Geriatric Palliative Care—Part I: Pain and Symptom Management
Mr. HD was an 86-year old man with a history of diabetes, hypertension, congestive heart failure, chronic kidney disease, and moderate dementia. He was admitted to the hospital from a subacute rehabilitation facility with three gangrenous toes on his right foot. Work-up at that time revealed a large arterial thrombus in the internal iliac artery extending to the femoral artery. At the time of hospitalization, the patient was delirious with episodes of lethargy and agitation. Mr. HD was evaluated by a vascular surgeon, who recommended an iliofemoral bypass procedure. As part of the preoperative evaluation, his cardiologist obtained a pharmacologic stress test, which revealed significant ischemia and an ejection fraction of 15%. It was deemed at that time that the patient’s cardiac risk was too high, and surgery was not performed. The nurse noted that Mr. HD moaned at times and held his right leg as if it were in pain. The palliative care service was consulted for management of his pain.
Palliative Care in an Aging Population
Palliative care is the interdisciplinary specialty that focuses on improving quality of life for patients with advanced illness and their families. It is offered simultaneously with all other appropriate medical care, and relieves patient and family suffering by providing expert pain and symptom management, as well as sophisticated communication regarding advance care planning, delivery of bad news, establishing goals of care, and decisions to withhold or withdraw medical treatments.1,2 The aging population, in combination with an increasingly fragmented healthcare system, makes the need for palliative care evident now more than ever. In Part I of this two-part article, the authors address the core palliative care skills of pain and symptom management. In the follow-up article, the authors will address communication skills.
Pain and Other Common Symptoms
Pain and symptom management is an essential proficiency when caring for patients with serious or terminal illnesses. Although being pain-free is a priority for patients living with serious and advanced illness,3 multiple studies in different settings and patient populations demonstrate a high prevalence of pain and other symptoms in the seriously ill.4-6
Pain in the geriatric patient
Pain is a common problem for older adults; its prevalence in the community is estimated to range between 20% and 45%. Pain in the geriatric patient can lead to depression, decreased socialization, insomnia, gait instability, and loss of functional capacity.7
Pain can be classified as nociceptive or neuropathic. Nociceptive pain can be further subdivided into somatic and visceral. Somatic pain results from direct stimulation of pain fibers in the cutaneous and deep tissues, as in arthritis or bone pain from metastatic disease, whereas visceral pain originates in the thoracic and abdominal cavities. Neuropathic pain is derived from direct damage to the central or peripheral nervous system, as exemplified by diabetic neuropathy or spinal stenosis.8
Given the prevalence of cognitive impairment in the geriatric population, proper assessment of pain is essential. The frequency of untreated pain in nursing home residents is as high as 25%.9-11 When assessing a patient for pain, the clinician should ask about the quality, points of radiation, severity, timing, instigating factors, and alleviating features. In addition, the impact of pain on quality of life and functional capacity should be addressed.
A variety of pain scales have been established to help quantify the severity of pain. Numeric rating scales (Figure) can be used for patients who have some level of cognitive function.12 In patients with more severe cognitive impairment, behavioral scales such as the Pain Assessment in Advanced Dementia (PAINAD) can be employed.13 Family members may also be helpful when assessing pain in cognitively impaired individuals by identifying unusual behaviors or actions typically associated with patient discomfort. However, clinicians should be aware that pain ratings between patients and families are not always concordant.14,15
In addition to quantifying pain severity, the effect of pain on a patient’s quality of life should also be determined. Simple questions such as “Does the pain make you stop doing things that you enjoy?” “Do you feel sad or depressed because of the pain?” and “Does the pain affect your ability to sleep?” can be asked quickly and easily during the assessment. For a more formal appraisal of the effects on a patient’s quality of life, instruments such as the Brief Pain Inventory that incorporate both pain assessment and its impact on quality of life can be employed.16
The treatment of somatic pain in the older patient
The treatment of pain in the geriatric patient can be more difficult than in younger patients. Physiologic changes such as diminished renal function, changes in body fat distribution, and alterations in hepatic metabolism can lead to higher levels of medications and a greater susceptibility to adverse effects.17 The American Geriatrics Society has published guidelines for the treatment of acute and chronic pain.7 Of note, since these guidelines were developed, results from several studies suggest that the use of cyclooxygenase-2 (COX-2) inhibitors is associated with serious adverse cardiovascular events, and the side-effect profile of these medications is not as benign as previously thought.18
Opioids are a mainstay therapy in chronic pain management; however, their use in the geriatric population is often limited by patients’ fear of addiction. Although physical dependence is unavoidable with opioids, psychological dependence or true addiction is extremely rare in older patients.7 Unlike acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), opioids do not have a maximum dose, can be used for long periods of time without concern for organ damage, and can be administered through a variety of routes (oral, intravenous, subcutaneous, transdermal, rectal)17 (Table I).
Frequency of administration is an important factor when prescribing opioids. Chronic pain or pain that is not expected to improve quickly should be treated with an around-the-clock regimen with as-needed doses (prn) for breakthrough pain. Sustained-release oral formulations can be administered in a standing manner every 8-12 hours, whereas short-acting oral and intravenous formulations should be administered every 3-4 hours around the clock. With this dosing schedule, one avoids periods of inadequate pain relief. Of note, sustained-release preparations cannot be administered through gastrostomy tubes. The onset of action of intravenous opioids is 8-10 minutes, and oral opioids is 30-60 minutes. Breakthrough medications should be offered at least every hour.19 Special concern should be taken when administering formulations of opioids combined with acetaminophen because frequent dosing can lead to high levels of acetaminophen; it is often safer to prescribe the opioid individually rather than in the combination product.
Common adverse side effects of opioids are nausea, constipation, and pruritis. In older patients, sedation, fecal impaction, and urinary retention are additional notable consequences of opioid use. Constipation should be expected in all patients treated with opioids, so prophylactic stool softeners and laxatives should be given. Sedation and delirium are often cited as reasons that opioids are not given to geriatric patients; however, there is a paucity of evidence to substantiate this claim. Furthermore, studies have shown that proper pain management decreases the incidence of delirium.20 Although there are no specific guidelines concerning dosing adjustments in the geriatric population, the authors recommend starting older patients on low doses, monitoring them closely, and titrating slowly.
Neuropathic pain and adjuvant pain medications
Neuropathic pain is often described as a burning or shooting sensation. Adjuvant medications are particularly useful in the treatment of neuropathic pain; opioids are also effective (Table II).
Tricyclic antidepressants (TCAs) have been shown to be effective in both somatic and neuropathic pain.21 Although the most concerning adverse effect is cardiotoxicity, and use of TCAs is not recommended in patients with prolonged Q-T intervals or bundle branch blocks, other adverse effects such as orthostasis, sedation, confusion, urinary retention, and exacerbation of narrow-angle glaucoma are much more frequent and are more likely to limit their use in geriatric patients.22
Other medications that have been evaluated for the treatment of neuropathic pain include selective serotonin reuptake inhibitors (SSRIs), mixed reuptake inhibitors, anticonvulsants, and topical lidocaine. Of the SSRIs and mixed reuptake inhibitors, paroxetine, citalopram, duloxetine, and venlafaxine have been shown to be efficacious in controlled trials.23-26 Both the SSRIs and mixed reuptake inhibitors are useful in the geriatric patient because of their favorable side-effect profiles.
Anticonvulsants have been a mainstay therapy for neuropathic pain. Gabapentin, a newer anticonvulsant, is recommended as a first-line treatment for neuropathic pain because of its efficacy and safety profile.27 Common side effects of gabapentin are somnolence and ataxia. In the geriatric patient, it should be started at a dose of 100 mg before bedtime, and can be titrated up every 3 days with a maximal dose of 3.6 g. Lamotrigine, another newer anticonvulsant, has also been shown to be efficacious in neuropathic pain.28 Carbamazepine, an older antipsychotic, is classically used for trigeminal neuralgia, but the side-effect profile and potential for drug interactions make its use limited in the geriatric population.
Local anesthetics can be very useful in the treatment of both neuropathic and localized pain. Transdermal lidocaine has a very low risk of adverse effects and should be considered for pain in the older patient. The patch should be applied for 12 hours and removed for 12 hours each day to avoid tachyphylaxis.29
Management of Other Symptoms
Pain is not the only symptom experienced by seriously ill patients (Table III). As in the evaluation of pain, the assessment of non-pain symptoms should include severity, timing, exacerbating factors, and effect on quality of life. In order to quantify the severity of symptoms, the Edmonton Symptom Assessment System (ESAS) and Memorial Symptom Assessment Scale (MSAS) can be used.30,31 These tools allow patients to quantify their symptoms severity on a numeric scale and are easily employed in the clinical setting.
Dyspnea is a common symptom, particularly in patients with pulmonary disease or congestive heart failure; however, dyspnea is commonly reported in patients with other illnesses and may be due to muscle wasting, acid-base disturbances, or anxiety. An easy way to quantify dyspnea is the severity at varying levels of exertion; however, in patients who cannot walk or communicate, the clinician can note the respiratory rate or use of accessory muscles.32
For symptomatic treatment of dyspnea, oxygen and opioids are the mainstay therapies.33 Oxygen acts to improve dyspnea both by correcting hypoxemia and through direct stimulation of the trigeminal nerve in the nasal cavity. Systemic opioids have been shown to reduce dyspnea in randomized controlled trials. No randomized controlled trials have demonstrated this effect with nebulized opioids.34,35 Opioids act by decreasing respiratory drive and, more importantly, by reducing the subjective sensation of breathlessness.36 Other medications such as benzodiazepines and bronchodilators play a role in the treatment of dyspnea in specific cases of anxiety and air flow obstruction, respectively.
Fatigue is a common symptom in patients with severe illnesses. It can easily be assessed by asking patients whether they can perform simple activities, eat, or interact with others.
The clinician should first determine whether there is a correctible cause of fatigue, such as anemia, depression, or medications. Treatment of fatigue can be difficult when there is not a clear etiology. Although there are no randomized controlled trials of nonpharmacologic treatments of fatigue, several studies have shown that energy conservation techniques and proper spacing of activities can be useful.37 Psychostimulants have been the major pharmacologic therapy for fatigue. In an uncontrolled trial in patients with advanced cancer, participants had less fatigue after 3 days of methylphenidate treatment.38 The common side effects of methylphenidate are restlessness, blurred vision, and loss of appetite. The manufacturer cautions its use in patients who have hypertension or a propensity to tachyarrhythmias. Small studies have shown that methylphenidate is safe for use in the geriatric population.39 Tricyclic antidepressants and steroids may be beneficial in cancer-related fatigue, but their use in the geriatric population is limited by their adverse-effect profiles.
Anorexia is a common side effect in patients with both life-threatening illnesses and progressive chronic illnesses. Fatigue, nausea, and depression may contribute to anorexia, and treatment of these conditions may improve appetite.
Pharmacologic treatment of anorexia can be difficult in the elderly patient. For years, corticosteroids were the first-line treatment for cancer-related anorexia, but given the side-effect profile and the fact that some studies have shown that their effect on anorexia may be time-limited, they are often not a good long-term option.40 Megestrol acetate, a progesterone analog, is now used more frequently for the treatment of cancer- and AIDS-related anorexia. Multiple randomized controlled trials have demonstrated its efficacy, and a Cochrane Database review, which included 30 trials, found that megestrol was efficacious in appetite stimulation and led to improved quality of life in patients with cancer and AIDS.41 The medication has a number of side effects including adrenal insufficiency, hyperactivity, edema, hot flashes, and gastrointestinal side effects. There have also been reports of deep venous thromboses and fatal pulmonary emboli with megestrol therapy.41
Nausea is the sensation of impending vomiting, and can accompany vomiting or occur independently. It can be caused by disorders of the gastrointestinal tract such as obstruction or gastroparesis, central nervous system disturbances, and metabolic derangements. Opioids, chemotherapeutic agents, and a number of commonly prescribed pharmaceuticals are common causes of acute nausea that improves with time.42
Given the multitude of etiologies for nausea and vomiting, the American Gastroenterological Association has developed a set of guidelines for the assessment and treatment of these conditions. In these guidelines, the etiology of nausea is classified into five categories: central, endocrinologic, iatrogenic, obstructive, and mucosal. Treatment should be based on the most likely class of etiology.42
The treatment of nausea and vomiting should first aim to correct dehydration and electrolyte imbalances. If possible, the causative agent should be removed. For symptomatic treatment of nausea and vomiting, there are a variety of options. Antiemetics act on the central nervous system to repress nausea. The major categories of antiemetics are anticholinergic agents, histamine blockers, phenothiazines, and serotonin 5-HT antagonists. Antidopaminergic agents, such as haloperidol and metoclopramide, have both antiemetic and prokinetic properties.
Depression and sadness are common symptoms at the end of life, with reported prevalence rates of 15-60%.43 The single question, “Are you depressed?” has been validated as a good screening tool in terminally ill patients.44
The reasons for depression and sadness are often multifactorial in patients at the end of life. Depression may be the result of physical symptoms, existential concerns, and a predisposition to the condition. Studies have shown that treatment of pain and other physical symptoms can improve depression.45 Untreated depression is associated with a greater desire for a hastened death, which may lead to diminished functional capacity and poorer quality of life.44
Treatment of depression in the terminally ill patient can be difficult. The mainstay class of medications is the SSRIs; however, it can take up to 6 weeks to attain an adequate response. In patients whose prognoses are limited, methylphenidate can be used, and is particularly helpful in those with anergia and anhedonia.46 A newer stimulant, modafinil, has been used at the end of life, but there are no studies comparing its efficacy to methylphenidate.43
Delirium is a common problem in patients who are dying, with a prevalence of 30-80% in the last weeks of life.32,47 In the terminally ill patient, the etiology of delirium is often multifactorial, and the differential diagnosis should include medications, infections, organ failure, intracranial processes, metabolic derangements, and withdrawal.48 Treatment of delirium should aim to correct the underlying etiology; however, the burden of diagnostic tests should be weighed against their benefits in the last weeks of life.49 The authors believe that delirium at the end of life can be profoundly distressing and should always be treated; however, there are no prospective controlled trials of pharmacologic management of terminal delirium in the elderly.50 One study of younger patients with AIDS found that treatment with haloperidol and chlorpromazine improved terminal delirium, whereas lorazepam did not.51 Newer antipsychotic agents may be useful, but they have not been studied specifically at the end of life.52 In these situations in which antipsychotics are not effective, and pain or delirium is particularly distressing, sedation with short-acting agents such as lorazepam, midazolam, or propofol should be employed.53,54
The primary aim in palliative care should be to relieve suffering. The case presentation showed that while curative treatment may not always be possible, treatment of pain and symptoms can significantly affect a patient’s quality of life.
In the first part of this series, the authors have reviewed the principles of the assessment and treatment of common symptoms experienced by older adults with serious and advanced illness. Pain and symptom management is one form of suffering. Suffering can take many forms and include concerns about goals, spiritual issues, and family. In the second part of this article, the authors will review the role of the physician in communicating with patients and families and the establishment of realistic goals for the most effective patient palliative care.
The authors report no relevant financial relationships.
From the Lilian and Benjamin Hertzberg Palliative Care Institute, Brookdale Department of Geriatrics and Adult Development, Mount Sinai School of Medicine, New York, NY.
1. Morrison RS, Meier DE. Clinical practice. Palliative care. N Engl J Med 2004;350(25):2582-2590.
2. American Academy of Hospice and Palliative Medicine, Center to Advance Palliative Care, Hospice and Palliative Nurses Association, Last Acts Partnership, and National Hospice and Palliative Care Organization. National Consensus Project for Quality Palliative Care: Clinical Practice Guidelines for quality palliative care, executive summary. J Palliat Med 2004;7(5):611-627.
3. Singer PA, Martin DK, Kelner M. Quality end-of-life care: Patients’ perspectives. JAMA 1999;281(2):163-168.
4. The SUPPORT Principal Investigators. A controlled trial to improve care for seriously ill hospitalized patients. The study to understand prognoses and preferences for outcomes and risks of treatments (SUPPORT). JAMA 1995;274(20):1591-1598.
5. Emanuel EJ, Fairclough DL, Slutsman J, Emanuel LL. Understanding economic and other burdens of terminal illness: The experience of patients and their caregivers. Ann Intern Med 2000;132(6):451-459.
6. Field MJ, Cassel CK; Institute of Medicine Committee on Care at the End of Life, Institute of Medicine. Approaching Death: Improving Care at the End of Life. Washington, D.C.: National Academy Press; 1997.
7. AGS Panel on Persistent Pain in Older Persons. The management of persistent pain in older persons. J Am Geriatr Soc 2002;50(6 suppl):S205-S224.
8. Warfield CA, Bajwa ZH, eds. Principles and Practice of Pain Medicine. New York, NY; McGraw-Hill, Medical Pub. Div; 2004.
9. Won A, Lapane K, Gambassi G, et al. Correlates and management of nonmalignant pain in the nursing home. SAGE Study Group. Systematic Assessment of Geriatric drug use via Epidemiology. J Am Geriatr Soc 1999;47(8):936-942.
10. Miller SC, Mor V, Wu N, et al. Does receipt of hospice care in nursing homes improve the management of pain at the end of life? J Am Geriatr Soc 2002;50(3):507-515.
11. Won AB, Lapane KL, Vallow S, et al. Persistent nonmalignant pain and analgesic prescribing patterns in elderly nursing home residents. J Am Geriatr Soc 2004;52(6):867-874.
12. Herr KA, Garand L. Assessment and measurement of pain in older adults. Clin Geriatr Med 2001;17(3):457-78, vi.
13. Warden V, Hurley AC, Volicer L. Development and psychometric evaluation of the Pain Assessment in Advanced Dementia (PAINAD) scale. J Am Med Dir Assoc 2003;4(1):9-15.
14. Ferrell BA, Ferrell BR, Rivera L. Pain in cognitively impaired nursing home patients. J Pain Symptom Manage 1995;10(8):591-598.
15. Weiner D, Peterson B, Keefe F. Chronic pain-associated behaviors in the nursing home: Resident versus caregiver perceptions. Pain 1999;80(3):577-588.
16. Tan G, Jensen MP, Thornby JI, Shanti BF. Validation of the Brief Pain Inventory for chronic nonmalignant pain. J Pain 2004;5(2):133-137.
17. Goldstein NE, Morrison RS. Treatment of pain in older patients. Crit Rev Oncol Hematol 2005;54(2):157-164.
18. Brophy JM. Cardiovascular risk associated with celecoxib. N Engl J Med 2005;352(25):2648-2650.
19. Inturrisi CE. Clinical pharmacology of opioids for pain. Clin J Pain 2002;18(4 suppl):S3-S13.
20. Morrison RS, Magaziner J, Gilbert M, et al. Relationship between pain and opioid analgesics on the development of delirium following hip fracture. J Gerontol A Biol Sci Med Sci 2003;58(1):76-81.
21. Saarto T, Wiffen PJ. Antidepressants for neuropathic pain. Cochrane Database Syst Rev 2005;(3):CD005454.
22. Small GW. Tricyclic antidepressants for medically ill geriatric patients. J Clin Psychiatry 1989;50(suppl):27-33.
23. Sindrup SH, Bjerre U, Dejgaard A, et al. The selective serotonin reuptake inhibitor citalopram relieves the symptoms of diabetic neuropathy. Clin Pharmacol Ther 1992;52(5):547-552.
24. Sindrup SH, Gram LF, Brosen K, et al. The selective serotonin reuptake inhibitor paroxetine is effective in the treatment of diabetic neuropathy symptoms. Pain 1990;42(2):135-144.
25. Lussier D, Huskey AG, Portenoy RK. Adjuvant analgesics in cancer pain management. Oncologist 2004;9(5):571-591.
26. Rowbotham MC, Goli V, Kunz NR, Lei D. Venlafaxine extended release in the treatment of painful diabetic neuropathy: A double-blind, placebo-controlled study. Pain 2004;110(3):697-706.
27. Dworkin RH, Backonja M, Rowbotham MC, et al. Advances in neuropathic pain: Diagnosis, mechanisms, and treatment recommendations. Arch Neurol 2003;60(11):1524-1534.
28. McCleane GJ. Lamotrigine in the management of neuropathic pain: A review of the literature. Clin J Pain 2000;16(4):321-326.
29. Gammaitoni AR, Alvarez NA, Galer BS. Safety and tolerability of the lidocaine patch 5%, a targeted peripheral analgesic: A review of the literature. J Clin Pharmacol 2003;43(2):111-117.
30. Chang VT, Hwang SS, Feuerman M. Validation of the Edmonton Symptom Assessment Scale. Cancer 2000;88(9):2164-2171.
31. Chang VT, Hwang SS, Kasimis B, Thaler HT. Shorter symptom assessment instruments: The Condensed Memorial Symptom Assessment Scale (CMSAS). Cancer Invest 2004;22(4):526-536.
32. Plonk WM Jr, Arnold RM. Terminal care: the last weeks of life. J Palliat Med 2005;8(5):1042-1054.
33. Booth S, Wade R, Johnson M, et al; Expert Working Group of the Scientific Committee of the Association of Palliative Medicine. The use of oxygen in the palliation of breathlessness. A report of the expert working group of the Scientific Committee of the Association of Palliative Medicine. Respir Med 2004;98(1):66-77. [Erratum in: Respir Med 2004;98(5):476.]
34. Bruera E, MacEachern T, Ripamonti C, Hanson J. Subcutaneous morphine for dyspnea in cancer patients. Ann Intern Med 1993;119(9):906-907.
35. Abernethy AP, Currow DC, Frith P, et al. Randomised, double blind, placebo controlled crossover trial of sustained release morphine for the management of refractory dyspnoea. BMJ 2003;327(7414):523-528.
36. Chandler S. Nebulized opioids to treat dyspnea. Am J Hosp Palliat Care 1999;16(1):418-422.
37. Morrow GR, Shelke AR, Roscoe JA, et al. Management of cancer-related fatigue. Cancer Invest 2005;23(3):229-239.
38. Bruera E, Driver L, Barnes EA, et al. Patient-controlled methylphenidate for the management of fatigue in patients with advanced cancer: A preliminary report. J Clin Oncol 2003;21(23):4439-4443.
39. Galynker I, Ieronimo C, Miner C, et al. Methylphenidate treatment of negative symptoms in patients with dementia. J Neuropsychiatry Clin Neurosci 1997;9(2):231-239.
40. Bruera E, Roca E, Cedaro L, et al. Action of oral methylprednisolone in terminal cancer patients: A prospective randomized double-blind study. Cancer Treat Rep 1985;69(7-8):751-754.
41. Berenstein EG, Ortiz Z. Megestrol acetate for the treatment of anorexia-cachexia syndrome. Cochrane Database Syst Rev 2005;(2):CD004310.
42. Quigley EM, Hasler WL, Parkman HP. AGA technical review on nausea and vomiting. Gastroenterology 2001;120(1):263-286.
43. Lyness JM. End-of-life care: Issues relevant to the geriatric psychiatrist. Am J Geriatr Psychiatry 2004;12(5):457-472.
44. Chochinov HM, Tataryn D, Clinch JJ, Dudgeon D. Will to live in the terminally ill. Lancet 1999;354(9181):816-819.
45. Lyness JM, Caine ED, King DA, et al. Depressive disorders and symptoms in older primary care patients: One-year outcomes. Am J Geriatr Psychiatry 2002;10(3):275-282.
46. Rozans M, Dreisbach A, Lertora JJ, Kahn MJ. Palliative uses of methyl-phenidate in patients with cancer: A review. J Clin Oncol 2002;20(1):335-339.
47. Conill C, Verger E, Henriquez I, et al. Symptom prevalence in the last week of life. J Pain Symptom Manage 1997;14(6):328-331.
48. Michaud L, Burnand B, Stiefel F. Taking care of the terminally ill cancer patient: Delirium as a symptom of terminal disease. Ann Oncol 2004;15(suppl 4):iv,199-203.
49. Casarett DJ, Inouye SK; American College of Physicians-American Society of Internal Medicine End-of-Life Care Consensus Panel. Diagnosis and management of delirium near the end of life. Ann Intern Med 2001;135(1):32-40.
50. Jackson KC, Lipman AG. Drug therapy for delirium in terminally ill patients. Cochrane Database Syst Rev 2004;(2):CD004770.
51. Breitbart W, Marotta R, Platt MM, et al. A double-blind trial of haloperidol, chlorpromazine, and lorazepam in the treatment of delirium in hospitalized AIDS patients. Am J Psychiatry 1996;153(2):231-237.
52. Daniel DG. Antipsychotic treatment of psychosis and agitation in the elderly. J Clin Psychiatry 2000;61(suppl 14):49-52.
53. Quill TE, Byock IR. Responding to intractable terminal suffering: The role of terminal sedation and voluntary refusal of food and fluids. ACP-ASIM End-of-Life Care Consensus Panel. American College of Physicians-American Society of Internal Medicine. Ann Intern Med 2000;132(5):408-414. [Erratum in: Ann Intern Med 2000;132(12):1011.]
54. Lo B, Rubenfeld G. Palliative sedation in dying patients: “We turn to it when everything else hasn’t worked.” JAMA 2005;294(14):1810-1816.