Phenobarbital and Alcohol Withdrawal Syndrome: A Systematic Review and Meta-Analysis

Abstract

Alcohol withdrawal syndrome (AWS) is a complication frequently encountered among patients who are chronic alcohol abusers. It is considered to have a significant impact on the United States healthcare system.It not only has a toll on the healthcare spending but also contributes to significant morbidity and mortality. Benzodiazepines are considered first line in the treatment of AWS. Since patients with alcohol use disorder have downregulated gamma aminobutyric acid (GABA) receptors, this often leads to benzodiazepine resistance. Phenobarbital is also used in the management of alcohol withdrawal syndrome. Here we present a systematic review and meta-analysis of the efficacy and safety of the drug.We conducted an electronic database search for relevant studies published between the inception of the project and November 20, 2022, in three databases, including Medline/PubMed, Embase, and Cochrane Library. Our study included all original studies with prime focus on the baseline characteristics of patients admitted to the intensive care unit (ICU) for alcohol withdrawal syndrome and management/monitoring protocol implemented for its treatment. The primary outcomes that were the focus of our study consisted of changes in the length of hospital stay, length of ICU stay, and changes in scoring systems (for alcohol withdrawal assessment and monitoring) following the implementation of phenobarbital. The secondary outcomes included complications such as intubation and mortality.Based on our analysis, the mean difference in hospital stay was statistically significant at -2.6 (95% CI, -4.48, -0.72, P=0.007) for phenobarbital compared to the benzodiazepine group. We were unable to comment on the heterogeneity in our meta-analysis due to the standard deviation not being reported in one study. 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 (95% CI, -1.17, 0.09, P=0.07), with considerable heterogeneity (I 2 =77%, P=0.002). Our meta-analysis also investigated the risk of intubation between the phenobarbital and the control/comparative group. There was statistically significant difference in the incidence of intubation, relative risk (RR) 0.52 (95% CI, 0.25, 1.08, P=0.08), with considerable heterogeneity (I 2 =80%, P=0.0001).Our study concludes that phenobarbital is an effective tool in the management of AWS in an ICU setting. However, various studies have reported contradictory results, and vital information appears to be lacking. Moreover, there is a lack of uniformity in terms of phenobarbital dosing. Drug administration should be adapted according to the severity of the symptoms. Further studies need to be conducted discussing the safety profile and adverse effects of the drug when it comes to the management of alcohol withdrawal syndrome.

SAEM GRACE: Phenobarbital for alcohol withdrawal management in the emergency department: A systematic review of direct evidence

“…Importantly, combination therapy was not associated with additional adverse events, while multiple studies reported adverse events associated with benzodiazepine monotherapy. These findings are consistent with those of prior reviews, which have also found combination therapy to have some potential benefits in treating AWS over benzodiazepine monotherapy, particularly in more severe cases of AWS 42–45 . The prior reviews focus on ICU settings or were conducted prior to the current review.…”

“…These findings are consistent with those of prior reviews, which have also found combination therapy to have some potential benefits in treating AWS over benzodiazepine monotherapy, particularly in more severe cases of AWS. [42][43][44][45] The prior reviews focus on ICU settings or were conducted prior to the current review.…”

Load and go: Assessing safety outcomes of patients discharged from the emergency department after receiving phenobarbital for alcohol withdrawal

“…No patients in the case series PB cohort ( n = 33) developed AW or AE compared to other literature, where 48% and 19% of patients developed AW or AE in the cohort ( n = 52), respectively 12 . A recent meta‐analysis demonstrated a similar decrease in hospital LOS with PB usage compared to BZD usage 13 …”

“…12 A recent meta-analysis demonstrated a similar decrease in hospital LOS with PB usage compared to BZD usage. 13 In this case series, three patients returned to the ED within a short duration of time after PB administration. All patients had been instructed not to drive or drink alcohol for at least 7 days after receiving PB.…”

Phenobarbital versus Lorazepam for the Management of Alcohol Withdrawal Syndrome (AWS) in Hospitalized Patients- A Retrospective Cohort Study

“…One meta-analysis that compared PB with lorazepam for treatment of AWS in an ICU setting showed a reduction in the length of hospital stay by 2.6 days in favor of PB. Still, the study was limited due to the lack of uniformity or a standardized phenobarbital dosing regimen across different studies [28]. Another study that compared PB with BDZs for AWS in an ICU setting demonstrated a decreased duration of AWS and ICU LOS without differences in hospital LOS or adverse events [29].…”