Roberts I, Yates D, Sandercock P et al. Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial. Lancet 2004; 364: 1321-1328.
RHH Journal Club. February 16th, 2012. Dr Pavan Kumar
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Do patients with acute head injury, treated with methylprednisolone have improvements in mortality or neurological outcome?
Corticosteroids have been used to treat head injuries for more than 30 years. In 1997, findings of a systematic review suggested that these drugs reduce risk of death by 1–2%. The CRASH trial—a multicentre international collaboration—aimed to confirm or refute such an effect by recruiting 20 000 patients. In May, 2004, the data monitoring committee disclosed the unmasked results to the steering committee, which stopped recruitment.
10 008 adults with head injury and a Glasgow coma score (GCS) of 14 or less within 8 h of injury were randomly allocated 48 h infusion of corticosteroids (methylprednisolone) or placebo. Primary outcomes were death within 2 weeks of injury and death or disability at 6 months. Prespecified subgroup analyses were based on injury severity (GCS) at randomisation and on time from injury to randomisation. Analysis was by intention to treat. Effects on outcomes within 2 weeks of randomisation are presented in this report.
Compared with placebo, the risk of death from all causes within 2 weeks was higher in the group allocated corticosteroids (1052 [21·1%] vs 893 [17·9%] deaths; relative risk 1·18 [95% CI 1·09–1·27]; p=0·0001). The relative increase in deaths due to corticosteroids did not differ by injury severity (p=0·22) or time since injury (p=0·05).
There is no reduction in mortality with methylprednisolone in the 2 weeks after head injury. The cause of the rise in risk of death within 2 weeks is unclear.
This clinical trial carries a lot of credibility as it is large, multi-centred, blinded, randomised control study. The study has a few drawbacks
- It did not describe the general management of the patients like what strategies were being used/adhered for neuroprotection and was everyone adhering to them strictly.
- Mortality rates vary between different countries, would it have influenced the overall mortality?
- No clear explanation of why the mortality is high in treatment group. Steroids induced hyperglycaemia and secondary adrenal deficiency contributed to higher mortality!!!!
- Early closure of trial resulted in apparent excess of death (3%) but overall mortality in meta-analysis is 2%.
Take home message
High dose steroids increase mortality so do avoid them in patients with significant head injury.