Complex Regional Pain Syndrome

Dr. Tashana Haye

Edited by Rosa Velazquez


50 year old right hand-dominant female presents with wrist pain. She states that 3 months ago she broke her right wrist and it was treated with a cast that she wore for 6 weeks. She followed up with her orthopedic surgeon, who states that she is well healed at this time and she's currently doing physical therapy.

She states that her pain since the injury has been waxing and waning and seems like it flares. Today, her pain is a 10/10 and she cannot move her wrist.

You reorder an X-ray and it appears to be a healed fracture. What does she have? What are your next steps?

Complex Regional Pain Syndrome

CRPS is a complication for conservatively or surgically treated wrist fractures. It is an exaggerated inflammatory response to a traumatic injury due to over-activity of the sympathetic nervous system. This can result in edema, pain, and limitations of range of motion.

There is no curative effective treatment.

ACEP Recommendations

  1. Initial bolus of 0.2-0.3 mg/kg of ketamine infused over 10 minutes.

  2. An infusion of ketamine (0.2 mg/kg/hr) for 4-6 hours

After treatment, the patient can go home. Opioids should be avoided. Refer patient to physiotherapy and a comprehensive pain program.

Can Vitamin C supplementation prevent CRPS-1 after wrist fractures?

Aïm F, Klouche S, Frison A, Bauer T, Hardy P. Efficacy of vitamin C in preventing complex regional pain syndrome after wrist fracture: A systematic review and meta-analysis. Orthop Traumatol Surg Res. 2017 May;103(3):465-470. doi: 10.1016/j.otsr.2016.12.021. Epub 2017 Mar 4. PMID: 28274883.


Methods & Materials

  1. Medline via Pubmed, Cochrane Central Register of Controlled Trials, Embase

  2. Included randomized placebo controlled trials of the efficacy in preventing CRPS-I after a wrist fracture

  3. Primary Outcome: Proportion of patient’s with CRPS-I within one year after the injury

  4. Statistical Analysis Heterogeneity of studies were interpreted. RR with their 95% confidence intervals were computed

    1. Funnel Plot used to assess publication bias

    2. Descriptive stats were computed via GraphPad Prism with which P values <0.5 considered significant

Study Characteristics

  1. All were RCTs with the occurrence of CRPS-I within the first year as the primary outcome.

  2. Patients: 875 total of whom 62.5% received vitamin C and the rest received a placebo

    1. Female/Male ratio: 0.3

    2. Mean Age: 59.6

Wrist fractures

Treatment group:

  • Extra-articular: 54.8%

  • Articular: 40.2%

  • Unclassified: 5%

Placebo group:

  • Extra-articular: 50.3%

  • Articular: 38.6%

  • Unclassified: 11.1%

Treatment Characteristics

Vitamin C started on the day of injury for 50 days in all three studies

500mg dose in two studies

200, 500, & 1500 mg in the remaining studies

Wrist fractures

  • Nonoperative: 85.1%

  • Operative: 14.9%


The relative risk of CRPS-1 after a wrist fracture was not significantly diminished in the group given vitamin C at any dose

However, when isolated to the 500mg vitamin C versus the placebo, the risk was significantly reduced

In patients with wrist fractures, taking a vitamin C supplement of 500mg can prevent CRPS-1. This meta-analysis shows that the relative risk is 0.54 when receiving vitamin C when compared to the placebo group.

  • Eliminated all studies with the exception of three with unclear reasoning

  • Both positive studies came from the same lab

    • Attempts to repeat the findings resulted in a negative study

  • Heterogeneity

    • 65% cited as nonsignificant, but is a significant amount



Aïm F, Klouche S, Frison A, Bauer T, Hardy P. Efficacy of vitamin C in preventing complex regional pain syndrome after wrist fracture: A systematic review and meta-analysis. Orthop Traumatol Surg Res. 2017;103(3):465-470. doi:10.1016/j.otsr.2016.12.021

Ducharme J. Tips for Managing Complex Regional Pain Syndrome - Page 2 of 2. ACEP Now. Published April 1, 2019. Accessed September 11, 2021.

Goebel A, Bisla J, Carganillo R, et al. A randomised placebo-controlled Phase III multicentre trial: low-dose intravenous immunoglobulin treatment for long-standing complex regional pain syndrome (LIPS trial). Southampton (UK): NIHR Journals Library; 2017 Nov. (Efficacy and Mechanism Evaluation, No. 4.5.) Appendix 3, Research diagnostic criteria (the ‘Budapest Criteria’) for complex regional pain syndrome. Available from: