Neurosurgery notes/Trauma/Management of trauma/Non surgical/Steroids in non-surgical

Steroids in non-surgical

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Non surgical

General

  • Not useful in post traumatic cytotoxic cerebral oedema
    • Only useful for vasogenic cerebral oedema
  • High-dose methylprednisolone is associated with increased mortality.
  • Non-glucocorticoid steroids (e.g. 21-aminosteroids, AKA lazaroids, including tirilazad) and the synthetic glucocorticoid triamcinolone have also failed to show overall benefit.

Advantage (mainly in experimental models)

  • Restoration of altered vascular permeability in brain oedema
  • Reduction of cerebrospinal fluid production
  • Attenuation of free radical production

Disadvantage

  • Significant side effects may occur with steroids, including
    • Coagulopathies,
    • Hyperglycaemia with its undesirable effect on cerebral oedema and
    • Increased incidence of infection (due to immunosuppression).

Evidence

  • Alderson et al., 1997 metaanalysis
    • No evidence for a beneficial effect of steroids to improve outcome in TBI patients.
  • CRASH 1 trial
    • The study was halted after approximately 62 months, prior to reaching full enrollment, when the Data Monitoring Committee’s interim analysis showed clear deleterious effect of treatment on survival.
    • The deleterious effect of steroids was not different across groups stratified by injury severity.
    • Mortality at 2
      • Weeks Severe TBI Treatment: 39.8% vs. placebo 34.8% RR 1.14, 95% CI 1.05 to 1.23, p=0.0013. (calculated for this report based on counts provided by study authors)
      • All Patients Treatment 21.1% vs. placebo 17.9%
    • The deleterious effect of steroids was not different across groups stratified by injury severity

Steroids in head injury

  • CRASH trial is the large multi-centre international RCT looking at effect of methylprednisolone on risk of death and disability after head injury.
  • Placebo-controlled randomized trial (PRCT)
      • Class of evidence
      I
      Randomization
      Methyl prednisolone infusion versus placebo
      Number of patients
      10,008
      Follow-up
      Primary outcomes:
      - Death within 2 weeks of injury
      - Death and disability at 6 months
      Secondary outcomes: None
      Percentage of patients followed up at each stage?
      - 100% at 2 weeks
      - 96.7% at 6 months
      Number of centres
      239 centres in 49 countries worldwide
      Stratification
      Presence or absence of generalized motor seizures
    • Results
        • Outcome
        Methyl prednisolone group
        Placebo group
        Statistical significance
        Death within 2 weeks
        21.1%
        17.9%
        p = 0.001
        Death at 6 months
        25.7%
        22.3%
        p = 0.0001
        Disability at 6 months
        Severe 11.9%
        Moderate 17.6%
        Severe 13.6%
        Moderate 16.9%
        None