Neuroprotective Agents as an Adjuvant Treatment in Patients With Acute Spinal Cord Injuries: A Qualitative Systematic Review of Randomized Trials.

STUDY DESIGN: This was a systematic literature review. OBJECTIVE: The objective of this study was to evaluate randomized clinical trials that address potential neuroprotective agents used to improve neurological outcome in patients with spinal cord injury (SCI). SUMMARY OF BACKGROUND DATA: Clinical treatment of acute SCI has evolved significantly, but neurological recovery of severely injured patients remains modest. Neuroprotective agents may act to limit secondary damage in the sequence of pathophysiologic insults that occur after primary SCI. METHODS: We performed a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines of all clinical randomized trials that evaluated potential neuroprotective agents (drugs, stem cells, and any type of medicative interventions) in neurological outcome of acute SCI. All the studies were graded according to their level of evidence in accordance with the Oxford Level of Evidence-based Medicine. RESULTS: A total of 16 randomized clinical trials were included and fully analyzed in our review. The following 12 substances/drugs were analyzed: methylprednisolone (MP), naloxone, tirilizad, nimodipine, Sygen, autologous incubated macrophages, autologous bone marrow cells, minocycline, erythropoietin, ganglioside, vitamin D, and progesterone. Modest benefits were attributed to minocycline and Sygen (without statistical significance), and some benefits were obtained with erythropoietin and progesterone plus vitamin D in neurological outcome. For MP, the benefits are also controversial and may be attributed to statistical artifacts and with a high risk of adverse effects. The other substances did not change the final outcome. All studies were considered as grade B of recommendation (100%) and levels of evidences as B2 (81.25%) and B3 (18.75%). CONCLUSIONS: Our review reported some potential substances that may improve neurological outcome in acute SCI: MP, vitamin D associated with progesterone, and erythropoietin. Their potential benefits were modest in the evaluated studies, requiring further randomized clinical trials with large samples of patients, without statistical artifacts, for routine clinical use. Furthermore, potential adverse effects must be considered with the use of neuroprotective agents in SCI. Until then, the use of these substances may be experimental or restricted to specific clinical situations.