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

Abstract

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. 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 (260mg intravenous push × 1 followed by 130mg intravenous push every 15min as needed) from January2013 to July 2015, and front-loaded phenobarbital doses (10mg/kg intravenous infusion over 30min) from July 2015 to January 2017. In total, 87 patients met inclusion criteria for this study:41received low-intermittentphenobarbital and 46 receivedfront-loadedphenobarbital). 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 86mg [IQR 24-197] vs. 228mg [115-298], P < 0.01) and reduced need for any continuous sedative infusion (OR 7.7 [95% CI 1.6-27], P < 0.01). There was no difference in respiratory failure or hypotension. Front-loaded phenobarbital dosing, when compared to low-intermittent phenobarbital dosing, for benzodiazepine-resistant alcohol withdrawal was associated with significantly lower mechanical ventilation incidence and continuous sedative use.