The devil’s in the detail. A cautionary tale of steroids and spinal cord injury

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?

Study design:

Multicenter. Randomised. Double blind. Placebo controlled trial.

Methodology (PICO)

Population:

  • Patients with acute spinal cord injury, over the age of 13 years
  • Randomized within 12 hours of the injury

Intervention/Control:

  • 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)

Primary Outcome:

  • 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

Validity

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

Blinded

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

 Results

Primary outcome:

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

Secondary outcomes:

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

 

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