Steroids in Traumatic Brain Injury
Corticosteroids should NOT be used in the management of traumatic brain injury, as they increase mortality without improving functional outcomes. 1
Evidence Against Steroid Use
FDA Drug Label Warning
The FDA label for methylprednisolone explicitly states: "High doses of systemic corticosteroids, including methylprednisolone sodium succinate, should not be used for the treatment of traumatic brain injury." 1 This warning is based on a multicenter, randomized, placebo-controlled study showing increased mortality at both 2 weeks and 6 months in patients with cranial trauma treated with methylprednisolone. 1
The CRASH Trial Evidence
The landmark Corticosteroid Randomization After Significant Head injury (CRASH) trial definitively demonstrated that corticosteroids increase mortality in TBI patients, with a relative risk of death of 1.18 (95% CI: 1.09-1.27). 2 This practice-changing trial "debunked the decades old practice of corticosteroid treatment after TBI." 2
Meta-Analysis Findings
- High-dose steroids: Pooled relative risk of death is 1.14 (95% CI: 1.06-1.21), demonstrating clear harm 3
- Short-term use: Pooled relative risk of death is 1.15 (95% CI: 1.07-1.23) 3
- The largest Cochrane review (20 trials, 12,303 participants) found no benefit and potential harm, with the CRASH trial showing significant mortality increase 4
Current Guideline Recommendations
The Brain Trauma Foundation guidelines, based on the CRASH trial findings, recommend against giving steroids in TBI. 5 This represents a complete reversal from historical practice patterns. 2
Potential Exception: Delayed Vasogenic Edema
While the standard recommendation is clear, emerging evidence suggests a very narrow potential exception that requires further validation:
Delayed Pericontusional Edema (Investigational)
- Timing: 5-7 days post-injury (not acute phase) 6, 5
- Population: Mild-to-moderate TBI with cerebral contusions and delayed vasogenic edema 6, 5
- Dosing: Low-dose dexamethasone 12 mg/day tapered over 5-10 days 6, 5
- Rationale: Vasogenic edema (delayed phase) may respond differently than cytotoxic edema (acute phase) 6, 5
Critical caveat: This approach is based only on small retrospective case series (9 and 27 patients) and directly contradicts FDA warnings and established guidelines. 6, 5 These studies explicitly acknowledge they are the "first" and "third" to document this approach, indicating extremely limited evidence. 6, 5
Why Steroids Fail in Acute TBI
Mechanism of Harm
- Biphasic edema: TBI causes initial cytotoxic edema followed by vasogenic edema 6
- Wrong timing: All major trials (including CRASH) used steroids during the acute cytotoxic phase when they are ineffective 6, 5
- Immunosuppression: Increased infection risk without offsetting benefit 4, 3
- No ICP benefit: Steroids fail to lower intracranial pressure in severe TBI 7
Adverse Effects
- Increased mortality (primary concern) 1, 4, 3
- Infections (pooled RR 1.04 for high-dose) 3
- Gastrointestinal bleeding (pooled RR 1.26 for high-dose) 3
- Hyperglycemia and metabolic complications 1
Clinical Algorithm
For acute TBI (first 48-72 hours):
- Do NOT administer corticosteroids regardless of severity 1, 4
- This applies to mild, moderate, and severe TBI 5, 3
For delayed deterioration (>5 days post-injury):
- Standard care remains NO steroids per FDA and guidelines 1, 5
- If considering investigational low-dose approach for delayed vasogenic edema: requires documented contusions, clear delayed deterioration, and absence of severe initial injury 6, 5
- This remains experimental and contradicts established guidelines 6, 5
Common Pitfalls to Avoid
- Do not extrapolate from spinal cord injury: The NASCIS protocols for methylprednisolone in spinal cord injury do NOT apply to TBI 2
- Do not use "stress dose" steroids: Even low-dose protocols in the acute phase show no benefit for death or disability (pooled RR 0.95) 3
- Do not confuse historical practice with current evidence: Pre-CRASH era recommendations are obsolete 2