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© 2003 American Society for Clinical Oncology
Interventional Pain Therapy for Intractable Abdominal Cancer Pain
From the Department of Anesthesiology, Mayo Clinic Scottsdale, Scottsdale, AZ, and Department of Anesthesiology, Mayo Clinic Rochester, Rochester, MN. Address reprint requests to David P. Seamans, MD, Department of Anesthesiology, Mayo Clinic Scottsdale, 13400 East Shea Blvd, Scottsdale, AZ 85259; email seamans.david{at}mayo.edu.
PAIN MANAGEMENT can be a challenge in certain patients with cancer because of inadequate analgesia and/or intolerable side effects from systemic analgesic medications. In these circumstances, interventional pain management techniques have the potential to provide improved pain control with decreased side effects,1 and they can be cost-effective in certain cases.
A 61-year-old woman with metastatic colon cancer presented with complaints of intractable abdominal pain. Since her initial diagnosis of colon cancer with liver metastases 14 years earlier, she had undergone multiple surgeries, including sigmoid colon resection, excision of hepatic metastases (on two separate occasions), and excision of a pulmonary metastasis. In addition, she had received several courses of chemotherapy. The patient did not complain of pain until 7 months before our initial evaluation. At that time, her local physician prescribed oxycodone and acetaminophen to control her abdominal pain. Two months later, she was started on sustained-release morphine, the dose of which was eventually increased to 1,200 mg total per day (over a 3-month period). The sustained-release morphine was supplemented with immediate-release morphine solution (600 mg) up to four times per day for breakthrough pain. Approximately 3 weeks before our initial evaluation, her local care team gradually switched her to fentanyl patches (Duragesic patch; Janssen Pharmaceutica, Titusville, NJ) with continued use of oral morphine solution for breakthrough pain. The decision by her local care team to switch to fentanyl was presumably due to inadequate analgesia combined with increasing opioid side effects, especially sedation. Over the 3-week period, her pain continued to worsen, despite increasing numbers of fentanyl patches. At our initial evaluation, the patient was using a total of 30 100-µg/h (3,000 µg/h total) fentanyl patches at a time. The patches were being changed every 3 days, and the large number of them required placement over her chest, abdomen, back, and portions of all four extremities. During our first meeting, the patient was very somnolent but still complaining of severe, constant, sharp, aching, and "knife-like" upper and lower abdominal pain. She rated her pain intensity at 7 out of 10 on a numerical rating scale (0 = no pain and 10 = worst pain possible), with frequent exacerbation to a pain rating of 10 associated with even minimal movement. Her family reported that sedation and episodes of confusion had progressively worsened with the increasing number of fentanyl patches. Previous computed tomographic scans (6 months earlier) demonstrated enlarging metastatic lesions involving the capsule of the liver and para-aortic lymph nodes.
The patient was hospitalized to manage her intractable pain and sedation. In the first 24 hours after admission, 10 patches were removed while continuous intravenous infusion of fentanyl was provided with a patient-controlled analgesia pump. Given her complaint of upper abdominal pain likely related to widespread metastases involving the liver capsule and para-aortic adenopathy, we performed a neurolytic celiac plexus block, which decreased her pain rating from 7 to 10 down to 4. With improved pain control, all of the fentanyl patches were removed over the next 72 hours, while the patient was still being provided with fentanyl by continuous intravenous infusion and patient-controlled analgesia pump. Her mental status improved with these changes. On day 3 after admission, the patient’s candidacy for possible implantation of a morphine spinal delivery system was assessed using a 4-mg intrathecal test dose of morphine. She had a good prognostic response (pain rating, 1 to 2) to the intrathecal morphine for nearly 6 hours without adverse effects. The next day, we repeated the intrathecal morphine test dose with 6 mg of morphine, which provided her with even better analgesia (pain rating, 0) for nearly 8 hours without adverse effects. We proceeded to implant a spinal drug delivery system (SynchroMed infusion pump; Medtronic, Minneapolis, MN) with an indwelling intrathecal catheter (Indura; Medtronic). The implanted spinal infusion pump was programmed to continuously deliver intrathecal morphine at a rate of 6 mg every 24 hours. The patient was discharged 1 week after admission without any complaints of pain (pain rating, 0) and with a markedly improved mental status. The patient was evaluated on three subsequent occasions after her admission. Both at 4 weeks and 8 weeks after discharge, she continued to report her pain rating at 0 to 1. The patient and her family felt she had made a dramatic and sustained improvement in her pain control, functional abilities, quality of life, and satisfaction with her life. Three months after her spinal pump placement, the patient experienced increasing upper abdominal discomfort. The intrathecal morphine infusion rate was incrementally increased. These adjustments improved her discomfort and she died, relatively comfortably, approximately 5 months after her hospital discharge.
This case illustrates the potential benefits of adjunctive analgesic therapies and alternative routes of opioid administration. Systemic opioid therapy did not provide this patient with adequate pain control despite causing severe sedation. Neurolytic celiac plexus block can be a useful adjunctive interventional analgesic technique for upper abdominal visceral cancer pain.2 The celiac plexus is primarily a sympathetic nervous system structure mediating nociceptive transmission from the upper abdominal viscera, including the liver and biliary tree, pancreas, kidneys, omentum, and the alimentary tract extending from the stomach to the large bowel (to the level of the splenic flexure). The placement of bilateral percutaneous needles from the midback to the celiac plexus (at the anterolateral border of the L1 vertebral body) allows injection of neurolytic agents, such as alcohol or phenol. The resultant neurolysis can interrupt the transmission of upper abdominal visceral pain to the CNS for 3 to 6 months. It is important to note the presence of alternate pain pathways in abdominal pain that are not blocked by neurolytic celiac plexus block. These typically require the continued use of opioid analgesics. However, by providing opioid-sparing analgesia, a neurolytic celiac block can potentially be useful in patients, such as our patient, who are experiencing intolerable opioid dose-related side effects. Neurologic complications engender the greatest concerns associated with neurolytic celiac block. The incidence of these complications is extremely rare (0.15%), but they can be associated with sensory or motor deficits of the lower extremities and can affect bowel or bladder function.2 Intraspinal drug delivery, including intrathecal or epidural routes, can be a highly effective analgesic technique for the management of cancer pain.1,3 Although the vast majority of patients with cancer pain (estimated at > 90%) can be effectively managed with the use of systemic opioids,4,5 certain patients, such as our patient, are unable to attain a favorable balance between analgesia and side effects from systemic opioid therapy. Intraspinal drug delivery allows minute quantities of drug to be delivered to the spinal cord to modulate important neurochemical receptors involved in pain transmission. The dose of intrathecal morphine, the most commonly used intraspinal drug, is approximately 1% of the required intravenous morphine dose needed to achieve equivalent analgesia. This decreased total opioid dose may result in fewer systemic opioid-related side effects, such as sedation and constipation.
The economic issue associated with implantable spinal drug delivery systems can be an important consideration. There are few cost analyses to compare analgesic modalities used to treat refractory pain because of the complexities associated with cost assessment. In comparison with systemic analgesic therapy, the implantable spinal pump generates most of the total cost at the time of pump placement because of both the cost of the pump hardware and the involved procedure. Previous study has suggested that these devices may be cost-effective after 18 to 30 months compared with systemic analgesic therapy.6 In our case, however, the patient required especially large doses of opioids in a sustained-release transdermal fentanyl patch, which generated estimated costs of approximately $10, 000 per month. We compared the costs of intrathecal therapy with the estimated cost of continued systemic opioid therapy at the baseline doses of our patient (Table 1
Consistent with all medical interventions, the risks and potential complications of intraspinal drug therapy must be carefully considered in each patient with cancer pain. These potential complications may be related to either the side effects of the intraspinal drug or the intraspinal delivery device. Intraspinal drugs usually involve opioids, which may cause drug-related side effects, including pruritus, urinary retention, constipation, nausea and vomiting, sedation, and dysphoria. Morphine, the most commonly used intraspinal opioid, has not been associated with neurotoxic effects in the spinal cord even with long-term intraspinal therapy. Complications associated with the intraspinal drug delivery device may require removal of the system. The most serious complication, infection, is very uncommon. Other device-related problems may include mechanical malfunction, catheter obstruction or breakage, CSF leakage, and hematoma.1 Thus, the potential complications associated with intraspinal drug therapy are relatively uncommon but must be considered in each patient. Lastly, the use of intrathecal morphine requires the availability of a team that can manage the therapy and service the device. The existence of such an infrastructure is essential to the potential success of this line of therapy.
We thank Jan C. Buckner, MD, Michael K. Gornet, MD, Derek A. Duke, MD, and Charles L. Loprinzi, MD, for their roles in the care of this patient.
Supported in part by Foundation for Anesthesia, Education and Research, Rochester, MN.
1. Lamer TJ: Treatment of cancer-related pain: When orally administered medications fail. Mayo Clin Proc 69:473–480, 1994[Medline] 2. Wong GY, Brown DL: Celiac plexus block for cancer pain, in Urmey W (ed): Techniques in Regional Anesthesia and Pain Management. Philadelphia, PA, WB Saunders, 1997, pp 18–26 3. Onofrio BM, Yaksh TL: Long-term pain relief produced by intrathecal morphine infusion in 53 patients. J Neurosurg 72:200–209, 1990[Medline] 4. Ventafridda V, Caraceni A, Gamba A: Field-testing of the WHO Guidelines for Cancer Pain Relief: Summary report of demonstration projects, in Foley KM, Bonica JJ, Ventafridda V (eds): Proceedings of the Second International Congress on Pain, Volume 16: Advances in Pain Research and Therapy. New York, NY, Raven Press, Ltd, 1990, pp 451–464 5. Ventafridda V, Tamburini M, Caraceni A, et al: A validation study of the WHO method for cancer pain relief. Cancer 59:850–856, 1987[CrossRef][Medline] 6. Hassenbusch S: Cost modeling for alternate routes of administration of opioids for cancer pain. Oncology 13:63–67, 1999 (suppl)[Medline]
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Copyright © 2003 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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