Evaluation of a Phenobarbital-Based Protocol for Severe Alcohol Withdrawal in Critically Ill Patients

Abstract

Background: Phenobarbital offers several possible advantages to benzodiazepines including a longer half-life and anti-glutamate activity, and is an alternative for the treatment of alcohol withdrawal. The objective of this analysis was to evaluate the safety and efficacy of a phenobarbital protocol for alcohol withdrawal newly implemented at our institution. Methods: This was a single-center, retrospective analysis of adult patients admitted to the medical/surgical/burn/trauma intensive care unit (ICU) with or at risk of severe alcohol withdrawal. Patients who were admitted prior to guideline implementation and received scheduled benzodiazepines (PRE) were compared to those who received phenobarbital post guideline update (POST). The primary outcome was ICU length of stay (LOS). Results: Upon analysis, 68 patients in the PRE and 64 patients in the POST were identified for inclusion. The median APACHE II score was significantly higher in the POST (4.5 [3:9] vs 10 [5:13], P < 0.001). ICU (2 [1:2] vs 2 [2:5], P = 0.002) and hospital (4.5 [3:6] vs 8 [6:12], P < 0.001) LOS were significantly longer in the POST. There was no difference in mortality or duration of mechanical ventilation. More patients required propofol or dexmedetomidine on day one in the POST ( P < 0.001). Conclusion: Patients in the POST had significantly longer ICU and hospital LOS, and had a higher baseline severity of illness. Future research is needed to evaluate the efficacy and safety of phenobarbital compared to benzodiazepines for severe alcohol withdrawal.

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

“…In the pooled analysis of ICU stay length, six studies with a total of 569 patients were included. Based on the results, there was no statistically significant difference regarding the length of stay in the intensive care unit, 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) (Figures 3, 4) [12][13][14][16][17][18]. We also examined the incidence of intubation between the experimental and control groups.…”

“…The baseline characteristics of the included studies are summarized in Table 1. A total of nine studies were included: one retrospective case series with more than 11 participants and including original data [10], seven retrospective studies [11][12][13][14][15][16][17], and one abstract with data relevant to the study design [18]. The sample sizes of the included studies ranged from 31 to 135 individuals.…”

“…The pooled analysis included six studies involving 624 patients. Phenobarbital vs. control had no significant differences in the incidence of intubation, with relative risk, or RR, 0.52 (95% CI, 0.25, 1.08, P=0.08), with considerable heterogeneity (I 2 =80%, P=0.0001) (Figures 5, 6) [13][14][15][16][17][18].…”

“…In the post-guideline era, patients admitted to the ICU for the management of AWS were administered benzodiazepine and phenobarbital in a protocolized manner [17]. We found that the majority of the studies included in our study included patients with a prior history of AWS, polysubstance abuse, and alcohol withdrawal seizures [10,[12][13][14][15][16][17].…”

“…The management protocols implemented for the treatment of AWS in an ICU setting in both control and experimental groups have been described in depth in Table 2 and experimental arms received dexmedetomidine, clonidine, propofol, and antipsychotics [13]. A total of 11 patients in the experimental group and 26 patients in the control group received propofol and dexmedetomidine for the management of alcohol withdrawal syndrome in the study conducted by Saukkonen et al [18].…”