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As the illicit opioid landscape diversifies, emergency physicians must adapt protocols to address novel adulterants such as medetomidine, according to the CDC.

According to recent CDC reports, in 2024, multiple US cities reported clusters of opioid overdoses and withdrawal syndromes complicated by medetomidine, a veterinary sedative increasingly detected in illicit fentanyl. In Chicago, 12 confirmed and 26 probable medetomidine-related overdoses out of 181 emergency medical service (EMS) responses featured profound bradycardia and poor naloxone response. Philadelphia and Pittsburgh documented more than 160 and 10 hospitalizations, respectively, for fentanyl withdrawal refractory to standard therapies but responsive to dexmedetomidine. “The emergence of medetomidine in the illegal drug supply can complicate responses to suspected opioid-involved overdoses and necessitates educating persons who use drugs, clinicians, and public health personnel about the adverse effects of medetomidine,” stated study author Amy Nham, PharmD, MPH, CDC Epidemic Intelligence Service Officer, and colleagues.

Chicago Overdose Cluster: Bradycardia & Naloxone Resistance

According to reports, between May 11 and 17, 2024, Chicago’s West Side EMS teams encountered a surge of suspected opioid overdoses marked by severe bradycardia (heart rate <60 bpm in 87% of confirmed cases), pinpoint pupils, and persistent central nervous system depression despite naloxone administration. All toxicology-confirmed samples detected both fentanyl and medetomidine. Hypertension (≥180 mm Hg) occurred in 42%, and hypoxemia (oxygen saturation <90%) occurred in 47%. Bradycardia was refractory to naloxone in 92% of cases. Management focused on high‐dose naloxone, airway support, IV fluids, and atropine for bradycardia, given the absence of an approved α₂-antagonist for human use.

Philadelphia & Pittsburgh: A New Withdrawal Phenotype

According to another CDC report, late in 2023, Philadelphia drug‐checking programs identified medetomidine in 72% of tested opioid samples—surpassing xylazine prevalence. More than 160 patients developed an atypical withdrawal syndrome unresponsive to buprenorphine or clonidine but responsive to dexmedetomidine, its human‐approved analogue. Pittsburgh reported ten analogous cases. Presentation included severe agitation, hypertension, and tachycardia, persisting despite standard regimens for treatment of withdrawal. These observations suggested that medetomidine’s pharmacodynamics exacerbate or alter the opioid withdrawal toxidrome, according to researchers.

Implications for Emergency Medicine

In light of these findings, the report authors provided the following recommendations for emergency medicine physicians:

• Heightened suspicion: Consider medetomidine adulteration when overdoses feature profound bradycardia, atypical withdrawal, or poor naloxone response.
• Supportive care remains paramount: Continue titrated naloxone, secure airway and ventilation, administer IV fluids, and treat bradycardia with atropine.
• Withdrawal management: In refractory cases, dexmedetomidine infusion may ameliorate symptoms, although evidence is limited.
• Coordination with public health departments: Promptly report atypical cases to local health departments and participate in drug‐checking initiatives to guide community interventions.

The study authors noted that as the illicit opioid landscape diversifies, emergency medicine physicians must adapt protocols to address novel adulterants such as medetomidine, ensuring rapid identification, tailored supportive care, and collaboration with public health authorities to mitigate morbidity and mortality.