Optimal Phenobarbital Loading Dose for Alcohol Withdrawal

Alcohol withdrawal syndrome (AWS) is a common cause of hospitalization and can result in severe autonomic and neurologic complications. Benzodiazepines are first-line therapy, though phenobarbital is increasingly used due to its GABAergic and glutamate-antagonist effects. While a 10 mg/kg loading dose is commonly recommended, real-world practice often employs lower dosing, questioning the necessity of this target. This study aimed to evaluate the efficacy of lower initial phenobarbital doses compared to the recommended 10 mg/kg for management of severe AWS.

This single-center retrospective study was conducted at a Level I trauma academic medical center. Adults presenting to the emergency department with AWS, an initial CIWA-Ar score greater than or equal to 9, and receipt of intravenous phenobarbital between January 2020 and June 2025 were included. The primary outcome was cumulative phenobarbital dose required to achieve a CIWA-Ar score <9. Secondary outcomes included time to symptom control, cumulative phenobarbital dose within 24hrs of admission, ICU admission, intubation, hypotension, hospital length of stay, and adjunct benzodiazepine use. Descriptive statistics were used for analysis.

A total of 183 patients were included. The median cumulative intravenous phenobarbital dose required to achieve a CIWA-Ar score <9 was 390 mg [IQR 260–650], corresponding to approximately 4.94 mg/kg based on median actual body weight (79.4 kg [66.7–90.9]). Median time to CIWA <9 was 3.0 hours [1.4–7.3]. The mean cumulative phenobarbital dose within the first 24 hours of admission was 640.4 ± 353.1 mg. ICU admission occurred in 101 patients (55.2%). Adjunct benzodiazepines were required in 34 patients (18.6%). Endotracheal intubation occurred in 2 patients (1.0%). Hypotension occurred in 8.7% (SBP <90 mmHg) and 26.8% (DBP <60 mmHg). Median inpatient length of stay was 79.2 hours [50.0–112.3].

Lower initial phenobarbital doses were effective for achieving rapid alcohol withdrawal symptom control, with low intubation rates and limited benzodiazepine use. These findings suggest that lower cumulative doses may be sufficient, and that achieving a 10 mg/kg target may not be necessary for adequate management of severe alcohol withdrawal in select patients.