Propranolol in Traumatic Brain Injury
Primary Recommendation
Propranolol should be administered to patients with severe traumatic brain injury requiring ICU admission, starting within 24-48 hours of injury at a dose of 1 mg intravenous every 6 hours, as this intervention reduces mortality by approximately 60% while maintaining hemodynamic safety. 1, 2, 3
Evidence for Mortality Benefit
The Eastern Association for the Surgery of Trauma (EAST) guideline provides a conditional recommendation in favor of in-hospital β-blocker use after TBI, based on meta-analysis of 9 studies showing a pooled odds ratio of 0.39 (95% CI 0.27-0.56, p<0.0001) for mortality reduction. 1
Most recent high-quality evidence from 2025 demonstrates that propranolol administered within 48 hours of severe TBI reduces 30-day mortality from 30.77% to 22.7% (OR 0.66,95% CI 0.48-0.92, p=0.01) in a propensity-matched cohort of 762 patients. 3
A 2016 prospective study showed propranolol was independently associated with lower mortality after adjusting for confounders (adjusted OR 0.25, p=0.012). 2
Patient Selection Criteria
Administer propranolol to patients meeting ALL of the following criteria: 1, 2
- Severe TBI (Glasgow Coma Scale 3-8) or moderate TBI (GCS 9-12) requiring ICU admission 1, 2
- Admission within 24-48 hours of injury 2, 3
- Systolic blood pressure maintained >110 mmHg 1, 4
- No symptomatic bradycardia or hypotension 1
- ICU setting with continuous cardiovascular monitoring available 1
Dosing Protocol
Start propranolol at 1 mg intravenous every 6 hours within 24 hours of ICU admission, continuing for a minimum of 48 hours. 5, 2
- This low-dose regimen does not increase bradycardia or hypotensive events compared to controls 5
- Mean duration of therapy in successful protocols was 10±14 doses 5
- Propranolol is preferred over other beta-blockers because it is nonselective, centrally-acting (crosses blood-brain barrier), and available in both IV and oral formulations 1
Hemodynamic Safety Monitoring
Maintain systolic blood pressure >110 mmHg at all times, as even single episodes of hypotension (SBP <90 mmHg) markedly worsen neurological outcomes. 6, 4
- Have vasopressors (phenylephrine or norepinephrine) immediately available and use them rapidly if hypotension occurs 6
- Monitor heart rate hourly for the first 72 hours 5
- Paradoxically, propranolol-treated patients had FEWER bradycardia events (1.6 vs 5.8, p=0.05) compared to controls in prospective evaluation 5
Mechanisms of Benefit
Propranolol provides neuroprotection through multiple pathways beyond simple heart rate control: 7, 8
- Reduces catecholamine surge (norepinephrine decreased from 529 to 207 pg/ml, p<0.001) 8
- Improves cerebral perfusion and reduces neuroinflammation 7
- Decreases neural injury, cell death, and p-tau accumulation 7
- Attenuates TBI-induced immunodeficiency 7
- Provides cardioprotection by mitigating myocardial oxidative stress 7
Additional Clinical Benefits
Beyond mortality reduction, propranolol administration is associated with: 5, 3, 8
- Decreased ICU length of stay (10 vs 19.1 days, p=0.05) 5
- Reduced hospital length of stay (15.4 vs 30.4 days, p=0.02) 5
- Lower rates of neurosurgical intervention 3
- Fewer seizures 3
- Reduced cardiac arrest episodes 3
- Improved Glasgow Coma Scale scores by day 7 (GCS 13 vs 10, p=0.006) 8
Critical Pitfalls to Avoid
Do NOT withhold propranolol due to unfounded concerns about bradycardia or hypotension—the evidence shows these events are NOT increased with low-dose propranolol. 5
- The EAST guideline's conditional (rather than strong) recommendation reflects only the observational nature of existing studies, not safety concerns 1
- No recorded complications occurred with propranolol administration in prospective evaluation 5
- The recommendation is conditional on avoiding symptomatic bradycardia/hypotension, not on avoiding the medication itself 1
Contraindications
Absolute contraindications to propranolol in TBI: 1
- Symptomatic bradycardia (not asymptomatic low heart rate)
- Refractory hypotension despite vasopressor support
- Inability to maintain SBP >110 mmHg
- Lack of ICU-level cardiovascular monitoring
Comparison to Other Beta-Blockers
While propranolol has the most evidence, consideration may be given to alternative agents in specific circumstances: 1
- Labetalol (mixed alpha/beta receptor blocker) as alternative
- Esmolol (rapidly metabolized IV agent) for more titratable control
- However, propranolol remains the best-studied agent with the most robust mortality data 1, 2, 3
Integration with Overall TBI Management
Propranolol should be incorporated into comprehensive severe TBI management alongside: 4