REVIEW OF: Hawa F et al, Cureus 2021;13(2):e13282        

TYPE OF STUDY: Multisite retrospective cohort study        

Benzodiazepines such as lorazepam (Ativan) and chlordiazepoxide (Librium) have long been considered the gold standard treatment for alcohol withdrawal syndrome (AWS). However, phenobarbital may have advantages over benzodiazepines. Phenobarbital’s gradual time of onset minimizes reinforcing effects; its very long half-life (100 hours) prevents breakthrough withdrawal symptoms between doses; and it is generally safe in liver disease. Prior trials have shown that benzos and barbiturates are both effective for AWS management, but how does phenobarbital actually compare with benzos in clinical settings when it comes to length of stay (LOS)?        

This three-site, retrospective cohort study compared outcomes between patients with AWS who were treated with lorazepam versus phenobarbital. Investigators pooled 606 patients admitted for alcohol intoxication or withdrawal across three sites. The primary outcome was LOS, and secondary outcomes were 30-day readmissions (all-cause and alcohol-related), 30-day emergency department visits, and need for ICU transfer.        

543 lorazepam-treated patients and 63 phenobarbital-treated patients were included in the analysis. The two groups were similar in terms of demographics and in their medical and psychiatric comorbidities. Investigators found that the phenobarbital group had a statistically significant decrease in LOS relative to the lorazepam group (2.8 vs 3.6 days, p<0.001). The phenobarbital cohort also demonstrated a statistically significant reduction in 30-day all-cause readmissions (11% vs 14%), 30-day alcohol-related readmissions (10% vs 12%), and 30-day emergency department visits (11% vs 19%).        

There were several limitations to this study. First, there were many more patients in the lorazepam group, creating potential for systematic statistical error. The retrospective nature of the study meant that investigators could not control for preferences and biases. Severely ill patients were not included in the analysis; those requiring ICU care or addiction medicine consultation were excluded, potentially limiting the study findings to milder AWS cases. And finally, the skewed demographics (68% of the patients were male and 93% were White) might limit the generalizability of the results.        

Carlat Take        

This study suggests that phenobarbital is a reasonable alternative to lorazepam for AWS, with an added possible advantage of shorter LOS and lower 30-day readmission rates. As an already established treatment, using phenobarbital for AWS management is a reasonable consideration for inpatient settings, as long as it is managed by someone familiar with its use.