Methylprednisolone Use in Acute Spinal Cord Injury

Michael G. Fehlings, MD, PhD, FRCSC, FACS, discusses the guidelines and controversy surrounding use of methylprednisolone in patients with acute SCI.

New guidelines suggest that a 24-hour infusion of high-dose methylprednisolone be offered to adult patients who present within 8 hours of acute spinal cord injury, but not to patients who present 8 or more hours after injury. The guidelines were developed under the guidance of AOSpine North America, AOSpine International, and the American Association and Congress of Neurological Surgeons (AACNS), and were published in a special focus issue of the open-access Global Spine Journal.

Based on the guidelines, the decision of whether or not to use methylprednisolone in acute spinal cord injury (SCI) is left up to the physician. However, physicians should explain the risks and benefits of methylprednisolone patients using a shared decision-making approach, said Michael G. Fehlings, MD, PhD, FRCSC, FACS, who led the multidisciplinary group that developed the guidelines.
intravenous drug infusionHigh-dose methylprednisolone should be offered to adult patients who present within 8 hours of acute spinal cord injury.Controversy Stems from 3 RCTs
The controversy surrounding use of methylprednisolone in patients with acute SCI stems from the 3 randomized controlled National Acute Spinal Cord Injury Studies (NASCIS), explained Dr. Fehlings, who is Professor of Neurosurgery and Co-Director of the University of Toronto Spine Program in Ontario, and Chair of the AOSpine International Spinal Cord Injury Knowledge Forum.

NASCIS I compared high (1000 mg) vs low dose (100 mg) methylprednisolone given for 10 days after acute SCI, and showed no difference in motor or sensory outcomes, Dr. Fehlings said.1 When the study was initiated, it was felt that it would be unethical to conduct a placebo-controlled study on this topic, Dr. Fehlings explained.

In light of NASCIS I findings, it was no longer felt that a placebo-controlled study of methylprednisolone would be unethical, and NASCIS II was initiated to compare 3 treatment arms:2

  1. Methylprednisolone (30 mg/kg bolus and 5.4 mg/kg/hr for 23 hours)
  2. Naloxone (5.4 mg/kg bolus and 4.0 mg/kg/hr for 23 hours)
  3. Placebo

The results showed that while methylprednisolone did not improve outcomes when given within 24 hours of acute SCI, a subanalysis showed that this protocol was associated with improved neurological outcomes in motor and sensory testing when given within 8 hours of acute SCI.

“Based on these findings, methylprednisolone became widely used and was considered defacto standard of care for acute SCI,” Dr. Fehling said. “In fact, a number of lawsuits arose in cases where methylprednisolone was not administered following acute SCI. However, there was a sense among the spine community that perhaps it was not appropriate that methylprednisolone be considered a standard of care in absence of careful review by professional societies.”

Medical/Legal Controversies
A 2002 guideline from Congress of Neurological Surgeons (CNS) and the American Association of Neurological Surgeons (AANS) listed methylprednisolone as a reasonable option for acute SCI, but stated that the level of evidence did not support this practice as a standard of care because the positive effects from NASCIS II were seen in a secondary analysis, the effect size was small, and there was a potential for complications, Dr. Fehlings told SpineUniverse.3

“Had things been left at that level—ie, to leave the decision in the hands of physicians—our group would not have felt it necessary to revisit this topic,” Dr. Fehlings said. “However, in 2013, CNS/AANS guidelines group published a level 1 recommendation against use of methylprednisolone in the routine management of acute SCI.4 There was a huge outcry about this recommendation, because there was no evidence from randomized controlled trials suggesting that methylprednisolone was unsafe or harmful.”

The 8-Hour NASCIS I Cutpoint was Pre-Planned
As part of the latest assessment, a formal systematic review was performed by Spectrum Research, and a multidisciplinary guidelines group evaluated the evidence and developed recommendations.

“One of the main criticisms of the NASCIS II trial was that the positive effect was found in a posthoc analysis,” Dr. Fehlings said. “However, the AOSpine group obtained a copy of the original NIH grant for the study and found that the 8-hour analysis was preplanned.”

“Our guidelines group determined that a 24-hour infusion of methylprednisolone is a reasonable treatment option when given within 8 hours of injury, and left it up to the physician’s judgment on whether the treatment would be beneficial to the individual patient based on presentation and an assessment of the risks and benefits of treatment,” Dr. Fehlings said.

“The reality is that when things are in a grey area in medicine, the decision should be left in the hands of the clinician,” Dr. Fehlings said.

Complications associated with methylprednisolone in acute SCI were more likely to occur with 48-hour administration than with 24-hour administration, as shown in NASCIS III, Dr. Fehlings explained.5

Patient Preference Should Be Considered
Dr. Fehlings also noted that patients should be included in the treatment decision, with a majority of patients with acute SCI recently surveyed subsequent to hospital discharge being in favor of receiving methylprednisolone with “little concern” regarding the potential side effects (eg, wound infection and deep venous thrombosis).6

“These findings are consistent with the feedback we received from patients and patient advocates, as well as from the entire multidisciplinary guidelines group, in which the consensus was overwhelmingly in favor of considering methylprednisolone a reasonable treatment option,” Dr. Fehlings said.

View the special focus issue of the open-access Global Spine Journal.

Disclosure
Dr. Fehlings disclosed no relevant financial relationships.

Updated on: 11/03/17
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