771342

case-report2018
SCVXXX10.1177/1089253218771342Seminars in Cardiothoracic and Vascular AnesthesiaCardinale and Gilly

Case Report
Seminars in Cardiothoracic and

Opiate-Free Tricuspid Valve Replacement:

Vascular Anesthesia
1­–7
© The Author(s) 2018
Case Report Reprints and permissions:
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DOI: 10.1177/1089253218771342
https://doi.org/10.1177/1089253218771342
journals.sagepub.com/home/scv

Jeffrey P. Cardinale, MD, PhD1 and George Gilly, MD1

Abstract
The utility of opioid pain medications for perioperative analgesia is well described. However, opioids have many dangerous
side effects including respiratory depression, acute tolerance, hyperalgesia, and chronic opioid dependence. Multimodal
approaches continue to be used in more invasive and complex surgical procedures for enhanced recovery and decreased
postoperative complications from opioid administration. The current case report centers on a 30-year-old male
recovering from opioid addiction presenting with severe tricuspid regurgitation scheduled to undergo a tricuspid valve
replacement. The patient requested an opioid-free procedure, and a multimodal plan was developed for intraoperative
and postprocedure management. This case represents a completely opioid-free valve replacement surgery and recovery.

Keywords
tricuspid valve repair, opiate free, opioids, narcotic free, narcotics

Introduction leaflet of the competent TV. Blood cultures yielded a diag-

Opioids are a central tenet of perioperative pain manage-
ment. However, opioid use is under increasing scrutiny
due to multiple well-documented and potentially danger-
ous side effects, including somnolence, brainstem and
respiratory depression, urinary and gastrointestinal issues,
acute tolerance, hyperalgesia, and chronic opioid depen-
dence.1-3 Multimodal, opioid-sparing, and opioid-free
approaches continue to grow in popularity as seen by their
use in more invasive and complex surgical procedures
(Table 1).4 These approaches result in improved recovery
from surgical procedures as well as decreasing the reper-
cussions associated with intra- and postoperative opi-
oids.5-7 An exhaustive literature search demonstrated an
absence of documented opioid-free cardiovascular surgi-
cal procedures. This case report describes an opioid-free
tricuspid valve (TV) replacement in a patient with severe
tricuspid regurgitation (TR).
Case Report
A 30-year-old man presented to an outside facility with left
arm abscess, fatigue, and fever. The patient had a medical
history significant for intravenous drug use from which he
was successfully weaned via outpatient addictive and pain
management services approximately 1 month prior to his
initial presentation. The patient’s first and all subsequent
urine toxicology results were negative for opioids. Two-
dimensional transthoracic echo demonstrated a mobile ech-
odensity (~2 × 1 cm) adherent to the mid-distal anterior
nosis of methicillin-sensitive Staphylococcus aureus endo-
carditis. This patient was felt to be a poor surgical candidate
at that time, and he was discharged home on antibiotics.
Two months later he was admitted to our institution for
acute shortness of breath secondary to septic pulmonary
emboli. His hospital course was complicated by acute renal
failure necessitating 4 rounds of hemodialysis. He under-
went a kidney biopsy during which the patient received
fentanyl (100 µg). He reported feeling “high”; and although
he did not clinically display symptoms of withdrawal, he
was concerned about experiencing such symptoms if he
were to require opioids for future procedures.
Transesophageal echocardiographic examination demon-
strated a 3.7 × 1 cm pedunculated, mobile, homogeneous
TV vegetation, TV flail with severe TR, and a depressed
ejection fraction of 40% to 45%. He was subsequently
scheduled for a TV replacement (TVR). Given his recent
recovery from opioid addiction and reaction to postopera-
tive fentanyl, the patient expressed his desire to avoid opi-
oids for his TVR. The patient expressed understanding that
inadequate analgesia can serve as a relapse trigger and that
opioids may be necessary for adequate pain control due to
the scope and invasiveness of the surgical procedure.
1
Ochsner Health System, New Orleans, LA, USA
Corresponding Author:
Jeffrey P. Cardinale, Ochsner Health System, 1514 Jefferson Hwy, New
Orleans, LA 70121-2429, USA.
Email: jcardi2@gmail.com
2 Seminars in Cardiothoracic and Vascular Anesthesia 00(0)

Table 1.  Definition of Anesthetic Approaches to Pain Management.

Multimodal The pharmacologic combination of 2 or more analgesics or techniques aimed at different pain
mechanisms for analgesia.
Opioid-sparing A multimodal approach that more specifically aims to minimize perioperative opioids but does
not eliminate their use in pain management.
Opioid-free A multimodal approach with a goal to completely avoid perioperative opioid use.

Figure 1.  Preoperative transesophageal echocardiography shows severe tricuspid regurgitation (A) and the postoperative repair
(B) following bicuspidization and annuloplasty.

Furthermore, when opioids are medically prescribed and
appropriately managed, relapse can be minimized. To fol-
low the patent’s pain control requests, an opioid-free multi-
modal management approach was agreed upon by the
patient, the primary cardiothoracic (CT) surgical team, the
intraoperative anesthetic team, and the hospital’s anesthe-
sia-led acute pain service (APS), which specializes in acute
and chronic pain as well as addiction management.
The patient underwent a TVR with bicuspidization and
annuloplasty with a 28-mm rigid ring via a median ster-
notomy approach and cardiopulmonary bypass. Prior to
induction, the patient received 6 mg midazolam. Induction
medications included lidocaine (100 mg), propofol (150
mg), rocuronium (5 mg), and succinylcholine (140 mg),
and surgical anesthesia was maintained with inhaled iso-
flurane. Bispectral index monitoring was employed to
monitor anesthetic depth throughout the case. Multimodal
pain control included 50 mg of ketamine (0.5 mg/kg dose
administered on induction) as well as 1000 mg intravenous
acetaminophen and 8 mg dexamethasone following induc-
tion and central line placement. A dexmedetomidine infu-
sion (0.5 µg/kg/h) and a lidocaine infusion (2.7 mg/h
[based on 0.03 mg/kg/h dosing]) were initiated after induc-
tion for intraoperative pain management and maintained
throughout cardiopulmonary bypass. The patient also
received a 25 mg bolus of ketamine (0.25 mg/kg dose)
prior to incision and at the start of sternal wound closure.
After approximately 3 hours the case concluded; post-
valve replacement transesophageal echocardiographic
examination showed no TR or TV stenosis (Figure 1). The
lidocaine infusion was discontinued with skin closure and
the patient was extubated in the operation room; his dex-
medetomidine infusion was weaned off within an hour of
arriving to the intensive care unit. He was also transported
on insulin and epinephrine infusions and both infusions
were successfully titrated off within several hours of case
completion. At this juncture, his opioid-free regimen was
managed by the APS. The postoperative treatment included
acetaminophen (1 g every 6 hours), celecoxib (200 mg
daily), aspirin (325 mg daily), and pregabalin (150 mg
nightly). Pain management success was determined by a
combination of vital signs, the patient’s level of agitation
and anxiety, “as needed” pain medication requests, and
self-assessment of his pain levels. His stated goal was <6
Cardinale and Gilly 3
to 7/10 on the standard 1 to 10 numeric pain visual analog
scale. On postoperative day 1, the patient was able to
ambulate without issue. He reported a 6/10 pain at rest and
8/10 pain with movement. Methocarbamol (750 mg 3
times daily) and alprazolam (0.5 mg twice daily as needed)
were added to his treatment schedule. On postoperative
day 2 he reported some improvement in his pain levels
(5/10 pain at rest; 7/10 pain with movement). He stated his
pain was very tolerable, vital signs were stable, and he
exhibited no visual signs of discomfort. His chest tubes
had minimal bloody output, so the nonsteroidal anti-
inflammatory drug (NSAID) ketorolac (15 mg every 6
hours as needed) was added on to widen his pain coverage.
On postoperative day 3, the patient stated his pain was
manageable with minimal “as needed” pain medication
requests. Postoperative laboratory values were stable, and
his chest tubes were removed. The patient was discharged
home with aspirin (325 mg daily), methocarbamol (750
mg 3 times daily), alprazolam (0.5 mg twice daily as
needed), and naproxen (500 mg twice daily) as per the
APS recommendations. At his postoperative follow-up
visits, the patient’s toxicology screenings remained nega-
tive for opioids, and he was very satisfied with his surgical
and recovery pain regimen.
Discussion
In the early 2000s, published research detailed the growing
phenomenon of opioid-induced hyperalgesia and the asso-
ciated increase in opioid addiction and abuse.1,2,3 As con-
cern mounted at all levels of patient care, anesthesiologists
quickly realized the need for an alternative means of peri-
operative pain control. Multimodal techniques were insti-
tuted to minimize opioid use during anesthesia. These pain
management modalities continue to evolve as both
research and comfort with their implementation grows.
This case demonstrates that in even the most challenging
surgical circumstances, minimal or opioid-free anesthetic
approaches can succeed with a willing patient, surgical
team, and support staff.
Opioids are a mainstay of current surgical practice
because they can effectively target the central mediators of
pain perception. However, perioperative pain results from
multiple mechanisms in addition to central signaling,
including direct neuronal injury (ie, compression, transec-
tion, etc) and indirectly via the inflammatory process (i.e.
cytokines) and other noxious signaling mediators (i.e.
Substance P).8 Targeting these various intermediaries is the
goal of the multimodal approach (Table 2). These
approaches can also include the use of neuraxial and
regional techniques (Table 3). Commonly used medica-
tions include traditional anti-inflammatories (i.e. aspirin,
acetaminophen, etc), NSAIDs, steroids, and local anesthet-
ics (i.e. lidocaine). These medications decrease the local
and systemic inflammatory and cytokine responses associ-
ated with surgical trauma and perioperative pain. Other
centrally acting analgesics are N-methyl-D-aspartate recep-
tor antagonists (i.e. ketamine) and α2-agonists (i.e. dexme-
detomidine). The utility of ketamine in cardiovascular
anesthesia has been shown to provide excellent hemody-
namic stability during induction in patients with poor ven-
tricular function, though caution should be observed in
patients with coronary artery disease or stenotic heart
lesions secondary to the potential of ketamine to induce
tachycardia.9 Moreover, it has been shown to attenuate the
inflammatory response to cardiopulmonary bypass, though
the clinical benefits remain uncertain.9 With regard to opi-
oid-dependent patients, ketamine has a good safety profile
and lowers the needs for intra- and postoperative opioid
consumption, especially in patients who consume higher
amounts of opioids.10,11 Dexmedetomidine has also been
shown to be efficacious in detoxification of opioid-depen-
dent patients as well as reduce the 1 year mortality in
patients undergoing cardiac surgery.12,13 Complementary
analgesic options include anticonvulsants (i.e. gabapenti-
noids such as neurontin or pregabalin) for neuropathic pain
and antispasmodics (i.e. methocarbamol) to decrease mus-
cle reactivity secondary to the inflammatory process, which
can exacerbate pain sensation. Antidepressants/anxiolytics
(i.e. diazepam) are also a viable option to assist in disinhib-
iting the patient from the current pain state.
Our case utilized many of the above-mentioned options,
but our first step involved clear communication and plan-
ning with the CT surgical team regarding appropriate care
and outcome goals. Epidural and regional approaches were
discussed; however, the CT surgical team preferred to
avoid epidural and regional anesthesia secondary to bleed-
ing concerns. For our pharmacologic approach, we fol-
lowed published recommendations by administering
acetaminophen and ketamine following induction but prior
to incision.6,14 Acetaminophen (intravenous or oral), espe-
cially in conjunction with NSAID administration, can
improve pain control and reduce postoperative opioid
requirements.5 Intraoperative dexamethasone was adminis-
tered as per our institution’s CT surgery anesthetic
approach. While aspirin and NSAIDs were utilized in the
reported case, caution is advised. Treatment regimens
should be tailored to the individual patient’s kidney func-
tion. Furthermore, gastric irritation and bleeding are possi-
ble consequences of aspirin and NSAID use.15 Ketamine
administered as an initial bolus dose reduces postoperative
hyperalgesia, opioid receptor “wind-up,” and tolerance.6,16
Ketamine can also be administered as an infusion for intra-
operative surgical pain, although this was not done with our
patient and instead bolus doses were administered at times
during potentially painful/stimulating points of the proce-
dure (incision and separation from cardiopulmonary
bypass). Lidocaine infusions have been shown to reduce
4 Seminars in Cardiothoracic and Vascular Anesthesia 00(0)

Table 2.  Nonopioid Analgesic Classes, Medication Examples, Mechanism of Action, Benefits, and Risks (Not Comprehensive).

Class Medications Mechanism of Action Benefits Risks

Aminophenols Acetaminophen Unknown, possible Effective for Liver toxicity; overdose
(paracetamol) endocannabinoid noninflammatory pain; potential
modulation, and COX antipyretic
reduction
Salicylates Aspirin COX-1 and COX-2 Anti-inflammatory Irreversible platelet inhibition;
inhibition risk of GI bleeding
NSAIDs Ibuprofen; ketorolac; Reversible nonselective COX Anti-inflammatory; Reversible platelet inhibition;
naproxen inhibition antipyretic risk of GI bleeding; worsen
renal function
COX-2 inhibitors Celecoxib ↓ Inflammation and pain Reduced GI effects versus Potential ↑ risk of MI, stroke,
NSAIDs; no effect on and death
platelet function
Steroids Dexamethasone; ↑ Risk of infection, muscle
Intracellular receptor targets, Anti-inflammatory and
prednisone complex ↓ stress and immune weakness, severe allergic
response reactions, and psychosis;
long-term use may cause
adrenal insufficiency
Local anesthetics Lidocaine; bupivacaine Blockade of neuronal Na Anti-inflammatory and anti- Hypotension and bradycardia,
channel conductance hyperalgesic actions heart block, local anesthetic
systemic toxicity
NMDA antagonist Ketamine; magnesium; ↓ Glutamate/glycine binding Analgesic, amnestic and Sedation, hallucinations;
nitric oxide and ↓ neuronal excitation anesthetic properties; narrow therapeutic window
antihyperalgesic properties (Mag)
α2-agonists Dexmedetomidine; Central α2-agonism; Anesthetic properties Sedation and hypotension
clonidine ↓ noradrenergic without associated
neurotransmission (a major respiratory depression;
nociceptive pathway) analgesic effect lasting >48
hours
Antidepressants Fluoxetine; amitriptyline SSRI/SNRI; TCAs ↓ Psychogenic pain Anticholinergic actions and ↓
component seizure threshold
Anticonvulsants Carbamazepine; valproic ↓ Na, K conductance and ↑ Reduces burning or shock- Sedation, liver dysfunction,
acid; gabapentin; and GABA activity like neuropathic pain dizziness, and hypotension
pregabalin
Antispasmodics Methocarbamol Unknown, potential carbonic ↓ Muscle spasms Dizziness, ataxia, mood
anhydrase inhibition swings, and dysuria; both
tachycardia (fast heart rate)
and bradycardia
Anxiolytics Diazepam; lorazepam GABAA Reduces anxiety associated Sedation and addiction
with pain, ↓ muscle potential
spasms
Muscle relaxants Baclofen GABAB agonist Muscle spasms, especially Hallucinations, confusion,
with spinal cord injuries anxiety withdrawal potential

Abbreviations: COX, cyclooxygenase; GI, gastrointestinal; NSAID, nonsteroidal anti-inflammatory drug; MI, myocardial infraction; Na, sodium;
NMDA, N-methyl-D-aspartate; SSRI, selective serotonin reuptake inhibitor; SNRI, serotonin-norepinephrine reuptake inhibitor; TCA, tricyclic
antidepressant; K, potassium; GABA, γ-aminobutyric acid.

both intra- and postoperative pain.17 However, caution
must be taken with first and second degree heart conduc-
tion blocks as these could progress into a higher degree of
heart block via a direct mechanism. Moreover, history of
cardiovascular instability (i.e. congestive heart failure, low
baseline blood pressure, dysrhythmias, etc) and concomi-
tant use of α-agonists or β-blockers are considered relative
contraindications.17,18 In this case, the patient had a normal
electrocardiographic profile; although he had severe TR
and mildly depressed systolic function, the CT surgery and
anesthesia teams felt that this was a safe option. The benefi-
cial properties of dexmedetomidine include a moderate
reduction in acute pain, which has been shown to have
analgesic effects lasting greater than 48 hours. This periop-
erative application is advantageous despite the known com-
plications of hypotension and bradycardia.19 Postoperatively,
Cardinale and Gilly 5

Table 3.  Neuraxial and Regional Approaches for Pain Management for Surgeries Requiring Median Sternotomy.

Technique Mode of Action Benefits Risks

Thoracic epidural T2-T10 (typically T2-T6) approach Decreased catecholamine Epidural hematoma and intense
response, improved neurological assessment
gastrointestinal function postoperatively; Risk: 1:2100 and
postoperative, and earlier 1:2900. Placement failure rate ~15%.
extubation
Single shot spinal T2-T10 (typically T2-T6) approach Decreased catecholamine Epidural hematoma and intense
response and earlier neurological assessment
extubation postoperatively. Less well studied
versus epidural approach; Risk: 1:2100
and 1:2900. Placement failure rate
~15%.
Erector spinae nerve Ventral rami nerve branching off Simple and safe when compared Potential for cutaneous sparing and can
block the nerve root travels deep to with epidural, spinal, and miss the sternal nerve fibers.
the erector spinae muscle bundle paravertebral approaches
Paravertebral nerve Single shot or catheter placement The intercostal nerve passes Inadvertent pneumothorax,
block in the area immediately lateral to through the space without a neurological damage, and inadvertent
the intervertebral foramen fascial sheath (easier to block), intrathecal injection are still potential
less hypotension, and better complications. Currently not well
preserved respiratory function validated in studies.
Intercostal nerve Single injections for 2 or 3 Individually, quick and simple Short-acting and multiple intercostal
block intercostal spaces above and to perform; low risk of catheters can be sited but are generally
below the incision site sympathetic blockade too time-consuming and complicated
to be useful in everyday practice.
Inadequate posterior analgesia. Large
volumes needed if multiple injections
are performed (easy to exceed the
toxic dose).
Parasternal nerve Plane block between the visceral Single shot or catheter; easy to Local anesthetic can pool and miss
block and parietal pleura perform certain sections. Potential for
pneumothorax.

the multimodal combination of acetaminophen, celecoxib
(a cyclooxygenase-2 inhibitor), aspirin, pregabalin, metho-
carbamol, alprazolam, and ketorolac created an effective
coverage of multiple afferent pain pathways as he contin-
ued his recovery.
Although not included in our case, additional adjunc-
tive pain management techniques are available. Infusion
of magnesium, an N-methyl-D-aspartate receptor antago-
nist, has been shown to effectively reduce opioid adminis-
tration, without serious adverse effects, especially when
used in conjunction with ketamine. However, its imple-
mentation and safety in cardiovascular cases is lack-
ing.20,21 Numerous studies and case reports detail the use
of epidural anesthesia with associated reduction in opioid
consumption postoperatively. However, many surgical
centers prefer to avoid this approach if possible secondary
to potential complications and controversy regarding
safety due to the intraoperative anticoagulant require-
ments.22 Regional anesthesia appears to be the new fron-
tier in pain management for CT surgical cases. While the
use of regional anesthesia has not been a common practice
for our cardiac group, regional techniques, including
paravertebral and parasternal blocks for perioperative
comfort, show improved pain control postoperatively.23,24
Furthermore, since the occurrence of this case, our institu-
tion has started performing transversus thoracic plane
blocks with great success in earlier extubation, earlier
ambulation, improved postoperative pain management,
and improved patient satisfaction scores. Currently, we
are only including patients presenting for valve replace-
ment or coronary artery bypass grafting with fewer estab-
lished comorbidities but plan to expand to other
cardiovascular procedures and patient population sub-
types. Furthermore, as a CT surgical department we are
familiarizing ourselves with the appropriate technical
approach for more widespread future application of these
regional approaches. The complete elimination of opioid
therapy may not always be possible; however, minimizing
their use, especially considering the many side effects
associated with opioid use, does present a great opportu-
nity to refine the opioid-sparing approach. Regardless,
expanded knowledge of the many analgesic therapies can
aid in developing opioid-sparing and opioid-free options
to meet individual patient needs.
6 Seminars in Cardiothoracic and Vascular Anesthesia 00(0)
Conclusion
To our knowledge, reports of completely opioid-free major
cardiovascular surgery have not been reported. This case
details our approach to the patient’s request for a nonopioid
surgery and recovery. This was accomplished through the
effective communication and combined efforts of the pri-
mary CT surgery team, intraoperative anesthesia team,
APS team, and a motivated patient. The perioperative anal-
gesic plan provided adequate pain control for our patient.
Nevertheless, expanded knowledge of therapeutic guide-
lines, medication dosing, and administrative timing, along
with the development and refinement of neuraxial and
regional techniques, will increase the surgical and patient
options available for a more robust and reliable multimodal
approach. Future studies addressing these needs at all lev-
els of perioperative analgesic management are paramount.
Currently, the body of literature is advancing in other areas
of surgery, but due to the inherent complexity of CT sur-
gery, many of these management modalities have not yet
been fully investigated or are met with much resistance. As
our understanding of the benefits and consequences of
these approaches expands, their utility in more invasive,
complex surgeries, such as the TVR described, will only
aid in decreasing the deleterious effects of opioid adminis-
tration in our current patient populations.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
ORCID iD
Jeffrey P. Cardinale https://orcid.org/0000-0002-0674-2705
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