Background: Alcohol use disorder (AUD) Is present in 10% of adults and its prevalence is increasing. When patients with AUD are admitted to the hospital, half develop alcohol withdrawal syndrome (AWS), which can cause delirium, hallucinations, seizures, and even mortality if not treated appropriately. A fixed-dose phenobarbital strategy may be superior to the standard of care and guideline-recommended strategy of symptom-triggered benzodiazepines in the pharmacological management of alcohol withdrawal syndrome. Most research demonstrating phenobarbital’s effectiveness has been done in intensive care units (ICUs), but greater than 90% of patients hospitalized for AWS are cared for outside of ICUs. The aim of this project is to evaluate the effectiveness and safety of phenobarbital compared to lorazepam for patients with AWS admitted to an inpatient, non-ICU setting.

Methods: We performed a retrospective cohort study of patients admitted to an academic medical center and an affiliated community hospital. Patients were included in the evaluation if their primary admitting diagnosis was for an alcohol related disorder and they were treated with either the institution’s fixed-dose phenobarbital protocol or symptom-triggered lorazepam protocol. All admitting services were included. Patients were excluded if they were admitted directly to an ICU or transferred to an ICU within 12 hours of admission. A backward stepwise regression analysis was used to evaluate the primary outcome, hospital length of stay.

Results: In total, 754 patients were included, 310 in the phenobarbital group and 444 in the lorazepam group. Patients in the phenobarbital group were more likely to have had a previous alcohol withdrawal seizure, more likely to have experienced delirium tremens in the past, and more likely to have an illicit substance use disorder. After adjustment for baseline characteristics, we found no statistically significant difference (adjusted p=0.301) in mean hospital length of stay between the phenobarbital group (4.15 days) and the lorazepam group (3.87 days). Similarly, we found no differences in secondary outcomes (Table).

Conclusions: Our findings suggest that a fixed-dose phenobarbital protocol is similar to a symptom-triggered lorazepam protocol with regard to length of stay and other important outcomes. The four-day duration of our institution’s fixed-dose phenobarbital protocol likely influenced the LOS in that group. Given the increased baseline risk of severe AWS in our phenobarbital group, residual confounding is a possibility. A randomized controlled trial, possibly examining a shorter fixed-dose phenobarbital protocol, would be a reasonable next step.

IMAGE 1: Secondary Outcomes