2026 Eastern States Conference

Title: Comparing the Efficacy and Safety of Split versus Front Loading Dosing Strategies of Phenobarbital in Hospitalized Patients with Alcohol Withdrawal Syndrome
 
Authors: Jillian Johnson, PharmD; Jina Patel, PharmD, BCCCP, Peter P. Olivieri, MD, FCCP; Hyunuk Seung, MS
 
Learning Objective: At the conclusion of this presentation, the participant will be able to describe the differences in efficacy and safety outcomes between front loading and split loading dosing strategies of phenobarbital in alcohol withdrawal syndrome.
 
Background/Objective: The objective of this study is to compare efficacy and safety outcomes of front versus split loading doses of phenobarbital in patients with alcohol withdrawal syndrome to add to the limited available evidence.  

Methods: This is a retrospective chart review of patients hospitalized for the management of alcohol withdrawal syndrome (AWS) at Baltimore Washington Medical Center between May 2024-March 2026 and treated with phenobarbital. The primary objective of this study is to quantify the difference in benzodiazepine requirements during hospital stay in patients with AWS who are treated with a front or split loading dose of phenobarbital. The secondary objective is to quantify the difference in average Modified Minnesota Detoxification Scale (mMINDS) scores 24 hours after loading dose administration, length of intermediate care/intensive care unit stay, length of hospital stay, use of adjunctive agents (midazolam, dexmedetomidine, and/or propofol), and safety outcomes (need for supplemental oxygen, days requiring mechanical ventilation, occurrence of seizures). Participants were excluded if they had been admitted more than 48 hours prior to phenobarbital administration, received a midazolam infusion, propofol, or dexmedetomidine prior to phenobarbital, or were transferred from another hospital center.
 
Results: The split loading group had significantly higher total benzodiazepine requirements compared to the front loading group (44 vs 18 mg lorazepam equivalents; p=0.0017). There was no statistically significant difference in change in mMINDS scores between groups, but the front loading group had lower average 24 hour mMINDS scores post phenobarbital loading dose compared to the split loading group (4.6 vs 5.8; p=0.049). The split loading group had significantly longer ICU length of stay (3 vs 0 days; p=0.001) and hospital length of stay (5.5 vs 3 days; p=0.0048). There were no statistically significant differences adjunctive therapy requirements or safety outcomes.

Conclusions: The front loading dosing scheme of phenobarbital is associated with statistically significant lower benzodiazepine requirements, lower length of ICU stay, lower length of hospital stay, and lower 24 hour average mMINDS scores. Safety outcomes were similar among both groups. This suggests that front loading doses of phenobarbital may provide better control of symptoms of alcohol withdrawal while maintaining a similar safety profile to split loading doses.

Self-Assessment Question: True/False: Patients who received front loading doses of phenobarbital had significantly lower benzodiazepine requirements with no significant difference in ventilation duration compared to split loading doses