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  1. 1. CHAPTER 19 PALLIATIVE MEDICINE Leslye C. Pennypacker, M.D. GENERAL ISSUES1. What is palliative medicine? A multidisciplinary medical specialty focused on pain relief and other symptoms in patients with serious and/or life-limiting illnesses. In contrast to the traditional disease model of medical care that emphasizes cure, the goals of palliative care include: & Pain and symptom management & Establishment of care goals (advance planning) based on patient and family preferences & Functional optimization & Psychological and spiritual support to patient and family & Care coordination and delivery in a setting appropriate to the patient’s needs2. What is hospice care? A subset of palliative care that provides multidisciplinary, noncurative care to patients with a life expectancy of 6 months or less. Most hospice patients decline all aggressive interventions that are not directed toward pain and symptom management. Hospice care is frequently the final phase of palliative care (Fig. 19-1). Life-prolonging therapy Diagnosis of serious Medicare Death illness hospice Palliative care benefit Figure 19-1. Continuum of curative, palliative, and hospice care. (National Consensus Project for Quality Palliative Care: Clinical Practice Guidelines for Quality Palliative Care, 2nd ed. Pittsburgh, National Consensus Project for Quality Palliative Care, 2009.)3. Which patients should be considered for palliative care? All patients with serious and life-limiting illness. Palliative care may be provided anytime during a person’s illness, even from the time of diagnosis.4. Which patients should be considered for hospice care? Patients with a serious illness who have a life expectancy of 6 months or less.5. Where do most patients receive end-of-life care? Why? Over 80% of patients in the United States die in either an acute care or a nursing home setting. Unfortunately, many patients do not receive adequate supportive care and symptom management at the end of life because health professionals and facilities do not always encourage a transition of care from curative to comfort-oriented goals in these specific care settings. 585
  2. 2. 586 CHAPTER 19 PALLIATIVE MEDICINE 6. If a patient on hospice improves, do they leave hospice care and return to palliative or curative care? Yes. Patients can “graduate” from hospice care if their illness improves unexpectedly. Also, some patients may opt to discontinue hospice care if a new or promising treatment becomes available, but they can re-enroll if they subsequently decline. 7. What percentage of patients in the United States access hospice/palliative care at the end of life? Approximately 15%, with an average duration of hospice care of 3 weeks. 8. Who pays for end-of-life care in the United States? Medicare and Medicaid programs. In addition, some third-party and health maintenance organization (HMO) insurance carriers also provide coverage but programs and covered benefits may vary. In general, veterans in the United States can receive coverage for end-of-life care via their basic benefits program if they are enrolled in the Veterans Administration (VA) Health Care System. KEY POINTS: END OF LIFE CARE 1. Physicians should begin discussions of end-of-life preferences early in the course of a terminal illness. 2. Medicare now provides coverage for end-of-life discussions between physicians and patients during the annual physical exam beginning in 2011. This discussion can include designation of surrogate decision makers and expressed wishes for end-of-life care. (See also Chapter 1, Medical Ethics.) 3. Patients approaching the end of life should participate in most of the decisions regarding their care, either through previous directives or continued active participation. 9. Who is eligible for the Hospice Medicare Benefit? Patients with Medicare Part A (hospital insurance) and a diagnosis of a terminal illness with a probable life expectancy of 6 months or less. The patient’s doctor and the hospice medical director must certify the limited life expectancy. 10. What does the Hospice Medicare Benefit cover? & Physician services & Nursing care & Medical equipment (e.g., wheelchairs, walkers, and hospital beds) & Medical supplies (e.g., bandages and catheters) & Medications for symptom control and pain relief & Short-term care in the hospital, including respite care & Home health aide and homemaker services & Physical and occupational therapy & Speech therapy & Social worker services & Dietary counseling & Family grief counseling
  3. 3. CHAPTER 19 PALLIATIVE MEDICINE 58711. When can nursing home patients receive hospice/palliative care? When they develop a serious or life-limiting illness and choose to focus on symptom relief instead of cure. Hospice eligibility depends on the goals of care, not the site of care. Hospice/ palliative care can be provided in the nursing home and home setting in addition to some other residential care facilities.12. Can patients on hospice receive treatment in the hospital for an acute illness? Yes, but the patient may need to withdraw from hospice care during the hospitalization period. If appropriate, hospice services can be resumed at the time of discharge.13. Can hospice patients request cardiopulmonary resuscitation? Yes. Hospice programs cannot require that the patient or family request no resuscitation in order to receive services, but the majority of hospice patients do not want aggressive interventions of likely low benefit. Once enrolled in hospice, many patients who initially requested resuscitation later ask for no resuscitation. They are assured that pain relief and symptom management will continue.14. What percentage of hospice patients die at home in the United States? Approximately 66–75%. In-home death, though, requires the availability of family and caregivers who agree to support the patient during the dying process.15. What is the most common fear that prevents patients from accepting hospice care? Inadequate pain management. Many patients fear that if they accept hospice care, then they will be “giving up and accepting death” and that they may not receive adequate pain and symptom management. Ironically, patients cared for by hospice programs generally report improved pain and symptom management, and many recent studies have shown that survival after admission to hospice programs may be longer than in those cared for in the standard models of care. SYMPTOM MANAGEMENT PAIN :16. Do most patients experience pain at the end of life? Yes, in nearly 85% of cancer patients and 67% of noncancer patients.17. How can the physician assess the severity of a patient’s pain? Several pain scales are available to help quantitative assessment of pain (Fig. 19-2).18. What medications are commonly used for severe pain in hospice/palliative care patients? Opioid analgesics. Dosing should be tailored to the individual patient at the initiation of treatment and throughout the course of therapy. There are no absolute limitations on initial or maintenance doses because tolerance, metabolism, and response to treatment can vary widely between patients and within a given patient over time.19. What opioids are useful for treatment of mild-to-moderate pain? See Table 19-1.20. What opioids are useful for treatment for moderate-to-severe pain? See Table 19-2.
  4. 4. 588 CHAPTER 19 PALLIATIVE MEDICINE Simple Descriptive Pain Intensity Scale* No Mild Moderate Severe Very Worst pain pain pain pain severe possible pain pain 0–10 Numeric Pain Intensity Scale* 0 1 2 3 4 5 6 7 8 9 10 No Moderate Worst pain pain possible pain Visual Analog Scale (VAS)† No Pain as bad pain as it could possibly be * If used as a graphic rating scale, a line 10 cm long is recommended. † A line 10 cm long is recommended for VAS scales. Figure 19-2. Pain scales. (From Agency for Health Care Policy and Research: Management of Cancer Pain: Adults. Rockville, MD: U.S. Department of Health and Human Services, Public Health Services, 1994.) TABLE 19-1. O P I O I D S F O R M I L D - T O - M O D E R A T E P A I N Peak Duration Equianalgesic Effect of Effect Drug Route Dose (mg)* (hr) (hr) Comments Codeine PO 200 0.5 3–6 Ceiling for analgesia reached at doses > 240 mg/ day PO IV/IM 130 0.5 3–6 Oxycodone PO 20–30 0.5 3–6 No ceiling dose if given without fixed combinations; parenteral formulation not available (continued)
  5. 5. CHAPTER 19 PALLIATIVE MEDICINE 589 TABLE 19-1. OPIOIDS FOR MILD-TO-MODERATE PAIN—(continued) Peak Duration Equianalgesic Effect of Effect Drug Route Dose (mg)* (hr) (hr) Comments Hydrocodone PO 30 0.5 4–6 Only available as fixed combination with acetaminophen or aspirin IM ¼ intramuscular; IV ¼ intravenous; NA ¼ not available; PO ¼ oral. *Approximate potency relative to 10 mg of parenteral morphine. From Grossman SA, Nesbit S: Cancer pain. In Abeloff MA, Armitage JO, Niederhuber JE, et al (eds): Abeloff’s Clinical Oncology, 4th ed. Philadelphia, Churchill Livingstone, 2008.TABLE 19-2. STRONG OPIATES FOR MODERATE-TO-SEVERE CANCER PAIN Equianalgesic Duration ofDrug Route Dose (mg)* Effect (hr) CommentsOxycodone PO 20–30 3–6 No ceiling dose if given without fixed combinations; parenteral formulations not available. PO (SR) 12Morphine PO 30 4–6 Many PO formulations for individual patient needs. PO (SR) 8–12 IV/IM 10 3–5Hydromorphone PO 7.5 3–4 Good choice for SC due to potency. PR (?) Unknown IV/IM 1.5 3–4 (continued)
  6. 6. 590 CHAPTER 19 PALLIATIVE MEDICINE TABLE 19-2. STRONG OPIATES FOR MODERATE-TO-SEVERE CANCER PAIN— (continued) Equianalgesic Duration of Drug Route Dose (mg)* Effect (hr) Comments Meperidine PO 300 3–6 Not preferred due to CNS toxic metabolite that accumulates in renal failure. IV/IM 75 2–3 Levorphanol PO 4.0 6–8 Long T½ (11 hr) necessitates slow dose titration; drug accumulation may occur. IV/IM 2.0 6–8 Fentanyl TD (?) 12 Short T½ (1 hr); TD dose titration difficult with depot in SC adipose tissue; TD fentanyl 25 mg/hr 45 mg/ day PO morphine. IV/IM 0.1 0.5–1.0 Methadone{ PO 10 6–8 Despite long T½ (15– 150 hr), duration of analgesia is not prolonged; however, drug accumulation can result in toxicities Caution is warranted when converting to methadone in patients with high opioid tolerance. Oxymorphone PO 10 7–9 Now available as immediate-release formulations. (continued)
  7. 7. CHAPTER 19 PALLIATIVE MEDICINE 591 TABLE 19-2. STRONG OPIATES FOR MODERATE-TO-SEVERE CANCER PAIN— (continued) Equianalgesic Duration of Drug Route Dose (mg)* Effect (hr) Comments PO (SR) 12 IV 1 7–9 CNS ¼ central nervous system; IM ¼ intramuscular; IV ¼ intravenous; PO ¼ oral; SC ¼ subcutaneous; SR ¼ slow-release formulation; TD ¼ transdermal; (?) ¼ unknown. *Approximate potency relative to 10 mg of parental morphine. { Ripamonti C, Groff L, Brunelli C, et al: Switching from morphine to oral methadone in treating cancer pain: What is the equianalgesic dose ratio? J Clin Oncol 16:3216–3221, 1998; Moryl N, Santiago-Palma J, Kornick C, et al: Pitfalls of opioid rotation: substituting another opioid for methadone in patients with cancer pain. Pain 96:325–328, 2002; Bruera E, Neumann CM: Role of methadone in the management of pain in cancer patients. Oncology 13:1275–1282, 1999; Pereira J, Lawlor P, Vigano E, et al: Equianalgesic dose ratios for opioids: a critical review of proposals for long term dosing. J Pain Symptom Manage 22:672–687, 2001; Bruera E, Sweeny C: Methadone use in cancer patients with pain: a review. J Pall Med 5:127–138, 2002. From Grossman SA, Nesbit S: Cancer pain. In Abeloff MA, Armitage JO, Niederhuber JE, et al (eds): Abeloff’s Clinical Oncology, 4th ed. Philadelphia, Churchill Livingstone, 2008.21. How is methadone used? For continuous pain management. Methadone has a long half-life and can lead to sedation and respiratory depression if not carefully and slowly titrated. For patients with appropriate life expectancy and end-of-life care goals, the electrocardiogram (ECG) may need to be monitored to detect a prolonged QT interval since methadone can lead to torsades de pointes. Methadone may also be helpful for neuropathic pain. Gazelle G, Fine PG: Methadone for the treatment of pain. In Fast Facts and Concepts, ed 2, 2006. Available at: www.eperc.mcw.edu/fastfact/ff_075.htm.22. What are the most common side effects of opioid therapy? Constipation Mild sedation Nausea23. How is sedation due to opioid use managed? Stimulants such as caffeine, methylphenidate, dexmethylphenidate, and dextroamphetamine may be helpful, as are newer stimulants such as modafinil and armodafinil. However, modafinil and armodafinil have been primarily studied in patients with nonmalignant pain.24. Should the concern for respiratory depression preclude the use of opioids in frail patients nearing the end of life? No. Opioids, if dosed carefully and monitored appropriately, should not be withheld in patients nearing the end of life for fear of decreasing respiratory drive. In fact, most palliative care providers agree that opioids are considered the preferred medication for patients with air hunger and dyspnea. Often, patients will have an improvement in effective ventilation if their pain is well controlled.
  8. 8. 592 CHAPTER 19 PALLIATIVE MEDICINE 25. In addition to opioids, what other treatment modalities can be used for pain management at the end of life? Tricyclic antidepressants (TCAs) Anticonvulsants (clonazepam, gabapentin) Topical lidocaine (available as a patch or gel) Biphosphonates (for bone pain) Corticosteroids (for inflammatory related pain) Capsaicin (topical cream made from chili peppers) 26. How are nonsteroidal anti-inflammatory medications (NSAIDs) used for pain? Although effective pain relievers, the numerous side effects and risks of NSAIDs frequently outweigh the benefits of these medications in patients at the end of life with multiple organ dysfunction. The complications of NSAIDs use include dyspepsia, gastric bleeding and ulcers, nephrotoxicity, hepatotoxicty, and excessive bleeding owing to decreased platelet aggregation. For many patients at the end of life, particularly elderly patients, opioids are safer therapies. 27. In addition to pain, what other common symptoms occur at the end of life? See Table 19-3. TABLE 19-3. S Y M P T O M S A T T H E E N D O F L I F E : C A N C E R V E R S U S O T H E R C A U S E S OF DEATH Cause of Death Symptom Cancer (%) Other (%) Pain 84 67 Trouble breathing 47 49 Nausea and vomiting 51 27 Sleeplessness 51 36 Confusion 33 38 Depression 38 36 Loss of appetite 71 38 Constipation 47 32 Bedsores 28 14 Incontinence 37 33 Adapted from Seale C, Cartwright A: The Year Before Death, Aldershot, UK, Avebury, 1994. : SYMPTOM MANAGEMENT GASTROINTESTINAL 28. What are some management strategies for treatment of constipation? Patients receiving chronic opioid therapy should be encouraged to drink plenty of fluids, maintain regular physical activity as appropriate, and develop regular toileting habits. In addition, routine doses of stool softeners, laxatives, or both should be prescribed concurrently with the initiation of opioid therapy. Docusate (100 mg daily) and senna (2–8 tablets at bedtime) are frequently used in combination. Osmotic laxatives (lactulose or polyethylene
  9. 9. CHAPTER 19 PALLIATIVE MEDICINE 593 glycol) can be used both for acute relief of constipation and on a daily basis for patients who do not respond to stool softeners or mild laxatives, but some patients at the end of life may find the sweet taste unpleasant. More recently, subcutaneous methylnaltrexone was approved for treatment of opioid induced constipation and can be used long term. Thomas J, Karver S, Cooney GA, et al: Methylnaltrexone for opioid-induced constipation in advanced illness, N Engl J Med 258:2332–2343, 2008.29. List the most common causes of nausea and vomiting in palliative care patients. Vestibular Obstruction of bowel by constipation DysMotility of upper gastrointestinal tract Infection, Inflammation Toxins stimulating the chemoreceptor trigger zone in the brain (e.g., opioids) These causes can be remembered by the acronym VOMIT. Hallenbeck J: The causes of nausea and vomiting (V.O.M.I.T.). In Fast Facts and Concepts, ed 2, 2005. Available at: www.eperc.mcw.edu/factfact/ff_005.htm.30. What are some nonpharmacologic interventions to consider in patients with nausea and vomiting? Provide a peaceful, quiet environment. Minimize odors, if possible. Only offer requested foods. Offer smaller food portions more frequently. Consider the possibility of constipation as contributing factor to nausea, even in patients with minimal oral intake.31. What medications are helpful for the treatment of nausea and vomiting? For vestibular causes, scopolamine (as a patch) or promethazine may be helpful. Promethazine is also helpful for labyrinthitis seen in inflammation. Metoclopramide is helpful for upper intestinal dysmotility but can cause tardive dyskinesia and worsen depression symptoms. Prochloroperazine is helpful for opioid-induced nausea. Ondansetron is specifically indicated for chemotherapy induced nausea and vomiting but also may be helpful in other settings.32. Are there nonpharmacologic approaches to the treatment of bowel obstruction that should be considered? Yes. Enteral tubes may be used as suction. Procedures such as a decompressing ostomy are also helpful.33. What are the most common causes of diarrhea in palliative care patients? Impaction with resultant diarrhea around the impaction Medication side effects, most commonly antibiotics Malabsorption, particularly if the patient is receiving tube feedings Infection such as Clostridium difficile Bowel or pancreatic malignancy34. How should diarrhea be evaluated? History and physical examination Limited laboratory and microbiologic testing Reviewing medications for possible causes
  10. 10. 594 CHAPTER 19 PALLIATIVE MEDICINE 35. How can diarrhea be treated? Small sips of clear liquids to maintain hydration with parenteral hydration if needed and appropriate with end-of-life care goals. Avoidance of lactose products. Kaolin and pectin preparations for bulk formation, but these may take up to 48 hours to be effective. Loperamide. Aspirin and cholestyramine for radiation-induced enteritis. Pancreatic enzymes if pancreatic insufficiency present. Octreotide for severe secretory diarrhea (as seen in human immunodeficiency virus [HIV] infection). Antibiotic treatment for possible infectious diarrhea. Appropriate measures to prevent pressure ulcers due to diarrhea. Cherny NI: Evaluation and management of treatment-related diarrhea in patients with advanced cancer: A review, J Pain Symptom Manage 36:413–423, 2008. Ippoliti C: Antidiarrheal agents for the management of treatment-related diarrhea in cancer patients, Am J Health Syst Pharm 55:1573–1580, 1998. 36. Should all oral food and fluids be withheld from patients with impaired swallowing at the end of life? No. As a general rule, these patients can still be offered small bites of soft food and sips of fluids that they want for pleasure and taste. When unable to manage even these forms of alimentation, the patient’s mouth and lips can be moistened with topical moistened swabs. 37. What are some of the causes of hiccups in terminally ill patients? Liver disease, gastroesophageal reflux disease (GERD), diaphragmatic irritation, central nervous system (CNS) tumor, and medication side effects (i.e., steroids). 38. What medications are helpful for treatment of hiccups? Although at times nearly intractable, the antipsychotic chlorpromazine is U.S. Food and Drug Administration (FDA)–approved for hiccup treatment. Baclofen and gabapentine have also been found to be effective in trials. ´ ´ Hernandez JL, Pajaron M, Garcıa-Regata O, et al: Gabapentin for intractable hiccup, Am J Med 117:279–281, 2004. Ramirez FC, Graham DY: Treatment of intractable hiccup with baclofen: Results of a double-blind, randomized, controlled, cross-over study, Am J Gastroenterol 87:1789–1791, 1992. SYMPTOM MANAGEMENT DYSPNEA : 39. What are the most common causes of dyspnea at the end of life? Chronic obstructive Pleural effusion Ascites pulmonary disease Pulmonary embolism Pain (COPD) Pneumothorax Anxiety Pneumonia Excessive airway Congestive heart failure secretions (CHF) Anemia 40. Does supplemental oxygen help patients with dyspnea? Sometimes. If the oxygen is delivered by face mask, the patient may feel more short of breath and claustrophobic. Nasal cannulae are usually better tolerated even if lower oxygen flow rates are achieved.
  11. 11. CHAPTER 19 PALLIATIVE MEDICINE 59541. What medications are most helpful in end-of-life patients with dyspnea? Opioids (generally most effective) Diuretics for fluid overload Antibiotics for pneumonia, if consistent with the patient’s end-of-life care requests42. What nonpharmacologic interventions are helpful in relieving dyspnea? Repositioning Fans Gentle postural drainage Therapeutic thoracentesis (with or without pleurodesis) Paracentesis (if ascites prominent)43. What medications can help persistent cough? The best treatment is to treat the underlying disorder causing the cough, if possible. Oxygen, frequent suctioning, and increasing humidity can also help. Coughs due to infections may benefit from antibiotics for symptom relief. Opioids and steroids may also be helpful. Lozenges and over-the- counter preparations such as dextromethorphan can be tried in combination with opioids if necessary. SYMPTOM MANAGEMENT GENERAL :44. How should depression be assessed at the end of life? Because many of the physical symptoms of depression (low energy, sleep disorders, change in appetite or weight, psychomotor retardation) are also seen as part of the terminal illness, the mood symptoms of depression are important for assessment. These symptoms include feelings of hopelessness, guilt, helplessness, and sustained thoughts of suicide. Block SD: Assessing and managing depression in the terminally ill, Ann Intern Med 132:209–217, 2000.45. What medications are used for depression treatment? Selective serotonin reuptake inhibitors (SSRIs): Fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram. May have the best tolerated side effect profile. TCAs: Amitryptyline, imipramine, desipramine, nortriptyline. Serotonin norepinephrine reuptake inhibitor (SNRI): Venlafaxine. Norepinephrine dopamine modulators: Buproprion. Serotonin and norepinephrine uptake inhibitor: Desvenlafaxine. Psychostimulants: Dextroamphetamine, methylphenidate, modafinil, and armodafinil.46. How can pressure ulcers be prevented in palliative care/hospice patients? By use of a pressure-reducing mattress surface and regularly turning the patient (if bed-bound) to avoid prolonged pressure on one area. The skin should be inspected regularly and treatment started for early-stage ulcers or at-risk skin area. WEBSITES 1. American Academy of Hospice and Palliative Medicine: www.aahpm.org 2. Education for Physicians on End-of-life Care (EPEC): www.epec.net 3. End of Life/Palliative Education Resource Center (EPEREC): www.eperc.mcv.eduBIBLIOGRAPHY1. Quill T, Hollway RG, Shah MS, editors: Primer of Palliative Care, ed 5, Glenview, IL, 2010, American Academy of Hospice and Palliative Medicine.2. Walsh D, Caraceni AT, Fainsinger R, et al, editors: Palliative Medicine, Philadelphia, 2008, Saunders.