Is Phenobarbital an Effective Treatment for Alcohol Withdrawal Syndrome in the Emergency Department?

Alcohol withdrawal syndrome (AWS) is a potentially life-threatening condition commonly treated in the emergency department (ED). Phenobarbital may be used alone or in combination with benzodiazepines to treat AWS. Its long half-life, self-tapering quality, GABAergic properties—and the fact that it reduces glutamate (AMPA) receptor activity—suggest that it may be useful to treat AWS in the ED. Researchers conducted a systematic review of studies examining the administration of phenobarbital to treat moderate-to-severe AWS in the ED.

• Overall, there was limited literature examining the administration of phenobarbital to treat AWS (i.e., 7 articles that assessed a total of 1034 patients) in the ED. Research was of heterogeneous quality; small in size; used variable medication dosages and combinations; had a variety of comparison groups; and had significant risk of bias.
• Retrospective cohort (n=3) and chart review (n=2) studies had small sample sizes, but showed possible decreased repeat ED visits among patients with AWS discharged after treatment with phenobarbital alone or in combination with lorazepam.
• The 2 randomized controlled trials were small in size and heterogeneous. One was placebo controlled and showed a reduction in intensive care unit (ICU) admissions and length of stay. The other was a comparison of phenobarbital with relatively lower doses of lorazepam and showed no difference in admissions or ED length of stay.
• Some studies showed that administration of phenobarbital in combination with benzodiazepines was found to be benzodiazepine-sparing and associated with reduced ICU, ED, and hospital lengths of stay.

Comments: Studies examining the administration of phenobarbital in the ED are generally small in size and of mixed-to-low quality. Current preliminary direct evidence supports the use of phenobarbital to treat AWS in the ED and that it may reduce ICU admissions. Further studies are needed to examine its safety, symptom improvement, dosing strategies, and its administration in combination with benzodiazepines.

Elizabeth A. Samuels, MD, MPH, MHS

Reference: Punia K, Scott W, Manuja K, et al. Phenobarbital for alcohol withdrawal management in the emergency department: A systematic review of direct evidence for the SAEM GRACE initiative. Acad Emerg Med. 2023 [Epub ahead of print]. doi: 10.1111/acem.14788.