A retrospective evaluation of phenobarbital versus benzodiazepines for treatment of alcohol withdrawal in a regional Canadian emergency department

Comprehensive Summary

Pistore et al. compared phenobarbital versus benzodiazepine monotherapy for reducing emergency department (ED) length of stay in patients with alcohol withdrawal syndrome (AWS). This retrospective study analyzed outcomes from 83 patients across 185 ED encounters. The primary outcome was ED length of stay, with secondary outcomes including hospital admission rates. Median ED length of stay was similar between groups (phenobarbital: 4.0 hours vs. benzodiazepines: 4.0 hours, p=NS). However, phenobarbital monotherapy was associated with lower hospital admission rates compared to benzodiazepines. Out of the phenobarbital patients, 9.4% were hospitalized and 17.1% of benzodiazepine presentations were hospitalized (p = 0.20). No significant differences were observed in adverse events or need for adjunctive medications between groups.

Outcomes and Implications

Alcohol withdrawal syndrome (AWS) affects a substantial proportion of patients with alcohol use disorder who abruptly reduce or cease alcohol consumption. Untreated severe AWS can progress to delirium tremens with significant morbidity and mortality. Benzodiazepines have been the mainstay of AWS treatment for decades based on extensive evidence demonstrating efficacy in preventing seizures and delirium tremens. However, benzodiazepines require frequent dosing, can cause over-sedation, and may be challenging to taper in the inpatient setting. Phenobarbital has emerged as a potential alternative given its long half-life (allowing less frequent dosing), GABA-A receptor agonism (similar mechanism to alcohol), and some evidence suggesting it may reduce ICU admissions and hospital length of stay.