Complex Regional Pain Syndrome Type 1 and Evidence for Prophylaxis with Vitamin C

Complex Regional Pain Syndrome (CRPS) Type-1 may occur subsequent to an unpleasant event like trauma from orthopedic surgery. This pain is disproportionate to the initial traumatic event, not specific to a single nerve distribution, associated with excessive sweating at the regional site, feeling of extreme pain from very light touch and excessive reactions to touch that may be moderately painful. This definition is adapted from those of the International Association for the Study of Pain (IAPS).

A number of studies seem to point to prophylactic management with vitamin C antioxidant 500 mg daily for 50 days, with claims of level 1 evidence to support this regimen. Several therapeutic modalities like oral corticosteroids; parenteral infusion of bisphosphonates; and the anesthetic ketamine have also been suggested.

This article reviews the evidence claims for the prescription of Vitamin C 500 mg daily for 50 days post trauma surgery for prophylaxis against the development of Complex Regional Pain Syndrome Type-1 in wrist fractures but not exclusive to these joint/limbs alone.

There is lack of strong evidence to support many of the treatments proposed for CRPS. Lack of adequate control in many of the studies and the ambiguous nature of measuring the recovery profile of CRPS especially in the acute phase makes evaluation of available studies challenging. In other words most of the evidence put forward for the management of CRPS is not based on double blinded, randomized, and controlled trials. Two randomized, double blind, prospective studies by Zollinger et al suggest a 15% absolute risk reduction for patients randomly assigned to 500 mg of Vitamin C versus placebo. However, these studies are not class one level of evidence.

While the evidence may be inconclusive, trauma and surgery may point to an increase vitamin C requirement and probably suggests the background for the initial hypothesis. At this point it must be said, although the stronger evidence suggests 500 mg daily for 50 days, other investigators have experimented with higher or lower doses with varying response. It is also important to consider reports of increased risk of kidney stone formation for men administered 1000 mg doses or higher of vitamin C per day compared to those administered less than 90 mg a day. There is also an increased risk of hemolysis in G6PD deficient individuals who received high dose Vitamin C.

Since well designed, robust, double blinded, randomized, controlled trials are lacking it appears that the popular practice of giving vitamin C 500 mg daily for 50 days post trauma surgery is based on very little evidence. Suffice to say more robust clinical trials are required to support the validity of using vitamin C to prevent Complex Regional Pain Syndrome Type-1.

Reference

Besse J.L. Gadeyne S. Desme SG, Lerat JL, Moyen B. Effect of Vitamin C on prevention of complex regional pain syndrome type 1 in foot and ankle surgery. Foot and Ankle Surgery 2009: 15:179-82.

Cazeneuve JF, Leborgne JM, Kermad K, Hassan Y: Vitamin C and prevention of reflex sympathetic dystrophy following surgicalmanagement of distal radius fractures. Acta Orthop Belg. 2002. 68:481-484.

Christensen K, Jensen E.M, Noer I. The reflex dystrophy syndrome response to treatment with corticosteroids. Acta Chir Scand 1982:148: 653-5.

Finch P.M, Knusden L, Drummond P.D. Placebo-controlled trial of topical ketamine. Pain .2009: 146: 18-25.

Frank JE Diagnosis and management of G6PD deficiency.  Am Fam Physcian 2005: 72:1277-82.

Goebel A. Complex regional pain syndrome in adults. Rheumatology.2011; 50:1739-50.

Jaiman A, Lokesh, M., Neogi, D.S. Effect Of Vitamin C on Prevention of Complex regional pain syndrome type I in foot and ankle surgery (Letter to the editor). Foot and Ankle Surgery. 2007: 17 207.

Levine M Rumsey S.C, Daruwala R, Park JB. Wang Y. Criteria and recommendations for vitamin C intake. J Am Med Assoc 1999;281:1415-23.

Levine M. Wang Y. Padayatty SJ. Morrow J.A. new recommended dietary allowance of vitamin C for healthy young women. Proc Natl Acad Sci USA 2001-98:9842-6.

Marnix J, Sigtermans A, Van Hilten J.J, et al. Ketamine provides effective and long term pain relief in patients with complex regional pain syndrome type 1. Pain 2009;146: 304-31.

Natusch D. Complex regional pain syndrome. Orthopaedic and Trauma.2012;26(6)405-409.

Perez, R.S, Zollinger, P.E, Dijkstra, P.U, Thomassen-Hilgersom I.L, Zuurmond, W.W, Rosenbrand,K.C.J, Geertzen J.H, and the CRPS 1 task force. BMC Neurology. 2010; 10:20-33.

Taylor EN, Curhan G.C, Determinants of 24-hour urinary oxalate excretion. Clin J Am Soc ~Nehrol 2008: 3 1453-60.

Van de Veuse, A.C.,Stomp-van den Berg S.G,Kessels. A.H, Webber. W.E. Randomised controlled trial of gabapentin in Complex regional pain syndrome type 1. BMC Neurol 2004;4:13

Zollinger PE, Tuinebreijer WE, Kreis RW, Breederveld RS: Effect of vitamin C on frequency of reflex sympathetic dystrophy in wrist fractures: a randomized trial. Lancer 1999 354: 2025-2028.

Zolinger P.E, Tuinebreijer WE, Breederveld RS, Kreis RW. Can vitamin C Prevent complex regional pain syndrome in atients with wrist fractures? J Bone joint Surg Am. 2007: 89:1424-31.