Selection Criteria for Intrathecal Opioid Therapy: A Re-examination of the "Science"
Since the pioneering work of Wang et al.1 twenty-five years ago, intrathecal opioid delivery has been used to manage a wide variety of refractory pain conditions in patients whose responses to oral opioid analgesics has been unsatisfactory. While most chronic pain sufferers who require chronic opioid therapy can be managed with oral agents, problems with intolerable side effects and habituation preclude their long-term utilization among a subgroup of chronic pain patients. Coombs et al.2 reported the first successful surgical implantation of an intrathecal opioid pump in 1982. Subsequently, chronic pain conditions which have been found to be treated effectively through intrathecally-administered opioids have included nonmalignant conditions such as failed spinal surgery syndrome, spinal or radicular pain without spinal surgery, complex regional pain syndrome, osteoporotic crush fractures and chronic pancreatitis,3 multiple sclerosis and compression fractures,4 phantom limb pain, arachnoiditis and spinal cord injury,5 loin pain hematuria syndrome,6 severe burns,7 and rheumatoid arthritis8 as well as a number of types of cancer pain.4,9-13
The numerous studies which have supported the use of intrathecal opioid therapy (IOT) for cancer pain have served to make this type of treatment for cancer patients progressively less controversial over the years. However, problems with side effects and risk issues along with an inadequate understanding of the potential improvement in the quality of life of patients suffering from severe intractable pain from nonmalignant causes has perpetuated the controversy regarding the use of IOT among patients with chronic pain of benign cause. This controversy is curious given the lack of research findings suggesting that IOT is not appropriate for patients with intractable nonmalignant pain, particularly when so many investigators3-8,14,15 have determined that IOT can be so effective for these patients, with benefits clearly outweighing potential problems. A review of the literature suggests that only the results of a study by Yoshida and colleagues16 would suggest the general contraindication of IOT for nonmalignant chronic pain. It should be noted, however, that their conclusion was based upon complete data from only 14 patients, thereby impacting its reliability. IOT has also been found to be cost-effective when compared to conventional pain therapies among nonmalignant chronic pain sufferers.8,15,17,18
Concerns Associated With IOT
Despite the wealth of studies supporting the use of IOT with malignant and nonmalignant chronic pain patients, it would be a mistake to suggest that this method of delivering opioid analgesics is completely free of complications. Problems with the catheter, including kinking, obstruction, dislodgement and disconnection, are relatively common, reportedly occurring in 10% to 40% of cases.19 Cerebrospinal fluid leaks are typically evidenced during intrathecal catheter placement, with postspinal headaches reported in up to 31% of patients.20 While these headaches usually resolve spontaneously, some will require an autologous blood patch. Infection can be a problem associated with the implantation of indwelling opioid pumps, as is true for all surgical procedures. Deer et al.14 recently reported an infection rate of 2.2% among patients in a large multi-site study of patients receiving IOT. Aggressive prophylactic use of antibiotics, along with strict sterile technique, has been recommended as a means of reducing infection.19 Despite precautions and improvements in equipment and techniques, the need for additional surgery following the implantation of an intrathecal opioid pump was reported to be 40% in a 2001 Australian study.3 This figure approximated the percentage of patients requiring additional surgery due to complications reported by Tutak and Doleys.21
The accepted advantage of IOT over systemic opioids is the delivery of the opioid directly to the effective site of action in the spinal cord, thereby avoiding brain sites that produce the most troublesome side effects of oral opioids.22 Chronic oral opioid use has been associated with problems with working memory, vigilance/attention, psychomotor speed, and recognition.23,24 Nevertheless, reports in the literature indicate that severe side effects can be associated with long-term IOT. Penn22 noted that the same adverse effects of systemic opioids can occur in patients receiving IOT. These side effects may include nausea, vomiting, drowsiness, anorexia, weight loss and constipation. A study of cancer patients by Smith et al.,25 however, indicated that these adverse effects occurred at statistically lower rates in IOT patients than in patients receiving comprehensive medical management, which consisted primarily of oral opioid analgesics. Interestingly, the authors also found that the patients receiving IOT also lived longer than did those in the comprehensive medical management group. The incidence of sexual side effects among patients receiving IOT is extremely high. Several studies26-31 have associated IOT with hypothalamic-pituitary-gonadal suppression. Roberts et al.3 found that 71% of male and 48% of female IOT patients in their study reported decreased libido, with 59% of the males reporting erectile difficulties and 47% of the females under the age of 50 reporting menstrual abnormality. While the provision of gonadal steroids has been recommended,26,31 it is unclear whether practitioners providing IOT are routinely doing so. Accordingly, the possibility that serious and demoralizing sexual side effects of IOT go untreated exists.
The development of tolerance to intrathecally-administered opioids in long-term therapy has been expressed as a concern in the literature.5,32 However, a number of studies have suggested that tolerance is typically not problematic to the extent that it precludes continued IOT. Winkelmuller and Winkelmuller33 found that tolerance developed in only 7 of 120 nonmalignant chronic pain patients receiving IOT who were followed for an average of 3.4 years, with only 3 of the patients requiring removal of their pump. Other investigators of intrathecal administration of opioids to both cancer and non-malignant chronic pain patients34,20,10,35,36,3,37 have similarly found that tolerance to IOT is generally developed very gradually following initial dose titration, and is not likely to significantly interfere with long-term treatment. The use of intrathecally-administered adjuvants such as bupivicaine, lidocaine, clonidine, ziconotide, and neostigmine have been reported to reduce problems associated with tolerance.19,38 Opioid dosage escalation, of course, is considered to be a more salient issue in IOT of nonmalignant chronic pain than in the treatment of pain due to cancer.