Gabapentin in Phantom Limb Pain Management in Children and Young Adults: Report of Seven Cases

Transcription

1 78 Journal of Pain and Symptom Management Vol. 21 No. 1 January 2001 Clinical Note Gabapentin in Phantom Limb Pain Management in Children and Young Adults: Report of Seven Cases Lynn M. Rusy, MD, Todd J. Troshynski, MD, and Steven J. Weisman, MD Departments of Anesthesiology (LMR, TJT, SJW) and Pediatrics (SJW), Medical College of Wisconsin- Children s Hospital of Wisconsin, Milwaukee, Wisconsin, USA Abstract Seven children and young adults with phantom limb pain (PLP) were treated with gabapentin. PLP resolved in six patients within two months. One patient still had symptoms to a lesser degree. Mean follow up time was 1.74 years. Gabapentin may be a useful adjunct to pain management in patients with PLP symptoms. J Pain Symptom Manage 2001; 21:78 82 U.S. Cancer Pain Relief Committee, Key Words Gabapentin, phantom limb pain Introduction Phantom limb pain (PLP) is a sensation that may follow the surgical or traumatic removal of an extremity. Patients with PLP may be concerned about their credibility as they describe pain in a part of the body they no longer have. PLP may be described as stabbing, squeezing, tightness, burning, shooting, cramping or an unnatural position of the limb. Gabapentin has been used effectively in a variety of neuropathic pain syndromes. 1 Other anticonvulsants also have been useful in decreasing certain types of chronic pain. 2 We report a series of seven pediatric and young adult amputee patients with successful control of PLP within two months after initiation of gabapentin. Address reprint requests to: Lynn M. Rusy, MD, Children s Hospital of Wisconsin, 9000 West Wisconsin Avenue, PO Box 1997, Milwaukee, WI 53201, USA. Accepted for publication: February 22, Methods Charts were reviewed for all patients with PLP treated with gabapentin at the Children s Hospital of Wisconsin over a two-year period. The response to gabapentin was determined both by chart review and telephone interview. Patients gave verbal pain descriptions and reported presence or absence of PLP. Mean follow-up time since starting gabapentin was 1.74 years. Case Reports Seven patients, ages 7 28, are summarized in Table 1. Case 1 A 9-year-old, 40 kg girl had traumatic amputation of a lower extremity below the knee in a boating accident. Stump pain was managed with an intravenous opioid, followed by a short course of an oral opioid. Low dose amitriptyline (10 mg at night) was started. PLP began and interfered with sleep. The PLP, which was described as stabbing and feeling as if the absent leg was standing straight up in the air, be- U.S. Cancer Pain Relief Committee, /01/$ see front matter Published by Elsevier, New York, New York PII S (00)

2 Vol. 21 No. 1 January 2001 Gabapentin for Phantom Limb Pain 79 Table 1 Summary of Seven Patients in this Case Report Case No. Age/ Gender Weight (kg) Etiology Daily Gabapentin Dose mg/kg Additional Pain Meds and Treatment Time to Phantom Pain Free Other Pain Sites Followup time 1 9/F 40 Traumatic 2 25/M 70 Osteosarcoma; 3 28/F 60 Osteosarcoma; 4 9/F 40 Osteosarcoma; 5 25/F 60 Pelvic osteo; Hemipelvectomy 6 22/M 60 Osteosarcoma; 7 4/M 15 Traumatic 35 amitriptyline 1 month none 2 years 10 mg QHS 25 none 1 week none 2 years 14 epidural methyl prednisolone, oxycodone, transdermal fentanyl 2 weeks L5 degenerative joint disease 0.83 years 35 TENS 1 month none 2 years 40 transdermal fentanyl oxycodone 20 amitriptyline oxycodone 20 amitriptyline 10 mg QHS 2 months pelvic stump 3 years 2 weeks lung mets 1 year 1 month none 1.33 years below-knee amputation. gan one week following the accident. Gabapentin was started and was titrated to a dose of 500 mg three times daily. PLP disappeared and gabapentin was continued for three months. It was then decreased to twice daily due to difficulty taking the medicine while at school. Gabapentin was continued at this dose for nine months with no complaints of phantom pain. She stopped her amitriptyline on her own after 4 months. Gabapentin was then tapered over one month without return of phantom sensations. She was off all medications one year after the accident. Case 2 A 25-year-old, 70 kg man had below the knee amputation for osteosarcoma under combined epidural and general anesthetic. He presented with pain in the knee prior to the diagnosis of osteosarcoma. Postoperative pain was treated with the epidural for three days and then acetaminophen plus codeine was begun. He developed stabbing pain sensations in the absent right foot two weeks after the amputation. Gabapentin was started at 300 mg three times daily and was titrated to 500 mg three times daily. This completely eliminated these sensations. During chemotherapy, gabapentin was discontinued secondary to nausea and phantom sensations returned. This pain was partially treated with intravenous morphine. When his nausea was under control and oral intake was possible, phantom pain sensations were again eliminated with gabapentin. Six months after amputation, the gabapentin dose was reduced to 500 mg twice daily for another six months. He then tapered his gabapentin over two weeks without return of the painful sensations. Case 3 A 28-year-old, 60 kg woman had osteosarcoma diagnosed at age 22 with knee pain. She received chemotherapy and underwent below the knee amputation. Recurrence with a pulmonary nodule four years later required thoracotomy for resection. Poor compliance with follow-up resulted in minimal contact for two years, until she presented with severe back pain and stabbing phantom pain. She reported that she had the phantom pain since the amputation. Biopsy of the L5 vertebral body showed degeneration but no tumor recurrence and this pain was managed effectively with epidural steroids, hydrocodone plus acetaminophen and transdermal fentanyl. Phantom sensations were completely eliminated with gabapentin 300 mg three times daily. She moved to an-

3 80 Rusy et al. Vol. 21 No. 1 January 2001 other city and on phone contact she reported to have been using her gabapentin occasionally, only when phantom sensations were really bad, with good relief. Case 4 A 9-year-old, 40 kg girl with knee pain from osteosarcoma underwent below knee amputation and chemotherapy. Three weeks after surgery, she began experiencing sensations of stabbing pain in the absent foot like someone had driven a large stake in my foot. Gabapentin 200 mg three times daily was begun. After one week of therapy, she noted a slight improvement in her phantom pain during the day, but was frequently awakened in the night with foot pain in the absent foot. She was admitted to the hospital for chemotherapy and her nighttime dose of gabapentin was increased to 500 mg, but the pain still occurred. Contralateral transcutaneous electrical nerve stimulation (TENS) was added to the pain regimen and the gabapentin dose was increased to 500 mg three times daily. In addition, she took acetaminophen with codeine to help her sleep through the night. One month later, on a follow-up phone call, she reported that she was only taking gabapentin 500 mg three times daily. She added that she still sensed that the foot was there, but it was not painful. Six months later, she was able to wean off gabapentin over two weeks and has remained phantom pain free. Case 5 A 25-year-old, 60 kg woman with pelvic osteosarcoma presented initially with neuropathic pain from sacral involvement of her tumor. This was treated with amitriptyline and opioid analgesics, but improved only after radiation and chemotherapy. Later, she underwent hemipelvectomy at another institution and developed severe PLP. She also developed deep sacral pain following the amputation, which was treated with transdermal fentanyl and then controlled-release oxycodone. The PLP was treated with gabapentin 200 mg three times daily, which was rapidly escalated to 800 mg three times daily. At this dose, her PLP symptoms persisted and various other agents, including amitriptyline, mexiletine, lamotrigine, and venlafaxine hydrochloride were added, without much success. Amitriptyline and mexiletine were discontinued. After two months the patient requested that the gabapentin also be stopped and instructions were given to wean the dose over several weeks. When the dose was decreased to 600 mg three times daily, there was a dramatic increase in PLP and the dose was returned to 800 mg three times daily. Over the next two months, the PLP gradually decreased to a level of pain that was tolerable to her. She continues on gabapentin at a dose that varies between 800 mg three times daily and 1200 mg twice daily. Acupuncture and TENS were tried but made the pain worse. Case 6 A 22-year-old, 60 kg man diagnosed with osteosarcoma underwent a right at knee amputation six years earlier. He then developed a dramatic increase in PLP. He was started on gabapentin 300 mg twice daily and later increased this to 600 mg twice daily, after which PLP symptoms resolved almost completely. Unfortunately, he later developed right chest wall pain, which proved to be the result of recurrent metastatic osteosarcoma. This pain was treated with controlled-released morphine until he died four months later. Case 7 A 4-year-old, 15 kg boy had a traumatic below-the-knee amputation in a lawnmower accident. Problems including acute stump and skin graft site pain were treated with morphine and acetaminophen with codeine elixir, which was tapered over three weeks. While receiving these opioids, he also complained of PLP, which was described as a hook in the toes. He was started on gabapentin 100 mg twice daily. His hook pain was much worse at night, and the evening dose was increased to 200 mg and amitriptyline (10 mg) was added. Gabapentin was increased to 100 mg three times daily and the PLP stopped. He still senses his toes, but no longer feels the hook. Both amitriptyline and gabapentin were tapered and stopped one year after the accident without recurrence of his phantom pain. Discussion Children and young adults who undergo amputation for a variety of reasons, including can-

4 Vol. 21 No. 1 January 2001 Gabapentin for Phantom Limb Pain 81 cer, trauma, and congenital malformation, may develop PLP. Many analgesic modalities have reported to be ineffective for these symptoms. These include sympathetic blockade, tricyclic antidepressants, TENS, trigger point injections, psychotherapy, massage, biofeedback and, even dorsal rhizotomy or partial lobectomy. 3 When an intervention helps, relief is often temporary. It is commonly thought that patients with pain in the extremity prior to amputation are more likely to develop pain after amputation. Pre-emptive neural blockade prior to amputation may improve pain outcome. For example, sympathetic blockade with local anesthetics and opioids for three days prior to amputation has ben shown to decrease the incidence of PLP after one year. 4 Intravenous calcitonin also has been successfully reported to reduce PLP. 5 Compared to placebo, TENS applied to the contralateral extremity has been shown to be significantly more effective in decreasing the intensity of phantom sensations. 6 The etiology of PLP is not known. Chronic pain syndromes with similar symptoms can be caused by injuries involving peripheral nerves, the spinal cord, or the brain itself. Central mechanisms are thought to play a significant role in PLP. The dorsal horn undergoes various physical and biochemical changes after amputation 7 and may play a significant role in the integration of signals from damaged nerve stumps. Deafferentation can lead to structural changes and excessive neuronal firing in the peripheral nervous system, and this, too, may be involved in the pathogenesis of PLP. Anticonvulsants have been used in the management of chronic neuropathic pain. In the past, commonly used drugs included carbamazepine, phenytoin, clonazepam and valproic acid. Side effects of these drugs are numerous. Gabapentin is now often used and is perceived to be well tolerated and effective. 8 Side effects associated with gabapentin in adults are dose-related; the usual effective dose range is 1,800 to 3,600 mg per day. 9 The common side effects include sedation, dizziness, nausea, tremors, memory loss, edema, blurred vision and numbness. 1 Gabapentin was designed as a gamma aminobutyric acid (GABA) agonist, but this has not been documented as its mechanism of action. The anticonvulsant effects may be related to GABA, but its analgesic effects are hypothesized to be by another central inhibitory mechanism. Given spinally, gabapentin and its analogue, 3-isobutyl gama-aminobutyric acid, produced dose-dependent reversal of the thermal hyperalgesia evoked by mild thermal injury to the hind paws in rats. 10 In adults, diverse types of neuropathic pain have been reported to respond to gabapentin. 1,11 15 In a randomized controlled trial, Rothbotham et al. showed gabapentin to be effective in the treatment of both pain and sleep disturbances of postherpetic neuralgia. 14 In a similar trial, Backonja et al. had the same success both for pain and sleep disturbances, as well as positive effects on mood and quality of life, in diabetic patients with painful peripheral neuropathy. 13 While PLP may spontaneously regress, surveys of 8000 amputees have shown that at least 80% will experience significant stump pain or PLP one year after loss of the limb. 16 The incidence of PLP may even be higher in the pediatric population. Krane and Heller reported that 100% (24/24) of young amputees had phantom sensations and 83 percent had PLP. 17 Six of our seven patients had relief of phantom pain sensations within two months of starting gabapentin. It seemed that when the right dose was found, relief of the pain occurred suddenly. Minimal side effects occurred. four patients had mild dizziness, which resolved after the first few doses. Would these six patients have had spontaneous resolution of their phantom pain without the use of gabapentin, or did the gabapentin have a curative effect? Other medications and pain therapies were tried, with only marginal control of phantom symptoms. Gabapentin was able to control the symptoms with few side effects and no recurrences, even after stopping the medication. The patient who did not response well underwent more extensive surgical resection, hemipelvectomy, and this may have played a role in her continued PLP. Randomized controlled studies in children are warranted to further elucidate the value of gabapentin in PLP. Due to the infrequency with which pediatric amputee patients present for pain management, such studies may require multi-institutional collaboration. Based on this series of clinical observations, it appears that gabapentin may have a useful role in the

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