What is the role of hydrocortisone (cortisol) in patients with traumatic brain injury (TBI)?

Hydrocortisone in Traumatic Brain Injury: Not Recommended

Hydrocortisone is not recommended for patients with traumatic brain injury as it increases mortality and provides no benefit for neurological outcomes. 1

Evidence Against Corticosteroid Use in TBI

The evidence against corticosteroid use in TBI is strong and comes from high-quality research:

• The CRASH trial (Corticosteroid Randomization After Significant Head injury) conclusively demonstrated that corticosteroids increase mortality in TBI patients, debunking decades of previous practice 1
• A systematic review of 19 trials (n=12,269) found no mortality benefit from corticosteroids in trauma patients (RR=1.00,95% CI 0.89-1.13) 1
• The Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) made a conditional recommendation against corticosteroids for major trauma due to potential for clinically important side effects 1

Critical Illness-Related Corticosteroid Insufficiency (CIRCI) in TBI

While approximately 50% of patients with moderate or severe TBI may experience at least transient adrenal insufficiency 2, the evidence does not support routine corticosteroid supplementation:

• Factors associated with adrenal insufficiency in TBI include:

  • Younger age
  • Greater injury severity
  • Early ischemic insults
  • Use of etomidate and metabolic suppressive agents (high-dose pentobarbital or propofol) 2

• Two trials examined hydrocortisone specifically in trauma-associated CIRCI:

  1. In multiple trauma patients with CIRCI (n=113), hydrocortisone prevented hospital-acquired pneumonia (HR 0.47,95% CI 0.25-0.86) and increased mechanical ventilation-free days 1
  2. In head trauma patients with CIRCI (n=267), hydrocortisone showed no significant effect on hospital-acquired pneumonia (HR 0.80,95% CI 0.56-1.14) 1

Dosing Considerations

If considering corticosteroids for other indications in TBI patients, dose matters:

• High-dose corticosteroids are associated with increased mortality (RR 1.14,95% CI 1.06-1.21) 3
• Short-term use is also associated with increased mortality (RR 1.15,95% CI 1.07-1.23) 3
• Low-dose and longer-term use showed no significant effect on mortality or severe disability 3

Management Algorithm for TBI Patients

Instead of corticosteroids, follow this evidence-based approach:

1. Initial Assessment:

   • Evaluate TBI severity using Glasgow Coma Scale, particularly motor response, pupillary size and reactivity 1
   • Secure airway for patients with GCS ≤8 or deteriorating neurological status

2. Hemodynamic Management:

   • Maintain systolic blood pressure >110 mmHg and MAP >80 mmHg
   • Use vasopressors (phenylephrine, norepinephrine) to rapidly correct hypotension
   • Avoid hypotension as it's a risk factor for brain ischemia

3. Ventilation Parameters:

   • Maintain PaO₂ ≥97.5 mmHg
   • Target normoventilation (PaCO₂ 34-38 mmHg)
   • Use low tidal volume ventilation (6 ml/kg) with moderate PEEP
   • Avoid hyperventilation unless signs of imminent cerebral herniation

4. Intracranial Hypertension Management:

   • First-line: Head elevation at 20-30°, adequate sedation and analgesia, maintaining euvolemia, treating fever and seizures
   • Second-line: CSF drainage via external ventricular drain and osmotic therapy
   • Third-line: Consider decompressive craniectomy for refractory intracranial hypertension

5. Sedation Management:

   • Propofol is preferred for patients with intracranial bleeding due to its ability to decrease intracranial pressure 4
   • Midazolam can be used for hemodynamic stability with longer duration of action
   • Avoid barbiturates, bolus midazolam, or bolus opioids due to risk of hypotension

Monitoring Considerations

• Perform regular neurological assessments to track recovery and detect complications
• Consider continuous EEG monitoring for detecting nonconvulsive seizure activity
• Monitor cortisol levels in intubated TBI patients, particularly those receiving high-dose pentobarbital or propofol 2

Future Research Directions

Despite the current evidence against routine corticosteroid use in TBI, some researchers suggest that stress-dose hydrocortisone might have a role in specific situations:

• The CORTI-TC trial is investigating whether hydrocortisone with fludrocortisone in TBI patients with corticosteroid insufficiency prevents hospital-acquired pneumonia and improves long-term recovery 5
• Some researchers hypothesize that hydrocortisone's mineralocorticoid properties may reduce hyponatremia and brain swelling, and it might restore a balanced inflammatory response rather than inducing immunosuppression 6

However, until high-quality evidence demonstrates clear benefits, corticosteroids should not be used routinely in TBI management.