Geographic Trends in Nonfatal Overdose Involving or Exposed to Opioids and Xylazine Across U.S. Emergency Departments

Objective: Examine geographical differences in opioid/xylazine exposures among patients presenting to emergency departments (EDs) with opioid overdose in various sites throughout the United States. Methods: The Toxicology Investigators Consortium (ToxIC) Fentalog Study is an ongoing prospectively collected observational study with 10 participating medical centers in the United States. Patients presenting with nonfatal confirmed opioid-related overdoses at participating EDs, and residual serum samples available were included (n = 1397). Clinical data were extracted through chart review, and toxicological analyses included liquid chromatography quadrupole time-of-flight mass spectrometry. EDs were stratified by region (Northeast, South, Midwest, and West). Univariate modeling investigated whether patients’ regions predicted xylazine detection. Results: Approximately 20.8% (n = 290) of patients had confirmed xylazine exposure, and most had cooccurring fentanyl and fentanyl analog exposures (99.7%, n = 289). When compared with the Northeastern sites, the odds of xylazine exposure were significantly lower at the Western sites (OR: 0.03, 95% CI: 0.01–0.07) but not significantly lower at the Midwestern sites (OR: 0.78, 95% CI: 0.55–1.09) or the Southern sites (OR: 0.61, 95% CI: 0.33–1.07). Conclusions: One in 5 patients with an opioid-related overdose had cooccurring xylazine exposure. Although xylazine exposures remained predominant in the Northeast, patients in the Midwest and South did not have lower odds of detection. Future research should consider the implications of geographically tailored public health prevention initiatives.