Effect of Perioperative Vitamin C on the Incidence of Complex Regional Pain Syndrome: A Systematic Review and Meta-Analysis

Published:November 21, 2021DOI:


      Complex regional pain syndrome type 1 (CRPS-I) is a complex complication that occurs after limb extremity surgeries. Controversy exists regarding the effectiveness of vitamin C in reducing that condition. Therefore, we conducted this systematic review and meta-analysis to assess the role of vitamin C on CRPS-I and functional outcomes after distal radius, wrist, foot, and ankle surgeries. We searched Medline (via PubMed), Embase, the Cochrane Library,, and Google Scholar for relevant studies comparing perioperative vitamin C versus placebo after distal radius, wrist, foot, and ankle surgeries from infinity to May 2021. Continuous data such as functional outcomes and pain scores were pooled as mean differences, while dichotomous variables such as the incidence of complex regional pain syndrome and complications were pooled as odds ratios, with 95% confidence interval, using R software (meta package, version 4.9-0) for Windows. Eight studies were included. The timeframe for vitamin C administration in each study ranged from 42 to 50 days post-injury and/or surgical fixation. The effect size showed that vitamin C was associated with a decreased rate of CRPS-1 than placebo (odds ratio 0.33, 95% confidence interval [0.17, 0.63]). No significant difference was found between vitamin C and placebo in terms of complications (odds ratio 1.90, 95% confidence interval [0.99, 3.65]), functional outcomes (mean difference 6.37, 95% confidence interval [-1.40, 14.15]), and pain scores (mean difference -0.14, 95% confidence interval [-1.07, 0.79]). Overall, vitamin C was associated with a decreased rate of CRPS-I than placebo, while no significant difference was found regarding complications, functional outcomes, and pain scores. These results hold true when stratifying fracture type (distal radius, ankle, and foot surgeries) and vitamin C dose (500 mg or 1 g).
      Level of clinical evidence: 1


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