Front-Loaded Versus Low-Intermittent Phenobarbital Dosing for Benzodiazepine-Resistant Severe Alcohol Withdrawal Syndrome

Introduction Phenobarbital is frequently used to manage severe alcohol withdrawal. The purpose of this study was to compare the incidence of mechanical ventilation in patients with benzodiazepine-resistant alcohol withdrawal between front-loaded and low-intermittent phenobarbital dosing strategies. Methods In this retrospective before-after study, we analyzed patients that received phenobarbital for severe alcohol withdrawal syndrome in a tertiary medical ICU. Patients received low-intermittent phenobarbital doses (260 mg intravenous push × 1 followed by 130 mg intravenous push every 15 min as needed) from January 2013 to July 2015, and front-loaded phenobarbital doses (10 mg/kg intravenous infusion over 30 min) from July 2015 to January 2017. Results In total, 87 patients met inclusion criteria for this study: 41 received low-intermittent phenobarbital and 46 received front-loaded phenobarbital). The incidence of mechanical ventilation was 13 (28%) in the front-loaded dosing group vs. 26 (63%) in the low-intermittent dosing group (odds ratio 4.4 [95% CI 1.8–10.9]). The cumulative dose of phenobarbital administered and serum phenobarbital levels were similar between both groups, although the front-loaded group had significantly lower benzodiazepine requirements than the low-intermittent group (median 86 mg [IQR 24–197] vs. 228 mg [115–298], P