Rachel S Wightman1, Jeanmarie Perrone2, Rachel Scagos3, Maxwell Krieger4, Lewis S Nelson5, Brandon D L Marshall4. 1. Department of Emergency Medicine, The Warren Alpert Medical School of Brown University, 55 Claverick St, Providence, RI, 02903, USA. rachel_wightman@brown.edu. 2. Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Ground Silverstein, Rm. 260 3400 Spruce St, Philadelphia, PA, 19104, USA. 3. Rhode Island Department of Health, 3 Capitol Hill, Cannon Building, Providence, RI, 02908, USA. 4. Department of Epidemiology, Brown University School of Public Health, 121 South Main St, Box G-S-121-2, Providence, RI, 02912, USA. 5. Rutgers New Jersey School of Medicine, Medical Science Building, 185 South Orange Avenue, Newark, NJ, 07103, USA.
Abstract
BACKGROUND: Buprenorphine is a unique μ-opioid receptor partial agonist with avid receptor binding, nominal euphoric reward, and a ceiling effect on sedation and respiratory depression. Despite a pharmacologic profile that enhances safety, cases of fatal opioid overdose with buprenorphine on postmortem toxicology are reported, but details of these cases in the literature are limited. METHODS: A retrospective review of opioid-involved drug overdose fatalities in Rhode Island (RI) from 2016 to 2018 using the RI Department of Health State Unintentional Drug Overdose Reporting System (SUDORS) database. Deaths with buprenorphine on toxicology testing versus opioid-involved overdose deaths without buprenorphine were compared to assess the type and number of co-exposures. RESULTS: Of 534 opioid-involved deaths, 29 (5.4%) included buprenorphine and/or norbuprenorphine on toxicology. Most frequent co-exposures are as follows: fentanyl (75.9%), norfentanyl (72.4%), cocaine (41.4%), benzoylecgonine (41.4%), cannabinoids (31.0%), ethanol (31.0%), levamisole (31.0%), and free morphine (31.0%). An average number of co-exposures for fatalities with buprenorphine were 9.24 versus 6.68 in those without buprenorphine. In one case buprenorphine was the only drug listed to cause death; all other fatalities with buprenorphine on toxicology reported additional drugs contributing to death. CONCLUSION: Decedents with buprenorphine detected on toxicology testing commonly had documented polysubstance use. Although data are limited, buprenorphine may provide some risk mitigation against full agonist opioid overdose including fentanyl. Further work should explore the use of postmortem concentrations of buprenorphine, norbuprenorphine, and other opioid metabolites to determine the role of buprenorphine in fatal overdose pharmacology.
BACKGROUND: Buprenorphine is a unique μ-opioid receptor partial agonist with avid receptor binding, nominal euphoric reward, and a ceiling effect on sedation and respiratory depression. Despite a pharmacologic profile that enhances safety, cases of fatal opioid overdose with buprenorphine on postmortem toxicology are reported, but details of these cases in the literature are limited. METHODS: A retrospective review of opioid-involved drug overdose fatalities in Rhode Island (RI) from 2016 to 2018 using the RI Department of Health State Unintentional Drug Overdose Reporting System (SUDORS) database. Deaths with buprenorphine on toxicology testing versus opioid-involved overdose deaths without buprenorphine were compared to assess the type and number of co-exposures. RESULTS: Of 534 opioid-involved deaths, 29 (5.4%) included buprenorphine and/or norbuprenorphine on toxicology. Most frequent co-exposures are as follows: fentanyl (75.9%), norfentanyl (72.4%), cocaine (41.4%), benzoylecgonine (41.4%), cannabinoids (31.0%), ethanol (31.0%), levamisole (31.0%), and free morphine (31.0%). An average number of co-exposures for fatalities with buprenorphine were 9.24 versus 6.68 in those without buprenorphine. In one case buprenorphine was the only drug listed to cause death; all other fatalities with buprenorphine on toxicology reported additional drugs contributing to death. CONCLUSION: Decedents with buprenorphine detected on toxicology testing commonly had documented polysubstance use. Although data are limited, buprenorphine may provide some risk mitigation against full agonist opioid overdose including fentanyl. Further work should explore the use of postmortem concentrations of buprenorphine, norbuprenorphine, and other opioid metabolites to determine the role of buprenorphine in fatal overdose pharmacology.
Authors: Nabarun Dasgupta; Elise J Bailey; Theodore Cicero; James Inciardi; Mark Parrino; Andrew Rosenblum; Richard C Dart Journal: Pain Med Date: 2010-06-08 Impact factor: 3.750
Authors: Donna A Volpe; Grainne A McMahon Tobin; R Daniel Mellon; Aspandiar G Katki; Robert J Parker; Thomas Colatsky; Timothy J Kropp; S Leigh Verbois Journal: Regul Toxicol Pharmacol Date: 2011-01-06 Impact factor: 3.271
Authors: Jesse L Yedinak; William C Goedel; Kimberly Paull; Rebecca Lebeau; Maxwell S Krieger; Cheyenne Thompson; Ashley L Buchanan; Tom Coderre; Rebecca Boss; Josiah D Rich; Brandon D L Marshall Journal: PLoS Med Date: 2019-11-19 Impact factor: 11.069