Bracken MB, Shepard MJ, Collins WF et al. A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury: results of the Second National Acute Spinal Cord Injury Study. New England Journal of Medicine 1990; 322: 1405-1411.
RHH Journal Club. February 16th, 2012. Dr Kirsty Parsons
Full-text article (if available)
Do patients with acute spinal-cord injury, treated with methylprednisolone (in doses higher than in NASCIS I) or naloxone, have improvements in their neurological function?
Multicenter. Randomised. Double blind. Placebo controlled trial.
- Patients with acute spinal cord injury, over the age of 13 years
- Randomized within 12 hours of the injury
- Block randomization to methylprednisolone (active or placebo) and naloxone (active and placebo)
- Methylprednisolone 30mg/kg bolus over 15 mins, infusion of 5.4mg/kg/hr for 23 hours
- Naloxone 5.4mg/kg, infusion 4mg/kg/hr for 23 hours
- Resulted in 3 regimen study (methylprednisolone, nalaxone or placebo)
- Neurological function (motor, pinprick and light touch) on admission, 6 weeks and at 6 months
- Secondary outcomes:
- Stratified according to whether drug received > or < 8 hours from time of injury
- Safety: wound infection; GI bleeding rates and ‘other’ complications
Did groups start with a similar prognosis?
Yes, mostly white, males aged between 13 and 34 years
Numbers involved: 487 randomized (80% received drug within time limits; 92% received it drug according to protocol dose regime)
Randomisation – block randomized in each centre in groups of 9
Each drug prepared as an active and a placebo and had own pump
All phases of study (preparation and administration of drugs, neurological examinations and statistical analyses carried in a “blinded fashion”
Confounding factorsconsidered and more stats done to ensure conclusions not influenced by assumptions of analysis of variance
Follow up: Almost complete follow up – of surviving patients 97.9% underwent neurological examination at 6 weeks and 96.5% at 6 months
a) Methylprednisolone, given within 8 hours of acute spinal cord injury, results in greater improvements of neurological function when compared to placebo
Caution as this is post hoc analysis – primary outcome was negative
b) Naloxone or methylprednisolone given longer than 8 hours after injury has no statistically significant improvement in neurological function
No significant differences in wound infections, GI bleeding or “other” complications
Take home message/application of this research:
- Methylprednisolone given within hours of an acute spinal cord injury may result in a greater neurological recovery but excess t-tests done without correction.
- May or may not be translated into a functional improvement.
- Naloxone in doses studied does not contribute to any significant neurological improvement