Neuraxial Infusion for Pain Control: When, Why, and What to Do After the Implant

Introduction

The use of neuraxial infusion for cancer pain first requires appropriate education for the oncologist. Many oncologists are not familiar with intraspinal analgesia and may not be able to contribute to clinical decisions involved in patient selection and timing of therapy. There are no strict indications or guidelines for this technique, and each physician must develop his or her own approach based on knowledge of the therapy and clinical judgment. Physicians who treat cancer patients must understand ongoing patient management after a permanent system is implanted. Oncologists may believe that once a device is implanted, the work is done. Implantable infusion therapy, however—much like medical management—involves multiple medications, multiple dose titrations, and constant monitoring to establish a favorable analgesia-to-side-effect profile.

Barriers to Pain Relief

The acceptance of intraspinal therapy has been impeded by numerous barriers. These include:

• Lack of knowledge of the therapy.[1]
• Lack of double-blinded, randomized, controlled trials demonstrating the efficacy of this therapy and its superiority over conventional therapies; the current efficacy data are limited to prospective and retrospective surveys.
• Financial barriers
• Fear of invasiveness
• Barriers to providing pain relief in general.

Eight million people in the United States have cancer,[2] and 50% have pain, as estimated by the World Health Organization. Therefore, 4 million patients have cancer pain.[3] With optimal medical management, 75% to 90% of these patients attain pain relief. Four hundred thousand cancer patients in the United States have cancer pain each year that cannot be controlled with routine systemic therapy under the best of circumstances. True outcomes are actually much worse because of undertreatment.[4,5]

Medical therapies remain the mainstay of chronic cancer pain management. The World Health Organization Ladder for Chronic Cancer Pain Management (Figure 1) is a valuable tool, but was intended for both developing and developed countries and may not be sufficient for developed countries.[6] Between 75% and 90% of patients can have their pain controlled by following this ladder. It also provides a framework for managing patients with intractable pain. But the ladder offers no guidance for the management of side effects or the selection of patients for interventional therapies.

There are different approaches to managing the patient with pain that is poorly responsive to opioids. Oncologists are particularly good at managing side effects and know when palliative chemotherapy and palliative radiotherapy are indicated. They are not as familiar with neurolytic blocks, intraspinal infusion therapies, and neurosurgical options. In contrast, pain management physicians are more familiar with neurolytic blocks, infusion therapies, opioid rotation, and the use of coanalgesics. Clinicians must eliminate barriers between disciplines (Figure 2). The oncologist should understand when neurolytic blocks and infusion therapies are indicated and the pain physician must understand the full spectrum of palliative care with medical therapies, as well as when chemotherapy and radiation therapy are needed.

Role of Intraspinal Therapy

Although medical therapies remain the mainstay of pain control, side effects may limit the benefits of therapy. Side effects include sedation, mental cloudiness, and constipation.[7] It is at these times that we need to consider and position neuraxial infusion therapies in the spectrum of options.

Both the Agency for Health Care Policy and Research and the National Comprehensive Cancer Network have guidelines for interventional therapies such as neurolytic blocks and infusion therapies.[8] If these guidelines were followed, the number of patients who are treated with neurolytic blocks or infusion therapies would probably increase substantially.[9-11] There are also many more options for intraspinal treatment. With intrathecal clonidine(Drug information on clonidine), local anesthetics, and hydrophilic and lipophilic opioids, and even new drugs like intrathecal ziconitide, the role of interventional neuraxial infusions should be increasing.

It is possible that a more thoughtful approach to the use of invasive therapies might be based on assessment of the disease process and likelihood of responding to medical and interventional therapies. For example, a patient with pancreatic cancer may respond to a celiac plexus block early in the disease; this procedure has been shown to improve pain relief, mood, and, possibly, life expectancy.[12,13] If a patient with cancer has a new onset of back pain, the epidural metastasis must be considered, and radiation therapy may be recommended early. Likewise, there might be times when clinicians can predict that a patient would do poorly with systemic opioids, and could then intervene with intrathecal infusion approaches early to gain as much benefit as possible. More research is needed to explore this potential.

It is important for pain management specialists to discuss with colleagues in oncology the potential advantages of epidural and intrathecal infusions. Epidural and intrathecal infusions:

• Can be effective for multiple pains
• Are titratable
• Are nondestructive and safe
• Require low doses of opioids, and can have a lower side-effect liability than the systemic opioids
• Offer the possibility of adding intraspinal coanalgesics
• Can be cost-effective.[14]

Furthermore, neuraxial opioids have no motor, sensory, or sympathetic effects. The normal conversions from systemic to intrathecal opioids range anywhere from 200:1 to 600:1. The oral/epidural conversion for morphine(Drug information on morphine) is 30:1, and for oral/intrathecal conversion, 300:1. The lower dose needed to produce effects may lead to a better side-effect profile in most patients.[15]

Intrathecal Infusion Studies

The theoretical advantages of intraspinal therapy are complemented by several retrospective studies and case reports that intrathecal morphine is effective in the treatment of cancer pain.[15-18] Although most surveys of intraspinal therapy revealed high success rates, many patients entered into these surveys were not required to develop side effects prior to proceeding to an implanted device. It also is not clear how much work was done to control side effects before the patient received the implanted device, or whether opioid rotation was tried. For this reason, spinal therapy is usually still considered an approach for managing patients with pain that is refractory to an optimally administered systemic opioid regimen.

Need to Increase Awareness

Recently, a study assessing attitudes of oncologists toward interventional cancer pain management was conducted.[1] A series of qualitative (74) and quantitative (230) interviews were carried out in a sample group of 304 cancer health care specialists. Qualitative tests included focus group discussions and quantitative evaluations included computer-aided telephone interviews.

Pain assessment techniques used by cancer care personnel had little emphasis on the more accurate multidimensional assessment techniques. Extended release morphine sulfate preparations were found to be the most commonly prescribed analgesic in this project with lower doses (0 to 300 mg/day) considered to be within their margins of comfort by 73% of those studied. A total of 81% of oncologists reported patient referral to pain specialists to be a part of their current practice (Figure 3). The familiarity with intrathecal therapy was low, with only 46% having referred patients for intrathecal therapy in the previous 12 months. The invasive nature of device placement was deemed a drawback by 42% of physicians. The study indicates that continued education of both patient and physician is essential to ensure that all means of treatment are available to cancer pain patients.