Background: Alcohol withdrawal syndrome is a clinical syndrome with clinical manifestations of anxiety, insomnia, irritability, disorientation, hallucinations, seizures, and autonomic hyperactivity. Delirium tremens is the most severe manifestation of alcohol withdrawal. Although benzodiazepines are currently the first line for treatment of alcohol withdrawal, barbiturates are increasingly used for treatment as an alternative[1–3]. We need strong evidence to support the use of barbiturates in alcohol withdrawal management. This systematic review and meta-analysis is performed to examine the benefits of barbiturates in the management of alcohol withdrawal, either alone or as an adjuvant to benzodiazepine therapy, and to assess outcomes such as discharge rates from the emergency department (ED), intubation rates, hospital length of stay, mortality rates, and seizure prevention.
Methods: PubMed, EMBASE, Cochrane, and Web of Science were comprehensively searched since inception up to October 2020 for randomized control trials (RCT), prospective cohort, and retrospective cohort studies reporting outcomes in patients who received barbiturates (Phenobarbital, Barbital, Pentobartibal), benzodiazepines (Lorazepam, Diazepam, Chlordiazepoxide), or combination therapy for alcohol withdrawal. A total of 10 studies were identified. Two authors extracted the data from the selected studies. The meta-analysis was performed using RevMan (Cochrane software) for multiple variables, including discharge rates from the emergency department, intubation rates, hospital length of stay, mortality rates, and seizure prevention.
Results: A total of 1379 patients were included in this metanalysis from the 10 studies, of which two were RCTs and eight were retrospective studies. Five studies were performed in the emergency department setting and five studies were performed in the inpatient setting. Four studies compared Barbiturates against benzodiazepines, and six studies used barbiturates as an adjunct to benzodiazepines against benzodiazepine alone. Pooled data for the patients who were treated in the emergency department and received barbiturates either alone or adjunct therapy showed no difference in discharge rates, intubation rates, hospitalization rates, ICU admission rates, or seizures rates compared to patients who received benzodiazepines. Pooled data for the patients who were hospitalized and received barbiturates either alone or as adjunct therapy showed reduced hospital of stay 1.92 days (95% CI [-3.63 to – 0.22], P-value 0.03) compared to patients who received benzodiazepines. No differences in intubation rates or mortality rates were noted. Pooled data of intubation rates for patients favors fewer intubation rates who received benzodiazepines when compared to barbiturates alone with a risk ratio of 1.60 (95%CI [1.11 to 2.31], P-value 0.01).
Conclusions: Barbiturates can be used alone or as an adjunct to benzodiazepine for alcohol withdrawal in the ED setting safely with no significant difference in ED discharge rates, hospitalization rates, or seizure prevention rates. In the inpatient setting, the use of barbiturates as an adjunct therapy is supported with a decreased length of stay. Caution must be followed when using barbiturates alone in these alcohol withdrawal patients as higher intubation rates are noted. More randomized controlled trials are required to support the safety and benefits of barbiturates alone or as adjuvant in alcohol withdrawal patients.