Research Summary

Propranolol Reduces Sedative Needs in Mechanically Ventilated Patients

Miranda Manier, BA

Key Highlights

  • Enteral propranolol significantly reduced sedative requirements in mechanically ventilated patients.
  • Sedation scores were more frequently within target in the propranolol group.
  • No increase in adverse events or mortality was observed with propranolol.
  • Propranolol offers a low-cost, accessible strategy to preserve sedative supplies during drug shortages.

In a multicenter, randomized controlled trial, James Downar, MD, MHSc, and colleagues found that propranolol use in mechanically ventilated patients led to a significantly greater reduction in sedative requirements compared with standard care. Patients receiving propranolol achieved target sedation more consistently without an increase in adverse events or mortality.

During the COVID-19 pandemic, unprecedented surges in mechanical ventilation led to critical shortages of sedatives such as propofol and midazolam worldwide. While dexmedetomidine and benzodiazepines can be alternatives, their use is often limited by cost, side effect profile, or supply constraints. Agitation and delirium in critically ill patients are closely linked to sympathetic hyperactivity, suggesting a therapeutic role for beta-blockade. Propranolol, a nonselective beta-adrenergic antagonist with central nervous system penetration, has shown sedative-sparing benefits in observational studies, but its efficacy had not been tested prospectively in this population.

The investigators conducted an open-label, parallel-arm randomized controlled trial across three Canadian academic hospitals. Adult ICU patients anticipated to require mechanical ventilation beyond 48 hours and needing high-dose sedatives were eligible. Patients randomized to the intervention arm received enteral propranolol 20–60 mg every 6 hours, titrated to effect, while all patients received protocol-driven sedation with propofol or midazolam. The primary endpoint was the change in daily sedative dose from baseline to day 3. Secondary endpoints included the proportion of sedation scores within target and adverse event rates.

Between January 2021 and October 2022, 72 patients were enrolled, with 71 included in analyses. The cohort was predominantly male (69%) with a mean age of 54 years, and most were admitted for COVID-19 or non-COVID pneumonia. Propranolol was administered for a mean of 10 days, with an average daily dose of 90 mg. By day 3, the propranolol group demonstrated a significantly greater reduction in sedative requirements (54% vs 34%; P = .048) compared with controls. Additionally, target sedation scores were achieved more often in the propranolol group (48% vs 35%; P < .0001). No significant differences were found in opioid requirements, delirium incidence, mortality, or adverse event rates. Episodes of bradycardia were not increased in the propranolol group.

 “Propranolol is an inexpensive drug that effectively lowered the need for sedatives in critically ill patients managed in the COVID-19 pandemic,” Downar and colleagues concluded. “Propranolol may help preserve limited supplies of sedatives while achieving target sedation.”

Reference:
Downar J, Lapenskie J, Kanji S, et al. Propranolol as an anxiolytic to reduce the use of sedatives for critically ill adults receiving mechanical ventilation (PROACTIVE): an open-label randomized controlled trial. Crit Care Med. 2025;53(2):e257-e268. doi:10.1097/CCM.0000000000006534