Elsevier

The Lancet

Volume 354, Issue 9195, 11 December 1999, Pages 2025-2028
The Lancet

Articles
Effect of vitamin C on frequency of reflex sympathetic dystrophy in wrist fractures: a randomised trial

https://doi.org/10.1016/S0140-6736(99)03059-7Get rights and content

Summary

Background

The pathogenesis of reflex sympathetic dystrophy (RSD) is not clear, nor is there a definitive treatment for this syndrome. The morbidity, costs in health care, and loss of work time justify the search for a means to prevent post-traumatic dystrophy. Although the role of toxic oxygen radicals has not yet been clarified, we investigated vitamin C (ascorbic acid) as a prophylactic antioxidant drug.

Methods

123 adults with 127 conservatively treated wrist fractures were randomly allocated in a double-blind trial to take a capsule of 500 mg vitamin C or placebo daily for 50 days. Each participant's sex, age, side of fracture, dominance, fracture type, dislocation, reduction, and complaints with the plaster cast were recorded, and they were clinically scored for RSD. The follow-up lasted 1 year.

Findings

Eight patients were withdrawn after randomisation. 52 patients with 54 fractures (male 22%, female 78%; mean age 57 years) received vitamin C and 63 patients with 65 fractures (male 20%, female 80%; mean age 60 years) received placebo. RSD occurred in four (7%) wrists in the vitamin C group and 14 (22%) in the placebo group 15% (95% CI for differences 2–26). Other significant prognostic variables for the occurrence of RSD were complaints while wearing the cast (relative risk 0·17 [0·07–0·41]) and fracture type (0·37 [0·16–0·89]).

Interpretation

This prospective, double-blind study shows that vitamin C was associated with a lower risk of RSD after wrist fractures. Our hypothesis is that this beneficial effect of prophylaxis would be useful in other forms of trauma.

Introduction

The pathogenesis and treatment of reflex sympathetic dystrophy (RSD) are still a matter of debate. The large number of names given to this syndrome, such as causalgia of Mitchell,1 Sudeck's atrophy,2 algodystrophy, post-traumatic RSD, and complex regional pain syndrome type 1, confirms that this subject is a puzzle to many investigators.

RSD is characterised by a pseudo-inflammatory hot phase and a cold phase. In the first phase, the primary changes to the tissue are caused by sympathetic microcirculatory disturbances,3 whereas in the cold phase the tissue undergoes secondary trophic changes. The role of toxic oxygen radicals has been investigated in several studies.4, 5, 6

The morbidity of this syndrome, the costs in health care, and loss of working time justify the search for a preventive treatment. Research in burn injuries led us to try an antioxidant drug to prevent post-traumatic dystrophy. Matsuda and colleagues extensively investigated the effects of high-dose vitamin C therapy on dermal burns.7, 8, 9, 10 They found that vitamin C stops the progression of vascular permeability after burns7 and therefore reduces microvascular leakage of fluid and protein.8 Vitamin C also reduces lipid peroxidation after burns.9 Lipid peroxidation damages the microvascular endothelial cells, thereby increasing capillary permeability. The lipid peroxide in the cell membrane can only be scavenged by vitamin E, the primary lipid-soluble small-molecule antioxidant,11 producing a vitamin E free-radical complex.12, 13 In the extracellular fluid vitamin C, the terminal water-soluble small-molecule antioxidant,11 acts on this complex and removes the free radical moiety, regenerating vitamin E.14, 15 Vitamin C is a natural antioxidant that can scavenge hydroxyl radicals16 and superoxide radicals that produce hydroxyl radicals.10, 17 By scavenging these radicals, vitamin C stops free-radical reactions and prevents the propagation of chain reactions.11, 12, 13 Thus, vitamin C protects the capillary endothelium and circulating cells such as erythrocytes and leucocytes.10

There are very few substances that have such an impact on wounds after burns and the signs of inflammation at that stage as vitamin C. The link between these experiments in burn wounds, an animal model of inducing RSD,5 and patient studies6, 18 is an inflammatory component, and involvement of microangiopathy is suggested. Extrapolation of these results gave us the idea for the application of vitamin C as prophylaxis for RSD.

The recommended daily allowance of vitamin C is 60 mg according to the National Research Council of the USA. Healthy individuals need less vitamin C per day than those with chronic diseases.19 As a prophylactic antioxidant we chose to administer ten times the daily dose recommended in the Netherlands and gave 500 mg ascorbic acid in a capsule. This amount is still far below the overdose level. Our hypothesis was that the frequency of post-traumatic RSD after wrist fractures would be lower in the group receiving vitamin C than in a matched placebo group.

Section snippets

Study design

We studied adults (aged 18 years or older) who were admitted to the emergency department of our hospital (Red Cross Hospital, Beverwijk, Netherlands) with a fracture of the wrist (or both wrists). Only patients with fractures that were to be treated conservatively (immobilisation by a plaster cast, after reduction under local anaesthesia, if necessary) were enrolled in the study. Fractures with unacceptable reduction or secondary dislocation were operated on and excluded from this study.

Results

Between July, 1995, and August, 1997, 123 patients with 127 fractures of the wrist were enrolled. One patient had to be excluded because she had not taken any capsules. Seven others were excluded because they were operated on for unacceptable reduction or redislocation. The reason for the primary exclusion of 23 patients (of the original 146) was indication for reduction with fixation (external or internal), refusal of trial participation of the patients, and living elsewhere and therefore not

Discussion

This study shows that the administration of vitamin C in patients with a wrist fracture was associated with a lower frequency of RSD. Although 17 of the 18 patients with RSD were women, sex was not a significant factor in the occurrence of RSD in this study. The mean age of the female participants was such that most women, and all women developing RSD, were postmenopausal. In our protocol we did not assess the oestrogen status of the female participants, but none was receiving

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