Xylazine is a fentanyl contaminant which has been increasingly detected in drug overdose deaths in Maryland. This study explored risk factors and time trends of xylazine-related overdose deaths (XRODs) in Maryland from 2020 to 2023. This serial cross-sectional study utilized data from the Maryland Office of the Chief Medical Examiner on fentanyl overdose deaths that occurred from 2020 to 2023. XROD was defined as someone who died from overdose and had a positive postmortem blood xylazine test. Multivariable logistic regression modeled associations between demographic variables and presence of co-occurring substances with XROD. Annual population-based XROD rates were calculated for the overall sample and by race, age group, and sex. There were 8721 fentanyl overdose deaths in Maryland between 2020 and 2023. Among these, 1798 (20.6 %) were XRODs. Annual XROD rates peaked in 2021 and have declined since then. Although Black Marylanders experienced the highest overall burden of overdose, xylazine was significantly more likely to contribute to fentanyl overdose deaths among White individuals compared to Black individuals (aOR 1.18) and those aged 31-40 years compared to those 60 or older (aOR 1.25). Morphine (aOR 1.36), methadone (aOR 1.41), benzodiazepines (aOR 1.20), and tramadol (aOR 2.12) were associated with higher odds of XROD. XRODs are a major problem in Maryland, and there are significant differences in XROD mortality by race, age, and co-occurring substance use. Efforts to reduce xylazine-related mortality in Maryland should provide overdose prevention education and harm reduction services to the most vulnerable populations.
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