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

Objective: To determine whether vitamin C is effective in preventing complex regional pain syndrome (CRPS) in patients with distal radius fractures. Data Sources: MEDLINE (1946 to present), EMBASE (1974 to present), and The Cochrane Library (no date limit) were systematically searched up to September 6, 2014, using MeSH and EMTREE headings with free text combinations. Study Selection: Randomized trials comparing vitamin C against placebo were included. No exclusions were made during the selection of eligible trials on the basis of patient age, sex, fracture severity, or fracture treatment. Data Extraction: Two reviewers independently screened articles, extracted data, and applied the Cochrane Risk of Bias tool. Evidence was graded using the Grading of Recommendations Assessment, Development, and Evaluation approach. Data Synthesis: Heterogeneity was quantified using the chi(2) test and the I-2 statistic. Outcome data were combined with a random effects model. Results: Across 3 trials (n = 890) of patients with distal radius fractures, vitamin C did not reduce the risk for CRPS (risk ratio = 0.45; 95% confidence interval, 0.18-1.13; I-2 = 70%). This result was confirmed in sensitivity analyses to test the importance of missing data because of losses to follow-up under varying assumptions. Heterogeneity was explained by diagnostic criteria, but not regimen of vitamin C or fracture treatment. Conclusions: The evidence for vitamin C to prevent CRPS in patients with distal radius fractures fails to demonstrate a significant benefit. The overall quality of the evidence is low, and these results should be interpreted in the context of clinical expertise and patient preferences.