Evaluating Weight-Based Phenobarbital Dosing in Patients Hospitalized for Alcohol Withdrawal

Introduction: Phenobarbital (PB) has been associated with decreased length of stay, improved symptom management, and reduced risk of intubation compared to benzodiazepines (BZD) in prior studies. In recent years, shortages of first-line intravenous (IV) BZD led to the development of a weight-based PB protocol at ChristianaCare for moderate-to-severe alcohol withdrawal syndrome (AWS) in April 2024. The purpose of this study was to evaluate the safety and effectiveness of a weight-based PB protocol for moderate-to-severe AWS as compared to treatment with BZDs alone


Methods: This retrospective cohort study reviewed pre- and post-implementation of the PB protocol. Patients >18 years old who presented to the emergency department with a primary diagnosis of moderate-to-severe AWS were eligible for inclusion. The pre-implementation group included patients who had received BZDs from an AWS order set between April 2 to October 2, 2023. The post-implementation group included patients ordered the weight-based PB order set between April 2 to October 2, 2024. The primary outcome was the time to symptom control, defined as the time to a Clinical Institute Withdrawal Assessment (CIWA) score of ≤8. Secondary outcomes included symptom recurrence, daily BZD and PB dosing requirements, 30-day readmission rate, incidence of activation of rapid response teams (RRT), and mortality. Safety endpoints included the need for intubation and oxygen requirements.


Results: A total of 100 patients were included in the study with 50 patients in each arm. The primary outcome of time to a goal CIWA score of ≤8 was found to be lower in the PB group compared to the BZD group (9.38 hours vs 21.60 hours, p < 0.01). For secondary outcomes, there was a significant reduction in the BZD requirements in the PB group on day 1 of admission (1.35 mg vs 17.38 mg lorazepam equivalents, p < 0.01). Additionally, patients in the PB group experienced less symptom recurrence (34% vs 70%, p < 0.01 ). The 30-day readmission rate was higher in the PB group (54% vs 36%, p=0.04). There were no significant differences in oxygen requirements, intubation rates, incidence of RRTs, or in-hospital mortality between the two groups.


Conclusions: Treatment with PB was shown to significantly improve the time to symptom control in patients with moderate-to-severe AWS.