Clustered bar diagram for adjunct medications, physical restrain, sitter, and mechanical ventilation use for the patients on phenobarbital-based protocol versus benzodiazepine-based protocol. ICU stay was reported in all the studies included in the systematic review 10-18. Saukkonen et al. confirmed a difference in the length of stay in the ICU without mentioning a standard deviation in their study. The finding by Saukkonen et al. was promising as it demonstrated significantly fewer days of stay (1.91 days in the phenobarbital arm vs. 6.24 days in the benzodiazepine arm). As Saukkonen et al. only published a conference abstract, no meaningful data could be gathered to identify the cause Substance abuse of these contradictory findings 18.

Current evidence and clinical utility of phenobarbital for alcohol withdrawal syndrome

The 4‐day treatment included a loading dose of either 6 or 10 mg/kg based on ideal body weight (IBW) divided into three intramuscular doses; 3 h apart on day 1; followed by a tablet maintenance dose taper for days 2 through 4. If total body weight (TBW) was less than cutting back on alcohol symptoms IBW; then TBW was utilized for the dosing. Per protocol; nurses were authorized to administer a breakthrough parenteral dose of 65 mg every 6 h as needed for withdrawal symptoms. The recommended loading dose of either phenobarbital 6 mg/kg or 10 mg/kg was based on risk of sedation and respiratory compromise. Risk factors for sedation included age of 65 or older; hepatic dysfunction; or cirrhosis.

Table 2. Management protocols.

Our protocol was not specifically designed for the MICU and allows for further dosing discretion by physicians, which may affect the standardization of treatment and the overall efficacy of the protocol. We feel that by performing a multivariable regression analysis, we have addressed most of these limitations. Additionally, we acknowledge the relatively low total median BZD dose in our BZD group as a limitation, as it is possible that more aggressive BZD dosing might have improved outcomes in this group.

• Moreover, people who experience alcohol withdrawal seizures are at increased risk of developing recurrent seizures.
• Accordingly, the current evidence supports recommending phenobarbital for the treatment of alcohol withdrawal syndrome at a broad level.
• Our hospital is part of a larger healthcare system, and cases were redirected to other facilities based on MICU availability, which could have affected the results.
• Phenobarbital is a barbiturate medication that works on both GABA and glutamate receptors to help slow brain activity.
• The data that support the findings of this study are openly available as an Appendix S1.

How we reviewed this article:

If total body weight (TBW) was less than IBW, then TBW was utilized for the dosing. Per protocol, nurses were authorized to administer a breakthrough parenteral dose of phenobarbital 65 mg every 6 h as needed for withdrawal symptoms (Figure 1). Sensitivity analyses were completed to control for possible covariates of type of discharge (AMA vs. planned) and BAL. Two separate hierarchical linear regressions were conducted evaluating ICU LOS, hospital LOS, RASS mode score at 9–24 h, and RASS mode score at 24–48 h to determine if treatment was predictive of these clinical outcomes. Type of discharge was a statistically significant outcome, with a higher percentage of phenobarbital patients leaving AMA. Notably, even though the admission BAL was higher in the phenobarbital cohort, the initial RASS score was not statistically different between cohorts.

Figure 4. Funnel plot of the length of ICU stay for the phenobarbital vs. control group.

• Finally, the use of CIWA-Ar in the MICU has been subject to debate in the literature, as it relies on patient cooperation (27).
• Here we present a systematic review and meta-analysis of the efficacy and safety of the drug.
• Drug administration should be adapted according to the severity of the symptoms.
• Chronic alcoholism leads to a decrease in gamma aminobutyric acid (GABA) inhibitory receptors as part of a feedback mechanism to counteract the depressive effects of alcohol.
• Patients requiring mechanical ventilation in the study conducted by Gold et al. received propofol 17.

Disagreements were resolved by discussion and by referring to the senior author whenever necessary. A 2023 research review lists seizures as a common complication of AWS, noting that alcohol withdrawal seizures typically occur between 8 and 48 hours after quitting alcohol. The review adds that these seizures can occur in the absence of other AWS signs and symptoms. This study provides further evidence for lower doses of intramuscular phenobarbital and a shortened oral taper to treat AWS. A single intramuscular injection can deliver 390 mg of phenobarbital into the body while permitting a slow drug release into the bloodstream.

RevMan 5.4 (Cochrane Collaboration, Copenhagen) was used to develop the forest plot and funnel plot. We conducted a manual search of the references of our included papers in order to ensure that we did not miss any relevant studies. All original studies that reported the management of AWS in the ICU setting with phenobarbital were included in the analysis. Two independent reviewers screened the titles and abstracts of the papers, followed by a full-text screening to ensure that relevant papers were included in the systematic review.