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

J Med Toxicol. 2022 Jul;18(3):198-204. doi: 10.1007/s13181-022-00900-8. Epub 2022 Jun 6.

Abstract

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 < 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.

Conclusions: 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.

Keywords: Alcohol withdrawal; Benzodiazepine resistant; Intensive care unit; Mechanical ventilation; Phenobarbital.

MeSH terms

  • Alcohol Withdrawal Delirium* / diagnosis
  • Alcohol Withdrawal Delirium* / drug therapy
  • Alcoholism* / drug therapy
  • Benzodiazepines / adverse effects
  • Ethanol / adverse effects
  • Humans
  • Hypnotics and Sedatives / adverse effects
  • Length of Stay
  • Phenobarbital / adverse effects
  • Retrospective Studies
  • Substance Withdrawal Syndrome* / drug therapy

Substances

  • Hypnotics and Sedatives
  • Benzodiazepines
  • Ethanol
  • Phenobarbital