CAVEATS: Selection bias?
The study enrolled less than 20% of potentially eligible patients, raising the possibility that only patients who might benefit from vitamin C prophylaxis were enrolled. However, almost two thirds of those eligible were either never approached due to the emergency department being busy (43%), or refused randomization (14%) after they were informed in the consent process that there was evidence of benefit of vitamin C, based on the prior trial.8 Therefore, selection bias seems an unlikely explanation for the positive results. This is the second trial to show the same finding, which is reassuring.
No men had CRPS in either group in this study, so there is no evidence to show whether or not this intervention works in men. We are unaware of any physiologic reason to suggest that vitamin C would have a differential effect in men. In the earlier study, only 1 man (in the placebo group) got CRPS, for an absolute risk difference of 0.08 (95% CI, –0.07 to 0.27).8
What are the diagnostic criteria?
There is no universal agreement on the diagnostic criteria for CRPS. This study used Veldman’s criteria (TABLE 1), which is the standard criteria used in The Netherlands, and has the best inter-rater reliability of the current criteria.9 Criteria from the International Association of Studies in Pain are the most widely cited in the literature, but are not particularly specific or reproducible.9
CHALLENGES TO IMPLEMENTATION: Getting vitamin C started
Recommending 500 mg of vitamin C daily for 7 weeks is a simple and low-cost intervention. Many of our patients will be treated acutely in emergency rooms or by orthopedic surgeons. If these clinicians do not initiate the vitamin C, it may be some time before the primary physician can begin this therapy. We don’t have any information on whether a delay in initiation affects the efficacy of vitamin C.
The evidence presented here is for Colles’s fractures, but CRPS definitely follows other fractures. We are unaware of any physiologic reason why vitamin C therapy would behave any differently for other fracture locations.
It’s a mistake to think CRPS is rare
Perhaps the greatest challenge to implementation is the perception that CRPS is a rare phenomenon or at least generally resolves spontaneously.
The rate in the placebo group (1 in 10 diagnosed at 1 year) and the rates reported through systematic surveillance (1 in 4 diagnosed at some point following Colles’s fracture) struck both us and the clinicians reviewing this study as high.
We suspect symptoms are often missed or misdiagnosed. Even with resolution, the symptoms can be bothersome, and quite severe in a few cases (1% to 2%). We think vitamin C 500 mg/day for 7 weeks is well worth recommending.
PURLs methodology
This study was selected and evaluated using FPIN’s Priority Updates from the Research Literature (PURL) Surveillance System methodology. The criteria and findings leading to the selection of this study as a PURL can be accessed at www.jfponline.com/purls.
