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Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial

Michael B. Bracken, PhD; Mary Jo Shepard, MPH; Theodore R. Holford, PhD; Linda Leo-Summers, MPH; E. Francois Aldrich, MD; Mahmood Fazl, MD; Michael Fehlings, MD, PhD; Daniel L. Herr, MD; Patrick W. Hitchon, MD; Lawrence F. Marshall, MD; Russ P. Nockels, MD; Valentine Pascale, RPh; Phanor L. Perot, Jr, MD, PhD; Joseph Piepmeier, MD; Volker K. H. Sonntag, MD; Franklin Wagner, MD; Jack E. Wilberger, MD; H. Richard Winn, MD; Wise Young, MD, PhD

JAMA. 1997;277(20):1597-1604.

Abstract
Objective.
—To compare the efficacy of methylprednisolone administered for 24 hours with methyprednisolone administered for 48 hours or tirilazad mesylate administered for 48 hours in patients with acute spinal cord injury.

Design.
—Double-blind, randomized clinical trial.

Setting.
—Sixteen acute spinal cord injury centers in North America.

Patients.
—A total of 499 patients with acute spinal cord injury diagnosed in National Acute Spinal Cord Injury Study (NASCIS) centers within 8 hours of injury.

Intervention.
—All patients received an intravenous bolus of methylprednisolone (30 mg/kg) before randomization. Patients in the 24-hour regimen group (n=166) received a methylprednisolone infusion of 5.4 mg/kg per hour for 24 hours, those in the 48-hour regimen group (n=167) received a methylprednisolone infusion of 5.4 mg/kg per hour for 48 hours, and those in the tirilazad group (n=166) received a 2.5 mg/kg bolus infusion of tirilazad mesylate every 6 hours for 48 hours.

Main Outcome Measures.
—Motor function change between initial presentation and at 6 weeks and 6 months after injury, and change in Functional Independence Measure (FIM) assessed at 6 weeks and 6 months.

Results.
—Compared with patients treated with methylprednisolone for 24 hours, those treated with methylprednisolone for 48 hours showed improved motor recovery at 6 weeks (P=.09) and 6 months (P=.07) after injury. The effect of the 48-hour methylprednisolone regimen was significant at 6 weeks (P=.04) and 6 months (P=.01) among patients whose therapy was initiated 3 to 8 hours after injury. Patients who received the 48-hour regimen and who started treatment at 3 to 8 hours were more likely to improve 1 full neurologic grade (P=.03) at 6 months, to show more improvement in 6-month FIM (P=.08), and to have more severe sepsis and severe pneumonia than patients in the 24-hour methylprednisolone group and the tirilazad group, but other complications and mortality (P=.97) were similar. Patients treated with tirilazad for 48 hours showed motor recovery rates equivalent to patients who received methylprednisolone for 24 hours.

Conclusions.
—Patients with acute spinal cord injury who receive methylprednisolone within 3 hours of injury should be maintained on the treatment regimen for 24 hours. When methylprednisolone is initiated 3 to 8 hours after injury, patients should be maintained on steroid therapy for 48 hours.

Footnotes
The authors affiliations are listed at the end of this article, as is a complete list of the National Acute Spinal Cord Injury Study centers and personnel with financial disclosure information.

Reprints: Michael B. Bracken, PhD, Department of Epidemiology and Public Health, Yale University School of Medicine, 60 College St, PO Box 208034, New Haven, CT 06520-8034.

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