A Comparison of Phenobarbital Dosing Strategies for the Treatment of Alcohol Withdrawal Syndrome

Background: The preferred dosing strategy for phenobarbital in alcohol withdrawal syndrome (AWS) is not well established. Objective: We compared the effects of a 10- vs 20-mg/kg dose on the incidence of severe AWS and benzodiazepine use. Methods: This retrospective cohort study included patients who received a phenobarbital front-loaded dose with either 10 mg/kg or 20 mg/kg. The primary endpoints were severe AWS (Clinical Institute Withdrawal Assessment [CIWA] score ≥15, use of restraints, or seizures) and total lorazepam equivalents. Secondary endpoints were the frequency of intubation and intensive care unit (ICU) length of stay. Results: We included 135 patients (n = 71, 10 mg/kg; n = 64, 20 mg/kg). Demographics were similar except baseline CIWA, cirrhosis history, and benzodiazepine administration pre-phenobarbital were higher in the 10-mg/kg group. The incidence of severe AWS was higher in the 10-mg/kg group (56.3% vs 32.8%; P = .006), as was lorazepam administration 48-hour post-phenobarbital load (7 ± 10.3 vs 2.6 ± 5.9 mg; P < .001). After controlling for differences in baseline CIWA scores, there was no difference in severe AWS (odds ratio [OR] [95% CI] = 0.532 [0.215 to 1.315]), but benzodiazepine usage was lower in the 20-mg/kg group (B = −3.376, P = .046). The frequency of new intubation was 5.9% and 10.2% for the 10- and 20-mg/kg groups, respectively ( P = .483). No difference in ICU length of stay was noted (10 mg/kg, 4.5 ± 3.4 vs 20 mg/kg, 3.9 ± 3.6; P = .411). Conclusion and Relevance: A 20-mg/kg phenobarbital dose did not reduce severe AWS but may lower benzodiazepine usage in the early withdrawal period. A 20-mg/kg dose was not associated with increased intubations. Clinicians may consider this option when crafting phenobarbital dosing regimens in patients with severe AWS.