Benefit of Immediate Administration of High-Dose Steroids for Acute Spinal Cord Injury

ABSTRACT & COMMENTARY
Source: Bracken MB, 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; 227:1597-1604.

In this latest contribution of the national acute Spinal Cord Injury Study (NASCIS), a total of 499 patients were diagnosed within eight hours of injury and received a 30 mg/kg bolus of methylprednisolone (MP) or approximately 2000 mg for a 70 kg adult. They were then randomized into three groups: 24- or 48-hour infusion groups of MP at 5.4 mg/kg/hour, or tirilazad mesylate (TM) 2.5 mg/kg every six hours for 48 hours. TM is an investigational antioxidant that inhibits lipid peroxidation and reduces damage in animal models of spinal cord injury.

Patients were assessed at six weeks and six months for a change in motor function from initial presentation. Outcome was also calculated by a composite Functional Independence Measure (FIM) at these time periods. Compared with patients treated for 24 hours, those treated with MP for 48 hours had minor improvements in motor function at six weeks (P = 0.09) and six months (P = 0.07) following injury. Differences in rates of motor recovery between the 24- and 48-hour groups were not significant if initial therapy was started less than three hours from time of injury. However, for patients started 3-8 hours after injury, the 48-hour group was more likely to improve one full neurologic grade (P = 0.03) with a better FIM (P = 0.08) at six months. The 48- hour group, however, also had a slightly higher incidence of sepsis and pneumonia, but otherwise underwent similar complications and mortality (P = 0.97). Patients randomized to the TM group did slightly worse than both MP groups.

COMMENTARY

The initial landmark NASCIS study published in 1990 (N Engl J Med 1990;322:1405-1411; Neuro Alert 1990;8:37) demonstrated the benefit of early (< 8 hours) steroid treatment in reducing disability. However, spinal cord injury remains a huge clinical problem, as most patients are neurologically devastated. Clearly, better treatments are needed, but this latest study reinforces the small improvements that can be achieved with early steroid intervention: In patients with acute spinal cord injury who receive MP within three hours, the treatment regimen should continue for 24 hours; when MP is initiated 3-8 hours after injury, 48 hours of infusion may have some additional neurologic benefit but carries a slightly higher risk of infection. —ba