Qualitative and quantitative characteristics of xylazine-associated deaths detected using a post-mortem toxicology testing program

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Introduction The United States drug overdose crisis continues to evolve. Xylazine has been increasingly identified as an adulterant in illicit opioid supplies. The incorporation of novel adulterants, like xylazine, into the illicit drug supply adds complexity to post-mortem toxicology testing, public health messaging, substance use mitigation, and the treatment of people who use drugs. Methods We assessed trends, decedent characteristics, drug co-detection, and blood concentrations of xylazine-positive post-mortem cases in Michigan. We utilized a toxicology testing program capable of detecting several opioids and non-opioids in post-mortem blood samples within 72 hours. Results A total of 279 deaths were xylazine-positive between October 2019 and June 2023, with 100 percent positive for fentanyl. Only 30 percent of xylazine-involved samples were positive for naloxone, while 21.2 percent of xylazine-negative and opioid-positive samples were positive for naloxone. The percentage of xylazine-positive deaths increased from 3.2 percent in 2021 to 4.7 percent in January–June 2023. A median of five total drug groups were present among xylazine-positive deaths. Post-mortem xylazine concentrations for 55 decedent blood samples ranged from 5.2 to 200 µg/L. Discussion Our study demonstrated increases in xylazine detection among post-mortem cases. Our findings are consistent with national trends of increasing xylazine presence among drug-involved deaths. Our range of detected post-mortem xylazine blood concentrations was consistent with what has been reported in previous literature. Fentanyl was detected in 100 percent of xylazine-positive overdose deaths. Naloxone detection was relatively low, highlighting the continued importance of increasing naloxone access and distribution. Deaths associated with xylazine often involved multiple other drugs. Limited human clinical xylazine research precludes accurate interpretation and attribution of causality from these data. Conclusions Overdose-related deaths with xylazine detection are increasing in Michigan and across the United States. Further clinical and toxicological research can help contextualize the clinical significance of xylazine in opioid overdose, clarify epidemiologic and clinical research, and inform appropriate public health messaging.