ORN Summer 2025 - Medetomidine: Clinical Implications of an Emerging Adulterant-Recording - Medetomidine: Clinical Implications of an Emerging Adulterant

Video Transcription

Video Summary

Dr. Michael Lynch, an expert in emergency medicine and toxicology, presented on metatomidine, an emerging adulterant increasingly found in Pennsylvania’s fentanyl supply. Metatomidine, an alpha-2 adrenergic agonist structurally similar to dexmedetomidine and clonidine, has become prevalent since mid-2024, replacing xylazine in many samples. It causes prolonged sedation and a uniquely severe withdrawal syndrome distinct from typical opioid withdrawal, characterized by intense nausea, vomiting, tachycardia, hypertension, agitation, and autonomic instability. This withdrawal can be life-threatening and often necessitates prolonged ICU care.<br /><br />Clinically, patients present with bradycardia and hypotension, prolonged sedation unresponsive to naloxone, and require careful supportive care. Severe withdrawal typically begins within hours of last use and is difficult to manage with standard treatments—the usual antiemetics like ondansetron are often ineffective, with dopamine antagonists preferred. High-dose oral alpha-2 agonists (clonidine, guanfacine) are first-line, but many require IV dexmedetomidine infusions at doses higher than typical ICU sedation protocols. Transitioning from dexmedetomidine to oral agents and tapering is critical. Opioid withdrawal management remains essential concurrently.<br /><br />Testing for metatomidine in real time is limited, and education about naloxone use remains crucial—naloxone reverses opioid effects but not metatomidine sedation. The presence of metatomidine complicates outpatient buprenorphine inductions, warranting adjunct alpha-2 agonist use and close monitoring.<br /><br />Unlike xylazine, metatomidine has not been linked with severe skin wounds. Its effect on overdose mortality is unclear but likely additive to fentanyl effects. The clinical experience is still evolving, with ongoing challenges in recognizing and managing this complex syndrome to improve outcomes.

Keywords

Metatomidine

Alpha-2 adrenergic agonist

Fentanyl adulterant

Prolonged sedation

Severe withdrawal syndrome

Dopamine antagonists

Dexmedetomidine infusion

Naloxone resistance

Buprenorphine induction complications

Emergency toxicology