Emergency Department Opioid Withdrawal Management Across the Alpha-2 Agonist Adulterated Fentanyl Era in Philadelphia,PA: A Multi-Site Study

Abstract

Background:

The rapid emergence of alpha-2 agonist adulterants (xylazine, medetomidine) in some illicit fentanyl supplies has transformed opioid withdrawal presentations and introduced challenges with induction of medications for opioid use disorder (MOUD). This study compared outcomes of a standardized opioid withdrawal order set across 2 emergency departments with differing operational profiles, stratified by the predominant adulterant in the regional fentanyl supply.

Methods:

Retrospective analysis of all encounters utilizing a standardized withdrawal order set at an academic referral center and a community hospital in Philadelphia, PA, from September 2022 through December 2025. Encounters were stratified into xylazine-predominant (September 2022 through July 2024) and medetomidine-predominant (August 2024 through December 2025) eras. The primary outcome was the rate of premature departure disposition. Secondary outcomes included MOUD receipt in the emergency department and clinical presentation patterns.

Results:

A total of 3877 encounters were included (3086 academic; 791 community). Monthly visits more than doubled across the era transition at both sites. Withdrawal-related chief complaints increased from 16.2% to 42.7%, with a corresponding shift in primary diagnosis toward opioid withdrawal. Premature departure rates did not differ across eras, but were higher at the academic center (7.4% vs 3.3%; adjusted OR 2.40, 95% CI 1.58-3.64) and varied significantly by arrival time, with evening and overnight arrivals showing higher rates (P = .006). Overall MOUD receipt declined from 46.8% to 27.9% (OR 2.27, P < .001) across the era transition.

Conclusions:

Encounters for withdrawal treatment surged during a period of drug supply adulteration. Increased visits and a decline in MOUD uptake coincided with medetomidine emergence. Premature departures in this cohort were most associated with operational factors, including treatment site and arrival time, and not era.