Impact of Early Initiation of Phenobarbital for Alcohol Withdrawal Syndrome in the Critically Ill

Introduction: Alcohol withdrawal syndrome (AWS) has been associated with increased hospital and intensive care unit (ICU) length of stay (LOS), increased need for and duration of mechanical ventilation (MV), increased mortality, higher rates of hospital acquired complications including delirium and infection, and increased cost of care. Standardized protocols for treatment of AWS including symptom- driven management are associated with improved outcomes. However, to date there is limited data regarding the impact of early administration of phenobarbital in addition to standardized symptom-driven management on outcomes in AWS, which is what we aimed to assess with this single center analysis.


Methods: A single center retrospective pre- and post-protocol implementation study was performed. Patients 18 years of age and older with AWS in the ICU between 2012 and 2018 (pre-protocol) and November 2021 and December 2022 (post-protocol) were included in the analysis. The primary outcome was need for MV and secondary outcomes included benzodiazepine utilization, indication for and duration of MV, incidence of delirium and hospital acquired infections, ICU and hospital LOS, and mortality.


Results: A total of 283 medical and surgical ICU patients were included in the analysis. Severity of illness scores on ICU admission were balanced between groups. There was no statistically significant difference in the overall need for MV (69.3% vs 67.5%, p= 0.743). However, when the need for MV was analyzed by indication, there was a significant reduction in MV due to development of refractory agitation or somnolence during hospital admission (20.9 % vs 6.7 %, p =0.0011). Post-protocol there was a statistically significant decrease in hospital length of stay (10.96 vs 7.75 days), mortality (31.9% vs 10.8%), hospital acquired pneumonia (38.7% vs 24.2%), delirium (76.1% vs 74.2 %), seizures (14.7% vs 6.7%), benzodiazepine utilization (4.11 vs 0.79 mg lorazepam equivalents per day) and use of restraints (90.8% vs 78.3%).


Conclusions: Protocolized management of alcohol withdrawal syndrome with early initiation of phenobarbital was associated with a significant reduction in the need for MV for refractory agitation or somnolence, reduction in mortality rate by 20%, and a decrease in cost of care.