Palliative and End-of-Life Care

Educational Objectives

The goal of this program is to improve the care of patients with terminal illnesses. After hearing and assimilating this pro­gram, the participant will be better able to:

1.   Describe advanced care planning options and discuss them with patients and families.

2.   Evaluate patients’ desire for prognostic information and select the optimal timing and approach for discussion of palliative care with patients.

3.   Choose management strategies for anorexia in patients with terminal illnesses.

4.    Summarize the benefits of hospice care.

5.   Describe symptoms suffered by patients at the end of life and prescribe appropriate medical therapies for their treatment.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the plan­ning committee to disclose relevant financial relationships within the past 12 months that might create any personal con­flicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, Drs. Hagman and MacMillan and the planning committee reported nothing to disclose. In their lectures, Drs. Hagman and MacMillan present information that is related to off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Hagman spoke at the 2008 American College of Physicians (Washington Chapter) Scientific Meeting, held November 6–8, 2008, in Seattle, WA, and presented by the American College of Physicians, Internal Medicine. Dr. MacMillan’s lec­ture was recorded at Clinical Pharmacotherapy 2009: Practical Information for Physicians, Nurses, and Pharmacists, held April 17-19, 2009, in Napa, CA, and sponsored by UC Davis Health System, Office of Continuing Medical Education and Department of Pharmacy. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

Making Decisions About Palliative Care

Melissa (Moe) Hagman, MD, Assistant Professor of Medicine, Division of General Internal Medicine, and As­sociate Program Director, Internal Medicine, University of Washington School of Medicine, Seattle, WA

Approach to discussion: study of interaction between hope and desire for prognostic information among 55 patients with terminal disease; 4 patterns  —  feelings swing between totally hopeful and completely discouraged (amount of information desired depended on stage); scales and balance (hopeful but realistic; wanted information but not too much); yin-yang (hope and bad news coexisted); redirected hope (from hope for cure to other things, eg, survive to certain date); ask all patients how much information they want

Advance directive: Five Wishes form  —  includes designation of durable power of attorney (DPOA) for health care, type of medical treatment desired, degree of comfort desired, desired treatment, and level of information shared with loved ones; does not direct paramedics about wishes regarding code; Physician Orders for Life-Sustaining Treatment Paradigm (POLST) form  —  provides instructions for resuscitation, types of medical interventions, use of antibiotics and artificial nutrition and hydration; does not designate DPOA; living will registry  —  available in Washington; patient sends copy of documents to central database and receives card to carry in wallet

Discussing palliative care with patients: timing  —  at time of diagnosis of life-limiting disease; if physician expects patient’s death in next 6 to 12 mo; if patient has frequent hospital admissions; if chronic disease progresses; or if patient with chronic untreatable disease presents with life-threatening event that could allow natural death; set safe context for discussion  —  open with questions about patient’s goals for their experience; questions  —  identify stake­holders; ask about patient’s understanding of situation, sources of strength, hopes, fears, and past experiences with serious illness; keys to successful discussion  —allowing patient and family time to speak increases patient satisfac­tion and helps reduce anxiety, posttraumatic stress disorder (PTSD), and depression among family members

Hospice eligibility for patients with dementia: criteria include total dependency for activities of daily living (ADLs); lack of meaningful verbal communication (6 or fewer words); hospitalization for pneumonia, pyelonephri­tis, sepsis, or other serious complication in previous 6 mo; stage 3 or 4 pressure ulcers; or loss of ³10% of body weight in previous 6 mo; patient must have any 3

Benefits of hospice: nurse on-call 24 hr/day; skilled hospice certified nursing assistant (CNA); spiritual support; comprehensive emotional and grief support, with special programs for children; hospice volunteers

Anorexia: obtain history and laboratory or radiographic data (if appropriate), and perform physical examination to seek cause; if possible, treat underlying cause (eg, reflux, constipation); appetite stimulants  —  options include al­cohol, steroids, megestrol, delta-9-tetrahydrocannabinol, and androgens; do not increase lean body mass or lon­gevity; may provide patients with enjoyment of eating

Artificial hydration and nutrition (AHN): ask about patient’s goals; during nutritional deficiency, central nervous system endorphins may cause mild euphoria; intravenous (IV) fluids do not relieve dry mouth; percutaneous en­doscopic gastrostomy (PEG) tubes and total parenteral nutrition (TPN) do not prolong life and may increase suf­fering (eg, dyspnea from pulmonary edema or ascites, pneumonia from aspiration, discomfort from tube or IV, possible need for restraints in patients with dementia, loose stools); appropriate for patients with malignancies of head and neck or upper gastrointestinal tract who are having definitive surgery or receiving radiation or chemo­therapy, selected ambulatory patients (eg, patients with HIV), and patients with amyotrophic lateral sclerosis (ALS); for patients with dementia, tube feeding does not prolong survival, prevent aspiration, improve pressure ulcers, improve function, or give comfort

Study results: not randomized; median survival of 59 days among 23 patients who received PEG and 60 days among 18 patients who did not

Family concerns: encourage alternative activities to show care for patient; in case of conflicting wishes, perform therapeutic trial of feeding tube for specific time (eg, 3 days), reassess, and continue only if pre-agreed goals met

Letter of condolence: difficult but appreciated by family

Questions and answers: why does POLST form have full resuscitation option? allows patient to specify wishes for other measures, eg, AHN; also, documentation of wish for resuscitation on POLST form indicates that patient has discussed their wishes for this option; can duration of hospice exceed 6 mo? yes; most groups follow Medicare guidelines, which require that attending physician expects patient’s death within 6 mo; patient’s condition re-evalu­ated at 90 days after admission and every 60 days thereafter; patient may remain in hospice as long as expectation of death within 6 mo remains after these evaluations; some insurance companies pay only for specific period, but many hospices provide charity care afterwards; do gastroenterologists believe that PEG tubes prevent aspiration? literature does not support conclusion that PEG tubes that end in stomach prevent aspiration; tubes that terminate in jejunum may prevent aspiration

Symptom Management in Palliative Medicine

John MacMillan, MD, Associate Professor of Internal Medicine, and Director of Hospitalist Service, Division of Pulmonary and Critical Care Medicine, University of California, Davis Health System

Introduction: at end of life, concern that symptoms reducing quality of life; diagnosis aided by asking whether symptoms related to illness or to treatment, eg, drug side effects; polypharmacy common in elderly; review medica­tion list and stop unnecessary or inappropriate drugs; this often results in improvement of symptoms; minimize pharmacologic interventions

Nausea and vomiting (NV): consider possible causes

Opioids: act on chemotactic trigger zone (rich in dopaminergic receptors) and on vestibular system (may manifest after changing position); data unclear whether NV side effects similar for all opioids; patients eventually become tolerant; constipation only side effect of opioids for which no tolerance develops; if NV mild, continue drug until tolerance develops; if NV severe, rotate to other opioids; antiemetics  —  speaker prefers haloperidol, scopolamine (anticholinergic) or promethazine (Phenergan); antihistamine diphenhydramine (Benadryl) also works well; 5HT3 antagonists (eg, ondansetron) not generally helpful for managing opioid-mediated NV; haloperidol most potent antidopaminergic, followed by prochlorperazine; promethazine has minimal antidopaminergic properties; metoclopramide (Reglan) binds few receptors relevant to NV and useful only for problems with motility and dis­tention

Bowel obstruction: most often associated with pelvic cancer, especially ovarian and colon; symptoms include NV and cramping abdominal pain; treatments surgical, interventional, and medical; usually possible to avoid IV and nasogastric tube

Surgical treatment: includes venting gastrostomy tubes for small bowel obstructions but not for colonic obstruc­tions

Drug therapy: cocktail of opioids, anticholinergic agent, and somatostatin (octreotide); opioids  —  help relieve pain; evidence suggests they do not increase risk for paralytic ileus; dopamine antagonist  —  eg, haloperidol; much lower dose (ie, 0.5 to 2 mg every 4-6 hr) of haloperidol required than for psychosis (³5 to 10 mg); anticholinergics  —  relieve cramps and pain due to spasms; agents include glycopyrrolate or scopolamine; glyco­pyrrolate administered IV or PO) and does not cross blood-brain barrier or cause changes in mental status; sco­polamine administered by patch and crosses blood-brain barrier; consider prokinetic drugs for partial small bowel obstruction and discontinue if pain increases; octreotide  —  inhibits splanchnic blood flow and decreases secretions from intestinal mucosa to diminish distention; administered IV or subcutaneously; effective dose usu­ally <400 mg/day

Cough: highly debilitating; 40% of patients suffer from cough at end of life; drugs associated with cough include an­giotensin-converting enzyme (ACE) inhibitors, nonsteroidal anti-inflammatory agents (NSAIDs), and propel­lants in inhaled medications

Treatment: American College of Chest Physicians (ACCP) recommends against use of prescription and over-the-counter cough syrups; sweet syrups (eg, honey) possibly effective for relief of cough; opioids  —  first-line therapy for cough in patients with cancer; all opioids have similar effect; for patients already taking an opioid, study sug­gested low dose of oxycodone effective; expectorants  — consider for wet cough; guaifenesin or inhaled acetyl­cysteine; avoid in patients with reactive airway disease because of bronchospasm; consider nebulized 3% to 10% hypertonic saline instead; use caution in patients with impaired cough reflex because of risk for aspiration; benzonate  —  local anesthetic; second-line in addition to opioids; anticholinergics  —  play role if upper airway se­cretions contribute to cough (eg, scopolamine and glycopyrrolate); inhaled lidocaine  —  (used off-label) or bupi­vacaine block upper airway stretch receptors; patients must not eat or drink for 1 hr after inhalation as precaution against aspiration

Constipation: experienced by 90% of patients in advanced phases of illness; mostly due to opioids; prevention criti­cal, and all patients on opioids need bowel regimen; constipation can cause fecal impaction and diarrhea; digital rectal examination and history important; preventive regimen includes stool softener, eg, docusate (Colace), and stimulant laxative, eg, senna or bisacodyl (Dulcolax); add osmotic laxative if necessary

Induced by opioids: tolerance rarely develops; not centrally mediated, limited to gut; previously used oral naloxone (opioid antagonist with poor bioavailability); however high doses needed cause opioid withdrawal and reversal of analgesia; methylnaltrexone  —  mu receptor antagonist that works only in gut; given as subcutaneous injection; lower dose works better; in studies, »60% of patients have bowel movement (BM) within 4 hr and 70% within first 24 hr; in clinical use, »54% have BM; no tolerance observed; average dose 8 mg (based on weight); comes in prefilled syringe; side effects include abdominal cramping, gas, and diarrhea

Metastatic bone pain: almost 500,000 new patients per year; often associated with cancers of lung, breast, and pros­tate and multiple myeloma; goals of treatment include control of pain and prevention of fractures

Medical therapy: consider calcitonin because of low risk, although often not efficacious, and effect short-lived when present; opioids  —  effective only »50% of time; NSAIDs  —  treat inflammation in bone; avoid indometha­cin in elderly patients because of associated CNS toxicity and mental status changes; ibuprofen (eg, Motrin) at anti-inflammatory doses (ie, 600 to 800 mg/day); corticosteroids  —  mechanism similar to that of NSAIDs; dose not standardized; prednisone and dexamethasone (eg, Decadron) most commonly prescribed; dexamethasone used at 16 to 32 mg/day for bone pain; start at 2 to 4 mg twice daily because of dose-limiting toxicity; discon­tinue if not effective after 7 days at 16 to 24 mg; prednisone used at 30 to 40 mg/day; dexamethasone has lower mineralocorticoid activity than prednisone; bisphosphonates  —  (eg, zoledronic acid and pamidronate) decrease bone pain; most effective in breast and prostate cancer; inhibit bone resorption by osteoclasts; reduce number of fractures and skeletal events by 30%; reduce pain by 30% to 40% in 30% to 50% of patients; effects last 3 to 4 wk; if first infusion not effective, try second infusion, but if still ineffective, discontinue for pain (may continue for fractures)

Radiation therapy: effects on pain seen in 2 days to 2 weeks; limited by number of areas affected by metastasis

Radiopharmaceuticals: best evidence for efficacy in breast and prostate cancer; helpful with multiple foci of metas­tasis; improve pain in »30% of patients; patient must have >12 wk of life remaining; analgesia occurs as soon as 3 days, usually 2 wk; worsened pain (flare) within first week because of inflammatory effect (actually good prog­nostic sign); myelosuppression can occur (cancer patients who already have myelosuppression from tumor not candidates)

Neuropathic bone pain: component of bone pain; early data show benefit of gabapentin (Neurontin) or pregabalin

Psychiatric symptoms: depression not part of dying but manageable symptom; antidepressants can help achieve bet­ter pain control; anxious depression often misdiagnosed as anxiety disorder; methylphenidate  —  fastest acting anti­depressant; appropriate for patients with life expectancy of weeks; response observed within 1 or 2 doses; well tolerated in geriatric population; begin dose at 2 to 5 mg once daily and add 2.5 mg if no effect; ultimately may need only 5 mg twice daily; duloxetine (Cymbalta) and venlafaxine (Effexor) appropriate for patients with depres­sion and neuropathic pain; fluoxetine and venlafaxine appropriate to activate patients with psychomotor retarda­tion; mirtazapine (Remeron) useful for depression with insomnia; also stimulates appetite in patients without severe depression when given at 7.5 mg at night; citalopram, escitalopram, and paroxetine helpful for depression with anxiety

Suggested Reading

Abernethy AP et al: Detailing of gastrointestinal symptoms in cancer patients with advanced disease: new methodologies, new in­sights, and a proposed approach. Curr Opin Support Palliat Care 3:41, 2009; Al-Khafaji A, Min Cho S: Making palliative care more “palatable.” Crit Care Med 37:2492, 2009; Biermann JS et al: Metastatic bone disease: diagnosis, evaluation, and treatment. J Bone Joint Surg Am 91:1503, 2009; Dalal S et al: Is there a role for hydration at the end of life? Curr Opin Support Palliat Care 3:72, 2009; Desandre PL, Quest TE: Management of cancer-related pain. Emerg Med Clin North Am 27:179, 2009; Di Giulio P et al: Dying with advanced dementia in long-term care geriatric institutions: a retrospective study. J Palliat Med 11:1023, 2008; Guay DR: Methylnaltrexone methobromide: the first peripherally active, centrally inactive opioid receptor-antagonist. Consult Pharm 24:210, 2009; Innes S, Payne S: Advanced cancer patients’ prognostic information preferences: a review. Palliat Med 23:29, 2009; Jacobsen J, Jackson VA: A communication approach for oncologists: understanding patient coping and communicating about bad news, palliative care, and hospice. J Natl Compr Canc Netw 7:475, 2009; Kierner KA et al: Attitudes of patients with malignancies towards completion of advance directives. Support Care Cancer May 31, 2009 [Epub ahead of print]; Messinger-Rappaport BJ et al: Advance care planning: Beyond the living will. Cleve Clin J Med 76:276, 2009; Monturo C: The artificial nutrition debate: still an issue … after all these years. Nutr Clin Pract 24:206, 2009; Phelps AC et al: Religious coping and use of intensive life-prolong­ing care near death in patients with advanced cancer. JAMA 18:301, 2009; Price A, Hotopf M: The treatment of depression in pa­tients with advanced cancer undergoing palliative care. Curr Opin Support Palliat Care 3:61, 2009; Rondeau DF, Schmidt TA: Treating cancer patients who are near the end of life in the emergency department. Emerg Med Clin North Am 29:341, 2009; Sanft TB, Von Roenn JH: Palliative care across the continuum of cancer care. J Natl Compr Canc Netw 7:481, 2009; Wee B: Chronic cough. Curr Opin Support Palliat Care 2:105, 2008; Wright AA et al: Associations between end-of-life discussions, patient mental health, medical care near death, and caregiver bereavement adjustment. JAMA 300:1665, 2008; Zaider T, Kissane D: The assess­ment and management of family distress during palliative care. Curr Opin Support Palliat Care 3:67, 2009.