A postmortem diphenhydramine concentration below a quoted 5 µg/mL “lethal” boundary did not exclude a fatal contribution in a Berlin investigation. Two adult cases classified with diphenhydramine as the only drug in toxic concentrations fell below that boundary. Their findings challenge rigid classification without establishing a lower universal lethal number.
What population produced these observations?
Eckes and colleagues reviewed Berlin autopsies from January 2000 through December 2010. Diphenhydramine was identified in 73 of 8,131 autopsies. They selected 20 cases of suicidal intoxication involving its detection for the published analysis.
Six were classified as combined intoxications with a relevant diphenhydramine contribution, five as cases with diphenhydramine the only substance in toxic blood concentrations, and four as cases without relevant contribution. Three cardiac-only and two gastric-only cases were considered separately because attribution was uncertain.
Those categories incorporated toxicological interpretation and circumstances. They were not outcomes independently assigned in a blinded test of a concentration threshold. The study did not calculate sensitivity or specificity for 5 µg/mL.
The two below-boundary cases
A 50-year-old woman had peripheral-blood diphenhydramine at 2.7 µg/mL. The approximate postmortem interval was four days. The report noted punctate bleeding on heart tissue and a history of arrhythmias.
An 81-year-old woman had a reported value of 3.59 µg/mL, rounded to 3.6 in the summary table. She had been missing during winter and was found after approximately 67 days. Autopsy disclosed substantial atherosclerosis and coronary heart disease, a left-kidney tumor and evidence of tablet intake. Putrefaction was present.
The authors discussed intoxication probably in combination with hypothermia in the second case. Calling diphenhydramine the only drug in toxic concentrations therefore did not establish that no disease, environmental factor or other low-level substance could have mattered.
The quoted boundary was not a biological switch
The paper questioned a 5 µg/mL boundary drawn from earlier forensic literature. Its authors also noted uncertainty over whether that reference combined clinical drug-monitoring and postmortem measurements. Those contexts should not be treated as identical.
Within the same five-case category, diphenhydramine blood results ranged from 2.7 to 70.0 µg/mL. Such a selected distribution does not establish a probability of death at any one concentration, or show that every person above its lowest value would die.
Analytical results still need specimen and timing context
Autopsy specimens were analyzed by high-performance liquid chromatography, with detailed methods referred to an earlier publication. Femoral blood was generally used unless cardiac-only sampling was indicated. The report did not reproduce complete detection, quantitation, recovery and precision validation for each matrix.
The measurements describe collected postmortem specimens. They were not paired with blood taken during life and did not establish how much redistribution or degradation occurred in these two individuals. The 67-day interval especially cannot be silently treated as equivalent to promptly collected blood.
What conclusion is supported?
The two cases support evaluating concentration alongside disease, environment, other substances, specimen history and the investigation. They do not independently validate a new cutoff, reconstruct dose or establish impairment before death. A quoted lethal range can inform review without replacing case-specific reasoning.
Population also matters: see diphenhydramine findings in seven pediatric autopsies. Those separate childhood observations should not be substituted for adult reference data.
Primary source
Eckes L, Tsokos M, Herre S, Gapert R, Hartwig S. Toxicological identification of diphenhydramine (DPH) in suicide. Forensic Science, Medicine, and Pathology. 2013;9:145–153. Published online 2012. doi:10.1007/s12024-012-9383-5.
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