title: Sedative and hypnotic drugs--fatal and non-fatal reference blood concentrations.
abstract: In postmortem investigations of fatal intoxications it is often challenging to determine which drug/s caused the death. To improve the interpretation of postmortem blood concentrations of sedative and hypnotic drugs and/or clonazepam, all medico-legal autopsies in Sweden - where these drugs had been detected in femoral vein blood during 1992-2006 - were identified in the databases of the National Board of Forensic Medicine. For each drug, concentrations in postmortem control cases - where the cause of death was not intoxication and where incapacitation by drugs could be excluded - were compiled as well as the levels found in living subjects; drugged driving cases and therapeutic drug monitoring cases. Subsequently, fatal intoxications were assessed with regards to the primary substances contributing to death, and blood levels were compiled for single and multiple drug intoxications. The postmortem femoral blood levels are reported for 16 sedative and hypnotic drugs, based on findings in 3560 autopsy cases. The cases were classified as single substance intoxications (N=498), multiple substance intoxications (N=1555) and postmortem controls (N=1507). Each autopsy case could be represented more than once in the group of multiple intoxications and among the postmortem controls if more than one of the included substances were detected. The concentration ranges for all groups are provided. Overlap in concentrations between fatal intoxications and reference groups was seen for most substances. However, the concentrations found in single and multiple intoxications were significantly higher than concentrations found in postmortem controls for all substances except alprazolam and triazolam. Concentrations observed among drugged drivers were similar to the concentrations observed among the therapeutic drug monitoring cases. Flunitrazepam was the substance with the highest number of single intoxications, when related to sales. In summary, this study provides reference drug concentrations primarily to be used for improving interpretation of postmortem drug levels in obscure cases, but which also may assist in drug safety work and in pharmacovigilance efforts.
authors: Department of Drug Research/Clinical Pharmacology, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Department of Clinical Pharmacology, County Council of Östergötland, Linköping, Sweden.
authors: Anna Kristina
authors: AK
authors: Jönsson
authors: Forensic Medicine Laboratory, Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
authors: Carl
authors: C
authors: Söderberg
authors: Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway.
authors: Ketil Arne
authors: KA
authors: Espnes
authors: Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
authors: Johan
authors: J
authors: Ahlner
authors: Section of Forensic Medicine, Department of Community Medicine and Rehabilitation, Umeå University, Umeå, Sweden.
authors: Anders
authors: A
authors: Eriksson
authors: Department of Drug Research/Clinical Pharmacology, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
authors: Margareta
authors: M
authors: Reis
authors: Forensic Medicine Laboratory, Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden. Electronic address: henrik.druid@ki.se.
authors: Henrik
authors: H
authors: Druid
mesh_terms: D000368:Aged; D001334:Automobile Driving; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D016903:Drug Monitoring; D053593:Forensic Toxicology; D006801:Humans; D006993:Hypnotics and Sedatives / Q000097:blood* / Q000506:poisoning; D013058:Mass Spectrometry; D008875:Middle Aged; D012016:Reference Values; D015813:Substance Abuse Detection; D013548:Sweden
chemical_list: D006993:Hypnotics and Sedatives
keywords: Benzodiazepines; Forensic toxicology; Intoxication; Poisoning; Postmortem; Toxicity