Anesthesia (3)

Complex regional pain syndrome (CRPS) with resistance to local anesthetic block: a case report. (State University of New York at Stony Brook, Stony Brook, NY) J Clin Anesth 2000;12:67–71.
A case of complex regional pain syndrome (CRPS) Type 1 in a 12-year-old girl is presented. The patient did not respond to the usual therapeutic modalities used to treat CRPS including physical therapy, lumbar sympathetic block, epidural local anesthetic block, intravenous lidocaine infusion, or other oral medications. Of note is the fact that during epidural block the patient demonstrated a resistance to local anesthetic neural blockade in the area of the body involved with the pain problem. The mechanism of this resistance could be related to the changes in the dorsal horn cells of the spinal cord, secondary to activation of N-methyl-D-aspartate receptors, which may play a role in the pathophysiology of this pain syndrome.     

Complex Regional Pain Syndrome in the ambulatory surgical care setting.

This article provides an historical synopsis from the 17th century to the present regarding the disease process known as Complex Regional Pain Syndrome (CRPS) Type I. An overview of the disease symptoms, plausible theories, and a review of the pain cycle, relief measures, and a case scenario are reported. The focus of pain blockade was chosen because this was the intervention used in this particular case. The author presents the holistic standpoint of the importance of incorporating complementary alternative medical practices (CAMP) to enhance a positive outcome for this client. OBJECTIVES: -Based on the content of this article, the reader should be able to (1) distinguish the main characteristic between CRPS Type I (reflex sympathetic dystrophy) and CRPS Type II (causalgia); (2) identify symptoms related to CRPS Type I; and (3) identify the stages of CRPS and state potential interventions used in the treatment of CRPS Type I.     

Efficacy of stellate ganglion blockade for the management of type 1 complex regional pain syndrome

INTRODUCTION: The purpose of this study was to examine the efficacy of stellate ganglion blockade (SGB) in patients with complex regional pain syndromes (CRPS I) of their hands. METHODS: After IRB approval and patient informed consent, 25 subjects, with a clinical diagnosis of CRPS I of one hand as defined by the International Association for the Study of Pain (IASP) criteria, had three SGB's performed at weekly intervals. Laser Doppler fluxmetric hand perfusion studies were performed on the normal and CRPS I hands pre- and post-SGB therapy. No patient was included in this study if they used tobacco products or any medication or substance that could affect sympathetic function. The appropriate parametric and nonparametric data analyses were performed and a p value <0.05 was used to reject the null hypothesis. RESULTS: Symptom onset of CRPS I until the initiation of SGB therapy ranged between 3 to 34 weeks. Following the SGB series, patient pain relief was as follows: group I, 10/25 (40%) had complete symptom relief; group II, 9/25 (36%) had partial relief and group III, 6/25 (24%) had no relief. The duration of symptoms until SGB therapy was: group I, 4.6 +/- 1.8 weeks, group II, 11.9 +/- 1.6 weeks and group III, 35.8 +/- 27 weeks. Compared with the normal control hand, the skin perfusion in the CRPS I affected hand was greater in group I and decreased in groups II and III. DISCUSSION: The results of our study demonstrate that an inverse relationship exists between hand perfusion and the duration of symptoms of CRPS I. On the other hand, a positive correlation exists between SGB efficacy and how soon SGB therapy is initiated. A duration of symptoms greater than 16 weeks before the initial SGB and/or a decrease in skin perfusion of 22% between the normal and affected hands adversely affects the efficacy of SGB therapy.     

The symptoms of complex regional pain syndrome type 1 alleviated with lamotrigine: A report of 8 cases

Complex regional pain syndrome type 1 (CRPS) comprises the symptom complex of burning nondermatomal pain, intermittent swelling and discoloration, allodynia, and abnormalities of sudomotor function. Not all patients respond to blockade of the sympathetic nervous system. In this case report we highlight 8 cases with intractable CRPS Type 1 in which the patients derived benefit from the use of lamotrigine in terms of both pain relief and relief of other symptoms.     

Diagnostic and treatment measures in patients with sympathetically maintained pain

The term "sympathetically maintained pain" (SMP) describes a symptom that might accompany a variety of diseases (CRPS, (post-) herpetic and post-injury neuralgia), which might transform into sympathetically independent pain (SIP) after some time. Patients with SMP present a bunch of disorders of the autonomic and sensory system, but the only reliable way to diagnose a pain as SMP is a positive response to an intervention at the sympathetic nervous system. Three ways of influencing the sympathetic system are commonly used: (a) local anesthetic sympathetic blockade (SB), (b) intravenous regional sympathectomy (IVRS) and (c) ganglionic local opioid application (GLOA). A review of current literature shows that SB has certain advantages in diagnostic sensitivity, whereas GLOA might be slightly superior in therapy of some diseases with longstanding pain history. Obviously, the therapeutic benefit of all interventions is complete independent of the accompanying autonomic disorder and of a blockade of efferent fibers. A new heuristic model of the SMP mechanism is presented, including both experimental and clinical data. For reducing the risks of false positive or negative diagnosis of SMP and SIP, a diagnostic algorithm is proposed. This includes optimizing the technique, changes of interventional measures, and adequate monitoring both of analgesia and as well of the extend of efferent sympathetic blockade (e.g. measurement of sympathetic reflexes). The treatment recommendations in patients with SMP vary in dependence of the kind of disease. In SMP, invasive measures play an important, but only limited role within the comprehensive treatment concept. As an example a three-stage, symptom-adapted treatment algorithm is demonstrated for CRPS, including also drug therapy, psychologic and physiotherapeutic approaches.     

Clinical and physiologic evaluation of stellate ganglion blockade for complex regional pain syndrome type I

OBJECTIVE: The efficacy of peripheral sympathetic interruption after stellate ganglion blockade was assessed by a sympathetic function test. Results were compared with clinical signs such as temperature changes, pain reduction, and the development of Horner syndrome to evaluate the correlation with clinical investigations. DESIGN: Stellate ganglion blockade with local anesthetics was carried out via an anterior paratracheal approach in 33 patients suffering from complex regional pain syndrome type I. Patients were examined before and after the procedure. For assessment of sympathetic nervous function, the vasoconstrictor response to sympathetic stimuli was assessed using laser Doppler flowmetry. Clinical parameters like surface temperature changes (thermography), pain relief (visual analogue scale), and Horner syndrome were monitored. RESULTS: Twenty-three (70%) of 33 patients developed an increase in temperature difference between the treated hand and the contralateral hand of more than 1.5 degreesC after the procedure, which is a clinical sign of sympathicolysis. In 48% (n = 11) of these patients, the sympathetic function test showed an undisturbed sympathetic nervous function. In 10 patients, no significant increase in temperature difference was observed. Although these patients presented with a normal sympathetic vasoconstrictor response, 4 felt pain relief of more than 50%, suggesting a placebo effect. Only 7 patients with pain relief revealed both clinical sympathicolysis and extinguished sympathetic nervous function and qualified for sympathetically maintained pain. CONCLUSIONS: Clinical investigation is not reliable in the assessment of stellate ganglion blockade. Proof of sympathetically maintained pain based on pain relief after stellate ganglion blockade is not conclusive.     

Complex regional pain syndromes: the influence of cutaneous and deep somatic sympathetic innervation on pain

OBJECTIVES: Complex regional pain syndromes (CRPS) can be relieved by sympathetic blockade. Different sympathetic efferent output channels innervate distinct effector organs (ie, cutaneous vasoconstrictor, muscle vasoconstrictor. and sudomotor neurons, as well as neurons innervating deep somatic tissues like bone, joints, and tendons). The aim of the present study was to elucidate in CRPS patients the sympathetically maintained pain (SMP) component that exclusively depends on cutaneous sympathetic activity compared with the SMP depending on the sympathetic innervation of deep somatic tissues. METHODS: The sympathetic outflow to the painful skin was modulated selectively in awake humans. High and low cutaneous vasoconstrictor activity was produced in 12 CRPS type 1 patients by whole-body cooling and warming (thermal suit). Spontaneous pain was quantified during high and low cutaneous vasoconstrictor activity. By comparing the cutaneous SMP component with the change in pain that was achieved by modulation of the entire sympathetic outflow (sympathetic ganglion block), the SMP component originating in deep somatic structures was estimated. RESULTS: The relief of spontaneous pain after sympathetic blockade was more pronounced than changes in spontaneous pain that could be induced by selective sympathetic cutaneous modulation. The entire SMP component (cutaneous and deep) changes considerably over time. It is most prominent in the acute stages of CRPS. CONCLUSIONS: Sympathetic afferent coupling takes place in the skin and in the deep somatic tissues, but especially in the acute stages of CRPS, the pain component that is influenced by the sympathetic innervation of deep somatic structures is more important than the cutaneous activation. The entire sympathetic maintained pain component is not constant in the course of the disease but decreases over time.     

Complex regional pain syndrome: a review of diagnostics, pathophysiologic mechanisms, and treatment implications for certified registered nurse anesthetists

The pathophysiologic mechanisms for complex regional pain syndrome (CRPS) are complex and elusive. The proposed etiologic mechanisms for CRPS include inflammatory responses, peripheral or central sensitization, and sympathetic dysfunction. Anesthesia care of patients with CRPS is challenging. Treatments including physiotherapy, peripheral vasodilators, sympathetic blockade, analgesics, and other systemic medications can help optimize mobility, perfusion, and pain relief for affected patients.     

Spinal cord stimulation for complex regional pain syndrome: an evidence-based medicine review of the literature

OBJECTIVES: The purpose of this investigation is to assess the evidence for efficacy of SCS in the management of pain in patients with CRPS. METHODS: Search strategy: Electronic databases such as Medline and Cochrane Library were queried using key words such as "spinal cord stimulation," "reflex sympathetic dystrophy (RSD)," and "complex regional pain syndrome (CRPS)."Selection criteria: Relevant published randomized controlled trials (RCT), cohort studies, case-control studies, case series, and case reports that described SCS as the primary treatment modality for patients with CRPS were eligible for inclusion.Data collection and analysis: Data extracted from qualified studies were summarized in sections of methodology, demographics, SCS equipment, primary and secondary outcomes, and complications. RESULTS: Thirteen studies using the primary search strategy and 7 studies from their reference lists were considered. Five of these 20 studies were discarded. One RCT, 2 prospective observational, and 12 retrospective observational studies were eventually considered. The methodological quality of all studies was poor except for the single RCT study. DISCUSSION: Although limited in quality and quantity, available evidence from the examined literature suggests that SCS is effective in the management of pain in patients with CRPS (grade B/C). Clinically useful information extracted from the available studies is very limited in guiding clinicians in the rational use of SCS for pain management in CRPS patients. Future attempts to investigate the efficacy of SCS in CRPS patients should involve methodologically robust designs such as randomized studies that have sufficient power.     

Spinal cord stimulation for complex regional pain syndrome: a systematic review of the clinical and cost-effectiveness literature and assessment of prognostic factors.

OBJECTIVE: To review the clinical and cost-effectiveness of spinal cord stimulation (SCS) in the management of patients with complex regional pain syndrome (CRPS) and identify the potential predictors of SCS outcome. DESIGN: Systematic review of the literature and meta-regression. METHODS: Electronic databases were searched for controlled and uncontrolled studies and economic evaluations relating to the use of SCS in patients with either CRPS type I or II. RESULTS: One randomised controlled trial, 25 case series and one cost-effectiveness study were included. In the randomised controlled trial in type I CRPS patients, SCS therapy lead to a reduction in pain intensity at 24 months of follow-up (mean change in VAS score -2.0), whereas pain was unchanged in the control group (mean change in VAS score 0.0) (p<0.001). In the case series studies, 67% (95% CI 51%, 84%) of type I and type II CRPS patients implanted with SCS reported pain relief of at least 50% over a median follow-up period of 33 months. No statistically significant predictors of pain relief with SCS were observed in multivariate meta-regression analysis across studies. An economic analysis based on the randomised controlled trial showed a lifetime cost saving of approximately 58,470 (60,800 US dollars) with SCS plus physical therapy compared with physical therapy alone. The mean cost per quality-adjusted life-year at 12-month follow-up was 22,580 (23,480 US dollars). CONCLUSIONS: SCS appears to be an effective therapy in the management of patients with CRPS type I (Level A evidence) and type II (Level D evidence). Moreover, there is evidence to demonstrate that SCS is a cost-effective treatment for CRPS type I.     

Radiofrequency lesions of the stellate ganglion in chronic pain syndromes: retrospective analysis of clinical efficacy in 86 patients

OBJECTIVE: Stellate ganglion (SG) blockade is used for the treatment of chronic pain syndromes in which the sympathetic nervous system is hypothesized to be involved. A possible treatment modality to achieve long-term pain reduction is blockade of the SG by means of a radiofrequency lesion (RF-SG). To evaluate the outcome of RF-SG as a therapy for different chronic pain syndromes, we reviewed 86 RF-SG procedures. DESIGN: Medical records containing treatment information were reviewed systematically. A systematic MEDLINE literature review search on SG blockade was also performed. RESULTS: In our clinic, 39.5% of 221 patients who received a prognostic SG block subsequently underwent RF-SG. Of these patients, 40.7% noted a more than 50% reduction of pain, 54.7% reported no effect on pain, and 4.7% showed worsening of pain. The mean follow-up interval was 52 weeks. The computer-assisted literature search resulted in 31 studies: 12 about complications and 19 about the efficacy of SG blockade. A review of these studies showed partial pain relief in 41.3% of patients, complete pain relief in 37.8%, and no pain relief in 20.9%. CONCLUSIONS: The efficacy of RF-SG blockade seems to be in line with that of other SG blockade procedures reported in the literature. Our retrospective study shows that an RF-SG block is most likely to be of benefit for patients suffering from complex regional pain syndrome type 2, ischemic pain, cervicobrachialgia, or postthoracotomy pain. Clinical efficacy remains to be proven in a randomized controlled trial, however.     

Complex regional pain syndrome

Complex regional pain syndrome (CRPS), formerly known as reflex sympathetic dystrophy, is a regional, posttraumatic, neuropathic pain problem that most often affects 1 or more limbs. Like most medical conditions, early diagnosis and treatment increase the likelihood of a successful outcome. Accordingly, patients with clinical signs and symptoms of CRPS after an injury should be referred immediately to a physician with expertise in evaluating and treating this condition. Physical therapy is the cornerstone and first-line treatment for CRPS. Mild cases respond to physical therapy and physical modalities. Mild to moderate cases may require adjuvant analgesics, such as anticonvulsants and/or antidepressants. An opioid should be added to the treatment regimen if these medications do not provide sufficient analgesia to allow the patient to participate in physical therapy. Patients with moderate to severe pain and/or sympathetic dysfunction require regional anesthetic blockade to participate in physical therapy. A small percentage of patients develop refractory, chronic pain and require long-term multidisciplinary treatment, including physical therapy, psychological support, and pain-relieving measures. Pain-relieving measures include medications, sympathetic/somatic blockade, spinal cord stimulation, and spinal analgesia.     

MULTIDISCIPLINARY PAIN ABSTRACTS: 34

Because recent studies emphasized the role of peripherally distributed N-methyl-D-aspartate (NMDA) receptors in processing the nociceptive information, the authors investigated whether peripheral application of the ointment containing ketoconazole (KET) is able to attenuate the symptoms of local neuropathic pain. They applied ointment containing KET (0.25%–1.5%) to the affected area on limbs in five patients with complex regional pain syndrome type I (CRPS I) and in two patients with type II (CRPS II). One to 2 weeks later, they observed improvement of the report of pain intensity, measured by the visual analog scale, in four patients with acute early dystrophic stage of CRPS I. Swelling of the affected limbs subsided as well. No apparent changes were noticed in one patient with chronic atrophic stage of CRPS I and in both patients with CRPS II. The authors concluded that topical application of KET appears to be beneficial for the patients with acute early dystrophic stage of CRPS I because of either its local anesthetic effect or NMDA receptor antagonist action. Patients with chronic atrophic stage of CRPS I and CRPS II patients do not appear to respond to this treatment.     

Clinical Science (37)

Pain relief in complex regional pain syndrome due to spinal cord stimulation does not depend on vasodilation. (Maastricht University Hospital, Maastricht, The Netherlands) Anesthesiology 2000;92:1653–1660. This study aimed to assess whether pain relief in complex regional pain syndrome (CRPS after spinal cord stimulation (SCS) is, in fact, dependent on vasodilation. In addition, the study attempted to determine which of the potential mechanisms may cause the vasodilatory effect that is generally found after SCS. Twenty‐four of 36 patients with unilateral CRPS responded to the test of SCS. Twenty‐two of the 24 responders (hand, n = 14; foot, n = 8) who had undergone previous sympathectomy were enrolled in the study. In addition, 20 control subjects (10 controls for each extremity) were studied. By means of laser Doppler flowmetry, the skin microcirculation of the patients was measured bilaterally while the SCS system was switched off and while it was activated. Control subjects were tested only once. The ratio of the rest flow at heart level and the dependent position was defined as the vasoconstricted index. Both in affected hands and feet, patients were found to have lower vasoconstriction indices (P < 0.01) as compared with controls, indicating a decreased sympathetic tone. Applying SCS did not result in any microcirculatory change as compared with the baseline or the contralateral clinically unaffected side. Conclude that the study failed to show that SCS influences skin microcirculation in patients with CRPS and a low sympathetic tone. Therefore, it was also concluded that pain relief in CRPS due to SCS is possible without vasodilation. Because sympathetic activity was greatly decreased in the patients, these results support the hypothesis that the vasodilation that is normally found with SCS is due to an inhibitory effect on sympathetically maintained vasoconstriction. Comment by Hemmo A. Bosscher, MD. SCS probably provides pain relief independent of increases in blood flow to the affected area. There may be several weaknesses in this study. All patients underwent prior sympathectomy. As every pain management specialist knows, the results of these procedures are variable. That leaves a group of pain patients with CRPS I that is either predominantly sympathetically mediated or sympathetically independent, with variable degrees of sympathetic blockade. In addition, only part of the peripheral circulation is measured with a device which accuracy has not yet been confirmed. Many variables are introduced in this study making a statement that there are no differences between the treatment group and the control somewhat strong. In my opinion: pain relief in complex regional pain syndrome due to spinal cord stimulation may not depend on vasodilatation.     

Complex regional pain syndrome type I associated with amyotrophic lateral sclerosis

BACKGROUND: (CRPS I [formerly called reflex sympathetic dystrophy]) is a syndrome with pain and signs of autonomic dysfunction after trauma or immobilization; the pathophysiologic mechanisms of CRPS I, however, remain unknown. DESIGN: The authors present a case of CRPS I associated with amyotrophic lateral sclerosis. Along with the motor paresis due to amyotrophic lateral sclerosis, pain, swelling, and signs of autonomic disturbance occurred. CONCLUSIONS: This case supports the hypothesis that immobilization is one of the major contributing factors for CRPS I.     

Intradermal injection of norepinephrine evokes pain in patients with sympathetically maintained pain

Tissue injuries, with or without involvement of nerves, may lead to ongoing pain and hyperalgesia to external stimuli. In a subset of patients, the pain is maintained by sympathetic efferent activity (SMP). We investigated if the peripheral administration of the alpha-adrenergic agonist, norepinephrine (NE), in physiologically relevant doses resulted in pain in patients with SMP. To establish the dose of intradermal NE required to induce cutaneous vasoconstriction, NE (1 nM-10 microM, 30 microl) was injected under a laser Doppler probe on the volar forearm of seven normal subjects. A decrease in blood flow was evident at a dose of 10 microM. Twelve patients (five male, seven female) diagnosed to have SMP based on the decrease in pain by a local anesthetic sympathetic blockade (70+/-6%) were enrolled in the study. Pain ratings were obtained continuously for 5 min after intradermal injections of saline and NE (0.1-10 microM) into their hyperalgesic zone and the mirror-image contralateral side. Injections were done during the period of pain relief following a local anesthetic sympathetic blockade. Similar injections were made in eight control subjects. On the affected side of the patients, the two highest concentrations of NE (1 and 10 microM) caused significantly more pain than saline (P<0.05, ANOVA). In contrast, there was no significant pain induced by the NE injections in the unaffected side and in control subjects. Six of nine patients tested reported a marked decrease in pain and hyperalgesia following infusion of phentolamine (1 mg/kg over 10 min). Two of the three patients who did not receive pain relief following phentolamine infusion also did not report pain to the NE injections. We conclude that NE injections produce pain in SMP patients at doses that are at the threshold for producing vasoconstriction. These studies support a role for cutaneous adrenoceptors in the mechanisms of sympathetically maintained pain.     

Complex regional pain syndrome. Sympathetic reflex dystrophy and causalgia

Complex regional pain syndromes (CRPS) occur as the inadequate response to painful trauma in a distal extremity. With CRPS I (sympathetic reflex dystrophy), no lesion of the nerve is present. Aside from sensory disturbances, burning deep spontaneous pain and mechanical allodynia are characteristic. Disturbances in the skin blood circulation,sweating,edema,and trophic disturbances of the skin, joints, and bones are typical. Reduction in muscle strength, tremor, and late dystonic changes comprise the motor disturbances. All symptoms are distributed in the distal extremity and not limited to the region of the peripheral nerves. Complex regional pain syndrome II (causalgia),develops following a partial peripheral nerve lesion. The distally generalized symptoms are identical. Successful therapy depends on an early start of interdisciplinary treatment. In addition to the pain therapy,physiotherapy plays a decisive role in rehabilitation. During the acute phase, freedom from pain at rest and retrogression of the edema must be achieved. With slight spontaneous pain, a conservative therapeutic method may be applied (analgesics, rest, raised position). In case of insufficient improvement and in difficult cases, the effect of intervention (sympathetic blockade) should be tested and possibly a blockade series performed. After reduced spontaneous pain,physiotherapy should be increased stepwise.     

The Effect of Ketamine Infusion in the Treatment of Complex Regional Pain Syndrome: a Systemic Review and Meta-analysis

Purpose of Review

Complex regional pain syndrome (CRPS) is a painful debilitating neurological condition that accounts for approximately 1.2% of adult chronic pain population. Ketamine, an NMDA receptor antagonist, is an anesthetic agent that has been used by some pain specialists for CRPS. There is a growing body of clinical evidence to support the use of ketamine in the treatment of neuropathic pain, especially CRPS. This meta-analysis study was aimed to examine the efficacy of ketamine in the treatment of CRPS.

Recent Findings

A search of Embase, Pubmed, Web of Knowledge, Cochrane, Clinical Trial.gov, and FDA.gov between Jan 1, 1950, and August 1, 2017, was conducted to evaluate ketamine infusion therapy in the treatment of CRPS. We selected randomized clinical trials or cohort studies for meta-analyses. I ² index estimates were calculated to test for variability and heterogeneity across the included studies. The primary outcome is pain relief. The effect of ketamine treatment for complex regional pain syndrome was assessed by 0–10 scale numerical rating pain score. The secondary outcome is the pain relief event rate, which is defined as the percentage of participants who achieved 30% or higher pain relief in each of the qualified studies. Our meta-analysis results showed that the Ketamine treatment led to a decreased mean of pain score in comparison to the self-controlled baseline (p?<?0.000001). However, there is a statistical significance of between-study heterogeneity. The immediate pain relief event rate was 69% (95% confidence interval (CI) 53%, 84%). The pain relief event rate at the 1–3 months follow-ups was 58% (95% CI 41%, 75%).

Summary

The current available studies regarding ketamine infusion for CRPS were reviewed, and meta-analyses were conducted to evaluate the efficacy of ketamine infusion in the treatment of CRPS. Our findings suggested that ketamine infusion can provide clinically effective pain relief in short term for less than 3 months. However, because of the high heterogeneity of the included studies and publication bias, additional random controlled trials and standardized multicenter studies are needed to confirm this conclusion. Furthermore, studies are needed to prove long-term efficacy of ketamine infusion in the treatment of CRPS.