Second US National Acute Spinal Cord Study (NASCIS 2) compared 24 hours
of methylprednisolone (MP) with placebo in 333 patients with acute spinal
At six months, patients who had received steroids within eight hours of
injury appeared to have greater improvement in motor function, and in
sensation to pinprick and touch. Similar results were reported in a Japanese
trial of the same regimen.2 Some doctors believe these
results are sufficient evidence of benefit to justify treating spinal
cord injury patients with corticosteroids, whereas others do not.3
Those who are unconvinced argue that the evidence of benefit is from a
sub-group analysis in a relatively small trial. Without new evidence
from a much larger randomised-controlled trial it is unlikely that clinical
uncertainty about corticosteroids in spinal cord injury will be resolved.
So what are the lessons for the CRASH trial?
The CRASH trial
has been designed to determine reliably the effects of short-term corticosteroid
infusion on death and on disability following significant head injury.
With 1200 patients recruited, the CRASH trial is already the largest
randomised controlled trial in head injury ever conducted. Over
the next five years the trial aims to recruit a total of 20,000 patients.
A really large trial like CRASH will provide reliable evidence about
the effectiveness of corticosteroids in head injury, so that on-going
clinical uncertainty, such as for corticosteroids in spinal cord injury,
will be considerably reduced.
There are many reasons
for conducting the CRASH trial now:
CRASH trial is currently recruiting patients in 66 centres in 20 countries
and we expect many more centres to join the trial over the next few
years. The enthusiastic response to the CRASH trial from emergency
physicians, neurosurgeons, and intensive care physicians, signals the
strong international commitment to resolving uncertainties around the
effectiveness of interventions in neurotrauma. Management of the
increasing global burden of head injury must be addressed in a similar
way to that adopted so successfully in ischaemic heart disease.
Prevention and the understanding of basic pathophysiology must be complemented
by well-conducted large simple trials.
1. Bracken MB, Shepard MJ, Collins WF, et al. A randomised controlled
trial of methylprednisolone or naloxone in the treatment of acute spinal
cord injury. N Eng J Med 1990;322:1405-11.
2. Otani K, Abe H, Kadoya S, et al. Beneficial effect of methylprednisolone
sodium succinate in the treatment of acute spinal cord injury (translation
of Japanese). Sekitsui Sekizui J 1994;7:633-47.
3. Short DJ,
El Masry WS, Jones PW. High dose methylprednisolone in the management
of acute spinal cord injury - a systematic review from a clinical perspective.
Spinal Cord 2000;38:273-286.