High-Dose Methylprednisolone for Acute Spinal Cord Injury — Do Serious Side-Effects Outweigh Potential Benefit?
High-Dose Methylprednisolone for Acute Spinal Cord Injury—Do Serious Side-Effects Outweigh Potential Benefit?
ABSTRACT & COMMENTARY
By Matthew Fink, MD
Vice Chairman, Professor of Clinical Neurology, Weill Medical College, and Chief of Division of Stroke and Critical Care Neurology at NewYork-Presbyterian Hospital
Dr. Fink reports no consultant, stockholder, speaker’s bureau, research, or other relationship related to this field of study.
Synopsis: High-dose methylprednisolone (MP) appears to cause severe acute corticosteroid myopathy (ACM) in patients with acute traumatic spinal cord injury (ASCI), and along with other steroid-related complications, casts doubt on the benefit of MP treatment for ASCI.
Source: Qian T, et al. High-Dose Methylprednisolone May Cause Myopathy in Acute Spinal Cord Injury Patients. Spinal Cord. 2005;43:199-203.
The use of high-dose methylprednisolone (mp) for treatment of acute traumatic spinal cord injury (ASCI) has been used worldwide since the publication of the National Acute Spinal Cord Injury Studies (Bracken, et al. N Engl J Med. 1990;322:1405-1411 and Bracken, et al. J Neurosurg. 1992;76:23-31). The protocol recommends the highest dosage of any corticosteroid used during a 24-hour period for any reported clinical condition (MP 30 mg/kg IV in the first hour and maintained on 5.4 mg/kg/hr for the next 23 hours). Since the publication of the NASCIS, no other group has replicated the results, and several have pointed out the increased risk of steroid-induced complications, including hyperglycemia, sepsis and pneumonia.
Qian and colleagues diagnosed acute corticosteroid myopathy (ACM) in 5 consecutive patients treated with the NASCIS protocol. Muscle biopsy performed 3 to 7 days after MP treatment demonstrated acute myofiber necrosis and severe type II muscle atrophy in 4 of 5 patients. The fifth patient had a normal biopsy, but this was performed within the first 24 hours, before one would expect to see pathologic changes. All 5 patients had EMG findings consistent with myopathy-positive sharp waves and fibrillations in all muscles tested 2 to 4 weeks after injury. Three additional patients with ASCI who were not treated with corticosteroids underwent the same studies, muscle biopsy, and EMGs, and were found to be completely normal.
Commentary
Since the publication of the NASCIS, many investigators have questioned the validity of the study conclusion, that high-dose MP treatment is better than placebo in patients with ASCI. In a detailed meta-analysis of the literature that reviewed all available studies to date, Short, et al. (Spinal Cord. 2000;38:273-286) was unable to find any study that replicated the results of the NASCIS. They also pointed out that the only significant findings came from a post-hoc, sub-group analysis of patients treated within 8 hours of injury, and that the group had improvement in sensory symptoms only. At one year follow-up, the NASCIS investigators stated "considering all randomized patients at 1 year, there were no significant differences in the neurological function by the treatment group." The MP group showed a slight advantage (sensory examination) over placebo, but one must decide if this translates into clinical significance, as well as statistical significance.
Qian, et al have now demonstrated that high-dose MP causes severe ACM. This syndrome has been well documented in a variety of clinical conditions, particularly in acute asthma and in other critically ill patients who undergo paralysis with neuromuscular blocking agents. In patients with ASCI, the development of ACM from high-dose MP may explain the difference in clinical course between steroid-treated and placebo-treated patients from the NASCIS. The investigators may have observed the recovery from ACM, rather than from ASCI.
In addition to other steroid complications, ACM may cause respiratory impairment by causing myofiber necrosis of diaphragmatic muscle, resulting in prolonged mechanical ventilation. Along with hyperglycemia, sepsis, and pneumonia, ACM makes the use of high-dose MP hazardous in patients with ASCI. The NASCIS protocol for ASCI is not supported by current standards of evidence-based medicine and should not be considered a standard of care. Additional neuroprotective strategies should be developed for the treatment of ASCI using placebo controls.
By Matthew Fink, MD Vice Chairman, Professor of Clinical Neurology, Weill Medical College, and Chief of Division of Stroke and Critical Care Neurology at NewYork-Presbyterian Hospital Dr. Fink reports no consultant, stockholder, speakers bureau, research, or other relationship related to this field of study.Subscribe Now for Access
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