Balancing Barbiturates: Early Phenobarbital Dosing Strategies for Alcohol Withdrawal Syndrome

Introduction: Phenobarbital (PHB) may present advantages over benzodiazepines (BZD) for alcohol withdrawal syndrome (AWS), but the optimal dosing strategy of PHB in early management of AWS is unknown. This study compared the impact early low-dose PHB versus high-dose PHB on clinical outcomes in patients with AWS.


Methods: This multi-center, retrospective cohort study evaluated adults with AWS treated with intravenous PHB in the emergency department and medical intensive care unit (ICU) between July 2020 and January 2025. Outcomes of patients who received low-dose PHB (≤ 5 mg/kg) were compared to those who received high-dose (>5 mg/kg) over 24 hours. The primary outcome was ICU length of stay (LOS). Secondary outcomes included hospital LOS, mechanical ventilation, adjunctive therapy use, and patient disposition.


Results: The final analysis included 40 low-dose and 45 high-dose PHB patients. Median 24-hour cumulative PHB dose was 130 mg in the low-dose group and 585 mg in the high-dose (p < 0.05). Patients in the low-dose group had a similar ICU LOS to the high-dose group (3.5 vs 2.9 days; p = 0.126). There was no difference between hospital LOS (p = 0.546) and the incidence of mechanical ventilation (p = 0.381). BZD use was lower in the high-dose group (97.5% vs 82.2%; p < 0.05). Use of other adjunctive medications and discharge disposition did not differ.


Conclusions: Higher PHB loading doses did not significantly reduce ICU LOS compared to lower doses, suggesting unclear benefit in escalating dosing beyond 5 mg/kg in the first 24 hours of treatment for AWS.