SLR - October 2015 - Gary Gansen

Vitamin C to Prevent Complex Regional Pain Syndrome in Patients With Distal Radius Fractures: A Meta-Analysis of Randomized Controlled Trials

Reference: Evaniew N, McCarthy C, Kleinlugtenbelt YV, Ghert M, Bhandari M. Vitamin C to Prevent Complex Regional Pain Syndrome in Patients With Distal Radius Fractures: A Meta-Analysis of Randomized Controlled Trials. J Orthop Trauma. 2015 Aug; 29(8): 235-41.

Scientific Literature Review

Reviewed By: Gary Gansen, DPM
Residency Program: Trinity Regional Medical Center

Podiatric Relevance: Complex regional pain syndrome (CRPS) is a severely debilitating condition that can occur after a traumatic injury. Much of the current literature has focused on distal radial fractures; however, there are now some articles that make mention of its frequency in foot and ankle trauma. This includes ankle fractures as well as elective operative trauma. Some results have shown benefit of vitamin C administration in the peri-trauma period reducing the occurrence of CRPS. Due to the relatively low side effect profile of vitamin C, we, as podiatric physicians should be made aware of the potential efficacy of vitamin C in reducing the occurrence of CRPS. The following article is a meta-analysis of randomized controlled trials that looked at the efficacy of vitamin C preventing CRPS.

Methods: Only randomized controlled trials comparing vitamin C against placebo in patients with distal radius fractures were included. Observational studies were excluded. No exclusions were made during selection with regard to age, sex, treatment, vitamin C regimen, or publication date. A literature search was conducted utilizing MEDLINE, EMBASE, and The Cochrane Library up to September 6, 2014. Heterogeneity was quantified using the χ2 test and the I2 statistic.

Results: 127 articles were identified by search criteria. Three trials were included in the final meta-analysis (n= 890 fractures). Two trials included patients being treated operatively and nonoperatively. One trial included only nonoperative treatment. Two trials randomized patient to 500 mg of vitamin C daily for 50 days versus placebo. One trial randomized patients to 200, 500, or 1500 mg of vitamin C daily for 50 days versus placebo. CPRS was diagnosed with Veldman criteria in two studies and with Atkins criteria in the other. All three trials reported incidence of CRPS at one year (n= 890). The pooled relative risk for CRPS with vitamin C compared to placebo was 0.45. The relative risk of CRPS at 6 weeks according to one trial was 1.24 with vitamin C. Heterogeneity was resolved with how CRPS was diagnosed. Heterogeneity was not resolved with regiment of vitamin C or fracture treatment.

Conclusions: The authors state that the results are conflicting and do not show statistical significance in preventing CRPS in patients with distal radius fractures. The authors point out the differing diagnostic criteria that are currently utilized. Atkins criteria requires fewer clinical features than the Veldman criteria. They make the point that there currently is no gold standard test for CRPS. Suggested risk factors that increase the incidence of CRPS include female sex, older age, and medium to low-energy trauma. They do acknowledge that these results contradict an earlier meta-analysis. They state this may be due to the inclusion of the latest trial and/or that the previous study included foot and ankle injuries. While this meta-analysis does not include any foot and ankle studies, traumatic injuries to most joints of the body are physiologically inter-related. We must use this study alongside others to make an evidence based medical decision on vitamin C and the occurrence of CRPS with foot and ankle trauma.

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