The diagnosis of reflex sympathetic dystrophy/complex regional pain syndrome (RSD/CRPS) can be made in the following context. A history of trauma to the affected area associated with pain that is disproportionate to the inciting event plus one or more of the following:
Thus patients do not have to meet all of the clinical manifestations listed above to make the diagnosis of RSD/CRPS. The new CRPS classification system acknowledges this fact by stating that some patients with RSD/CRPS may have a third type of CRPS by categorizing it as "otherwise not specified." There seems to be a small group of patients whose pain following trauma resolves over time, leaving the patient with a movement disorder. The pain and symptoms of RSD/CRPS may exceed both the magnitude and duration of symptoms expected from the normal healing process expected from the inciting event. Similarly, the RSD/CRPS diagnosis is precluded by the existence of known pathology that can be explained by the observed symptoms and degree of pain. There are "grades" of this syndrome described in the literature with symptoms ranging from minor to severe.
The staging of RSD/CRPS is a concept that is dying. The course of the disease seems to be so unpredictable between various patients that staging is not helpful in the treatment of RSD/CRPS. Not all of the clinical features listed below for the various stages of RSD/CRPS may be present. The speed of progression varies greatly in different individuals. Stage I and II symptoms begin to appear within a year. Some patients do not progress to Stage III. Furthermore, some of the early symptoms (Stage I and II) may fade as the disease progresses to Stage III. The following stages are presented in these guidelines merely for historical significance.
There is no laboratory test that can stand alone as proof of RSD/CRPS. However, there are a couple of tests (thermogram and bone scan) which can be useful in providing evidence for RSD/CRPS.
The single most important modality for treating the patient with RSD/CRPS is education. The informed consent process should be the focus of education. The physician defines the potential benefits, risks, alternatives (and costs). From the start, the therapeutic goals must be defined and accepted by the patient:
The cornerstone in the treatment of RSD/CRPS is normal use of the affected part as much as possible. Therefore, all modalities of therapy (drugs, nerve blocks, transcutaneous electronic nerve stimulation [TENS], physical therapy, etc.) are employed to facilitate movement of the affected region of the body. Although physical therapy is an important treatment modality, significant misuse and overuse of this modality may occur. Often the physical therapist will treat the patient with RSD/CRPS the same as a stroke or a nerve plexus injury, (which will fail due to extreme pain and possible injury with passive manipulation). The primary goal of the physical therapist should be to teach the patient how to use their affected body part through activities of daily living. Swimming pool exercises are very helpful, especially for RSD/CRPS of the lower extremity where weight-bearing can be problematic. The goal of physical therapy should be to create independence from the health care system in the shortest period. Learning that "to hurt is not to harm" is difficult, but it is essential to avoid re-injury. Learning the non-protective nature of pain due to RSD/CRPS takes time.
For patients who are significantly impaired in their ability to mobilize their extremity, it is urgent to offer the patient the opportunity to determine the contribution of their sympathetic nervous system to their pain. This is accomplished by a sympathetic nerve block to the affected extremity (Figure 2, "Treatment Protocol" in the original guideline). Future therapeutic options for the patient will depend on whether their pain is determined to be sympathetically maintained pain (SMP) or sympathetically independent pain (SIP). Published reports suggest that the best response to sympathetic blocks will occur if the blocks are given as soon as possible during the course of the disease.
The "LET'S TRY THIS NOW" approach is to be deplored because it indicates that the physician has not defined a strategy to achieve specific therapeutic goals in the shortest period of time. It also adds to the confusion, frustration, anxiety and depression of the patient, which may intensify the patient's pain and adversely affect the doctor-patient relationship.
- Establish a written treatment protocol:
Initiate the safest, simplest, and most cost-effective therapies first. (Refer to Figure 2 in the original guideline for details). If the patient fails to progress in mobilizing the extremity, it is essential to offer the patient a series of 3 sympathetic blocks immediately. The purpose of the sympathetic blocks is three-fold: to treat, to diagnose if the pain is sympathetically maintained and to provide prognostic information. The sympathetic block provides a prognostic indicator if sympathectomy or other treatment modalities would be the next appropriate step. Sympathetic blocks are discussed in detail below.
After the physician has completed a defined course of treatment (e.g., a series of 3-6 sympathetic blocks), it would be helpful to prepare an update report that would document the patient's response to the course of treatment. The report should reflect a basis for further treatment and it should address future rehabilitation needs. Sharing a copy of the update report with the patient will help ensure that all parties are kept informed. Sharing the report with the patient helps keep the patient and physician focused on achieving appropriate therapeutic goals. An update report should address five areas of care:
- Procedures (e.g., nerve blocks)
- Medications
- Physical/occupational therapy
- Psychosocial issues
- New laboratory tests or consults
- Psychosocial modalities must be considered in all patients with RSD/CRPS:
Psychiatric illness or personality disorder does not cause RSD/CRPS but it is likely that personality contributes to the disease. Patients with severe, advanced stage RSD/CRPS usually undergo a psychosocial evaluation during the series of sympathetic blocks or prior to offering the patient more invasive treatments. In some cases, a formal psychosocial evaluation should be initiated much earlier in the course of treatment. For example, children with RSD/CRPS may require a thorough evaluation to determine the family support structure and the coping mechanisms needed by the family for optimal rehabilitation of the child.
The psychosocial evaluation should always be done by an expert in chronic pain and should always include an assessment of pain coping skills and drug abuse potential. Stress is a known cause of exacerbation of this disease, making emergency treatment more necessary. A lot of memorials sent to fund RSD/CRPS research are the result of suicides! The potential for committing suicide needs to be assessed. The patient may need to participate in a formal pain management program as an outpatient or an inpatient. Chronic pain patients referred for a psychosocial evaluation tend to be defensive. An MMPI or other psychological test can help identify the psychosocial problems. Patients must be properly motivated to improve their coping skills; otherwise, application of these psychosocial modalities is a waste of time. Relaxation techniques (e.g. breathing exercises) as well as biofeedback and self-hypnosis may be appropriate treatment modalities for some patients.
- Sequential Drug Trials:
Try to initiate sequential trials for each modality of therapy. The application of multiple therapies at the same time, a shotgun approach, makes it almost impossible to evaluate and optimize an individual therapy for safety and efficacy. Patients must be advised that the optimal dose for medications varies greatly among patients. Therefore, it is usually necessary to gradually increase the dose of their medication to the point of significant toxicity in order to determine optimal dose. The dose is then reduced to the next lower level. Thus it is important for the patient to become familiar with all of the potential side effects of a medication before trying it. Sequential trials with many different drugs may be required to determine the best medication for the patient.
Medications are generally prescribed according to the following characteristics of the pain:
- Constant pain
- Pain causing sleep problems
- Inflammatory pain or pain due to recent tissue injury
- Spontaneous jabs (paroxysmal dysesthesias and lancinating pain)
- Sympathetically maintained pain (SMP)
- Muscle cramps
Medications Used to Treat Chronic Pain:
"Off-labeling" prescribing means that a government (e.g., the U.S. Food and Drug Administration [FDA]) approved the medication for one purpose but it is used by physicians for another purpose. For example, aspirin is a pain medication but it can also be used to decrease the risk of a heart attack by inhibiting the aggregation of platelets. Off-label prescribing is a common practice in treating various chronic pain problems. Some of these drugs have been proven to be effective in decreasing pain due to nerve injury (neuropathic pain) in well-controlled clinical trials. Since RSD/CRPS is believed to be caused by nerve injury (neuropathic pain), these drugs are used to treat this condition as well. The patient should consider weaning themselves from these various medications periodically with the treating physician's knowledge to determine for themselves that the medication is actually helping to alleviate their symptoms. Some medications need to be weaned slowly (e.g. narcotics, baclofen) to minimize withdrawal symptoms.
Medications Commonly Used to Treat RSD/CRPS Based on the Type of Pain Include:
For constant pain associated with inflammation:
- Nonsteroidal anti-inflammatory agents (e.g., aspirin, ibuprofen, naproxen, indomethacin, etc.)
For constant pain not caused by inflammation:
- Agents acting on the central nervous system by an atypical mechanism (e.g., tramadol)
For constant pain or spontaneous (paroxysmal) jabs and sleep disturbances:
- Anti-depressants (e.g. amitriptyline, doxepin, nortriptyline, trazodone, etc.)
- Oral lidocaine (mexilitine - some what experimental)
For spontaneous (paroxysmal) jabs:
- Anti-convulsants (e.g., carbamazepine, gabapentin may relieve constant pain as well)
For widespread, severe RSD/CRPS pain, refractory to less aggressive therapies:
Oral opioid. The use of opioids (e.g. narcotics with names such as Darvon, Vicodin, Loratab, Percocet, morphine, codeine, etc) to treat RSD/CRPS is debated and there are potential hazards. Therefore, in order to ensure appropriate informed consent, it is recommended that the patient sign a doctor-patient "contract" (Refer to the "Opioid Treatment Protocol" in the original guideline for details).
Patients may require immediate and adequate pain relief. In some cases it may take time to transpire from the time of the patient's first visit to the time of adequate treatment. In all probability, the pain and degenerative cycle would progress. Since the abuse potential is minimal when narcotics are used for severe pain, practitioners should not withhold narcotic treatment, if the patient demonstrates pain relief with this medication.
For the treatment of sympathetically maintained pain (SMP):
- Clonidine Patch. Studies suggest that clonidine may decrease pain in RSD/CRPS by inhibiting the sympathetic nervous system. A treatment protocol for using the Clonidine Patch to treat RSD/CRPS can be found in the journal Regional Anesthesia.
For muscle cramps (spasms and dystonia) which can be very difficult to treat:
- Klonopin (clonazepam)
- Baclofen
For localized pain related to nerve injury:
- Capsaicin cream. (This medication is applied to the skin and behaves like hot peppers. The effectiveness of capsaicin cream in the treatment of RSD/CRPS has not been determined).
- Physical and Occupational Therapy:
Patients need to be educated on how to use their affected body part through activities of daily living. For example, for lower extremity RSD/CRPS, patients may need to be taught weight bearing versus non-weight bearing exercises. Hydrotherapy is usually medically necessary for muscle (myofascial) pain and spasms. Application of pressure (massage) and/or moist heat applications can sometimes relieve severe muscle cramps. The physical therapist can also teach the patient how to use a TENS unit (a noninvasive electrical device that stimulates the surface of the skin). Pool therapy can be very effective for improving mobility
- Sympathetic Blocks:
There are three reasons to consider sympathetic blockade to facilitate the management of RSD/CRPS. First, the sympathetic block may provide a permanent cure or partial remission of RSD/CRPS. Second, by selectively blocking the sympathetic nervous system the patient (and physician) will gain further diagnostic information about what is causing the pain. The sympathetic block helps determine what portion of the patient's pain is being caused by malfunction of their sympathetic nervous system. Third, the patient's response to a sympathetic block provides prognostic information about the potential merits of other treatments.
The maximum sustained benefit from a series of sympathetic blocks is usually apparent after a series of 3 to 6 blocks. Even if the original site is unresponsive to sympathetic blockade, future exacerbation of RSD/CRPS symptoms at the same site or at a distant site may be responsive to 1 to 3 sympathetic blocks. THE GOAL IS ALWAYS TO TREAT BUT DON’T OVER TREAT. (Refer to the treatment section of the original guideline for additional details and rationale for sympathetic blockade.)
- Sympathectomy:
If there is a significant decrease in pain following the sympathetic block, the patient is said to have sympathetically maintained pain (SMP). If there is not a significant decrease in pain, the patient has sympathetically independent pain (SIP). Only patients with SMP should be considered for a sympathectomy. Patients are advised to expect no more relief of their pain from a permanent block, i.e. sympathectomy, than they received from either a SGB or a LSB. Thus the patient must really pay attention to the magnitude of pain relief and improvement in function following each sympathetic block. Sympathectomy is a relatively invasive procedure with potential complications and should be pursued by the patient only if they are certain about the temporary therapeutic benefits that they received from a series of SGBs or LSBs.
Recently, laparoscopic sympathectomy has been developed for sympathectomy of the upper extremity. This technique requires the placement of three small holes temporarily in the side of the chest wall while the patient is under general anesthesia. For the lower extremity, the patient has the choice of dissolving (destroying) the sympathetic nerves with phenol injected through a needle while the patient is awake (percutaneous phenol sympathetic neurolysis) or a surgical sympathectomy under general anesthesia. Other techniques for sympathectomy have also been used. The patient must be informed of the pros and cons of each approach.
Post-sympathectomy pain (neuralgia) is a potential complication of all types of sympathectomy. Post-sympathectomy pain is typically proximal to the original pain (e.g. proximal means that the pain may appear for the first time in the groin or buttock region for sympathectomy of the lower extremity and pain in the chest wall region for sympathectomy of the upper extremity). Patients may think that their RSD/CRPS has spread to a new region after sympathectomy because the pain feels similar to their original RSD/CRPS pain. The post-sympathectomy pain usually resolves on its own or with 1-3 sympathetic blocks. Thus for some patients, sympathectomy may be a two-step procedure; destruction of sympathetic nerves followed by a sympathetic block.
Published data suggests that sympathectomy in properly selected RSD/CRPS patients may provide one of the most effective treatments for RSD/CRPS. The selection criteria for sympathectomy are critical in achieving long-term success.
- Placebo:
The placebo effect (decreased pain due to an inactive treatment such as a sugar pill) must be considered in the treatment of RSD/CRPS. Although the figure of 33% is commonly quoted in papers and textbooks as the percentage of people who will respond to a placebo, it is misleading because the "percentage" varies enormously (from close to 0 to 100%) depending on the exact circumstances. Physician and patient must have an understanding about the placebo effect, otherwise the patient is at risk of being over-treated. Recognition of placebo versus specific pain-relieving treatment may be difficult, but there are some distinguishing characteristics.
- The greater the invasiveness of the procedure itself, the greater the placebo effect.
- The greater the expectation for pain relief, the greater will be the placebo effect.
- The placebo tends to be of less duration. For example, close monitoring of the patient's pain for hours and days after each sympathetic nerve block has shown that the pain-reducing effect of the saline (placebo) injection subsides within the first few hours, whereas that of the local anesthetic injection persists for several days.
- The placebo tends to be less reproducible with each successive treatment.
Therefore, it may be of great potential therapeutic value to provide each patient with a series of multiple sympathetic blocks separated by brief intervals (e.g. one week) simply to determine whether such blocks are effective treatments.
The time-course of pain relief and improvement in function must be monitored closely by the patient. The actual local "anesthetic" effect of a sympathetic block lasts for only a few hours. But patients with SMP usually experience pain relief that far outlasts the duration of the local anesthetic effect. This type of extended relief of pain and improvement in mobility beyond the duration of the nerve block is believed to indicate an element of "reflex" activity or a "vicious cycle" in the affected region of the body, either from muscle spasm or from sympathetic over-activity.
Intentional or not, some patients may not reliably report the effects of sympathetic blocks. As noted, a good sympathetic block provides a feeling of warmth that will act as a "cue." Some patients respond to that change in sensation by anticipating the results or stating it as a genuinely perceived reduction in pain. Others may deceitfully report pain relief, since they believe that such a report is necessary for further treatment, attention, or other desired gain. Some patients may feel that some "treatment" is better than no treatment at all, even if the treatment is ineffective.
- Other Types of "Sympathetic Blocks":
A sympathetic blocker (alpha adrenergic antagonist), phentolamine, given I.V. has been advocated as a diagnostic test for SMP. However, false negative tests have been reported as high as 43%. Moreover, this approach is somewhat elaborate and requires considerable technician time and expense. The phentolamine test is a diagnostic procedure while a sympathetic block is a diagnostic, prognostic and therapeutic procedure. However, the phentolamine test may be valuable treatment option in the situation where a sympathetic block is not possible or when multiple extremities are involved.
Epidural blocks are less specific for blocking the sympathetic nervous system and, therefore, they are not as useful for diagnostic and prognostic objectives. The infusion of local anesthetic through the epidural catheter may cause temporary weakness in the legs, making walking dangerous. Placement of long-term epidural catheters to treat RSD/CRPS still occurs in practice. Perhaps this is because anesthesiologists are more familiar with the epidural catheter technique than with the selective sympathetic block technique. The long-term epidural catheter approach is more expensive and patients are placed at more risk for certain rare life-threatening complications, e.g. infection (epidural abscess). Often a short (2-5 days) hospitalization will be necessary to determine the clinically most appropriate dose of the epidural agent for constant infusion. Dislodgment of the epidural catheter is a relatively common problem. The use of a lumbar sympathetic catheter may provide a more specific sympathetic block than an epidural catheter, but the lumbar sympathetic catheter is more likely to become dislodged during exercise. There is a place for the use of epidural and lumbar sympathetic catheters in the treatment of RSD/CRPS but the physician should justify these techniques on a case by case basis.
Another technique used to carry out a sympathetic block involves the intravenous injection of sympathetic blocking agents (e.g. guanethidine, bretylium and clonidine) into an extremity and limiting spread of the agent to the entire body by applying a tourniquet to the extremity. This method requires placing an IV in the painful extremity and may be technically extremely difficult due to severe swelling (edema) of the extremity. The patient may not be able to confirm that they actually received a sympathetic block because the "cue", a warming sensation in the extremity, may not be felt. Furthermore, there is no evidence that this technique is more effective than the usual sympathetic blocks for the diagnosis and treatment of RSD/CRPS. The IV tourniquet technique using a sympathetic blocking agent may be considered as an option for patients who must take blood thinners (anticoagulants) where a SGB or a LSB may cause major bleeding.
- Spinal Cord Stimulation (SCS):
Spinal cord stimulation (SCS) uses low intensity, electrical impulses to trigger selected nerve fibers along the spinal cord (dorsal columns), which are believed to stop pain messages from being transferred to the brain. SCS replaces the area of intense pain with a more pleasant tingling sensation called paresthesia. The tingling sensation will remain relatively constant and should not hurt. There is some experimental evidence that SCS may enhance the flow of blood to the affected extremity by blocking the sympathetic nervous system.
A temporary trial, with a temporary electrode, should be performed first before implanting permanent electrode(s). Given that SCS is a relatively invasive, costly procedure and given that RSD/CRPS patients are often desperate and frustrated, a baseline psychosocial evaluation that addresses pain management issues should be considered. Although rare, spinal infection and paralysis are potential complications. The ability to insert the electrode through a small needle has reduced the risk of the procedure and has facilitated the trial with a temporary electrode.
Treating RSD/CRPS with SCS poses unusual clinical and technical problems. RSD/CRPS tends to be an unpredictable disease from a technical standpoint. The need to focus SCS on the most painful region must be kept in mind, which is more difficult in RSD/CRPS, because the location of the worst pain may change. Furthermore, the pain from RSD/CRPS may spread to distant parts of the body, requiring multiple successive implanted stimulators to cover the largest possible area. Therefore, even when RSD/CRPS is limited to one extremity, it is wise to widen stimulation to zones to which the pain might spread.
Because of the risks and high costs of spinal cord stimulation, the treatment is reserved for severely disabled patients. A recent well-controlled study shows that with careful selection of patients and successful test stimulation, SCS is safe, reduces pain, and improves the health-related quality of life in patients with severe RSD/CRPS.
The External Battery System Versus the Internal Battery System for Spinal Cord Stimulation
In order to make an informed choice about SCS, the patient and physician should consider the pertinent differences between the internal and external battery systems (refer to the original guideline document for details on comparisons between internal and external battery systems for spinal cord stimulation).
Radiofrequency (RF) vs. Implantable Pulse Generator (IPG) Neurostimulation Systems
An informed choice of SCS system by the patient and physician should be made after considering the patient’s current pain patterns and the possibility of progression of the RSD and the pertinent differences between RF and IPG systems (refer to the original guideline document for further discussion).
- Morphine Pump:
It is well-recognized that a single injection of morphine into the spinal fluid (within the intrathecal space) produces a selective pain-blocking effect on the spinal cord. This selective effect on the spinal cord spares the patient from many of the serious side effects caused by morphine when it is given orally (e.g. sedation). Soon after this discovery, enthusiasm developed to implant permanent morphine pumps to treat non-cancer chronic pain, especially after Medicare began to approve this surgical procedure for reimbursement. The implantation of a morphine pump is a relatively invasive and expensive treatment modality. Despite almost 20 years of testing, no scientific evidence has emerged that long-term use of the morphine pump offers an advantage over oral morphine for treating various chronic pain syndromes, including RSD/CRPS. In fact, many patients with the implanted morphine pump take oral morphine at the same time. The same complications sometimes associated with oral morphine use are also found with the morphine pump, such as development of drug tolerance, nausea, constipation, weight gain, decreased sex appetite (libido), swollen legs (edema), and increased sweating. In addition, malfunction of the pump system (dislodgement of the catheter) can be a significant problem.
A recent study suggests that with careful selection of patients, the implantation of a pump for the spinal infusion of baclofen may be a valuable means for treating a certain type of muscle cramp called dystonia in patients with severe RSD/CRPS.
- How to Determine the Effectiveness of Treatments for RSD/CRPS:
Refer to the original guideline document for details on the natural history of RSD/CRPS, placebo or nonspecific effects of treatment, and specific effects of treatment.
- RSD/CRPS in Children:
A 30-minute video on RSD/CRPS in children was peer-reviewed by an international panel of experts. (Refer to the original guideline document for further details on the video.)
