ED-EXACT in Opioid Overdose: Emergency Department Evaluation of Xylazine-Associated Clinical Toxicity in Opioid Overdose - PROJECT SUMMARY/ABSTRACT: This K23 career development award will enable the candidate, Jennifer Love, MD, MSCR, to become an independent clinician-scientist focused on improving emergency care for patients with opioid use disorder (OUD) who are exposed to xylazine and novel adulterants. Xylazine, an alpha-2 agonist and veterinary medication, has been increasingly detected with fentanyl. In 2023, xylazine- adulterated fentanyl and its health effects were declared a national toxicologic emergency. Due to its rapid emergence, limited knowledge exists regarding xylazine’s health effects. Some studies have reported prolonged sedation and necrotizing skin wounds among patients. In her pilot work, Dr. Love examined clinical effects of xylazine exposure in emergency department (ED) opioid overdose patients and found lower incidence of cardiac arrest and coma among patients exposed to xylazine. In her later work, she found that xylazine exposure was more often associated with bradycardia in the ED. In this K23, Dr. Love will develop and refine a clinical registry for ED opioid overdose patients exposed to xylazine and novel adulterants. The registry will integrate health record, toxicologic, serum biomarker and clinical outcomes data. Using qualitative interviews with people who use drugs and addiction medicine specialists, Dr. Love will refine the registry’s data elements and outcomes to reflect meaningful, targeted data collection. Dr. Love’s specific aims include (1) creating a clinical registry for xylazine-associated overdose and comprehensive ED care; (2) measuring xylazine and its metabolites in serum/blood and urine using laboratory and point-of-care assays; and (3) refining registry data elements and outcomes using perspectives of individuals with knowledge of xylazine and adulterants. To achieve her aims, Dr. Love will engage in focused curriculum and didactic coursework in data management, forensic toxicology, and qualitative research and analysis. Dr. Love will build upon her experience as an emergency medicine physician and toxicologist to gain new skills in qualitative research using semi-structured interviews, forensic laboratory analysis, clinical data management, and database quality assurance. Dr. Love has assembled an expert mentorship team of nationally funded researchers and clinicians in emergency medicine, medical toxicology, and addiction medicine. The proposed research and career development plan will allow Dr. Love to develop expertise in (1) clinical database management, (2) forensic toxicology and (3) qualitative research. The K23 will enable her transition to an independent clinical investigator focused on understanding acute and longitudinal outcomes for OUD patients exposed to xylazine and adulterants in evolving drug markets. Project completion will produce a clinical registry for opioid overdose patients who are exposed to xylazine and other adulterants, and form the basis for Dr. Love’s subsequent R01 proposal. Her future R01 will expand the registry to hospital sites across the US. The registry will critically advance ED-based toxicologic and addiction care for patients exposed to xylazine-adulterated fentanyl.
