Pain Management at the End
of Life (The Hospice Patient)

Gary Reisfield, M.D., Community Hospice of Northeast Florida

Assessment is a critical and particularly challenging problem in this patient population because it exists in the context of terminal illness with its host of unique psychosocial factors. Accurate assessment is the cornerstone of effective, specific treatment. Treatment guidelines have been promulgated by the World Health Organization in the form of a three-step analgesic ladder. This simple, logical, step-wise approach to pain management is effective in the vast majority of terminally ill patients. More sophisticated techniques allow for pain control in nearly all remaining patients.

An exhaustive review of pain management techniques is beyond the scope of this article. Approaches, which we have found useful, or potentially useful, at Community Hospice of Northeast Florida, will be addressed.

Assessment

Accurate assessment and frequent reassessment are the cornerstones of effective treatment in the terminally ill patient. Assessment should include a thorough history, including pain history and psychosocial history; physical examination, including neurological examination; and review of radiographic studies.

If the pain is physical, what is the likely cause? Likely possibilities include:

1. Tumor effect, including disease progression, metastases, paraneoplastic syndromes.
2. Treatment side-effects, e.g. chemotherapy-induced mucositis or neuropathy, radiation-induced plexopathy, opioid-induced obstipation.
3. Diagnostic procedures, e.g. post-lumbar puncture headache.
4. Pain unrelated to terminal illness. These patients still get pain from tension headaches, arthritis, and angina.

What is the pain mechanism? This has important treatment implications.

1. Nociceptive. Pain arising from nociceptors which are located throughout the body and are responsive to chemical, thermal, and mechanical stimuli.
   1. Somatic. Due to activation of nociceptors in deep or cutaneous tissue. It is typically opioid responsive and amenable to neural interruption.
   2. Visceral. Due to activation of nociceptors or sympathetic afferent fibers. May be exquisitely responsive to plexus block.
2. Neuropathic. Aberrant somatosensory processing caused by injury to central or peripheral neural tissue. Often responsive to tricyclic antidepressants (TCAs), anti-convulsants, local anesthetics, and NMDA receptor antagonists. May be responsive to high dose opioids.
   

What is the pain pattern?

1. Constant or near-constant. Best treated with a long-acting or around-the-clock analgesics.
2. Intermittent. May be amenable to intermittent dosing of rapid-acting, short- to intermediate duration analgesic. With this pain pattern, around-the-clock dosing may cause unacceptable side effects, including sedation during pain-free periods, and inadequate analgesia during painful episodes.
3. Breakthrough.
4. Incident. Related to specific activities. Responsive to analgesics administered prior to anticipated painful events.
5. End-of-dose failure. Pain predictably occurs before the next scheduled analgesic dose. Treated by increasing the dose of regularly scheduled analgesic or decreasing the interval between doses.
   

If pain is not physical, what are its origins? Non-biological factors should be investigated during the initial assessment. Treatment failure or responses that don't quite make sense should prompt careful reevaluation. Pain is a multidimensional phenomenon, composed of not only nociceptive and neuropathic components, but psychological, spiritual, and existential determinants as well. Morphine is not effective for the cataclysmic social disruption of terminal illness. No nerve block will lessen the anguish caused by rapid physical decline and impending death. Exploring the psychosocial aspects of pain is time consuming and emotionally demanding for the physician. It is easy to implicitly discourage patients from raising these issues. We may subtly encourage them to somaticize their complaints. By quickly rounding with one hand on the doorknob, querying for specific locations, precise qualities, and severity on a one-to-ten scale, may encourage patients to relate their pain in terms they sense we want to hear. The interdisciplinary hospice team, composed not only of physicians and nurses, but social workers, pastoral care workers, and psychologists, focuses on recognizing and addressing these non-biologic aspects of pain.

Treatment

In 1990 the World Health Organization formulated a three-step analgesic ladder as a guide to improving the treatment of cancer pain. ¹ It has proven to be useful and is applicable to other pain problems in the hospice setting. Principles include:

1. Administering medications by the clock, rather than on an as-needed basis. The logic is to maintain reasonably constant blood levels. Provision should also be made to provide analgesics for breakthrough pain.
2. Administering medications by mouth. The oral route is simple, convenient, cost-effective, commensurate with patient independence and control, and allows for rapid titration.
3. Administering medications by the analgesic ladder as follows:

Step 1 (for mild to moderate pain)

Treatment begins with a non-steroidal anti-inflammatory drug (NSAID), with an adjuvant if needed (see below). NSAIDs, which work by inhibiting the enzyme cyclooxygenase, reduce production of pain sensitizing prostaglandins and leukotrienes. ² They can be extraordinarily effective as sole agents, particularly if pain is due to an inflammatory lesion or an osseous source. If efficacy is unsatisfactory after several days at maximal recommended dosages, it is worth trialing agents from other NSAID classes. Non-acetylated salicylates, e.g. choline magnesium salicylate, are frequently used in the hospice setting. They have little effect on platelet aggregation and may be less toxic to gastric mucosa. ³

Common adjuvants include the tricyclic antidepressants (e.g. amitriptyline, nortriptyline, desipramine), which act centrally, activating descending inhibitory neural pathways; anti-convulsants (e.g. gabapentin, phenytoin, clonazepam), working by as-yet unknown mechanisms; and anti-arrythmics (e.g. lidocaine, mexiletene), which apparently stabilize damaged neural cell membranes by interfering with inward sodium current, thereby blocking the action potential.

Step 2 (for moderate or continued pain)

Treatment continues with an NSAID with or without an adjuvant, and a weak opioid is added. The NSAID and adjuvant, working by different mechanisms than the opioid, continue to be useful. They may provide additive or synergistic analgesia and may be opioid-sparing, thereby reducing opioid side effects and delaying tolerance. Note that the use of fixed dose NSAID/opioid combination drugs may be limited by the potential for NSAID toxicity.

Step 3 (severe or continued pain)

A strong opioid is substituted for a weak one, while treatment continues with an NSAID and adjuvant. Opioids, in contradistinction to NSAIDs, exhibit no ceiling effect, i.e. dose beyond which no further analgesia is obtained. The proper dose is whatever dose is necessary to produce analgesia without producing unacceptable side effects. Lack of efficacy or unacceptable side effects with a given opioid should prompt substitution of another opioid. One caveat is that meperidine has no place in the long-term management of pain in this setting. It has a short duration of action and has a metabolite - normeperidine - with the potential to produce serious CNS toxicity. ⁴ Opioid addiction, defined as the compulsive use of the medication, resulting in physical, psychological, or social harm to the user and continued use despite that harm is rarely seen in this setting and prescribing should not be influenced by an unfounded fear of creating addiction.

Beyond the analgesic ladder

Other pharmaceuticals. A variety of other classes of medications may prove to be useful in specific circumstances. Examples include:

1. Corticosteroids. May provide symptomatic relief from metastases to brain and other neural structures.
2. Psychostimulants, e.g. dextroamphetamine, methylphenidate, may decrease opioid-induced sedation, potentiate opioid analgesia, and ameliorate depressive symptoms.
3. Bisphosphonates may decrease the pain associated with osteoclastic metastases.
4. Radiopharmaceuticals, e.g. Sr-89 can be helpful in the management of painful osteoblastic lesions.

Other routes of administration

Subcutaneous (SC) and intravenous (IV). Indications include inability to tolerate the oral route (e.g. persistent nausea and vomiting, dysphagia, aspiration risk), impractical quantity of oral tablets, and unstable and severe pain situation. The SC route is favored in the hospice setting when a permanent IV access device is not in place. It can take the form of continuous subcutaneous infusion (CSCI) and patient-controlled subcutaneous analgesia (PCSA). A 25-27 gauge butterfly needle, placed SC, is comfortable, durable, and easily placed. Analgesia is generally comparable to that afforded by the IV route.

Rectal. Slightly more invasive and less convenient than the oral route, the rectal route can be quite effective. First pass metabolism may be reduced because the inferior and middle rectal veins drain into the systemic circulation, bypassing the hepatic circulation and, hence, first-pass metabolism. Many analgesics, including controlled- and immediate-release opioids and NSAIDs are well absorbed. Limitations include diarrhea, anorectal lesions, low white cell or platelet counts.

Transdermal. Available only for fentanyl, this system provides plasma levels comparable to continuous IV infusion with the convenience of every three-day dosing. ⁵ The patch is relatively expensive. Furthermore, there is considerable delay in reaching steady-state blood levels and slowly declining blood levels when the patch is removed ⁶, making it less useful when rapid titration or frequent dosage changes are necessary.

Neuraxial. Perhaps the most important advance in the management of intractable pain in recent years has been intraspinal (intrathecal and epidural) pharmacotherapy. Indications include generalized or multifocal pain states, failure of pharmacotherapy by less invasive routes, or inability to tolerate other routes due to side effects. Efficacy of intraspinal opioid therapy for various pain etiologies, in descending order is continuous somatic; continuous visceral; intermittent somatic; intermittent visceral; neuropathic; cutaneous and fistulas. ⁷ A variety of medications have been used with success, including opioids, local anesthetics, NMDA antagonists, alpha-2 agonists, and others. ⁸ The great advantages of intraspinal pharmacotherapy over neurodestructive procedures include its titratability, reversibility, and applicability to widely disseminated lesions of both nociceptive and neuropathic etiologies.

Neuroablative procedures. Although sometimes useful as a component of a multimodal therapeutic approach, nerve blocks are not a panacea. While some pain states are quite amenable to block, e.g. celiac plexus block for pancreatic cancer and other upper abdominal pain states, they have largely been supplanted by neuraxial analgesia. Limitations include CNS plasticity, with axonal regrowth and deafferentation pain; unmasking other pain states which must be treated; tumor progression or metastases which may require further blocks; impermanence; and collateral damage to nontargeted tissue (e.g. motor nerves). These blocks often require at least one diagnostic (local anesthetic) session followed by one or more ablative (alcohol or phenol) session. The logistics of this series of procedures can be impractical in the hospice setting. Specific block indications include multiple medication intolerances; preference to avoid opioids for social, cultural, religious reasons; inability of patient or family to handle dosing schedule for analgesic medications; well-localized or specific pain syndromes.

Neurosurgical approaches. Expert use of pharmacotherapies and mainstream use of neuraxial therapies have made the need for palliative neurosurgery a rare event. They are expensive, logistically difficult, and dependent on the availability of a neurosurgeon with the interest, time, and expertise in these palliative techniques.

Potentially useful procedures include:

Percutaneous cordotomy. Interruption of anterolateral spinothalamic tract produces contralateral loss of pain and temperature sensation. The percutaneous approach offers obvious advantages in the hospice patient population. Indications include severe, unilateral pain in the torso or lower extremity. Published results indicate significant analgesia in 90% of patients immediately following the procedure and 50% at one year. The procedure can be repeated if necessary. Complications include paresis, ataxia, bladder dysfunction, mirror-image pain, de-afferentation pain (delayed). ⁹

Midline C1-2 myelotomy. CT-guided radiofrequency lesioning of the central cord. Indications include bilateral upper or lower extremity or pelvic pain. Relief is often incomplete and transient. ¹⁰

Intraventricular opioid infusion. Indications include craniofacial pain, upper-body pain, including brachial plexopathy. ¹¹

Pituitary ablation (chemical) for refractory, diffuse cancer pain, especially from osseous metastatic disease and in hormonally sensitive tumors.

Factors determining choice of technique also include pain site, pain mechanism, patient functional status, life expectancy, and availability of community resources (e.g. anesthesia, neurosurgery).

Summary

Nearly all pain can be relieved with the expert use of common medications administered by non-invasive routes. Careful assessment and frequent reassessment are the keys to effective, targeted treatments. Addiction is extraordinarily rare in this setting and fears of creating addiction should not be a concern in prescribing opioids in doses sufficient to control pain. Medications should be used to their full potential: those with an analgesic ceiling (e.g. NSAIDS, many adjuvants) should be titrated upward until analgesia is obtained, maximum recommended dosage has been reached, or side effects supervene. Those without an analgesic ceiling, particularly opioids, should be titrated upward until analgesia is obtained or intolerable side effects appear. Finally, pain is a multidimensional symptom. Successful treatment depends on identifying and addressing specific psychosocial concerns that contribute to the individual's overall suffering.

References

1. Jacox A, Carr DB, Payne R et al. Management of Cancer Pain. Clinical Practice no. 9, AHCPR Publication no. 94-0592. Rockville MD: U.S. Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research, 1994b; pp 41-45.

2. Portenoy RK, Kanner RM, Nonopioid and adjuvant analgesics. In: Portenoy RK, Kanner RM (eds). Pain Management: Theory and Practice. Philadelphia: FA Davis Co., 1996, p 220.
3. Mohamed SA, Mohamed K, Borsook D. Choosing a pharmacotherapeutic approach: nonopioid and adjuvant analgesics. In: Borsook D, LeBel AA, McPeek B (eds). The Massachusetts General Hospital Handbook of Pain Management. Boston: Little, Brown and Co., 1996, p 80.
4. Kaiko RF, Foley KM, Grabinsky P et al: Central nervous system excitatory Effects of meperidine in cancer patients. Ann Neurol 1983; 13:180.
5. Nimmo WS, Duthie DJR. Plasma fentanyl concentrations after transdermal or IV infusion of fentanyl (abstract). Anesthesiology 1986; 65: 559.
6. Physicians Desk Reference (54^th ed.) Medical Economics Co., Inc. Oradell, NJ, 2000.
7. Arner S, Arner B. Differential effects of epidural morphine in the treatment of cancer related pain. Acta Anaesthesiologica Scandanavica 1985; 29:32.
8. Buchheit T, Rauck R. Subarachnoid techniques for cancer pain therapy: when, why, and how? Curr Rev Pain 1999; 3(3): 198-205.
9. Arbit E. Neurosurgical considerations and options for cancer-related pain. In: Payne R, Patt RB, Stratton Hill C (eds.). Assessment and Treatment of Cancer Pain. Progress in Pain Research and Management, v 12. Seattle: IASP Press, 1998, pp216-217.
10. Ibid. p 217.
11. Ibid. p 219.

Jacksonville Medicine / May, 2001

What's New · Northeast Florida Medicine Journal · Know Your Physician · Legal & Legislative
· DCMS Alliance · Academy of Medicine · Member Websites · Community Health
About the DCMS · Meetings Calendar · Member Benefits · Employment Connection · Home

Duval County Medical Society   ·   555 Bishopgate Lane  ·   Jacksonville, FL  32204
Phone: (904) 355-6561   ·     FAX:  (904) 353-5848   
General Email: dcms@dcmsonline.org    ·   Webmaster's Email: mdoran@dcmsonline.org
Privacy Policy and Disclaimers