Ketamine Treatment for Intractable Pain in a Patient with - PDF by saj38576

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									                                                                     Pain Physician 2008; 11:3:339-342 • ISSN 1533-3159



            Case Report



                     Ketamine Treatment for Intractable Pain in
                     a Patient with Severe Refractory Complex
                     Regional Pain Syndrome: A Case Report

                        Peyman Shirani, MD1-3, Alicia R. Salamone, BA3, Paul E. Schulz, MD3,
                        and Everton A. Edmondson, MD1,2

      From: 1Interventional Neurology, Inc.,
   Houston, TX; 2Department of Neurology,
  The Methodist Hospital, Houston, TX; and
3
 Department of Neurology, Baylor College of
                                                 In this case report, we describe the effect of ketamine infusion in a case of
                    Medicine, Houston, TX.       severe refractory complex regional pain syndrome I (CRPS I). The patient was
                                                 initially diagnosed with CRPS I in her right upper extremity. Over the next 6
  Dr. Shirani and Ms. Salamone are with the      years, CRPS was consecutively diagnosed in her thoracic region, left upper ex-
     Baylor College of Medicine, Houston, TX.
                                                 tremity, and both lower extremities. The severity of her pain, combined with
Dr. Schulz is Vice-Chair of Education, and Co-
Director of the Center for Neurodegenerative     the extensive areas afflicted by CRPS, caused traumatic emotional problems
  Disorders at the Department of Neurology,      for this patient. Conventional treatments, including anticonvulsants, bisphos-
     Baylor College of Medicine, Houston, TX.    phonates, oral steroids and opioids, topical creams, dorsal column spinal cord
       Dr. Edmondson is with the Methodist       stimulation, spinal morphine infusion, sympathetic ganglion block, and sym-
                        Hospital, Houston, TX.   pathectomy, failed to provide long-term relief from pain. An N-methyl-d-as-
                   Address correspondence:       partate (NMDA) antagonist inhibitor, ketamine, was recently suggested to be
                          Paul E. Schulz, MD     effective at resolving intractable pain. The patient was then given several infu-
                   Department of Neurology       sions of intravenous ketamine. After the third infusion, the edema, discolor-
                       6501 Fannin, NB-302       ation, and temperature of the affected areas normalized. The patient became
                 Houston, Texas 77030-3498       completely pain-free. At one-year of follow-up, the patient reported that she
                   E-mail: pschulz@bcm.edu
                                                 has not experienced any pain since the last ketamine infusion.
Disclaimer: There was no external funding in
         the preparation of this manuscript.     Treatment with intravenous ketamine appeared to be effective in completely
                  Conflict of interest: None.    resolving intractable pain caused by severe refractory CRPS I. Future research
         Manuscript received: 03/05/2008         on this treatment is needed.
  Revised manuscript received: 04/14/2008
     Accepted for publication: 04/24/2008        Key words: Ketamine, Complex Regional Pain Syndrome (CRPS), treat-
                                                 ment
                      Free full manuscript:
             www.painphysicianjournal.com
                                                 Pain Physician 2008; 11:3:339-342




C        omplex regional pain syndrome I (CRPS I)
         causes chronic pain and predominately affects
         women between the ages of 36 to 46 (1).
The diagnostic criteria defined by the International
Association for the Study of Pain (IASP) include
                                                                         3) no other known cause (2).
                                                                              CRPS typically occurs after injury (1). Although
                                                                         the pathophysiology of CRPS is not completely under-
                                                                         stood, mechanisms such as neurogenic inflammation,
                                                                         immunological mechanisms and the role of the cen-
1) severe pain not explained by injury, allodynia, or                    tral nervous system have been proposed (3-6).
     hyperalgesia;                                                            Management of CRPS can be challenging as this
2) evidence of edema, vasomotor in the location of                       disorder is difficult to treat. Common treatments for
     the pain, such as cold or warm, red or cyanotic                     CRPS include steroids, sympathetic block, oxygen radi-
     skin; and                                                           cal scavengers, antidepressants, antiepileptics, opioids,


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                                    Pain Physician: May/June 2008:11:339-342



physical therapy, and transcutaneous electrical nerve            Thrombosis was ruled out with the Color-Doppler
stimulation (7). Prevention therapies such as early ac-    ultrasound test. Laboratory tests (CBC, ESR, ANA, and
tivity and vitamin C have been commonly prescribed.        BUN) and nerve conduction studies were within nor-
Presently, limited evidence exists for supporting the      mal limits. Roentgenography of the affected arm re-
efficacy of these therapies (8-10).                        vealed patchy osteoporosis in the carpal bones. With
     Activation of N-methyl-d-aspartate (NMDA) re-         the patient’s clinical symptoms and radiological find-
ceptors may be involved in the induction and main-         ings, she met IASP criteria for CRPS as well as the more
tenance of sensitivity to pain in several chronic pain     recently proposed clinical criteria for the diagnosis of
disorders, such as neuropathic pain and CRPS. Accord-      CRPS (1,15).
ingly, NMDA receptor antagonists such as ketamine                The patient underwent 4 right stellate blocks with
and memantine can be used for the treatment of pain        7 mL of 0.25% bupivacaine; however, pain relief was
patients with these disorders (11-13). Although data       brief and lasted only a few weeks. A thoracic surgeon
on this indication in the literature is limited, several   performed a right stellate cervical sympathectomy via
case reports and case series suggest efficacy for ket-     transthoracic approach, which proved to be an unsuc-
amine in treatment of many chronic pain disorders, in-     cessful treatment. Pain spread to involve the thoracic
cluding peripheral neuropathy, chronic post-traumatic      vertebrae and right shoulder, with the onset of hyper-
neuropathic pain, postherpetic neuralgia, spinal cord      pathia, allodynia, edema, and bluish coloration, also
injury pain, neuropathic pain associated with multiple     felt to be “spread” of CRPS I.
sclerosis and Guillain–Barré syndrome, orofacial pain,           Due to the severity of pain and failure of treat-
CRPS, phantom limb pain, and fibromyalgia (14). We         ments with amitriptyline, gabapentin, opioids, and li-
describe in this case report, a patient with severe re-    docaine cream over the period of a few months, a cer-
fractory CRPS I, which, while unresponsive to conven-      vical spinal stimulator was implanted. Three months
tional treatment for a period of 6 years, was complete-    after using the stimulator, with no relief from pain, a
ly resolved following 3 trials of ketamine infusion.       double morphine pump was implanted at T3-T4 and
                                                           L4-L5. Pain was controlled for 4 months, until the pa-
Case RepoRt                                                tient was admitted to the hospital with symptoms of
     A 41-year-old right-handed woman without past         chemical meningitis, whereupon the morphine pumps
medical history injured her right elbow and wrist dur-     were removed.
ing an accident in 2000. She was taken to the emer-              Four months later, the patient’s right leg exhib-
gency room, where an X-ray of the affected extremity       ited swelling and pain, and had a decrease in range
was performed. The patient was discharged with the         of motion in the knee and ankle. All of the labora-
diagnosis of contusion. However, pain in this area in-     tory tests were normal, and her symptoms and signs
creased gradually and she was referred to an orthope-      exactly followed the pattern of her right arm. After
dic clinic. A second X-ray and a bone scan were stated     an additional 5 months, the patient began showing
to be normal, and the patient was diagnosed with           the same symptoms and signs in her left arm and leg.
a hidden fracture. Pain continued to increase over 4       Clinical and radiological findings pointed to a diagno-
weeks. Following the removal of the cast, the patient      sis of CRPS I in the new locations.
was referred to our interventional pain clinic at The            The patient was admitted to the hospital and
Methodist Hospital with pain and swelling of the up-       started on oral steroids and intravenous (IV) lidocaine,
per right limb.                                            which were ineffective for pain management. Her dis-
     On presentation, the patient had hyperesthesia in     order had caused traumatic emotional problems for
the right upper extremity, particularly below the el-      the patient, including depression and anxiety, and
bow, to the point that she was apprehensive of the         then divorce. Numerous medications were unsuccess-
exposure of air blowing upon the affected limb. In         ful, including the anti-epileptic drug gabapentin, oral
addition, she had diffuse, non-pitting edema in the        glucocorticoids, topical lidocaine cream, opioids, IV li-
right hand and forearm. Hypertrichosis was found           docaine, bisphosphonates, and calcitonin.
in her right upper extremity, and the right hand was             In November of 2006, after 6 years of ineffective
colder compared to the left. Passive and active range      treatment, the patient was taken to an operating
of motion of her right elbow and wrist were restrict-      room and given 50 mg IV ketamine over a period of 30
ed, while other limbs were completely normal.              minutes under anesthetic supervision, but without se-


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                                     Ketamine Treatment for Intractable Pain



dation. As an optimal dosage procedure has not been         fected areas (1,15). This disorder began in the right
identified for CPRS, a procedure similar to that of Za-     upper extremity and moved successively to her thorac-
rate and colleagues (16) and Correll and colleagues         ic area, right lower extremity, and finally her left-sided
(17) was used. Zarate et al (16) demonstrated that          extremities. Following treatment with IV ketamine,
0.5mg/kg over 40 minutes was an effective dose for al-      her pain completely resolved.
leviating depression. It appeared that this dose prob-           The treatment for CRPS is still debated. The
ably resulted in an NMDA effect that was sustained for      treatment for this patient included anticonvulsants,
at least one week, and therefore could also be effec-       bisphosphonates, oral steroids and opioids, topical
tive for treating chronic pain in CPRS. One author (EE)     creams, dorsal column spinal cord stimulation, spinal
began using this dosage and found alleviation of pain       cord morphine pump, sympathetic ganglion block and
in approximately 140 cases of intractable pain of neu-      sympathectomy. None of these treatments, however,
ropathic origin or CPRS; however, he found that doses       provided long-term pain relief.
over 50 mg were more likely to result in psychiatric             The pathophysiology underlying CRPS I is unclear;
side effects. A fixed dose of 50 mg began to be used        however, recent research suggests that sensitization
for adults as it appeared to be effective with less sig-    of the central nervous system may be the source of
nificant side effects. Hence, a 50 mg/30 min treatment      pain in CRPS 1 (2). In CRPS, afferent neurons in the
was used for the patient described in this case report,     spinal cord may have an increased rate of release of
and has become a standard dose for the authors for          glutamate, which may pathologically activate NMDA
the treatment of pain.                                      receptors, leading to central sensitization and hyper-
     The patient had a hypertensive reaction to the         excitability (12). This is supported by the finding that
first infusion, and labetalol and hydralazine were          ketamine, an NMDA receptor antagonist, may provide
used to abate this reaction. The patient’s pain level       pain relief in CRPS (13). After 3 infusions of intrave-
decreased from 10 to 3 on a 10-point scale and re-          nous ketamine (each one week apart), the patient’s
mained at that level for 5 days. In order to prevent a      pain completely resolved after the last infusion and at
second hypertensive reaction, midazolam was added           her one-year follow-up visit, she remained pain-free.
to the procedure, providing a significant reduction in           Adverse effects of ketamine may include psy-
blood pressure and heart rate elevation in following        chotomimetic effects, including hallucinations and
sessions. Ketamine infusion was performed a second          agitation. Ketamine can also cause a hypertensive
time on day 7, resulting in complete resolution of pain     reaction, nausea, vomiting, increased salivation, and
for 7 days. Ketamine was infused a third and final          muscle spasms. In efforts to decrease these side ef-
time, whereupon the edema, discoloration, and tem-          fects, patients can be given ketamine in a supervised
perature of the affected areas normalized. Following        environment with co-administration of a benzodiaz-
the last infusion, the patient was completely free of       epine such as of the relaxant midazolam (18,19).
pain for the first time in 6 years. After each infusion,
the patient seemed slightly euphoric. She developed
                                                            ConClusion
a migraine-like headache for 3 days after first infu-            Early treatment in CRPS is well known to be ben-
sion that she felt was similar to past migraines, but she   eficial for patient outcome, and can protect against
did not present with any other side effects during her      complications (20). Additionally, it is our experience
treatment. At a one-year follow-up visit, the patient       with refractory CRPS that performing multiple proce-
reported continuing physical therapy and psychother-        dures can lead to a myriad of complications and pro-
apy, and has not experienced any pain since the last        long the course of disease. Although this is only one
ketamine infusion.                                          case report, and thus we cannot conclude anything
                                                            from it, it is of interest that ketamine appeared to be
DisCussion                                                  beneficial after 6 years of ineffective long-term treat-
     We describe a patient with a 6-year history of         ments. Furthermore, it is conceivable that early treat-
severe, refractory CRPS I. The patient met IASP crite-      ment with ketamine in CRPS, may be beneficial. None-
ria and the new diagnostic criteria for CRPS with the       theless, more research on this treatment is needed to
presentation of hyperesthesia, allodynia, non-pitting       better define its efficacy in CRPS.
edema, colder temperature, and hypertrichosis in af-




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                                              Pain Physician: May/June 2008:11:339-342




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