What is the role of propranolol (beta-blocker) in preventing neurostorming in patients with Traumatic Brain Injury (TBI)?

Propranolol for Prevention of Neurostorming in Traumatic Brain Injury

Propranolol is conditionally recommended for use in patients with traumatic brain injury (TBI) to prevent neurostorming and improve outcomes, particularly in reducing mortality. 1

Mechanism and Benefits

Propranolol helps prevent neurostorming after TBI through several mechanisms:

• Blocks excessive sympathetic activity that occurs after brain injury
• Reduces catecholamine levels (norepinephrine, epinephrine, dopamine)
• Crosses the blood-brain barrier due to its lipophilic properties
• Prevents impairment of cerebral autoregulation
• Inhibits interleukin-6 (IL-6) upregulation, reducing neuroinflammation 2

Evidence for Efficacy

The Eastern Association for the Surgery of Trauma guideline provides a conditional recommendation for beta-blockers in TBI, with propranolol being the most frequently studied agent. Meta-analysis of cohort studies showed:

• 61% reduction in adjusted odds of in-hospital mortality (pooled OR 0.39,95% CI: 0.27-0.56) 1
• In a subgroup analysis, propranolol specifically was associated with lower mortality while other beta-blockers did not show significant mortality benefits 1

Recent prospective studies further support propranolol's benefits:

• Early propranolol administration (within 24 hours) was independently associated with lower mortality (adjusted OR 0.25) 3
• Propranolol reduced catecholamine levels by day 7 (norepinephrine 206.87 vs. 529.33 pg/ml, epinephrine 69.00 vs. 190.73 pg/ml, dopamine 32.90 vs. 78.00 pg/ml; all P<0.001) 4
• Improved Glasgow Coma Scale scores by day 7 (13 vs. 10, P=0.006) 4
• Improved cerebral perfusion (152% improvement vs. placebo) and reduced cerebral hypoxia (24.2% reduction) 5

Dosing and Administration

Based on the available evidence, the following dosing regimen is recommended:

• Start within 24 hours of TBI (ideally within 12 hours of ICU admission)
• Initial dose: 1 mg IV every 6 hours 6, 3
• Continue for a minimum of 48 hours 6
• Monitor for adverse effects, particularly bradycardia and hypotension

Safety Considerations

Low-dose propranolol appears to be safe in TBI patients:

• No increase in hypotensive events compared to controls 6
• May actually have fewer bradycardia episodes than controls (1.6 vs. 5.8 events, P=0.05) 6
• No significant differences in rates of congestive heart failure or bronchospasm 1

Implementation Algorithm

1. Patient Selection:

   • Patients with moderate-to-severe TBI (Head AIS score 3-5 or GCS ≤12)
   • No contraindications to beta-blockers (severe bradycardia, heart block, cardiogenic shock)

2. Timing:

   • Initiate within 24 hours of injury, after hemodynamic stabilization

3. Monitoring:

   • Hourly heart rate and blood pressure for first 72 hours
   • Daily neurological assessment (GCS)
   • Monitor for signs of improved neurostorming (reduced tachycardia, hypertension, tachypnea, hyperthermia)

4. Duration:

   • Minimum 48 hours
   • Consider continuing throughout ICU stay based on clinical response

Clinical Pitfalls and Caveats

• Avoid in patients with:

  • Severe bradycardia (HR <50 bpm)
  • Hypotension (SBP <90 mmHg)
  • High-grade heart block
  • Severe bronchospastic disease

• Careful monitoring required in:

  • Elderly patients
  • Patients with pre-existing cardiac disease
  • Patients on other negative chronotropic medications

• Evidence limitations:

  • Most studies are observational rather than randomized controlled trials
  • Optimal duration of therapy not well established
  • Long-term functional outcomes not thoroughly studied

While the evidence quality is rated as low to very low, the consistent mortality benefit across multiple studies and favorable safety profile support the use of propranolol in TBI patients to prevent neurostorming, particularly when initiated early after injury.