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

Aims To present the substances and their concentrations detected postmortem 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 nation-wide 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 postmortem 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 postmortem, determined through records of toxicology of postmortem 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 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.