Dexmedetomidine is an α 2 -receptor agonist commonly used for sedation and analgesia in ICU patients. Dexmedetomidine is known to provide sympatholysis and also to have direct atrioventricular and sinoatrial node inhibitory effects. In rare instances, orthotopic lung transplantation has been associated with disruption of autonomic innervation of the heart. The combination of this autonomic disruption and dexmedetomidine may be associated with severe bradycardia and/or asystole. Since orthotopic lung transplant patients with parasympathetic denervation will not respond with increased heart rate to anticholinergic therapy, bradyarrhythmias must be recognized and promptly treated with direct acting beta agonists to avoid asystolic cardiac events

Allen-John Christopher

Brigid Colleen Flynn

E A Vandermeersch

M J C Carmona

M R Chakravarthy

Paul David Weyker

Webb

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Case Reports in Anesthesiology
Volume 2012, Article ID 203240, 4 pages
doi:10.1155/2012/203240
Case Report
Asystole after Orthotopic Lung Transplantation: Examining the
Interaction of Cardiac Denervation and Dexmedetomidine
Christopher Allen-John Webb,1 Paul David Weyker,1 and Brigid Colleen Flynn1, 2
1 Columbia University College of Physicians and Surgeons, Columbia University Medical Center, New York, NY 10032, USA
2 Division of Critical Care, Department of Anesthesiology, Columbia University Medical Center,
622 West 168th Street PH 5-505, New York, NY 10032, USA
Correspondence should be addressed to Brigid Colleen Flynn, bf2184@columbia.edu
Received 22 July 2012; Accepted 10 September 2012
Academic Editors: M. J. C. Carmona, M. R. Chakravarthy, and E. A. Vandermeersch
Copyright © 2012 Christopher Allen-John Webb et al. This is an open access article distributed under the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
properly cited.
Dexmedetomidine is an α2-receptor agonist commonly used for sedation and analgesia in ICU patients. Dexmedetomidine is
known to provide sympatholysis and also to have direct atrioventricular and sinoatrial node inhibitory effects. In rare instances,
orthotopic lung transplantation has been associated with disruption of autonomic innervation of the heart. The combination
of this autonomic disruption and dexmedetomidine may be associated with severe bradycardia and/or asystole. Since orthotopic
lung transplant patients with parasympathetic denervation will not respond with increased heart rate to anticholinergic therapy,
bradyarrhythmias must be recognized and promptly treated with direct acting beta agonists to avoid asystolic cardiac events.
1. Introduction
Bradycardia and asystole in the cardiothoracic intensive
care unit (CTICU) setting can be due to a broad range
of etiologies. Certain patients may be more predisposed to
bradyarrhythmias and/or asystole due to a combination of
factors such as the surgical procedure, medications being
administered, and preexisting patient comorbidities. We
report a case of severe bradycardia leading to asystole after a
bilateral orthotopic lung transplantation (OLT) in a patient
receiving dexmedetomidine sedation. We consider the possi-
bility that cardiac sympathetic denervation secondary to the
OLT in conjunction with atrial-ventricular node conduction
delay caused by the dexmedetomidine may have led to the
asystolic event.
2. Case Description
A 55-year-old woman with sarcoidosis was admitted to the
CTICU after receiving a bilateral OLT involving significant
tracheal dissection. On postoperative day 1, sedation was
weaned, and she was communicating appropriately while
intubated and desired to have an epidural catheter placed
for pain control prior to extubation. Timing of the epidural
for patients on anticoagulation was in accordance with
the American Society of Regional Anesthesia and Pain
Medicine guidelines [1]. Two hours prior to the procedure,
the patient was started on a dexmedetomidine infusion
at 0.5 micrograms/kilogram/hour for anxiolysis during the
procedure. Since bradycardia is oftentimes associated with
large boluses and high-dose infusions of dexmedetomidine,
we decided to start the infusion at a lower dose two hours
prior to procedure. She remained spontaneously breathing,
comfortable, and cooperative. Her hemodynamics remained
unchanged during the initiation of the dexmedetomidine
infusion.
With her assistance and the endotracheal tube remaining
in place, she was placed in a sitting position for epidural
placement, and 50 micrograms of intravenous fentanyl was
given for additional analgesia. Hemodynamic and respira-
tory stability was maintained with a sinus rhythm of 95 beats
per minute, blood pressure of 130/63 mmHg, and SpO2 of
95% and was consistent with her vitals prior to initiating
the dexmedetomidine infusion. After obtaining the sitting
position, her sinus rhythm deteriorated to bradycardia of 30
beats per minute, and she subsequently became hypotensive.
2 Case Reports in Anesthesiology
She became agitated, ceased following commands, and
became unresponsive. The dexmedetomidine infusion was
immediately stopped, and one milligram of intravenous
atropine was administered for the bradycardia with no effect.
The bradycardia continued to decline and deteriorated to an
asystolic event confirmed by arterial pressure monitoring,
and cardiopulmonary resuscitation (CPR) was initiated.
After 3–5 minutes of CPR, an additional 1-milligram bolus
of intravenous atropine was administered along with a 1-
milligram bolus of intravenous epinephrine, resulting in a
heart rate of 130 beats per minute and a systolic blood pres-
sure of 220 mmHg, which rapidly decreased to 130 mmHg.
Her hemodynamic profile remained stable, and the epidural
placement was aborted. Transesophageal echocardiogram
(TEE) failed to show any signs of a pulmonary embolus.
Differential diagnosis for the asystolic arrest included
myocardial infarction, pulmonary embolism (PE), relative
hypovolemia, a vasovagal event, the Bezold-Jarisch reflex,
cardiac sarcoidosis, and direct atrial-ventricular conduction
inhibition by dexmedetomidine. Our patient had increased
troponin levels; however, these were difficult to interpret due
to the CPR efforts and the previous day’s lung transplan-
tation operation. Her electrocardiogram remained in sinus
rhythm after the resuscitation with no ST abnormalities, and
her TEE was unchanged from her baseline, arguing against
a saddle embolus or myocardial infarction as the cause
of the arrest. While patients with systemic inflammatory
diseases are at risk for developing a deep venous thrombosis,
this patient was on prophylactic subcutaneous heparin.
Cardiac sarcoidosis was also considered; however, this was
less likely given that during the preoperative evaluation she
denied any previous history of arrhythmias or knowledge
of cardiac sarcoidosis. In terms of relative hypovolemia,
our patient’s fluid balance was negative; however, she was
maintaining adequate perfusion pressures with sufficient
urine output. Additionally, her ICU bed had previously
been positioned in the semirecumbent position with no
hemodynamic instability. Unfortunately, she never regained
consciousness following the arrest. Computed tomography
(CT) of her head and electroencephalogram (EEG) did not
demonstrate pathology explaining her comatose state, and
she did not meet the criteria for brain death. She remained
unresponsive and expired almost a month later from massive
gastrointestinal bleeding. On postmortem autopsy, several
small pulmonary infarcts consistent with pulmonary emboli
were noted. However, the significance and timing of these
infarcts could not be established with certainty.
3. Discussion
Dexmedetomidine, a D-enantiomer of medetomidine, is a
highly selective agonist of G-protein-coupled α2-adrenergic
receptors. These receptors are further categorized into three
main subtypes which exist in the periphery (α2A), brain, and
spinal cord (α2B,α2C) [2, 3]. Dexmedetomidine is a useful
sedative/analgesic commonly used in the ICU for several
reasons. It has been shown to decrease time on the ventilator
[4], decrease length of ICU stay [3], decrease anxiety, and
have opioid-sparing effects due to its analgesic properties
[5, 6]. Particularly, in postthoracotomy patients, it has been
shown that intravenous dexmedetomidine, in addition to
a thoracic epidural bupivicaine infusion, decreases opioid
requirements and may decrease the potential for respiratory
depression [6]. A significant advantage of dexmedetomidine
is its potential attenuation of delirium in ICU patients
[6]. This delirium-sparing effect may be due to action on
α2 receptors in the locus ceruleus producing a sedative
state similar to physiologic sleep. Lastly, dexmedetomidine
is especially beneficial for postsurgical patients in that it
preserves the respiratory drive, provides sympatholysis and
decreases the inflammatory response [7].
The most common side effects during dexmedetomidine
infusion are hypotension and bradycardia [3]. According to
the manufacturers of Precedex (Hospira, Inc., Lake Forest,
IL), 14% of patients experience bradycardia defined as a
heart rate < 40 bpm or >30% decrease from baseline. Other
authors have reported an incidence of bradycardia of up to
42% [4]. Bradycardia seen with dexmedetomidine is likely
due to sympatholysis in addition to direct inhibitory effects
on the sinoatrial (SA) and atrial-ventricular (AV) nodes
[8]. This bradycardia usually resolves with cessation of the
infusion or treatment with an anticholinergic agent. We
believe that dexmedetomidine-induced SA and AV nodal
depression proved refractory to anticholinergic medication
(atropine) owing to cardiac denervation occurring at the
time of lung transplantation.
It is known that during heart transplantation, both sym-
pathetic and parasympathetic denervation occur leading to
an increase in basal heart rate as the heart rate and electrical
activity of the transplanted heart become entirely dependent
on the intrinsic electrical system of the heart rather than
relying on the neurological input from the recipient. The
milieu of the denervated heart is complicated by the fact
that while separation of sympathetic and parasympathetic
occurs centrally, there is evidence that postganglionic fibers
remain functional in these patients [9]. In other words,
following cardiac transplantation, the sinus node becomes
decentralized rather than totally denervated [10]. Surgical
decentralization of the sinus node may be associated with
supersensitivity to catecholamine stimulation [10], because
α and β receptors are still present on the heart. The
decentralized heart will continue to respond to directly
acting catecholamine agents, such as epinephrine, isopro-
terenol, and dobutamine [11]. However, due to interruption
of parasympathetic tone, the heart is not responsive to
anticholinergic agents.
However, there is less knowledge of cardiac decen-
tralization following lung transplantation. The operative
dissection, especially that surrounding the trachea, likely
leads to interruption of sympathetic and parasympathetic
pathways to the heart [12]. This was illustrated in a study
by Schaefers et al. which demonstrated that lung transplant
recipients displayed abnormal responses to carotid sinus
massage and Valsalva maneuvers [12]. In fact, half of the
patients studied had no response to atropine, similar to what
was observed in our patient. Following OLT, it is thought that
reinnervation may occur at around 12 months.
Case Reports in Anesthesiology 3
While atrial arrhythmias following lung transplantation
can occur during the immediate postoperative period,
bradycardia is less defined in the literature. Atrial arrhyth-
mias following lung transplantation are commonly due to
inflammation or edema at the pulmonary vein left atrial
anastomoses [13]. The arrhythmias occur early during the
postoperative period and decrease over time [13].
Previous case reports have emerged citing dexmedeto-
midine as a contributing source of bradycardia followed
by asystole in various settings [14–16]. In these reports
and in our patient, it is likely that a combination of
factors contributed to the asystolic arrest. While the use of
concomitant sedatives with sympatholytic properties, that
is, fentanyl, may have augmented the bradycardia and/or
asystole associated with dexmedetomidine, it is likely that
cardiac sympathetic decentralization following OLT placed
our patient at significant risk for an asystolic event especially
when sedated with dexmedetomidine. To our knowledge,
only one other case report has described dexmedetomidine-
induced asystole in a patient status after double lung
transplant [16]. However, the transient bradycardia and
asystole in that patient are confounded by the presence of
pulmonary hypertension and a preexisting vagal response
to coughing which led to hypoxemia [16]. Additionally,
treatment with atropine or glycopyrrolate was not required
in this patient. Our case is unique given that our patient
demonstrated a refractory response to atropine and required
epinephrine for management of the asystolic arrest.
Clinicians must be aware of the possibility of cardiac
chronotropic alterations following OLT, similar to that
following heart transplantation. Acknowledging the valuable
and beneficiary role that dexmedetomidine plays in the man-
agement of OLT patients, we would suggest that heightened
vigilance and prompt recognition of dysrhythmias when
using dexmedetomidine in these patients may prevent a life-
threatening event.
Authors’ Contributions
C. A.-J. Webb, P. D. Weyker, and B. C. Flynn helped write the
paper, all authors approved the final paper.
Conflict of Interests
The authors state that they have no conflict of interests.
Disclosure
Written consent could not be obtained from the patient since
she is currently deceased. No current contact information for
next of kin could be obtained. Since she is currently deceased,
she does not qualify as a human subject according to the
definition set forth by the Institutional Review Board (IRB)
of Columbia University Medical Center. As such, the paper
did not qualify for IRB review.
Acknowledgment
The authors would like to thank Joshua S. Mincer, M.D. and
Ph.D., for reviewing the paper.
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Case Report Asystole after Orthotopic Lung Transplantation: Examining the Interaction of Cardiac Denervation and Dexmedetomidine

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Case Report Asystole after Orthotopic Lung Transplantation: Examining the Interaction of Cardiac Denervation and Dexmedetomidine

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