Buprenorphine-Related Deaths in North Carolina from 2010 to 2018

Buprenorphine (BUP) is a commonly prescribed medication for the treatment of opioid use disorder (OUD). As prescriptions increase in North Carolina, BUP is more frequently encountered statewide in routine postmortem casework. Between 2010 and 2018, there were 131 select cases investigated by the Office of the Chief Medical Examiner where BUP was detected in peripheral blood and considered a primary cause of death (COD), with no other opioids present and no other non-opioid substances found in the lethal range. The decedents ranged in age from 14 to 64 years, with 67% male. The mean/median peripheral blood concentrations were 4.1/2.1 ng/mL for BUP and 7.8/3.4 ng/mL for its metabolite, norbuprenorphine. These postmortem blood concentrations overlap antemortem therapeutic concentrations in plasma reported in the literature for opioid-dependent subjects receiving sublingual maintenance therapy. The pathologist considered scene findings, prescription history, autopsy findings, toxicological analysis and decedent behavior prior to death to conclude a drug-related COD. Many of the deaths were complicated by the presence of other central nervous system depressants along with contributory underlying cardiovascular and respiratory disease. The three most prevalent additive substances were alprazolam, ethanol and gabapentin, found in 67, 36 and 32 cases out of 131, respectively. Interpreting BUP involvement in a death is complex, and instances may be underestimated in epidemiological data because of the lack of a defined toxic or lethal range in postmortem blood along with its good safety profile. As expansion of access to OUD treatment becomes a priority, awareness of the challenges of postmortem interpretation is needed as increased use and diversion of BUP are inevitable.