Octreotide-induced asystolic events in an intensive care

unit patient with gastrointestinal bleeding

Luke Simon Olivera Yuhico, MDa,*, Vinod Gundu, MBBSa, Robert Lenox, MDb
a
Department of Medicine, SUNY Upstate Medical University, Syracuse, New York
b
Department of Medicine, Division of Pulmonary and Critical Care, SUNY Upstate Medical University, Syracuse, New York

article info abstract

Article history: Octreotide is a somatostatin analogue used to control upper gastrointestinal

Received 1 February 2012 bleeding. We report a case of a patient with no significant cardiac history who
Accepted 11 April 2012 had multiple asystolic events during an octreotide infusion at a relatively low
Online 30 May 2012 dose. Although octreotide leading to bradycardia and heart block has been
documented in several case reports, to our knowledge, octreotide-associated
asystole has not been described. It is pertinent that physicians must be aware
of this significant cardiac effect for vigilant cardiac monitoring and manage-
ment, preferably in an intensive care setting. Furthermore, this suggests that
although dose- and route-related effects have been described, some individuals
may be susceptible at low doses, even in the absence of heart disease. There
were no further recurrences after the drug was discontinued.

Octreotide, a somatostatin analogue, has been used in Case Report

the control and stabilization of patients with acute
gastrointestinal (GI) bleeding. Although octreotide is
more commonly associated with GI side effects, such
as nausea or cramping, several case reports have noted
cardiac disturbances primarily in the form of brady-
cardia or conduction blockade with octreotide infu-
sions. Knowledge of these effects is critical to use of
this drug for medical management, particularly given
the labile condition of an unstable patient with GI
bleeding. In the following case, we present a patient
with no significant cardiac history who experienced
multiple asystolic events while receiving an octreotide
infusion. These were not noted to recur after the
infusion was discontinued.
A 65-year-old women presented with a 2-week history
of intermittent epigastric discomfort, melena, coffee-
ground emesis, and presyncope. She was hypoten-
sive, and nasogastric lavage revealed 500 mL of bright
red blood. In addition to fluid support and vitamin K
administration, she was given an 80 mg intravenous
bolus of pantoprazole and then administered both
a pantoprazole infusion at 8 mg/h and an octreotide
infusion at 50 mg/h. Upper GI endoscopy was attemp-
ted; however, this was initially unsuccessful because
of a severe gag reflex and active bleeding. The patient
was admitted to the intensive care unit, intubated

* Corresponding author: Luke Simon Olivera Yuhico, MD, SUNY Upstate Medical University, 750 East Adams St. Syracuse, NY 13210.
E-mail addresses: luke_yuhico@yahoo.com, yuhicol@upstate.edu (L. S. O. Yuhico).
0147-9563/$ - see front matter Published by Elsevier Inc.
doi:10.1016/j.hrtlng.2012.04.010
 h e a r t & l u n g 4 1 ( 2 0 1 2 ) e 1 8 ee 2 0
for airway protection, and sedated on a propofol drip
with the plan to perform the endoscopy in a more
controlled setting. Endoscopy revealed a duodenal
ulcer for which treatment involved epinephrine injec-
tion and clips.
On day 2, the patient developed a bradycardic rh-
ythm that quickly disintegrated into asystole. This
asystolic event lasted for 10 seconds, after which car-
diopulmonary resuscitation led to normal sinus rh-
ythm. The patient had no history of bradycardia or
significant cardiac disease. Her outpatient medications
had all been held since the time of admission. She was
placed on a scopolamine patch and atropine as needed.
The cardiology service was consulted, and they estab-
lished that there were no clinical manifestations of
sinus node dysfunction and that this was likely a drug-
related event, with possible offenders being propofol or
octreotide. Propofol sedation was then switched to
midazolam, but the octreotide infusion was continued
because of the gastrointestinal bleed.
On day 3, the patient had 2 more asystolic events
and multiple bradycardic episodes with heart rates as
low as 26 to 40 beats/min, all of which were responsive
to atropine. Octreotide infusion was stopped. After
discontinuation, there were no more recurrences
of bradycardic or asystolic episodes. The temporal
correlation between the onset and the termination of
the cardiac effects with the initiation and discontinu-
ation of the octreotide infusion suggested a causal
relationship. The rest of her hospital stay was un-
eventful until discharge.
Discussion
Octreotide acetate is a long-acting octapeptide that
mimics natural somatostatin by inhibiting serotonin
release and secretion of gastrin, growth hormone,
glucagon, insulin, serotonin, gastrin, vasoactive intes-
tinal peptide, secretin, motilin, and pancreatic poly-
peptide. It decreases splanchnic blood flow, GI motility,
and intestinal secretion of water and electrolytes.1
Other than in GI bleed, octreotide acetate is also used
to treat acromegaly in adults and to control symptoms
in profuse secretory diarrhea in metastatic carcinoid or
vasoactive intestinal peptide-secreting tumors, insuli-
noma, glucogonoma, and ZollingereEllison syndrome.1
Common adverse effects of octreotide treatment
include nausea, abdominal cramps, diarrhea, malab-
sorption of fat, and flatulence. Although infrequent,
bradycardia associated with octreotide has been re-
ported in various clinical settings.2-8 McCormick et al7
described a significant decrease in pulse rate and
cardiac output and increase in systemic vascular
resistance immediately after an octreotide bolus.
Tuncer et al8 described atropine-responsive brady-
cardia, complete heart block, and hypotension on the
60th hour of octreotide infusion, with persistence of
e19
the heart block (despite correction of bradycardia) until
6 days after discontinuation.8 Dilger et al4 reported
octreotide-induced bradycardia, Mobitz II, and third-
degree heart block after a large bolus administration.
On the contrary, Herrington et al2 described brady-
cardia but without any heart block. Some hemody-
namic studies also show unchanged heart rates and
blood pressures despite changes in systemic vascular
resistance or hepatic blood flow.9,10 To our knowledge,
our case is the first in which octreotide was associated
with asystolic events.
The most plausible explanation for asystole after
octreotide in our case is through its direct effects on
the heart, being an analogue of somatostatin that is
known to slow the sinus rate, depress atrioventricular
conduction, decrease myocardial contractility, and
decrease the propagation velocity along the cardiac
conduction system. Studies on somatostatin in both
the human and the animal heart have described its
negative inotropic and chronotropic cardiovascular
effects.11-16 Other mechanisms postulated are in-
creased systemic vascular resistance leading to bra-
dycardia through a baroreceptor-induced reflexive
response to this increase in systemic blood pressure7 or
through suppression of vasoactive intestinal peptide,1
which is known to increase the heart rate in vivo
even more so than norepinephrine.17
Cardiovascular effects also seem to be dose and
route related. They are less observed when octreotide
is delivered subcutaneously.18 Some studies also
demonstrate that lower dose infusions at 50 mg/h9 or
100 mg/h19 show less significant cardiovascular effects
compared with larger doses given at 250 mg/h.13,20
However, in our case these repeated bradycardic and
asystolic events occurred at a relatively low-dose
infusion rate of only 50 mg/h. This suggests that apart
from dose or route-related risk, it is likely that some
individuals are also more susceptible than others, with
varying degrees of cardiac sensitivity to the drug.
Conclusions
Octreotide can lead to significant cardiovascular
effects, primarily in the form of negative inotropism
and chronotropism. Asystolic events must be consid-
ered by physicians as possible side effects of octreotide
infusion, apart from bradycardia and heart block.
Given the current evidence, it may be advisable to
deliver this medication in lower concentrations with
close cardiac monitoring, preferably in an intensive
care setting. Although dose- and route-related effects
have been described with this medication, there is also
a likely higher susceptibility in some individuals that
may predispose them to greater risk of cardiac
involvement, regardless of dose, route, or past cardiac
disease. When octreotide is indicated for therapy,
physicians must be vigilant of these significant adverse
e20 h e a r t & l u n g 4 1 ( 2 0 1 2 ) e 1 8 ee 2 0
effects to promptly treat hemodynamic compromise if
this occurs.
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