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A multidisciplinary task force graded literature evaluating treatment effects for CRPS-I according to their strength of evidence, published between to June Treatment recommendations based on the literature findings were formulated and formally approved by all Dutch professional associations involved in CRPS-I treatment.
For pain treatment, the WHO analgesic ladder is advised with the exception of strong opioids. For neuropathic pain, anticonvulsants and tricyclic antidepressants may be considered. For inflammatory symptoms, free-radical scavengers dimethylsulphoxide or acetylcysteine are advised. To promote peripheral blood flow, vasodilatory medication may be considered. Percutaneous sympathetic blockades may be used to increase blood flow in case vasodilatory medication has insufficient effect.
To decrease functional limitations, standardised physiotherapy and occupational therapy are advised. Adequate perioperative analgesia, limitation of operating time, limited use of tourniquet, and use of regional anaesthetic techniques are recommended for secondary prevention of CRPS-I.
Based on the literature identified and the extent of evidence found for therapeutic interventions for CRPS-I, we conclude that further research is needed into each of the therapeutic modalities discussed in the guidelines.
Complex Regional Pain Syndrome type I CRPS-I is a condition that causes multiple problems for both patients and practitioners, due to the large variety of available treatment options. The IASP International Association for the Study of Pain definition of the syndrome reads as follows: "CRPS Type I is a syndrome that usually develops after an initiating noxious event, is not limited to the distribution of a single peripheral nerve, and is apparently disproportioned to the inciting event.
It is associated at some point with evidence of oedema, changes in skin blood flow, abnormal sudomotor activity in the region of the pain, or allodynia or hyperalgesia" [ 1 ]. A distinction was made between CRPS type I, formerly known as reflex sympathetic dystrophy RSD , and type II, where a nerve lesion can be detected formerly known as causalgia [ 1 , 2 ].
The condition often starts in an arm or leg, and is characterized by a combination of autonomic, sensory and vasomotor symptoms. Pain, temperature asymmetry impaired movement, change in skin colour, hyperaesthesia, hyperalgesia, hyperpathy, tremor, involuntary movements, muscle spasms, paresis, pseudoparalysis, skin, muscle and bone atrophy, hyperhidrosis and changes in hair and nail growth have been reported in patients with this syndrome [ 3 ].
It usually requires long-term, intensive medical therapy whereby many CRPS-I patients are no longer able to perform their usual social role in everyday life. Various sets of diagnostic criteria are used side by side, and many different therapies have been applied to this patient group.
The complexity of this problem, the fact that various disciplines are involved in treatment, and the consequences for the patient's psychosocial functioning mean that a clear, uniform set of guidelines is essential. In the light of the foregoing considerations, a multidisciplinary task force was instigated by the Dutch Society of Rehabilitation Specialists and the Dutch Society of Anaesthesiologists in order to draw up evidence-based guidelines for CRPS-I treatment.
A multidisciplinary task force was set up in the autumn of An even spread between geographical locations, balanced representation of the various societies and bodies involved, and a fair division between members with an academic background and those from a non-academic background was ensured.
Members of the task force were further subdivided into project groups addressing specific areas of CRPS treatment. Reference lists of articles identified were screened for relevant articles that did not come up in the database search, and recent guidelines were consulted.
Studies were selected based on their methodological strength meta-analyses, systematic reviews, randomized controlled trials RCT's and controlled trials CT's.
Systematic reviews and meta-analyses, considered to have the highest evidential strength, were given precedence over individual articles included in the review. In case these studies were not available, comparative cohort studies, comparative patient control trials or non-comparative trials were used in the evaluations. Other important criteria were: adequate size, adequate follow-up, adequate exclusion of selection bias, and whether the results obtained can be generalized to the Dutch health care system.
The search covered the period from to June , although some studies published prior to or after this period were also used for the guidelines. The members of the project group assessed the quality of these studies on the basis of evidence-based guideline development EBGD assessment forms. These descriptions ranged from clear statements about efficacy "It is proven that The project group members produced texts, either individually or in subgroups. These texts comprised background information with respect to the intervention and studies assessed, conclusions regarding the efficacy of the intervention according to strength of evidence and additional considerations concerning treatment related issues i.
All texts including recommendation were discussed at plenary meetings and approved after comments had been taken into account. The plenary project group met ten times to discuss draft texts. The draft guidelines were sent for external review to the participating professional societies see acknowledgements for details and were presented and discussed at an open national meeting.
Once all comments had been taken into account, the guidelines were adopted by the full project group and sent to the participating professional organisations for final approval. Formal endorsement was obtained in December The conclusions for each treatment modality including strength of evidence and underlying literature will be presented in italics in the result section. The final recommendations for the different treatment modalities will be described at the end of this article.
A practical algorithm based on these guidelines is presented in additional file 2. Database and cited reference search revealed 94 relevant studies after selection. These included 25 studies on oral or topical drug interventions, 42 studies on invasive treatments, 15 on paramedical interventions, 4 on primary and 8 on secondary prevention of CRPS.
Treatment interventions for children with CRPS, comprising 8 studies were described separately. Although analgesics are often used when treating patients with CRPS-I, and their use is described in various treatment protocols and guidelines [ 6 - 8 ], the scientific support for their administration to patients with CRPS-I is very limited.
Sixty-one CRPS-I patients were retrospectively evaluated with respect to the effects of 60 mg of keterolac administered by means of a regional intravenous blockade [ 10 ]. Patients with allodynia had significantly less response to the treatment. Conflicting data have been published with regard to the use of NSAIDs in patients with neuropathic pain [ 11 ]. No significant differences were found between the extent of pain reduction and the average time for ESES to become effective. On average, the morphine group reported 20 side-effects a day, against 2 a day in the placebo group.
An uncontrolled study with 9 CRPS I and II patients evaluated the effects of continuous infusion of morphine in the axillary plexus following stellate blockade [ 13 ]. Significant pain reduction at rest and at movement and increased grip strength were found.
However, the steady-state morphine concentrations were lower than the minimally effective analgesic concentration. Systematic reviews on their use for neuropathic pain have found tramadol to be effective [ 14 ].
Positive short-term effects have also been reported for strong acting opioids administered for neuropathic and musculoskeletal pain [ 15 ]. There is insufficient evidence for the effects of infusion of morphine to the axillary plexus on pain in CRPS-I patients level 3: Azad et al. No significant differences were found between active and placebo treatment with respect to initial peak pain reduction [ 16 ]. An uncontrolled open study investigated the long term effects mean follow up 32 months, range months of epidural administration of bupivacaine to 14 patients with CRPS-I in the knee [ 17 ].
Treatment was continued with continuous administration of a narcotic. No pain control data were described, however, 11 patients were seen to have a complete improvement of CRPS-I symptoms at the end of the follow-up. There is insufficient evidence to allow any statement about the efficacy of local anaesthetics administered to the sympathetic ganglia in CRPS-I patients level 3: Price et al. There is insufficient evidence to allow any statement about the efficacy of epidural administered local anaesthetic to CRPS-I patients.
Due to use of different interventions the efficacy of epidural administration of local anaesthetics cannot be determined level 3: Cooper et al. The average duration of pain reduction data of 20 patients was 9. The side-effects were intoxication, hallucinations, dizziness, nausea, light-headedness and blurred vision. There are indications that intravenous administration of a sub-anaesthetic dose of ketamine reduces pain in CRPS-I patients level 3: Correll et al.
Two placebo-controlled, randomized studies have been found that examined the use of gabapentin in neuropathic pain patients. Dizziness, sleepiness and fatigue occurred significantly more often in patients taking gabapentin than in patients taking placebo. There are indications that gabapentin administered at doses of to mg every 24 hours in the first eight weeks can cause some reduction in pain symptoms suffered by patients with CRPS-I.
There is limited evidence that gabapentin reduces sensory abnormalities such as hyperaesthesia and allodynia. There is no evidence that anticonvulsants such as carbamazepine, pregabalin and phenytoin are effective in reducing pain in CRPS-I patients level 4.
There is no evidence that antidepressants are effective in reducing pain in patients with CRPS-I level 4. Doses of this strength can only be spread onto patients' skin if the painful body part is first numbed by epidural anaesthesia. No scientific conclusions can yet be drawn from this open-label study. A prospective crossover study [ 22 ] with 20 patients found a positive effect of dimethylsulphoxide DMSO on the function of the affected limb.
B ; Goris et al. B , Zuurmond et al. No controlled studies have been carried out on the treatment of either dystonia or spasms in patients with CRPS-I. Two descriptive studies report that anticholinergics have never produced lasting effects [ 29 , 30 ].
There is insufficient evidence of the efficacy of muscle relaxants in treating movement disorders associated with CRPS-I, such as dystonia and muscle spasms level 3: Bathia et al.
C , Van Hilten et al. C , Jankovic et al. C , Marsden et al. C , Schwartzman et al. One study described the use of botulin toxin A to treat 14 patients with very severe tonic dystonia of the hand 'clenched fist' [ 31 ]. An 'overall' improvement in pain and muscle relaxation was achieved in four out of five hands, but the extent of improvement was not described. Other articles report that botulin toxin injections never work, or only work for a short period, and rarely lead to improvement in functionality [ 27 , 29 ].
C , Jancovic et al. Only the latter study was preceded by a double-blind placebo-controlled crossover screening procedure aimed to ascertain whether patients would be suitable for having a programmable pump for ITB fitted.
Comparison with a placebo revealed that baclofen significantly improved outcomes. Six patients underwent the implant procedure and were monitored for 1. Zuniga et al. Pain, allodynia and autonomic disorders responded well to ITB. The main side-effects of the screening process and continuous administration of ITB are post-puncture headache, diminished consciousness and urine retention [ 33 ]. C , Zuniga et al.
All the studies found corticosteroids to have a very pronounced beneficial effect. Little is known as to the duration and dosage level 3: Christensen et al. C , Grundberg et al. C , Kozin et al.
Evidence based guidelines for complex regional pain syndrome type 1
In search for the etiology of the complex regional pain syndrome