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Complex regional pain syndrome (CRPS) with resistance to local anesthetic block: a case report
Case Reports Complex Regional Pain Syndrome (CRPS) with Resistance to Local Anesthetic Block: A Case Report Farrokh R. Maneksha, MD,* Himayun Mirza, MD,† Paul J. Poppers, MD‡ Department of Anesthesiology, Health Sciences Center,State University of New York at Stony Brook, Stony Brook, NY
We present a case of complex regional pain syndrome (CRPS) Type 1 in a 12-year-old girl. 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. © 2000 by Elsevier Science Inc. Keywords: Anesthesia, local; complex regional pain syndrome; pediatrics; reflex sympathetic dystrophy.
Introduction Complex regional pain syndrome (Type 1), also known as reflex sympathetic dystrophy (RSD), has been reported to occur in children. With appropriate treatment, the usual
*Associate Professor of Clinical Anesthesiology †Fellow, Division of Pain Management, Department of Anesthesiology ‡Distinguished Professor and Chairman of Anesthesiology Address correspondence to Dr. Maneksha at the Department of Anesthesiology, Health Sciences Center, Level 4, State University of New York at Stony Brook, Stony Brook, NY 11794-8480, USA. Received for publication June 24, 1999; revised manuscript accepted for publication October 13, 1999. Journal of Clinical Anesthesia 12:67–71, 2000 © 2000 Elsevier Science Inc. All rights reserved. 655 Avenue of the Americas, New York, NY 10010
course of the disease in children seems to be relatively benign. Therapeutic modalities that yield gradual resolution of symptoms include aggressive physical therapy, nonopioid analgesics, sympathetic nerve blocks, and behavioral modification.1–3 We report a case of CRPS in a 12-year-old girl, who did not respond to the usual treatment modalities. This case was remarkable due to a resistance to local anesthetic, limited to the area of the patient’s body where the pain was localized, when injected through an epidural catheter.
Case Report A 12-year-old previously healthy girl was referred to the chronic pain service for evaluation. The child presented with the history of a fall 5 months before our initial examination, with soft tissue injury to the right ankle. There was no radiographic evidence of any bony injury. One week later, she started to complain of worsening pain and some numbness in the right big toe. An orthopedic surgeon found a mass over the area of the saphenous nerve. At biopsy the mass turned out to be necrotic fatty tissue. The patient’s symptoms worsened with time. Swelling and a blotchy cyanosis developed over the right foot extending up to the midcalf. The foot turned cold and weight bearing provoked severe pain. Motion at all joints in the foot and ankle was severely limited. Her pain was of a continuous and burning nature. In addition, she had episodes of sharp stabbing pain, accompanied by spasms in the calf and foot. The patient could not wear socks or shoes due to severe pain. Her sleep was interrupted at night when her foot brushed against the covers. On a scale 0952-8180/00/$–see front matter PII S0952-8180(99)00126-9
Case Reports
of 0 to 10, her average pain was rated between 8/10 and 10/10. The orthopedic surgeon had prescribed hydrocodone 7.5 mg plus acetaminophen 750 mg on an as needed basis for severe pain and a course of physical therapy, which was unsuccessful due to increased pain with any manipulation of the foot. The child appeared to be emotionally stable with no history of psychological problems or any evidence of chronic pain behavior. Examination revealed a healthy well-developed girl weighing 52 kg, with a swollen, cyanotic, and cold right foot and ankle with significant hyperesthesia and allodynia. Maximum tenderness was over the area where the orthopedic surgeon had biopsied the mass on the medial aspect of the ankle. Motion was restricted at all joints in the foot and ankle due to severe pain. No weight bearing was possible on the right foot. Strong arterial pulses were palpable in both lower extremities. A diagnosis of CRPS (Type 1) or RSD was made, based on the history and physical examination, and a therapeutic plan formulated. This plan consisted of starting the patient on a course of gabapentin, which was increased from 100 mg three time a day (tid) to 300 mg tid, and amitryptiline 10 mg per day. The hydrocodone was replaced with tramadol 50 mg tid. A series of lumbar sympathetic blocks also was planned. Intravenous (IV) regional blocks (Bier blocks) with bretyllium or ketorolac also were considered, but it was felt that the patient would not be able to tolerate the procedure at that time due to the severe pain in the foot. Psychological evaluation of the child was recommended to the parents. Physical therapy was planned to be restarted, once the pain had been adequately controlled with sympathetic blocks. Pharmacologic therapy provided minor relief of the patient’s symptoms over a 2-week period, and the patient subsequently was scheduled to receive a lumbar sympathetic block. This procedure was carried out with light sedation in the prone position at the level of the second lumbar vertebra. The block caused a temperature elevation in the right foot from less than 29°C (below the minimum temperature of the skin probe), to 37°C. The color of the foot improved dramatically as the temperature rose. Pain relief was minimal, the pain score decreasing from 10/10 to 8/10. The patient initially refused to have a repeat block due to the discomfort of the procedure, but after further discussion it was decided to attempt another block 3 days later with deep sedation. However, again, there was minimal pain relief despite a dramatic increase in temperature. Because of failure of the lumbar sympathetic blocks, an epidural local anesthetic block was administered through a catheter placed at the level of L2–L3 under deep sedation. After recovery, she received a total of 15 mL lidocaine 0.5% through the epidural catheter, resulting in a temperature rise of 5°C in the right foot. However, the patient experienced no pain relief from this block. It was decided to proceed with administration of bupivacaine 0.25% through the epidural catheter. A total of 20 mL was injected in 5-mL increments over a period of 15 minutes, which resulted in a sensory block up to T4 68
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dermatome. The patient still complained of pain in her right foot and ankle. On examination, her foot still had intact sensory function up to the midcalf where her pain began. Above this level, she had complete sensory loss. In her left lower extremity, she had a complete sensorimotor block. She was able to discriminate between the temperature of an alcohol wipe and a cotton swab applied to the area of her right foot and ankle. The patient also did not report any decrease in her pain symptoms. We postulated that the problem probably was due to hypersensitivity that had developed in the dorsal horn of the spinal cord. She the was scheduled for a trial lidocaine infusion, possibly followed with a ketamine infusion, in an attempt to decrease the sensitivity in the dorsal horn. She received lidocaine 250 mg over a 10-minute period through an IV placed in her right upper extremity. This dose produced minor symptoms of toxicity with perioral tingling and some slurring of speech, but no change in symptoms. Subsequently, ketamine 10 mg was infused slowly, causing considerable sedation but no change in pain levels. After recovery from the ketamine, a bolus of fentanyl 25 g IV was given, without any effect. At this time, the patient seemed to become more uncomfortable, developing severe spasms in her foot. The patient was subjected to further psychological evaluation, which was normal. She then became an inpatient to receive a continuous lumbar sympathetic block for 5 days, with accompanying physical therapy. At discharge, the patient’s pain score had decreased from 10/10 to 7/10.’ Weight bearing with crutches now was possible. The patient continued treatment with intensive physical therapy and pharmacotherapy with gabapentin and amitriptyline. Currently, she is doing well, with pain scores ranging between 3/10 and 4/10, and she has increased her daily activities considerably.
Discussion The development of localized resistance to the sensory effects of local anesthetics in the course of therapy of CRPS has not been reported to date, and is the rationale for presenting this case. In addition to the etiology, pathophysiology, and treatment of CRPS, the possible etiology of this resistance is reviewed. CRPS (Type 1) has been defined as a complex pain problem with accompanying signs of sympathetic dysfunction (previously known called reflex sympathetic dystrophy) subsequent to minor trauma and which may even occur in the absence of trauma. The hallmarks of this problem4 include severe burning or stabbing pain with allodynia and hyperesthesia (especially to cold sensation), accompanied by movement disorder (painful or stiff joints) and muscle spasms. In the early stages, there may be swelling and increased skin temperature, with redness or cyanosis. This situation usually gives way to decreasing skin temperature with pallor and dystrophic changes of the skin. There may be hair loss, slowed nail growth, and increased sweating in the area. If untreated, this condition may lead to an atrophic, painful, and useless extremity. In some cases, as the disease progresses, the pain may spread
CRPS and local anesthetic block: Maneksha et al.
to other extremities or to areas of the body not previously involved in the disease process. Psychological dysfunction may predispose certain individuals to develop CRPS.5 Diagnostic tests used to confirm the presence of CRPS may include thermographic techniques,6 triple phase bone scan,7 systemic administration of alpha-blockers,8 regional anesthesia techniques9 such as stellate ganglion block, lumbar sympathetic block, and differential epidural and spinal block, and regional IV block with alphablockers. The pathophysiology of CRPS remains an enigma. Many theories focus on peripheral mechanisms, whereas others surround spinal cord dysfunction.10 Peripheral changes seen in CRPS11 may include neural membrane or receptor dysfunction12 in the area of injury and in surrounding areas, which increases their sensitivity to neural mediators, such as norepinephrine, prostaglandins, serotonin, substance P, and histamine, which may be present in the area of injury. Central theories include increased sensitivity and dysfunction of wide dynamic range (WDR) neurons,13 which are the second-order sensory neurons in the dorsal horn of the spinal cord. Activation of N-methylD-aspartate (NMDA) receptors14,15 on the WDR neurons may cause sensory dysfunction with hyperalgesia and allodynia. WDR neurons in surrounding dermatomes, sympathetic neurons in the lateral horns of the spinal cord, and motor neurons may be activated with consequent spread of pain, hyperalgesia and allodynia, sympathetic hyperactivity, and muscle spasm. Therapy of CRPS should be started as early as possible, involving multiple modalities. Physical therapy16 plays the most important role in the treatment of CRPS. As the disease process continues, it is extremely important to continue physical therapy to maintain function in the affected extremity. When the patient, because of severe pain, cannot tolerate physical therapy, other modalities, such as pharmacologic intervention and regional anesthetic techniques, should be used in conjuction with physical therapy to decrease pain. Pharmacologic interventions17–20 include the use of antiepileptic drugs, antidepressant medication, systemic or regional use of alpha-blockers, nonopioid and opioid analgesics, and NMDA-receptor blockers. A variety of regional anesthetic techniques21–25 have been used to treat CRPS. A number of sympathetic and somatic nerve blocks to the area involved are extremely useful in controlling the symptoms. If pain relief from these procedures does not last for a reasonable duration of time, a continuous block technique for 3 to 5 days can be carried out as an inpatient procedure for longer lasting pain relief. Intravenous regional anesthesia (Bier block)26 –31 using phenoxybenzamine, reserpine, guanethidine, bretylium, and ketorolac may be equivalent to local anesthetic sympathetic block in treating CRPS. Intravenous infusion of lidocaine32–35 has been used to relieve neuropathic pain that fails to respond to other modalities of treatment. In our patient, we tried a combination of some of these therapeutic approaches without much success. The interesting feature that prompted us to report this case is that there seemed to have developed a resistance to
local anesthetic blockade localized to the area of pain. Epidural block gave rise to anesthesia (both sensory and motor) from the T4 dermatome down to the sacral dermatomes. However, the area where the pain was localized escaped blockade and sensation remained intact to light touch, pressure, pinprick, and temperature. It could be argued that the patient had an anatomical anomaly in the epidural space,36 which prevented the local anesthetic drug from affecting the involved nerve roots. On reviewing the history and physical examination, we felt that this situation was unlikely. In general, if a patient fails to gain pain relief in the presence of an otherwise effective somatic epidural block, it is presumed that there is either a central nervous system (CNS) lesion or a psychosomatic disorder.37 We have observed three patients in our pain center in whom a diagnostic differential epidural block did not yield complete pain relief in the presence of a high level of somatic blockade. These patients, who lacked any evidence of CNS disease, were thought to have some degree of psychosomatic pain disorder and consequently were referred to a psychologist for evaluation. On evaluation, two of the three patients had psychobehavioral problems that were responsible for their pain and that improved with further therapy. The other patient refused psychological evaluation. In this case, there was no evidence for either CNS or pschosomatic problems. Chronic neuropathic pain is known to cause changes in the CNS leading to resistance to various modalities of treatment. Many of these changes are due to the “wind-up” phenomenon seen when NMDA-receptor channels open and cause WDR neuron dysfunction. As a result, other neural systems behave in an abnormal fashion. We cannot exclude the possibility that the observed phenomenon occurred subsequent to such a change in the CNS. In researching the literature, we found two reports that describe the experimental development of tachyphylaxis to local anesthetic block by thermal hyperalgesia.38,39 In one instance, the observed phenomenon was reversed with an NMDA-receptor antagonist and, in the other instance, with a nitric oxide antagonist. The significance of these articles in relation to our report is at present undetermined, but the response of neural blockade to thermal hyperalgesia, which was reversed with drugs acting on the WDR neurons, may have some connection with the reported phenomenon in our case. It also has been observed, in a rat model, that chronic alcohol consumption produces an unexplained tolerance to local anesthetic blockade.40 On further investigation into the published literature, we found a link to the effects of alcohol on the NMDA receptor. There are two reports41,42 of alcohol causing stimulation of the NMDA receptor via presynaptic release of excitatory amino acids, in a manner similar to which chronic pain may effect the WDR neuron in the spinal cord. These observations may explain the tolerance to local anesthetic seen in our patient. In conclusion, this report is presented to stimulate further efforts to elucidate this phenomenon of resistance to local anesthetic block that was observed in this patient. J. Clin. Anesth., vol. 12, February 2000
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Questions that need to be addressed are: is this phenomenon caused by the chronic pain syndrome, and if so, what is the exact mechanism of this problem and what could be done to reverse this phenomenon. It also raises questions about the conclusions we draw from various procedures we perform such as the “differential epidural block,” which has been used in the diagnosis of chronic pain problems. Many physicians who practice pain management are faced with patients who seem to be resistant to the usual modalities of treatment and continue to suffer in spite of all efforts to relieve their suffering. We are sure that continuing research into the pathophysiology and pharmacology of CNS will bring relief to these unfortunate people in the future.
References 1. Wilder RT, Berde CB, Wolohan M, Vieyra MA, Masek BJ, Micheli LJ: Reflex sympathetic dystrophy in children. Clinical characteristics and follow-up of seventy patients. J Bone Joint Surg Am 1992;74:910 –9. 2. Ashwal S, Tomasi L, Neumann M, Schneider S: Reflex sympathetic dystrophy syndrome in children. Pediatr Neurol 1988;4: 38 – 42. 3. Ruggeri SB, Athreya BH, Doughty R, Gregg JR, Das MM: Reflex sympathetic dystrophy in children. Clin Orthop 1982;163:225–30. 4. Walker SM, Cousins MJ: Complex regional pain syndromes, including “reflex sympathetic dystrophy” and “causalgia.” Anaesth Intensive Care 1997;25:113–25. 5. Bruehl S, Carlson CR: Predisposing psychological factors in the development of reflex sympathetic dystrophy. A review of the empirical evidence. Clin J Pain 1992;8:287–99. 6. Bruehl S, Lubenow TR, Nath H, Ivankovich O: Validation of thermography in the diagnosis of reflex sympathetic dystrophy. Clin J Pain 1996;12:316 –25. 7. Mailis A, Meindok H, Papagapiou M, Pham D: Alterations of the three-phase bone scan after sympathectomy. Clin J Pain 1994;10: 146 –55. 8. Olcott C 4th, Eltherington LG, Wilcosky BR, Shoor PM, Zimmerman JJ, Fogarty TJ: Reflex sympathetic dystrophy—the surgeon’s role in management. J Vasc Surg 1991;14:488 –92;. 9. Dzwierzynski WW, Sanger JR: Reflex sympathetic dystrophy. Hand Clin 1994;10:29 – 44. 10. Baron R, Janig W: Pain syndromes with causal participation of the sympathetic nervous system. Anaesthesist 1998;47:4 –23. 11. Drummond PD, Finch PM, Gibbins I: Innervation of hyperalgesic skin in patients with complex regional pain syndrome. Clin J Pain 1996;12:222–31. 12. Raja SN, Choi Y, Asano Y, Holmes C, Goldstein DS: Arteriovenous differences in plasma concentrations of catechols in rats with neuropathic pain. Anesthesiology 1995;83:1001– 8. 13. Roberts WJ: A hypothesis on the physiological basis for causalgia and related pains. Pain 1986;24:297–311. 14. Rogers JN, Valley MA: Reflex sympathetic dystrophy. Clin Podiatr Med Surg 1994;11:73– 83. 15. Wilder RT, Berde CB, Wolohan M, Vieyra MA, Masek BJ, Micheli LJ: Reflex sympathetic dystrophy in children. Clinical characteristics and follow-up of seventy patients. J Bone Joint Surg Am 1992;74:910 –9. 16. Gedalia A, Adar A, Kornmehl P: Reflex sympathetic dystrophy in children. Harefuah 1990;119:197– 8. 17. Mellick GA, Mellicy LB, Mellick LB: Gabapentin in the manage70
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CRPS and local anesthetic block: Maneksha et al. 39. Lee KC, Wilder RT, Smith RL, Berde CB: Thermal hyperalgesia accelerates and MK-801 prevents the development of tachyphylaxis to rat sciatic nerve blockade. Anesthesiology 1994;81:1284 – 93. 40. Fassoulaki A, Drasner K, Eger EI 2d: Is chronic ethanol consumption associated with tolerance to intrathecal lidocaine in the rat? Anesth Analg 1990;70:489 –92.
41. Krystal JH, Petrakis IL, Webb E, et al: Dose-related ethanol-like effects of the NMDA antagonist, ketamine, in recently detoxified alcoholics. Arch Gen Psychiatry 1998;55:354 – 60. 42. Weight FF, Aguayo LG, White G, Lovinger DM, Peoples RW: GABA- and glutamate-gated ion channels as molecular sites of alcohol and anesthetic action. Adv Biochem Psychopharmacol 1992;47:335– 47.
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We present a case of complex regional pain syndrome (CRPS) Type 1 in a 12-year-old girl. 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. © 2000 by Elsevier Science Inc. Keywords: Anesthesia, local; complex regional pain syndrome; pediatrics; reflex sympathetic dystrophy.
Introduction Complex regional pain syndrome (Type 1), also known as reflex sympathetic dystrophy (RSD), has been reported to occur in children. With appropriate treatment, the usual
*Associate Professor of Clinical Anesthesiology †Fellow, Division of Pain Management, Department of Anesthesiology ‡Distinguished Professor and Chairman of Anesthesiology Address correspondence to Dr. Maneksha at the Department of Anesthesiology, Health Sciences Center, Level 4, State University of New York at Stony Brook, Stony Brook, NY 11794-8480, USA. Received for publication June 24, 1999; revised manuscript accepted for publication October 13, 1999. Journal of Clinical Anesthesia 12:67–71, 2000 © 2000 Elsevier Science Inc. All rights reserved. 655 Avenue of the Americas, New York, NY 10010
course of the disease in children seems to be relatively benign. Therapeutic modalities that yield gradual resolution of symptoms include aggressive physical therapy, nonopioid analgesics, sympathetic nerve blocks, and behavioral modification.1–3 We report a case of CRPS in a 12-year-old girl, who did not respond to the usual treatment modalities. This case was remarkable due to a resistance to local anesthetic, limited to the area of the patient’s body where the pain was localized, when injected through an epidural catheter.
Case Report A 12-year-old previously healthy girl was referred to the chronic pain service for evaluation. The child presented with the history of a fall 5 months before our initial examination, with soft tissue injury to the right ankle. There was no radiographic evidence of any bony injury. One week later, she started to complain of worsening pain and some numbness in the right big toe. An orthopedic surgeon found a mass over the area of the saphenous nerve. At biopsy the mass turned out to be necrotic fatty tissue. The patient’s symptoms worsened with time. Swelling and a blotchy cyanosis developed over the right foot extending up to the midcalf. The foot turned cold and weight bearing provoked severe pain. Motion at all joints in the foot and ankle was severely limited. Her pain was of a continuous and burning nature. In addition, she had episodes of sharp stabbing pain, accompanied by spasms in the calf and foot. The patient could not wear socks or shoes due to severe pain. Her sleep was interrupted at night when her foot brushed against the covers. On a scale 0952-8180/00/$–see front matter PII S0952-8180(99)00126-9
Case Reports
of 0 to 10, her average pain was rated between 8/10 and 10/10. The orthopedic surgeon had prescribed hydrocodone 7.5 mg plus acetaminophen 750 mg on an as needed basis for severe pain and a course of physical therapy, which was unsuccessful due to increased pain with any manipulation of the foot. The child appeared to be emotionally stable with no history of psychological problems or any evidence of chronic pain behavior. Examination revealed a healthy well-developed girl weighing 52 kg, with a swollen, cyanotic, and cold right foot and ankle with significant hyperesthesia and allodynia. Maximum tenderness was over the area where the orthopedic surgeon had biopsied the mass on the medial aspect of the ankle. Motion was restricted at all joints in the foot and ankle due to severe pain. No weight bearing was possible on the right foot. Strong arterial pulses were palpable in both lower extremities. A diagnosis of CRPS (Type 1) or RSD was made, based on the history and physical examination, and a therapeutic plan formulated. This plan consisted of starting the patient on a course of gabapentin, which was increased from 100 mg three time a day (tid) to 300 mg tid, and amitryptiline 10 mg per day. The hydrocodone was replaced with tramadol 50 mg tid. A series of lumbar sympathetic blocks also was planned. Intravenous (IV) regional blocks (Bier blocks) with bretyllium or ketorolac also were considered, but it was felt that the patient would not be able to tolerate the procedure at that time due to the severe pain in the foot. Psychological evaluation of the child was recommended to the parents. Physical therapy was planned to be restarted, once the pain had been adequately controlled with sympathetic blocks. Pharmacologic therapy provided minor relief of the patient’s symptoms over a 2-week period, and the patient subsequently was scheduled to receive a lumbar sympathetic block. This procedure was carried out with light sedation in the prone position at the level of the second lumbar vertebra. The block caused a temperature elevation in the right foot from less than 29°C (below the minimum temperature of the skin probe), to 37°C. The color of the foot improved dramatically as the temperature rose. Pain relief was minimal, the pain score decreasing from 10/10 to 8/10. The patient initially refused to have a repeat block due to the discomfort of the procedure, but after further discussion it was decided to attempt another block 3 days later with deep sedation. However, again, there was minimal pain relief despite a dramatic increase in temperature. Because of failure of the lumbar sympathetic blocks, an epidural local anesthetic block was administered through a catheter placed at the level of L2–L3 under deep sedation. After recovery, she received a total of 15 mL lidocaine 0.5% through the epidural catheter, resulting in a temperature rise of 5°C in the right foot. However, the patient experienced no pain relief from this block. It was decided to proceed with administration of bupivacaine 0.25% through the epidural catheter. A total of 20 mL was injected in 5-mL increments over a period of 15 minutes, which resulted in a sensory block up to T4 68
J. Clin. Anesth., vol. 12, February 2000
dermatome. The patient still complained of pain in her right foot and ankle. On examination, her foot still had intact sensory function up to the midcalf where her pain began. Above this level, she had complete sensory loss. In her left lower extremity, she had a complete sensorimotor block. She was able to discriminate between the temperature of an alcohol wipe and a cotton swab applied to the area of her right foot and ankle. The patient also did not report any decrease in her pain symptoms. We postulated that the problem probably was due to hypersensitivity that had developed in the dorsal horn of the spinal cord. She the was scheduled for a trial lidocaine infusion, possibly followed with a ketamine infusion, in an attempt to decrease the sensitivity in the dorsal horn. She received lidocaine 250 mg over a 10-minute period through an IV placed in her right upper extremity. This dose produced minor symptoms of toxicity with perioral tingling and some slurring of speech, but no change in symptoms. Subsequently, ketamine 10 mg was infused slowly, causing considerable sedation but no change in pain levels. After recovery from the ketamine, a bolus of fentanyl 25 g IV was given, without any effect. At this time, the patient seemed to become more uncomfortable, developing severe spasms in her foot. The patient was subjected to further psychological evaluation, which was normal. She then became an inpatient to receive a continuous lumbar sympathetic block for 5 days, with accompanying physical therapy. At discharge, the patient’s pain score had decreased from 10/10 to 7/10.’ Weight bearing with crutches now was possible. The patient continued treatment with intensive physical therapy and pharmacotherapy with gabapentin and amitriptyline. Currently, she is doing well, with pain scores ranging between 3/10 and 4/10, and she has increased her daily activities considerably.
Discussion The development of localized resistance to the sensory effects of local anesthetics in the course of therapy of CRPS has not been reported to date, and is the rationale for presenting this case. In addition to the etiology, pathophysiology, and treatment of CRPS, the possible etiology of this resistance is reviewed. CRPS (Type 1) has been defined as a complex pain problem with accompanying signs of sympathetic dysfunction (previously known called reflex sympathetic dystrophy) subsequent to minor trauma and which may even occur in the absence of trauma. The hallmarks of this problem4 include severe burning or stabbing pain with allodynia and hyperesthesia (especially to cold sensation), accompanied by movement disorder (painful or stiff joints) and muscle spasms. In the early stages, there may be swelling and increased skin temperature, with redness or cyanosis. This situation usually gives way to decreasing skin temperature with pallor and dystrophic changes of the skin. There may be hair loss, slowed nail growth, and increased sweating in the area. If untreated, this condition may lead to an atrophic, painful, and useless extremity. In some cases, as the disease progresses, the pain may spread
CRPS and local anesthetic block: Maneksha et al.
to other extremities or to areas of the body not previously involved in the disease process. Psychological dysfunction may predispose certain individuals to develop CRPS.5 Diagnostic tests used to confirm the presence of CRPS may include thermographic techniques,6 triple phase bone scan,7 systemic administration of alpha-blockers,8 regional anesthesia techniques9 such as stellate ganglion block, lumbar sympathetic block, and differential epidural and spinal block, and regional IV block with alphablockers. The pathophysiology of CRPS remains an enigma. Many theories focus on peripheral mechanisms, whereas others surround spinal cord dysfunction.10 Peripheral changes seen in CRPS11 may include neural membrane or receptor dysfunction12 in the area of injury and in surrounding areas, which increases their sensitivity to neural mediators, such as norepinephrine, prostaglandins, serotonin, substance P, and histamine, which may be present in the area of injury. Central theories include increased sensitivity and dysfunction of wide dynamic range (WDR) neurons,13 which are the second-order sensory neurons in the dorsal horn of the spinal cord. Activation of N-methylD-aspartate (NMDA) receptors14,15 on the WDR neurons may cause sensory dysfunction with hyperalgesia and allodynia. WDR neurons in surrounding dermatomes, sympathetic neurons in the lateral horns of the spinal cord, and motor neurons may be activated with consequent spread of pain, hyperalgesia and allodynia, sympathetic hyperactivity, and muscle spasm. Therapy of CRPS should be started as early as possible, involving multiple modalities. Physical therapy16 plays the most important role in the treatment of CRPS. As the disease process continues, it is extremely important to continue physical therapy to maintain function in the affected extremity. When the patient, because of severe pain, cannot tolerate physical therapy, other modalities, such as pharmacologic intervention and regional anesthetic techniques, should be used in conjuction with physical therapy to decrease pain. Pharmacologic interventions17–20 include the use of antiepileptic drugs, antidepressant medication, systemic or regional use of alpha-blockers, nonopioid and opioid analgesics, and NMDA-receptor blockers. A variety of regional anesthetic techniques21–25 have been used to treat CRPS. A number of sympathetic and somatic nerve blocks to the area involved are extremely useful in controlling the symptoms. If pain relief from these procedures does not last for a reasonable duration of time, a continuous block technique for 3 to 5 days can be carried out as an inpatient procedure for longer lasting pain relief. Intravenous regional anesthesia (Bier block)26 –31 using phenoxybenzamine, reserpine, guanethidine, bretylium, and ketorolac may be equivalent to local anesthetic sympathetic block in treating CRPS. Intravenous infusion of lidocaine32–35 has been used to relieve neuropathic pain that fails to respond to other modalities of treatment. In our patient, we tried a combination of some of these therapeutic approaches without much success. The interesting feature that prompted us to report this case is that there seemed to have developed a resistance to
local anesthetic blockade localized to the area of pain. Epidural block gave rise to anesthesia (both sensory and motor) from the T4 dermatome down to the sacral dermatomes. However, the area where the pain was localized escaped blockade and sensation remained intact to light touch, pressure, pinprick, and temperature. It could be argued that the patient had an anatomical anomaly in the epidural space,36 which prevented the local anesthetic drug from affecting the involved nerve roots. On reviewing the history and physical examination, we felt that this situation was unlikely. In general, if a patient fails to gain pain relief in the presence of an otherwise effective somatic epidural block, it is presumed that there is either a central nervous system (CNS) lesion or a psychosomatic disorder.37 We have observed three patients in our pain center in whom a diagnostic differential epidural block did not yield complete pain relief in the presence of a high level of somatic blockade. These patients, who lacked any evidence of CNS disease, were thought to have some degree of psychosomatic pain disorder and consequently were referred to a psychologist for evaluation. On evaluation, two of the three patients had psychobehavioral problems that were responsible for their pain and that improved with further therapy. The other patient refused psychological evaluation. In this case, there was no evidence for either CNS or pschosomatic problems. Chronic neuropathic pain is known to cause changes in the CNS leading to resistance to various modalities of treatment. Many of these changes are due to the “wind-up” phenomenon seen when NMDA-receptor channels open and cause WDR neuron dysfunction. As a result, other neural systems behave in an abnormal fashion. We cannot exclude the possibility that the observed phenomenon occurred subsequent to such a change in the CNS. In researching the literature, we found two reports that describe the experimental development of tachyphylaxis to local anesthetic block by thermal hyperalgesia.38,39 In one instance, the observed phenomenon was reversed with an NMDA-receptor antagonist and, in the other instance, with a nitric oxide antagonist. The significance of these articles in relation to our report is at present undetermined, but the response of neural blockade to thermal hyperalgesia, which was reversed with drugs acting on the WDR neurons, may have some connection with the reported phenomenon in our case. It also has been observed, in a rat model, that chronic alcohol consumption produces an unexplained tolerance to local anesthetic blockade.40 On further investigation into the published literature, we found a link to the effects of alcohol on the NMDA receptor. There are two reports41,42 of alcohol causing stimulation of the NMDA receptor via presynaptic release of excitatory amino acids, in a manner similar to which chronic pain may effect the WDR neuron in the spinal cord. These observations may explain the tolerance to local anesthetic seen in our patient. In conclusion, this report is presented to stimulate further efforts to elucidate this phenomenon of resistance to local anesthetic block that was observed in this patient. J. Clin. Anesth., vol. 12, February 2000
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Case Reports
Questions that need to be addressed are: is this phenomenon caused by the chronic pain syndrome, and if so, what is the exact mechanism of this problem and what could be done to reverse this phenomenon. It also raises questions about the conclusions we draw from various procedures we perform such as the “differential epidural block,” which has been used in the diagnosis of chronic pain problems. Many physicians who practice pain management are faced with patients who seem to be resistant to the usual modalities of treatment and continue to suffer in spite of all efforts to relieve their suffering. We are sure that continuing research into the pathophysiology and pharmacology of CNS will bring relief to these unfortunate people in the future.
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