Phenobarbital versus CIWA-Guided Benzodiazepines for Alcohol Withdrawal in the Emergency Department
Date First Published:
November 29, 2025
Last Updated:
November 29, 2025
Report by:
Lyanette Irizarry MD, Sean Farley MD, Senior EM Resident, EM Faculty (Corewell Health/Michigan State University Emergency Medicine Residency Program)
Search checked by:
Jeffrey Jones MD, Research Director
Three-Part Question:
In {adult emergency department patients with moderate to severe alcohol withdrawal syndrome} does [treatment with a single or multi-dose phenobarbital protocol], compare to [a symptom-triggered benzodiazepine protocol guided by Clinical Institute Withdrawal Assessment] result in [reduced ICU admissions, total sedation dosage, ED length of stay, or incidence of delirium tremens]?
Clinical Scenario:
A 42-year-old male with longstanding history of alcohol use disorder present to the ED with tremors, agitation and elevated CIWA score. You initiate symptom-triggered lorazepam (Ativan) per protocol but wonder whether phenobarbital could reduce the risk of ICU transfer, improve sedation control, and shorten the patient's ED stay.
Search Strategy:
Medline 1966-09/25 using PubMed, Cochrane Library (2025), and Embase
Search Details:
“Alcohol withdrawal syndrome” or AWS” and “phenobarbital” or “barbiturate” AND “benzodiazepine” OR “lorazepam” OR “diazepam” and “CIWA” OR “symptom-triggered” AND “ICU admission” OR “length of stay” OR “delirium tremens”. Limit to to adults AND Meta-analysis
Outcome:
24 total articles were found; four were recently published and addressed the clinical question.
Relevant Paper(s):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| Phenobarbital treatment of alcohol withdrawal in the emergency department: a systematic review and meta-analysis. Lee CM, Choi H, Han H, et al. May 2024 USA | 1507 patients in 2012 treatment encounters for AWS | Systematic review & meta-analysis of 8 studies comparing treatment with PB to BZD controls | Proportion of patients (1) admitted to the intensive care unit (ICU), (2) admitted to the hospital, (3) readmitted to the ED after discharge, and (4) who experienced adverse events. | Pooled relative risk of ICU admission for those treated with PB versus BZD was 0.92 (95% confidence interval [CI] 0.54-1.55). Risk for admission to the hospital was 0.98 (95% CI 0.89-1.07) and for any adverse event was 1.1 (95% CI 0.78-1.57) | Low to moderate quality evidence; moderate to high risk of bias; moderate statistical heterogeneity; confounding by severity, comorbidities, and system factors. |
| Phenobarbital for alcohol withdrawal syndrome: a systematic review. Punia K, Kennedy NW, Kaplan LJ, Sarmiento K. May 2024 Ontario, Canada | Adults ≥18 yrs ED patients with AWS | Systematic review: seven studies met inclusion criteria. Across all seven studies, 1034 adult patients were assessed | AWS complications, admission to a monitored setting, control of symptoms, adverse effects, and adjunctive medications were accessed | Treatment of AWS with phenobarbital resulted in lower odds of a subsequent ED visit. Phenobarbital was also associated with higher discharge rate compared to benzodiazepine-only treatments. For the two RCTs, phenobarbital did not differ significantly from benzodiazepine for most outcomes, although concomitant treatment with phenobarbital was associated with lower benzodiazepine use and intensive care unit admission. | Heterogeneous study designs; small number of studies; reliance on observational data limits conclusions on equivalence. |
| Evaluation of phenobarbital based approach in treating patient with alcohol withdrawal syndrome: A systematic review and meta-analysis Pourmand A, AlRemeithi R, Kartiko S, et al. July 2023 USA | Of the 1934 patients in these studies, 765 (41.7%) were treated with phenobarbital and 1169 (58.3%) were treated with other modalities for alcohol withdrawal. | Meta-analysis to compare the clinical outcomes for patients diagnosed with AWS in ED and ICU settings. | Rate of intubation among patients who received phenobarbital, compared with benzodiazepines, rates of seizures, hospital, and ICU length of stay (LOS). | Treating AWS patients with phenobarbital did not affect their risk for intubation, as the risk for intubation was similar between the phenobarbital and the control group (RR 0.70, 95% CI 0.36–1.38, P = 0.31). In addition, patients who were treated with phenobarbital were found to have similar rates of seizures (RR 0.73, 95% CI 0.29–1.89) and length of stay in the hospital (Standardized Mean Difference −0.02, 95% CI −0.26, 0.21) or the ICU (SMD −0.02, 95% CI −0.21, 0.25) when compared with patients receiving benzodiazepines. | The studies use different scales to measure and serve as an indication to initiation of AWS treatment. All observational studies within these studies involved a small patient sample size. Many studies did not report demographic information in similar or standard categories. |
| Phenobarbital and Alcohol Withdrawal Syndrome: A Systematic Review and Meta-Analysis Umar Z, Haseeb Ul Rasool M, Muhammad S, et al. Jan 2023 USA/Pakistan | Seven studies that included patients admitted to the intensive care unit (ICU) for alcohol withdrawal syndrome and management/monitoring protocol implemented for its treatment | Meta-analysis of the safety and efficacy of phenobarbital compared to benzodiazepines in the management of alcohol withdrawal syndrome. | Patient's length of hospital stay, length of stay in the intensive care unit, and interventions such as intubations during hospitalization for alcohol withdrawal syndrome | The mean difference in hospital stay was statistically significant at -2.6 (P=0.007) for phenobarbital compared to the benzodiazepine group. There was no statistically significant difference regarding the length of stay in the intensive care unit compared to the control/comparative arm, with a mean difference of -1.17 (P=0.07). There was statistically significant difference in the incidence of intubation, relative risk (RR) 0.52 ( P=0.08). | Inclusion of retrospective studies, significant heterogeneity, small sample size, a few critical parameters were reported in only three studies, some studies did not provide data on adverse effects, and the lack of uniform rules or guidelines for administering phenobarbital. |
Author Commentary:
The existing literature on phenobarbital for alcohol withdrawal syndrome (AWS) in the emergency department is growing but remains inconsistent. Retrospective cohort studies suggest potential benefits, including reductions in ICU admissions, hospital length of stay, and healthcare costs. However, systematic reviews and meta-analyses reveal poor methodological quality, moderate to high heterogeneity, and confounding factors that limit strength and generalizability of pooled conclusions. Phenobarbital monotherapy has not consistently demonstrated superiority, though combination therapy with benzodiazepines appears promising.
Bottom Line:
Current evidence is insufficient to recommend phenobarbital as a definitive superior treatment to benzodiazepines for alcohol withdrawal in the ED. Nonetheless, preliminary data suggest phenobarbital may be a safe and effective option, particularly as adjunctive therapy. Larger, rigorously designed randomized controlled trials with multi-site collaboration are needed to definitively establish phenobarbital’s role and inform standardized clinical protocols.
References:
- Lee CM, Choi H, Han H, et al.. Phenobarbital treatment of alcohol withdrawal in the emergency department: a systematic review and meta-analysis.
- Punia K, Kennedy NW, Kaplan LJ, Sarmiento K.. Phenobarbital for alcohol withdrawal syndrome: a systematic review.
- Pourmand A, AlRemeithi R, Kartiko S, et al.. Evaluation of phenobarbital based approach in treating patient with alcohol withdrawal syndrome: A systematic review and meta-analysis
- Umar Z, Haseeb Ul Rasool M, Muhammad S, et al.. Phenobarbital and Alcohol Withdrawal Syndrome: A Systematic Review and Meta-Analysis