Evaluation of the Use of Phenobarbital and Benzodiazepines in the Management of Alcohol Withdrawal Syndrome in Patients Requiring Neurological/Neurosurgical Critical Care: A Propensity-Matched Analysis.

ABSTRACT

Objective There is growing interest in the use of phenobarbital for alcohol withdrawal syndrome in critically ill patients, though experience in neurologically injured patients is limited. The purpose of this study was to compare the safety and effectiveness of phenobarbital-containing alcohol withdrawal regimens versus benzodiazepine monotherapy in the neurocritical care unit. Methods We conducted a retrospective cohort study of adult patients admitted to the neurocritical care unit from January 2014 through November 2021 who received pharmacologic treatment for alcohol withdrawal. Treatment groups were defined as benzodiazepine monotherapy versus phenobarbital alone or in combination with benzodiazepines. The primary outcome was the percentage of patients requiring intubation after receiving alcohol withdrawal treatment. Secondary outcomes included all-cause, in-hospital mortality, intensive care unit length of stay, discharge disposition, change in Glasgow Coma Scale (GCS) score, and the use of adjunctive agents. Results We analyzed data from 156 patients, with 77 (49%) in the benzodiazepine group and 79 (51%) in the phenobarbital combination group. The groups were well-balanced for baseline characteristics, though more males (67, 85%) were in the phenobarbital group. Only three (1.9%) patients received phenobarbital monotherapy, and the rest (153, 98.1%) received combination therapy. The percentage of patients requiring mechanical ventilation was significantly higher in the phenobarbital combination group compared to benzodiazepine monotherapy (39% (n=31) versus 13% (n=10); OR 4.33, 95% CI 1.94-9.66; p<0.001). The use of adjunctive propofol and dexmedetomidine was higher in the phenobarbital group (propofol 35% (n= 28) versus 9% (n=7) and dexmedetomidine 30% (n=24) versus 5% (n=4), respectively). Patients in the phenobarbital group also had lower GCS scores and higher Clinical Institute Withdrawal Assessment of Alcohol (CIWA-Ar) scores during their intensive care unit admission, possibly suggesting more severe alcohol withdrawal. There was no difference in intensive care unit length of stay, all-cause, in-hospital mortality, discharge disposition, or therapeutic adjuncts. Conclusions Combination therapy of phenobarbital plus benzodiazepines was associated with higher odds of requiring mechanical ventilation. Few patients received phenobarbital monotherapy. Additional studies are needed to better compare the effects of phenobarbital monotherapy versus benzodiazepines in neurocritical patients.