What are the implications of the CRASH (Corticosteroid Randomisation After Significant Head injury) 1 study results on the treatment of acute significant head injuries?

CRASH-1 Study Results: Corticosteroids Increase Mortality in Traumatic Brain Injury

The CRASH-1 trial definitively demonstrated that corticosteroids (methylprednisolone) increase mortality in traumatic brain injury patients and should never be used for this indication. 1, 2

Key Findings from CRASH-1

The landmark CRASH 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

Mortality Outcomes

• 14-day mortality: 21.1% in the corticosteroid group versus 17.9% in placebo (relative risk 1.18,95% CI 1.09-1.27, p=0.0001) 2
• 6-month mortality: 25.7% in the corticosteroid group versus 22.3% in placebo (relative risk 1.15,95% CI 1.07-1.24, p=0.0001) 1
• The increased mortality risk was consistent across all injury severities and time intervals from injury 1, 2

Disability Outcomes

• Death or severe disability at 6 months occurred in 38.1% of corticosteroid-treated patients versus 36.3% of placebo patients (relative risk 1.05,95% CI 0.99-1.10, p=0.079) 1

Current Clinical Practice Guidelines

All major guidelines now strongly recommend AGAINST corticosteroid use in traumatic brain injury with Grade 1- (strong negative recommendation). 3

Specific Recommendations

• The Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017 guidelines conditionally recommend against corticosteroids in major trauma, citing the CRASH trial as practice-changing evidence that "debunked the decades old practice of corticosteroid treatment after TBI" 4
• High-dose steroids are explicitly listed among therapies to be avoided in critically ill patients 3
• Meta-analysis of 19 trials (n=12,269) in trauma patients showed no mortality benefit (RR=1.00,95% CI 0.89-1.13) regardless of dose 4

Historical Context and Lessons Learned

The CRASH trial serves as a cautionary tale about translating observational data into clinical practice. 4

Pre-CRASH Evidence

• Prior to CRASH, a meta-analysis suggested corticosteroids might reduce mortality by 1-2%, leading to widespread use for over 30 years 5, 2
• The systematic review that prompted the CRASH trial showed apparent benefit but was likely influenced by selection bias in observational studies 4

The Parallel to Beta-Blockers

• Current guidelines draw explicit parallels between the CRASH experience and ongoing beta-blocker research in TBI, emphasizing the need for large randomized trials before adopting therapies based on observational data alone 4
• Despite compelling observational data (OR 0.39 for mortality with beta-blockers), experts remain cautious given how dramatically CRASH contradicted prior beliefs 4

Critical Pitfalls to Avoid

Do not confuse TBI management with other neurological conditions where steroids have proven benefit. 3

• Dexamethasone remains appropriate for tumor-associated cerebral edema and spinal cord compression, but these mechanisms differ fundamentally from traumatic brain injury 3
• The mechanism of harm from corticosteroids in TBI remains unclear, but increased infection risk, hyperglycemia, and gastrointestinal bleeding are documented concerns 3

Alternative Management Strategies for Cerebral Edema in TBI

Since corticosteroids are contraindicated, focus on evidence-based alternatives: 3

First-Line Interventions

• Ensure proper ventilation with tracheal intubation and mechanical ventilation, monitoring end-tidal CO2 to maintain appropriate levels 3
• Consider external ventricular drainage for persistent intracranial hypertension after sedation and correction of secondary brain insults 3
• Maintain serum glucose between 8-10 mmol/L (144-180 mg/dL), as both hyperglycemia and hypoglycemia worsen outcomes 3, 6

Second-Line Interventions

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

Prognostic Calculator Limitations

The CRASH trial database was used to develop a prognosis calculator, but this tool significantly overestimates mortality and poor outcomes in patients receiving modern ICP-targeted therapy. 7

• In one study, the calculator predicted 44.6% mortality versus actual 4.3% mortality (absolute risk reduction 33.1%) 7
• The calculator should not be used for treatment decisions in individual patients, as it may lead to inappropriate withdrawal of care 7