Lipid therapy for the treatment of a refractory amitriptyline overdose
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CASE REPORT N RAPPORT DE CAS
Lipid therapy for the treatment of a refractory
amitriptyline overdose
Mathew B. Kiberd, BSc*; Samuel F. Minor, MD*3
ABSTRACT pharmaceuticals.2–13 We report the use of lipid therapy
Tricyclic antidepressant (TCA) overdose is a leading cause of in a case of refractory pulseless wide-complex tachy-
death among intentional overdoses. Intravenous lipid emul- cardia resulting from an amitriptyline overdose.
sion therapy is an emerging antidote for local anesthetic
toxicity, and there is animal evidence that lipid therapy may
CASE REPORT
be efficacious in TCA overdose. Furthermore, case reports in
humans have described the use of lipid therapy to reverse
the toxicity of other lipophilic drugs. Here we report a 25- A 50 kg, 25-year-old female was discovered uncon-
year-old female presenting with coma and hemodynamic scious in her house near several empty bottles of
instability following intentional ingestion of amitriptyline. amitriptyline. The patient had a history of anorexia and
She had multiple episodes of pulseless wide-complex
depression and had stockpiled multiple amitriptyline
tachycardia despite conventional treatment with chest com-
pressions, cardioversion, lidocaine, epinephrine, norepi- prescriptions from different physicians specifically for
nephrine, magnesium sulphate, sodium bicarbonate, the purpose of committing suicide. The total number
activated charcoal, and whole bowel irrigation. Twenty and dose were not recorded, and there were possible
percent lipid emulsion was administered intravenously (an coingestions of her regular medications, which
initial 150 mL bolus, followed by an infusion at 16 mL/h and a
included fluoxetine, escitalopram, olanzapine, quetia-
second bolus of 40 mL) over 39 hours (total dose 814 mL) yet
resulted in no dramatic changes in hemodynamics or level of pine, and gabapentin. Paramedics found her to be
consciousness. However, there was a decrease in the unresponsive with a Glasgow Coma Scale score of 3, a
frequency of wide-complex tachycardia during the lipid heart rate of 60 beats/min, a wide QRS (186 ms), and a
emulsion infusion and a recurrence of wide-complex tachy- blood pressure of 60 mm Hg systolic. She was
cardia shortly after the infusion was stopped. The patient
was discharged from the intensive care unit 11 days later
intubated without sedation and taken to the emergency
with no lasting physiologic sequelae. department (ED).
In the ED, the patient went into a pulseless wide-
Keywords: amitriptyline, intravenous fat emulsions, tricyclic complex tachycardia three times over the next 2 hours.
antidepressive agents Each episode was treated with chest compressions,
synchronized cardioversion, lidocaine, and epinephr-
Tricyclic antidepressant (TCA) overdose is an impor- ine. After cardioversion, the patient reverted to sinus
tant cause of mortality following intentional overdose rhythm with a wide QRS duration and a prolonged Q–
despite timely and aggressive treatment.1 Intravenous Tc interval (Figure 1). A norepinephrine infusion was
lipid emulsion therapy is an exciting new treatment for begun for hypotension, and she received 2 g magne-
lipophilic drug overdoses. Lipid therapy is widely sium sulphate, 350 mL 8.4% sodium bicarbonate, 50 g
advocated for local anesthetic toxicity2 and is increas- activated charcoal, and 4 L polyethylene glycol-3350
ingly reported in the literature for overdoses of other (GoLYTLEY) over 2 hours.
From the Departments of *Medicine and 3Surgery, Dalhousie University, Halifax, NS.
Correspondence to: Dr. Samuel F. Minor, Department of Medicine, Dalhousie University, Rm 813 Victoria Bldg, 1278 Tower Road, Halifax, NS
B3H 2Y9.
Submitted July 29, 2010; Revised January 30, 2011; Accepted March 4, 2011.
This article has been peer reviewed.
ß Canadian Association of Emergency Physicians CJEM 2012;14(3):193-197 DOI 10.2310/8000.2011.110486
CJEM N JCMU 2012;14(3) 193
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Figure 1. EKG demonstrating wide
QRS and prolonged Q-Tc.
On arrival at the intensive care unit (ICU), the feeding. Given that it was not apparent that the lipid
patient had lactate 7.6 mmol/L, pH 7.66, sodium emulsion had any positive effect, we were concerned
150 mmol/L, and potassium 3.0 mmol/L. She required that a more aggressive prolonged infusion could cause
a low-dose norepinephrine infusion intermittently for a toxicity. This infusion dose was substantially lower
target mean arterial pressure . 65 mm Hg, but after than the 0.25 mL/kg/min commonly recommended for
the initial resuscitation, hypotension was not a reversal of local anesthetic toxicity, typically adminis-
dominant feature. A sodium bicarbonate infusion was tered over less than an hour. Although there was no
used for a target pH . 7.5, and the hypokalemia and appreciable change in conduction intervals after
hypocalcemia were treated. Over the next hour, the administration of the lipid, the patient did have a
patient had three further episodes of pulseless wide- relatively stable cardiac rhythm. After 3 hours, the
complex tachycardia, which were treated with syn- patient had another episode of pulseless wide-complex
chronized cardioversion and each time reverted to a tachycardia, which was converted into a stable wide-
wide-complex sinus rhythm with a prolonged Q–Tc complex normal sinus rhythm with synchronized
interval. cardioversion, followed by another 40 mL bolus of
Given that the patient continued to have episodes of 20% lipid, 20 mmol potassium chloride (for a
wide-complex tachycardia with traditional therapy, potassium of 3.1 mmol/L), and 1g calcium chloride
other treatment options were explored. A literature (for a calcium of 1.82 mmol/L). Figure 2 summarizes
search found an animal model where lipid therapy the treatment and timing of wide-complex tachycardia
reversed the toxicity from clomipramine, another treated with electrical cardioversion.
TCA.11 Also, two case reports of lipid therapy reversing For the next 36 hours, the patient received an
the toxicity of other lipophilic drug overdoses were infusion of 20% lipid at 16 mL/h, 3% hypertonic
found.12,13 Based on this literature, the patient was saline, and sodium bicarbonate. During this interval,
administered a 150 mL bolus of 20% lipid (Intralipid, there were no further episodes of wide-complex
Baxter, Deerfield, IL). Although the intended dose of tachycardia, despite a QRS duration of 120 to
20% lipid was 100 mL (2 mL/kg), another 50 mL was 240 ms and a Q–Tc interval of 511 to 661 ms. Fifty
given by nursing error. After the initial bolus of lipid, millilitres of sodium bicarbonate was administered
there was no change in the QRS duration, blood whenever the QRS duration lengthened to more than
pressure, or Glasgow Coma Scale score. Despite this 120 ms, and the QRS duration consistently narrowed
apparent lack of effect, the patient was started on a following each bolus.
continuous infusion of 20% lipid at 16 mL/h because After 36 hours, the intravenous lipid emulsion
of the long half-life of the ingested drugs. We selected infusion was discontinued. Over 36 hours, our patient
a familiar and safe dose of 16 mL/h derived from had received a total of 814 mL of 20% lipid (i.e.,
typical dosing used during total parenteral nutrition 16.3 mL/kg or 3.3 g of fat/kg body weight). Three
194 2012;14(3) CJEM N JCMU
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https://www.cambridge.org/core/terms. https://doi.org/10.2310/8000.2011.110486Lipid therapy for amitriptyline overdose
Figure 2. Summary of the treatment and timing of wide-complex tachycardia treated with electrical cardioversion.
hours after discontinuing the lipid infusion, the QRS admission and in-hospital death among all intentional
duration widened again. There was no change in the overdoses.14 The current mainstay of therapy is sodium
sodium or pH targets, and the patient had a normal bicarbonate, which treats the wide-complex ventricular
potassium. The patient became progressively hypoten- arrhythmias and hypotension that characteristically
sive and again developed pulseless wide-complex develop. Vasopressors, gastrointestinal decontamina-
tachycardia requiring synchronized electrical cardio- tion, antiarrhythmic therapy, electrical cardioversion,
version. A 100 mg bolus of lidocaine was administered, and antiseizure medications are often used in the
but lipid therapy was not restarted. One and a half management of TCA overdose,15 yet such overdoses
hours later, the patient had yet another episode of may be refractory to therapy.25
pulseless, wide-complex tachycardia requiring syn- The role of intravenous lipid emulsion therapy in
chronized electrical cardioversion and again was refractory TCA overdose is uncertain, reflecting
successfully converted into a normal sinus rhythm. uncertainty in the mechanism of action and clinical
After this, the patient had no further episodes of effectiveness of this new antidote as its use is
arrhythmia or hypotension. For the next 72 hours, she extrapolated beyond cases of local anesthetic toxicity.
continued to have a prolonged QRS duration and As a class, TCAs are generally highly lipophilic and
prolonged QTc interval requiring intermittent treat- could be sequestered in the ‘‘lipid sink’’ created by the
ment with sodium bicarbonate until day 8 postadmis- lipid infusion.3,5,9,11,16–19 Animal studies and human case
sion. The patient was discharged from hospital with no reports describe the use of lipid emulsion in the
physiologic or gross neurologic compromise. treatment of clomipramine (a TCA), verapamil,
propranolol, bupropion/lamotrigine, and quetiapine/
DISCUSSION sertraline.11–13,20–22
When our patient demonstrated repeated episodes of
Although intentional TCA overdose carries only a 3% wide-complex tachycardia despite conventional therapy,
mortality rate, it represents a leading cause of ICU we felt that we had to explore nonconventional
CJEM N JCMU 2012;14(3) 195
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https://www.cambridge.org/core/terms. https://doi.org/10.2310/8000.2011.110486Kiberd and Minor
therapies. Unfortunately, we did not observe a convin- 3. Cave G, Harvey M. Lipid emulsion therapy in lipophilic
drug toxicity. Ann Emerg Med 2008;51:449-50; author reply
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5. Corman SL, Skledar SJ. Use of lipid emulsion to reverse
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We used a relatively low rate of lipid infusion, which 21, doi:10.1111/j.1365-2044.2008.05830.x.
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line in our case. Our patient also had possible nate in a rabbit model of clomipramine toxicity. Ann Em-
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contributed to cardiac toxicity. Although TCAs as a emulsion in the resuscitation of a patient with prolonged
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Competing interests: None declared.
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