PRACTICE INSIGHTS

Key Articles and Guidelines for the

Emergency Medicine Pharmacist
Michael C. Thomas, Pharm.D., Nicole M. Acquisto, Pharm.D., Asad E. Patanwala, Pharm.D.,
Kyle A. Weant, Pharm.D., and Stephanie N. Baker, Pharm.D.
Compilations of articles important to the pharmacist practicing in the
emergency department have not been published. Consistent with other
specialty areas of practice, a collection of important literature is valuable for
both the new and experienced clinician. A diverse breadth of medical
problems are represented that were felt to be the most pertinent issues facing
the emergency medicine pharmacist; however, it is not intended to be a
complete representation of available literature.
Key Words: drug therapy, emergency department, ED, ER, key articles,
guidelines.
(Pharmacotherapy 2011;31(12):454e491e)

OUTLINE
Analgesia and Sedation
Cardiovascular Emergencies
Coagulation
Diabetic Emergencies
From the South University School of Pharmacy,
Savannah, GA (Dr. Thomas), the University of Rochester
Medical Center, Rochester, NY (Dr. Acquisto), the
University of Arizona College of Pharmacy (Dr. Patanwala),
and University of Kentucky HealthCare (Drs. Weant and
Baker).
The provision of pharmaceutical care in the emergency
department (ED) requires knowledge of a multitude of
clinical scenarios. Compiling the essential literature is
important for the new and seasoned emergency medicine
practitioner. The primary author of this manuscript
(M.C.T.) was an author on the first in the series of
annotated bibliographies (Erstad BL, Jordan CJ, Thomas
MC. Key articles and guidelines relative to intensive care
unit pharmacology. Pharmacotherapy 2002;22:1594610).
All authors of this manuscript are members from the
Emergency Medicine Practice and Research Network of the
American College of Clinical Pharmacy and collectively
developed topics considered important to the pharmacist
practicing in the ED setting.
For
reprints,
please
visit
http://www.
pharmacotherapyjournal.org. For correspondence, please
contact Michael C. Thomas, Pharm.D., South University
School of Pharmacy, 709 Mall Boulevard, Savannah, GA
31406; e-mail: mcthomas@southuniversity.edu.

Infectious Diseases
Neurology and Psychiatry
Respiratory
Resuscitation
Shock
Toxicology
Traumatic Injury
Pharmacy Services and Patient Safety
Emergency Preparedness

Analgesia and Sedation

Pain Management
Todd KH, Ducharme J, Choiniere M, et al. Pain
in the emergency department: results of the pain
and emergency medicine initiative (PEMI)
multicenter study. J Pain 2007;8:4606.
This was a prospective, multicenter cohort
study conducted in 20 U.S. and Canadian EDs.
Included were 842 patients aged 8 years or older
with a presenting pain score of 4 or more (010
numeric rating scale). Patients completed
structured interviews and data were abstracted
from medical records. Although the median pain
score in this cohort was 8, only 60% were given
analgesics. Patients who were given analgesics

KEY ARTICLES FOR THE EMERGENCY MEDICINE PHARMACIST Thomas et al

received them after a median of 90 minutes.
Approximately three-fourths of the patients had
moderate to severe pain upon discharge from the
ED. This study highlights that even though pain
intensity is high in the ED, analgesics remain
under-utilized, there are significant delays to
treatment and pain management needs to be
improved.
Holdgate A, Pollock T. Systematic review of the
relative efficacy of non-steroidal antiinflammatory drugs and opioids in the treatment
of acute renal colic. BMJ 328:1401 doi:
10.1136/bmj.38119.581991.55.
The intent of this systematic review was to
identify randomized controlled trials comparing
opioids to non-steroidal anti-inflammatory drugs
(NSAIDs) for acute renal colic. The main
outcomes of interest were pain scores, time to
pain relief, need for rescue analgesia, pain
recurrence and adverse effects. A total of 20
trials (n = 1613 patients) were included in the
final analyses. The trials used 7 different NSAIDs
and 5 different opioids, most of which were given
via the parenteral route (intravenous or
intramuscular). Pooled analysis of trials that
used an NSAID other than ketorolac, showed
greater pain reduction (4.6 mm) on a 100-mm
visual analogue scale. The addition of trials
using ketorolac did not change the results.
However, note that this difference is unlikely to
be clinically significant. A pooled analysis of
studies that reported the need for rescue
analgesia showed that patients receiving NSAIDs
were less likely to need analgesic rescue (relative
risk [RR] 0.75, 95% confidence interval [CI] 0.61
to 0.93). There was no significant difference in
time to pain relief. There was a less incidence of
adverse effects, primarily vomiting, in patients
receiving NSAIDs (RR 0.35, 95% CI 0.23 to
0.53). However, this may be dependent on the
type of opioid used. For instance, studies using
pethidine showed a higher risk for vomiting.
The authors concluded that NSAIDs achieve a
greater analgesic response to opioids and may
reduce the short-term need for rescue therapy
compared to opioids.
Patanwala AE, Keim SM, Erstad BL. Intravenous
opioids for severe acute pain in the emergency
department. Ann Pharmacother 2010;44:18009.
This is a review article that discusses clinical
trials pertaining to the selection and dose of
intravenous opioids in the ED. A total of 10
comparative studies in the ED were retrieved. An

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additional three studies were conducted in the

pre-hospital setting. The article includes a table
of all comparative studies and includes the dose
used, pain reduction and adverse events. The
most common opioids used and special patient
populations for their selection are discussed.
Dosing strategies for optimal pain management
and relevant protocols are provided. Note that
due to the large number of relatively small trials
related to opioids conducted in this setting, the
authors were unable to include each trial
individually. However, this review serves as a
starting point for the reader to evaluate each of
these important studies.
Zempsky WT, Joseph P. Cravero JP. Relief of
pain and anxiety in pediatric patients in
emergency medical systems. Pediatrics
2004;114;134856.
This guideline document was developed by the
American Academy of Pediatrics Committee on
Pediatric Emergency Medicine, and Section of
Anesthesiology and Pain Medicine. This article
discusses the management of pain and anxiety
from the context of pre-hospital care and the ED.
It includes creation of an appropriate
environment to minimize distress and strategies
for pain assessment. Guidelines are provided for
the use of oral analgesics such as acetaminophen,
ibuprofen, and opioids. The use of topical
analgesia for minor procedures is also discussed.
These include a eutectic mixture of local
anesthetics (EMLA), liposomal 4% lidocaine
cream (LMX4) and other combination agents
such as lidocaine, epinephrine and tetracaine
(LET). The use of oral sucrose in neonates is
also discussed. The guidelines state that there is
no evidence that pain management masks
symptoms and interferes with adequate
assessment and diagnoses. Finally, the need for
sedation protocols and quality improvement
programs are discussed.
Procedural Sedation
Godwin SA, Caro DA, Wolf SJ, et al. American
College of Emergency Physicians. Clinical policy:
procedural sedation and analgesia in the
emergency department. Ann Emerg Med
2005;45:17796.
This clinical policy developed by the American
College of Emergency Physicians is broad in its
scope and covers major questions related to
procedural sedation and analgesia in the ED. It
includes a discussion of resources needed in

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PHARMACOTHERAPY Volume 31, 2011

terms of personnel and equipment, preprocedural fasting, patient assessment and

monitoring, as well as the safety of medications
that are typically utilized. No specific dosing
information of sedative or analgesics is provided.
The policy simply reviews evidence regarding the
safety of these agents.
American Society of Anesthesiologists Task
Force on Sedation and Analgesia by NonAnesthesiologists. Practice guidelines for
sedation and analgesia by non-anesthesiologists.
Anesthesiology 2002;96:100417.
This guideline was developed by the American
Society of Anesthesiologists Task Force on
Sedation
and
Analgesia
by
NonAnesthesiologists. It is applicable to procedures
performed in a variety of settings, including the
ED. The guideline is broad in its scope and
provides recommendations regarding preprocedure patient evaluation and preparation,
appropriate patient monitoring, as well as
administration of sedatives and analgesics. The
task force recommends that intravenous sedatives
and analgesics should be administered in small
incremental doses to achieve desired end points
of analgesia and sedation. Patient rescue and the
use of reversal agents are also discussed.
Innes G, Murphy M, Nijssen-Jordan C,
Ducharme J, Drummond A. Procedural sedation
and analgesia in the emergency department.
Canadian Consensus Guidelines. J Emerg Med
1999;17:14556.
This guideline was developed by the
Emergency Medicine Working Committee of the
Canadian Association of Emergency Physicians.
It provides an overview of procedural sedation
and analgesia in the ED. This includes presedation preparation and fasting, physician skills,
staffing, equipment required, monitoring, drug
administration and post-sedation care. The
guideline does not provide specific
recommendations regarding selection or dosing
of sedatives and analgesics. However, important
principles of drug administration are discussed,
such as: titration to desired patient dependent
endpoints, slow drug infusion (e.g., over 1 to 2
minutes) rather than rapid boluses and the
availability of reversal agents during procedures.
Miner JR, Burton JH. Clinical practice advisory:
emergency department procedural sedation with
propofol. Ann Emerg Med 2007;50:1827.
This clinical practice advisory is a review
article written in response to the popularity and

widespread use of propofol in the ED. The

authors provide detailed information regarding
the indications for use, contraindications, dosage
and administration, monitoring, and potential
adverse effects. The authors incorporate most
previous trials of propofol in their discussion.
Loh G, Dalen D. Low-dose ketamine in addition
to propofol for procedural sedation and analgesia
in the emergency department. Ann Pharmacother
2007;41:48592.
In this review article, a literature search was
performed to determine if low-dose ketamine in
combination with propofol was safer and more
effective than propofol alone for procedural
sedation in the ED. A total of 11 comparative
trials were included; 5 pediatric and 6 adult
studies. Most had small sample sizes and were
conducted in non-ED settings. Overall, the
addition of ketamine to propofol did not change
time to hospital discharge when compared to
propofol alone. In the pediatric studies there was
more pronounced hypotension in the propofol
only groups, however the requirement for
intervention was not reported. There was no
difference with regard to the occurrence of
vomiting or emergence reactions. In the adult
studies, the increased risk for cardio-respiratory
depression in the propofol only group was
conflicting and reported in only two studies. In
one study, patients had greater nausea and
emergence reactions in the ketamine-propofol
combination group. The authors concluded that
there was insufficient evidence to support that
routine use of ketamine in combination with
propofol instead of propofol alone.
Mace SE, Barata IA, Cravero JP, et al. Clinical
policy:
evidence-based
approach
to
pharmacologic agents used in pediatric sedation
and analgesia in the emergency department. Ann
Emerg Med 2004;44:34277.
This clinical policy developed by the American
College of Emergency Physicians focuses on the
safe and effective use of common medications
used for pediatric procedural sedation and
analgesia in the ED. These include: etomidate,
fentanyl/midazolam combination, ketamine,
methohexital, pentobarbital, and propofol.
Critical issues are presented in a question and
answer format followed by a level of evidence
recommendation. This policy does not address
the dosage, administration or monitoring for
each of these agents. Rather, an evidence-based
approach is used to provide broad

KEY ARTICLES FOR THE EMERGENCY MEDICINE PHARMACIST Thomas et al

recommendations regarding the safety and
effectiveness of each of these agents.
Mace SE, Brown LA, Francis L, et al. Clinical
policy: critical issues in the sedation of pediatric
patients in the emergency department. Ann
Emerg Med 2008;51:37899.
This clinical policy was developed by the
American College of Emergency Physicians to
supplement a previous policy that focused on
medications for pediatric sedation and analgesia
in the ED. The use of two sedatives, nitrous
oxide and chloral hydrate are discussed. In
addition, the policy addresses the use of oral
sucrose during minor, painful procedures in
neonates. Recommendations are also provided
for pre-procedural fasting and safe discharge after
the procedure.
Rapid Sequence Intubation
Hohl CM, Kelly-Smith CH, Yeung TC, Sweet
DD, Doyle-Waters MM, Schulzer M. The effect
of a bolus dose of etomidate on cortisol levels,
mortality, and health services utilization: a
systematic review. Ann Emerg Med
2010;56:10513.
This was a qualitative and quantitative
systematic review of the literature. The primary
objective was to evaluate the effect of a single
bolus dose of etomidate on adrenal function
compared to other induction agents used for
rapid sequence intubation. The effect of
etomidate was also evaluated with respect to
mortality, length of stay in the intensive care unit
(ICU) and hospital, and duration of mechanical
ventilation. A total of 20 studies were included,
18 randomized controlled studies, one
nonrandomized study and one retrospective
comparison. The authors rated the quality of
randomized controlled trials using the Jadad
scoring system. However, none were excluded
from the analysis, since only 1 trial was
considered to be high quality. Between 1 and 4
hours post-induction there were statistically
significant differences between the etomidate and
control groups with regard to mean cortisol
levels. The mean differences were 6.1, 13.3, 12.6
and 16.4 mcg/dL at 1, 2, 3 and 4 hours postinduction, respectively. There were no
statistically significant differences beyond this
time frame. None of the studies showed any
difference in mortality, which was consistent with
the pooled analysis (odds ratio [OR] 1.14, 95%
CI 0.81 to 1.60, p=0.59). Only one trial showed

457e

a longer duration on the ventilator (6.3 versus

1.5 days, p=0.007), ICU length of stay (8.1 versus
3 days, p=0.011) and hospital length of stay (13.9
versus 6.4 days, p=0.007) with etomidate use.
However, this was a small study including only
30 patients and the etomidate patients had higher
baseline Injury Severity Scores (Hildreth AN,
Mejia VA, Maxwell RA, et al. Adrenal suppression
following a single dose of etomidate for rapid
sequence induction: a prospective randomized
study. J Trauma 2008;65:573579). The authors
of this systematic review concluded that a single
dose of etomidate transiently decreases cortisol
levels, but has not been shown to increase
mortality.
Tekwani KL, Watts HF, Sweis RT, Rzechula KH,
Kulstad EB. A comparison of the effects of
etomidate and midazolam on hospital length of
stay in patients with suspected sepsis: a
prospective, randomized study. Ann Emerg Med
2010;56:4819.
In this randomized controlled trial, 122
patients with suspected sepsis received either
etomidate (0.3 mg/kg) or midazolam (0.1 mg/kg)
for rapid sequence intubation in the ED. The
primary outcome was the difference in hospital
length of stay between the groups. There were
no baseline differences between groups. In the
intent-to-treat analysis, there was no statistical
difference in the primary outcome of hospital
length of stay between etomidate and midazolam
(7.3 versus 9.5 days, p=0.17). ICU length of stay
and days on the ventilator were also similar
between groups. Mortality was 43% and 36% in
the etomidate and midazolam groups,
respectively. There was no statistically significant
difference in the Kaplan-Meier survival analysis
(p=0.22). The authors concluded that there was
no significant difference in hospital length of stay
between the groups. Note that this study was not
powered to show a mortality difference.
However, according to a post-hoc analysis, the
authors comment that the study was adequately
powered to show 25% difference mortality
between groups. Larger studies are needed to
confirm this finding. This trial is important
because it was conducted in patients with sepsis;
a patient population that is particularly at risk for
adrenal insufficiency, and in whom the use of
etomidate is typically discouraged.
Albert SG, Ariyan S, Rather A. The effect of
etomidate on adrenal function in critical illness: a
systematic review. Intensive Care Med
2011;37:90110.

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PHARMACOTHERAPY Volume 31, 2011

The primary objective of this systematic review

was to determine all cause mortality at 28 days
for etomidate versus comparator drugs.
Mortality data was reported in 14 (n=3,516) of
the 21 trials included in the meta-analysis.
Those receiving etomidate had a higher mortality
rate compared with the control groups (RR 1.19,
95% CI 1.10 to 1.30). Etomidate also caused
more adrenal insufficiency (RR 1.64, 95% CI 1.52
to 1.77). The subset of trials that did not include
patients with sepsis did not find an increased risk
of death; however, mortality was increased when
trials were examined which included patients
with sepsis (RR 1.22, 95% CI 1.11 to 1.35). The
authors concluded that etomidate is associated
with adrenal insufficiency and an increased
mortality rate. They recommend a re-analysis of
the data or a well designed randomized
controlled trial to examine the effect of
concomitant corticosteroids with etomidate on
these outcomes.
Jabre P, Combes X, Lapostolle F, et al. Etomidate
versus ketamine for rapid sequence intubation in
acutely ill patients: a multicentre randomised
controlled trial. Lancet 2009;374:293300.
This multicenter, randomized, controlled study
was conducted in France. The study enrolled
655 patients who needed emergent intubation.
Patients were randomized to receive either
etomidate 0.3 mg/kg or ketamine 2 mg/kg as an
induction agent. The primary outcome was
morbidity, which was defined as the maximum
sequential organ failure assessment (SOFA) score
in the first three days after intubation. This did
not differ significantly between the etomidate and
ketamine groups (10.3 versus 9.6, p=0.056,
respectively). Also, there was no difference
between secondary outcomes, such as 28-day
mortality, vasopressor use, duration of
mechanical ventilation or length of stay in the
ICU. However, a greater percentage of patients in
the etomidate group had adrenal insufficiency.
This did not influence 28-day mortality. The
authors concluded that ketamine is a safe and
effective alternative to etomidate and should be
considered in patients with sepsis.
Perr y JJ, Lee JS, Sillberg VA, Wells GA.
Rocuronium versus succinylcholine for rapid
sequence induction intubation. Cochrane
Database
of
Systematic
Reviews
2008;2:CD002788.
This is a systematic review and meta-analysis
of controlled clinical trials comparing

rocuronium and succinylcholine for rapid

sequence intubation. The primary outcome was
a comparison of intubating conditions provided
by the two neuromuscular blockers. A
comprehensive search of the literature resulted in
the inclusion of 37 studies in the meta-analysis
(n = 2690 patients). Overall, succinylcholine
provided superior intubating conditions
compared to rocuronium. However, there was
significant heterogeneity between studies.
Interestingly, there was no difference in the
primary outcome in studies that used higher
doses of rocuronium (0.9 to 1.2 mg/kg). The
authors concluded that rocuronium should only
be used as an alternative, when succinylcholine is
contraindicated.
Reynolds SF, Heffner J. Airway management of
the critically ill patient: rapid-sequence
intubation. Chest 2005; 27:13971412.
Although the target audience for this review
article is ICU physicians, most of the information
provided is applicable to emergency medicine.
This article provides an overview of fundamental
airway management concepts. It emphasizes the
pharmacology of medications used for preinduction, induction and neuromuscular
blockade. The article includes tables with dose,
indications, cautions and pharmacokinetic
information for the agents discussed. This article
is a good starting point for clinicians
familiarizing themselves with important concepts
related to rapid sequence intubation.
Cardiovascular Emergencies
Acute Coronary Syndromes
Anderson JL, Adams CD, Antman EM, et al.
ACC/AHA 2007 guidelines for the management
of patients with unstable angina/non-ST-elevation
myocardial infarction: executive summary. A
report of the American College of
Cardiology/American Heart Association Task
Force on Practice Guidelines (Writing
Committee to Revise the 2002 Guidelines for the
Management of Patients with Unstable
Angina/Non-ST-Elevation Myocardial Infarction).
Circulation 2007;116:80377.
This is a guideline developed by the American
College of Cardiology and the American Heart
Association in collaboration with the American
College of Emergency Physicians and other
organizations. The standard classifications for
recommendations are made using the precision of
treatment effect (level A, B or C) and the size of

KEY ARTICLES FOR THE EMERGENCY MEDICINE PHARMACIST Thomas et al

the effect (Class I, IIa, IIb, or III). The focus of
the guideline is on the diagnosis and
management of the patient with an acute
coronary syndrome without ST elevation.
Antman EM, Anbe DT, Armstrong PW, et al.
ACC/AHA guidelines for the management of
patients with ST-elevation myocardial infarction.
A report of the American College of
Cardiology/American Heart Association Task
Force on Practice Guidelines (Writing
Committee to Revise the 1999 Guidelines for the
Management of Patients with Acute Myocardial
Infarction). Circulation 2004;110:e82e293.
This is the latest full guideline published by the
American College of Cardiology and the American
Heart Association for the management of patients
with ST-segment elevation myocardial infarction.
Updates to this guideline are published, but only
include the changes and are not stand-alone
documents. This comprehensive guideline makes
recommendations related to pre-hospital care,
management in the ED including reperfusion
strategies, complete hospital care, recovery and
secondary prevention. Implications for the ED
include early detection with electrocardiograms
and cardiac specific biomarkers, management of
ischemic pain with oxygen, nitrates and morphine,
antithrombotic therapy with aspirin, and early
reperfusion with fibrinolytics or percutaneous
coronary interventions.
Antman EM, Hand M, Armstrong PW, et al.
2007 focused update of the ACC/AHA 2004
guidelines for the management of patients with
ST-elevation myocardial infarction. A report of
the American College of Cardiology/American
Heart Association Task Force on Practice
Guidelines. Circulation 2008;117:296329.
Focused
updates
provide
new
recommendations based on emerging data
without the exhaustive evaluation of complete
guideline development. This focused update
recommends stopping non steroidal antiinflammatory drugs at presentation and during
hospitalization. In addition, beta-blockade
should be initiated within 24 hours unless there
are contraindications. The use of intravenous
beta blockers is limited to patients who are
hypertensive without contraindications.
Anticoagulants should be administered for at
least 48 hours and up to 8 days. Preference is
given to low molecular weight heparin because of
concerns for the development of heparin induced
thrombocytopenia. Other changes included

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defining appropriate candidates and ancillary

drug use for percutaneous coronary intervention.
Kushner FG, Hand M, Smith SC, et al. 2009
focused updates: ACC/AHA guidelines for the
management of patients with ST-elevation
myocardial infarction (Updating the 2004
guideline and 2007 focused update) and
ACC/AHA/SCAI guidelines on percutaneous
coronary intervention (updating the 2005
guideline and 2007 focused update): A report of
the American College of Cardiology
Foundation/American Heart Association Task
Force on Practice Guidelines. J Am Coll Cardiol
2009;54:220541.
This focused update changed the
recommendation for the use of glycoprotein
IIb/IIIa inhibitors before arrival to the cardiac
catherization laboratory for primary
percutaneous coronary intervention to uncertain.
Starting glycoprotein IIb/IIIa at the time of
percutaneous coronary intervention is
reasonable. Loading doses of prasugrel (60 mg)
or clopidogrel (300-600 mg) are recommended as
early as possible before percutaneous coronary
intervention. Patients at high risk of bleeding
should be considered for bivalrudin for
anticoagulation. Additional recommendations
are made relative to glucose control, contrast
media selection in patients with chronic kidney
disease, and the use of advanced physiological
measurements during percutaneous coronary
intervention.
Krumholz HM, Anderson JL, Bachelder BL, et
al. ACC/AHA 2008 performance measures for
adults with ST-elevation and non ST-elevation
myocardial infarction: A report of the American
College of Cardiology/American Heart
Association Task Force on Performance Measures
(Writing Committee to Develop Performance
Measures for ST-Elevation and Non ST-Elevation
Myocardial
Infarction).
Circulation
2008;118:25962648.
Ensuring patients receive optimal evidence
based care in the emergency department is
important. In collaboration with the American
College of Emergency Physicians, the American
College of Cardiology with the American Heart
Association developed performance measures
that can be used for quality control purposes.
These performance measures are consistent with
other organizations such as the Joint
Commission and the Centers for Medicare and
Medicaid Services.

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PHARMACOTHERAPY Volume 31, 2011

Harrington RA, Becker RC, Cannon CP, et al.

Antithrombotic therapy for non-ST-segment
elevation acute coronary syndromes. American
College of Chest Physicians Evidence-Based
Clinical Practice Guidelines (8th Edition). Chest
2008;133:670S707S.
Graded recommendations from the American
College of Chest Physicians are provided relative
to antithrombotic therapy. Specifically, all
patients should receive aspirin or alternatively
clopidogrel if there is a contraindication to
aspirin. Additional antiplatelet therapy with a
thienopyridine and glycoprotein IIb/IIIa
inhibitors is based on the presence of high risk
features and the timing of invasive strategies.
Anticoagulation recommendations are also made
based on the type, invasive versus conservative
management strategies.
Goodman SG, Menon V, Cannon CP, Steg G,
Ohman EM, Harrington RA. Acute ST-segment
elevation myocardial infarction. American
College of Chest Physicians Evidence-Based
Clinical Practice Guidelines (8th Edition). Chest
2008;133:708S775S.
A supplement from the American College of
Chest Physicians details evidence based
recommendations for the care of patients with
ST-segment elevation myocardial infarction.
Recommendations are made for appropriate use
of fibrinolysis, antiplatelet therapy, and the use of
anticoagulants.
Arrhythmias
Fuster V, Rydn LE, Cannom DS, 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). Circulation
2006;114:e257e354.
Practice guidelines from the American College
of Cardiology, the American Heart Association,
and the European Society of Cardiology are
presented in this comprehensive guideline. A
detailed discussion of the mechanisms causing
atrial fibrillation, the clinical consequences and
evaluation of patients, and treatment are
presented. Much of this guideline focuses on

chronic issues related to rate and rhythm control

and anticoagulation. Management of patients
presenting to the emergency department is also
embedded within the guideline document.
Specific recommendations are made for
ventricular rate control based on the presence of
heart failure, pharmacological cardioversion, and
direct current cardioversion.
Singer DE, Albers GW, Dalen JE, et al.
Antithrombotic therapy in atrial fibrillation.
American College of Chest Physicians EvidenceBased Clinical Practice Guidelines (8th Edition).
Chest 2008;133:546S592S.
Recommendations for the appropriate choice
of antiplatelet and anticoagulant medications are
based on multiple patient factors including past
medical history of stroke, transient ischemic
attack, systemic embolism, or the presence of risk
factors for developing an ischemic stroke. In
addition to long term antithrombotic recommendations for patients with atrial fibrillation,
other situations covered include atrial flutter,
valvular heart disease, atrial fibrilliation
associated with cardiac surgery, and anticoagulation for elective and emergent cardioversion.
Zipes DP, Camm AJ, Borggrefe M, et al.
ACC/AHA/ESC 2006 guidelines for management
of patients with ventricular arrhythmias and the
prevention of sudden cardiac death: a report of
the American College of Cardiology/American
Heart Association Task Force and the European
Society of Cardiology Committee for Practice
Guidelines (Writing Committee to Develop
Guidelines for Management of Patients with
Ventricular Arrhythmias and the Prevention of
Sudden Cardiac Death). J Am Coll
Cardiol2006;48:e247e346.
The American College of Cardiology, the
American Heart Association, and the European
Society of Cardiology developed evidence based
recommendations for patients with ventricular
arrhythmias. Domains included in this
comprehensive document include noninvasive
and electrophysiological testing and the role of
medications, ablation, and surgical procedures
for long term management. Acute management
of ventricular arrhythmias is also presented
which may serve as a useful guide for the
pharmacist practicing in the ED. An additional
useful tool is a table that reviews important drug
interactions contributing to arrhythmogenesis.

KEY ARTICLES FOR THE EMERGENCY MEDICINE PHARMACIST Thomas et al

Hypertensive Urgency and Emergency
Amin A. The EMCREG-International Consensus
Panel Recommendations: Parenteral medication
for hypertension with symptoms. Ann Emerg
Med 2008;51:S10S15.
This article was part of a larger series of
consensus recommendations devoted to
hypertension in the ED setting. Summary
recommendations are provided, however they are
not graded based on the level of evidence. A useful
table contained within the document outlines
recommended treatment approaches, potential
adverse events, and clinical pearls. An additional
table describes appropriate doses, indications, and
precautions of antihypertensive medications.
Varon J. Treatment of acute severe hypertension.
Current
and
newer
agents.
Drugs
2008;68:28397.
This comprehensive review article outlines the
classification of hypertension, management of
severe hypertension, and pharmacological agents.
Dose, indication, and pharmacokinetics are
reviewed for commonly used drugs to treat severe
hypertension and include enalaprilat, labetalol,
esmolol, clevidipine, nicardipine, nifedipine,
fenoldopam, hydralazine, diuretics, nitroglycerin,
and sodium nitroprusside.
Coagulation
Warfarin Reversal
Ansell J, Hirsch J, Hylek E, Jacobson A,
Crowther M, Palareti G. Pharmacology and
management of the vitamin K antagonists. Chest
2008;133:160S198S.
Rapid reversal of excessive anticoagulation is
sometimes necessary. Even though the
guidelines presented outline appropriate use of
warfarin including dosing and monitoring, there
are evidence based recommendations to manage
elevated international normalized ratios or
serious bleeding in patients taking warfarin. For
serious or life threatening bleeding, intravenous
vitamin K is recommended to be administered
with fresh frozen plasma, prothrombin complex
concentrates, or recombinant activated factor VII
(rFVIIa).
Vigu B. Bench-to-bedside review: optimising
emergency reversal of vitamin K antagonists in
severe haemorrhagefrom theory to practice.
Crit care 2009;13:20918.

461e

This review outlines the evidence for the

therapeutic options for reversal of
anticoagulation caused by vitamin K antagonists.
A detailed discussion is provided on the use of
fresh frozen plasma and prothrombin complex
concentrates. Important practical issues are
addressed including relative rates of reversal,
viral safety, thrombogenicity, and dosing of
reversal agents.
Lessinger CA, Blatt PM, Hoots WK, Ewenstein
B. Role of prothrombin complex concentrates in
reversing warfarin anticoagulation: A review of
the literature. Am J Hematol 2008;83:13743.
Prothrombin complex concentrates replace
deficient clotting factors and are listed as an
option to rapidly reverse anticoagulation. Fresh
frozen plasma is commonly used to rapidly
reverse excessive anticoagulation and is the
standard of care in the United States. In other
parts of the world, prothrombin complex
concentrates are first line. This review details the
relative amounts of coagulation factors and data
comparing prothrombin complex concentrates to
vitamin K or fresh frozen plasma. It also details
dosing and potential complications.
Thrombosis
Kearon C, Kahn SR, Angelli G, Goldhaber S,
Raskob GE, Comerota AJ. Antithrombotic
therapy for venous thromboembolic disease.
American College of Chest Physicians EvidenceBased Clinical Practice Guidelines (8th Edition).
Chest 2008;133:454S545S.
Familiarity with the American College of Chest
Physicians guidelines for the treatment of
thromboembolism is paramount for the
pharmacist in the ED. Evidence based
recommendations are provided for treating
pulmonary embolism and deep vein thrombosis.
The cornerstone of management is
anticoagulation with a parenteral drug such as
unfractionated heparin, low molecular weight
heparin, or fondaparinux. Severe cases may
require administration of thrombolytics,
systemically or locally, or surgery to remove the
clot. Recommendations are also provided for
long term management primarily with vitamin K
antagonists.
Diabetic Emergencies
Kitabchi AE, Umpierrez GE, Miles JM, Fisher
JN. Hyperglycemic crises in adult patients with

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PHARMACOTHERAPY Volume 31, 2011

diabetes. Diabetes Care 2009;32:133543.

This is a consensus statement from the
American Diabetes Association. It reviews the
epidemiology, pathogenesis, precipitating factors,
diagnoses and management of diabetic
ketoacidosis and hyperglycemic hyperosmolar
state. It contains a detailed algorithm regarding
the various treatment options including dosing
information, which is supplemented by discussion
of fluid therapy, the use of insulin, correction of
electrolyte abnormalities and acidosis.
Wolfsdorf J, Glaser N, Sperling MA. Diabetic
ketoacidosis in infants, children, and adolescents:
A consensus statement from the American
Diabetes Association.
Diabetes Care
2006;29:11509.
This is a consensus statement from the
American Diabetes Association. The article
highlights key differences between adults and
pediatric patients with regard to diabetic
ketoacidosis. The pathophysiology and
precipitating factors in pediatrics are briefly
discussed. The majority of the article provides
detailed information regarding the management
of diabetic ketoacidosis in pediatrics.
Infectious Diseases
Intra-abdominal

classification and etiology of adult intraabdominal infections, surgical and pharmacologic

management. Other aspects of management
including when to start antimicrobial therapy
and coverage of enterococci and Candida spp. are
discussed. This article provides excellent
background information on intra-abdominal
infections, how this type of infection differs from
other sources of infection, and the difference
between uncomplicated and complicated.
Furthermore, the authors explain the rationale
behind selecting appropriate empiric
antimicrobials.
Meningitis
Tunkel AR, Hartman BJ, Kaplan SL, et al.
Practice guidelines for the management of
bacterial meningitis. Clin Infect Dis
2004;39:126784.
The IDSA developed these practice guidelines
to aid providers in both the diagnosis and
management of bacterial meningitis; they are
representative of data published through May
2004.
Included in the guidelines are
management algorithms for both adult and
pediatric patients. There are also four tables in
the reading that review various aspects of
pharmacotherapy
including:
empiric
antimicrobial choices based on Gram stain
results, empiric antimicrobial therapy based on
patient age and predisposing conditions (e.g.
head trauma), specific antimicrobial therapy
based on the pathogen isolated and susceptibility
data, and dosing regimens for neonates, infants
and children, and adults.

Solomkin JS, Mazuski JE, Bradley JS, et al.

Diagnosis and management of complicated intraabdominal infection in adults and children:
guidelines by the Surgical Infection Society and
the Infectious Diseases Society of America. Clin
Infect Dis 2010;50:13364.
The Surgical Infection Society and the
Infectious Diseases Society of America (IDSA)
updated the guidelines for both complicated and
uncomplicated intra-abdominal infections in
2009. These guidelines replace those from 2002
and 2003 and include recommendations for both
pediatric and adult patients. Appropriate timing
of initiation of antimicrobial therapy,
recommended antimicrobial regimens for both
community-acquired and health care-associated
infections, pharmacokinetic considerations, the
role of surgery, and duration of therapy are
addressed.

Kim KS. Acute bacterial meningitis in infants and

children. Lancet Infect Dis 2010;10:3242.
Even though practitioners should refer to the
bacterial meningitis practice guidelines
established by the IDSA, this review provides
more recent information. The author performed a
Medline search with date limits of January 2000
to June 2009, but earlier original articles were
included if they formed the foundation for more
recent studies. An excellent overview of
epidemiology and pathogenesis in addition to
information on diagnosis and antimicrobial
treatment is provided.

Blot S, De Waele JJ. Critical issues in the clinical

management of complicated intra-abdominal
infections. Drugs 2005;65:161120.
This review article briefly describes the

Miranda J, Tunkel AR. Strategies and new

developments in the management of bacterial
meningitis. Infect Dis Clin N Am
2009;23:92543.

KEY ARTICLES FOR THE EMERGENCY MEDICINE PHARMACIST Thomas et al

The authors of this review address important
pharmacologic principles that must be
understood for the successful treatment of
bacterial meningitis and provide a concise
overview of the various antimicrobial agents that
may be used. Principles discussed include
antimicrobial penetration of the blood-brain
barrier, activity of the pharmacologic agents in
purulent cerebrospinal fluid, and intrinsic
pharmacodynamic properties of the various
antimicrobials. Recent experimental and clinical
data are also included in the review.
De Gans J, Van De Beek D, for the European
Dexamethasone in Adulthood Bacterial
Meningitis Study Investigators. Dexamethasone
in adults with bacterial meningitis. N Engl J Med
2002;347:154956.
A prospective, randomized, double-blind,
multicenter trial was conducted to evaluate
dexamethasone therapy in adult patients with
bacterial meningitis. There were 301 patients
randomized to receive either dexamethasone 10
mg or placebo 15 to 20 minutes before or with
the first dose of antibiotics. The therapy was
continued for a total of four days and was
administered every 6 hours. One hundred and
fifty seven patients received dexamethasone and
144 patients were randomized to placebo.
Dexamethasone was associated with a reduction
in the risk of an unfavorable outcome, defined as
a Glasgow Outcome Scale score at eight weeks of
1 to 4 (RR 0.59, 95% CI 0.37 to 0.94, p=0.03). A
reduction in mortality was noted with
dexamethasone as well (RR of death 0.48, 95%
CI 0.24 to 0.96, p=0.04). Based on these results,
the authors concluded that treatment with
dexamethasone improves outcomes in adult
patients with bacterial meningitis. In addition,
the authors stated that dexamethasone does not
increase the risk of gastrointestinal bleeding as
two cases were reported in the dexamethasone
group and five were reported in the placebo
group.
Nau R, Sorgel F, Prange HW. Pharmacokinetic
optimization of the treatment of bacterial central
nervous system infections. Clin Pharmacokinet
1998;35:22346.
This
review
discusses
important
pharmacokinetic and pharmacodynamic concepts
in successfully treating central nervous system
(CNS) infections. In addition to addressing these
concepts, the article discusses the increase in
emergence of resistant organisms as treatment

463e

failure could result. Topics that are discussed

include the various factors affecting the entry of
pharmacologic agents into the central nervous
system, pharmacokinetic issues surrounding the
treatment of bacterial infections (i.e., blood-CNS
barrier), estimating drug concentrations in
cerebrospinal fluid (CSF), pharmacodynamics
concerns, and treatment. The treatment section
elaborates upon both empiric and pathogendirected treatment before focusing on the various
antibiotic classes utilized in the treatment of
bacterial meningitis and other CNS infections.
Respiratory Tract
Mandell LA, Wunderink RG, Anzueto A, et al.
Infectious Diseases Society of America/American
Thoracic Society consensus guidelines on the
management of community-acquired pneumonia
in adults. Clin Infect Dis 2007;44(suppl
2):S2772.
Prior to the publication of these consensus
guidelines, the IDSA and the American Thoracic
Society (ATS) both had their own respective
guidelines for community-acquired pneumonia
(CAP). These two organizations formed a joint
committee and developed a unified guideline. A
strong recommendation with level I supporting
evidence (evidence from well-conducted,
randomized controlled trials) suggests
determining a severity-of-illness score such as the
CURB-65 in order to identify patients who could
potentially be treated as outpatients. Diagnostic
testing is still controversial in this patient
population, but a chest radiograph or other
image with an infiltrate and microbiologic data in
addition to signs and symptoms of pneumonia
are required for diagnosis. However, this is a
moderate recommendation with level III evidence
(evidence from case studies and expert opinion).
Patients who were previously healthy with no
risk factors for drug-resistant Streptococcus
pneumoniae infection should be treated in the
outpatient setting with a macrolide or
doxycycline. If comorbidities are present or the
patient is at risk for drug-resistant S. pneumoniae
infection, they should receive a respiratory
fluoroquinolone (strong recommendation; level
I) or a !-lactam plus a macrolide (strong
recommendation; level I). This same treatment
regimen is recommended for patients treated in a
hospital ward. For patients admitted to the ICU,
the empiric regimen is similar but coverage for
methicillin-resistant Staphylococcus aureus

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PHARMACOTHERAPY Volume 31, 2011

(MRSA) and Pseudomonas aeruginosa should be

considered. As with other infections, empiric
therapy should be streamlined once the etiology
is known. Treatment duration and time to first
antibiotic dose are also discussed. This guideline
does not pertain to immunocompromised
patients. For these patients, the IDSA and ATS
refer providers to the guidelines for health careassociated pneumonia (HCAP).

penicillin which continues to be the drug of

choice. However, if the patient is allergic to
penicillin, alternative antimicrobials are available
and include erythromycin and clindamycin.
Patients suspected of having a recurrent episode
and treatment, if indicated, are also discussed.

The American Thoracic Society and the

Infectious Diseases Society of America.
Guidelines for the management of adults with
hospital-acquired, ventilator-associated, and
healthcare-associated pneumonia. Am J Respir
Crit Care Med 2005;171:388416.
These guidelines address hospital-acquired
pneumonia (HAP), HCAP, and ventilatorassociated pneumonia (VAP) and were also
prepared by a joint committee of the IDSA and
the ATS. One of the key recommendations in
this guideline is that patients with HCAP be
treated for the same multi-drug resistant
pathogens as those patients with HAP and VAP.
Risk factors for HCAP are often overlooked or
difficult to identify in patients who present to the
ED, but include patients who were hospitalized
for two or more days within the past 90 days,
nursing home or long-term care facility residents,
patients who receive hemodialysis in the hospital
or clinic setting, and those who have received
intravenous antibiotic therapy, chemotherapy, or
wound care within the past 30 days. Other
points discussed in this guideline are cultures
that should be obtained, early antibiotic therapy,
combination therapy, therapy alternatives for
multi-drug resistant pathogens, duration of
antibiotic therapy, and antibiotic de-escalation.

Centers for Disease Control and Prevention.

Sexually transmitted diseases treatment
guidelines, 2010. MMWR Morb Mortal Wkly Rep
2010;59:1116.
These guidelines are an update to the
guidelines that were published in 2006. The
Centers for Disease Control (CDC) utilized a
multistage process when updating the guidelines.
This process included an evidence-based
literature review and the development of a draft
that was presented to a group of consultants
knowledgeable in the treatment of this patient
population in April 2009. Four topics were
discussed in detail before the guidelines were
updated. These subjects included alleviation of
signs and symptoms, treatment of infection,
prevention of sequelae, and prevention of
transmission. Eleven areas were noted to include
new information, but a change that has affected
clinical practice since the update was made
available to practitioners is the dose of
intramuscular ceftriaxone for Neisseria
gonorrhoeae. Since N. gonorrhoeae is known for
its ability to develop resistance to antimicrobial
therapies, the dose of ceftriaxone was increased
from 125 mg to 250 mg for all suspected cases of
N. gonorrhoeae. If intramuscular ceftriaxone is
not an option, the oral alternative remains
cefixime 400 mg as a single dose.

Bisno AL, Gerber MA, Gwaltney JM, Kaplan EL,

Schwartz RH. Practice guidelines for the
diagnosis and management of group A
streptococcal pharyngitis. Clin Infect Dis
2002;35:11325.
The objective of the IDSA guideline on group A
streptococcal pharyngitis was to provide an
update to the previous guideline published in
1997. This article focuses on both the diagnosis
and treatment of children and adults in whom
group A streptococcal pharyngitis is suspected. If
pharyngitis is included in the patients differential
diagnosis, physicians must determine which
confirmatory tests should be done, if any. If a
diagnosis of group A streptococcal pharyngitis
results, the patient should be treated with

Sexually Transmitted Diseases

Skin and Soft-tissue Infections

Stevens DL, Bisno AL, Chambers HF, et al.
Practice guidelines for the diagnosis and
management of skin and soft-tissue infections.
Clin Infect Dis 2005;41:13731406.
This guideline discusses infections ranging
from impetigo to those that are necrotizing and
require emergent surgical evaluation.
Staphylococcus aureus and Streptococcus pyogenes
are common causes of skin and soft-tissue
infections and selection of appropriate empiric
antimicrobial therapy is critical. For patients
with minor infections, empiric treatment
recommendations include semi-synthetic

KEY ARTICLES FOR THE EMERGENCY MEDICINE PHARMACIST Thomas et al

penicillins, first- or second-generation
cephalosporins, macrolides, or clindamycin.
However, providers should be aware that
approximately 50% of MRSA strains have
inducible or constitutive resistance to
clindamycin. Trimethoprim-sulfamethoxazole
and the tetracyclines are noted to cover most
community-acquired MRSA strains, but these
patients should be reevaluated in 24 to 48 hours
to ensure that they are responding to treatment.
If a patient presents with a severe infection or
returns to the ED with a progressing infection
despite empiric antibiotic therapy, a more
aggressive regimen based on Gram stain results
or culture and susceptibility data will be
required. Vancomycin, linezolid, or daptomycin
should be considered in those cases where MRSA
is suspected. In addition to impetigo, erysipelas,
cellulitis, and necrotizing infections, infections
secondary to animal or human bites, surgical site
infections, and infections in patients who are
immunocompromised are also discussed.
Abrahamian FM, Talan DA, Moran GJ.
Management of skin and soft-tissue infections in
the emergency department. Infect Dis Clin N Am
2008;22:89116.
This review article is unique as it discusses
skin and soft-tissue infections from the
perspective of the emergency medicine provider.
This group of practitioners usually initiates
empiric antimicrobial therapy without culture
and susceptibility results and may perform minor
surgical care. The authors focus on common
pitfalls in treatment, the role of blood and wound
cultures, patient disposition, MRSA infections,
and the various presentations that may be seen in
the ED. An emphasis is placed on MRSA
infections since the prevalence of the
community-acquired strain has increased and
plays an important role in the selection of
empiric antimicrobial therapy. Misclassifying
deep abscesses as cellulitis is common, so
providers should consider this in patients who
return to the ED after being started on empiric
therapy.
Lipsky BA, Berendt AR, Deery HG, et al.
Diagnosis and treatment of diabetic foot
infections. Clin Infect Dis 2004;39:885910.
Diabetic foot infections are associated with
high morbidity and are another skin and softtissue infection that is commonly evaluated in
the ED. S. aureus and other aerobic Grampositive cocci are the most common pathogens.

465e

For those patients who have chronic wounds or

have recently been treated with antimicrobials
Gram-negative rods should also be considered
when making recommendations for empiric
antimicrobial therapy. Anaerobic pathogens tend
to be associated with foot ischemia and gangrene.
These guidelines recommend selecting empiric
antimicrobials based on the severity of the
patients infection and the suspected pathogen.
For severe and more extensive infections, broadspectrum agents that cover Gram-positive cocci
including MRSA if indicated, Gram-negative
rods, and anaerobes should be considered. The
guidelines also discuss osteomyelitis in this
patient population.
Hartoch RS, McManus JG, Knapp S, Buettner
MF. Emergency management of chronic wounds.
Emerg Med Clin N Am 2007;25:20321.
As the population ages, emergency medicine
providers find themselves caring for patients with
both acute and chronic infections. Epidemiology
and pathophysiology of chronic wounds as well
as a description of normal tissue repair are
discussed.
The authors elaborate on the
different examples of chronic wounds and their
management. This review provides more
information on diabetic foot ulcers, venous stasis
ulcers, and pressure ulcers. The management
section of the article provides details on
cleansing, nourishment, protection, and specific
recommendations for the three types of chronic
wounds mentioned previously.
Liu C, Bayer A, Cosgrove SE, et al. Clinical
practice guidelines by the Infectious Diseases
Society of America for the treatment of
methicillin-resistant Staphylococcus aureus
infections in adults and children. Clin Infect Dis
2011;52:e1855.
Since MRSA plays a role in both communityand healthcare-associated infections, the IDSA
convened a panel of experts to develop the first
set of guidelines on infections caused by this
pathogen. The expert panel met on seven
occasions, and feedback was provided by
additional external peer reviewers. Once the
guideline was complete, it was reviewed and
endorsed by the Pediatric Infectious Diseases
Society, the American College of Emergency
Physicians, and the American Academy of
Pediatrics. The panel set out to address eleven
clinical questions in this guideline specific to the
management of skin and soft-tissue infections
due to community-acquired MRSA and recurrent

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PHARMACOTHERAPY Volume 31, 2011

MRSA.
The treatment of bacteremia,
endocarditis, pneumonia, bone and joint
infections, and CNS infections are also discussed.
The guideline elaborates on the role of adjunctive
therapies, vancomycin dosing and monitoring,
vancomycin susceptibility testing and its role in
therapy, persistent MRSA bacteremia and
vancomycin treatment failures, and the
management of MRSA in neonates.
Urinary Tract
Gupta K, Hooton TM, Naber KG, et al.
International clinical practice guidelines for the
treatment of acute uncomplicated cystitis and
pyelonephritis in women: a 2010 update by the
Infectious Diseases Society of America and the
European Society for Microbiology and Infectious
Diseases. Clin Infect Dis 2011; 2:e10320.
An expert panel was convened by the IDSA and
the European Society for Microbiology and
Infectious Diseases to update the 1999 guidelines
for uncomplicated urinary tract infections. It is
important to note that women with acute
uncomplicated cystitis or pyelonephritis are the
focus of this discussion. Acute uncomplicated
cystitis is one of the most common infections in
healthy women yet resistance among the
common pathogens has increased since 1999. A
five
day
course
of
nitrofurantoin
monohydrate/macrocrystals 100 mg twice daily
or a three day course of trimethoprimsulfamethoxazole (one double-strength tablet)
twice daily are recommended for acute
uncomplicated cystitis. Three day regimens of
the fluoroquinolones can be considered as they
are also an effective treatment but should be
reserved for complicated urinary tract infections
(UTIs). Similar to those patients suspected of
having catheter-associated (CA) UTIs, urine
culture and susceptibility results should be used
to ensure appropriate treatment of patients with
pyelonephritis. Ciprofloxacin 500 mg twice daily
for seven days is recommended for the treatment
of acute pyelonephritis. This therapy may or
may not include an initial intravenous dose.
Alternatives to an intravenous fluoroquinolone
include long-acting antimicrobials such as
ceftriaxone or an aminoglycoside.
Hooton TM, Bradley SF, Cardenas DD, et al.
Diagnosis, prevention, and treatment of catheterassociated urinary tract infection in adults: 2009
international clinical practice guidelines from the
Infectious Diseases Society of America. Clin

Infect Dis 2010;50:62563.

This IDSA guideline addresses the most
common healthcare-associated infection, CA
bacteriuria. Diagnostic criteria, strategies to
reduce the risk of CA-UTIs, and management of
patients with CA asymptomatic bacteriuria or
symptomatic UTIs are among the topics
discussed.
Empiric antibiotics are not
recommended prior to catheter placement, at the
time of removal, or prior to replacement as they
do not reduce CA-UTIs or CA-bacteriuria. If a
CA-UTI is suspected, a urine specimen should be
obtained prior to starting antimicrobial therapy.
In addition, indwelling catheters should be
replaced if they have been in place for more than
two weeks.
Vaccinations
Rhee P, Nunley MK, Demetriades D, Velmahos
G, Doucet JJ. Tetanus and trauma: a review and
recommendations. J Trauma 2005;58:10828.
This review article discusses the history,
pathogenesis, clinical manifestation, and
immunization and prophylaxis of tetanus.
Tetanus remains a problem worldwide except in
the United States as the immunization program
has been in effect. Prior to determining the
appropriate prophylaxis, the patients wound
needs to be classified as tetanus-prone, wounds
that are oxygen deficient as Clostridium tetani is
an obligate anaerobe, or non-tetanus-prone.
Abscesses, open fractures, and puncture wounds
are usually classified as tetanus-prone. For adult
patients, the Td booster shot is recommended.
In patients who have an unclear history of
tetanus immunization, their vaccination status is
unknown, or if patients did not complete the
primary series, tetanus immunoglobulin should
be administered in addition to the vaccine. The
most recent guidelines for tetanus vaccination are
available through the Advisory Committee on
Immunization Practices (ACIP) website: http://
www.immunize.org/acip/.
Nigg AJ, Walker PL. Overview, prevention, and
treatment of rabies. Pharmacotherapy
2009;29:1182-95.
Postexposure prophylaxis for rabies is a
multimodal process that is utilized to decrease an
individuals likelihood of developing rabies
following a potential exposure. This review
article discusses this single-stranded RNA virus,
its transmission, and clinical manifestation. In

KEY ARTICLES FOR THE EMERGENCY MEDICINE PHARMACIST Thomas et al

the United States, Imovax Rabies and RabAvert
are available for use and both are a single 1 mL
dose that is to be administered intramuscularly.
Following administration, local injection-site
reactions and systemic reactions have been
described. Rabies immune globulin provides
passive
immunization
via
antibody
neutralization. Unlike the vaccine, the dose of
immune globulin is weight-based (i.e., 20 IU/kg).
As much of the immune globulin as possible
should be administered around the wound.
However, if this is not feasible, the remainder of
the dose can be given intramuscularly in an
extremity opposite from the vaccine. Following
the administration of the first dose of the vaccine,
arrangements will need to be made for the
patient to receive additional doses of the vaccine
3, 7, and 14 days after the initial dose. Exposure
prevention, pre-exposure prophylaxis, and
treatment of patients who are diagnosed with
rabies are also discussed in this article. The most
recent guidelines for rabies exposures is available
through the ACIP website: http://
www.immunize.org/acip/.
Neurology and Psychiatry
Acute Agitation
Nobay F, Simon BC, Levitt MA, Dresden GM. A
prospective, double-blind, randomized trial of
midazolam versus haloperidol versus lorazepam
in the chemical restraint of violent and severely
agitated patients. Acad Emerg Med
2004;11:7449.
This prospective, randomized, double-blind
study investigated the efficacy and side effects of
intramuscular midazolam (5 mg), lorazepam (2
mg), or haloperidol (5 mg) in 111 violent and
severely agitated patients. Adequate sedation was
defined by the Modified Thomas Combativeness
Scale. Approximately half of all patients had a
prior psychiatric history. They found that
midazolam had a significantly shorter time (> 10
minutes shorter) to sedation than the other two
agents as well as a shorter time to arousal (> 40
minutes shorter) (p<0.05 for both). No
significant differences were found between the
groups with regards to their impact on
hemodynamic parameters. Limitations included
the lack of a placebo group and the use of a
convenience sample. In addition, over half of the
patients had an unknown history of alcohol and
drug use, making extrapolation of these results
challenging. This study highlights the potential

467e

advantage midazolam may have over lorazepam

in this setting. However, this must be taken
within the context of the fact that there was no
dosage adjustment for patient weight.
Martel M, Sterzinger A, Miner J, Clinton J, Biros
M. Management of acute undifferentiated
agitation in the emergency eepartment: a
randomized double-blind trial of droperidol,
ziprasidone, and midazolam. Acad Emerg Med
2005;12:116772.
In this study, 144 patients were randomized to
receive droperidol 5 mg, ziprasidone 20 mg, or
midazolam 5 mg by intramuscular injection.
Adequate sedation, as measured by the Altered
Mental Status Scale, was achieved in significantly
more patients in the midazolam group at the 15
minute mark (p=0.01) but this group also had
significantly more recurrent agitation at the 45
minute time point (p=0.03). Significantly more
patients in the midazolam group required rescue
medications compared with the other two groups
(p<0.05). No cardiac dysrhythmias were noted
in any group and respiratory depression was not
significantly different between the groups. These
results are somewhat limited by the inclusion of a
bias sample based on the unavailability of
research personnel. The majority of patients in
this investigation also suffered from alcohol
intoxication therefore limiting extrapolation to
other populations. However, this study does add
to available literature by both comparing
different classes of agents in a prospective fashion
as well as comprehensively evaluating side effect
profiles.
Battagia J. Pharmacological management of acute
agitation. Drugs 2005;66:120722.
This review provides a detailed description of
the various therapies available for the
management of acute agitation and focuses on
benzodiazepines as well as typical and atypical
antipsychotics. It also provides a discussion of
the use of combination therapies as well as a
proposed clinical management guideline.
Emphasis is placed on reviewing the primary
literature in support of each agent.
Drug and Alcohol Withdrawal
Mayo-Smith MF, Beecher LH, Fischer TL, et al.
Management of alcohol withdrawal delirium. An
evidence-based practice guideline. Arch Intern
Med 2004;164:140512.

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PHARMACOTHERAPY Volume 31, 2011

A working-group from the American Society of

Addiction
Medicine
consisting
of
multidisciplinary practitioners in various areas of
practice reviewed nine prospective studies (19662001) in a meta-analytic fashion. This group
provides a structured grading of the available
evidence and resulting recommendations. Most
notably, they determined that sedative-hypnotic
agents were more effective than neuroleptic
agents in reducing the duration of delirium and
mortality. The authors found a RR of death when
using neuroleptic agents of 6.6 (95% CI 1.2 to
34.7). They also provided an analysis of the
costs of therapy and an example of potential
therapeutic regimens. In addition, they discuss
possible side effects of various regimens and
present monitoring recommendations.
Daeppen JB, Gache P, Landr y U, et al.
Symptom-triggered vs. fixed-schedule doses of
benzodiazepine for alcohol withdrawal: a
randomized treatment trial. Arch Intern Med
2002;162:111721.
This prospective, double-blind, controlled trial
randomized 117 patients with alcohol
dependence to either one group that received
oxazepam in response to the development of
signs of alcohol withdrawal or on a fixedschedule every six hours. Patients in the
symptom-triggered group were significantly less
likely to be given oxazepam (p<0.001) and
received a significantly lower mean dose (37.5
mg vs 231.4 mg, p<0.001). There were no
significant differences between the groups with
regards to alcohol-withdrawal seizures or
measures of comfort. All patients were located in
alcohol detoxification units, limiting
generalizability to other practice areas. This
study provides support for the hypothesis that
patients at risk for alcohol withdrawal can be
safely managed on a symptom-triggered basis
thus limiting excessive and unnecessary
pharmacotherapy.
Kosten TR, OConner PG. Management of drug
and alcohol withdrawal. N Engl J Med
2003;348:178695.
This comprehensive review article discusses a
wide array of drugs of abuse including alcohol,
benzodiazepines, opioids, cocaine, and
amphetamines. A description is provided
regarding the unique presentation and
symptomatology of each withdrawal crisis as well
as the underlying mechanism. The authors
discuss in detail the various therapeutic options

and their specific roles in individual medication

withdrawal syndromes through the use of the
primary literature.
Migraines
Silberstein SD. Practice Parameter: evidencebased guidelines for migraine headache (an
evidence-based review): report of the Quality
Standards Subcommittee of the American
Academy
of
Neurology.
Neurology
2000;55:75462.
This practice parameter was developed by the
Quality Standards Subcommittee of the American
Academy of Neurology. A multidisciplinary
panel of seven organizations participated in the
US Headache Consortium: The American
Academy of Family Physicians, American
Academy of Neurology, American Headache
Society, American College of Emergency
Physicians, American College of PhysiciansAmerican Society of Internal Medicine, American
Osteopathic Association and the National
Headache Foundation. This manuscript reviews
the comprehensive management of migraine,
including diagnosis and acute, preventative, and
non-pharmacologic treatments for migraine.
Available evidence concerning migraine
pharmacotherapy is graded in a standardized
manner and its role in the overall spectrum of
care is summarized. Documented adverse effects
are also reviewed for each therapy. Consensus
recommendations are provided by the
subcommittee for each therapy. These guidelines
recommend the use of triptans or
dihydroergotamine in patients with moderate to
severe migraines. For mild to moderate
migraines, they recommend NSAIDs or
combination products including NSAIDs and
caffeine.
Evers S, Afra J, Frese A, et al. EFNS guideline
on the drug treatment of migraine-a revised
report of an EFNS Taskforce. Eur J Neurol
2009;16:96881.
These recommendations were developed by the
European Federation of Neurological Societies
and provide recommendations on drug treatment
of migraine attacks and prophylaxis. Studies
published in three different languages were
reviewed, evaluated, and graded. For the acute
treatment of migraine, NSAID therapy and
triptans are recommended preceded by
metoclopramide administration. For severe
attacks they recommend intravenous

KEY ARTICLES FOR THE EMERGENCY MEDICINE PHARMACIST Thomas et al

acetylsalicyclic acid or subcutaneous
sumatriptan.
Although somewhat less
comprehensive than the US Headache
Consortium Recommendations, this guideline
provides a more recent update and evaluation of
the literature.
Loder E. Triptan therapy in migraine. N Engl J
Med 2010;363:6370.
This article reviews the available evidence
regarding triptan therapy for the treatment of
migraine through the use of a case vignette. It
discusses the different formulations as well as the
various side-effects concerning therapy. It
compares and contrasts this available evidence
with the recommendations provided in both the
US Headache Consortium Guidelines and those
guidelines provided by the European Federation
of Neurological Societies.
Davis E. Evaluation and management of migraine
in the emergency department. Emerg Med
Reports 2008;29:13344.
This article provides an overview of the
pathophysiology of migraine and details abortive
and preventative therapies commonly used in the
ED. Each medication class including NSAIDs,
antiemetics, triptans, ergot derivatives, and
opioids are discussed and the pertinent literature
reviewed.
Hemorragic Stroke
Morgenstern LB, Hemphill JC 3rd, Anderson C,
et al. Guidelines for the management of
spontaneous intracerebral hemorrhage: a
guideline for healthcare professionals from the
American Heart Association/American Stroke
Council. Stroke 2010;41:210829.
This guideline provides recommendations
regarding the comprehensive care of patients
presenting with acute spontaneous intracerebral
hemorrhage (ICH). Individual studies are
presented in various evidentiary tables and
recommendations are graded based on a detailed
grading algorithm.
Initial emergency
management is discussed all the way through to
the prevention of recurrence. Recommendations
are provided on pharmacotherapeutic targets of
blood pressure, glucose and seizure management.
Bederson JB, Connolly Jr ES, Batjer HH, et al.
Guidelines for the management of aneurysmal
subarachnoid hemorrhage: a statement for
healthcare professionals from a special writing

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group of the Stroke Council, American Heart

Association. Stroke 2009;40:9941025.
These consensus guidelines are provided by the
American Heart Association and affirmed by the
American Academy of Neurology. Individual
recommendations are classified and graded in a
structured manner based on the available
evidence. Comprehensive recommendations are
provided both for initial management as well as
the treatment of subsequent cerebral vasospasm.
Anderson CS, Huang Y, Arima H, et al. Effects of
early intensive blood pressure-lowering treatment
on the growth of hematoma and perihematomal
edema in acute intracerebral hemorrhage: the
intensive blood pressure reduction in acute
cerebral haemorrhage trials (INTERACT). Stroke
2010;41:30712.
This study is an expansion of the original
INTERACT trial published in 2008 that was a
randomized controlled trial in which the authors
demonstrated a potentially positive impact of
intensive blood pressure lowering on cerebral
hematoma expansion when initiated within the
first six hours. This report elaborated on those
results by exploring the effects of treatment on
hematoma and perihematomal edema over 72
hours. This study included 404 patients with
ICH, elevated systolic blood pressure (150-220
mm Hg) in whom antihypertensives were able to
be initiated within 6-hrs of the event. Patients
were randomly assigned to intensive therapy
(target blood pressure < 140 mmHg) or standard
guideline-based management of blood pressure
(target blood pressure of 180 mm Hg) using
routine intravenous agents. Those in the
treatment group at 24 and 72 hours had
significantly lower hematoma volumes than the
guideline-based group (overall difference of 2.8
mL, 95% CI 1.04 to 4.56, p=0.002). No
significant difference was noted in edema
volumes (overall difference of 2.38 mL, 95% CI 0.45 to 5.22, p=0.10). The authors concluded
that early intensive blood pressure lowering
therapy attenuated hematoma growth over 72hrs
with no appreciable effects on perihematomal
edema. This study provides support for the
hypothesis that intensive and early
antihypertensive therapy can directly impact
hematoma expansion. However this study is
limited by the lack of data regarding clinical
outcomes and its overall impact on edema.
Detailed information regarding the agents used
and the overall achievement of target blood
pressure parameters is also not provided.

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Mayer SA, Brun NC, Begtrup K, et al. Efficacy

and safety of recombinant activated factor VII for
acute intracerebral hemorrhage. N Engl J Med
2008;358:212737.
In this Phase 3 trial exploring the impact of
rFVIIa in the setting of ICH, 841 patients were
randomized to receive either placebo, 20 g of
rFVIIa per kg of body weight or 80 g/kg within
4 hours after the onset of stroke. The primary
outcome of interest was incidence of severe
disability or death according to the modified
Rankin scale at 90 days. The group receiving the
higher rFVIIa dose had significantly reduced
growth in volume of the cerebral hemorrhage
compared with placebo (p<0.001). However,
there was no significant difference among the
three groups in the proportion of patients with
poor clinical outcomes. Arterial thromboembolic
serious adverse events were more frequent in
those receiving 80 g/kg compared with the
placebo group (p=0.04). These results are
conflicting to those from the previous Phase 2b
trial published by the same investigators (Mayer
SA, Brun NC, Begtrup K, et al. N Engl J Med
2005;352:77785) in which they found a
reduction in hematoma growth and an
improvement in functional outcome at 90 days.
The authors largely attribute these differences in
outcomes to baseline differences between the two
randomized groups. The authors conclusion is
that rFVIIa reduces hematoma growth but not
the rate of death or severe disability after ICH.
Ischemic Stroke
Albers GW, Amarenco P, Easton JD, Sacco RL,
Teal P. Antithrombotic and thrombolytic therapy
for ischemic stroke: American College of Chest
Physicians evidence-based clinical practice
guidelines
(8th
edition).
Chest
2008;133(suppl):630S69S.
These guidelines provide the highest
recommendation for the administration of tissue
plasminogen activator (tPA) if the treatment is
initiated within 3 hours of clearly defined
symptom onset. For those that present >3 hrs
out, this committee does not recommend using
tPA. For patients with acute ischemic stroke who
are not receiving thrombolysis, this group
recommends the use of early aspirin therapy.
This committee also provides graded
recommendations regarding secondary stroke
prevention. These recommendations were
published prior to the publication of the ECASS

III trial, and therefore the authors were unable to

consider those results in their recommendations.
Adams HP Jr, del Zoppo G, Alberts MJ, et al.
Guidelines for the early management of adults
with ischemic stroke: a guideline from the
American Heart Association/American Stroke
Association Stroke Council, Clinical Cardiology
Council, Cardiovascular Radiology and
Intervention Council, and the Atherosclerotic
Peripheral Vascular Disease and Quality of Care
Outcomes in Research Interdisciplinary Working
Groups: the American Academy of Neurology
affirms the value of this guideline as an
educational tool for neurologists. Stroke
2007;38:16551711.
These guidelines update those published in
2003 and utilize the American Heart Association
Stroke Councils Levels of Evidence grading
algorithm to rate the available evidence. These
are comprehensive guidelines that include
recommendations regarding initial management
of these patients in the field through their
admission to the hospital. It discusses not only
the role of intravenous administration of tPA but
also intra-arterial administration of thrombolytics
and mechanical interventions. It also discusses
the use of anticoagulant agents, antiplatelet
agents, and the roles of volume expansion,
vasodilators and induced hypertension.
National Institute of Neurological Disorders
and Stroke rt-PA Stroke Study Group. Tissue
plasminogen activator for acute ischemic stroke.
N Engl J Med 1995;333:15817.
To assess the risk-benefit ratio of treatment
with tPA (0.9 mg/kg) in the first three hours of
stroke onset, 624 patients were enrolled in this
randomized, double-blind, placebo-controlled
trial. No significant improvement in National
Institutes of Health Stroke Scale Score (NIHSS)
or resolution in neurologic deficits was noted
within 24 hours of the onset of stroke. However,
the investigation did find that clinical outcomes
were significantly improved in the treatment
group at three months (OR 1.7, 95% CI 1.2 to
2.6). Symptomatic ICH occurred in 6.4% of
patients given tPA but in only 0.6% of patients
given placebo (p<0.001). Mortality was not
different between the two groups (p=0.30)
Hacke W, Kaste M, Bluhmki E, et al.
Thrombolysis with alteplase 3 to 4.5 hours after
acute ischemic stroke. N Engl J Med
2008;359:131729.
In this double-blind, parallel-group trial

KEY ARTICLES FOR THE EMERGENCY MEDICINE PHARMACIST Thomas et al

published by the European Cooperative Acute
Stroke Study investigators, 821 patients with
acute ischemic stroke were randomized to receive
intravenous tPA (0.9 mg/kg) or placebo.
Originally, patients were able to receive study
drug within 3 to 4 hrs after the onset of
symptoms, however this was later expanded to 3
to 4.5 hours after slow patient enrollment and
other publications of efficacy. Patients that
received tPA were less likely to have disability at
90 days as assessed by the modified Rankin Scale
(52.4% vs. 45.2%, p=0.04) however no changes
in mortality were noted (7.7% vs. 8.4%, p=0.68).
The incidence of ICH and symptomatic ICH were
higher in the treatment group (27% vs. 17.6%,
p=0.001, 2.4% vs. 0.2%, p=0.008, respectively).
The authors concluded that treatment with tPA 3
to 4.5 hours after stroke onset significantly
improves outcomes without a higher rate of
symptomatic ICH than treatment initiated less
than three hours.
Del Zoppo GJ, Saver JL, Jauch EC, Adams Jr HP.
Expansion of the time window for treatment of
acute ischemic stroke with intravenous tissue
plasminogen activator: a science advisory from
the American Heart Association/American Stroke
Association. Stroke 2009;40:29458.
This science advisory from the American Heart
Association and the American Stroke Association
provides an update to the previous guidelines
published in 2007. They state that tPA should be
administered to eligible patients who can be
treated within the 34.5 hour time period after a
stroke. They do note that additional exclusion
criteria apply to this population, largely based on
the ECASS III exclusion criteria. These
additional criteria include: patients older than 80
years of age, those taking oral anticoagulants
with an international normalized ratio 1.7,
those with a baseline NIHSS >25, and those with
both a history of stroke and diabetes.
Palesch YY, Hill MD, Ryckborst KJ, Tamariz D,
Ginsberg M. The ALIAS pilot trial: a doseescalation and safety study of albumin therapy
for acute ischemic stroke-II: neurologic outcome
and efficacy analysis. Stroke 2006;37:210714.
In this pilot, Phase I trial, 82 subjects with
acute ischemic stroke received 25% albumin
(dose range, 0.342.05 g/kg) beginning within 16
hours of stroke onset. The authors compared the
highest three dose tiers (1.372.05 g/kg) to the
lowest three tiers (0.341.03 g/kg) and to
historical cohort data determined by the NINDS

471e

tPA stroke study. The probability of a good

clinical outcome at the highest three albumin
doses was 81% greater than the lowest three (RR
1.81, 95% CI 1.112.94) and was 95% greater
than the historical cohort (RR 1.95, 95% CI
1.472.57). The tPA treated patients who
received higher dose albumin were more likely to
achieve a good outcome than those receiving
lower-dose albumin (RR 2.75 95% CI 1.325.73).
Based on this data, a phase II, National Institutes
of Health funded, randomized, double-blind,
placebo-controlled multicenter trial is currently
underway.
Seizures
Meierkord H, Boon P, Engelsen B, et al. EFNS
guideline on the management of status
epilepticus in adults. Eur J Neurol 2010; 17:
348355.
This consensus guideline from the European
Federation of Neurological Societies provides an
evaluation of the available literature in addition
to graded recommendations. Pharmacotherapeutic recommendations are provided
regarding both the management of intial status
epilepticus as well as refractory status
epilepticus.
Treiman DM, Meyers PD, Walton NY, et al. A
comparison of four treatments for generalized
convulsive status epilepticus. N Engl J Med
1998;339:7928.
This double-blind multicenter study
randomized 384 patients with generalized status
epilepticus to one of four therapies: lorazepam,
0.1 mg/kg; diazepam, 0.15 mg/kg, followed by
phenytoin 18 mg/kg; phenytoin 18 mg/kg; and
phenobarbital 15 mg/kg. The primary outcomes
were termination of seizure activity within 20
minutes of the start of therapy and no recurrence
within 60 minutes. Status epilepticus was
terminated in 64.9% of patients randomized to
lorazepam, 58.2% of those randomized to
phenobarbital, 55.8% of those randomized to
diazepam and phenytoin, and 43.6% of those
randomized to phenytoin. The only significant
difference was found between the lorazepam and
phenytoin groups (p=0.002). This study was
important in emphasizing the importance of early
benzodiazepine or barbiturate therapy in the
termination of status epilepticus.
Alldredge BK, Gelb AM, Isaacs SM, et al. A
comparison of lorazepam, diazepam, and placebo

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PHARMACOTHERAPY Volume 31, 2011

for the treatment of out-of-hospital status

epilepticus. N Engl J Med 2001;345:631-7.
In this double-blind, out-of-hospital study, 205
patients were randomized to intravenous
diazepam 5 mg, intravenous lorazepam 2 mg, or
placebo by paramedics. The primary outcome of
interest was termination of status epilepticus.
Termination at arrival in the ED occurred in
59.1% of the patients treated with lorazepam, in
42.6% of patients treated with diazepam, and in
21.1% of patients treated with placebo
(lorazepam vs. placebo: OR 4.8, 95% CI 1.9 to
13.0; diazepam vs. placebo: OR 2.3, 95% CI 1.0
to 5.9; lorazepam vs. diazepam: OR, 1.9; 95% CI
0.8 to 4.4). No significant difference was found
in the rates of respiratory or circulatory
complications.
Respiratory
Acute Severe Asthma
National Asthma Education and Prevention
Program. Expert Panel Report 3 (EPR-3):
Guidelines for the diagnosis and nanagement of
asthma-summary report 2007. Journal Allergy
Clin Immunol 2007;120(5 Suppl):S94S138.
These guidelines provide recommendations for
the management of asthma across the continuum
of care from maintenance therapy to the acute
management of exacerbations. It describes the
role of beta-2 adernergic agonists, anticholinergic
agents, systemic and inhaled corticosteroids. It
also recommends against the use of
methylxanthines, the routine use of antibiotics,
mucolytic agents, and the use of aggressive
hydration.
Papiris SA, Manali ED, Kolilekas L,
Triantafillidou C, Tsangaris I. Acute severe
asthma: new approaches to assessment and
treatment. Drugs 2009;69:236391.
This review article provides a very
comprehensive analysis of the current state of
acute severe asthma management as well as a
detailed
review
of
the
various
pharmacotherapeutic modalities.
This
manuscript also describes the pathophysiology of
the underlying condition in great detail as well as
the various mechanical ventilator support
options. It also provides a description of the use
of helium and oxygen mixtures (heliox) and their
potential role in therapy.
Lazarus S. Emergency treatment of asthma. N

Engl J Med 2010;363:75564.

This article presents a comprehensive review of
the treatment of this condition through the use of
a case vignette. The author also provides a
critical review of the available guidelines as well
as recommendations for the treatment of patients
on discharge from the ED. Areas of uncertainty
are discussed including the use of intravenous
magnesium sulfate, heliox, and oral leukotriene
inhibitors.
COPD Exacerbations
National Collaborating Centre for Chronic
Conditions. Chronic obstructive pulmonary
disease: national clinical guideline for
management of chronic obstructive pulmonary
disease in adults in primary and secondary care.
Thorax 2004;59(suppl 1):1232.
These
guidelines
provide
detailed
recommendations regarding the diagnosis and
management of both chronic and acute
management of chronic obstructive pulmonary
disease (COPD).
Composed by a
multidisciplinary group, these recommendations
grade the available evidence and touch on
multiple facets of the care of this patient
population, including a comprehensive analysis
of available pharmacotherapeutic options and
areas for future research.
Quon BS, Gan WQ, Sin DD. Contemporary
management of acute exacerbations of COPD: a
systematic review and metaanalysis. Chest
2008;133:75666.
This meta-analysis examined available
publications concerning systemic corticosteroids,
antibiotics, and noninvasive positive pressure
ventilation in the treatment of acute COPD
exacerbations. Two authors identified and
reviewed 10 studies involving systemic
corticosteroids, 11 studies regarding antibiotic
use, and 14 studies concerning noninvasive
positive pressure ventilation. The authors found
that compared with placebo, systemic
corticosteroids were effective in reducing
treatment failures by 46% (95% CI 0.41 to 0.71).
Antibiotics were found to reduce in-hospital
mortality by 78% (95% CI 0.08 to 0.62) and
treatment failure by 46% (95% CI 0.32 to 0.92).
Noninvasive positive pressure ventilation
reduced the risk of intubation by 65% (95% CI
0.26 to 0.47) and in-hospital mortality by 55%
(95% CI 0.30 to 0.66). The authors concluded

KEY ARTICLES FOR THE EMERGENCY MEDICINE PHARMACIST Thomas et al

that systemic corticosteroids are effective in
reducing treatment failures and antibiotics reduce
both mortality and treatment failures in those
requiring hospitalization.
Lindenauer PK, Pekow PS, Lahti MC, Lee Y,
Benjamin EM, Rothberg MB. Association of
corticosteroid dose and route of administration
with risk of treatment failure in acute
exacerbation of chronic obstructive pulmonary
disease. JAMA 2010;303:235967.
This pharmacoepidemiological retrospective
cohort study collected data on 79,765 patients at
414 US hospitals regarding the use of low dose
steroid therapy compared with high dose
intravenous therapy in patients presenting with
an acute exacerbation of COPD. The authors
found that the risk of treatment failure among
patients treated orally was not worse than for
those treated intravenously (OR 0.93, 95% CI
0.84 to 1.02). After propensity-matching, the
risk of treatment failure was significantly lower
among orally treated patients (OR 0.84, 95% CI
0.75 to 0.95), as was length of stay (OR 0.92,
95% CI 0.01 to 0.94) and total cost (OR 0.93,
95% CI 0.91 to 0.94). These findings contribute
important information regarding how to
approach the use of corticosteroid therapy in this
setting, something that has become a mainstay of
practice. The limitations of this study include
the observational and retrospective design, as
well as the lack of randomization and the
resulting need for propensity-matching.
Esophageal Impactions
Eisen GM, Baron TH, Dominitz JA, et al.
Guideline for the management of ingested
foreign
bodies.
Gastrointest
Endosc
2002;55:8026.
This guideline produced by the American
Society for Gastrointestinal Endoscopy reviews
the available literature and provides
comprehensive recommendations regarding the
appropriate utilization of endoscopy. This
guideline recommends the use of glucagon 1 mg
intravenously in an attempt to relax the
esophagus in the setting of esophageal food
impaction. This recommendation is supported
by two studies that enrolled a total of 22 patients,
however an in-depth discussion of this analysis is
not provided.
Tibbling L, Bjorkhoel A, Jansson E, Stenkvist
M. Effect of spasmolytic drugs on esophageal

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foreign bodies. Dysphagia 1995;10:1267.

In this multicenter, randomized, placebocontrolled, double-blind study the authors
evaluated the use of diazepam intravenously
(dose range 2.5 to 10 mg) plus glucagon 1 mg
intravenously for the relief of esophageal food
impaction in 43 patients. Patients in the
treatment group had a 38% rate of disimpaction
compared to 32% in the placebo group (p=NS).
This study is limited by its small sample size and
the baseline exclusion of patients with an
underlying esophageal pathology.
Sodeman TC, Harewood GC, Baron TH.
Assessment of the predictors of response to
glucagon in the setting of acute esophageal food
bolus impaction. Dysphagia 2004;19:1821.
In this retrospective review of 222 patients, the
authors compared the relief of acute esophageal
food bolus impaction in 106 patients who
received glucagon 1 mg intravenously to those
who did not. Success in the treatment group was
observed in 9.4% of the glucagon recipients and
17.2% in the control group. This study is limited
by the fact that multiple patients received
additional doses of glucagon making the analysis
of these results challenging.
Resuscitation
Advanced Cardiac Life Support (ACLS)
Neumar RW, Otto CW, Link MS, et al. Adult
advanced cardiovascular life support: 2010
American Heart Association guidelines for
cardiopulmonary resuscitation and emergency
cardiovascular care. Circulation 2010;122(suppl
3):S72967.
These are updated guidelines from the
American Heart Association for the management
of adult patients during respiratory or cardiac
arrest, symptomatic tachycardia or bradycardia
and the related literature and therapeutic
strategies available. There are several important
pharmacologic and non-pharmacologic changes
from the 2005 guidelines. Atropine is no longer
recommended for routine use in the management
of pulseless electrical activity or asystole.
Adenosine can now be considered for stable,
regular, monomorphic wide-complex tachycardia
for diagnosis or treatment. As an antiarrhythmic
agent for stable, wide complex tachycardia,
procainamide or amiodarone are recommended.
For unstable bradycardia, chronotropic agents
(dopamine or epinephrine) are recommended as

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PHARMACOTHERAPY Volume 31, 2011

equally effective to external pacing when

atropine is ineffective. Other changes include an
emphasis on chest compressions before airway
and breathing, the removal of look, listen, and
feel in the basic life support algorithm to
encourage immediate activation of the emergency
response system and the start of chest
compressions, continuous capnography for
endotracheal tube placement confirmation, and
the expansion of post-cardiac arrest management.
Draper HM, Eppert JA. Advanced cardiac life
support guidelines during in-hospital cardiac
arrest. Ann Pharmacother 2008;46974.
In this retrospective analysis of 74 consecutive
in-hospital respiratory or cardiac arrests from a
single center, the compliance to advanced cardiac
life support guidelines is evaluated. Of 650
documented treatment interventions, 10.6% were
noncompliant (i.e., error in dose, delay in
intervention, omission of indicated treatment, or
deviation from treatment guideline). When a
pharmacist was present on the resuscitation
team, compliance with advanced cardiac life
support treatment guidelines was more likely
(59.3% vs. 31.9%, p=0.03). This study
demonstrates the importance of the pharmacist
as part of the resuscitation team.
Dager WE, Sanoski CA, Wiggins BS, Tisdale JE.
Pharmacotherapy considerations in advanced
cardiac life support. Pharmacotherapy
2006;26:170329.
This review focuses on the pharmacologic
agents used during advanced cardiac life support
and the available evidence regarding selection of
these therapies is summarized. Specific
administration considerations are provided.
Although the recommendations in this article are
based off of the 2005 guidelines, much of the
information is still relevant following the 2010
update.
Vasoactive agents
Vandycke C, Martens P. High dose versus
standard dose epinephrine in cardiac arresta
meta-analysis. Resuscitation 2000;45:1616.
This meta-analysis of five randomized, doubleblind, controlled trials evaluated high dose
epinephrine (5 mg to 15 mg) compared to
standard dose epinephrine (1 mg) in the
management of cardiac arrest. Return of
spontaneous circulation (ROSC) as an outcome
measure favored high dose epinephrine in the

pooled analysis (OR 1.14, 95% CI 1.02 to 1.27).

Survival to hospital admission and hospital
discharge were not statistically significant,
however the authors state that the pooled odds
ratio for survival to hospital discharge showed a
trend towards favoring standard dose
epinephrine, (OR 0.74, 95% CI 0.53 to 1.03).
This article does not detail concerns with the use
of high dose epinephrine such as postresuscitation complications and adverse
neurologic outcomes.
Wenzel V, Krismer AC, Arntz R, Sitter H,
Stadlbauer KH, Lindner KH. A comparison of
vasopressin and epinephrine for out-of-hospital
cardiopulmonary resuscitation. N Engl J Med
2004;350:10513.
In this double-blind, randomized, controlled
trial vasopressin was compared to epinephrine in
1186 patients with out-of-hospital cardiac arrest.
Following two doses of study medication, open
label epinephrine was available for those without
ROSC. Overall, there were no differences in
survival outcomes between the two groups.
However, post hoc analysis of the asystole
subgroup noted that survival to both hospital
admission and discharge favored vasopressin in
those that had ROSC with study medication and
in those that received open label epinephrine
following vasopressin. Of note, those that
received both vasopressin and epinephrine had
worse neurologic outcomes, although not
statistically significant.
Gueugniaud PY, David JS, Chanzy E, et al.
Vasopressin and epinephrine vs. epinephrine
alone in cardiopulmonary resuscitation. N Engl J
Med 2008;359:2130.
Vasopressin and epinephrine compared to
epinephrine alone was evaluated in 2894 patients
with out-of-hospital cardiac arrest in this
multicenter, randomized, controlled trial. No
significant differences in outcome measures, such
as survival to hospital admission or neurologic
recovery were evident between the groups. Of
note, it is well known that early CPR and an
initial rhythm of ventricular fibrillation have
been associated with a greater chance of survival.
In each of the treatment groups, only 27% of
patients received bystander CPR, mean time to
advanced life support was 16 minutes, mean time
to study drug administration was 21 minutes and
9% of patients had an initial shockable rhythm
making survival outcomes difficult to assess.

KEY ARTICLES FOR THE EMERGENCY MEDICINE PHARMACIST Thomas et al

Antiarrhythmic Agents
Kendenchuk PJ, Cobb LA, Copass MK, et al.
Amiodarone for resuscitation after out-ofhospital cardiac arrest due to ventricular
fibrillation (ARREST). N Engl J Med
1999;341:8718.
This randomized, double-blind, placebo
controlled trial evaluated the use of amiodarone
after three precordial shocks in out-of-hospital
ventricular fibrillation (or pulseless ventricular
tachycardia) arrest. Survival to hospital
admission was greater in the patients that
received amiodarone (300 mg, n = 246)
compared to placebo (n = 258), 44% and 34%,
respectively, p=0.03. The mean time from
dispatch to study drug administration was 21
minutes and earlier administration was
associated with improved survival to hospital
admission. It is important to note that there was
no difference in the rate of survival to hospital
discharge and more patients in the amiodarone
group had hypotension or bradycardia requiring
treatment. These data resulted in amiodarone
replacing lidocaine as the first-line
antiarrhythmic agent in the American Heart
Association ACLS algorithms.
Dorian P, Cass D, Schwartz B, Cooper R,
Gelaznikas R, Barr A. Amiodarone as compared
with lidocaine for shock-resistant ventricular
fibrillation (ALIVE). N Engl J Med
2002;346:88490.
Amidodarone (5 mg/kg) compared to lidocaine
(1.5 mg/kg) for out-of-hospital ventricular
fibrillation arrest in patients resistant to 4 shocks
and epinephrine was evaluated in this
randomized, placebo-controlled trial. The
administration of amiodarone (n = 180) was
associated with a higher rate of survival to
hospital admission (22.8%) compared to
lidocaine (n = 167, 12.6%), p=0.009. Mean time
from dispatch to study drug administration was
25 minutes. Earlier administration of either
study drug improved survival to hospital
admission; however, there was no difference in
survival to hospital discharge.
Pediatric Advanced Life Support (PALS)
Kleinman ME, Chameides L, Schexnayder
SM, et al. Pediatric advanced life support: 2010
American Heart Association guidelines for
cardiopulmonary resuscitation and emergency
cardiovascular care. Circulation 2010;122(suppl

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3):S876908.
This guideline provides updated recommendations for pediatric respiratory and cardiac
arrest as well as for tachycardia, bradycardia, and
post-resuscitation management. Therapeutic
strategies for the resuscitation of special pediatric
patient populations including septic and
hypovolemic shock, single ventricle anatomy,
pulmonary hypertension, and toxicologic
emergencies are described. Most changes from
the 2005 guidelines are non-pharmacologic, with
the exception that intraosseous medication
administration is deemed safe and effective for all
resuscitation medications. Of note, although
ventilations have been deemphasized in the adult
ACLS guidelines, asphyxial arrests are more
common in the pediatric population and a
combination of ventilation and compressions are
supported.
Perondi MB, Reis A, Paiva EF, Nadkarni VM,
Berg RA. A comparison of high-dose and
standard-dose epinephrine in children in cardiac
arrest. N Engl J Med 2004;350:172230.
High dose epinephrine (0.1 mg/kg) was
compared to standard dose epinephrine (0.01
mg/kg) in this prospective, randomized, doubleblind trial. Sixty-eight children were included
following failure of an initial standard
epinephrine dose during in-hospital cardiac
arrest resuscitation management. The rate of
survival at 24 hours was lower in the high dose
epinephrine rescue group even after adjustment
for differences between the groups, adjusted odds
ratio for death was 7.9 (97.5% CI 0.9 to 72.5,
p=0.08). The authors caution that high dose
epinephrine rescue may be worse than standard
therapy.
Patterson MD, Boenning DA, Klein BL, et al.
The use of high-dose epinephrine for patients
with out-of-hospital cardiopulmonary arrest
refractory to prehospital interventions. Pediatr
Emerg Care 2004;21:22737.
This multicenter, randomized, controlled trial
compared high dose epinephrine (0.1 mg/kg
initial dose, 0.2 mg/kg subsequent doses) to
standard dose epinephrine (0.01 mg/kg initial
dose, 0.02 mg/kg subsequent doses) in 213
pediatric patients during out-of-hospital medical
or traumatic cardiopulmonary arrest. Overall,
there were no differences in return of
spontaneous circulation, 24 hour survival, longterm survival, or neurologic outcomes comparing
the two groups.

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PHARMACOTHERAPY Volume 31, 2011

Therapeutic Hypothermia
Peberdy MA, Callaway CW, Neumar RW, et al.
Post cardiac arrest care: 2010 American Heart
Association guidelines for cardiopulmonary
resuscitation and emergency cardiovascular care.
Circulation 2010;122:S76886.
This is a new section to the updated ACLS
guidelines for 2010. Among other therapies for
post-resuscitation care, therapeutic hypothermia
is discussed. It is recommended that all
comatose adult patients with ROSC after out-ofhospital ventricular fibrillation cardiac arrest
should receive therapeutic hypothermia (32C to
34C) for 12 to 24 hours. Furthermore,
therapeutic hypothermia may be considered for
comatose adult patients with ROSC after inhospital cardiac arrest of any initial rhythm or
after out-of-hospital cardiac arrest with an initial
rhythm of pulseless electrical activity or asystole.
Ber nard SA, Gray TW, Buist MD, et al.
Treatment of comatose survivors of out-ofhospital cardiac arrest with induced
hypothermia. N Engl J Med 2002;346:55763.
Animals studies have found that hypothermia
induced after ROSC may improve neurologic
outcome. In this randomized, controlled trial,
patients that were unconscious following an outof-hospital ventricular fibrillation arrest were
randomized to moderate hypothermia (n = 43) or
normothermia (n = 34). Moderate hypothermia
(33oC) or normothermia (37oC) was initiated in
the ambulance and maintained for 12 hours
following hospital arrival. At 18 hours, patients
were actively rewarmed for the next 6 hours.
Good outcome at discharge (discharged to home
or a rehabilitation facility) was higher in the
hypothermia group (49%) compared to the
normothermia group (26%).
Following
multivariate logistic-regression analysis with
adjustments for age and time from collapse to
ROSC, the OR for a good outcome at hospital
discharge was 5.25 (95% CI 1.47 to 18.76,
p=0.011), favoring the hypothermia group. There
were no clinically significant differences in pulse
rate, systemic vascular resistance, or cardiac
arrhythmias between the treatment groups.
The Hypothermia after Cardiac Arrest Study
Group. Mild therapeutic hypothermia to improve
the neurologic outcome after cardiac arrest. N
Engl J Med 2002;346;54956.
This multicenter, randomized controlled trial
with blinded assessment of the outcome included

those with a witnessed ventricular fibrillation

arrest and ROSC within 60 minutes from
collapse. Randomization occurred in the ED to
the therapeutic hypothermia group (n = 137,
target core temperature 32 to 34C) or
normothermia (n = 138). Intervention was
maintained for 24 hours, followed by passive
rewarming for the next 8 hours. Favorable
neurologic outcome (e.g., normal or mild
disability) at six months was evident in 55% of
those in the hypothermia group compared to
39% in the normothermia group (RR 1.40, 95%
CI 1.08 to 1.81). Therapeutic hypothermia also
reduced six month mortality, 55% compared to
41%, (risk ratio 0.74, 95% CI 0.58 to 0.95)
Arpino PA, Greer DM. Practical pharmacologic
aspects of therapeutic hypothermia after cardiac
arrest. Pharmacotherapy 2008;28:10211.
Physiologic changes during hypothermia alter
drug distribution and elimination. This article
reviews pharmacologic agents that are commonly
used in the setting of therapeutic hypothermia
and the pharmacokinetic and pharmacodynamic
changes that occur.
Shock
Anaphylaxis
Lieberman P, Kemp SF, Oppenheimer J, et al.
The diagnosis and management of anaphylaxis:
an updated practice parameter. J Allergy Clin
Immunol 2005;115:S483S523.
The goal of this manuscript was to provide
evidence based recommendations to medical
professionals related to anaphylaxis. A detailed
summary is provided for evaluation, acute
management, causes, patient education, and
prevention.
Sampson HA, Munoz-Furlong A, Campbell RL,
et al. Second symposium on the definition and
management of anaphylaxis: summary reportSecond National Institute of Allergy and
Infectious Disease/Food Allergy and Anaphylaxis
Network Symposium. Ann Emerg Med
2006;47:37380.
Proposed clinical criteria for establishing the
diagnosis of anaphylaxis are presented. In
addition, a brief review of the management of
anaphylaxis is provided. Epinephrine is the
cornerstone of treatment. The role of supportive
therapies are also outlined including the role of
oxygen, inhaled beta-agonists, fluids, vasopressors,

KEY ARTICLES FOR THE EMERGENCY MEDICINE PHARMACIST Thomas et al

antihistamines, corticosteroids, and glucagon.
Also included is a section on research needs.
Burn Management
Pham TN, Cancio LC, Gibran NS. American
Burn Association practice guidelines burn shock
resuscitation. J Burn Care Res 2008;29:25766.
Evidence based guidelines are presented related
to the initial resuscitation of the burn patient. A
review of formulas to estimate initial fluid
requirements, choice of resuscitation fluid, and
monitoring of response is presented.
Faucher L, Furukawa K. Practice guidelines for
the management of pain. J Burn Care Res
2006;27:65968.
This evidence based practice guideline is
devoted to the management of pain in the burn
victim. It provides a comprehensive review of
assessment, treatment goals, and the
management of pain using both pharmacologic
and nonpharmacologic modalities.
Sepsis
Dellinger RP, Levy MM, Carlet JM, et al.
Surviving sepsis campaign: international
guidelines for management of severe sepsis and
septic shock: 2008. Crit Care Med
2008;36:296327.
The Surviving Sepsis Campaign Guidelines
Committee convened to update the previous
editions. This clinical practice guideline was
developed to improve outcomes for patients with
severe sepsis and septic shock. These guidelines
provide evidence-based recommendations for
fluid resuscitation, vasopressor use, iontropic
therapy, antibiotic timing and use, steroids, and
glucose control.
Rivers E, Nguyen B, Havstad S, et al. Early-goal
directed therapy in the treatment of severe sepsis
and septic shock. N Engl J Med
2001;345:368377.
This prospective, randomized study was
conducted at an 850-bed academic tertiary care
hospital to assess the efficacy of early-goal
directed therapy in patients with severe sepsis
and septic shock prior to admission to the ICU.
Two hundred and sixty three patients were
enrolled in the study, 130 were randomized to the
early-goal directed therapy group and 133 were
assigned to standard therapy. Patients in the
early-goal directed therapy group had a central

477e

venous catheter placed that allowed central

venous oxygen saturation to be measured and
were treated in the ED for at least 6 hours before
being transferred to an inpatient bed. Early goal
directed therapy consisted of protocol directed
resuscitation to achieve a central venous pressure
of 8 to 12 mm Hg for non-intubated patients and
12 to 15 mm Hg for intubated patients, a mean
arterial pressure 65 mm Hg, and a central or
mixed venous oxygen saturation 70%. Protocol
parameters were met with crystalloid fluid
resuscitation, vasopressors, red blood cell
transfusions, or dobutamine. Urine output 0.5
mL/kg/hr was part of the protocol, however there
was not a therapy directed at achieving this
endpoint. Results revealed a lower in-hospital
mortality in the early-goal directed therapy group
(30.5%) compared to standard therapy (46.5%),
p=0.009. In addition, the 7 to 72 hours following
the initial resuscitation, patients in the early-goal
directed therapy group had a significantly higher
mean central venous oxygen saturation, a lower
lactate concentration, a lower base deficit, higher
pH values, and a lower mean APACHE II score
indicating less severe organ dysfunction
compared to the standard therapy group
Sakr Y, Reinhart K, Vincent JL, et al. Does
dopamine administration in shock influence
outcome? Results of the sepsis occurrence in
acutely ill patients (SOAP) study. Crit Care Med
2006;34:58997.
Per the Surviving Sepsis Campaign Guidelines,
norepinephrine and dopamine are considered the
first-line vasopressor agents during resuscitation.
Even though these agents are similar, there are
several pharmacologic differences. The SOAP
study group performed a multicenter,
observational study to determine if dopamine
administration was associated with poor
outcomes in patients with shock due to any
cause. This was also evaluated in a subgroup of
septic shock patients. Data from the SOAP
database identified 3,147 patients, of which 1,058
had shock (33.6%) and 462 (14.7%) had septic
shock. Of the shock patients, 375 (35.4%)
received dopamine and 683 (64.6%) never
received dopamine. Patients in the dopamine
group had higher ICU and hospital mortality
rates compared to those that did not receive
dopamine, 42.9% vs. 35.7%, p=0.02 and 49.9%
vs. 41.7%, p=0.01, respectively. Multivariate
analysis identified dopamine administration as an
independent risk factor for ICU mortality in
patients with shock.

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PHARMACOTHERAPY Volume 31, 2011

De Backer D, Biston P, Devriendt J, et al.

Comparison of dopamine and norepinephrine in
the treatment of shock. N Engl J Med
2010;362:77989.
Given the results of the previous study, a
prospective study was designed to compare
dopamine to norepinephrine. SOAP II was a
prospective, multicenter, randomized trial that
sought to determine if one of these vasopressor
agents was superior to the other. Patients who
were 18 years of age and required a vasopressor
for shock, defined as MAP < 70 mm Hg or
systolic blood pressure < 100 mm Hg despite
adequate fluid resuscitation, were included and
randomized to receive either dopamine or
norepinephrine as their initial vasopressor agent.
Open label norepinephrine was given if they
required greater than 20 g/kg/min of dopamine
or 0.19 g/kg/min of norepinephrine. A total of
1,679 patients were included, 858 received
dopamine and 821 received norepinephrine. No
difference in 28-day mortality was identified
between the groups. Despite this finding, more
arrhythmic events were noted in the dopamine
group compared to the norepinephrine group,
24.1% vs. 12.4%, respectively, p<0.001. In
addition, a subgroup analysis was performed and
revealed that patients with cardiogenic shock
who received dopamine had an increased rate of
death at 28 days.
Russell JA, Walley KR, Singer J, et al.
Vasopressin versus norepinephrine infusion in
patients with septic shock. N Engl J Med
2008;358:87787.
The VASST trial was a multicenter,
randomized, double-blind trial of 778 patients.
Patients with septic shock that were resistant to
fluids and were receiving a minimum of 5
mcg/min of norpinephrine were randomized to
receive vasopressin 0.010.03 units/min or
norepinephrine 515 g/min in addition to openlabel vasopressors. There were no differences in
28-day between the vasopressin and
norepinephrine groups, 35.4% vs. 39.3%,
respectively, p=0.26 or 90-day mortality, 43.9%
vs. 49.6%, respectively, p=0.11. The authors
conclude the vasopressin did not reduce
mortality in this patient population. Of note, this
study is the largest to date evaluating
vasopressin, and if vasopressin is used in therapy,
the 0.01 to 0.03 units/min dose should be used.
Kumar A, Roberts D, Wood KE, et al. Duration
of hypotension before initiation of effective

antimicrobial therapy is the critical determinant

of survival in human septic shock. Crit Care Med
2006;34:158996.
This retrospective cohort study evaluated 2,731
adult patients with septic shock from 14 ICUs
and 10 hospitals in Canada and the United
States. Overall, 2,154 patients received
appropriate empiric antimicrobial therapy
(78.9%) only after the onset of recurrent or
persistent hypotension. A relationship between
delay in starting appropriate antimicrobial
therapy and in-hospital mortality was identified,
adjusted odds ratio 1.119 per hour delay (95% CI
1.103 to 1.136; p <0.0001). For patients who
received appropriate therapy within the first hour
of documented hypotension, a survival rate of
79.9% was determined. In addition, for every
hour that antimicrobial therapy was delayed,
survival decreased by 7.6%. A multivariate
analysis demonstrated that time to initiation of
appropriate empiric antibiotics in this patient
population was the single strongest predictor of
outcome.
Gaieski DF, Pines JM, Band RA, et al. Impact of
time to antibiotics on survival in patients with
severe sepsis or septic shock in whom early goaldirected therapy was initiated in the emergency
department. Crit Care Med 2010;38:104553.
This was a retrospective analysis of a cohort of
patients with severe sepsis and septic shock
treated with early goal-directed therapy in an ED
at a single center. Two hundred sixty-one
patients were evaluated to determine the
association between the time to antibiotic
therapy and mortality. The median time from
triage to appropriate antibiotics for the entire
cohort was 119 minutes (interquartile range
[IQR], 76 to 192 minutes) and from qualification
for early goal-directed therapy to appropriate
antibiotics was 42 minutes (IQR, 0 to 93
minutes). After dichotomizing the data, a
mortality benefit to early antibiotics was seen in
those that received antibiotics in 1 hour
compared to those receiving antibiotics > 1 hour
from triage, 19.5% vs. 33.2%, repectively, p=0.02.
When evaluating these two time endpoints from
qualification for early goal-directed therapy to
antibiotics, there was a mortality benefit in the
1 hour group compared to > 1 hour, 25% vs.
38.5%, p=0.03. These data show the mortality
benefit to giving appropriate antibiotics in the ED
within 1 hour in this patient population.
Annane D, Sebille V, Charpentier C, et al. Effect

KEY ARTICLES FOR THE EMERGENCY MEDICINE PHARMACIST Thomas et al

of treatment with low doses of hydrocortisone
and fludrocortisone on mortality in patients with
septic shock. JAMA 2002;288:86271.
This placebo-controlled, randomized, doubleblind study was conducted in two parallel groups
in 19 intensive care units to assess the effect of
low dose corticosteroid therapy on 28-day
survival in patients with septic shock. Patients
were randomized to receive hydrocortisone 50
mg intravenous every 6 hours and fludrocortisone 50 g tablet once daily (n = 151) or
placebo (n = 149) for 7 days. All patients received
a corticotropin stimulation test. Overall, 229
patients were nonresponders (defined by a
response of 9 g/dL or less), 114 in the
corticosteroid group and 115 in the placebo
group. There were 70 responders, 36 in the
corticosteroid group and 34 in the placebo group.
No significant difference was noted in 28-day
survival among the responder group, however, in
the non-responder group there were 60 deaths in
the corticosteroid group and 73 deaths in the
placebo group (53% vs. 63%, respectively,
p=0.02). A difference was also seen in
vasopressor therapy withdrawal by day 28 in the
nonresponder group, 57% in the corticosteroid
group compared to 40% in the placebo group
(hazard ratio, 1.91, 95% CI 1.29 to 2.84,
p=0.001). The authors concluded that a 7-day
course of hydrocortisone and fludrocortisone
reduced the risk of death in patients with septic
shock and relative adrenal insufficiency. Adverse
events such as superinfection and gastrointestinal
bleeding were similar between the two groups.
Sprung CL, Annane D, Keh D, et al.
Hydrocortisone therapy for patients with septic
shock. N Engl J Med 2008;358:11124.
The previous trial (Annane D, et al.) found a
survival benefit primarily in patients with septic
shock who remained hypotensive after at least
one hour of resuscitation with fluids and
vasopressors and no response to corticotropin
stimulation who received hydrocortisone and
fludrocortisone. This multicenter, randomized,
double-blind, placebo-controlled trial sought to
evaluate a more broad population of patients
with the onset of septic shock within the
previous 72 hours.. Patients were randomized to
receive intravenous hydrocortisone 50 mg every
6 hours for 5 days then a dose taper over a 6-day
period or placebo. A total of 499 patients were
enrolled in the study, 233 (125 in the
hydrocortisone group and 108 in the placebo
group) were nonresponders to corticotropin and

479e

254 (118 in the hydrocortisone group and 136 in

the placebo group) patients were responders. No
difference was seen in 28-day mortality in the
patients who did not have a response to
corticotropin (39.2% in the hydrocortisone group
vs. 36.1% in the placebo group, p=0.69) or in
those patients who did respond (28.8% in the
hydrocortisone group vs. 28.7% in the placebo
group; p=1.00). However, shock was reversed
more quickly in patients who received
hydrocortisone compared to those who received
placebo. There were also more adverse events
noted in the hydrocortisone group including
superinfection, new sepsis, and septic shock.
The authors conclude that hydrocortisone did
not improve survival or reversal of shock overall
or in patients who did not have a response to
corticotropin. Based on these results, response to
the corticotropin stimulation test does not
provide useful information as to which patients
would benefit from hydrocortisone therapy.
Bernard GR, Vincent JL, Laterre PF, et al.
Efficacy and safety of recombinant human
activated protein C for severe sepsis. N Engl J
Med 2001;344:699709.
The PROWESS study was a randomized,
double-blind, placebo-controlled, multicenter
trial to determine if recombinant human
activated protein C (rhAPC) decreases mortality
in patients with severe sepsis. Patients were
included if they had a known or suspected
infection based on clinical data, had three or
more signs of systemic inflammation, and had at
least one organ dysfunction secondary to sepsis.
Randomization occurred within 24 hours of
enrollment identification and patients received
rhAPC 24 mcg/kg/hr for 96 hours or placebo.
The infusion was stopped one hour before any
percutaneous procedure or major surgery and
was restarted one and 12 hours, respectively, in
the absence of bleeding. Enrollment was
suspended during the second interim analysis of
data as the mortality rate differences exceeded
the a priori guideline. A total of 850 patients were
randomized to the rhAPC group and 840
received placebo. The rate of all cause mortality
at 28 days was 24.7% in the rhAPC group and
30.8% in the placebo group. Treatment with
rhAPC was associated with an absolute reduction
in the risk of death of 6.1% (p=0.005). However,
the incidence of bleeding was higher in the
rhAPC group than in the placebo group (3.5% vs.
2%; p=0.06).
Abraham E, Laterre PF, Garg R, et al.

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PHARMACOTHERAPY Volume 31, 2011

Drotrecogin alfa (activated) for adults with severe

sepsis and a low risk of death. N Engl J Med
2005;353:133241.
The ADDRESS trial was conducted at the
request of the Food and Drug Administration to
determine the efficacy of rhAPC in patients with
severe sepsis and a low risk of death based on
subgroup analyses from the PROWESS trial. This
randomized, double-blind, placebo-controlled,
multicenter trial enrolled patients with severe
sepsis and a low risk of death from 516 centers in
34 countries. An interim analysis was performed
when 1,500 patients were enrolled and early
termination was recommended in accordance
with futility guidelines as there was less than a
5% chance of meeting the reduction in the risk of
death endpoint. A total of 2,613 patients were
included in data analysis at termination, 1,316 in
the rhAPC group and 1,297 in the placebo group.
There was no difference in 28-day mortality
(18.5% in the rhAPC group vs. 17% in the
placebo group, p=0.34) or in in-hospital
mortality (20.6% vs. 20.5%, p=0.98). Despite
these findings, there was a higher rate of serious
bleeding in the rhAPC group compared to
placebo. The authors concluded that rhAPC
should not be administered to patients with
severe sepsis and a low risk of death (i.e., those
with single-organ failure or an APACHE II score
< 25).
Toxicology
Mokhlesi B, Leiken JB, Murray P, Corbridge TC.
Adult toxicology in critical care: Part I: general
approach to the intoxicated patient. Chest
2003;123:57792.
This comprehensive review details signs
physical exam findings for common poisonings
and initial treatment strategies. Multiple tables
are included which list drugs that affect
temperature, heart rate, pupil size, mental status,
and muscle tone. In addition, toxidromes of
common drug classes are reviewed with
associated treatments. A discussion of common
lab findings and their interpretation is also
included. Initial supportive care, gastric
decontamination, enhanced elimination
techniques, and a general discussion of antidotes
is also reviewed.
Mokhlesi B, Leikin JB, Murray P, Corbridge TC.
Adult toxicology in critical care: Part II: specific
poisonings. Chest 2003;123:897922.

This comprehensive review presents

information on common poisoning situations.
Each clinical scenario details potential sources of
the poisoning, mechanism for toxicity, physical
and laboratory findings, and treatment.
Decontamination
American Academy of Clinical Toxicology and
European Association of Poisons Centres and
Clinical Toxicologists. Position paper: ipecac
syrup. Clin Toxicol 2004;42:13343.
This position paper reviews animal and clinical
data,
potential
indications,
dosage,
contraindications, and complications associated
with syrup of ipecac administration. Gastric
decontamination with syrup of ipecac is not
recommended routinely for poisonings. Similar
to other gastric decontamination strategies, syrup
of ipecac must be administered within 60
minutes of a toxic ingestion. As a result of
induced emesis, other more effective therapies
may not be able to be administered to the victim.
American Academy of Clinical Toxicology and
European Association of Poisons Centres and
Clinical Toxicologists. Position paper: singledose activated charcoal. Clin Toxicol
2005;43:6187.
Single dose activated charcoal adsorbs poisons
in the gastrointestinal tract. To be effective
administration should occur within 60 minutes
of the ingestion. Even though there is some
adsorption beyond one hour, the clinical benefits
are unknown. Activated charcoal should not be
used routinely and never when there is a risk for
aspiration of gastric contents. Included is a
comprehensive table that summarizes data
including the percent reduction from single-dose
activated charcoal and a variety drugs.
American Academy of Clinical Toxicology and
European Association of Poisons Centres and
Clinical Toxicologists. Position statement and
practice guidelines on the use of multi-dose
activated charcoal in the treatment of acute
poisoning. Clin Toxicol 1999;37:73151.
This position statement reviews the clinical
and animal evidence for using multi-dose
activated charcoal. To be effective drugs must
undergo re-circulation through the gastrointestinal tract. The only indications when this
therapy is considered is for potentially life
threatening ingestions of carbamazepine,

KEY ARTICLES FOR THE EMERGENCY MEDICINE PHARMACIST Thomas et al

dapsone, phenobarbital, quinine, or theophylline. Dosing is continued until the patients
condition is improved.
American Academy of Clinical Toxicology and
European Association of Poisons Centres and
Clinical Toxicologists. Position paper: cathartics.
Clin Toxicol 2004;42:24353.
The lack of evidence to support cathartics led
the American Academy of Clinical Toxicology
and European Association of Poisons Centres and
Clinical Toxicologists to recommend against
using cathartics in the management of
poisonings.
American Academy of Clinical Toxicology and
European Association of Poisons Centres and
Clinical Toxicologists. Position paper: whole
bowel irrigation. Clin Toxicol 2004;42:84354.
Consistent with other gastric decontamination
strategies, this position paper recommends
against the routine use of whole bowel irrigation
(WBI). Specific situations where WBI can be
considered include ingestion times greater than
two hours and a potentially toxic amount of a
sustained release or enteric coated drug. It can
also be considered for enhanced elimination of
packets of illicit drugs or for iron ingestions.
American Academy of Clinical Toxicology and
European Association of Poisons Centres and
Clinical Toxicologists. Position paper: gastric
lavage. Clin Toxicol 2004;42:93343.
The use of gastric lavage is rarely indicated. It
can be considered when the potential benefit
outweighs the potential risks. The decision is
patient specific and is dependent on the type and
of exposure as well available alternative
therapies. It is associated with potential
complications including perforation, aspiration,
cardiac conduction disturbances, hypoxia, and
laryngospasm. A review of clinical and animal
data, indications, contraindications, and
complications are presented.
Proudfoot AT, Krenzelok EP, Vale JA. Position
paper on urine alkalinization. Clin Toxicol
2004;42:126.
A position paper dedicated to urine
alkalinization reviewed the rationale, literature,
indication, contraindications, and complications
of use. By increasing the urine pH, enhanced
elimination of some toxins is possible. Urine
alkalinization for moderate to severe salicylate
toxicity (not requiring dialysis) should be

481e

considered a first line treatment option. It can

also be considered for poisonings associated with
chlorpropamide, 2,4-dichlorophenoxyacetic acid,
diflunisal, fluoride, mecoprop, methotrexate, and
phenobarbital.
Antidotes
Dart RC, Borron SW, Caravati EM, et al. Expert
consensus guidelines for stocking of antidotes in
hospitals that provide emergency care. Ann
Emerg Med 2009;54:38694.e1.
These guidelines provide recommendations
from a diverse expert panel on antidote stocking
at hospitals that provide emergency care.
Information on the amount of antidote to have
available, location within the hospital, and the
mechanism of delivery (e.g., automated
dispensing cabinet in the ED) are offered.
Trujillo M, Guerrero J, Fragachan C, et. al.
Pharmacologic antidotes in critical care
medicine: a practical guide for drug
administration. Crit Care Med 1998;26:37791.
Since the use of antidotes for several
intoxications and exposures may be infrequent,
this article provides complete information in a
format that allows quick access for the clinician.
Specific recommendations for the initial and
maintenance dose, preparation, special
considerations and precautionary information,
and secondary effects are available for an
extensive list of antidotes.
Prescott LF, Illingworth RB, Crtichley JA,
Stewart MJ, Adam RD, Proudfoot AT.
Intravenous N-acetylcysteine: the treatment of
choice for paracetamol poisoning. Br Med J
1979;2:10971100.
The incidence of severe liver damage was
evaluated in 100 paracetamol ingestions treated
with intravenous N-acetylcysteine compared to
57 control patients treated with supportive care
only in this case control study. All patients
presented within 24 hours of ingestion and had a
paracetamol serum concentration consistent with
probable hepatic toxicity (four hour serum
concentration > 200 mg/L). Of those treated
with intravenous N-acetylcysteine (150 mg/kg
over 15 minutes, 50 mg/kg over 4 hours, and 100
mcg/kg over 16 hours) within 10 hours of
ingestion (n = 67), only one patient (treatment
initiated between 8 and 10 hours) developed
severe liver damage compared to 28/57 (49%) of

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PHARMACOTHERAPY Volume 31, 2011

those receiving supportive treatment alone. The

efficacy of N-acetylcysteine was further evident in
the high risk group (four hour paracetamol
serum concentration > 300 mg/L). One patient
developed severe liver damage following
treatment with N-acetylcysteine within 10 hours
compared to 25/28 (89%) in the supportive
treatment group. The authors concluded that the
critical ingestion to treatment interval is eight
hours and N-acetylcysteine treatment initiation
beyond 15 hours is ineffective. Of note, in
practice the initial dose of N-acetylcysteine is
infused over 60 minutes to theoretically decrease
the incidence of related anaphylaxis.

purified digoxin-specific antibody fragments

(Fab) for life-threatening digitalis toxicity
(median digoxin serum concentration 8 ng/mL).
Eighty percent of patients had complete
resolution of cardiac symptoms, 10% had partial
response, and 10% had no response to Fab
treatment. The time to initial response was 19
minutes (range 0 to 60 minutes) from infusion
completion. Of patients that experienced cardiac
arrest as a result of digitalis toxicity, 30/56 (54%)
survived the hospitalization. Development of
hypokalemia occurred in six patients (4%) and
exacerbations in congestive heart failure in four
patients (3%) as a result of Fab treatment.

Smilkstein MJ, Knapp GL, Kulig KW et al.

Efficacy of oral N-acetylcysteine in the treatment
of acetaminophen overdose. Analysis of the
national multicenter study (1976 to 1985). N
Engl J Med 1988;319:155762.
The outcomes of 2,540 patients treated with
oral N-acetylcysteine following acetaminophen
ingestion are described in this multicenter openlabel trial. Similar to Prescott et al, all patients
presented within 24 hours of ingestion and were
categorized as either probable hepatic toxicity or
high-risk based on the four hour acetaminophen
serum concentration. Treatment with oral Nacetylcysteine (140 mg/kg once, then 70 mg/kg
every four hours for 17 doses) within 10 hours
was associated with hepatotoxicity in 6.1% of
patients in the probable group and 8.3% in the
high risk group. Treatment initiation between 10
and 24 hours was associated with the
development of hepatotoxicity in 26.4% and
34.4% of patients in the probable and high-risk
groups, respectively. In contrast to Prescott et al,
treatment initiation beyond 16 hours was
effective in 59% of patients.

Brent J, McMartin K, Phillips S, et al.

Fomepizole for the treatment of ethylene glycol
poisoning. N Engl J Med 1999;340:8328.
Nineteen consecutive patients with confirmed
ethylene glycol toxicity and treatment with
fomepizole are described. Plasma glycolate
concentrations and urinary excretion of oxalate,
the predominant circulating metabolites of
ethylene glycol, decreased following fomepizole
administration. Nine patients with a high serum
creatinine concentration at enrollment had a
decrease in renal function during therapy, but
those with a normal serum creatinine had no
change in renal function. One death from
cardiogenic shock occurred due to severe acidosis
and myocardial infarction prior to presentation.
These findings indicate that early treatment and
prevention of ethylene glycol metabolism and
toxic metabolite accumulation is necessary.
There were no adverse effects attributed to
fomepizole.

Prescott L. Oral or intravenous N-acetylcysteine

for acetaminophen poisoning? Ann Emerg Med
2005;45:40913.
This editorial dissects the available efficacy and
safety data for N-acetylcysteine use in
acetaminophen toxicity and discusses common
controversies including optimal route of
administration, dose, and treatment duration.
Antman EM, Wenger TL, Butler VP, et al.
Treatment of 150 cases of life-threatening
digitalis intoxication with digoxin-specific Fab
antibody fragments: Final report of a multicenter
study. Circulation 1990;81:174452.
This prospective multicenter open-label
clinical trial describes the efficacy and safety of

Brent J, McMartin K, Phillips S, et al.

Fomepizole for the treatment of methanol
poisoning. N Engl J Med 2001;344:4249.
Eleven consecutive patients with confirmed
methanol toxicity and treatment with fomepizole
are described. Plasma formic acid concentrations,
the major toxic metabolite of methanol, decreased
in all patients following initiation of fomepizole.
This reduction correlated with metabolic acidosis
resolution and improvement of visual
disturbances. Two deaths occurred due to severe
acidosis and anoxic brain injury. Adverse effects
thought to be related to fomepizole included
phlebitis, dyspepsia, anxiety, agitation, transient
tachycardia, and transient rash.
Brent J. Fomepizole for ethylene glycol and
methanol poisoning. N Engl J Med
2009;360:221623.

KEY ARTICLES FOR THE EMERGENCY MEDICINE PHARMACIST Thomas et al

This review details the pathophysiology of
toxic alcohol ingestions, discusses all of the
available literature regarding fomepizole
treatment, and provides clinical management
recommendations.
Dart RC, Seifert SA, Boyer LV, et al. A
randomized multicenter trial of crotalinae
polyvalent immune Fab (ovine) antivenom for
the treatment for crotaline snakebite in the
United
States.
Arch
Intern
Med
2001;161:20302036.
This is the only randomized controlled trial of
antivenom use in North America available. It
was designed to evaluate two different dosing
strategies following achievement of initial
control, as-needed or scheduled Crotalidae
polyvalent immune Fab antivenin (Fab AV) in 31
patients. The as-needed group received no
further Fab AV unless envenomation related local
or systemic effects, or coagulopathy were evident.
Patients in the scheduled group received 2 vials
of Fab AV every 6 hours for 3 doses. No patients
in the scheduled group received additional doses
beyond the study treatment, however 50% of the
patients in the as-needed group required an
additional dose of Fab AV. The authors
determined that there was no difference in the
efficacy of terminating antivenom effects between
the groups, however, patients will likely require
additional doses of Fab AV beyond those required
to obtain initial control.
Weant KA, Johnson PN, Bowers RC, Armitstead
JA. Evidence-based, multidisciplinary approach
to the development of a crotalidae polyvalent
antivenin (CroFab) protocol at a university
hospital. Ann Pharmacother 2010;44:44755.
This article describes the development of a Fab
AV protocol at one institution. A review of the
available literature regarding Fab AV as well as
discussion regarding snakebite assessment
scoring systems and recommendations for patient
evaluation, Fab AV use, preparation, monitoring,
and follow-up provide practical information for
the clinician.
Traumatic Injury
Massive Transfusion
Lier H, Bttiger BW, Hinkelbein J, Krep H,
Ber nhard M. Coagulation management in
multiple trauma: a systematic review. Intensive
Care Med 2011;37:57282.

483e

Bleeding and coagulopathy associated with

trauma contributes to decreased survival.
Although most blood products are not
considered drugs, the emergency medicine
clinical pharmacist should have an
understanding of the pathophysiology and
treatment recommendations related to this
condition. This systematic review included 230
articles. In addition to monitoring and treatment
with blood products, there is a review with
associated recommendations on prothrombin
complex concentrates, antifibrinolytics,
desmopressin, factor XIII, rFVIIa, and
antithrombin.
Wafaisade A, Maegele M, Lefering, et al. High
plasma to red blood cell ratios are associated with
lower mortality rates in patients receiving
multiple transfusion (4 red blood cell units <
10) during acute trauma resuscitation. J Trauma
2011;70;819.
Resuscitation strategies to aggressively manage
trauma-induced coagulopathy and uncontrolled
bleeding include the administration of fresh
frozen plasma units (FFP) in a 1:1 ratio with
packed red blood cells (pRBC) during acute
trauma care. The benefit to this strategy has been
shown in the massive transfusion population (>
10 pRBC units) finding high ratio blood product
administration (1:1.4 vs. 1:2.5 and 1:8) to be
independently associated with improved survival
to hospital discharge, primarily by decreasing
death from hemorrhage (Borgman MA, Spinella
PC, Perkins JG, et al.
J Trauma
2007;63:805813). This retrospective analysis of
1,362 patients from the German Trauma registry
evaluated patients that received multiple
transfusions, however were not considered a
massive transfusion (4 red blood cell units <
10). Three groups were analyzed according to
FFP:pRBC ratio, low (< 1:1), balanced (1:1), and
high ratio (> 1:1). The rate of in-hospital
mortality was 26.8%, 21.7%, and 15.2%,
respectively, p=0.001, favoring the high ratio
group. Multivariate logistic regression identified
a high FFP:pRBC ratio as an independent
predictor for survival (OR, 0.52, p=0.013). Ongoing pRBC and FFP transfusions in the ICU
were also significantly lower in the high ratio
group compared to the balanced and low ratio
groups. Although, a non-pharmacologic
intervention, it is important for pharmacists that
encounter this patient population to understand
resuscitation efforts.

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PHARMACOTHERAPY Volume 31, 2011

Boffard KD, Riou B, Warren B, et al.

Recombinant factor VIIa as adjunctive therapy
for bleeding control in severely injured trauma
patients: two parallel randomized, placebocontrolled, double-blind clinical trials. J Trauma
2005;59:818.
Massive hemorrhage is a leading cause of death
in trauma. This study sought to determine the
efficacy and safety of off-label rFVIIa in patients
with blunt or penetrating trauma requiring blood
product transfusion. Patients were randomized
to receive rFVIIa (200 g/kg, 100 g/kg 1 hour
later, and 100 g/kg 3 hours later) or placebo
following eight units of pRBC within 12 hours
from injury. In the blunt trauma patients (n =
143), pRBC transfusion was reduced (estimated
reduction 2.6 units, p=0.03) in the rFVIIa group
compared to placebo. Massive transfusion
requirements (> 20 units RBC) was also less in
the rFVIIa group (14% vs. 33%, p = 0.03). In the
penetrating trauma patients (n = 134), there was
not a significant reduction in RBC requirements
(estimated reduction 1.0 units, p=0.10) or
massive transfusion requirements (7% vs. 19%,
p=0.08) with rFVIIa administration compared to
placebo. The clinical significance of these data
and cost effectiveness of this off-label
intervention has remained controversial. No data
available with off-label rFVIIa have been able to
show a mortality benefit in this patient
population. Although, there were no differences
in thromboembolic events in this study between
the treatment groups, this remains a concern
with the administration of rFVIIa.
Crush Injury
Brown CV, Rhee P, Chan L, et al. Preventing
renal failure in patients with rhabdomyolysis: Do
bicarbonate and mannitol make a difference? J
Trauma 2004;56:11916.
In patients with traumatic rhabdomyolysis, the
combination of bicarbonate and mannitol are
frequently used to prevent renal failure although
data are limited. This retrospective review
sought to evaluate its use in trauma patients with
elevated creatine kinase (CK). Abnormal CK
levels (CK > 520 units/L) were evident in 1,771
patients with a mean peak CK of 4,923 units/L
(range 521258,900 units/L). Peak CK values >
5,000 units/L were associated with renal failure
(peak creatinine > 2.0 mg/dL). Of the 382
patients in this high CK group, 40% received

bicarbonate and mannitol therapy and 60% did

not. Overall, there were no differences in the
incidence of renal failure, dialysis, and mortality
comparing bicarbonate and mannitol therapy to
fluid resuscitation alone. Even at similar CK
levels, 5,000 to 15,000 units/L (n=301), 15,000
to 30,000 units/L (n=49), and > 30,000 units/L
(n=32), there were no differences. Of note, there
with a trend toward improved outcomes in those
with CK > 30,000 units/L, however this did not
reach statistical significance possibly due to Type
II error. To date, this is the largest cohort of
posttraumatic rhabdomyolysis patients evaluated.
Malinoski DJ, Slater MS, Millins RJ. Crush
injury and rhabdomyolysis. Crit Care Clin
2004;20:17192.
This review describes the pathophysiology of
traumatic rhabdomyolysis and crush injury and
the treatment of consequent myoglobinuric renal
failure.
Jagodzinski N, Weerasinghe C, Porter K. Crush
injuries and crush syndromea review. Part 1:
the systemic injury. Trauma 2010;12:6988.
Jagodzinski N, Weerasinghe C, Porter K. Crush
injuries and crush syndromea review. Part 2:
the local injury. Trauma 2010;12:13348.
This two-part series provides a comprehensive
discussion of the pathophysiology of traumatic
rhabdomyolysis and review of the available
literature for treatment modalities, including
early fluid resuscitation, alkaline diuresis, and
mannitol as it pertains to the systemic injury and
compartment syndrome.
Spinal Cord Injury
American Association of Neurological Surgeons
and Congress of Neurological Surgeons Joint
Section on Disorders of the Spine and
Peripheral Nerves. Pharmacological therapy after
acute spinal cord injury: guidelines for the
management of acute cervical spine and spinal
cord injuries. Neurosurgery 2002;50(3
suppl):S6372.
This chapter provides an extensive evidencebased systematic review of all literature available
through 2001 for the administration of
corticosteroids following spinal cord injury. The
authors summarize that the medical evidence
does not support a significant clinical benefit
from methylprednisolone administered for 24 or

KEY ARTICLES FOR THE EMERGENCY MEDICINE PHARMACIST Thomas et al

48 hours in patients with acute spinal cord injury
and that the administration has been associated
with an increased rate of medical complications.
However, the authors go on to state that the
group recommends methylprednisolone as an
option that should only be undertaken with the
knowledge that the evidence suggests harmful
side effects more consistently than clinical
benefits.
Kortbeek JB, Al Turki SA, Ali J, et al. Advanced
trauma life support, 8th edition, the evidence for
change. J Trauma 2008;64:163850.
The most recent revision of the American
College of Surgeons Committee on Advanced
Trauma Life Support removed the previous
recommendation that methylprednisolone
administration in non-penetrating spinal cord
injury is an accepted treatment. The 8th edition
currently reads that there is insufficient evidence
to support the routine use of steroids in spinal
cord injury.
Bracken MB, Shepard MJ, Collins WF, et al. A
randomized,
controlled
trial
of
methylprednisolone or naloxone in the
treatment of acute spinal-cord injury: results of
the second national acute spinal cord injury
study. N Engl J Med 1990;332:140511.
The NASCIS I trial compared two treatment
groups, methylprednisolone 100 mg bolus, and
then 100 mg daily for 10 days or
methylprednisolone 1000 mg bolus, followed by
1000 mg daily for 10 days (Bracken MB, Collins
WF, Freeman DF, et al. Efficacy of
methylprednisolone in acute spinal cord injury.
JAMA 1984;251:4552). There was no control
group. The study was unable to detect a
difference in neurologic recovery (sensory or
motor) between the groups at 6 weeks and 6
months after injury. Animal data suggested that
the dose of methylprednisolone used in NASCIS I
was below the theoretically therapeutic
threshold. This article describes the NASCIS II
trial, a randomized, double-blind, placebocontrolled evaluation of patients randomized
within 12 hours of injury. Treatment consisted of
methylprednisolone 30 mg/kg bolus, then 5.4
mg/kg/hr for 23 hours (n = 162), naloxone at the
same dose (n = 154), or placebo (n = 171).
Patients receiving methylprednisolone within 8
hours of injury were reported to have significant
improvements in motor function (p=0.03), and
sensation (pin prick, p=0.02 and light touch,

485e

p=0.03) at 6 months, although not significant at

6 weeks. Rates of wound infections and
gastrointestinal bleeding were higher in the
methylprednisolone group, although not
statistically significant. The NASCIS II trial has
been highly criticized for no minimum motor
impairment required for inclusion, the failure to
measure patient functional recovery, reporting of
right sided motor scores only, and the lack of
standardized medical and surgical treatment
available among centers.
Bracken MB, Shepard MJ, Holford TR, et al.
Administration of methylprednisolone for 24
hours or 48 hours or tirilazad mesylate for 48
hours in the treatment of acute spinal cord
injury: results of the third national acute spinal
cord injury randomized controlled study. JAMA
1997;277:1597604.
The NASCIS III trial compared the efficacy and
safety of methylprednisolone administered for 24
hours (n = 166), 48 hours (n = 166), or tirilazad
mesylate for 48 hours (n = 167). Patients were
randomized and received treatment within 8
hours of injury. The dose of methylprednisolone
was similar to that in the NASCIS II trial. In the
intent-to-treat analysis, compared to
methylprednisolone for 24 hours and tirilazad,
the 48 hour methylprednisolone group showed
more motor function recovery at 6 weeks and 6
months, p=0.09 and p=0.07, respectively.
Evaluating treatment initiation between 3 and 8
hours from injury, motor function recovery was
statistically significant at 6 weeks, p=0.04, and 6
months,
p=0.01
in
the
48
hour
methylprednisolone group. Improvement in
sensory function was no different between the
groups. Methylprednisolone for 48 hours was
associated with an improvement in the overall
functional independence measure (p=0.08),
however, there was no difference in mobility,
locomotion, communication, or social cognition
within this assessment compared to the other
groups.
Patients in the 48 hour
methylprednisolone group had higher rates of
severe sepsis (p=0.07) and pneumonia (p=0.02).
The authors conclude that it may be more
difficult to interrupt posttraumatic spinal cord
pathophysiology for those treated after 3 hours
and recommend methylprednisolone treatment
for 24 hours when initiated within 3 hours of
injury and for 48 hours if treatment is initiated
between 3 and 8 hours after injury. Similar
criticisms exist for this trial as for the NASCIS II.

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PHARMACOTHERAPY Volume 31, 2011

Traumatic Brain Injury

Brain Trauma Foundation, American
Association of Neurological Surgeons (AANS),
Congress of Neurological Surgeons (CNS), and
the AANS/CNS Joint Section of Neurotrauma
and Critical Care. Guidelines on the
management of severe traumatic brain injury, 3rd
edition. J Neurotrauma 2007;24:S1199.
These collaborative guidelines provide
literature
evaluation
and
expert
recommendations on various topics related to the
pharmacotherapeutic management of patients
with traumatic brain injuries. These include
hyperosmolar therapy, infection prophylaxis,
deep vein thrombosis prophylaxis, anesthetics,
analgesics, and sedatives, antiseizure prophylaxis
and steroid use.
The SAFE Study Investigators. Saline or
albumin for fluid resuscitation in patients with
traumatic brain injury (SAFE-TBI). N Engl J Med
2007;357:87484.
The Saline versus Albumin Fluid Evaluation
(SAFE) study was a multicenter, double-blind,
randomized controlled trial comparing fluid
resuscitation with 4% albumin to normal saline
on mortality in intensive care unit patients. This
post hoc analysis of data from the SAFE trial
evaluates 460 patients with a traumatic brain
injury. Baseline demographic characteristics and
severity of brain injury were similar between
those that received 4% albumin (n = 231) and
saline (n = 229). Overall, mortality at 24 months
was higher in the albumin group (33.2%)
compared to the saline group (20.4%), RR 1.65
(95% CI, 1.17 to 2.26, p=0.003). In both groups,
85% of the deaths occurred by day 28. In
patients with severe traumatic brain injury
(Glascow Coma Scale score [GCS] 3 to 8), 41.8%
in the albumin group and 22.2% in the saline
group had died at 24 months, RR 1.88 (95% CI,
1.31 to 2.70, p<0.0001). There was no difference
in 24 month mortality in patients with moderate
traumatic brain injury (GCS 9 to 12). Of
survivors at 24 months, there were fewer
favorable neurologic outcomes in the albumin
group (47%) than in the saline group (60.6%).
These results were similar in those with severe
traumatic brain injury. These data support
normal saline resuscitation following traumatic
brain injury.
Cooper DJ, Myles PS, McDermott FT, et al.
Prehospital hypertonic saline resuscitation of
patients with hypotension and severe traumatic

brain injury. JAMA 2004;291:13507.

This double-blind, randomized controlled trial
evaluates pre-hospital hypertonic saline
resuscitation in 229 patients with traumatic brain
injury and multisystem blunt trauma injury. It
was hypothesized that aggressive resuscitation
and reversal of hypotension in the traumatic
brain injury population would be associated with
favorable 6 month neurologic outcomes. Patients
with a GCS score < 9 and a systolic blood
pressure < 100 mm Hg were randomized to
receive 250 mL of 7.5% sodium chloride or
Ringers lactate solution followed by open label
conventional fluid resuscitation. Baseline
demographics and total amount of fluid
resuscitation between the groups were similar.
There was no difference in the proportion of
favorable neurologic function at 6 months,
survival to hospital discharge, or 6 month
survival.
Forsyth LL, Liu-DeRyke X, Parker D, Rhoney
DH. Role of hypertonic saline for the
management of intracranial hypertension after
stroke and traumatic brain injury.
Pharmacotherapy 2008;28:46984.
The literature available regarding hypertonic
saline use for intracranial pressure reduction in
the adult and pediatric population following
traumatic brain injury is difficult to evaluate
based on the retrospective and observational
design. This article provides the rationale for
osmotic therapy use in addition to a
comprehensive review of the available literature
and practical considerations for the clinician.
Wakai A, Roberts IG, Schierhout G. Mannitol
for acute traumatic brain injury (review).
Cochrane Database Syst Rev 2007, Issue 1.
Art.No.: CD001049.DOI: 10.1002/14651858.
CD001049.pub4.
This systematic review of randomized
controlled trials evaluates the efficacy of
mannitol for lowering intracranial pressure
compared to alternative interventions or placebo.
Four trials were included; intracranial pressure
(ICP)-directed mannitol treatment compared to
mannitol administration based on neurological
signs, mannitol versus phenobarbital, mannitol
versus hypertonic saline, and mannitol versus
placebo. Based on this review, the authors
concluded that ICP-directed mannitol has a small
benefit compared to mannitol administration
directed by physical indicators (RR for death
0.83, 95% CI 0.47 to 1.46). Mannitol therapy for

KEY ARTICLES FOR THE EMERGENCY MEDICINE PHARMACIST Thomas et al

raised ICP may have a benefit on mortality
compared to phenobarbital (RR for death 0.85,
95% CI 0.52 to 1.38), but may have negative
effects compared to hypertonic saline (RR for
death 1.25, 95% CI 0.47 to 3.33). Insufficient
data was available to evaluate mannitol versus
placebo since the length of follow-up in this trial
was only two hours.
The CRASH Trial Collaborators. Effect of
intravenous corticosteroids on death within 14
days of 10,008 adults with clinically significant
head injury (MRC-CRASH trial): randomized
placebo-controlled
trial.
Lancet
2004;364:13218.
This multicenter, randomized, placebocontrolled trial sought to evaluate the early
administration of methylprednisolone in patients
with clinically significant brain injury on the risk
of death at two weeks and death or disability at 6
months. Adult patients with a GCS score of 14
or less following head injury were randomized to
receive methylprednisolone (2 g loading dose
over 1 hour followed by 0.4 gm/hr for 48 hours,
n = 5,007) or placebo (n = 5,001) within 8 hours
of injury. The study was halted prior to reaching
full enrollment due to results of the interim
analysis. The rate of death from all causes at two
weeks in the corticosteroid group was 21.1% and
in the placebo group was 17.9%, RR 1.18 (95%
CI 1.09 to 1.27, p=0.0001). The relative increase
of death in the corticosteroid group did not differ
by injury severity or time to injury. These results
clearly contest the use of corticosteroids for this
indication, although the exact mechanism for the
association with increased mortality is unknown.
Bratton SL, Chestnut RM, Ghajar J, et al.
Guidelines for the management of severe
traumatic brain injury. XIII. Antiseizure
Prophylaxis. J Neurotrauma 2007;24(supp 1):
S836.
These guidelines for the role of antiseizure
prophylaxis in the management of severe
traumatic brain injury were produced by the
Brain Trauma Foundation. They state that there
is insufficient data to support a Level 1
recommendation for this topic. These guidelines
do not recommend the prophylactic use of
phenytoin or valproate for preventing late
posttraumatic seizures. However they do suggest
that anticonvulsants may be indicated to decrease
the incidence of early post-traumatic seizures,
defined as those within seven days of injury, but
add that the occurrence of post-traumatic

487e

seizures is not associated with worse outcomes.

The evidence for this recommendation is based
on five randomized, double-blind trials that were
reviewed. The limitation of this recommendation
is that all of these studies evaluated clinically
recognizable seizures and provide no evidence
concerning those with non-convulsive seizures.
Temkin NR, Dikmen SS, Wilensky AJ, et al. A
randomized, double-blind study of phenytoin for
the prevention of post-traumatic seizures. N Engl
J Med 1990;323:497502.
This randomized, double-blind, placebo
controlled trial evaluated the efficacy of
phenytoin for seizure prevention following head
trauma in 404 patients. Eligible patients were
randomized to phenytoin (20 mg/kg intravenous
load, followed by maintenance therapy) or
placebo within 24 hours from injury and
continued on study therapy for 12 months.
Phenytoin maintenance doses, were adjusted to
maintain a free phenytoin serum concentration
between 0.75 to 1.5 mg/L. At 7 days, the
phenytoin group had a cumulative seizure rate of
3.6% compared to 14.2% in the placebo group,
p<0.001. However, from day 8 to 24 months
there was no difference in the rate of late seizures
between the groups, p>0.02 These data provide
support that phenytoin is efficacious only for the
prevention of early seizures in patients with posttraumatic head injury.
Jones KE, Puccio AM, Harshman KJ, et al.
Levetiracetum versus phenytoin for seizure
prophylaxis in severe traumatic brain injury.
Neurosurg
Focus
2008;25:E3.
DOI:
10.3171/FOC.2008.25.10.E3.
Levetiracetam is an attractive alternative since
serum concentrations do not have to be
monitored and it is not known to have significant
pharmacokinetic drug interactions. This report
was a case controlled study of 32 patients
receiving 7 days of levetiracetam compared to 41
phenytoin
control
patients.
An
electroencephalogram (EEG) was performed if
there was a suspicion of seizure on the basis of
mental status changes, persistent coma, or if
clinical seizure activity was evident. Fifteen
patients in the levetiracetam group required EEG
monitoring and 8 patients were found to have
abnormal findings (one patient had seizure
activity and 7 patients with seizure tendency). In
the phenytoin group, 12 patients required EEG
monitoring, with subsequent normal results. The
authors concluded that seizure activity was

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PHARMACOTHERAPY Volume 31, 2011

similar between the groups, however

levetiracetam was associated with a higher
incidence of abnormal EEG findings, p=0.003.
Szaflarski JP, Sangha KS, Lindsell CJ, Shutter
LA. Prospective, randomized, single-blinded
comparative trial of intravenous levetiracetam
versus phenytoin for seizure prophylaxis.
Neurocrit Care 2010;12:16572.
This was a prospective, single-center,
randomized controlled trial of levetiracetam
compared to phenytoin in patients for early
seizure prevention in 52 patients with severe
traumatic brain injury or subarachnoid
hemorrhage. Following enrollment, continuous
EEG monitoring was initiated for 72 hours and
study medication was continued for 7 days.
There were no differences between the groups in
early seizure occurrence, however Disability
Rating Scale scores at 3 months and Glascow
Outcomes Scale score at 6 months favored the
levetiracetam group. At this point there is
insufficient data on the efficacy of levetiracetam
for early seizure prevention in post-traumatic
brain injury.
Antimicrobial Prophylaxis
Luchette FA, Bone LB, Born CT, et al. East
practice management guidelines work group:
practice management guidelines for prophylactic
antibiotic use in open fractures, 2000 (Accessed
May 17, 2011 at http://www.east.org).
This guideline from the Eastern Association for
the Surgery of Trauma provides recommendations
for selecting appropriate empiric antimicrobial
therapy for patients with Type I, II, or III open
extremity fractures. Data support the use of
empiric antibiotics in patients with open fractures
especially for those with injuries to the skull,
hand, digits, knee, and ankle. For Type I and II
fractures, antimicrobials effective against S. aureus
are recommended. Gram-negative organisms
have been isolated from Type III open fractures
after initial debridement, therefore additional
Gram-negative coverage with an aminoglycoside
should be administered. High-dose penicillin
should be added when there is concern for
fecal/Clostridial contamination (e.g., farm related
injuries). Duration of therapy recommendations
are provided; antibiotics should be discontinued
24 hours after wound closure for patients with
Type I or II fractures, whereas antibiotics should
be continued for either 72 hours after the time of
injury or not more than 24 hours after soft tissue

coverage of the wound in those with Type III

fractures.
Hoff WS, Bonadies JA, Cachecho R, Dorlac WC.
East practice management guidelines work
group: update to practice management guidelines
for prophylactic antibiotic use in open fractures,
2009. (Accessed May 17, 2011 at
http://www.east.org)
An update to the open fracture prophylaxis
guidelines was presented at the 21 st Annual
Assembly of the Eastern Association for the
Surgery of Trauma in January 2008. In the
update, two additional recommendations were
added. Fluoroquinolones alone do not have an
advantage over the combination of a
cephalosporin and aminoglycoside and may
actually have a detrimental effect on the healing
process. The other new recommendation pertains
to the use of single-dose aminoglycoside dosing
which has been determined to be both effective
and safe in patients with Type II and III
fractures. Emphasis was also placed on starting
antimicrobials with Gram positive coverage as
soon as possible following injury.
Luchette FA, Borzotta AP, Croce MA, et al.
Practice management guidelines for prophylactic
antibiotic use in penetrating abdominal trauma,
2007. (Accessed May 17, 2011 at
http://www.east.org).
In order to prepare the guidelines for
prophylactic antibiotics in patients with
penetrating abdominal injuries, the authors
performed a MEDLINE search from 19761997.
From a comprehensive search of the medical
literature, 39 articles were identified and used to
produce the guidelines. A single preoperative
dose of prophylactic antibiotics is standard of
care for this group of trauma patients. An
antimicrobial with broad-spectrum aerobic and
anaerobic is recommended. Therapy should be
continued for only 24 hours if injury to any
hollow viscus is identified. A discussion of
antimicrobial therapy in patients with
hemorrhagic shock is presented since
vasoconstriction affects antibiotic distribution.
However, insufficient data exists in this area and
further research is needed.
Pharmacy Services and Patient Safety
ASHP Council on Pharmacy Practice. ASHP
Statement on Pharmacy Services to the
Emergency Department. Am J Health-Syst Pharm.
2008;65:2380-3.

KEY ARTICLES FOR THE EMERGENCY MEDICINE PHARMACIST Thomas et al

This position statement was developed by the
ASHP Section of Clinical Specialists and
Scientists Advisory Group on Emergency Care. It
serves as a guide for institutions regarding the
provision of pharmacy services to the ED that are
needed for safe and effective patient care. It
outlines the need for pharmacy services in this
setting from a patient safety perspective. This
position statement is not prescriptive, but is
rather broad in its scope, describing the types of
services that may be provided, acknowledging
the inherent variability and needs of different
institutions. Types of patient care activities and
services are discussed as they apply to both
critically ill and ambulatory patients. It also
elaborates on the role of pharmacy services with
regard to emergency preparedness, quality
improvement, education and professional
development. This statement addresses
pharmacy services overall, rather than services of
emergency medicine pharmacists which is
currently being drafted by the same group at the
time of this writing.
Rothschild JM, Churchill W, Erickson A, et al.
Medication errors recovered by emergency
department pharmacists. Ann Emerg Med
2010;55:51321.
In this prospective, multicenter, observational
study, the impact of emergency medicine
pharmacists on reducing medication errors was
evaluated. All four sites had established
emergency medicine pharmacist programs and
were academic, level 1 trauma centers with bed
sizes ranging from 29 to 124 beds. Trained
observers (pharmacy residents) observed
emergency medicine pharmacists and recorded
medication interventions made by the
pharmacist. Overall, 226 observation sessions
were conducted over a 787-hour time frame (3.5
hours per session). The pharmacists recovered
505 medication errors with an overall rate of
recovery being 7.8 errors per 100 patients and
2.9 errors per 100 medications. The most
common medication class involved was
antimicrobial agents (32.1%), followed by central
nervous system agents (16.2%), anticoagulants
and thrombolytics (14.1%), cardiovascular agents
(12.7%) and hormonal agents (6.7%). Most of
the medication errors were recovered during the
prescribing stage of the medication use process
(92.3%). Categorization by severity was as
follows: potentially life threatening (4.6%),
serious (47.8%), significant (36.2%), and
insignificant or unable to determine (11.3%).

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The authors concluded that emergency medicine

pharmacists are able to identify and intercept
medication errors. However, this was not a
controlled study and clinical outcomes were not
measured. Future controlled studies will require
a determination of cost-effectiveness of an
emergency medicine pharmacist, evaluation of
outcomes such as patient harm and a comparison
to other personnel such as additional nurses
focused on medication error recovery or
technologies such as computerized physician
order entry and decision support systems.
Patanwala AE, Warholak TL, Sanders AB,
Erstad BL. A prospective observational study of
medication errors in a tertiary care academic
emergency department. Ann Emerg Med
2010;55:5226.
In this prospective observational study an
investigator (emergency medicine pharmacist)
observed ED nurses for a total of 336 hours.
These observational sessions were conducted
continuously in 12-hour shifts. Shifts were
divided equally between day (0700 to 1900) and
night (1900 to 0700) and included all days of the
week. All phases of the medication use process,
including medication errors were observed for
patients cared for by the nurse being observed.
The study showed that 59.4% of patients had at
least one or more errors, and 37% had errors that
reached them. The latter were errors that were
made upstream in the medication use process
and were not caught by staff before reaching the
patient. Fortunately, only one of these errors
may have resulted in temporary patient harm.
Note that the observer attempted to intervene if
errors reached the patient and were likely to
cause harm. Errors categorized according to stage
of occurrence were prescribing (53.9%),
transcribing (10.7%), dispensing (0.6%), and
administering (34.8%). A logistic regression
analysis was performed to determine variables
predictive of medication errors. Significant
variables were boarded patient status (OR 2.15,
95% CI 1.03 to 4.5), number of medication
orders (OR 1.25, 95% CI 1.12 to 1.39), number
of medications administered (OR 1.22, 95% CI
1.07 to 1.38), and nursing employment status
(less error if full time) (OR 0.37, 95% CI 0.16 to
0.86). The authors concluded that medication
errors are common in the ED and most occur in
the prescribing and administering phases of the
medication use process.
Cohen V, Jellinek SP, Hatch A, Motov S. Effect of
clinical pharmacists on care in the emergency

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PHARMACOTHERAPY Volume 31, 2011

department: A systematic review. Am J HealthSyst Pharm. 2009;66:135361

The focus of this systematic review was to
retrieve articles that addressed the involvement of
pharmacists in the ED or interventions made by
the pharmacist in this setting and their associated
outcomes. A total of 17 articles met criteria for a
subsequent qualitative analysis. This review
contains tables with that delineate institute
specific details where these studies were
conducted, such as type of hospital (e.g.,
academic), location, ED beds, number of
admissions and type of pharmacy services
provided. Interestingly, 91.7% of the institutions
in these articles that deployed emergency
medicine pharmacists were academic medical
centers in large metropolitan areas. It also
contains a summary of the pharmacist activities
that were reported in these articles. This article
comprehensively characterizes ED pharmacy
services and related studies that were published
prior to 2009.
Lada P, Delgado G. Documentation of
pharmacists interventions in an emergency
department and associated cost avoidance. Am J
Health-Syst Pharm 2007;64:638
This was a evaluation of prospectively collected
data related to interventions made by emergency
medicine pharmacists at a single center.
Pharmacists were present in the ED 24-hours per
day, 7 days per week. There were 2150
interventions documented by the pharmacists
during a 4-month time frame. During each 24hour time period there was a mean of 17.5
interventions. Based on these values the authors
extrapolated that this would total approximately
6400 interventions per year. The 5 most
common interventions included provision of
drug information, dose adjustments, responding
to nursing questions, formulary changes and
initiation of drug therapy. The authors
reclassified the interventions based on a previous
investigation which attributed costs avoided to
each type of intervention (Lee AJ, Boro MS,
Knapp KK et al. Clinical and economic outcomes
of pharmacist recommendations in a Veterans
Affairs medical center. Am J Health-Syst Pharm.
2002; 59:20707). Using this scheme, the
authors calculated cost avoided of $1,029,776
during the study period and $3,089,328 when
extrapolated to one year. There are several
methodological flaws (e.g., generalization of
costs associated with each type to adverse drug
event) and this was not a formal economic

analysis. However, these findings are important

even if costs avoided were a small fraction of the
number calculated by these investigators. Future
studies are needed using formal economic
models and robust assumptions.
Emergency Preparedness
American Society of Health-System
Pharmacists. ASHP statement on the role of
health-system pharmacists in emergency
preparedness. Am J Health-Syst Pharm
2003;60:19935.
This statement from the American Society of
Health-System Pharmacists encourages
pharmacists to be involved with emergency
preparedness at the local, regional, state, and
federal levels as applicable to their practice. After
the events of September 11, 2001, it became clear
that hospital and health-system pharmacists must
be prepared to respond to events that result in a
large number of casualties. Four general
principles as well as advice to pharmacists in
different roles in the health-system (e.g.,
pharmacy directors, pharmacists, state societies,
etc.) are described. Pharmaceutical distribution
and medical management of patients during
disasters are two of the key roles mentioned.
These roles and others described are often the
primary responsibility of the emergency medicine
pharmacist as the ED serves as the gateway to the
healthcare system.
Kman NE, Nelson RN. Infectious agents of
bioterrorism: a review for emergency physicians.
Emerg Med Clin N Am 2008;26:51747.
This review article describes potential biologic
weapons that have been termed category A
agents by the CDC. These agents are of
particular interest to the CDC as they have the
highest potential to be used as biologic weapons.
Characteristics that are shared by these agents
include ease of dissemination, the potential
impact on public health, and the potential to
result in high mortality and public panic.
Anthrax, smallpox, the hemorrhagic fever
viruses, the Plague, botulinum toxin, and
tularemia are the agents discussed in this article.
Each agent is discussed in detail in regards to
background, epidemiology, transmission, clinical
manifestations, diagnosis, treatment, and public
health and infection control measures.
Lee JJ, Johnson SJ, Sohmer MJ. Guide for mass
prophylaxis of hospital employees in preparation

KEY ARTICLES FOR THE EMERGENCY MEDICINE PHARMACIST Thomas et al

for a bioterrorist attack. Am J Health-Syst Pharm
2009;66:5705.
This article provides a stepwise approach to
hospital based mass prophylaxis for employees
and the community. Insight into regional
prophylaxis for an event that is not confined is
also discussed.
This process involves
collaborating with other pharmacists in
neighboring jurisdictions, antibiotic selection,
protocol development, securing finances, and
storing the antibiotic stockpile and keeping
inventory current. Furthermore, the authors
describe an online toolkit that is available to
pharmacists and a comprehensive reference.
Pincock LL, Montello MJ, Tarosky MJ, Pierce
WF, Edwards CW. Pharmacist readiness roles for

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emergency preparedness. Am J Health-Syst

Pharm 2011;68:6203.
A brief commentary describing how
pharmacists in various practice settings (e.g.,
ambulatory care clinics, community pharmacies,
home health pharmacies, and hospital
pharmacies) can prepare for disaster-readiness
roles is provided. Disaster-readiness roles are
categorized as either pharmacy related or
operational (e.g., administration, finance,
communication, logistics, public information,
and triage). Emphasis is placed on clearly
defining roles and responsibilities prior to an
event occurring, establishing competencies, and
becoming personally prepared for participation in
this practice environment.