537: Management of Combined Opioid and Medetomidine Withdrawal at an Academic Medical Center

Introduction: In May 2024, a new adulterant medetomidine was detected in illicit opioid supplies in Philadelphia. By June, it was found in the majority of samples. The rise of medetomidine, a synthetic α2 adrenoreceptor agonist, coincided with a surge of patients experiencing a unique withdrawal syndrome characterized by severe autonomic dysfunction, including hypertensive emergency, tachycardia, emesis, and tremor, requiring management in the intensive care unit (ICU). Here, we describe the implementation of new treatment guidelines for these patients and the early experience at a single academic medical center. Methods: A collaboration of addiction medicine, pharmacy, emergency medicine, and ICU specialists developed a standardized medication protocol for patients with opioid withdrawal with severe autonomic dysfunction. The regimen included treatment with dexmedetomidine infusion (an enantiomer of medetomidine), clonidine (an α2 agonist), long- and short-acting opioids, and multimodal symptom management with agents such as olanzapine and ketamine. Results: We reviewed a sample of 61 patients who had 69 ICU admissions for opioid withdrawal from September 2024 to July 2025. Median ICU length of stay (LOS) was 46.1 hours (interquartile range IQR 23.2-68.9) and median hospital LOS was 58.0 hours (IQR 36-84). 58 patients received oral clonidine (84.1%) at a median dose of 0.3mg (IQR 0.2-0.4) every 6-8 hours. 54 patients (78.3%) received dexmedetomidine infusion with 28 patients (51.9%) requiring the maximum approved dose of 1.5mcg/kg/hr (median highest dose received 1.5 mcg/kg/hr IQR 0.8-1.5). Median duration of dexmedetomidine infusion was 36.1 hours (IQR 22.1-52.6). Conclusions: Patients with concomitant opioid and medetomidine withdrawal often required multiple days in the ICU to receive high-dose dexmedetomidine for extended periods, along with multimodal symptomatic treatment. Our experience highlights the challenge of managing withdrawal in the rapidly evolving landscape of opioid adulterants and the importance of timely development and implementation of effective treatment protocols.