Phenobarbital Versus Benzodiazepines for Alcohol Withdrawal in the Medical Intensive Care Unit (ICU): A Retrospective Cohort Study

Background: Phenobarbital (PHB) is a safe and efficacious alternative to benzodiazepines (BZD) for treating severe alcohol withdrawal (AWS). However, the safety of utilizing PHB for patients initially treated with BZD is unknown. Objective: To evaluate the safety and efficacy of PBH compared to BZDs in severe AWS in the medical intensive care unit (ICU). Methods: This was a retrospective cohort study comparing critically ill patients admitted for AWS who received BZDs or PHB. The primary outcome was time to persistent resolution of altered mentation. Secondary outcomes included development and duration of delirium, need for mechanical ventilation, development of withdrawal seizures, and ICU and hospital length of stay. Results: Ninety-five patients were evaluated (53 in PHB group, 42 in BZD group). Before study medication, less BZD patients demonstrated abnormal mentation compared with PHB patients (RASS < -2: 2.39% vsvs. 28.12%, respectively, and RASS > +2: 9.9% vsvs. 48.76%; P <0.001 for both). No difference was seen between groups for the primary outcome (1.8 hours for BZD cohort vsvs. 13.81 hours for PHB cohort; P =0.22). More patients in the BZD cohort developed a seizure after study medication administration (5.67% vs 0%, respectively; P =0.02). No significant difference was seen in other secondary outcomes. Conclusions: This study provides support for use of PHB after BZD if patients remain in uncontrolled withdrawal. Despite significant doses of BZDs before PHB, patients in the PHB cohort demonstrated similar clinical and safety outcomes compared to BZD alone.