Abstract

Background

Complex regional pain syndrome (CRPS) is a painful and disabling condition that usually manifests in response to trauma or surgery and is associated with significant pain and disability. CRPS can be classified into two types: type I (CRPS I) in which a specific nerve lesion has not been identified and type II (CRPS II) where there is an identifiable nerve lesion. Guidelines recommend the inclusion of a variety of physiotherapy interventions as part of the multimodal treatment of people with CRPS. This is the first update of the review originally published in Issue 2, 2016.

Objectives

To determine the effectiveness of physiotherapy interventions for treating pain and disability associated with CRPS types I and II in adults.

Search methods

For this update we searched CENTRAL (the Cochrane Library), MEDLINE, Embase, CINAHL, PsycINFO, LILACS, PEDro, Web of Science, DARE and Health Technology Assessments from February 2015 to July 2021 without language restrictions, we searched the reference lists of included studies and we contacted an expert in the field. We also searched additional online sources for unpublished trials and trials in progress.

Selection criteria

We included randomised controlled trials (RCTs) of physiotherapy interventions compared with placebo, no treatment, another intervention or usual care, or other physiotherapy interventions in adults with CRPS I and II. Primary outcomes were pain intensity and disability. Secondary outcomes were composite scores for CRPS symptoms, health‐related quality of life (HRQoL), patient global impression of change (PGIC) scales and adverse effects.

Data collection and analysis

Two review authors independently screened database searches for eligibility, extracted data, evaluated risk of bias and assessed the certainty of evidence using the GRADE system.

Main results

We included 16 new trials (600 participants) along with the 18 trials from the original review totalling 34 RCTs (1339 participants). Thirty‐three trials included participants with CRPS I and one trial included participants with CRPS II. Included trials compared a diverse range of interventions including physical rehabilitation, electrotherapy modalities, cortically directed rehabilitation, electroacupuncture and exposure‐based approaches. Most interventions were tested in small, single trials. Most were at high risk of bias overall (27 trials) and the remainder were at 'unclear' risk of bias (seven trials). For all comparisons and outcomes where we found evidence, we graded the certainty of the evidence as very low, downgraded due to serious study limitations, imprecision and inconsistency. Included trials rarely reported adverse effects.

Physiotherapy compared with minimal care for adults with CRPS I

One trial (135 participants) of multimodal physiotherapy, for which pain data were unavailable, found no between‐group differences in pain intensity at 12‐month follow‐up. Multimodal physiotherapy demonstrated a small between‐group improvement in disability at 12 months follow‐up compared to an attention control (Impairment Level Sum score, 5 to 50 scale; mean difference (MD) ‐3.7, 95% confidence interval (CI) ‐7.13 to ‐0.27) (very low‐certainty evidence). Equivalent data for pain were not available. Details regarding adverse events were not reported.

Physiotherapy compared with minimal care for adults with CRPS II

We did not find any trials of physiotherapy compared with minimal care for adults with CRPS II.

Authors' conclusions

The evidence is very uncertain about the effects of physiotherapy interventions on pain and disability in CRPS. This conclusion is similar to our 2016 review. Large‐scale, high‐quality RCTs with longer‐term follow‐up are required to test the effectiveness of physiotherapy‐based interventions for treating pain and disability in adults with CRPS I and II.

Author(s)

Keith M Smart, Michael C Ferraro, Benedict M Wand, Neil E O'Connell

Abstract

Plain language summary

Does physiotherapy improve pain and disability in adults with complex regional pain syndrome?

Key messages

We are very uncertain if physiotherapy treatments improve the pain and disability associated with complex regional pain syndrome (CRPS).

We are very uncertain because the clinical trials we found:

‐ were not conducted or reported as well as they could have been (or both);

‐ included small numbers of patients with CRPS;

‐ tested a large range of different types of physiotherapy treatments; and

‐ because there were a limited number of trials that investigated any particular physiotherapy treatment.

We are very uncertain if physiotherapy treatments cause unwanted side effects; more evidence is required to clarify this.

Good‐quality clinical trials are required to further investigate whether or not physiotherapy treatments improve the pain and disability associated with CRPS.

Treating pain and disability in adults with complex regional pain syndrome

Complex regional pain syndrome is a painful and disabling condition that can occur after trauma or surgery and is associated with significant pain and disability. CRPS can be classified into two types: type I (CRPS I) in which a specific nerve injury has not been identified and type II (CRPS II) where there is an identifiable nerve injury. Guidelines recommend that physiotherapy rehabilitation should be included as part of the treatment for CRPS. Physiotherapy for CRPS could include a range of treatments and rehabilitation approaches, such as exercise, pain management, manual therapy, electrotherapy or advice and education, either used alone or in combination. Physiotherapy is recommended because it is thought that it may improve the pain and disability associated with CRPS.

What did we want to find out?

We wanted to find out if physiotherapy treatments improve pain and disability in adults (aged over 18) with CRPS.

What did we do?

We searched for clinical trials that involved adults with CRPS, which compared physiotherapy treatments to placebo treatments or routine care or which compared different physiotherapy treatments to each other.

We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as trial methods, size and length of follow‐up.

What did we find?

We found 33 clinical trials that involved 1317 people in total with CRPS type I of the upper or lower limb, or both. The trials investigated the effect of a range of physiotherapy treatments. We found only one trial involving 22 people with CRPS type II.

Here we present the findings from comparisons between different physiotherapy treatments and placebo treatments or routine care and for comparisons of different physiotherapy treatments to each other.

Reducing pain

We are uncertain if any of the physiotherapy treatments investigated in the clinical trials we identified help reduce the pain associated with CRPS.

Reducing disability

We are uncertain if any of the physiotherapy treatments investigated in the clinical trials we identified help reduce the disability associated with CRPS.

Side effects

We are uncertain if any of the physiotherapy treatments investigated in the clinical trials we identified cause any unwanted side effects.

What are the limitations of the evidence?

Clinical trials were small and most have been conducted in ways that could introduce errors into their results. This limited our confidence in the evidence.

How up to date is the evidence?

The evidence is up to date to July 2021.

Author(s)

Keith M Smart, Michael C Ferraro, Benedict M Wand, Neil E O'Connell

Reviewer's Conclusions

Authors' conclusions 

Implications for practice 

For adults with complex regional pain syndrome (CRPS)

The evidence is very uncertain about the effects of any of the physiotherapy interventions identified in this review, including multimodal physiotherapy, exposure‐based interventions and graded motor imagery, on the pain and disability of CRPS I at short‐, medium‐ or long‐term follow‐up when compared to various active control interventions. Despite the uncertainty, it is likely that, in line with contemporary clinical guidelines, physiotherapy and rehabilitation‐based interventions will continue to be recommended as first‐line treatments for people with CRPS.

For clinicians

There is insufficient evidence to draw any conclusions regarding the effectiveness of any of the physiotherapy interventions for CRPS I identified in this review. Multimodal physiotherapy, aerobic exercise, graded motor imagery, mirror therapy, virtual reality, TENS and 'exposure in vivo' may reduce pain and/or disability for people with CRPS I when compared to various active control interventions but the evidence is very uncertain. These effects were mainly only apparent at short‐term follow‐up. However, we have very little confidence in the current evidence. In light of the uncertainty we encourage clinicians to remain up to date with the evidence and consider ways to present this information in meaningful ways to patients that enables them to make informed decisions regarding their care. In this knowledge vacuum clinicians' treatment selection is extremely challenging and is likely to be based on their training, access to relevant expertise and support and personal preferences. Well designed, executed and reported randomised controlled trials (RCTs) are critical to better guide future patient care. We are unable to draw any conclusions regarding physiotherapy interventions for CRPS II since we found only one small clinical trial for people with CRPS II exclusively.

For policy makers and funders of interventions

The results of this review highlight the uncertainty regarding the effectiveness of any physiotherapy interventions for CRPS I or II. Despite the substantial uncertainty, clinical guidelines recommend rehabilitation therapies as a core treatment for CRPS. The challenge lies in an inability to specifically recommend any one or combined therapeutic approach. Such recommendations remain entirely contingent on the availability of data from future well‐designed and implemented clinical trials. We can say with certainty that the current state of the evidence supports the allocation of research funding for further clinical trials of physiotherapy for CRPS.

Implications for research 

General implications

Overall, given the existing limitations within the current body of evidence, there is a clear need for further research into physiotherapy interventions in people with CRPS but many challenges remain in addressing this problem. Given the relatively low incidence of CRPS, it is likely to be difficult to recruit adequate numbers of participants to clinical trials. It seems likely that the best chance of addressing this challenge is through multicentre, collaborative research projects aimed at recruiting participants from potentially larger pools of clinical populations. The use of telehealth/telerehabilitation trials could facilitate this. It seems unlikely that it will be possible to generate sufficient evidence to support the many individual modalities currently applied to people with CRPS. In this instance there remains a case for taking a pragmatic approach to developing contemporary multi‐modal, individually tailored 'best practice' models of physiotherapy care and prioritising trials of these programmes against usual or minimal care. Such trials might provide pragmatic estimates of effectiveness that best reflect the value of guideline recommended practice. Larger replication trials of graded motor imagery (GMI) and mirror therapy in particular would also be useful in order to provide more accurate estimates of treatment effect for these interventions, which current evidence suggests could offer meaningful clinical benefit.

Design implications

Large, high‐quality randomised controlled trials, with cost‐effectiveness analyses, are needed to investigate the effectiveness of physiotherapy interventions for CRPS. Where such sample sizes are not attainable, future RCTs should, at the very least, be prospectively registered and have a published trial protocol (in accordance with the SPIRIT guidelines; Chan 2013). Future trials should adhere to CONSORT guidance, including that related to the reporting of the development and evaluation of complex interventions (Möhler 2015). There should be a clear rationale outlining the mechanisms that underpin the intervention's effects and how the intervention might affect the outcomes of interest. Mechanism‐specific rehabilitation strategies, whereby treatment selection is based on clinical assessment findings that are thought to reflect the underlying mechanisms of a given patient's CRPS, have been suggested (Packham 2018). Furthermore, trialists should use established diagnostic criteria, clearly report the type and aetiology of CRPS under investigation and adequately describe interventions (according to the TIDieR guidelines; Hoffman 2014). It is our observation that rehabilitation‐based interventions for CRPS often require the ongoing active participation of patients, in the clinic, at home or both. They also have the potential to worsen patients' pain. We invite trialists to accurately report reasons for dropouts from trial arms in an attempt to record and quantify the potential burdensomeness and/or unacceptability of interventions to patients. Accurately reporting reasons for dropout might help rank treatments of apparently equivalent efficacy (or with similarly lacking evidence of efficacy) in terms of what is practicable and least likely to harm. Recommendations for the design of clinical trials of pain interventions are available (Busse 2015; Dworkin 2008; Dworkin 2009; Dworkin 2010; Turk 2008a; Turk 2008b). Finally, when therapeutic exercise is the main or significant component of an intervention, trialists could consider self‐assessing the therapeutic quality of the exercise programme included in their trial using the i‐CONTENT tool, for example (Hoogeboom 2020).

Measurement implications

The wide variety of outcome measures used together with the poor quality of reporting of trial data in a number of studies included in our review highlights the need for trialists to use core outcome sets (Grieve 2016b), adequately report their scoring properties and interpretation, report point estimates with measures of variation for all outcomes at all time points and follow up participants over clinically meaningful lengths of time. Doing so would facilitate comparisons across studies and the statistical pooling of outcome data. A core set of standardised outcome measures for use in CRPS clinical research that might enhance consistency of use and standards of reporting has been developed (Grieve 2017). There is a pressing need to improve the measurement and reporting of adverse effects in this field. In the absence of any consensus or evidence regarding cut‐points from which to interpret the magnitude of clinically important differences in pain intensity based on between‐group differences at post‐intervention time points (Dworkin 2009), trialists, clinicians, policymakers and funders may choose to follow IMMPACT or OMERACT guidance (Busse 2015; Dworkin 2008) until such time as further evidence to guide such decision‐making becomes available.

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