Beta-Blocker Therapy in Severe Traumatic Brain Injury: A Prospective Randomized Controlled Trial

World J Surg. 2020 Jun;44(6):1844-1853. doi: 10.1007/s00268-020-05391-8.


Background: Observational studies have demonstrated improved outcomes in TBI patients receiving in-hospital beta-blockers. The aim of this study is to conduct a randomized controlled trial examining the effect of beta-blockers on outcomes in TBI patients.

Methods: Adult patients with severe TBI (intracranial AIS ≥ 3) were included in the study. Hemodynamically stable patients at 24 h after injury were randomized to receive either 20 mg propranolol orally every 12 h up to 10 days or until discharge (BB+) or no propranolol (BB-). Outcomes of interest were in-hospital mortality and Glasgow Outcome Scale-Extended (GOS-E) score on discharge and at 6-month follow-up. Subgroup analysis including only isolated severe TBI (intracranial AIS ≥ 3 with extracranial AIS ≤ 2) was carried out. Poisson regression models were used.

Results: Two hundred nineteen randomized patients of whom 45% received BB were analyzed. There were no significant demographic or clinical differences between BB+ and BB- cohorts. No significant difference in in-hospital mortality (adj. IRR 0.6 [95% CI 0.3-1.4], p = 0.2) or long-term functional outcome was measured between the cohorts (p = 0.3). One hundred fifty-four patients suffered isolated severe TBI of whom 44% received BB. The BB+ group had significantly lower mortality relative to the BB- group (18.6% vs. 4.4%, p = 0.012). On regression analysis, propranolol had a significant protective effect on in-hospital mortality (adj. IRR 0.32, p = 0.04) and functional outcome at 6-month follow-up (GOS-E ≥ 5 adj. IRR 1.2, p = 0.02).

Conclusion: Propranolol decreases in-hospital mortality and improves long-term functional outcome in isolated severe TBI. This randomized trial speaks in favor of routine administration of beta-blocker therapy as part of a standardized neurointensive care protocol.

Level of evidence: Level II; therapeutic.

Study type: Therapeutic study.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use*
  • Adult
  • Brain Injuries, Traumatic / drug therapy*
  • Female
  • Glasgow Outcome Scale
  • Hospital Mortality
  • Humans
  • Male
  • Middle Aged
  • Propranolol / therapeutic use*
  • Prospective Studies
  • Young Adult


  • Adrenergic beta-Antagonists
  • Propranolol