Diphenhydramine toxicity: comparisons of postmortem findings in diphenhydramine-, cocaine-, and heroin-related deaths.

Diphenhydramine (DPH)-related deaths in adults are extremely rare, and detailed autopsy studies are rarer still. Toxicologic and anatomic findings in 4 cases of suicidal DPH overdose are described and compared with findings in a database of cocaine- and heroin-related deaths. Blood DPH levels were many times higher than those considered therapeutic (5000-35,000 ng/ml versus 50-100 ng/ml). Marked pulmonary edema with visceral congestion was a constant finding. Mean lung-body weight ratios for DPH, cocaine, heroin, and trauma controls were 0.015, 0.015, 0.019, and 0.013, respectively. When normalized for body weight in this fashion, edema in DPH-related deaths was comparable to that in cocaine-related deaths. Cardiac enlargement was apparent in 3 of the 4 DPH cases, 1 with marked myocardial fibrosis. The finding of increased heart size suggests that preexisting heart disease may provide the necessary substrate for lethal cases of DPH toxicity. Pulmonary edema in these cases remains unexplained, with edema in cases of heroin-related toxicity significantly worse than that produced by cocaine or DPH (p < .0001). Because DPH and cocaine can exert similar effects on the heart, a common mechanism may produce pulmonary edema in both. A different mechanism may account for heroin-related edema.