Phenobarbital Versus Lorazepam for Management of Alcohol Withdrawal Syndrome: A Retrospective Cohort Study

Abstract

Introduction Annually, 500,000 episodes of alcohol withdrawal syndrome (AWS) are severe enough to require clinical attention. A symptom-triggered lorazepam regimen remains the standard of care for the management of hospitalized AWS patients. However, phenobarbital has also been shown to be an effective adjunctive therapy for severe AWS, reducing benzodiazepine use in the emergency department (ED) and the intensive care unit (ICU). The purpose of this study is to compare hospital length of stay (LOS) for AWS patients using phenobarbital-based versus lorazepam-based treatment protocols as monotherapy for management of AWS on general medical units. Methods This is a retrospective cohort study over a two-year period (March, 2016 to March, 2018), conducted at three hospitals within the St. Joseph Mercy Health System. We included 606 patients with a primary diagnosis of AWS or alcohol intoxication who met our inclusion criteria (543 in the lorazepam cohort and 63 in the phenobarbital cohort). Adjusted comparisons were done using propensity scoring methods. Hospital LOS was set as the primary outcome. Secondary outcomes included all-cause 30-day readmission, alcohol-related 30-day readmission, 30-day ED visits after discharge, and need for ICU transfer during hospital stay. Results Patients who received phenobarbital had a statistically significant shorter hospital LOS as compared to patients who received lorazepam (2.8 versus 3.6 days, P < 0.001). Furthermore, the phenobarbital treatment group had statistically significant lower rates of all-cause 30-day readmission (11.11% versus 14.18%, P = 0.020) and 30-day ED visits after discharge (11.11% versus 18.6%, P = 0.015). No statistical significance was detected for alcohol-related 30-day readmission and the need for ICU transfer between the treatment groups. Conclusion This study suggests that phenobarbital may be a reasonable alternative to lorazepam in the management of AWS patients admitted to general medical units. Larger scale, well-executed, and adequately powered prospective studies and randomized controlled trials are needed to corroborate these findings.

Medical Management of Acute Alcohol Withdrawal in Hospitalized Patients at a Community Based Network of Hospitals: A Retrospective Cohort Study

“…In this study, patients who received phenobarbital had a statistically significant reduced length of stay and lower rates of 30-day readmission. Additionally, there was a trend but not statistically significant for ICU transfer in the phenobarbital group compared to the benzodiazepine group (3.23% compared to 7.04% p=0.1114) [8].…”

“…In other similar studies [8][9][10][11], there are varied outcomes in relation to ICU admission, intubation and 30-day readmission rates when comparing benzodiazepines and phenobarbital. This study further demonstrates variation in these outcomes.…”

“…The mechanism is different from benzodiazepines which only act on GABA receptors. Phenobarbital has a longer half-life of 80-120 hours compared to 14-20 of lorazepam which decreases administration burden and allows for gradual tapering of therapy [7,8,9].…”

Barbiturates Versus Benzodiazepine for the Treatment of Severe Alcohol Withdrawal Syndrome: A Systematic Review and Meta-Analysis of Clinical Trials

“…According to six studies [18-23], the pooled prevalence of patients who had a history of DT was 27% (CI 0.95, 0.42, I 2 =93%, n=204/778) in the BZD group (Figure 2A) and 30% (95%CI 0.18, 0.43, I 2 =90%, n=182/587) in the PB group (Figure 2B). Five studies [20][21][22][23][24] reported CIWA-AR. The median CIWA-AR score in patients who received BZD was 9.046 plus minus 5.87, and that in patients who received PB was 10.3 plus minus 7.2.…”

“…The pooled prevalence of intubation was reported by 5 trials [18, [20][21][22][23] as 4% (95% CI 0.00, 0.12, I 2 = 86%, n=23/359) in the BZD group and 4% (95% CI 0.02, 0.06, I 2 =5%, n=17/444) in the PB group [18] (Figure 7A and 7B). Re-admissions reported in the BZD treatment group were 11.97%, and 9.52% in the PB treatment group [24]. The prevalence of other adjunct medication usage was reported by three trials [18,20,21]…”