CLINICAL QUESTION: Can vitamin C prevent reflex sympathetic dystrophy following a wrist fracture?
BACKGROUND: Reflex sympathetic dystrophy (RSD) may result in increased morbidity, health care costs, and time lost from work. It is not known whether prevention is possible. There is some evidence that oxygen radicals are involved in the pathogenesis of RSD. Antioxidants such as vitamin C have been shown to reduce morbidity in burn injuries. This led the investigators to test vitamin C for RSD prevention.
POPULATION STUDIED: The authors of this study enrolled 115 adults aged 24 to 88 years who were evaluated in an emergency department with a fracture of at least one wrist. Seventy-nine percent of the fractures occurred in women. All patients were treated conservatively using immoblization. Patients were excluded with unacceptable reduction or secondary dislocation or if they would be unavailable for follow-up.
STUDY DESIGN AND VALIDITY: This was a double-blind placebo-controlled trial. Subjects were randomised to receive 500 mg of vitamin C or placebo daily for 50 days following immobilization. Patients were assessed in person at 1, 4, 6, 12, and 26 weeks after the fracture and interviewed by telephone after 1 year. RSD was diagnosed when 4 of 6 symptoms were present throughout an area larger than the wrist: unexplained diffuse pain, difference in skin temperature relative to the other arm, difference in skin color relative to the other arm, diffuse edema, limited active range of motion, and occurrence or increase of these signs and symptoms after activity.
In general, this was a well-designed study. Researchers were prevented from knowing to which group the patient would be assigned in the trial (concealed allocation), which prevented selective enrolment of patients. Treatment and control groups were similar, and follow-up was adequate. Menopausal status of patients was not determined.
OUTCOMES MEASURED: The primary outcome measurement was the development of RSD.
RESULTS: RSD occurred in 4 (7%) fractures in the vitamin C group and 14 (22%) in the placebo group (relative risk [RR]=2.91; 95% confidence interval [Cl], 1.02-8.32). RSD occurred significantly more often in older patients (P=.008). There was no association between the occurrence of RSD and the side of the fracture, dominance, or the need to undergo reduction. There was a significant increase (RR=0.37; 95% Cl, 0.16-0.89) of RSD in type B and C fractures (AO classification). Early complaints while wearing the plaster cast are highly predictive of the occurrence of RSD (RR=0.17; 95% Cl, 0.07-0.41).
Vitamin C 500 mg per day for 50 days following a wrist fracture is effective for preventing RSD. Although this dose is 10-fold higher than the recommended daily allowance, it is still well below the overdose level. This inexpensive and relatively easy treatment seems especially prudent for older patients and those with early complaints while wearing the plaster cast. The high control group incidence of RSD (22%) has been found in other studies, and suggests that clinicians should pay close attention to the development of this complication in patients with wrist fractures.