METHYLPREDNISOLONE FOR ACUTE SPINAL CORD INJURY: AN INAPPROPRIATE STANDARD OF CARE.

Hurlbert RJ. J Neurosurg 2000 Jul;93(1 Suppl):1-7.

OBJECT: Since publication in 1990, results from the National Acute Spinal Cord Injury Study II (NASCIS II) trial have changed the way patients suffering an acute spinal cord injury (SCI) are treated. More recently, recommendations from NASCIS III are being adopted by institutions around the world. The purpose of this paper is to reevaluate carefully the results and conclusions of these studies to determine the role they should play in influencing decisions about care of the acutely spinal cord-injured patient.

METHODS: Published results from NASCIS II and III were reviewed in the context of the original study design, including primary outcomes compared with post-hoc comparisons. Data were retroconverted from tabular form back to raw form to allow direct inspection of changes in treatment groups. These findings were further analyzed with respect to justification of practice standards. Although well-designed and well-executed, both NASCIS II and III failed to demonstrate improvement in primary outcome measures as a result of the administration of methylprednisolone. Post-hoc comparisons, although interesting, did not provide compelling data to establish a new standard of care in the treatment of patients with acute SCI.

CONCLUSIONS: The use of methylprednisolone administration in the treatment of acute SCI is not proven as a standard of care, nor can it be considered a recommended treatment. Evidence of the drug's efficacy and impact is weak and may only represent random events. In the strictest sense, 24-hour administration of methylprednisolone must still be considered experimental for use in clinical SCI. Forty-eight-hour therapy is not recommended. These conclusions are important to consider in the design of future trials and in the medicolegal arena.

THE ROLE OF STEROIDS IN ACUTE SPINAL CORD INJURY: AN EVIDENCE-BASED ANALYSIS.

Hurlbert RJ. Spine 2001 Dec 15;26(24 Suppl):S39-46.

STUDY DESIGN: Literature review.

OBJECTIVES: The purpose of this article is to review the available literature and formulate evidence-based recommendations for the use of methylprednisone in the setting of acute spinal cord injury (SCI).

SUMMARY OF BACKGROUND DATA: Since the early 1990s, methylprednisolone has become widely prescribed for the treatment of acute SCI. Arguably, it has become a standard of care.

METHODS: Through an electronic database search strategy and by cross-reference with published literature, appropriate clinical studies were identified. They were reviewed in chronologic order with respect to study design, outcome measures, results, and conclusions. RESULTS: Nine studies were identified that attempted to evaluate the role of steroids in nonpenetrating (blunt) spinal cord injury. Five of these were Class I clinical trials, and four were Class II studies. All of the studies failed to demonstrate improvement because of steroid administration in any of the a priori hypotheses testing. Although post hoc analyses were interesting, they failed to demonstrate consistent significant treatment effects.

CONCLUSIONS: From an evidence-based approach, methylprednisolone cannot be recommended for routine use in acute nonpenetrating SCI. Prolonged administration of high-dose steroids (48 hours) may be harmful to the patient. Until more evidence is forthcoming, methylprednisolone should be considered to have investigational (unproven) status only.

HIGH DOSE METHYLPREDNISOLONE IN THE MANAGEMENT OF ACUTE SPINAL CORD INJURY - A SYSTEMATIC REVIEW FROM A CLINICAL PERSPECTIVE.

Short DJ, El Masry WS, Jones PW. Spinal Cord 2000 May;38(5):273-86.

STUDY DESIGN: Systematic literature review for primary data using predefined inclusion, exclusion and validity criteria. Primary outcome measure was standardised neurological examination or neurological function. Secondary outcomes; acute mortality, early morbidity.

OBJECTIVES: To access the literature available to clinicians systematically and evaluate the evidence for an effect of high dose methylprednisolone (MPSS) on neurological improvement following acute spinal cord injury (ACSI).

METHODS: Information retrieval was based on Medline search (1966 through December 1999) using the strategy 'spinal cord injury' and 'methylprednisolone' (or 'dexamethasone') with no other restrictions. Primary data publications using high dose steroids given within 12 h following spinal cord injury and reporting outcome measures separately for steroid and non-steroid treated groups were selected. Evaluation followed the guides of Guyatt et al7 (for the Evidence Based Working Group in Canada). Studies with questionable validity were excluded. Level of evidence and treatment recommendation utilised the Canadian Task Force on the Periodic Health Examination criteria.6 Experimental spinal cord injury studies on larger animals were included; small mammal experiments were considered beyond evaluation.

RESULTS: Three clinical trials and six cohort study publications were found to satisfy the review criteria. The evidence they provide supports 'the recommendation that the manoeuvre (high dose methylpredisolone) be excluded from consideration as an intervention for the condition'10 (acute spinal cord injury). Twelve larger animal publications were detailed. Validity and the functional significance of results was of concern in many. The weight of evidence lay with those studies demonstrating no definite effect of MPSS on functional outcome. In cat experiments with higher level cord damage, deaths in the MPSS treated groups were notable.

CONCLUSION: The evidence produced by this systematic review does not support the use of high dose methylprednisolone in acute spinal cord injury to improve neurological recovery. A deleterious effect on early mortality and morbidity cannot be excluded by this evidence.

PHARMACOLOGICAL THERAPY OF SPINAL CORD INJURY DURING THE ACUTE PHASE.

Pointillart V, et al. Spinal Cord 2000 Feb;38(2):71-6.

STUDY DESIGN: Prospective, randomized clinical trial.

SETTING: France.

OBJECTIVES: To evaluate the safety and effect on neurological outcome of nimodipine, methylprednisolone, or both versus no medical treatment in spinal-cord injury during the acute phase.

METHOD: One hundred and six patients who had spinal trauma (including 48 with paraplegia and 58 with tetraplegia) were randomly separated into four groups: M=methylprednisolone (30 mg x kg(-1) over 1 h, followed by 5.4 mg x kg(-1) x h(-1) for 23 h), N=nimodipine (0.015 mg x kg(-1) x h(-1) for 2 h followed by 0.03 mg x kg(-1)h(-1) for 7 days), MN (both agents) or P (neither medication). Neurological assessment (ASIA score) was performed by a blinded senior neurologist before treatment and at 1-year follow-up. Early spinal decompression and stabilization was performed as soon as possible after injury.

RESULTS: One hundred patients were reassessed at 1 year. Neurological improvement was seen in each group (P<0.0001), however no additional neurological benefit from treatment was observed. Infectious complications occurred more often in patients treated with M. Early surgery (49 patients underwent surgery within 8 h of their accident) did not influence the neurological outcome. The only predictor of the latter was the extent of the spinal injury (complete or incomplete lesion).

CONCLUSION: The present study confirms the absence of benefit of pharmacological therapy in this indication. Because of the paucity of clinical studies that demonstrate the efficacy of pharmacological treatment in spinal injury during the acute phase, systematic use of pharmaceutical agents should be reconsidered.