Post-mortem toxicological analyses of blood samples from 107 patients receiving opioid agonist treatment: substances detected and pooled opioid and benzodiazepine concentrations

Anne Berit Bech; Thomas Clausen; Helge Waal; Vigdis Vindenes; Hilde Erøy Edvardsen; Joachim Frost; Ivar Skeie

doi:10.1111/add.15211

Post-mortem toxicological analyses of blood samples from 107 patients receiving opioid agonist treatment: substances detected and pooled opioid and benzodiazepine concentrations

Addiction. 2020 Aug 1. doi: 10.1111/add.15211. Online ahead of print.

Authors

Anne Berit Bech^{1

2}, Thomas Clausen², Helge Waal^{2

3}, Vigdis Vindenes^{4

5}, Hilde Erøy Edvardsen⁴, Joachim Frost⁶, Ivar Skeie^{1

2}

Affiliations

¹ National Advisory Unit on Concurrent Substance Abuse and Mental Health Disorders, Innlandet Hospital Trust, Department of Mental Health, P.O. Box 104, 2381, Brumunddal, Norway.
² Norwegian Centre for Addiction Research (SERAF), Institute of Clinical Medicine, University of Oslo, P.O. Box 1171 Blindern, 0318, Oslo, Norway.
³ National Advisory Unit on Substance Use Disorder Treatment, Oslo University Hospital, Sognsvannsveien 21, Bygg 6, P.O. Box 4959 Nydalen, 0424, Oslo, Norway.
⁴ Department of Forensic Sciences, Oslo University Hospital, P. O. Box 4950, 0424, Oslo, Norway.
⁵ Institute of Clinical Medicine, University of Oslo, P. O. Box 1171 Blindern, 0318, Oslo, Norway.
⁶ Department of Clinical Pharmacology, St. Olav's Hospital Trondheim University Hospital, P.O. Box 3250 Torgarden, 7006, Trondheim, Norway.

PMID: 32738014
DOI: 10.1111/add.15211

Abstract

Aims: To present the substances and their concentrations detected post-mortem in patients receiving opioid agonist treatment (OAT) stratified by cause of death, estimate the pooled opioid and benzodiazepine concentrations using established conversion factors for blood concentrations from the Norwegian Road Traffic Act, and explore the association between drug-induced cause of death and the pooled opioid and benzodiazepine concentrations.

Design: Cross-sectional nationwide study.

Setting: Norway.

Participants: One hundred and seven patients who died during OAT (i.e. within 5 days after the last intake of OAT medication) between 1 January 2014 and 31 December 2015, with post-mortem femoral blood available for toxicology. Data were collected from hospital records, the Norwegian Cause of Death Registry and autopsy reports.

Measurements: Presence of alcohol and non-alcohol substances in the bloodstream at time of death, determined through records of toxicology of post-mortem femoral blood.

Findings: A median of four substances was detected across the causes of death. At least one benzodiazepine was detected in 81 (76%) patients. The median pooled opioid concentration was significantly higher in drug-induced deaths compared with other causes of death (362 ng/mL versus 182 ng/mL, P < 0.001), in contrast to the pooled benzodiazepine concentration (5466 versus 5701 ng/mL, P = 0.353). The multivariate regression analysis showed that only increasing pooled opioid concentration (ng/ML) was associated with increased odds of a drug-induced cause of death (odds ratio, 1.003; 95% confidence interval: 1.001-1.006).

Conclusions: In Norway, overall opioid concentration seems to play an important role in drug-induced deaths during opioid agonist treatment in patients prescribed methadone or buprenorphine. Patients prescribed buprenorphine tend to replace their agonist with full agonists, while patients prescribed methadone tend to have high opioid concentrations from methadone as the only opioid.