Reactions 1442 - 9 Mar 2013

O STrimipramine overdose

Fatal cardiac arrest and various other toxicities:9 case reports

In a retrospective study, six patients developed varioustoxicities and three patients developed fatal cardiac arrest,following overdoses of trimipramine.

Five women and one man, aged 23–46 years, ingested anoverdose of trimipramine 150–4000mg (2.5–41.5 mg/kg).Tests revealed plasma trimipramine concentrations of0.3–6.78 µmol/L approximately 3–8 hours after ingestion.Symptoms of trimipramine poisoning included somnolence,seizures, disorientation, agitation, tachycardia, right bundlebranch block, prolonged QTc interval, coma, suspectedpostictal state, hyperreflexia, muscular spasms,hypersalivation, ataxia and delirium [times from overdoses toreactions onsets not stated]. Treatments included gastriclavage, intubation, charcoal and sodium bicarbonate. One ofthe patients who developed somnolence made an uneventfulrecovery [not all outcomes stated].

Two women and a man, aged 38, 37 and 45 years,respectively, died due to refractory cardiovascular collapse.The first woman was found comatose approximately 18 hoursafter she ingested trimipramine 8.4g (129 mg/kg). Shesubsequently developed asystole, but transiently recoveredafter undergoing CPR for 1 hour. Two days later, she died dueto irreversible hypoxic brain damage. The second womandeveloped vomiting and was found in a deep comaapproximately 2–6 hours after she ingested trimipramine 25g(278 mg/kg). She received charcoal; however, she washaemodynamically unstable with a BP of 45/20mm Hg.Despite treatment with fluids, catecholamines, sodiumbicarbonate, magnesium and glucagon, she developedpulseless electrical activity and cardiocirculatory arrest, andsubsequently died. The man was found comatoseapproximately 30 minutes after he ingested trimipramine 10g(143 mg/kg). He was admitted, and received charcoal;however, he developed sinus bradycardia 2.5 hours later,followed by refractory hypotension and cardiac arrest. Despitetreatment with catecholamines, sodium bicarbonate and anexternal pacemaker, he died.

Author comment: Of the 230 cases, "[t]he causalrelationship between trimipramine overdose and clinicaleffect was rated probable in 204 cases and confirmed. . . in26 patients".Gutscher K, et al. Patterns of toxicity and factors influencing severity in acuteadult trimipramine poisoning. British Journal of Clinical Pharmacology 75:227-235, No. 1, Jan 2013. Available from: URL: http://dx.doi.org/10.1111/j.1365-2125.2012.04344.x - Switzerland 803083897

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