Intravenous Versus Intramuscular Phenobarbital for Initial Management of Alcohol Withdrawal

Introduction: Phenobarbital (PHB) has emerged as a first-line therapy for alcohol withdrawal syndrome (AWS), but the ideal dosing strategy and administration route is unclear. Intravenous (IV) PHB has a rapid onset and may require closer monitoring for adverse effects compared to the slower onset of intramuscular (IM) PHB. This study examined differences in efficacy, safety, and resource utilization when PHB is administered IV versus IM for AWS.


Methods: This single-center, retrospective, observational study included adult patients presenting to an Emergency Department (ED) between January 2022 and August 2023 who received at least one parenteral PHB dose using the institution’s AWS order set. Patients were excluded if they were pregnant, switched PHB route or left against medical advice prior to completion of PHB load, or if their encounter occurred within five days of prior PHB therapy. The institutional PHB protocol includes a 6 or 10 mg/kg loading dose, divided for administration over one hour for IV or nine hours for IM. Dose and route are selected by the provider. Outcomes including hospital length of stay (LOS), safety endpoints, and supplemental doses given within nine hours of protocol initiation were compared between those treated with IV versus IM PHB.


Results: This analysis included 198 patient encounters (IV n=97, IM n=101). No difference was found for hospital LOS between IV and IM groups (3.9 days for each group, p=0.739) or for any pre-specified subgroup. Safety outcomes of intubation, sedation, hemodynamic instability, respiratory depression, or rescue medication use were rare and similar between groups. The IV group received significantly more supplemental PHB than IM group (0.94 mg/kg vs 0.25 mg/kg, p< 0.001), with 51.5% of IV patients receiving any supplemental PHB compared to 14.9% of IM patients.


Conclusions: We did not identify safety or efficacy differences between patients receiving IV versus IM loads of PHB for AWS, but the faster onset of IV may have allowed for identification of breakthrough symptoms requiring supplemental doses. This study adds to the safety of PHB as first-line therapy for AWS and emphasizes the need for a streamlined IV dosing regimen for severe AWS to preserve nursing resources and overcome operational limitations in the busy ED setting.