To The Editor:
In the article "Can Vitamin C Prevent Complex Regional Pain Syndrome
in Patients with Wrist Fractures? A Randomized, Controlled, Multicenter
Dose-Response Study" (2007;89:1424-31), Zollinger et al. studied the
prophylactic effect of vitamin C on the prevalence of complex regional pain
syndrome in 416 patients with a wrist fracture. They concluded that vitamin C
is indeed effective, and they recommended giving 500 mg of vitamin C daily for
fifty days to each patient with a wrist fracture to prevent complex regional
pain syndrome.
Some limitations of this study mentioned in the article include a large
selection bias (416 of 2137 eligible patients were enrolled) and a low event
rate due to an unexpected low prevalence of complex regional pain syndrome
(4.2% compared with 22% in the authors' previous study1). This
means that only eighteen patients (eight of the 328 in the treatment group and
ten of the ninety-nine in the placebo group) fulfilled the criteria for
complex regional pain syndrome. In one patient with fractures of both wrists,
complex regional pain syndrome developed on one side, where the fracture
turned out to be badly reduced, and the other side healed without
complications. This example reveals dramatically how this study demonstrates a
strong confounder: although the number of fractures needing reduction was
equal in both groups, the quality of the reduction was not mentioned.
Open reduction and internal fixation of wrist fractures generally achieves
a better reduction than closed reduction with application of a cast.
Retrospective studies of surgically treated wrist fractures have therefore
demonstrated a lower incidence rate of complex regional pain syndrome, of
around 3.5%2. To my knowledge, no prospective study has ever
demonstrated an association between the incidence of complex regional pain
syndrome and the quality of reduction, but pain syndromes in general occur
more frequently when fractures are not adequately reduced.
Much scientific effort has been put in attempts to achieve prophylaxis and
treatment for complex regional pain syndrome with pharmacological means, but
these efforts did not result in any clinical recommendations3.
Conservative physical therapy has provided some benefit for patients with
complex regional pain syndrome4. Since the introduction of
functional and time-contingent "pain-exposure" physical therapy in
children with complex regional pain syndrome by Sherry et al. in
19995, more reports on this approach are to be expected for adult
patients as well.
A difference is therefore to be expected between patients with complex
regional pain syndrome who are treated by a physical therapist and those who
are not. The use of any form of physical therapy is not mentioned in this
paper, introducing another possible confounder. This paper therefore does not
provide support for the effectiveness of vitamin C in preventing complex
regional pain syndrome.