PSHP 2026 Residency Conference

Purpose
The purpose of this study was to characterize and assess the safety and efficacy of alpha-2 agonist utilization in the setting of fentanyl and presumed medetomidine withdrawal at a tertiary academic medical center in Philadelphia, PA.
 
Methods
This retrospective, single-center chart review evaluated patients admitted to an academic medical center between 1/1/2025 and 10/31/2025 with fentanyl and suspected medetomidine withdrawal and received an alpha-2 agonist(s) for withdrawal management. Patients were excluded if they received mechanical ventilation or vasopressors, experienced severe alcohol withdrawal, or underwent surgery during their withdrawal management. The primary objective was to characterize alpha-2 agonist use, including agent, dose, frequency, and route. Secondary objectives assessed safety and efficacy. Safety endpoints included incidence of hemodynamic instability and ICU disposition. Efficacy endpoints included incidence of ICU escalation and patient-directed discharge and the change in maximum Clinical Opiate Withdrawal Scale (COWS) scores within 72 hours of admission. 


Results
There were 100 included patients: 53 in the ICU and 47 on general medicine floors. All patients received clonidine, largely as oral tablets; 18% received tizanidine and 52% dexmedetomidine. The median maximum total daily dose of clonidine was 1.2 mg [IQR 1-1.6] for a median duration of 108.9 hours [IQR 72.7-159.7]. Dexmedetomidine had a median maximum infusion rate of 1.2 mcg/kg/hr [IQR 1-1.5] and a median of 27.3 hours [IQR 18.6-42]. Clonidine was held in 65% of patients (bradycardia). A heart rate <60 bpm occurred in 51% and a systolic blood pressure <90 mmHg in 5% of patients. The median COWS by day 2 had decreased from 22 [IQR 16.5-26] to 6 [IQR 4-8]. Many patients (58%) were discharged on clonidine, and 27% had self-directed discharge.


Conclusions
Alpha-2 agonists improved COWS scores over 72 hours and were well tolerated, with bradycardia being the most common adverse effect. Clonidine was the most frequently used alpha agonist, with dexmedetomidine reserved for ICU-level patients. Overall, these findings support the use of alpha-2 agonists for fentanyl with presumed medetomidine withdrawal management with careful hemodynamic monitoring and individualized dosing and tapering strategies.


This study was approved by the University of Pennsylvania Institutional Review Board (Protocol #859692).