Clinical Toxicology (2007) 45, 186–188 Copyright © Informa HealthcareISSN: 1556-3650 print / 1556-9519 onlineDOI: 10.1080/15563650600981186

LCLTCASE REPORT

Amitriptyline-induced Brugada pattern fails to respond to sodium bicarbonate

Amitriptyline-induced Brugada patternVIKHYAT S. BEBARTA, M.D.1 and JAVIER C. WAKSMAN, J.C., M.D., D.A.B.T.2

1Director of Medical Toxicology, Department of Emergency Medicine, Wilford Hall Medical Center, University of Texas Health Sciences Center at San Antonio, San Antonio, Texas, USA2Division of Toxicology and Pharmacology, University of Colorado Health Sciences Center, New Fields, Denver, Colorado, USA

This report describes a Brugada electrocardiographic pattern after tricyclic antidepressant intoxication that fails to resolve followingsodium bicarbonate treatment. A 50-year-old male ingested 13.6 grams of amitriptyline and presented in cardiopulmonary arrest. Afterinitial resuscitation, the patient developed a Brugada electrocardiographic pattern. The pattern persisted despite intravenous administrationof 700 mEq of sodium bicarbonate. Five hours after the last dose of sodium bicarbonate and 18 hours after initial presentation, the Brugadapattern resolved. No co-ingestants were ingested and an ischemic pattern was not seen on electrocardiogram. The serum amitriptyline levelwas >1000 ng/ml. Response of the tricyclic-induced Brugada pattern to sodium bicarbonate has not been previously reported.

Keywords Brugada syndrome; Tricyclic antidepressant; Dysrhythmia; Sodium bicarbonate

Introduction

The Brugada Syndrome was first described in 1992 as an asso-ciation of sudden death in individuals with a structurally normalheart and no evidence of coronary artery disease (1). Patientswith this syndrome had a characteristic electrocardiogram simi-lar to a right bundle branch block with downsloping ST seg-ment elevation in leads V1 through V3. Brugada syndrome issuspected to cause approximately 50% of what had initiallybeen described as idiopathic ventricular fibrillation (2).

Brugada syndrome is associated with sudden death and isthought to be mediated by myocardial sodium channel dysfunc-tion leading to slow inward current (1,3). The Brugada electro-graphic pattern (BEP) seen in Brugada Syndrome has beenreported after tricyclic antidepressant (TCA) overdose; however,its response to sodium bicarbonate has not been described (4–8).We describe the effects of sodium bicarbonate treatment in apatient with the BEP after a large amitriptyline overdose.

Case report

A 50-year-old previously healthy male presented to the emer-gency department after he acutely overdosed with approxi-mately 13.5 grams of amitriptyline approximately two hoursprior to arrival. Immediately upon presentation, the patientdeveloped a convulsive episode and became comatose andpulseless. An electrocardiogram displayed a wide complextachycardia. He was promptly resuscitated for recalcitrantwide complex tachycardia with intravenous epinephrine (2milligrams [mg]) and amiodarone (300 mg bolus followingcontinuous infusion). Since the electrocardiographic QRSinterval was greater than 160 milliseconds (ms) and thepatient’s history supported the ingestion of a drug from theTCA family, he received a total bolus dose of 350 milliequiv-alents (mEq) of intravenous sodium bicarbonate via serialdoses of 50 mEq. The QRS interval narrowed from 160 ms to124 ms, however, a BEP became apparent. Once hemody-namically stable, he underwent gastric lavage with verifiablepill fragments, received activated charcoal, lorazepam to treatgeneralized seizures, and dopamine at 20 mcg/kg/min tomaintain a systolic blood pressure greater than 100 mmHg.Further shortening of the QRS interval was noticed after thepatient received additional 350 mEq of sodium bicarbonateby bolus; however, the BEP remained unchanged (Fig. 1).Subsequent to the second course of sodium bicarbonatetherapy, the patient’s blood test results were arterial pH of7.56, serum sodium of 150 mEq/L (150 mmol/L), potassium3.0 mEq (3.5 mmol/L), magnesium 1.2 (2.4 mmol/L), serumTCA concentration greater than 1000 nanograms/milliliter

Received 27 July 2005; accepted 27 September 2005.Paper presented at North American Congress of Clinical Toxico-

logy in Seattle, WA—September 2004, and at the American Collegeof Emergency Physician’s Government Services Chapter Joint ServicesSymposium in San Antonio, TX—March 2005.

The views expressed in this article are those of the authors and do notreflect the official policy or position of the Department of the UnitedStates (U.S.) Air Force, Department of Defense, or the U.S. government.

Address correspondence to Vikhyat S. Bebarta, M.D., 25218Battle Lake, San Antonio, TX 78258, USA. E-mail: vikbebarta@yahoo.com

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Amitriptyline-induced Brugada pattern 187

(ng/ml) [3,600 nmol/L] (therapeutic range 150–250 ng/ml),serum troponin T less than 0.01 mcg/L, and creatine kinase-MB of 2.5 ng/ml (reference range 0–4.9). A repeat electrocar-diogram showed no electrocardiographic ischemic changes.The patient’s vitals signs stabilized (heart rate 112 perminute, blood pressure 109/62 mmHg, and pulse oximetry98%), and the Brugada electrocardiographic pattern resolvedfive hours after the last sodium bicarbonate bolus (Fig. 2).The patient had an uneventful clinical recovery. The patient’sother medications, which included oxcarbazepine, lorazepam,sertraline, and hydroxyzine, were unaccountable; however,the patient denied ingesting these medications. A urine drugscreen was not performed. He did not have a history or car-diac disease or dysrhythmias. The patient was extubated onhospital day five and discharged home on hospital day 11.

Discussion

The sodium channel mediated Brugada electrocardiographicpattern remained unchanged in this TCA overdose despitenarrowing of the QRS complex after sodium bicarbonateadministration. Brugada syndrome is thought to originatefrom myocardial sodium channel dysfunction and the electro-cardiographic pattern can be induced in some patients with aType IA antidysrhythmic drug (1). Tricyclic antidepressantsalso blocks sodium channels with a Type IA antidysrhyth-

mic effect (9,10). Previous reports have described an associ-ation of the Brugada electrocardiographic pattern aftertricyclic antidepressant use and overdose (4–8). However,none described the effects of sodium bicarbonate, a scientifi-cally demonstrated treatment to reverse TCA-inducedsodium channel blockade, on the Brugada pattern (9,10). Inthis case, the QRS interval narrowed following large dosesof sodium bicarbonate, but the Brugada pattern remainedunchanged.

Potential cofounders to this case need to be addressed.First, amiodarone was given prior to the appearance of theBEP. Amiodarone is a class III antidysrhythmic and is anantagonist to alpha and beta receptors, as well as calcium andinactivated sodium channels (11). No reports of amiodarone-induced BEP have been published. In addition, amiodaronehas been unsuccessfully used to treat patients with BrugadaSyndrome (3). Second, the patient denied ingestion of hisother medications; however, neither serum nor urine drugtesting was performed to confirm his history. No reports ofBEP have been published in association with his other medi-cations—hydroxyzine, oxcarbazepine, sertraline, or lorazepam.Finally, the patient did have mild hypokalemia and hypo-magnesemia, as would be expected, after administration of700 mEq of sodium bicarbonate. These electrolyte abnormal-ities are likely partly responsible for the prolonged correctedQT interval and flattened T waves on the electrocardiogram.However, during his initial resuscitation and initial appearance

Fig. 1. Brugada electrocardiographic pattern after large amitriptyline overdose. The electrocardiogram demonstrates the characteristicdownsloping ST segment elevation in leads V1–V3 found in Brugada syndrome. The patient had received a total of 700 mEq of sodiumbicarbonate via serial boluses of 50 mEq. This electrocardiogram was obtained immediately after administration of two sodium bicarbonateampules.

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188 V.S. Bebarta and J.C. Waksman

of the BEP, the patient’s potassium was within normal range;a magnesium level was not obtained. Hypokalemia is anunlikely cause for the BEP in this case.

It is possible that different mechanisms entitle the creationof the BEP after TCA overdose. Although there is sodiumchannel dysfunction in the Brugada syndrome and type IAantidysrhythmics have been reported to unmask the BEP insusceptible patients, sodium bicarbonate bolus did not affectthe BEP after this TCA overdose. The significance of theBrugada electrographic pattern in TCA-related morbidity andmortality remains to be elucidated.

Disclosures

The authors have no financial support or financial interest inthe subject matter discussed.

References

1. Gussak I, Antzelevitch C, Bjerregaard P, Towbin JA, Chaitman BR.The Brugada syndrome: clinical, electrophysiologic and geneticaspects. J Am Coll Cardiol 1999; 33:5–15.

2. Mattu A, Rogers RL, Kim H, Perron AD, Brady WJ. The Brugada syn-drome. Am J Emerg Med 2003; 21:146–151.

3. Brugada J, Brugada R, Brugada P. Right bundle-branch block and ST-segment elevation in leads V1 through V3: a marker for sudden death inpatients without demonstrable structural heart disease. Circulation1998; 97:457–460.

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5. Babaliaros VC, Hurst JW. Tricyclic antidepressants and the Brugadasyndrome: an example of Brugada waves appearing after the adminis-tration of desipramine. Clin Cardiol 2002; 25:395–398.

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7. Bolognesi R, Tsialtas D, Vasini P, Conti M, Manca C. Abnormal ven-tricular repolarization mimicking myocardial infarction after heterocy-clic antidepressant overdose. Am J Cardiol 1997; 79:242–245.

8. Tada H, Sticherling C, Oral H, Morady F. Brugada syndrome mimickedby tricyclic antidepressant overdose. J Cardiovasc Electrophysiol 2001;12:275.

9. Pentel PR, Benowitz NL. Tricyclic antidepressant poisoning. Manage-ment of arrhythmias. Med Toxicol 1986; 1:101–121.

10. Sasyniuk BI, Jhamandas V, Valois M. Experimental amitriptylineintoxication: treatment of cardiac toxicity with sodium bicarbonate.Ann Emerg Med 1986; 15:1052–1059.

11. Lewin NA, Nelson LS. Antidysrhythmic agents. In: Goldfrank L R, eds.Goldfran’s toxicologic emergencies. 7th ed. New York: McGraw-Hill,Medical Pub. Division, 2002:787–798.

Fig. 2. Electrocardiogram five hours after last sodium bicarbonate was administered, and 18 hours after initial presentation. The appearancewas similar to electrocardiograms obtained through hospital discharge and is assumed to be the patient’s baseline pattern.

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