Recently, I reviewed a pediatric spinal trauma case. The recommendation for steroids was the most controversial part of the case. One service recommended it, another didn’t. One service from another hospital where the patient was to be transferred recommended it, but another service at the same hospital adamantly was opposed to it.
So what’s the story?
Well, steroids became the standard of care in treatment of acute spinal cord injury in 1992 after the NASCIS (National Acute Spinal Cord Injury Study) II trial established that high-dose methylprednisolone (30mg/kg bolus, then a 5.4mg/kg drip over 23 hours) when given within 8 hours of spinal cord injury showed statistically significant improvement of motor function at 6 months when compared to naloxone or placebo. Simple, right? Nope. So… NASCIS II was actually a negative study. Level 1 evidence: there was no statistically significant improvement in the three groups at the 1-year mark. However, posthoc analysis of steroids given at the 8-hour mark (arbitrary number) revealed improvement. Hmm. Let’s keep in mind that this is no longer considered level 1 evidence as posthoc analysis is considered substantial bias. What about the other NASCIS trials? The NASCIS I trial in which high-dose methylprednisolone (100mg bolus, followed by 25mg q 6 hr x10d versus 1000mg bolus, then 250mg q6 hr x10d) did not show any significant difference in neurological outcome in 1 year. There was, however, a statistically significant increase in wound infections. The NASCIS III trial compared meythlprednisolone (initiated within 8 hours since this was now considered the standard of care) given for 24 hours and 48 hours and also tirilazad, a nonglucocorticoid 21-aminosteroid. Again, this was a negative study. There was no statistically significant difference between the three groups. Level 1 evidence. Yet, again, the researchers used posthoc analysis to determine that if the steroid was given within 0-3 hours in the 24 hour group, recovery was greater than if the steroid was given after 3 hours. They also concluded that if given between 3-8 hours, recovery was improved if steroid was continued to 48 hours. The same primary author of the NASCIS II and III trials, Bracken, then went on to write the Cochrane review on the subject and recommended that steroids are an important pharmacotherapy for use in patients with acute spinal cord injury. Wow.
The above results form the NASCIS study could never be reproduced in any independent retrospective studies or even a prospective study done in France (Petitjean et al. 1998)—save one Japanese study in which 41 patients were excluded to produce statistically significant results, therefore, we won’t mention it. In each study, there was no difference between a placebo group and high dose methylprednisolone group. In fact, atients treated in the high-dose steroid groups showed a trend towards increased septic complications. One study (Heary et al. 1997), which was a retrospective review of penetrating trauma patients with GSWs to the spine or spinal cord, established that there was indeed a significant increase in infections in the steroid group (again, no statistical significance in neurological improvement).
A word on pediatrics and high-dose steroid use for spinal cord injury: There are no randomized controlled trials in the pediatric population regarding steroid use. On the basis of current evidence, the use of steroids in the pediatric population is associated with an increase in the risk of infections without any neurological improvement. Therefore, it is not recommended in the pediatric population.
In my humble opinion, what’s the debate?
References:
Bracken, B. Steroids for acute spinal cord injury (Review). www.thecochranelibrary.com. Accessed June 2013.
Brohi, K. Steroids for spinal cord injury. www.trauma.org. Accessed June 2013.
Hall, E. Comparison of 24- and 48-Hour Methylpredniosolone and Tirilazad in NASCIS III. Spinal Cord Medicine. 2003.
Treatment of ASCIs—the Steroid Debate. www.ebmedicine.net. Accessed June 2013.
Aomar M et al. Assessment of neurological function and complications in a retrospective cohort of patients with acute spinal cord injury due to trauma treated with large-dose methylprednisolone. Rev Esp Anestesiol Reanim. Dec 2011;58(10):583-8.
Heary, RF et al. Steroids and gunshot wounds to the spine. Neurosurgery. 1997;41:576-83.
Petitjean M et al. Medical treatment of spinal cord injury in the acute stage. Ann Fr Anesth Reanim. 1998;17:114-22.
Pettiford et al. A review: the role of high dose methylprednisolone in spinal cord trauma in children. Pediatric Surgery Int. 2012;28:287-294.
sadia.hussain
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Agree completely, there is no longer any debate- don’t give steroids in SCI! Nice review Sadia, important stuff to know because often other services are not up to date on the literature and it’s often our responsibility to politely point it out to them so that our patients are not unnecessarily harmed.