II. Background
- Adulterant found in street Fentanyl used in Opioid Use Disorder
- May accompany other Fentanyl adulterants (e.g. Xylazine)
III. Mechanism
-
Alpha 2 Adrenergic Agonist
- Used in veterinary medicine as a Sedative and Analgesic
- Medetomidine is more potent that Xylazine at a2 receptors by a factor of 10x to 100x
- Medetomidine acts at presynaptic alpha-2 receptors
- Decreases Norepinephrine release
- Decreases sympathetic outflow
- Results in sedation, Bradycardia, Hypotension
- Medetomidine Withdrawal
- Dependence may develop with chronic use
- Severe sympathetic activation may occur with abrupt Medetomidine discontinuation
- Medetomidine is a racemic mix
- Active Dexmedetomidine
- Inactive Levomedetomidine
IV. Findings: Medetomidine and Opioid Intoxication
- Respiratory depression
- Typically reverses with Naloxone
- Hemodynamic changes
- Bradycardia
- Hypotension (may be initially hypertensive)
- Hypothermia
- Reduced sympathetic tone
- Sedation to coma, slurred speech
- Persists despite Naloxone
- Miscellaneous
V. Findings: Medetomidine Withdrawal
- Associated with chronic alpha 2 Agonist exposure
- Abrupt discontinuation of alpha 2 Agonist results in a sympathetic surge
- Occurs 6 to 24 hours after last exposure (peaks at 24 to 72 hours)
- Severe cases may last 1-2 weeks (days in mild cases)
- Hemodynamic changes
- Severe Hypertension
- Sinus Tachycardia
- Dysrhythmias
- Diaphoresis
- Neurologic changes
- Gastrointestinal
VI. Management: Medetomidine Withdrawal
- ABC Management
- Supportive Care
- Initiate alpha 2 Agonist
- Clonidine (mild to moderate cases)
- Dexmedetomidine (severe cases)
- Disposition
VII. References
- Swadron and Nordt (2026) Medetomidine Toxicity and Withdrawal, EM:Rap, 3/16/2026
- Lynch (2026) Ann Emerg Med +PMID: 41575403 [PubMed]