title: An unusual case of death probably triggered by the association of buprenorphine at therapeutic dose with ethanol and benzodiazepines and with very low norbuprenorphine level.
abstract: Buprenorphine is largely prescribed for maintenance treatment in opioid dependence due to its safety profile. Nevertheless, fatalities at therapeutic dose have been described when associated with other central nervous system depressants, such as ethanol or benzodiazepines. Here, we report a case of death due to association of buprenorphine at therapeutic dose with benzodiazepines and ethanol. Although toxicity has been often attributed to its metabolite norbuprenorphine rather than to buprenorphine itself, in our case, norbuprenorphine was not detected in urine and bile and only in traces in blood. Moreover, the presence in blood of free buprenorphine but not of glucuronide metabolites argues for an unusual early death, at the beginning of buprenorphine metabolism. We propose that in the context of prior toxic impregnation, buprenorphine directly (and not via its metabolite norbuprenorphine) acted as a triggering factor by blocking the ventilatory response, rapidly leading to fatal respiratory depression.
authors.affiliation: Department of Medical Pharmacology and Toxicology, CHRU Montpellier, University of Montpellier 1, Montpellier, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bardy
authors.forename: Philippe
authors.initials: P
authors.lastname: Cathala
authors.forename: Céline
authors.initials: C
authors.lastname: Eiden
authors.forename: Eric
authors.initials: E
authors.lastname: Baccino
authors.forename: Pierre
authors.initials: P
authors.lastname: Petit
authors.forename: Olivier
authors.initials: O
authors.lastname: Mathieu
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000009:adverse effects / Q000032:analysis*; D001569:Benzodiazepines / Q000009:adverse effects / Q000032:analysis; D001646:Bile / Q000737:chemistry; D002047:Buprenorphine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000032:analysis* / Q000097:blood; D002492:Central Nervous System Depressants / Q000009:adverse effects / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D000431:Ethanol / Q000009:adverse effects / Q000032:analysis*; D017809:Fatal Outcome; D053593:Forensic Toxicology; D005766:Gastrointestinal Contents / Q000737:chemistry; D006801:Humans; D008297:Male; D012131:Respiratory Insufficiency / Q000139:chemically induced*; D053719:Tandem Mass Spectrometry
chemical_list: D000701:Analgesics, Opioid; D002492:Central Nervous System Depressants; D001569:Benzodiazepines; D000431:Ethanol; D002047:Buprenorphine; C043585:norbuprenorphine
keywords: benzodiazepines; buprenorphine; conjugated metabolites; ethanol; forensic science; norbuprenorphine