Additional Evidence Against Steroids for Spinal Cord Injury

From: trauma-list-bounces@trauma.org on behalf of ecthompson [ecthompson@msn.com] Sent: 19 February 2004 12:27 PM To: ‘Trauma & Critical Care mailing list’ Subject: RE: Changing behavior… As a healthcare worker we all must do what we feel is in the best interest of our patients. We can’t deliver a therapy that we know or feel is harmful. This is ethically wrong. Here are some articles to help you feel better about NOT giving steroids. *****ANNALS OF SURGERY***** (REFERENCE 1 OF 5) 94029215 Galandiuk S, Raque G, Appel S, Polk HC The two-edged sword of large-dose steroids for spinal cord trauma. In: Ann Surg (1993 Oct) 218(4):419-25; discussion 425-7 ISSN: 0003-4932 OBJECTIVE: In 1990, large-dose steroid administration was advocated in spine-injured patients to lessen neurologic deficits. The authors undertook both prospective and retrospective studies to evaluate the response of such profound pharmacologic intervention. SUMMARY BACKGROUND DATA: Of all sources of nonfatal injury, spinal cord trauma remains the most devastating in both cost and impact on the quality of the patient’s life. One study found that routine large- dose steroid administration after injury lessened the extent of neurologic injury. After uncommonly prompt and broad lay press publicity, this practice was widely accepted. Biased by knowledge of the known immunosuppressive effects of steroids, the authors suspected that pneumonia was both more frequent and severe in steroid- treated patients. METHODS: Thirty-two patients with cervical or upper thoracic spinal injuries (C3-6, 20 patients; C6-7, 6 patients; and T1- 6, 6 patients) were studied at an urban level I trauma center from January 1987 to February 1993. Complete spinal cord injury was present in 22 of 32 patients; 14 patients received steroids postinjury. There was no difference in mean age, cord level, age- adjusted injury severity score, or the percent of injury severity score caused by the spinal injury. RESULTS: The length of hospital stay was longer in steroid-treated patients (S) than in nonsteroid (NS) patients, that is, 44.4 days versus 27.7 days, respectively (p = 0.065). Seventy-nine per cent of S patients had pneumonia compared with 50% of NS patients (p = 0.614). There was no statistical difference in the episodes of pneumonia per patient between the two groups (p > 0.05). Prospectively, the authors evaluated sequentially several parameters known to be important in human immune responses to bacterial challenges in nine S and five NS patients. In S patients, both the per cent and density of monocyte class II antigen expression and T-helper/suppressor cell ratios were lower than in NS patients. However, S patients did have an initially higher, earlier boost in some host defense parameters that rapidly declined, and their subsequent response was both blunted and delayed. These differences became even clearer when stratified according to cord level and incomplete versus complete cord status. Not surprisingly, infected patients, whether S or NS, had lower levels of monocyte antigen expression, CR3, and helper/suppressor ratios. CONCLUSIONS: These data do not permit a judgment to be made whether neurologic status was improved by S administration. It is known that vital immune responses were adversely affected, that pneumonia was somewhat more prevalent, and that hospitalization was prolonged and costs therefore increased by an average of $51,504 per admission. Further clinical studies will be needed to determine to what extent these observations offset the putative benefits of large-dose steroids in the treatment of spinal trauma. Registry Numbers: 83-43-2(Methylprednisolone) Institutional address: Department of Surgery Division of Neurosurgery University of Louisville School of Medicine Kentucky. *****CURRENT OPINION IN NEUROLOGY***** (REFERENCE 2 OF 5) 21579585 Short D Is the role of steroids in acute spinal cord injury now resolved? In: Curr Opin Neurol (2001 Dec) 14(6):759-63 ISSN: 1350-7540 Steroids have long been used in the context of acute spinal cord injury but the evidence for doing so is limited. The second National Acute Spinal Cord Injury Study trial had the potential to provide such evidence for the first time, as this was a placebo controlled, prospective, randomized trial. From the outset, however, some clinicians found the methodology and consequently the results unsatisfactory. This concern has been revisited within the evidence- based framework of critical appraisal of the accumulation of clinical studies. High-dose methylprednisolone cannot be justified as a standard treatment in acute spinal cord injury within current medical practice. Registry Numbers: 83-43-2(Methylprednisolone) Institutional address: Midlands Centre for Spinal Injuries Robert Jones and Agnes Hunt Orthopaedic and District Hospital NHS Trust Oswestry Shropshire SY10 7AG UK. debbie.short@rjahoh-tr.wmids.nhs.uk *****JOURNAL OF TRAUMA***** (REFERENCE 3 OF 5) 99082943 Nesathurai S Steroids and spinal cord injury: revisiting the NASCIS 2 and NASCIS 3 trials. In: J Trauma (1998 Dec) 45(6):1088-93 ISSN: 0022-5282 The National Acute Spinal Cord Injury Study (NASCIS) 2 and 3 trials are often cited as evidence that high-dose methylprednisolone is an efficacious intervention in the management of acute spinal cord injury. Neither of these studies convincingly demonstrate the benefit of steroids. There are concerns about the statistical analysis, randomization, and clinical end points. Even if the putative gains are statistically valid, the clinical benefits are questionable. Furthermore, the benefits of this intervention may not warrant the possible risks. This paper comments on these two clinical trials. Comment in: J Trauma. 2000 Mar;48(3):558-61 Comment in: J Trauma. 2001 Aug;51(2):421-3 Registry Numbers: 83-43-2(Methylprednisolone) Institutional address: Boston University School of Medicine and New England Regional Spinal Cord Center Boston Medical Center Massachusetts 02118-2393 USA. (REFERENCE 4 OF 5) 95018411 Prendergast MR, Saxe JM, Ledgerwood AM, Lucas CE, Lucas WF Massive steroids do not reduce the zone of injury after penetrating spinal cord injury. In: J Trauma (1994 Oct) 37(4):576-9; discussion 579-80 ISSN: 0022-5282 The National Acute Spinal Cord Injury Study II concluded in 1990 that high-dose methylprednisolone (MP) improved neurologic recovery after acute spinal cord injury (ASCI). We tested this conclusion by analysis of 54 patients with ASCI; 25 patients were treated without MP before 1990 whereas 29 patients were treated with MP after 1990. Neurologic deficit was assessed regularly, in most cases daily. Motor and sensory scores on admission, and best results at one-half week (days 2 to 4), 1 week (days 6 to 10), 2 weeks (days 11 to 21), 1 month, and 2 months were noted for both groups. Motor assessment was recorded in 22 muscle segments on a scale of 0 (complete deficit) to 5 (normal); the range, thus, was 0 to 110. The 23 patients with closed injuries demonstrated no difference in improvement with or without MP. In contrast, MP was associated with impaired improvement in the patients with penetrating wounds; the 15 patients with no MP therapy had an admission motor score of 49, which increased by 6.9 at one-half week, whereas the 16 patients treated with MP had an admission motor score of 48, which decreased by 0.3 at one-half week (p = 0.03). The neural status seen by day 4 persisted throughout the next 2 months. Changes in sensation paralleled the changes in motor function. We conclude that MP therapy for penetrating ASCI may impair recovery of neurologic function. Registry Numbers: 83-43-2(Methylprednisolone) Institutional address: Department of Surgery Wayne State University Detroit MI 48201. *****SPINE***** (REFERENCE 5 OF 5) 21665377 Hurlbert RJ The role of steroids in acute spinal cord injury: an evidence-based analysis. In: Spine (2001 Dec 15) 26(24 Suppl):S39-46 ISSN: 0362-2436 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. Comment in: Spine. 2001 Dec 15;26(24 Suppl):S55 Registry Numbers: 83-43-2(Methylprednisolone) Institutional address: Department of Clinical Neurosciences University of Calgary Foothills Hospital 1403 29th Street NW Calgary Alberta T2N 2T9 Canada. jhurlber@ucalgary.ca Questions? E Errington C. Thompson, MD Trauma/Surgical Critical Care Trinity Mother Frances Tyler, Tx ecthompson@tyler.net Don’t think you are Know you are – Morpheus (The Matrix)