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

Chen, Suzan MD*,†; Roffey, Darren M. PhD*,‡; Dion, Charles-Antoine BSc*,§; Arab, Abdullah MD*,∥; Wai, Eugene K. MD*,‡,§,∥

doi: 10.1097/AJP.0000000000000218
Review Articles

Objectives: Postoperative pain can contribute to increased risk for complications and lengthened hospital stays. The objective was to analyze the effects of perioperative vitamin C supplementation on postoperative pain and the development of complex regional pain syndrome I (CRPS I) in patients undergoing surgical procedures.

Materials and Methods: A systematic review of published literature was performed through April 2014. References from relevant studies were scanned for additional studies. Results were screened for relevance independently, and full-text studies were assessed for eligibility. Reporting quality was assessed using a modified Newcastle-Ottawa Scale.

Results: The search strategy yielded 710 studies, of which 13 were included: 7 on postoperative pain and 6 on CRPS I. In the final analysis, 1 relevant study found a reduction in postoperative morphine utilization after preoperative vitamin C consumption, whereas another showed no difference in postoperative pain outcomes between the vitamin C and control groups. A meta-analysis of 3 applicable CRPS I studies showed a decrease in postoperative CRPS I after perioperative vitamin C supplementation (relative risk=2.25; τ2=0).

Discussion: There is moderate-level evidence supporting the use of a 2 g preoperative dose of vitamin C as an adjunct for reducing postoperative morphine consumption, and high-level evidence supporting perioperative vitamin C supplementation of 1 g/d for 50 days for CRPS I prevention after extremity surgery. Additional studies are necessary to increase the level of evidence to determine the overall effectiveness and optimum dosage of vitamin C.

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*University of Ottawa Spine Program, The Ottawa Hospital

§Faculty of Medicine, University of Ottawa

Divisions of Neurosurgery

Orthopaedic Surgery, The Ottawa Hospital

Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada

Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website,

C.-A.D. received funding from Human Resources and Skills Development Canada, Ottawa, ON, Canada; via a 2013 Canada Summer Job. D.M.R. is currently receiving consulting fees from Palladian Health. The remaining authors declare no conflict of interest.

Reprints: Eugene K. Wai, MD, J-141, Division of Orthopaedic Surgery, The Ottawa Hospital, 1053 Carling Avenue, Ottawa, ON, Canada K1Y 4E9 (e-mail:

Received September 4, 2014

Received in revised form February 19, 2015

Accepted January 19, 2015

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