Background: In patients with severe, benzodiazepine-resistant alcohol withdrawal (AW), the use of adjunctive phenobarbital has been associated with decreased need for mechanical ventilation. However, no study has compared phenobarbital dosing regimens. We assessed the hypothesis that front-loaded, high-dose phenobarbital would be associated with a lower incidence of mechanical ventilation when compared to low-intermittent dosing
Methods: In this retrospective cohort study, we searched the electronic health record to identify adult ED patients who were admitted to the intensive care unit (ICU) and received phenobarbital for severe AW between 1/2013 and 12/2017. Severe AW was defined as CIWA score > 20, and treatment is lorazepam-based with adjunctive phenobarbital as the second-line agent. Two phenobarbital dosing regimens existed, including front-loaded dosing (10 mg/kg IV over 30 minutes) and low, intermittent dosing (260 mg IV push, followed by 130 mg IV push every 15 minutes as needed). The primary outcome measure was the incidence of mechanical ventilation. Secondary outcomes included ICU length of stay (LOS), the incidence of continuous sedative infusions for AW, and cumulative phenobarbital dosing. Statistics were by Mann-Whitney U and Chi-square tests, as appropriate.
Results: Of 44 patients meeting study criteria, 24 were in the front-loaded dosing group and 20 in the low-intermittent dosing group. There were no differences in baseline characteristics between groups, with median age 47 [IQR 40-54] years-old, 38 (86%) male, and median baseline CIWA score 22 [IQR 20-30] for the cohort.
The incidence of mechanical ventilation was 29% (n = 7) for front-loaded dosing and 60% (n = 12) for low-intermittent dosing, with absolute reduction 31% [95%CI 2.7-56] (p < 0.05). For front-loaded versus low-intermittent dosing, the need for continuous sedative infusions was 67% (n = 16) vs. 90% (n = 18) (p = 0.07), ICU LOS was 115 hours [IQR 81-182] vs. 141 hours [IQR 95-168] (p = 0.69), and cumulative phenobarbital dosing was 15 mg/kg [IQR 10-21] vs. 13 mg/kg [IQR 10-16] (p = 0.22).
Conclusion: In this study of patients admitted to the ICU with severe AW, front-loaded dosing of phenobarbital was associated with a lower incidence of mechanical ventilation when compared to low-intermittent dosing. Prospective validation of these findings is warranted.