Prolonged QT interval with markedly abnormal ventricular repolarization in diphenhydramine overdose

Diphenhydramine dependence through deep intramuscular injection resulting in myonecrosis and prolonged QT interval

“…High DPH concentrations may have cardiac toxic effects by inhibiting the cardiac fast sodium and potassium channels. This may present in prolonged QT interval and increase the risk of sudden death . The patient's QTc had returned close to the normal range after discontinuing DPH use.…”

“…The patient's QTc had returned close to the normal range after discontinuing DPH use. Compared with previous reported cases of DPH overdose, our patient developed the abuse gradually over a long time. Cardiac adaptation may explain why her prolonged QTc took a longer time to resolve.…”

Two Sudden and Unexpected Deaths of Patients with Schizophrenia Associated with Intramuscular Injections of Antipsychotics and Practice Guidelines to Limit the Use of High Doses of Intramuscular Antipsychotics

“…However, some of these diphenhydramine overdose studies with EKG data, including 126 cases of overdoses with no TdP case [48] and 1 case monitored for several days [50], suggested that diphenhydramine causes tachycardia and this has a major effect on protecting from TdP in situations of QTc prolongation.…”

“…We doubt that these doses of diphenhydramine had any relevance in the sudden deaths of these two patients because (1) TdP induced by diphenhydramine overdoses appears to require huge quantities measured in grams [44, 45], (2) diphenhydramine-induced tachycardia may protect from TdP in situations of QTc prolongation [48, 50], and (3) some animal models of clinical relevance in humans for drugs that prolong QTc cannot detect any effect for diphenhydramine doses trying to replicate clinical dosing [54]. …”

A 46-Year-Old Woman with Altered Mental Status and Garbled Speech

“…Diphenhydramine overdose has been reported to produce a central anticholinergic picture, with a propensity for sedation, psychosis, agitation, choreoathetosis, and seizures (1,(5)(6)(7)(8)(9)(10)(11)(12)(13). Peripheral anticholinergic toxicity in diphenhydramine overdose is a well-known phenomenon, including cardiac conduction delays and even hemodynamically significant myocardial suppression (15)(16)(17)(18)(19)(20). Alternatively, peripheral anticholinergic toxicity refers to the constellation of signs and symptoms observed after antagonism of peripheral nervous system muscarinic receptors.…”