(60) Low-Dose Dexmedetomidine: Repurposing an Intravenous Agent for Opioid & Alpha 2 Withdrawal

Background & Introduction: The volatile combination of synthetic opioids and alpha 2-adrenergic receptor agonists (xylazine, and more recently medetomidine) in the Philadelphia community has led to unprecedented withdrawal syndromes that are increasingly difficult to treat. While these new withdrawal syndromes and the increased prevalence of fentanyl/alpha 2 agonist use are not well understood, it has become a significant barrier to managing inpatient withdrawal. While pharmacologic alpha 2 agonist withdrawal is well described, severe veterinary based withdrawal is not. Our team has recently published an approach to manage acute opioid and alpha agonist withdrawal utilizing alpha agonists like tizanidine and clonidine. These medications proved efficacious at treating novel withdrawal syndrome until May 2024, when medetomidine, a more potent alpha 2 agonist veterinary sedative, entered the local drug supply. Because of the severe vomiting associated with concomitant opioid and alpha 2 withdrawal, and our promising results of improved withdrawal symptoms with aggressive alpha 2 agents, a pilot was started allowing the administration of low-dose intravenous dexmedetomidine (0.2 - 0.7 mcg/kg/hr) in intermediate care units, rather than only in the ICU. Data collected include demographics, chief complaint, adverse events, need for ICU upgrade, rate of patient directed discharge (PDD, formally ‘against medical advice’).

Case Description: We present a series of 10 patients who were presenting with features concerning for severe concomitant opioid and alpha-2-agonist withdrawal. All patients received medications from standardized non-medical opioid withdrawal order sets including short acting opioids, oral and transdermal alpha agonists and other adjuncts. All had progression of symptoms and required intravenous alpha-2-agonist therapy to control their symptoms. 8 patients were White, 1 Hispanic and 1 Black. Their median age was 40 and 80% were male. 5 arrived with 'Opioid Withdrawal' as their chief complaint, 3 with traumatic injuries and 2 with other medical complaints. The median duration of dexmedetomidine therapy was 65 hours. None required upgrade to ICU unit, 2 had infusions reduced or discontinued for hypotension and no other adverse effects were noted. 4 patients had PDD, with 2 referred directly to rehabilitation centers and 4 discharged home, 3 of whom on MOUD.

Conclusion & Discussion: The emerging hallmark presentation of opioid and alpha 2 withdrawal is characterized by severe hypertension, hyperactive followed by hypoactive encephalopathy, intractable nausea/vomiting, in addition to traditional opioid withdrawal symptoms. The constellation of this new, severe withdrawal toxidrome is becoming more common in the Philadelphia area. Our case series has demonstrated promising results of improved withdrawal symptoms when utilizing low-dose intravenous dexmedetomidine in combination with opioid agonist-based therapies.

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