
response after lung transplantation. Chest, 2000
15. Thistlethwaite PA, et al. Venovenous extracorporeal life support after pulmonary endarterectomy:
indications, techniques and outcomes. Ann Thorac Surg, 2006
16. D’Alonzo GE, et al. Survival in patients with primary pulmonary hypertension. Results from a national
prospective registry. Ann Intern Med, 1991
17. Martin JT, et al. JF: Safety of regional anesthesia in Eisenmenger’s syndrome. Reg Anesth Pain Med, 2002
18. Krowka MJ, et al. Hepatopulmonary syndrome and portopulmonary hypertension: A report of the
multicenter liver transplant database. Liver Transpl, 2004
19. Denault AY, Haddad F, Jacobsohn E, Deschamps A. Perioperative RV dysfunction. Curr Opin
Anaesthesiol, 2013
20. Hoeper M et al. Definitions and diagnosis of PH. J American Coll Cardiology, 2013
21. Galiè N et al. Updated Treatment Algorithm of PAH. J American Coll Cardiology, 2013
22. Buckberg GD, Coghlan HC, Torrent-Guasp F. Structure and Function of the Helical Heart and its Buttress
Wrapping. Semin Thorac Cardiovasc Surg. 2001
23. Nelsen AC, Laliberte KJ, Zaccardelli DS, et al. Pharmacokinetics of inhaled treprostinil sodium in healthy
volunteers. Am J Respir Crit Care Med. 2010;181:A338
24. Kumar P, et al. A Comprehensive Review of Treprostinil Pharmacokinetics via Four Routes of
Administration.. J Pharmacokinetics, 2016
25. Thunberg CA et al. Inhaled therapy for perioperative management of pulmonary artery hypertension.
Review. Ann Card Anaesth 2015.
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Sleep Apnea in Ambulatory Surgery: Evidence-Based Implementation of

Screening, Perioperative Management and Risk Modification
Satya Krishna Ramachandran MD Boston, MA
Introduction: Over 51 million surgical procedures were performed in the US in 2010 according to data
published by the Centers for Disease Control and Prevention, suggesting that current estimates are likely
to be significantly higher. Currently, the vast majority of surgical procedures are ambulatory in nature, of
which, a significant fraction are performed in stand-alone ambulatory centers. Sleep disordered
breathing and obstructive sleep apnea (OSA) in particular have been shown to increase the risk of
perioperative airway, cardiovascular, pulmonary and neurological complications, leading to increased
resource utilization. These statistics govern the significance of OSA in the field of anesthesiology. Sleep
disordered breathing is a prevalent condition in middle aged adults in USA, affecting up to 24% of males
and 9% of women. Certain surgical procedures are associated with higher prevalence, as they may
describe predominantly obese patient populations or surgery for treatment of OSA. Up to 80% of OSA
patients are estimated to be undiagnosed. Based on the largest perioperative studies available, the
diagnosis of sleep disordered breathing was observed in around 7% of patients undergoing urology,
abdominal, cardiovascular or orthopedic procedures. The corresponding estimates for purely
ambulatory surgery are unavailable for the Nationwide Inpatient Sample database, but for the sake of
this learning exercise, let us assume that the prevalence is half this (i.e., 4%). Assuming an 80%
undiagnosed rate, there are an additional 4 undiagnosed patients for each known OSA patient, putting
the undiagnosed OSA prevalence at around 12-25%. One recent review estimated the prevalence of OSA
in ambulatory surgery at 75%.
Ambulatory care practices are challenged by the increased complexity of care and medico-legal
concerns that accompany obstructive sleep apnea (OSA) patients. Over the last five years, greater clarity
has developed on the role of preoperative screening and perioperative techniques in reducing the risk of
complications. However, there is limited information on how to implement a comprehensive screening
and perioperative management care pathway for patients with suspected or known OSA. Through this
lecture, learners will be able to describe an evidence-based approach that takes into account the
preoperative screening or polysomnography results as well as the consequences of intraoperative
interventions namely: opioid sparing techniques, specific anesthetic agents, neuromuscular blocking
agent and reversal management. Additionally, the clinician will review the limitations and effectiveness
of postoperative monitoring and CPAP therapy in reducing complications in OSA patients.
1. IMPLEMENTATION OF A HOSPITAL-WIDE SCREENING PROGRAM FOR OSA PATIENTS

1.1 Ensuring hospital-wide participation
One of the biggest opportunities in the management of OSA patients is to move away from an
individual practitioner level of intervention to a hospital wide approach. This requires identification
of the right stakeholders and articulation of a clear case for change. Experts have cited the medico-
legal implications of sudden death in OSA patients as the incentive or primary justification for a
hospital-wide response. On the other hand, the rarity of sudden deaths at each health care facility
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may be a local disincentive to invest in a comprehensive program. However, evidence from

retrospective studies suggests that there is a clear association between screen positive patients (or
suspected OSA) and early postoperative respiratory complications (PRC) requiring tracheal
intubation or PAP therapy. This may be a more effective justification for a blanket screening
program for OSA than eliminating sudden postoperative death, given the fact that PRC incidence is
significantly higher, likely by several orders of magnitude. The treatment costs of PRC in a stand-
alone ambulatory center are significantly greater and probably more resource intensive when
compared to ambulatory units attached to advanced hospitals capable of delivering high quality
respiratory care. These considerations should enrich local discussions around resource investment
into perioperative OSA pathways.
1.1.1 Identifying the stake-holders: Several major healthcare systems have instituted formal
clinical protocols for identification of suspected OSA through preoperative screening in the
last 5-10 years. At the University of Michigan, all patients presenting to the preoperative
clinic are administered a screening tool. Other centers have gone one step further and
implemented OSA screening at any hospital visit, along with other screening tools directed
at targeted identification of patients at risk of venous thromboembolism. In order to
ensure that there are standardized expectations of when and how the screening should
occur, it is essential that all major stakeholders participate in the process planning and
execution. After local leadership approval, a group of dedicated team members should be
identified with representatives of anesthesia, surgery, perioperative nursing, sleep
medicine, respiratory therapy, risk management (or clinical safety) and clinical informatics,
if order entry systems are currently or planned to be computerized. Several models exist in
leading electronic health record (EHR) systems that describe the process of embedding OSA
screening within the EHR.
1.2 Choosing the right screening tool – using the patient outcome evidence model
In general, two independent actions need to occur to ensure the clinical effectiveness of a screening
or diagnostic test. First, a positive test should induce a change in treatment, and second, the
treatment should change the outcomes. Thus, the only goal of screening for OSA is to identify
patients at greatest risk of complications, for the purpose of allocating treatments or interventions
to achieve effective risk-reduction. It is essential to appreciate that the mere process of screening
alone doesn’t change outcomes, and it needs to be linked to perioperative interventions. The
predictive accuracy of various screening tests for OSA has been extensively evaluated. The STOP-
BANG questionnaire is probably the most widely used screening tool in the perioperative period
because of its ease of use. The dimensions of evaluation of test performance encompassing
technical accuracy and clinical precision have unique implications for anesthesiologists.
1.2.1 Deciding the optimal threshold for screening test: The technical accuracy of a screening
test is typically evaluated by assessing the sensitivity and specificity of the test. Other
measures of technical accuracy include likelihood ratios, diagnostic odds ratios, and area
under the receiving operating characteristics curve or c-statistic. In general, these measures
tend to be more stable across varying prevalence of OSA. Of these measures, sensitivity is
the more important one. Since the sum of sensitivity and false negative rates equals 100%,
we can estimate the number of patients who were screened negative, but actually had OSA.
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Sensitivity values above 90% are desirable, since false negative rates are less than 10%. No
screening test is 100% accurate, and in fact, the average sensitivity for most screening tests
is around 65-70%. This means that we will continue to miss 10-35% of patients with OSA
despite introduction of universal preoperative screening programs. While this may be
acceptable at the health services level, this statistic will be troubling for most clinical
anesthesiologists. There are two major factors that influence the test sensitivity in OSA:
1.2.1.1 The screening test threshold value is critically important in determining the
technical accuracy of the test. Lowering the test threshold value results in greater
the sensitivity. So STOP-Bang 3 has a higher sensitivity than STOP-Bang 5, meaning
less false negative rates.
1.2.1.2 The severity of OSA influences the technical accuracy– the sensitivity of the same
threshold of STOP-Bang increases with increasing severity of OSA. This occurs
because patients with severe OSA tend to express the STOP-Bang elements more
predictably than patients with mild or moderate disease.
1.2.1.3 The measures of clinical precision include positive and negative predictive values.
These measures are highly influenced by the prevalence of the target condition,
such that populations with low prevalence of OSA have significantly lower positive
predictive value. This relationship is seen most commonly by the reduced positive
predictive value with increasing OSA severity. This occurs since the prevalence of
severe OSA (apnea hypopnea index - AHI >30) is typically around one-third of the
prevalence of OSA diagnosis (AHI >5), which includes mild, moderate and severe
OSA. The clinical implication of this measure relates to resource wastage through
the allocation of interventions to patients falsely screened as having the condition.
1.2.1.4 There is extremely high heterogeneity of test performance: Each screening test
functions with varying accuracy in identifying OSA patients across different study
populations. This limits the ability of the clinician to extrapolate results from one
study to their patient population. Additionally, many of the original study
populations for the screening test were performed with >70% prevalence of OSA.
When these tests are used preoperatively, it is likely that the positive predictive
value will be significantly lower than described in the studies, since the actual
prevalence of OSA is expected to be between 10-25% in most large sized
ambulatory centers.
1.2.1.5 There is significant correlation between sensitivity and specificity or positive
predictive value. In other words, as sensitivity rises (with either reduction in test
threshold or presence of severe OSA), the specificity and positive predictive values
fall. This is seen even with superior tests like STOP-Bang. This also means that we
will have lower rates of missed OSA patients, but greatly increase the rates of false
positives. One specific downstream intervention linked to the cost of false positives
is the extended PACU observation period for patients with suspected OSA. Indeed,
several centers have opted for use of 23 hour facilities, in part because the large
burden of false positives for severe OSA results in the majority of patients being
observed for extended PACU observations not having OSA.
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These rather invasive implications of OSA screening test performance result in significant
challenges to clinical anesthesiologists, surgeons, ambulatory center staff and patients alike.
It is imperative that these stakeholders understand these implications to help set
expectations, develop local clinical pathways, and create shared goals for treatment that
include specific thresholds for escalation of care. Appropriate case selection is central to the
goal of complication-free ambulatory anesthesia for OSA patients. Most units choose a
STOP-Bang threshold between 3 and 5 for activating specific pathways of care, accepting the
relative risks of choosing the lower or higher threshold.
1.2.2 Operationalizing threshold-based actions: Once the threshold of the screening test has
been determined by local discussions, the task is to ensure that there are clear
unambiguous pathways to be followed from pre-admission through to hospital discharge.
These pathways may include preoperative exercise training, formal PSG and PAP therapy, or
intraoperative care bundles. In general, screen positive patients at any threshold should be
considered as having significant OSA and managed accordingly. Further details on
intraoperative risk reduction strategies are described in later sections.
1.2.3 In addition to identifying patients with suspected OSA for appropriate perioperative
management, it is important to recognize special categories of patients represent greater
risk of perioperative complications:
1.2.3.1 Specific respiratory conditions are associated with heightened risk in OSA patients
particularly COPD (overlap syndrome) and obesity hypoventilation syndrome. These
conditions are associated with diurnal hypoventilation, elevated CO2 levels and a
chronically depressed ventilatory response system. All of these factors increase risk
of adverse respiratory outcomes on exposure to anesthetic agents, neuromuscular
blocking drugs and opioid medications. While these increase the risk of respiratory
failure, they are more likely to mediate delayed anesthetic recovery, early
postoperative desaturation and delayed PACU discharge, making early
postoperative management particularly challenging.
1.2.3.2 Patients with chronic pain on opioid medications are another high risk category.
Chronic pain and OSA have a bidirectional causal relationship that is modifiable by
the application of PAP therapy for 4-6 weeks. In addition, specific pain phenotypes
are at greater risk of analgesic failure, resulting in need for large dose opioid rescue
and consequent respiratory complications, delayed PACU discharge, and overnight
admission. High risk candidates include patients who catastrophize, generalized
chronic pain syndromes suggesting centralized pain states, total daily morphine
equivalent doses greater than 100 mg and specific analgesic medications such as
buprenorphine (suboxone). Patients on high morphine equivalent doses >200 mg
per day are highly likely to have complex sleep apnea profiles, with dose-dependent
increase in respiratory arrhythmia. Patients with morphine equivalent doses >100
mg should be deferred for opioid tapering using previously described regimes.
1.2.3.3 Early postoperative morbidity was evaluated in a study of ambulatory surgery
eligible procedures in the NSQIP database. The risk factors were: overweight body
mass index, obese body mass index, chronic obstructive pulmonary disease, history
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of transient ischemic attack/stroke, hypertension, previous cardiac surgical

intervention, and longer operative time.
1.2.3.4 There were no adequately powered studies to identify the independent predictors
of complications specific to OSA patients in the course of this review. However,
expert opinion abounds in this area, with the most specific recommendations
coming from the SAMBA and SASM guidelines. An important consideration in these
guidelines is the determination of control of systemic disease. Presence of
uncontrolled systemic disease in patients with suspected OSA is not desirable in
ambulatory surgery patients.
1.2.3.5 The ASA physical score has recently been evaluated in a large meta-analysis,
showing excellent discrimination for the prediction of near-term and long-term
postoperative mortality in an extremely wide range of patient population. Similar
prediction ability exists for the presence of functional limitation in predicting major
postoperative morbidity. It is remarkable that this singular symptom of organ
dysfunction has comparable accuracy to more complicated models described in the
literature. The high predictive ability of cardiopulmonary exercise testing
corroborates this concept that functional limitation represents a watershed risk
category. Perhaps more importantly, functional limitation may be reversible.
Preoperative exercise has been linked with significant improvement in functional
outcomes after surgery, with reduced complication rates. This may suggest value in
delaying surgery in patients with functional limitation when it is combined with a
specific plan to improve preoperative function.
1.2.3.6 Sleepiness is yet to be formally evaluated as a prognostic sign for patients with OSA.
Presence of excessive daytime sleepiness can be quantified using the Epworth
Sleepiness Scale or other similar scales, and may indicate a brain that is more
susceptible to the residual sedative effects of anesthetic medications.
1.2.3.7 Although obesity rates in the US have stabilized over the last few years, the
prevalence of more severe obesity continues to rise. Acceptable BMI thresholds for
ambulatory surgery are variable across the US. The American Society for Metabolic
and Bariatric Surgery, proposes a BMI threshold of >60 kg/m2 for ambulatory
surgical procedures. Patients in higher obesity classes are more likely to have
significant daytime hypoventilation resulting in chronic hypercapnia. Although
obesity directly influences both airway and pulmonary function, spirometry is of no
added benefit unless COPD is suspected. Many centers advocate the routine use of
chest X-ray for all morbidly obese patients to screen for heart failure, cardiac
chamber enlargement, or abnormal pulmonary vascularity suggestive of pulmonary
hypertension, which warrants further cardiovascular investigation.
1.2.3.8 Electrocardiography (ECG) may have specific value in identifying patients with
clinically relevant cardiac disease related to obesity and OSA. The American College
of Cardiology and American Heart Association recommendations for perioperative
management of morbidly obese patients include ECG when at least one risk factor
for CHD and/or poor exercise tolerance. ECG evidence of right ventricular
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hypertrophy including right-axis deviation and right bundle-branch block could point
to pulmonary hypertension, while a left bundle-branch block may suggest occult
CHD. Additionally, ECG characteristics associated with severe OSA include presence
of conduction blocks, atrial and ventricular ectopy, arrhythmias, widened QRS
complexes, and QTc prolongation. Further testing, such as exercise and/or
pharmacological stress echocardiography, may be performed in presence of ≥3 risk
factors of CAD (i.e., history of CHD, history of congestive heart failure, history of
cerebro-vascular disease, preoperative treatment with insulin, and preoperative
serum creatinine levels >2 mg/dL).
1.3 Tracking efficiency and effectiveness of preoperative screening program: It is essential to
describe the metrics through which the quality of preoperative screening program is to be
evaluated. This provides much needed positive reinforcement and performance improvement
data to all team members involved in the screening and pathway management. Examples of
such metrics could include % of patients arriving to preoperative area with a completed screen,
% of patients leaving PACU with an incomplete screen, % of patients managed with desired
pathway etc. Effectiveness of the program requires tracking early PRC rates to identify changes
in complication rates.
2. FAST-TRACK PREOPERATIVE SLEEP MONITORING STUDIES
The access and timely availability of the diagnostic test (PSG) is variable across the US, with wait
times of 1 week to 9 months. The majority of patients presenting for surgery will typically have
inadequate time to be tested using traditional referral pathways. Therefore, it becomes important
to screen for OSA in the preoperative period, so anesthesiologists are able to appropriately manage
patients with suspected OSA. There is emerging evidence for the effectiveness of current OSA
clinical screening tests in predicting postoperative complications. Additionally, preoperative PAP
treatment is associated with significant reduction in cardiopulmonary complications after non-
cardiac surgery. Several centers now have the ability to provide fast track PSG or home sleep testing
in preoperative patients. These pathways have resulted in the shortening of wait times from several
weeks or months to a matter of days before definitive diagnosis of OSA is made. The integration of
preoperative clinic, sleep laboratory, anesthesia and surgical services, along with payer
participation, are essential for the successful implementation of such a program. It is important to
recognize that there is no current evidence that such a program is necessary for pure ambulatory
surgery units. Expert opinion does not recommend delaying surgery for the performance of
preoperative PSG.
2.1 Interpreting polysomnography (PSG) or home sleep monitoring results
2.1.1 Severity of OSA: This is measured as the apnea-hypopnea index (AHI), with values >30
per hour of sleep indicative of severe disease. Patients with severe OSA are likely to
have significant perioperative challenges in the ambulatory setting. These patients will
present with increased desaturation in the postanesthesia care unit (PACU), which in
turn leads to delayed discharge and hospital transfer.
2.1.2 Nadir desaturation or lowest saturation (LSAT) or minimum saturation, may be
suggestive of more serious cardiac risk. LSAT values <60% increase the risk of
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ventricular arrhythmia. The value of preoperative overight pulse oximetry as part of a

larger scale screening program has not yet been evaluated.
2.1.3 Positional apnea: refers to the worsening of apnea in certain positions (typically
supine) during sleep. Recent research suggests that patients with positional apnea may
benefit from changes in bed configuration, where a 30-45 degree head up reverse
Trendelenbug position is associated with a remarkable reduction in AHI.
2.1.4 If a titration study exists, effectiveness of PAP therapy is done by evaluating the
elimination or reduction in apneas or hypopneas during treatment.
2.1.5 History of anesthesia or sedation related complications: this is highly indicative of a
dynamic relationship between patient, surgical and pharmacological risk factors that
may recur with repeated exposure.
2.2 Alternative strategies to preoperative fast-track testing: There is no current evidence that
institution of a fast track testing center results in reduction of perioperative complication rates.
Expert opinion does not recommend delaying surgery for preoperative sleep testing, except
when significant systemic diseases coexist. In these situations, the case could be made for
enhancing access for testing and PAP initiation, where indicated. It is perhaps important to
recognize that PAP therapy doesn’t uniformly reduce risk in OSA patients, and several factors
including facial anatomy, patient demographics and expert support influence PAP adherence
metrics. At a minimum, patients need to be using the PAP device for at least 4 hours a night and
5 nights a week to be considered PAP adherent. Alternative risk reduction strategies are also
resource intensive and include:
2.2.1 Although this was previously considered an unattainable goal, several investigators
have shown that preoperative exercise training is associated with significant
improvements in cardiorespiratory function and postoperative outcomes within 3-8
weeks of initiation. Inspiratory muscle training for 2 weeks significantly reduced
postoperative pulmonary complications and the length of stay in hospital in one meta-
analysis.
2.2.2 Weight loss intervention programs are associated with significant reduction in the
severity of OSA. Effective weight reduction strategies typically include exercise, low
calorie diet and oversight or group activity. The large-scale success of such programs
across demographic divides has yet to be explored. In severe OSA patients, bariatric
surgery may be the most effective approach to overall risk reduction for subsequent
ambulatory surgical procedures.
2.2.3 Preoperative management of postoperative pain: Expectation setting for postoperative
analgesia including education of the airway and respiratory risks of opioid based
analgesia are essential. Education of regional analgesia and postoperative
breakthrough pain management may help improve utilization of non-opioid pathways
with concomitant benefits. Active surveillance and identification of high opioid users is
an essential first step to modifying postoperative analgesia and respiratory outcomes.
Using a statewide surveillance system to cast the net wide and capture opioid access
from multiple pharmacies helps validate patient reports of daily morphine equivalent
dose. Implementing an effective intervention process for these patients involves the
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anesthesiologist, surgeon, primary care practitioner and occasionally, an addiction

specialist. Implementing a protocol to identify buprenorphine treatment preoperatively
and determine appropriateness to perform surgery at ambulatory center.
3. KEY PERIOPERATIVE INTERVENTIONS AND EXPECTANT MANAGEMENT
3.1 Anesthetic interventions
3.1.1 General anesthetic agents: There is limited evidence on the differential benefits of
specific general anesthetic agents. Patients with increased arousal thresholds at
baseline (like those with obesity hypoventilation syndrome) may be at greatest
postoperative risk of excessive sedation and airway instability. Some evidence exists to
the value of low-dose ketamine administration in reducing intraoperative opioid
administration. Pre-clinical data point to a potential upper airway dilatory effect of low-
dose ketamine, secondary to the uncoupling of consciousness and upper airway
dilatory function. Low dose ketamine is associated with reduced intraoperative
anesthetic requirement and improved cognitive function in elderly patients.
3.1.2 Analgesic techniques: Previous studies have demonstrated a significant association
between usage of neuraxial anesthesia and reduction of complications in patients with
known OSA. Randomized controlled trials testing non-regional opioid reduction
strategies have failed to show significant reduction of postoperative sleep disordered
breathing. Further, retrospective studies point to likely increase in susceptibility to
small doses of opioids in patients who develop major respiratory events. There is
emerging evidence that early postoperative desaturation or oxygen requirement is
associated with a significant increase in the risk of developing PRC. A more practical
approach may include maximizing non-opioid adjunct administration and targeting
higher risk categories such as patients with OHS or COPD for avoidance of general
anesthesia.
3.1.3 Neuromuscular blocking agents and reversal: Avoidance of NMBA in general and
rocuronium in particular, may be associated with benefit in patients with suspected
OSA. Recent studies have also demonstrated the role of standardized clinical behaviors
around reversal of NMBA may reduce risk of complications after anesthesia and
surgery.
3.1.4 Intravenous fluids: Emerging evidence suggests that rapid crystalloid administration in
non-operative patients may be associated with significant airway edema development
and concomitant worsening of sleep apnea. This finding is preferentially seen in older
patients, and is being investigated as a potential modifiable risk in patients undergoing
surgery.
3.2 Non-anesthetic interventions
3.2.1 Preoperative positive airway pressure (PAP) therapy: The majority of expert evidence
has traditionally supported preoperative PAP therapy in reducing risk. Recent evidence
supports that view, with at least two retrospective studies showing an association
between preoperative PAP adherence (and OSA diagnosis) and reduced occurrence of
cardiorespiratory complications. Previous studies have shown that pain, cardiac rhythm
and postoperative cardiorespiratory outcomes of patients with OSA could be modified
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with PAP treatment. Reduced motor vehicle accidents related to sleepiness are
apparent within 2-5 days of institution of PAP, while improved pain sensitivity is
observed within 2 days on CPAP initiation and is significantly reduced at 6-8 weeks.
Improved complex apneas are observed within one night of initiation of non-invasive
servo ventilation therapy in chronic pain patients. The duration of preoperative PAP
treatment needed for modifying postoperative cardiopulmonary risk is currently
unknown, and may require 2-6 months of treatment. However, empiric PAP treatment
in patients with suspected OSA was not associated with improved outcomes,
suggesting that either the screening tool for allocating the treatment is deficient, or
that the minimum duration of PAP therapy needed for effective risk reduction was not
achieved. In contrast, the large numbers of patients across the US with known
diagnoses but without an integrated preoperative, surgical and anesthetic
management plan represents an excellent opportunity for developing effective care
pathways. OSA needs to be a major part of the perioperative surgical home (PSH) given
the evidence that postoperative outcomes are modifiable with PAP for an appropriate
duration. Patients are educated to bring their PAP devices with them when they come
for surgery, so they can be used if needed in the PACU.
3.2.2 Postoperative PAP therapy: The evidence to support the benefit of using early
postoperative PAP in patients with OSA is limited. One recent study demonstrated
reduced respiratory depression with the initiation of postoperative CPAP therapy.
However, adherence of newly instituted PAP therapy is poor in the postoperative
period, which may explain the lack of benefit. Additionally, PAP may be introduced late
in the evolution of PRC, which may impact effectiveness of therapy. The challenge in
standalone ambulatory centers in managing PAP requirements in the PACU results in
possible underutilization of treatment. On the other hand, the cost-benefit of
employing a respiratory therapist needs to be considered when planning for early
interventions in the ambulatory setting.
3.2.3 Postoperative monitoring – ambulatory context: Emerging evidence points to
increased risk association of early postoperative desaturation or oxygen requirement
and PRC. Patients who have recurrent desaturation events on exposure to room air
should be observed for longer and considered at greater risk of developing
complications.
Recommended reading and resources:
OSA overview
1. Chung F, et al. Anesth Analg 2008;107:1543–63
2. Joshi GP, et al. Anesth Analg 2012; 115: 1060-8
3. American Society of Anesthesiologists Task Force on Perioperative Management of patients with
obstructive sleep apnea. Anesthesiology. 2014;120:268-86
4. Chung F, et al. Anesth Analg 2016;123:452-73
OSA and postoperative outcomes
1. Mokhlesi B, et al Chest. 2013; 144:903–14.
2. Kaw R, et al. Br J Anaesth 2012; 109:897-906.
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3. Memtsoudis SG, et al. Anesth Analg 2014; 118:407–18.

4. Memtsoudis S, et al. Anesth Analg 2011; 112:113–21.
Preoperative screening/effectiveness
1. Ramachandran SK, et al. Anesthesiology 2009;110:928–39
2. Ramachandran SK, et al. Anesthesiology. 2011;115:44-53
3. Mathis MR, et al. Anesthesiology 2013; 119:1310-21
4. Young T, et al. Am J Respir Crit Care Med 2002; 165:1217–1239.
5. Finkel KJ, et al. Sleep Med 2009; 10:753-8.
6. Stierer TL, et al. J Clin Sleep Med 2010; 6:467–472
7. Chung F, et al. Anesthesiology 2008;108:812–21
8. Isono S, et al. Br J Anaesth 1998; 80:603-05.
Preoperative diagnosis/PAP outcomes
1. Abdelsattar ZM, et al. Sleep 2015:pii: sp – 00545–14.
2. Mutter TC, et al. Anesthesiology 2014; 121:707-18.
3. Liao P, et al. Anesthesiology 2013; 119:837-47.
4. Guralnick A, et al. J Clin Sleep Med 2012; 8:501-506.
5. Tregear S, et al. Sleep. 2010;33:1373-80.
6. Rossi VA, et al. Eur Heart J. 2012;33:2206-12
7. Khalid I, et al. Sleep. 2011 1;34:1687-91
8. Shapiro CM, et al. Sleep Breath. 2015
OSA and preoperative exercise outcomes
1. Mitchell LJ, et al. Sleep Med. 2014;15:1173-83
2. Snowdon D, et al. J Physiother. 2014;60:66-77
3. Jack S, et al. Best Pract Res Clin Anaesthesiol. 2011;25:461-72.
4. Singh F, et al. Surg Oncol. 2013;22:92-104.
OSA and weight loss
1. Ashrafian H, et al. Obes Surg. 2015;25:1239-50
Chronic pain and high dose taper management resources
1. Walker JM, et al. J Clin Sleep Med. 2007;3:455-61
2. http://anes.med.umich.edu/opioidtaper/opioidtaper.htm
3. http://anes.med.umich.edu/vault/1003149-1003149-
Buprenorphine_Suboxone__Subutex_Perioperative_Management.pdf#pagemode=bookmarks
Anesthetic and non-anesthetic interventions
1. Eikermann M, et al. Anesthesiology 2012;116:35-46
2. Pal D, et al. Br J Anaesth 2015;115 Suppl 1:i77
3. Simons JC, et al. Anesthesiology 2016;125:525-34
4. Yadollahi et al. Sleep 2014;37:1699-705
5. Lam T, et al. Anesth Analg 2016;122:1335-9
6. McLean DJ, et al. Anesthesiology 2015;122:1201-13
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Goal-Directed Therapy in Cardiac and Non-Cardiac High Risk Surgery:

Devices and Data
Davinder Ramsingh, M.D. Loma Linda, California
Robert H. Thiele, M.D. Charlottesville, Virginia
Introduction
Anesthesiologists have always had goals – for most modern anesthesiologists, common hemodynamic
goals often include normalizing system blood pressure and in some cases central venous pressure.(1) Yet
in the earliest days of anesthesia, before anesthesiology as a specialty even existed, simply allowing the
patient to survive the surgical procedure was the main goal of the individual providing the anesthesia. As
advances in pharmacology and technology (in particular, mechanical ventilation / gas delivery as well as
patient monitoring devices) accumulated, the anesthesiology community substantially reduced
intraoperative mortality. In fact, anesthesiology is specifically mentioned as an exemplary medical
subspecialty in the 1999 Institute of Medicine book To Err Is Human: Building a Safer Health System:
“Anesthesiology is an example of a local, but complex, high-risk, dynamic patient care system in
which there has been notably reduced error. Responding to rising malpractice premiums in the mid-
1980s, anesthesiologists confronted the safety issues presented by the need for continuing vigilance
during long operations but punctuated by the need for rapid problem evaluation and action. They
were faced with a heterogeneity of design in anesthesia devices; fatigue and sleep deprivation; and
competing institutional, professional, and patient care priorities. By a combination of technological
advances (most notably the pulse oximeter), standardization of equipment, and changes in training,
they were able to bring about major, sustained, widespread reduction in morbidity and mortality
attributable to the administration of anesthesia.” (p. 164)(2)
For the purposes of this review course, the term “Goal-Directed Therapy” (GDT) will be utilized to
describe any hemodynamic management algorithm that guides the anesthesiologist (or intensivist) in the
management of an anesthetized or critically ill patient. By this definition, an anesthesiologist endeavoring
to maintain mean arterial pressure (MAP) above 65 mm Hg is practicing GDT. As described above, we
all practice GDT. The important question(s) is(are) not whether or not we should have goals, but
what physiologic endpoints drive outcomes, in which patients, and at what cost?
Devices
Hemodynamic monitoring and management has greatly improved during the past decade. Technologies
have evolved from very invasive to non-invasive, and the philosophy has started to shift from a static
focused (blood pressure, central venous pressure, etc.) approach to now include a functional focused
(cardiac output, stroke volume, and fluid responsiveness) approach. As stated above the concept of GDT
has been ingrained in the care model of anesthesiologists from the specialties origination. However, the
parameters and the technologies used to obtain those parameters has rapidly grown in recent years,
ultimately for patient benefit.
First and foremost it is important to acknowledge that, no monitoring tool, no matter how accurate, by
itself has improved patient outcome (3). Hemodynamic monitoring systems are measurement tools and
their effects on outcomes are only as good as the protocols and training of the providers they are used
with. Over the past 40 years and especially in the past 15 years, technology has allowed the bedside
clinician to reconnect to the concept that end organ oxygenation is dependent on both flow (cardiac
output) and pressure (mean arterial pressure). This course will review from, past to present, the
hemodynamic monitoring devices utilized for inpatient care.
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Pulmonary artery catheter  (PAC)
Intermittent thermodilution obtained through the PAC has been considered the gold standard for cardiac
output (CO) monitoring in the clinical setting since the early 1970s. (4,5) Advancement in the mid 1990s
allowed for a more continuous cardiac output assessment via a catheter with a thermal filament and a
thermistor. (6) These catheters provide a continuous trend of CO, decrease operator workload, and
possibly reduce infection risk associated with bolus technique. It is important to note, however, that
cardiac output assessment via this technique fundamentally requires time and the CO displayed is an
average over the past 5 to 15 minutes. (6) Studies have indicated that this inherent time delays prevent
the rapid detection of acute changes in CO, resulting in some calling this technique a continual rather than
a continuous monitor (7). The PAC was widely used until the 1990s, when it started to dramatically
decrease in all settings (8) secondary to a shift in philosophy, replacement by newer technologies (9), and
also probably due to the widespread use of transesophageal echocardiography. Most studies focusing on
PAC and outcome have shown no positive association between PAC use for fluid management and
survival in the ICU (10-12) or in the high-risk surgery patient (13). This conclusion combined with the
relatively hight level of invasiveness, advanced level training for placement, and incorrect parameter
interpretation have lead to declining use of this system (14). However, the PAC still holds utility in the
assessment of right ventricular CO, pulmonary arterial pressures (15,16), and mixed venous oxygen
saturation monitoring (16,17) and is commonly used by cardiac anesthesiologists and surgeons.
Esophageal Doppler (EDM)
Simultaneous to the decline of PAC use, the development of esophageal doppler as a less invasive
hemodynamic monitoring system began. This technology utilizes the Doppler principle to assess the
velocity of flow in the descending aorta and estimates cardiac output by using a normogram based
estimate of the aortic cross sectional area. Compared to other minimally invasive cardiac output
systems, the esophageal doppler has strong evidence regarding improvement of outcome in patients
undergoing high-risk surgery (18-21) and was the first minimally invasive technology to suggest an
improvement for patients undergoing cardiac surgery (22). In addition, the evidence suggesting improved
outcomes with the use of EDM has lead to the National Health Service in the UK to list EDM as a
recommended technology for high-risk surgery (23). Limitations of EDM are largely secondary to the
fact that the waveform is highly dependent on correct positioning and requires frequent adjustments of
depth, orientation, and gain to optimize the signal (24). It is perhaps secondary to this limitation that has
made the technology slow to be adopted (25).
Arterial Pressure Waveform Analysis
These systems attempt to estimate stroke volume by sophisticated evaluation of the shape of the arterial
waveform. The benefits of these systems are that they are not user dependent and are very easy to use.
The main drawback of these systems is that they are highly dependent on vasomotor tone and on vascular
compliance (26). The technologies, in large part, differ based on how they address the issue of vascular
compliance, some require calibration and other do not (27). Additionally this technology provides a
relatively new parameter of stroke volume variation. Briefly, it is known that positive pressure
ventilation can impact preload. In the setting of controlled positive pressure ventilation and in the
absence of frequent arrthymias, if mechanical ventilation induces prominent respiratory variations in
stroke volume (SV) the patient’s heart is more likely to be working on the steep portion of the Frank–
Starling relationship and is thus preload dependent (26). This dynamic parameter has consistently been
shown to be superior to static parameters for the prediction of fluid responsiveness (28,29). Moreover
many studies have suggested that the use of a protocolized intraoperative fluid management strategy using
dynamic parameters, such as SVV, improvement postoperative outcome (30)
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Noninvasive Technologies
Photoplethysmography
As a current standard ASA monitor pulse oximetry is a well-known technology to anesthesiologist. By

emitting different wavelengths of light a pulse oximeter determines a ratio of absorbance of
oxyhemoglobin and deoxyhemoglobin in a tissue field. To determine arterial blood saturation the pulse
oximeter detects only the changing absorbance patterns that occur secondary to pulsations of arterial flow,
which produces the photoplethysmographic waveform. Recently technology has been developed that
analyses the amplitude change in this waveform (pleth variability index –PVI). Several small studies
have suggested the ability to use PVI to determine fluid responsiveness with similar restrictions as SVV
(31-34) . Important caveat to this parameter is that one requires a high amplitude signal (good peripheral
perfusion) to assess for volume responsiveness.
Bioimpedance and Bioreactance
These technologies are based on the ability to detect changes in impedance (using Ohms law) as
representation of intrathoracic blood volume. A small electric current is sent across the chest to detect
changes in impedance during a cardiac cycle. The large assumption with these technologies is that the
change impedance is exclusively related to changes in the intrathoracic blood (27).
However there are many factors that can affect change in impedance including: cardiac rhythms,
abnormal ventilatory patterns, motion artifacts, valvular heart diseases, electrocautery, changes in
hematocrit, excessive changes in body temperature, and an obese body habitus (35).
Volume Clamp Technologies
The volume clamp devices utilize an inflatable cuff with a photoplethysmograph that is placed on the
finger. At a very rapid rate (1000 times a second) the cuff pressure is adjusted to keep the diameter of the
peripheral arteries of the finger constant (determined by photoplethysmograph). The cuff pressure
required to maintain this stable transmittance is the same as the arterial blood pressure (27,36)
Since the success of this technique requires the diameter of the digit arteries to be unchanged one can see
that maintaining the finger as straight as possible is of critical importance. Similarly hand/finger motion
can also significantly alter the readings. From the generated pressure waveform  these technologies
apply waveform analysis algorithms to provide flow-guided parameters (stroke volume, SVV, etc.).
While these technologies seem promising, evaluation of its clinical utility is very much in its infancy.
There are some small studies suggesting its accuracy to PAC (37), arterial waveform analysis (38), and
echocardiography (39). Currently an ongoing study is evaluating the use of this technology (ClearSight,
Edwards Lifesciences) in a GDT protocol for patients undergoing colorectal surgery (the PANEX3 trial)
(40).
What hemodynamic monitoring system to use?

Since there is no “perfect” technology that can be used in all sectors of the patient care environment, the
decision to what technologies to use should be made at an institution level. Aligning the institutions
needs to the technology that has been proven to be useful in that area is critical. This approach has been
recently proposed by Alhashemi and colleagues and has been described as an integrative perspective for
the use of CO monitoring systems (41).
Data
Historical Background: The PA Catheter Era
While the intraoperative mortality rate directly attributable to anesthesia is difficult to estimate, certain
patient populations (e.g. trauma, sepsis) still have high mortality rates. The development of the PA
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catheter in the early 1970s, which allowed for the bedside measurement of pulmonary arterial pressures in
addition to cardiac index and mixed venous oxygen saturation (SvO2), gave anesthesiologists and
intensivists the ability to add a new suite of hemodynamic endpoints to their goal-directed
armamentarium.(4,5) Despite the lack of clinical outcomes data, by 1993, one in every 176 patients
admitted to a hospital in the United States received a PA catheter.(8) In fact, it would take almost a
quarter of a century for the scientific community to being to test these new metrics using robust studies
(e.g. randomized controlled trials).
In 1994, Hayes et al. randomized 109 critically ill patients to control (dobutamine to maintain CI > 2.8
L/min/m2) and intervention (dobutamine to maintain CI > 4.5 L/min/m2, DO2 > 600 mL/min/m2, and VO2
> 160 mL/min/m2) groups, and found a significant increase in mortality in the intervention group.(42)
Gattinoni et al. published a similar (but larger) study a year later, finding no difference in mortality when
CI or SvO2 were optimized.(43) Soon after, Shoemaker published a similar trial demonstrating improved
mortality in critically ill patients randomized to PA catheterization and maintenance of CI > 4.5 L/min/m2
and DO2 > 600 mL/min/m2.(44) Thus, the PA catheterization controversy was born.
By 2002, 21 (relatively small) randomized controlled trials had been conducted, the results of which
revealed “Statistically significant mortality reductions… when patients with acute critical illness were
treated early to achieve optimal goals before the development of organ failure, when there were control
group mortalities of >20% and when therapy produced differences in oxygen delivery between the
control and protocol groups” according to a meta-analysis by Shoemaker.(45)
This meta-analysis was followed by a series of prospective, randomized controlled trials that
demonstrated either no improvement in mortality when applied to critically ill patients, and in some cases
the potential for harm.(46-48) By 2004, PAC insertions in the United States had had decreased by 65%
from their peak in 1993, and more recent Canadian data suggests that use continues to fall. (8,49)
Intraoperative Goal-Directed Therapy and Enhanced Recovery

The failure of the PAC to convincingly improve mortality in large, prospective studies dealt a blow to
believers in GDT. However, on a separate, unrelated front, the idea that stroke volume optimization
through careful titration of fluids might improve “softer” outcomes (patient satisfaction, pain scores,
length of stay, complications, and cost of care) began to build momentum. Much of this early data was
produced in Europe by the developers of “Enhanced Recovery” protocols – comprehensive, multimodal
guidelines for the perioperative management of patients undergoing major surgery – many of whom used
esophageal Doppler devices. RCTs examining the isolated use of esophageal Doppler in almost 700
subjects show a reduction in length of stay of 3.7 days.(50-56) A pilot “before-after” implementation
study conducted by the National Health Service (U.K.) found a reduction of 3.6 days in over 1300
patients studied.(57) This positive result prompted the National Institute for Health (NHS) and NHS
Clinical Excellence (NICE) Group to release practice guidelines endorsing esophageal Doppler for GDT
in major surgery.(58) Similar results have been obtained using arterial waveform devices (length of stay
reduced 2.2 days in 546 subjects).(59-64)
While the relatively small studies looking specifically at the use of stroke volume measurement (and
in some cases, respiratory variation) to guide fluid administration have been positive, it is important to
point out that the only large, randomized controlled trial of a non-PAC GDT device in the perioperative
environment was negative.(65) Furthermore, as Enhanced Recovery algorithms have improved, some
authors have suggested that a “zero balance” or “restrictive” strategy might perform just as well as SV-
guided GDT in patients receiving all other components of Enhanced Recovery. While only three studies
(335 subjects) have been studied, preliminarily it appears that there is when Enhanced Recovery
principles are adhered to, the addition of GDT does not improve length of stay or the complication
rate.(66-68)
The Sepsis Literature
As in trauma patients, septic patients (many of whom will undergo surgical procedures) continue to
exhibit high mortality rates. Thus, it is unsurprising that Rivers’ early GDT trial of septic patients, which
reduced mortality from 47 to 30% in septic patients receiving GDT, was received with great enthusiasm.
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(69) This single center study included 263 patients but was criticized for its unusually high mortality rate
in the control group as well as a clear conflict of interest (the senior author patented the ScvO2 device
used in the study, which was assigned to the hospital [Henry Ford Hospital] where the study was
conducted). Three subsequent multicentered, randomized controlled trials spanning three continents and
including 4735 subects were all negative, casting doubt on the generalizability of Rivers’ findings.(70-72)
Putting GDT into Context

The related specialties of anesthesiology and critical care have been subjected to a series of “false
hopes” over the past several decades – steroids for spinal cord injury,(73,74) colloid administration for
fluid resuscitation,(75,76) steroids for acute respiratory distress syndrome,(77,78) dopamine for renal
failure,(79,80) parenteral hyperalimentation in critically ill patients,(81,82) strict glucose control,(83,84)
erythropoietin use in critically ill anemic patients,(85,86) and activated protein C in severely septic
patients(87,88) have all been shown to be helpful in either a series of small studies or one larger, high
impact study, adopted widely, and subsequently shown to be either not helpful or worse, harmful. In
some cases, it took almost a quarter of a century for the anesthesiology and critical care communities to
“de-adopt” these initially promising yet subsequently debunked treatment modalities. As patients live
longer and accumulate more comorbidities, as treatment options expand and medicine becomes more
complex, identifying perioperative treatment strategies that can withstand the impartial, cold-hearted
agnosticism of the scientific process (hypothesis generation, testing, and validation) will become
increasingly difficult. This is not to say that GDT is not useful – most current meta-analyses suggest that
it is(19,65,89) - but to put the body of literature in perspective. If the 59 the randomized controlled trials
including 16,889 subjects cannot settle the debate about crystalloids vs. colloids,40 it is unlikely that we
can make confident statements on the utility of GDT, especially as the consistently positive studies have
been smaller, based on the current literature. While deeply unsatisfying, we conclude that clinicians
cannot confidently support (or refute) the use of GDT in perioperative patients until larger, multicentered
studies including several thousand patients are performed, and then repeated.
Further Reading from the Authors:

Cannesson M, Ramsingh D, Rinehart J, Demirjian A, Vu T, Vakharia S, Imagawa D, Yu Z, Greenfield S,
Kain Z. Perioperative goal-directed therapy and postoperative outcomes in patients undergoing high-
risk abdominal surgery: a historical-prospective, comparative effectiveness study. Crit Care. 2015 Jun
19;19:261
Thiele RH, Bartels K, Gan TJ. Inter-device differences in monitoring for goal-directed fluid therapy. Can
J Anaesth. 2015 Feb;62(2):169-81
Thiele RH, Gan TJ. Hemodynamic monitoring devices. Best Pract Res Clin Anaesthesiol. 2014
Dec;28(4):305-7.
Thiele RH, Bartels K, Gan TJ. Cardiac output monitoring: a contemporary assessment and review.
Crit Care Med. 2015 Jan;43(1):177-85
Ramsingh DS, Sanghvi C, Gamboa J, Cannesson M, Applegate RL 2nd. Outcome impact of goal
directed fluid therapy during high risk abdominal surgery in low to moderate risk patients: a randomized
controlled trial. J Clin Monit Comput. 2013 Jun;27(3):249-57
Ramsingh D, Alexander B, Cannesson M. Clinical review: Does it matter which hemodynamic

monitoring system is used? Crit Care. 2013 Mar 5;17(2):208
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101

How to Establish a Perioperative Surgical Home in Your Institution

Zeev N. Kain, MD, MBA Orange/CA

The Perioperative Surgical Home (PSH)

Creating the PSH Team (total joint replacement as an example)

John Kotter. A sense of urgency. Harvard Business Press; (2008)

Common Neonatal Emergencies: You Can Never be Better Prepared

Mary Ellen McCann Boston, MA

Specific Conditions: (Table 2)

Tracheoesophageal Fistula (TEF)

Gastroschisis and Omphalocele

Pulmonary Hypoplasia and Congenital Diaphragmatic Hernia (CDH)

Minimally Invasive Surgery

Laparoscopic surgical approaches can be used for pyloromyotomy, gastrostomy, fundoplication,

Asphyxia  Depressed myocardial function

Infants of diabetic mothers  Hypoglycemia

Small for gestational age  Hypoglycemia

Large for gestational age  Birth injuries (brachial/phrenic nerve, fractured

Table 2. Perioperative Considerations for Complex Neonatal Surgery.

Surgical Diagnosis Preoperative Intraoperative Postoperative

Gastroschisis and RDS if premature Hypovolemia Oxygenation/Ventilation

CDH Over-expanded Epidural or narcotic- Epidural for post-op

TEF Aspiration Epidural or narcotic- Epidural for postop

NEC RDS if premature No epidural if septic ROP

Table 3. Types of Congenital Tracheoesphageal Fistulas (TEF) and Esophageal Atresia

Anatomic Characteristics Percent of Cases (%)

1. Ventral wall defects

Current Controversies in Adult Outpatient Anesthesia

The Hows And Whys Of Preoperative Evaluation

The Inappropriate Patient - Who's OK And Who's Not

Changes to the ASA Standards for Basic Anesthesia Monitoring

CMS Issues Revised Hospital Anesthesia Services Interpretive Guidelines

Does Choice of Anesthetic Affect the Rate of Cancer Recurrence?

Computer-Assisted Personalized Sedation (CAPS): Dead or Alive?

1. Chung F: Are discharge criteria changing? J Clin Anesth 1993; 5:64S-68S.

TABLE 1. DISCHARGE CRITERIA

• Awake, alert, oriented, responsive (or return to baseline)

Preventing CNS Complications During Anesthesia & Surgery

James E. Cottrell, M.D. Brooklyn, New York

THE YOUNG BRAIN

Have the data already changed clinical practice?

How might we fix this problem?

THE OLDER BRAIN

POCD After Non-Cardiac Surgery

POCD After Cardiac Surgery

- On-pump vs. Off-pump

- Anesthesia and Neurodegenerative Diseases

Potential Alleviating Factors

- Deeper vs. Lighter & Regional vs. General Anesthesia

- Anesthetics & Sedatives

- A Grab Bag of Adjuvants , Emboli Protection, Diet & Exercise

- Preconditioning & Perconditioning

23525593060 23625440646 23716781056 23817577439 23918201834 24020216397 241(google)NCT02169739

James R. Hebl, M.D. Rochester, MN

Clinical Pathways: An Overview

Clinical Pathway Components

Preoperative Patient Education

Table 1. Essential Clinical Pathway Components

Peripheral Nerve Blockade and Continuous Perineural Catheters

Early and Accelerated Rehabilitation

Clinical Pathways and Perioperative Outcomes

Clinical Pathways for Total Joint Arthroplasty

Clinical Pathways and Economic Outcomes