B55-25 Phenobarbital as an Adjunct for Weaning Continuous Sedation in Mechanically Ventilated Patients: A Case Series of Six Patients

Abstract Rationale Weaning from continuous sedation remains a significant challenge in mechanically ventilated patients, with 15-40% experiencing difficult or prolonged weaning despite advances in sedation protocols. Prolonged exposure to continuous sedatives leads to tolerance, physiologic dependence, and withdrawal, complicating ventilator liberation and prolonging intensive care unit (ICU) stays. Phenobarbital, a long-acting with dual GABA-ergic and anti-glutamatergic mechanisms, offers theoretical advantages for facilitating sedation weaning through sustained coverage without continuous infusion, especially in patients with substance use disorder who require higher doses of sedation to facilitate ventilation. However, data on phenobarbital use for sedation weaning in mechanically ventilated patients remains limited. We describe our experience using phenobarbital to facilitate weaning. Methods We present a case series of six mechanically ventilated participants admitted to the Medical Intensive Care Unit (April-September 2025) who received intravenous phenobarbital for sedation weaning after failing standard of care protocols (SOC). SOC include dexmedetomidine, fentanyl and propofol, with midazolam and ketamine used as add-on to the regimens whenever appropriate (Table 1). Primary outcome was time from phenobarbital initiation to successful extubation (remaining extubated ≥48 hours). Patients were stratified by weaning difficulty: 3 versus ≥3 spontaneous awakening/breathing trial (SAT/SBT) attempts. Descriptive statistics used given small sample size. Results Six patients (median age 36 years; 67% male) with opioid use disorder (100%), alcohol use (33%), and cocaine use (33%) were included. Participants were intubated due to respiratory failure (n = 4) or inability to protect airways (n = 2). Median mechanical ventilation duration before phenobarbital was 5 days (IQR 6). Failure to extubate was due to agitation while on standard weaning strategy. Median prior SAT/SBT attempts was 3 days (IQR 3). All patients were successfully extubated with median time from phenobarbital to extubation of 1 day (IQR 2). Median cumulative phenobarbital dose was 520 mg (IQR 519) or 9.2mg/kg, in the 3 SAT/SBT group versus 910 mg (IQR 420) or 11.2mg/kg in the ≥3 SAT/SBT group. The difficult weaning group had longer pre-phenobarbital ventilation (9 vs 3 days) and longer ICU stays (13.3 vs 4.3 days). No phenobarbital-related adverse events occurred; no patient required reintubation. Conclusions Adjunctive phenobarbital enabled rapid, safe ventilator liberation in patients who failed conventional sedation weaning strategies. This represents a novel clinical application beyond phenobarbital's traditional use for alcohol withdrawal, with potential to reduce ICU length of stay in patients with high sedation requirements. Prospective studies are needed to validate these findings and establish standardized protocols. This abstract is funded by: None