Coexistence and concentrations of ethanol and diazepam in postmortem blood specimens: risk for enhanced toxicity?
Both ethanol and diazepam are classified as depressants of the central nervous system and exert their effects via the GABAA receptor complex. We report the coexistence and concentrations of ethanol, diazepam, and its primary metabolite nordiazepam in a case series of 234 forensic autopsies collected over a ten-year period. Diazepam, nordiazepam, and ethanol were determined in femoral venous blood by highly selective gas chromatographic methods. The mean (median) femoral blood concentrations were ethanol 0.24 g/100 mL (0.25 g/100 mL), diazepam (D) 0.23 microg/g (0.10 microg/g), nordiazepam (ND) 0.24 micro/g (0.20 microg/g), sum (D + ND) 0.43 microg/g (0.30 microg/g), and the ratio D/ND was 1.19 (1.0). When cause of death was attributed to alcohol and/or drug intoxication (N = 50), the mean and median blood-ethanol concentration was higher, being 0.36 g/100 mL and 0.38 g/100 mL, respectively, whereas the mean (median) and range of blood-diazepam concentrations were about the same, 0.23 microg/g (0.10 microg/g) and 0.05 to 1.2 microg/g. The femoral-blood concentrations of diazepam and nordiazepam were highly correlated (r = 0.73), but there was no correlation between the concentrations of ethanol and diazepam (r = -0.15). In another 114 fatalities (all causes of death) with diazepam and/or nordiazepam as the only drugs present, the mean (median) and range of blood-diazepam concentrations were 0.22 microg/g (0.10 microg/g) and 0.03 to 3.5 microg/g. The pathologists report showed that none of these deaths were classed as drug intoxications. The impression gleaned from this study of ethanol-diazepam deaths is that high blood-ethanol concentration is the major causative factor. We found no evidence that concurrent use of diazepam enhanced the acute toxicity of ethanol, although interpretation is complicated by the high blood-ethanol concentration (median 0.38 g/100 mL), making it difficult to discern an added effect of diazepam.
Holmgren
P
P
Department of Forensic Toxicology, University Hospital, 581 85 Linköping, Sweden.
Jones
A W
AW
D002492:Central Nervous System Depressants / Q000097:blood*; D002849:Chromatography, Gas; D003975:Diazepam / Q000097:blood*; D004347:Drug Interactions; D000431:Ethanol / Q000097:blood*; D005554:Forensic Medicine; D018757:GABA Modulators / Q000097:blood*; D006801:Humans; D003708:Nordazepam / Q000097:blood*; D012307:Risk Factors
D002492:Central Nervous System Depressants; D018757:GABA Modulators; D000431:Ethanol; D003708:Nordazepam; D003975:Diazepam