Cardiotoxicity after massive amantadine overdose

Journal of Medical Toxicology, Sep 2008

Introduction Amantadine hydrochloride is an antiviral medication used as therapy for parkinsonism and as a cognitive enhancer. We report 2 cases of massive, acute ingestion of amantadine hydrochloride confirmed with serial serum levels. Case Reports A 47-year-old woman presented to the emergency department (ED) 30 minutes after ingesting 10 g of amantadine (150 mg/kg) by her report. Initial ECG revealed a sinus rhythm with rate of 93 bpm, and a QRS of 84 msec. While in the ED, the patient sustained a pulseless cardiac arrest and the monitor revealed ventricular tachycardia. She was successfully defibrillated. Postdefibrillation ECG showed a sinus rhythm (rate = 82 bpm), QRS of 236 msec, and QTc of 567 msec. The serum potassium was 1.0 mEq/L (1.0 mmol/L). The patient was given 300 ml (300 cc) 3% sodium chloride IV over 10 minutes. Ten minutes after completion of the hypertonic saline infusion, the patient’s ECG abnormalities resolved and the QRS was 88 msec. Her potassium was repleted over the next 11 hours postpresentation, and she also received an IV bolus of 4 g of magnesium sulfate immediately after the cardiac arrest. No further hypotension, dysrhythmia, conduction delay, or ectopy was noted during the patient’s hospital stay. The second case involved a 33-year-old female patient who presented 1 hour after ingesting 100 tablets of amantadine hydrochloride (100 mg/tab). Initial ECG revealed sinus tachycardia with a QRS of 113 msec, an R wave in lead aVR of 4–5 mm and a QTc of 526 msec. Her serum potassium was 3.0 mEq/L (3.0 mmol/L), her serum calcium was 9.4 mg/dl (2.35 mmol/L), and serum magnesium was 2.1 mg/dl (0.86 mmol/L) on labs drawn at initial presentation. The patient was intubated for airway protection, and her potassium was repleted and corrected over the next 9 hours. Her ECG abnormalities improved 8 hours after initial presentation and normalized at approximately 14 hours postingestion. The patient was discharged home 11 days after her ingestion. Conclusion Acute amantadine toxicity manifests with life-threatening cardiotoxicity. Concurrent, often profound, hypokalemia may complicate the administration of sodium bicarbonate in the management of cardiac dysrhythmias.

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Cardiotoxicity after massive amantadine overdose

Michael D. Schwartz 0 MD 0 3 Manish M. Patel 0 MD 0 3 Ziad N. Kazzi 0 MD 0 1 Brent W. Morgan 0 MD 0 2 0 Keywords: amantadine, overdose, torsades, hypokalemia There was no outside funding of any kind used for this study 1 Department of Emergency Medicine, University of Alabama-Birmingham , Birmingham, AL 2 Department of Emergency Medicine, Georgia Poison Center, Emory University School of Medicine , Atlanta, GA 3 Georgia Poison Center, Emory University School of Medicine , Atlanta, GA Introduction: Amantadine hydrochloride is an antiviral medication used as therapy for parkinsonism and as a cognitive enhancer. We report 2 cases of massive, acute ingestion of amantadine hydrochloride confirmed with serial serum levels. Case Reports: A 47-year-old woman presented to the emergency department (ED) 30 minutes after ingesting 10 g of amantadine (150 mg/kg) by her report. Initial ECG revealed a sinus rhythm with rate of 93 bpm, and a QRS of 84 msec. While in the ED, the patient sustained a pulseless cardiac arrest and the monitor revealed ventricular tachycardia. She was successfully defibrillated. Postdefibrillation ECG showed a sinus rhythm (rate 82 bpm), QRS of 236 msec, and QTc of 567 msec. The serum potassium was 1.0 mEq/L (1.0 mmol/L). The patient was given 300 ml (300 cc) 3% sodium chloride IV over 10 minutes. Ten minutes after completion of the hypertonic saline infusion, the patient's ECG abnormalities resolved and the QRS was 88 msec. Her potassium was repleted over the next 11 hours postpresentation, and she also received an IV bolus of 4 g of magnesium sulfate immediately after the cardiac arrest. No further hypotension, dysrhythmia, conduction delay, or ectopy was noted during the patient's hospital stay. The second case involved a 33-year-old female patient who presented 1 hour after ingesting 100 tablets of amantadine hydrochloride (100 mg/tab). Initial ECG revealed sinus tachycardia with a QRS of 113 msec, an R wave in lead aVR of 4-5 mm and a QTc of 526 msec. Her serum potassium was 3.0 mEq/L (3.0 mmol/L), her serum calcium was 9.4 mg/dl (2.35 mmol/L), and serum magnesium was 2.1 mg/dl (0.86 mmol/L) on labs drawn at initial presentation. The patient was intubated for airway protection, and her potassium was repleted and corrected over the next 9 hours. Her ECG abnormalities improved 8 hours after initial presentation and normalized at approximately 14 hours postingestion. The patient was discharged home 11 days after her ingestion. Conclusion: Acute amantadine toxicity manifests with life-threatening cardiotoxicity. Concurrent, often profound, hypokalemia may complicate the administration of sodium bicarbonate in the management of cardiac dysrhythmias. - Amantadine hydrochloride is an infrequently encountered pharmaceutical agent in acute poisoning cases. Case reports in the literature suggest that amantadines toxicity is twofold, with chronic overdosageeither by intentional ingestion of a small amount, by therapeutic misadventure, or by unintentional accumulation of the drug due to pharmacokinetic alterationsmanifesting as neurotoxicity (hallucinations, disorientation, confusion, and acute toxic psychosis). In large overdoses, amantadine causes significant cardiotoxicity, manifested primarily by widening of the QRS complex, QT prolongation, ventricular ectopy, and unstable ventricular dysrhythmias which, in many of the literature cases we reviewed, have proven fatal. and 250 mg of diphenhydramine. The amounts were admitted by the patient. In addition to these 2 medications, she received depot haloperidol intramuscularly every month (last dose 3 weeks previously) and reported using ephedra (Metabolife) sporadically. The patient smoked cigarettes, but did not use illicit drugs or alcohol. Per her mother, with whom she lived, the patient did not have access to any other medications. Initial vital signs were blood pressure 120/80 mm/Hg, heart rate 70 bpm, respirations 16 breaths/minute, and temperature 36.1C. The patient was placed on oxygen via nasal cannula and an IV line was initiated. An electrocardiogram (Figure 1) on arrival to the ED revealed sinus rhythm at a rate of 93 bpm, with QRS duration of 84 msec. The QTc was 403 msec. The patient was alert and oriented to person, place, time, and situation. Her pupils were 4 mm, equal, and reactive to light; mucous membranes were moist and bowel sounds were normal. Her neurological examination was unremarkable. There was no jugular venous distension; lung sounds were clear to auscultation and heart sounds were normal. As the ED physician completed the physical examination, the patient suffered a pulseless cardiac arrest. The monitor revealed ventricular tachycardia and the patient was immediately defibrillated once at 200 joules, with subsequent return of spontaneous circulation. Postdefibrillation vital signs revealed a pulse of 60 bpm, a blood pressure 70/50 mmHg, and agonal respirations. A dopamine infusion was started at 20 g/kg/min. Endotra (...truncated)


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Michael D. Schwartz, Manish M. Patel, Ziad N. Kazzi, Brent W. Morgan. Cardiotoxicity after massive amantadine overdose, Journal of Medical Toxicology, 2008, pp. 173-179, Volume 4, Issue 3, DOI: 10.1007/BF03161197