Presentation and management of acute medetomidine withdrawal

Medetomidine, a potent α2-adrenergic agonist, is an emerging contaminant in the US illicit opioid supply. It is a racemic mixture that includes the sedative dexmedetomidine and can lead to severe and complicated withdrawal symptoms requiring novel management strategies. In this therapy update, we provide insights on the identification and management of medetomidine withdrawal based on our clinical experiences with it over the past year.

Medetomidine withdrawal can occur precipitously, typically 4 to 6 hours after last use in regular users, and lead to severe symptoms and complications including agitation, tremors, and widespread sympathetic activation. Prompt identification of withdrawal is vital to initiate oral and transdermal α2-agonist therapy, often at doses higher than those required for labeled indications. Severe nausea and vomiting are typically present and may be refractory to standard treatments and prevent oral therapies from being administered. Intravenous dexmedetomidine is recommended for those for whom oral α2-agonist therapy is ineffective or who are unable to tolerate enteral therapies. This may require aggressive dose titration and infusion rates that are above those in typical sedation protocols. In addition to α2 withdrawal, patients may have withdrawal from concomitant opioids, benzodiazepines, or other substances that requires additional treatment.

Medetomidine withdrawal can lead to severe hemodynamic and autonomic complications that require a multimodal treatment strategy. Clinicians should be familiar with the signs, symptoms, and timing of medetomidine withdrawal along with the complex management that is required.