Can Vitamin C Prevent Complex Regional Pain Syndrome in Patients with Wrist Fractures?
A Randomized, Controlled, Multicenter Dose-Response Study
P.E. Zollinger, MD1, W.E. Tuinebreijer, MD, PhD, MSc, MA2, R.S. Breederveld, MD, PhD3 and R.W. Kreis, MD, PhD3
1 Department of Orthopaedic Surgery, Ziekenhuis Rivierenland, President Kennedylaan 1, 4002 WP Tiel, The Netherlands. E-mail address: PE.Zollinger@tiscali.nl<!– var u = "PE.Zollinger", d = "tiscali.nl"; document.getElementById("em0").innerHTML = '‘ + u + ‘@’ + d + ”//–>
2 Relweg 59, 1949 EC Wijk aan Zee, The Netherlands
3 Departments of Surgery (R.S.B., R.W.K.) and Burn Wounds (R.W.K.), Red Cross Hospital, Vondellaan 13, 1942 LE Beverwijk, The Netherlands
Investigation performed at the Department of Surgery, Red Cross Hospital, Beverwijk, The Netherlands; the Department of Orthopaedics and Surgery, Haga Hospital (Leyenburg), The Hague, The Netherlands; and the Department of Orthopaedics and Surgery, Reinier de Graaf Group, Delft, The Netherlands
Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants in excess of $10,000 from Stichting Achmea Slachtoffer en Samenleving (SASS). Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.
Background: Complex regional pain syndrome type I is treated symptomatically. A protective effect of vitamin C (ascorbic acid) has been reported previously. A dose-response study was designed to evaluate its effect in patients with wrist fractures.
Methods: In a double-blind, prospective, multicenter trial, 416 patients with 427 wrist fractures were randomly allocated to treatment with placebo or treatment with 200, 500, or 1500 mg of vitamin C daily for fifty days. The effect of gender, age, fracture type, and cast-related complaints on the occurrence of complex regional pain syndrome was analyzed.
Results: Three hundred and seventeen patients with 328 fractures were randomized to receive vitamin C, and ninety-nine patients with ninety-nine fractures were randomized to receive a placebo. The prevalence of complex regional pain syndrome was 2.4% (eight of 328) in the vitamin C group and 10.1% (ten of ninety-nine) in the placebo group (p = 0.002); all of the affected patients were elderly women. Analysis of the different doses of vitamin C showed that the prevalence of complex regional pain syndrome was 4.2% (four of ninety-six) in the 200-mg group (relative risk, 0.41; 95% confidence interval, 0.13 to 1.27), 1.8% (two of 114) in the 500-mg group (relative risk, 0.17; 95% confidence interval, 0.04 to 0.77), and 1.7% (two of 118) in the 1500-mg group (relative risk, 0.17; 95% confidence interval, 0.04 to 0.75). Early cast-related complaints predicted the development of complex regional pain syndrome (relative risk, 5.35; 95% confidence interval, 2.13 to 13.42).
Conclusions: Vitamin C reduces the prevalence of complex regional pain syndrome after wrist fractures. A daily dose of 500 mg for fifty days is recommended.
Level of Evidence: Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence.
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