What is the role of corticosteroids (such as methylprednisolone) in the treatment of significant head injuries in patients of all ages?

CRASH Trial and Corticosteroids in Head Injury

Do not use corticosteroids (including methylprednisolone) in patients with traumatic brain injury—the CRASH trial definitively demonstrated increased mortality with corticosteroid treatment, and current guidelines strongly recommend against their use.

Evidence from the CRASH Trial

The CRASH (Corticosteroid Randomisation After Significant Head Injury) trial was a landmark randomized controlled trial that fundamentally changed the management of traumatic brain injury (TBI):

• The trial enrolled 10,008 adults with head injury and Glasgow Coma Scale (GCS) ≤14 within 8 hours of injury, randomizing them to 48-hour methylprednisolone infusion versus placebo 1, 2

• Death within 2 weeks occurred in 21.1% of the corticosteroid group versus 17.9% in the placebo group (relative risk 1.18,95% CI 1.09-1.27, p=0.0001) 2

• At 6 months, mortality remained higher in the corticosteroid group: 25.7% versus 22.3% (relative risk 1.15,95% CI 1.07-1.24, p=0.0001) 1

• The risk of death or severe disability at 6 months was also increased: 38.1% versus 36.3% (relative risk 1.05,95% CI 0.99-1.10, p=0.079) 1

• The harmful effect of corticosteroids did not differ by injury severity or time since injury, meaning steroids were harmful across all TBI severities 1, 2

Current Guideline Recommendations

Based on the CRASH trial findings, professional societies have issued clear recommendations:

• The Brain Trauma Foundation recommends against giving steroids in traumatic brain injury with a Grade 1- (strong negative recommendation) and strong agreement among experts 3, 4

• The Society of Critical Care Medicine and European Society of Intensive Care Medicine (2017) suggest against the use of corticosteroids in major trauma (conditional recommendation, low quality of evidence) 5

• High-dose steroids are specifically listed among therapies to be avoided in critically ill patients 3

• The FDA does not approve methylprednisolone for TBI treatment 3

Why Corticosteroids Fail in TBI

The meta-analysis underlying these guidelines examined 19 trials (n=12,269) investigating corticosteroids in multiple trauma:

• There was no mortality benefit regardless of dose: low-dose corticosteroids showed RR 1.03 (95% CI 0.86-1.22) and high-dose showed RR 0.98 (95% CI 0.81-1.18) 5

• Corticosteroids did not increase gastrointestinal bleeding (RR 1.22,95% CI 0.90-1.65) or superinfection (RR 0.93,95% CI 0.80-1.08), but the lack of benefit combined with potential for harm led to the recommendation against use 5

Critical Pitfalls to Avoid

• Do not extrapolate from spinal cord injury protocols: The American Association of Neurological Surgeons explicitly advises against extrapolating from spinal cord injury treatment protocols (such as NASCIS methylprednisolone protocols) to TBI management—these are completely different conditions 3, 4

• Do not confuse TBI management with tumor-associated edema or spinal cord compression, where dexamethasone has established benefits 3

• "Stress dose" steroids in acute TBI show no benefit for death or disability, with a pooled relative risk of 0.95 4

Alternative Management Strategies for Cerebral Edema in TBI

Instead of corticosteroids, use these evidence-based approaches:

First-line interventions:

• Ensure proper ventilation with tracheal intubation and mechanical ventilation with end-tidal CO₂ monitoring to maintain appropriate CO₂ levels 3
• Consider external ventricular drainage for persisting intracranial hypertension after sedation and correction of secondary brain insults 3
• Maintain serum glucose concentration between 8-10 mmol/L (144-180 mg/dL) in severe TBI patients 3, 6

Second-line interventions:

• Consider decompressive craniectomy to control intracranial pressure in cases of refractory intracranial hypertension after multidisciplinary discussion 3
• Avoid prolonged hypernatremia when attempting to control intracranial pressure 3

Clinical Impact

The CRASH trial's findings have had global significance:

• The trial demonstrated that corticosteroids should not be used routinely in the treatment of head injury, reversing decades of practice 1

• Studies using the CRASH prognosis calculator in patients treated with modern ICP-targeted therapy show that the calculator overestimates mortality risk (predicted 44.6% vs actual 4.3%) and unfavorable outcome (predicted 69.3% vs actual 42.6%), suggesting modern management strategies are superior to historical approaches 7