Steroids in Acute Spinal Cord Injury

OK, I have to admit that I do like to discuss these controversial topics.  If we don’t look at the data and have an open discussion, we’ll be doing something simply because it was deemed to be a standard of care prematurely.  The main studies that you want to review for this topic are NASCIS (National Acute Spinal Cord Injury Studies) I, II, and III, as well as a Japanese article also looking at the topic.  There is also a Cochrane review from Jan 2012 that’s helpful as well.

The original NASCIS trial (NASCIS I) found no difference in motor function or pinprick/sensation from baseline with IV methylprednisolone use, but the doses used were much lower than the doses used in the animal studies that first suggested a possible benefit.  Therefore, NASCIS II was performed to look at high dose methylprednisolone in acute spinal cord injury.  Patients received either methylprednisolone, naloxone, or placebo within the first twelve hours of injury.  The methylprednisolone was high dose and given for 24 hours.  Overall there was no benefit in the methylprednisolone group, but sub-group analysis showed a small benefit in motor function in the patients that received the IV steroids within the first 8 hours.  After that study, many began to define high dose methylprednisolone as standard of care after acute spinal cord injury.  The Japanese study mentioned attempted to repeat the NASCIS II using the 8 hour timeline as the main outcome, and it showed a benefit.  However, the opponents of steroids in acute spinal cord injury noted that the randomization was not defined and only 3/4 of the patients enrolled were listed in the data.  NASCIS III attempted to compare a 24 hour regiment with a 48 hour regimen and found no benefit.

In talking to many residents, it seems many people jump directly to the assumption that steroids shouldn’t be given in acute spinal cord injury.  That is likely not the case, and there may be a role for steroids, depending on the specific situation and your neurosurgeon consultant’s recommendations/beliefs.  In the US, a survey of spine surgeons reported 91% of them use steroids in acute spinal cord injury, although only 24% of them believe there is a clinical benefit.  Once the label of “standard of care” is attached, it’s hard to remove.  The Cochrane review reported that high-dose methylprednisolone is the only approved pharmacologic treatment of acute spinal cord injury that has been proven by prospective, randomized studies.  The review admitted the treatment must be started within 8 hours to see the benefit, but it didn’t mention the post-hoc analysis aspect.  The Canadians no longer define steroids as a standard of care but instead call it a treatment option.  Until better data emerge, we’re still forced to decide between a possible benefit from post-hoc analysis vs going against a “standard of care.”

I recommend the www.ebmedicine.net article “Treatment of ASCIs – the Steroid Debate” (http://www.ebmedicine.net/topics.php?paction=showTopicSeg&topic_id=82&seg_id=1620) and “Methylprednisolone for acute spinal cord injury:  not a standard of care” by Herman Hugenholtz.  Both offer succinct reviews and constructive criticism of the NASCIS trials.

Rest of sources: the NASCIS studies

Bracken, 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.  N Engl J Med.  1990; 322:1405-1411.

Young, Bracken, et al.  The Second National Acute Spinal Cord Injury Study.  J Neurotrauma.  1992, 9 Suppl 1:S397-405.

Bracken, et al.  Administration of Methylprednisolone for 24 or 48 Hours or Tirilazad Mesylate for 48 Hours in the Treatment of Acute Spinal Cord Injury.  JAMA.  1997;277(20):1597-1604.