Palliative care is specialized medical care for people with serious illness that focuses on the best quality of life for both the patient and his or her family. [1] [2] To palliate comes from the Latin word "palliare," meaning "to cloak," or to ease symptoms without curing the underlying disease. The primary goal of palliative care is to provide quality of life for the patient and family, achieved through an interdisciplinary approach that includes symptom control and support for the patient and family. Palliative care is focused on providing patients with relief from the symptoms, pain, and stress of a serious illness - whatever the diagnosis. The interdisciplinary team consists of doctors, nurses, and other specialists who work with a patient's other doctors to provide an extra layer of support. Palliative care is appropriate at any age and at any stage in a serious illness, and can be provided together with curative treatment.

Hospice is a philosophy and delivery system of care that focuses on the palliative care needs of the patient unit (patients and caregivers), to relieve suffering and promote comfort during the end-of-life transition when curative therapy is no longer desired and/or an option.

  • Palliative care should be integrated into the daily clinical practice of patient care, regardless of the underlying illness or stage of disease.

  • Hospice care should be considered for patients facing life-threatening illness with anticipated life expectancy of ≤6 months.

Outpatient palliative care services

Palliative care addresses the physical, psychological, social, and spiritual issues of a patient's disease process. The Centers for Medicare and Medicaid define palliative care as patient and family-centered care that optimizes quality of life by anticipating, preventing, and treating suffering; throughout the continuum of illness, palliative care involves addressing physical, intellectual, emotional, social, and spiritual needs, and aims to facilitate patient autonomy, access to information, and choice. [3] The team elicits the patient's goals of care and focuses on improving the quality of life and promoting comfort by therapies that are in line with the patient's goals. This may involve managing pain and non-pain symptoms, enhancing communication and education, assisting with difficult decision making and treatment choices, advance-care planning, disposition planning, providing emotional and spiritual support, and providing grief and bereavement services. These services are usually provided as a complement to disease-directed therapies. Outpatient palliative care has been shown to improve quality of life, improve symptom control, decrease emergency department visits and hospital admissions, improve survival, and lower medical costs. [4]

Services provided

  • There is great variability in community palliative care services. The advanced practice provider or physician may provide home visits about every other week. Any recommendations for management are then communicated to a patient's primary-care physician. Treatment and personal-care services are not provided.

  • Outpatient palliative care clinics are increasing in availability and help to bridge the gap between inpatient and home palliative care services.

Hospice-care services

Hospice care falls under the larger umbrella of palliative care. Hospice is a philosophy of care that focuses on the described palliative care needs of the patient unit, to relieve suffering and promote comfort during the end-of-life transition when curative therapy is no longer desired and/or an option. The Centers for Medicare and Medicaid define hospice care as a comprehensive set of services identified and coordinated by an interdisciplinary group to provide for the physical, psychosocial, spiritual, and emotional needs of a terminally ill patient and/or family members, as delineated in a specific patient plan of care. [3] Addressing a patient's psychosocial and spiritual transition from curative to palliative therapies and goals is part of the hospice process. This is accomplished through an interdisciplinary team approach, which may include physicians, nurses, nursing aides, social workers, case managers, chaplains, dietitians, pharmacists, therapists, and trained volunteers. [5] To be eligible for hospice care, a patient must be willing to relinquish Medicare-reimbursed services for therapies focused on cure or life prolongation and must be certified by the attending physician and the hospice physician as having a terminal illness with a life expectancy of up to 6 months, should the illness run its normal course. [5] Patients may continue to receive hospice care past 6 months if the physician attests that the patient's prognosis remains 6 months or less. [6] Patients may opt to relinquish hospice services at any time.

Services provided

  • In contrast to outpatient home palliative care services, hospice services provide comprehensive patient care. Coverage from the Hospice Medicare Benefit includes interdisciplinary team services, such as physician and nursing services. Many hospices provide up to 1 to 4 hours per day of nursing/certified nursing-assistant care at home up to 5 days a week, depending on an individual patient's needs. [5] Home-care coverage is not 24 hours a day. However, the Medicare Hospice Benefit includes a continuous-care option that is available during periods of crisis to keep the patient at home.

  • Patients are recommended and/or required to have a care provider for home hospice, usually provided by family and/or friends. Durable medical equipment is covered, along with medications related to the hospice diagnosis for pain and symptom control. Inpatient hospice services provide 24-hour-a-day personal care and interdisciplinary services during times of crisis for acute symptom management. Facility room and board are covered for patients with a status of "general inpatient" for acute symptom control. Room and board are not covered for routine residential care (i.e., nursing homes) under Medicare.

Need for palliative care

The 2012 estimated life expectancy at birth in the US is 78.8 years: 76.4 years for males, and 81.2 years for females. [7] Advancements in public health and technology have modified the leading causes of death to be the end result of chronic illnesses. In 2012, the leading causes of death in the US were heart disease, cancer, stroke, and chronic lower respiratory diseases. Globally, the leading causes of death in 2012 were heart disease, stroke, lower respiratory tract infections, and chronic obstructive pulmonary disease. [8]

The older population is growing at a rate faster than that of the world's total population. [9] The percentage of older people is projected to more than double globally in the next half century. One in every 5 Americans will be older than the age of 65 by the year 2030. [10] The aging population poses unique socioeconomic consequences worldwide. A new challenge, as outlined by the United Nations, will be "to ensure that people everywhere will be enabled to age with security and dignity and continue to participate in their societies as citizens with full rights". [9] The healthcare-delivery system is changing to be responsive to the needs of people with chronic, debilitating illnesses and end-of-life issues. Palliative care will have a key role during this transition.

Many gaps exist in end-of-life care. In a multicenter landmark study, only 47% of physicians knew when their patients desired do-not-attempt-resuscitation (DNAR) status, with only 51% of these patients having a written DNAR order. [11] Despite >50% of patients dying in the hospital, 49% to 100% of patients and 63% of caregivers state that home is the preferred place of death. [11] [12] In addition, symptom control is not optimal, with surrogates reporting 50% of their loved ones having moderate to severe pain >50% of the time during the last 3 days of life. [11] Families of patients who have died have rated the quality of end-of-life care to be lower in 2011-2013 relative to 2000. [13]

The 2014 Institute of Medicine (IOM) report, Dying in America: Improving Quality and Honoring Individual Preferences Near the End of Life, calls for major reform in the US health system to ensure high-quality, affordable, and sustainable end-of-life care for Americans. [14] The consensus report emphasizes quality end-of-life care that is consistent with patients' values, goals, and preferences as a national priority. The report offers recommendations for improving end-of-life care in five areas:

  • Delivery of person-centered, family-oriented end-of-life care

  • Clinician-patient communication and advance care planning

  • Professional education and development

  • Policies and payment systems to support high-quality end-of-life care

  • Public education and engagement.

Palliative care has been shown to improve patient outcomes and provide lower cost of care and intensive care utilization. [15] [16] [17] [18] [19] [20] [21] Outpatient palliative care services provided to patients with advanced cancer receiving standard care improved quality of life and mood compared with patients receiving only standard care, with no differences in survival. [22] Home palliative care services decrease symptom burden and increase the chance of dying at home for patients with cancer. [23] In addition, patients with newly diagnosed metastatic non-small cell lung cancer who received palliative care in addition to standard care had better quality of life and mood, and longer survival, than patients receiving only standard care. [24] Initiating palliative care earlier on in cancer care has also been shown to improve survival. [25] The American Society of Clinical Oncology advocates integrating palliative care principles into the care of patients with advanced cancer, and incorporating quality palliative care into oncology training and certification. [26] [27]

In September 2011, the Joint Commission on Accreditation of Health Care Organizations launched the Advanced Certification Program for Palliative Care, recognizing hospital inpatient programs that demonstrate exceptional patient- and family-centered care and optimize quality of life for patients with serious illness. The standards for palliative care certification are built on the National Consensus Project's Clinical Practice Guidelines for Quality Palliative Care and the National Quality Forum's National Framework and Preferred Practices for Palliative and Hospice Care Quality. [28]

Role of prognostication

Physicians are not accurate in prognostication of patients' risk of death. Survival predictions of terminally ill patients at time of hospice referral were only 20% accurate (within 33% of actual survival). [29] Not only were physicians overoptimistic, but they also overestimated survival by a factor of 5.3. Factors that decreased prognostic accuracy were less-experienced physicians and longer duration of doctor-patient relationship. Overoptimistic prognostication makes planning for the future more difficult and may lead to late hospice referrals. Terminally ill cancer patients are more likely to request life-extending therapies over comfort measures if they hold overoptimistic survival prospects. [30] [31] The Institute for Clinical Systems Improvement supports healthcare providers asking the question "Would you be surprised if your patient died within the next 2 years?" to assist in identifying the population who would benefit from palliative care. [32] In the cancer population, asking "Would I be surprised if this patient died in the next year?" has been shown to identify patients who are at greatly increased risk of 1-year mortality. [33] [34]

Prognosis is often communicated by providing a time range that encompasses average life expectancy (i.e., hours-days, days-weeks, weeks-months, months-years). [35] The patient and family should be cautioned that these are rough estimates, that physicians are usually inaccurate in their estimates, and that the estimate may change over time depending on the patient's disease course and events.

Prognostication indices

  • Numerous prognostic indices have been developed over recent decades that can be used to guide clinical practice and medical decision making. Prognostication tools improve physicians' clinical-prognostic estimate. [36] These include:

    • Palliative Performance Scale (PPS): initial PPS score on admission to a hospice palliative care unit predicts survival, [37] including for patients admitted to the hospital with palliative care consults. [38] PPS is significantly associated with hazard of death in ambulatory cancer patients. [39]

    • Palliative Prognostic Score (PaP): PaP scores of patients admitted to the hospital with palliative care consults predict survival, [40] including for patients admitted to the hospital with exclusively noncancer diagnoses seen by a palliative care service. [41]

    • Functional Measures as Predictors of Mortality: 3 functional measures (impairment in instrumental activities of daily living, Mini-Mental State Examination score of <20, and shortened Geriatric Depression Scale score of 7 or higher) predict short- and long-term mortality in older patients admitted to the hospital. [42]

    • CARING criteria: 5 prognostic indicators (cancer as the primary diagnosis, 2 or more admissions to the hospital in the past year for a chronic illness, residence in a nursing facility, intensive care unit admission with multi-organ failure, 2 or more noncancer hospice guidelines) identified on hospital admission predict risk of death in 1 year. [43] [44]

    • Prognostigram: patient-specific prognostic tool for adult cancer patients that generates patient-unique survival curves. [45] [Washington University in St Louis: Prognostigram]

    • ePrognosis: online repository of published geriatric prognostic indices where clinicians can access evidence-based information on patient prognosis. [ePrognosis: estimating prognosis for elders]

Goals of care

Determining a patient's goals of care is the key principle underlying palliative medicine. [46] A 7-step protocol to elicit goals of care is a helpful tool for this process. [47] [48]

Create the environment

  • Secure a place where you can sit down, have privacy, and minimize interruptions. Ensure that the right people are present: for example, caregiver, medical durable power of attorney (MDPOA)/proxy medical decision maker, family, friends, social worker, and chaplain.

Determine what the patient and family know

  • Clarify upfront what the patient and family understand about the current situation. Update the patient and family on the patient's condition and correct any misunderstandings.

Explore what the patient's and family's hopes are

  • Discuss what brings the greatest value, meaning, and joy to the patient's life. Focus on what you can do to help achieve those goals. Identify things that you cannot do because they are not possible or are not in line with achieving the goals of care.

Offer realistic goals and discuss options to achieve those goals

  • Set goals before determining the treatment plan. Assist in shared decision making by suggesting realistic goals and making recommendations on the care plan that will achieve the patient's goals. Work through unreasonable or unrealistic expectations. Redirect unrealistic hopes to realistic ones.

Respond empathically

  • Be prepared to respond to any emotions that may arise. Listening to and acknowledging the emotion is often enough to provide a sense of respect and comfort.

Make a plan, summarize, document, communicate, and follow through

  • Establish a plan for the next steps (e.g., where you go from here). Summarize the plan to ensure that everyone is on the same page. Document the plan in the chart. Communicate the plan to others in the medical team. Schedule a follow-up meeting as indicated.

Periodically review and revise

  • Review and revise the goals of care when the patient has a significant change in health status, limited life expectancy, change in setting of care, or change in treatment preferences. Goals may change near the end of life. [49]

Comprehensive palliative care assessment

A comprehensive palliative care assessment enables an individualized care plan to be prepared. [50] A key part of the assessment is to prioritize the patient's and family's concerns and problems. However, it should be recognized that it is not always possible to do a comprehensive assessment on one visit. Furthermore, in some circumstances any immediate issues (e.g., a person in severe pain) may require action before the full assessment can be completed.

Assessment may be facilitated by the use of palliative care assessment tools. [Palliative care Outcome Scale (POS)] [Alberta Health Services: Edmonton Symptom Assessment System Revised]

Assessment should include the following:

History of illness

  • Review the patient's disease course, including the primary illness and pertinent secondary diagnoses. Summarize the previous treatments and patient's response.

Physical symptoms

  • Physical assessment is best organized by symptoms and functional activities, rather than organ system. The physical exam can be used to confirm findings from the history. Occasionally, diagnostic tests are helpful if they change the care plan and are in line with the patient's goals of care.

Psychological symptoms

  • Inquire about mood/affect, emotions, fears, hopes, cognitive state, coping mechanisms, and unresolved issues.

Decision-making capacity

  • Evaluate global and decision-specific capacity. Begin advance-care planning discussions.

Social assessment

  • Evaluate the family, community, financial, and environmental circumstances that are affecting the patient.

Spiritual assessment

  • Inquire about personal meaning and value of the patient's life and illness, faith, religious denomination, and desired pastor services.

Practical needs

  • Determine caregiver, dependent, domestic, and residential needs and how this will change as the patient's illness progresses.

Grief and bereavement

  • Evaluate current and anticipated losses. Determine bereavement needs of patient and family, including risk assessment for complicated grief. Continue advance-care-planning discussions and planning for the last hours.

Illness trajectories

Patients with advanced illness can be categorized broadly by the clinical course of their disease process. This concept of chronic-illness trajectories can be helpful in estimating prognosis, revisiting goals of care, and anticipating the patient's physical, psychological, social, and spiritual needs. Three distinct illness trajectories have been described for patients with chronic, progressive illness: cancer, organ failure, and dementia/frailty trajectories. [51]

Cancer trajectory

  • Patients have a slow, gradual decline for prolonged periods, followed by a short period of rapid decline, which leads to death.

Organ failure trajectory (e.g., congestive heart failure, COPD)

  • Patients have a slow, gradual decline with periods of acute exacerbations and rapid deterioration from which they have a partial recovery. The exacerbations become more frequent and severe with time, with any one of these exacerbations placing the patient at high risk of death. Eventually, one of the exacerbations leads to death, which may then seem to be more of a sudden event, as the timing of death is less clear. [52]

Dementia/frailty trajectory

  • Patients have a slow, progressive decline with small ups and downs of physical and cognitive function. Frequently, death follows a secondary illness, such as pneumonia.

Overview of common symptoms experienced by patients in the palliative care setting


  • There are 3 main types of pain: nociceptive (somatic and visceral), neuropathic, and psychosocial-spiritual pain. Nociceptive pain occurs from noxious stimuli activating afferent pain nerves. Somatic pain arises from the skin, muscle, or bone and is often described as a well-localized pain that is stabbing, throbbing, or aching. Visceral pain involves organs, is not well localized, and is described as cramping, dull, aching, or sharp. Neuropathic pain arises from injury to or abnormal stimulation of nerves. Sharp, shooting, burning, and tingling are descriptors of neuropathic pain. Up to 76% of patients with cancer are in pain. [53]

  • Pain can be assessed using the following scales: Numerical Analog Scale, Visual Analog Scale, Verbal Descriptive Scale, Face Scale, FLACC (Face, Legs, Activity, Cry, and Consolability) Scale, Modified FLACC Tool, and PABS (Pain Attitudes And Beliefs) Scale. [54]


  • This can arise from multiple etiologies, including COPD, asthma, pneumonia, pleural or pericardial effusions, pulmonary edema, pulmonary embolism, anemia, ascites, acidosis, hypoxia, hypercapnia, and anxiety. [55] Dyspnea is observed in 21% to 90% of patients with cancer. [56]

  • Dyspnea can be assessed using the following scales: Borg Scale, Functional Dyspnea Scale, Number Counting, and Visual Analog Scale.


  • This may be caused by medications (e.g., opioids, anticholinergics, iron, antihypertensives), metabolic abnormalities (e.g., hypercalcemia, hypothyroidism), gastrointestinal etiologies (e.g., bowel obstruction, tumor, anal fissures, hemorrhoids), neurologic causes (e.g., nerve or spinal cord compression, visceral neuropathy), environmental factors (e.g., inactivity, poor intake, poorly accessible toilet facilities), and psychological factors (e.g., depression, anxiety). [55] Constipation occurs in 35% to 65% of patients with cancer [53] and 15% to 90% of patients with opioid-induced constipation for noncancer pain. [57]

  • Constipation can be assessed using either the Modified Constipation Assessment Scale or the Patient Assessment of Constipation Tool.


  • Typical presentations that should lead to an assessment of depression include: low mood, tearfulness, irritability, and distress; withdrawal, loss of interest or pleasure in daily activities; intractable physical symptoms or symptoms disproportionate to the degree of disease; feelings of hopelessness, helplessness, worthlessness, or guilt; and suicidal behavior, requests for physician-assisted death/euthanasia, a wish to end it all, or refusing care.

  • Depression can be affected by medications (e.g., chemotherapy, corticosteroids, interferon), physiologic factors (e.g., pain or other symptoms), and psychological factors (e.g., spiritual issues, feelings of burden, loss of control, physical impairment, poor social support). [55] Between 14% and 31% of patients with advanced disease have depression. [58]

  • Depression can be assessed using the following: Beck Depression Inventory, Geriatric Depression Scale, Zung Depression Scale, Cornell Scale for Depression in Dementia, or asking the patient "Are you depressed?" [32] [59]


  • Anxiety can be affected by medications (e.g., corticosteroids, psychostimulants, caffeine, alcohol, beta-agonists, theophylline), drug and/or alcohol withdrawal, delirium, depression, and insomnia. Approximately 70% of terminally ill patients have anxiety. [60]

  • Anxiety can be assessed using the Hamilton Anxiety Rating Scale.


  • Fatigue can be exacerbated by medications (e.g., chemotherapy, corticosteroids, interferon, anticholinergics, sedative-hypnotics, opioids, antihistamines), anemia, infection, hypercalcemia, hyponatremia, hypothyroidism, pain, depression, deconditioning, and sleep disruption. [61] Between 74% and 91% of patients with cancer are found to be fatigued. [53] [61] [62]

  • Fatigue may be assessed using the Multidimensional Assessment of Fatigue Scale, Multidimensional Fatigue Inventory, Fatigue Symptom Inventory, Visual Analog Scale, or Numerical Analog Scale.


  • Anorexia may be a result of medications (e.g., psychostimulants, antidepressants, chemotherapy, interferon), infection, depression, pain, nausea, mucositis, dysphagia, and odynophagia. Anorexia is observed in 62% to 76% of patients with cancer and 70% of patients with advanced cancer. [53] [63]

  • Anorexia may be assessed using the Functional Assessment Anorexia/Cachexia Therapy Scale (FAACT).


  • This is usually due to multifactor etiologies, including medications (e.g., analgesics, anticholinergics, antihistamines, sedative-hypnotics), pain [64] [65] or other symptoms, metabolic abnormalities (e.g., hypercalcemia, hyponatremia, hypernatremia, uremia), environmental factors (e.g., excessive stimuli, unfamiliar environment), and physiologic factors (e.g., dehydration, infection, urinary retention, constipation, hypoxia, and hypercarbia). [55] Delirium is observed in 60% of patients with cancer. [53] Delirium in the intensive care unit is identified in nearly one third of patients, associated with longer lengths of stay, increased mortality, and cognitive impairment after discharge. [66]

  • Delirium may be assessed using the Confusion Assessment Method, Confusion Assessment Method for the Intensive Care Unit, Delirium Assessment Scale, or Delirium Rating Scale.


  • Nausea may be caused by medications (e.g., opioids, chemotherapy, iron, digitalis, nonsteroidals), constipation, obstruction, pain, direct tumor effects, metabolic abnormalities (e.g., uremia, hypercalcemia), infection, and increased intracranial pressure. [55] Nausea is observed in 6% to 68% of patients with cancer. [53] [67]

  • Nausea may be assessed using the Visual Analog Scale.

Symptoms are usually not isolated but tend to occur in clusters. The Modified Edmonton Symptom Assessment Scale and the Memorial Symptom Assessment Scale are tools used to assess multiple symptoms.

Overview of treatment of the seriously ill patient

The role of the palliative care team is to incorporate the information from the detailed assessment and develop a treatment plan that matches the patient's goals of care, including expert symptom-specific control. Symptom management is complex because there are often multiple symptoms. General clinicians should seek advice or help from a specialist in palliative care when management is difficult.

Pain management

  • Pain is an unpleasant sensory and emotional experience that simply is "whatever the patient says it is". [68] [69] Pain is the most common reason patients seek health care. [70] Approximately 25 million Americans experience acute pain each year, with another 50 million experiencing chronic pain. Opioids are the mainstay of therapy for cancer pain. [71] There is evidence that opioids are also effective for noncancer pain. [72] [73] Opioids are more effective than placebo for nociceptive and neuropathic pain. [74] [75] [76]

  • Potentially reversible causes of pain should be identified. Nonpharmacologic interventions include: [68] [77] [78] [79] [80] [81] [82] [83] [84] [85]

    • Patient and family education

    • Self-help techniques

    • Cognitive-behavioral coping strategies

    • Music therapy

    • Complementary therapies (e.g., massage therapy, reflexology)

    • Physical exercise/therapy

    • Counseling

    • Addressing the psychosocial and spiritual issues.

  • The World Health Organization (WHO) analgesic ladder provides a stepwise approach to the use of analgesic drugs in cancer pain. [75] [84] [86] [87] Approximately 71% to 100% of patients can achieve pain control by following the WHO ladder guidelines. [75] The ladder starts with the use of nonopioid analgesics for mild pain, then weak opioids for moderate pain, and strong opioids for severe pain.

  • Each step can be complemented by the use of adjuvant pain medications. Near constant pain should be treated "by the mouth (given orally), by the clock (scheduled), by the ladder (WHO analgesic ladder)". [75] [84] [87]

  • No one opioid has been shown to have superior analgesic efficacy. [88] [89] [90] [91] [92] However, morphine is the preferred drug for moderate to severe pain, owing to its familiarity, low cost, and having been studied the most. [84] [87] [93] [94] [95] Immediate-release opioid preparations are normally scheduled every 4 hours, with additional breakthrough dosing that may be given up to every 1 hour as needed. [84] [86] [96] [97] [98] Steady state is reached within approximately 24 hours. Sustained-release opioid preparations can be started after the patient has been on stable doses of immediate-release formulas for approximately 48 hours. [75] When titrating opioids, the dose can be increased by 25% to 50% for mild to moderate pain and 50% to 100% for moderate to severe pain. [96] Sustained-release preparations can be titrated up after a minimum of 48 to 72 hours. [99]

  • The optimal dose of opioid is the dose that controls the patient's pain with the least amount of adverse effects. [86] [100]

  • Methadone has unique pharmacokinetics with dosing principles that do not apply to the above recommendations. Its use in patients for pain requires the assistance of a specialist experienced in the use of methadone. [77] [87]

  • Immediate-release opioids are used for breakthrough pain dosing. [96] Approximately 5% to 15% of the total 24-hour opioid requirement is used for the breakthrough dose. [96] The breakthrough dose can be offered once the peak analgesic effect has been reached. This is approximately 1 hour for oral opioids, 30 minutes subcutaneously, and 10 minutes by the intravenous route.

  • Opioids are primarily cleared by the kidneys. [96] The active metabolite of morphine, morphine-6-glucuronide, can accumulate in renal failure and lead to oversedation with respiratory depression. [84] [101] Hydromorphone and fentanyl are safer choices in renal failure.

  • Adjuvant analgesics are medications with a primary purpose other than treating pain but that also have analgesic properties. [77] They may be used alone or in combination with opioids to treat pain. Adjuvants are particularly useful in the management of neuropathic pain. [68] [102] Agents with the lowest adverse-effect profiles should be chosen first. Therapy should begin with the lowest possible dose and titrated up to effect.

  • Palliative radiation therapy and/or palliative chemotherapy may be used to decrease pain in selected patients with cancer. [84] [103]

  • Neuraxial analgesia can be considered for refractory malignant pain. [104]

Complications of opioid therapy

  • Constipation

    • Prevention and treatment of opioid-induced constipation is with laxatives (e.g., stimulant laxatives). Patients given scheduled opioids should receive scheduled laxatives. [86] [87] [103] [105]

  • Nausea and vomiting

    • Tolerance to opioid-induced nausea usually develops within 3 to 7 days. [86] Antiemetics, especially antidopaminergic antiemetics, are effective for opioid-induced nausea. [86] [87] [96]

  • Delirium

    • Tolerance to opioid-induced delirium may develop within 3 to 7 days. [86] Opioid rotation or lowering the dose of opioids with the use of adjuvant analgesics may improve symptoms of delirium. Low-dose haloperidol is effective in the pharmacologic management of opioid-induced delirium.

  • Sedation

    • Tolerance to opioid-induced sedation usually develops within 3 to 7 days. [86] Psychostimulants (e.g., methylphenidate) can be used to counteract persistent opioid-induced sedation. [86] [87] [96]

  • Pruritus

    • Low doses of antihistamines can be used to counteract opioid-induced pruritus. [96]

  • Hyperalgesia and allodynia

    • Opioid-induced hyperalgesia occurs when a patient paradoxically becomes more sensitive to pain, usually seen with high-dose opioid therapy. [106]

    • Allodynia is pain evoked by stimuli that are not normally painful (e.g., the touch of a bed sheet). [106] This can be seen in patients being treated for intractable pain with high and escalating opioid doses. The mechanism is not well understood but is thought to involve neuroadaptive changes of the nervous system leading to a pronociceptive upregulation. [100] [106] Lowering the opioid dose by rotating opioids or using adjuvant analgesics can improve these symptoms. [107] [108]

  • Respiratory depression

    • Tolerance to respiratory depression develops over time. Temporarily holding the opioid and lowering the dose may be all that is needed in mild cases of respiratory depression. Diluted naloxone titrated to patient response may be used in more severe cases. [84] [86]

  • Myoclonus

    • Low-dose benzodiazepines can be used to treat myoclonus due to opioids. [86]

  • Dry mouth

    • Preventive measures for dry mouth include good oral hygiene, sugar-free chewing gum, ice chips, and saliva substitute.

  • Urinary retention

    • This is usually relieved by itself but intermittent straight catheterizations or a temporary Foley catheter may be necessary in more extreme cases.

Nonopioid analgesics

  • Broad classes of adjuvant analgesics include nonsteroidal anti-inflammatory drugs (NSAIDs), antidepressants, anticonvulsants, corticosteroids, and local anesthetics. [77] [84] [86] [103]

  • NSAIDs are effective in treating pain from soft-tissue inflammation, bone metastasis, serositis, and postoperative pain. [84] [86]

  • Corticosteroids, such as dexamethasone or methylprednisolone, are effective in treating pain from soft-tissue inflammation, visceral distention, nerve compression, increased intracranial pressure, and bone metastasis.

  • First-line therapy for neuropathic pain is gabapentin, pregabalin, and serotonin-noradrenaline reuptake inhibitors (SNRIs). [76] Tricyclic antidepressants (TCAs) are considered first-line therapy as well; however, they are limited by their adverse-effect profile. [84] Nortriptyline and desipramine are favored over amitriptyline owing to their lower adverse-effect profile. The combination of morphine and gabapentin has been found to be more effective in treating neuropathic pain than either agent alone. [109] Duloxetine is effective in treating chemotherapy-induced peripheral neuropathy. [110] Topical agents and botulinum toxin A are recommended for peripheral neuropathic pain only. [76]

  • Pain from bone metastasis can be treated with NSAIDS, [86] [111] [112] corticosteroids, [112] bisphosphonates, [112] [113] [114] [115] radiation therapy, and radioisotopes (e.g., strontium 89). [116] [117] [118] [119] Calcitonin does not decrease pain compared with placebo. [120] Multiple-fraction (30 Gy) radiation therapy and single-fraction radiation therapy had similar improvements in pain control. [116] [121] [122] Adding strontium 89 to radiation therapy produced complete pain relief. [111] [118] Single-fraction radiation (8 Gy) therapy should be considered and is recommended as the standard of care, rather than multifraction radiation therapy regimens, for the palliation of painful bone metastasis and/or for the prevention of morbidity. [119] [123] [124] [125] A response rate of about 45% can be expected in patients who receive palliative radiation therapy for painful bone metastasis in the last 12 weeks of life, which is lower than that found in patients with a longer life expectancy. [123]

  • There is strong evidence to treat cancer pain with NSAIDs, opioids, radionuclides, and radiation therapy. [126] [127] There is less consistent evidence to treat cancer pain with bisphosphonates. There is no evidence addressing pain management in patients with advanced heart failure or dementia.


  • Potentially reversible causes of dyspnea should be identified.

  • Using fans or cool ambient temperature, eliminating respiratory irritants, avoiding excess fluids, using relaxation techniques, breathing control, neuro-electrical muscle stimulation, chest wall vibration, walking aids, reflexology, acupuncture, optimizing patient body position, and considering placing the patient near a window can all lessen the sensation of dyspnea. [32] [55] [83] [103] [128] [129]

  • First-line therapy for symptomatic control of dyspnea is opioids. [32] [56] [126] [127] [129] [130] [131] Opioids decrease dyspnea given by the oral or parenteral route. [56] [129] [132] [133] Nebulized opioids are either no more effective than placebo [56] [129] [130] [133] [134] or are equivalent to the oral or subcutaneous route. [126] [127] [132] Evidence is strong for the use of opioids in treating dyspnea for patients with COPD and weak for patients with cancer, and no evidence has addressed dyspnea management in patients with advanced heart failure. [126] [127] [135] [136]

  • Oxygen therapy can reverse hypoxemia but not necessarily dyspnea. Giving oxygen to cancer patients with and without hypoxemia improved oxygen saturations, with no significant difference in dyspnea when oxygen versus air was given. [137] Supplemental oxygen did not provide additional symptomatic relief compared with room air for patients with refractory dyspnea due to life-limiting illness. [138] In nonhypoxemic cancer patients, there was no significant difference between supplemental oxygen and air in decreasing dyspnea during exercise. [139] The evidence to support the use of oxygen therapy for dyspnea in cancer patients is weak. [126] [127] However, there is strong evidence to support the use of oxygen therapy for dyspnea during exercise in patients with COPD. [126] [127] [140] Simply having air blowing across the face can improve the sensation of dyspnea. [22] [129]

  • For patients with COPD, there is strong evidence to support the use of beta-agonists to treat dyspnea and the use of pulmonary rehabilitation to treat dyspnea during exercise. [126] [127]

  • Using anxiolytics in the treatment of dyspnea is not well established. Alprazolam did not improve dyspnea in COPD patients at rest or with exertion. [141] There is no overall beneficial effect of benzodiazepines for the relief of dyspnea in patients with advanced cancer and COPD. [142] However, adding midazolam to morphine in end-stage cancer patients with life expectancy of <1 week and severe dyspnea improved reports of dyspnea. [143]

  • In a Cochrane review of nonpharmacological interventions, the authors concluded that breathing training, walking aids, neuro-electrical muscle stimulation, and chest wall vibration were effective in relieving breathlessness in advanced stages of disease. [128] There was a low strength of evidence to support the use of acupuncture/acupressure. [128]

  • The most common adverse effects of opioid therapy for dyspnea are nausea/vomiting and constipation. Respiratory depression is very rare and does not occur when opioids are titrated against the symptom and increased slowly, which is good practice. There is no evidence to support a higher risk of respiratory depression in the treatment of dyspnea with opioids. [144] [145]


Constipation can best be defined as the passage of hard, dry stools less frequently than the patient's usual bowel-habit pattern, rather than the number of stools per day or week. [146] Constipation tends to be multifactorial, with opioid-induced constipation a common symptom in patients with advanced illness.

  • Potentially reversible causes of constipation should be identified.

  • Offending medications should be stopped or minimized, toilet facilities made accessible, a bowel routine established, the gastrocolic reflex used, and fluid intake and activity should be encouraged if consistent with goals of care to avoid constipation. [55] [105] [147]

  • Laxatives accelerate laxation and are categorized into bulk-forming, osmotic, stimulant, lubricating, and detergent laxatives. No one laxative regimen has been shown to be superior to another. [148] However, using bulk-forming laxatives in palliative care is usually not recommended because they may exacerbate constipation in patients who are dehydrated or less mobile. [32] [149] [150]

  • Opioid-induced constipation is treated frequently with a stimulant laxative, such as senna, with or without a stool softener as an adjunct. [32] [147] [151] A low-quality study of constipation in cancer patients admitted to the hospital revealed that adding docusate to a senna protocol was less effective in inducing laxation than senna alone. [152] A randomized, controlled trial in hospice patients found no significant benefit of adding docusate to senna. [153] There is inadequate evidence assessing the effectiveness of docusate in laxation, [154] and, indeed, the use of docusate is not recommended by consensus recommendations for patients with advanced, progressive illness. [105]

  • Adding a second agent from a different laxative class, such as an osmotic laxative, can be considered if stimulant laxatives alone are not effective. More recently, research has looked at mu-opioid receptor antagonists in treating opioid-induced constipation. Methylnaltrexone does not cross the blood-brain barrier, acting predominantly on the gastrointestinal mu-opioid receptors. [146] The selective blockade of peripheral opioid receptors may relieve constipation without precipitating opioid withdrawal. Subcutaneous methylnaltrexone improved median time to laxation compared with placebo in patients with opioid-induced constipation on baseline laxative regimens, [148] [155] [156] and it should be considered for opioid-induced constipation for patients who have failed to respond to optimal laxative therapy. [87] [105] [157]

  • Suppositories, such as bisacodyl, and enemas, such as a mineral oil enema followed by a large-volume enema, can be used for more refractory constipation.

  • Adverse effects of laxatives include bloating, abdominal cramping, nausea, and diarrhea.


Depression is a general term with different subtypes involving a low mood state accompanied by various somatic, psychological, and cognitive symptoms. [58] Somatic symptoms, such as weight loss, fatigue, sleep disturbance, and loss of energy, are normally present at the end of life and are not reliable indicators of depression in terminally ill people. [158] [5] [32] [159] The psychological and cognitive symptoms of anhedonia, worthlessness, helplessness, hopelessness, and despair are more helpful in the diagnosis of depression at the end of life. [32]

  • Identify potentially reversible causes of depression.

  • Nonpharmacologic interventions include the use of cognitive therapies, behavioral therapies, psychotherapy, an interdisciplinary team approach, massage, aromatherapy, and music therapy. [32] [55] [82] [160] [161] [162] [163] [164]

  • Antidepressants and psychostimulants are first-line medications for the treatment of depression in advanced illness. [32] [58] [159] [165] There is no evidence for the superiority of treatment interventions in treating depressive disorders in patients with cancer and advanced illness. [164] [166] [167] Psychostimulants (e.g., methylphenidate) reduce symptoms of depression in the short term [168] and are recommended for patients with life expectancies of weeks or less. [32] [159] [166] Selective serotonin-reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) have been shown to improve depressive symptoms in patients with a life-limiting illness. [169] [170] For patients with longer life expectancies, SSRIs or serotonin-norepinephrine reuptake inhibitors (SNRIs) are recommended. [32] TCAs are considered second-line owing to the increased adverse-effect profile.

  • There is strong evidence to support the treatment of depression in cancer with TCAs and SSRIs. [126] [127] There is no evidence addressing depression management in advanced heart failure or dementia.

  • Adverse effects of psychostimulants include restlessness, loss of appetite, hypertension, tachyarrhythmias, and seizures. [61] Adverse effects of SSRIs and SNRIs include gastrointestinal intolerance, anxiety, headaches, anorexia, sexual dysfunction, hyponatremia, serotonin syndrome, and bleeding risk. [166] Adverse effects of TCAs include confusion, sedation, dry mouth, ileus, blurred vision, urinary retention, hyponatremia, orthostatic hypotension, and arrhythmias.


Anxiety is a general term encompassing multiple subtypes of anxiety disorders, arising frequently from a fear or panic state. Symptoms of anxiety and panic at the end of life have not been well studied. [81] [171] [172]

  • Identify potentially reversible causes of anxiety.

  • Nonpharmacologic interventions include cognitive therapies, behavioral therapies, psychotherapy, interdisciplinary team approach, music therapy, reflexology, massage, and aromatherapy. [60] [82] [83] [173]

  • There is insufficient evidence regarding the effectiveness of pharmacotherapy for anxiety in palliative care. [167] [174] [175] First-line medications for acute anxiety are short-acting benzodiazepines. [32] [173] Other considerations include antidepressants, antipsychotics, and buspirone.

  • Adverse effects of benzodiazepines include paradoxical agitation, sedation, and respiratory depression.


Fatigue is a multidimensional syndrome with 3 major components that interfere with usual function: generalized weakness, easy fatigability, and mental fatigue. [61]

  • Identify potentially reversible causes of fatigue.

  • Nonpharmacologic interventions include coping strategies, music therapy, reflexology, cognitive therapies, behavioral therapies, psychotherapy, exercise, and an interdisciplinary-team approach. [61] [160] [176] [177] [178] [179] [180] [181] [182]

  • Drug therapies for fatigue have had limited benefits. The most commonly used medications for fatigue are psychostimulants and corticosteroids. [61] Methylphenidate has shown improvement in fatigue in patients with cancer and with AIDS. [61] [62] [183] [184] [185] Long-acting methylphenidate did not improve reports of fatigue in cancer patients, but benefit was shown in a subset of patients with advanced cancer. [186] Inconclusive evidence exists for the efficacy of amantadine, pemoline, and modafinil in multiple sclerosis and for carnitine and donepezil in cancer-related fatigue. Limited data suggest that pemoline is effective in patients with HIV. [185] Corticosteroids (e.g., dexamethasone and methylprednisolone) may decrease fatigue temporarily in patients with cancer. [61] [62] [185] [187]

  • Hematopoietic growth factors (e.g., erythropoietin and darbopoietin) can improve fatigue in anemic cancer patients undergoing chemotherapy. [183]

  • Secondary agents with limited to no evidence in improving fatigue include progestational steroids, paroxetine, and testosterone. [62] [183]

  • Adverse effects of psychostimulants include restlessness, loss of appetite, hypertension, tachyarrhythmias, and seizures. [61] Adverse effects of corticosteroids include gastrointestinal intolerance, edema, anxiety, steroid psychosis, hyperglycemia, and hypertension; long-term adverse effects include immunosuppression, adrenal insufficiency, proximal muscle weakness, and osteoporosis.


The anorexia-cachexia syndrome is a syndrome involving the loss of appetite and involuntary weight loss, best described in cancer patients. [63]

  • Identify potentially reversible causes of anorexia.

  • Nonpharmacologic interventions include offering small, frequent meals; avoiding forced eating; controlling pain; and addressing accompanying social, psychological, and spiritual issues.

  • First-line drugs for the anorexia-cachexia syndrome are progestins and corticosteroids. [63] Megestrol and corticosteroids are equally effective as an appetite stimulant. The progestins megestrol and medroxyprogesterone increase appetite and weight in patients with cancer, but there is not enough evidence to support improved quality of life. [63] [188] The use of megestrol in older nursing home patients has been associated with increased mortality without a significant increase in weight. [189] The corticosteroids methylprednisolone, prednisolone, and dexamethasone increase appetite temporarily in patients with cancer. [63] [190]

  • There are insufficient data to support the use of the following medications in the anorexia-cachexia syndrome: cannabinoids, eicosapentanoic acid, metoclopramide, hydrazine sulfate, cyproheptadine, pentoxifylline, melatonin, erythropoietin, androgenic steroids, ghrelin, interferon, NSAIDs, and thalidomide. [61] [63] [178] [191]

  • There is no strong evidence to support the use of enteral nutrition in nonsurgical cancer therapy. [62] [192] [193] There is some evidence that net harm can be caused by the use of parenteral nutrition in cancer patients undergoing chemotherapy and radiation therapy. [62] [192]

  • No evidence for clinical benefit of nutritional supplementation has been demonstrated in a variety of clinical settings, including cancer and chronic lung or liver disease, palliative care, and critical-care settings. [32] [194]

  • There is no evidence that medically assisted hydration in palliative care patients improves clinical outcomes or lengthens survival. [194]

  • In one randomized, controlled trial of hospice patients with advanced cancer, parenteral hydration did not improve symptoms, quality of life, or survival. [195]

  • There is no evidence that artificial nutrition and hydration improves clinical outcomes in patients with advanced dementia. [32] [196] [197] [198] [199]

  • Feeding tubes are not recommended in patients with advanced dementia. Instead, hand feeding should be offered and is at least as good as tube feeding for the outcomes of death, aspiration pneumonia, functional status, and comfort. [200]

  • Tube feeding in advanced dementia is associated with agitation, greater use of physical and chemical restraints, greater healthcare use due to tube-related complications, and development of new pressure ulcers. [200]

  • Adverse effects of progestins include lower-extremity edema, venous thromboembolic disease, male impotence, and gastrointestinal intolerance. [188] Adverse effects of corticosteroids include gastrointestinal intolerance, edema, anxiety, steroid psychosis, hyperglycemia, and hypertension; long-term adverse effects include immunosuppression, adrenal insufficiency, proximal muscle weakness, and osteoporosis.


Delirium is an acute confusional state with a fluctuating course, accompanied by inattention and either disorganized thinking or altered level of consciousness. [201] [202]

  • Identify potentially reversible causes of delirium.

  • Medications are the most common cause of delirium in patients admitted to the hospital. [55] Discontinue all nonessential medications, encourage gentle reorientation, familiarize the environment, minimize excessive environmental stimuli, optimize the sleep-wake cycle, avoid sleep deprivation, and use sensory aids (e.g., glasses, hearing aids, dentures) to minimize the risk of delirium. [55] [203]

  • Multicomponent interventions, a series of nonpharmacologic strategies, can significantly reduce the risk of incident delirium among hospitalized older patients. [167]

  • Treat underlying pain [64] [65] or other symptoms because these may be contributing frequently to delirium.

  • There is insufficient evidence regarding the role of pharmacotherapy in the management of delirium in terminally ill people. [204] The general consensus of delirium management is low-dose haloperidol for first-line medication therapy. [32] [202] [203] [204] [205] [206] There is no evidence that low-dose haloperidol (<3 mg per day) has more adverse drug effects than the atypical antipsychotics olanzapine and risperidone in the management of delirium. [207] High-dose haloperidol (>4.5 mg per day) has greater extrapyramidal adverse effects than the atypical antipsychotics. The atypical antipsychotics have been associated with increased risk for death in delirium-complicating dementia. [202] [208] Conventional antipsychotics are at least as likely as atypical antipsychotics to increase the risk of death in older patients. [209] One small study in patients with advanced acquired immunodeficiency syndrome revealed that haloperidol and chlorpromazine are equally effective in managing delirium. [204] The lorazepam arm was terminated early secondary to excessive sedation.

  • Chlorpromazine may be used when a more sedating effect is needed in agitated delirium. Benzodiazepines are used frequently as second-line agents, with a lack of data supporting their use. [210]

  • Patients with advanced cancer experiencing hypoactive delirium may benefit from methylphenidate. [211]

  • Adverse effects of antipsychotics include extrapyramidal effects, akathisia, neuroleptic malignant syndrome, QTc prolongation, and sedation. A baseline ECG to evaluate the QTc interval should be obtained in patients initiated on antipsychotics who have cardiac risk factors for arrhythmias, when consistent with their goals of care. [212] Adverse effects of benzodiazepines include paradoxical agitation, sedation, and respiratory depression.


Nausea is the subjective, unpleasant sensation of needing to vomit. [150] [213] Vomiting is a neuromuscular reflex that results in the forceful expulsion of gastric contents through the mouth. The vomiting center in the medulla of the brain is thought unlikely to exist as a discrete structure. An area of loosely organized neurons in the medulla is believed to coordinate the emetic reflex and has been termed the central pattern generator. [213]

There are 4 main pathophysiologic mechanisms and neurotransmitters that mediate the central pattern generator: chemoreceptor trigger zone (serotonin, dopamine, acetylcholine, histamine), gastrointestinal system (serotonin, acetylcholine), vestibular apparatus (histamine, acetylcholine), and cerebral cortex (learned responses, pressure receptors). [150]

Using drugs that focus on a mechanism-based approach can be effective in relieving nausea and vomiting in 80% to 90% of patients at the end of life. [151] The neurotransmitters serotonin (5-HT 3), dopamine, and substance P seem to be particularly important in mediating chemotherapy-induced nausea. [213] Opioid-induced nausea is mediated largely by dopamine. [151]

  • Identify potentially reversible causes of nausea.

  • Nonpharmacologic interventions include minimizing or discontinuing offending medications; using distraction, visualization, relaxation techniques, and/or music therapy; offering small, frequent meals with bland food; controlling pain; and addressing accompanying social, psychological, and spiritual issues. [55] [214]

  • Combination therapy with a serotonin antagonist, dexamethasone, and aprepitant is recommended for acute nausea from chemotherapeutic agents of high and moderate emetic risk. [215] The addition of olanzapine may improve symptoms and quality of life. [216]

  • Nausea from opioids or multiple etiologies is best treated by targeting the dopamine (D2) receptor with medications, such as metoclopramide, prochlorperazine, or haloperidol. [87] [151] [217] [218] [219]

  • Refractory nausea should be treated with multiple agents that target different neurotransmitter receptors scheduled around the clock.

  • Adverse effects of serotonin receptor antagonists include headache, constipation, fatigue, and dry mouth. [151] Dopamine receptor antagonists can be associated with extrapyramidal symptoms and akathisia. Anticholinergics and antihistamines can lead to confusion, sedation, dry mouth, ileus, blurred vision, and urinary retention.

Tools to document advance-care planning

Advance-care planning is the process by which patients communicate and document treatment preferences and guide their medical care through periods of decisional incapacity. [220] Advance directives are tools meant to facilitate end-of-life decision making based on patients' goals of care. [221] Understanding patients' end-of-life treatment preferences promotes patient autonomy and dignity while avoiding unwanted therapies. Despite their importance, advance directives are used rarely. Approximately 25% of patients complete written advance directives, of whom only approximately 25% actually discuss them with their physicians. [222] Over 70% of seriously ill patients have never discussed advance directives with their physicians. [223] Less than half of seriously ill patients with cancer admitted to the hospital have an advance directive. [224] The multicenter SUPPORT study revealed that only 47% of physicians knew when their patients preferred do-not-attempt-resuscitation (DNAR) status. [11]

End-of-life wishes are more likely to be honored with advance-care planning in older patients. [225] [226] Patients who completed an advance directive spent fewer days in the hospital in the last year of life and had lower hospital costs. [227] Advance care planning has been shown to reduce the relative risk of ICU admission for patients at high risk of death by 37%. [21] In patients receiving dialysis, advance care planning was associated with improvements in patient-surrogate preparation for end-of-life decision making. [228] In addition, family members of patients who died had lower levels of stress, anxiety, depression, and post-traumatic stress disorder when the patient had advance care planning. [228] The legal requirements for each country will differ. In some countries, the following provisions are available:

Medical living will

  • Documents patients' wishes prospectively regarding initiating, withholding, and withdrawing certain life-sustaining medical interventions. Becomes effective when a patient lacks decisional capacity.

Cardiopulmonary resuscitation (CPR) directive

  • Documents wishes to refuse unwanted resuscitation attempts and ensures the likelihood that emergency medical services are aware of those wishes.

Medical durable power of attorney (MDPOA)

  • Documents an appointed "agent" to make future medical decisions, effective when the patient becomes incapacitated.

Medical proxy decision maker

  • Documents a decision maker to make future medical decisions under the substituted judgment standard effective when the patient becomes incapacitated and does not have an MDPOA. Most states use a hierarchy system to designate a medical proxy, whereas a few states appoint a medical proxy that is agreed on by all interested parties.


  • Documents a court-appointed decision maker to make future medical decisions for a patient who is incapacitated. This process is usually done as a last resort when there is no MDPOA or medical proxy decision maker.

Physician Orders for Life-Sustaining Treatment (POLST) [229]

  • Order set that translates patient preferences for life-sustaining therapies into medical orders.

  • Primarily intended for seriously ill people with life-limiting or terminal illnesses.

  • Portable and transferable between healthcare settings.

  • Patients with POLST forms are more likely to have treatment preferences documented and honored. [21] [230] [231] [232] [233] [234] [228]

Tools to facilitate advance-care planning discussions: [235] [236]

Palliative sedation and physician-assisted death

Palliative sedation therapy (PST)

  • Despite aggressive, high-quality palliative symptom management, some patients develop symptoms that are refractory to standard therapies. PST can relieve such refractory symptoms, which cause intractable suffering at the very end of life.

  • PST is a procedure in which sedative medications are given to reduce consciousness in a terminally ill patient, to relieve intolerable suffering from refractory symptoms. [237] [238] [239] [240]

  • Sedation is used as an option for symptom control, titrated carefully to the cessation of symptoms and not for the purpose of euthanasia. [239] [240] Symptoms are considered refractory when further interventions are not capable of providing relief, are associated with unacceptable morbidity, and/or are unlikely to provide relief within a reasonable time frame. [237] [238] [239] [240]

  • Professional consensus supports the use of PST for refractory symptoms in the following situations: when severe, intolerable physical symptoms (e.g., pain, agitated delirium, nausea/vomiting) are refractory to aggressive symptom-specific interventions; when the patient is in the final stages of the dying process; when a do-not-attempt-resuscitation (DNAR) order is completed and the patient (or surrogate if the patient lacks decision-making capacity) has given informed consent. [237] [239] [240]

  • The most frequent reasons for providing PST are delirium (55%), dyspnea (27%), pain (18%), and nausea/vomiting (4%). [239] [240] Using PST for the relief of psychological and existential suffering alone is controversial and not accepted widely in practice. [237] [238] [239] [240]

  • PST is supported by the principle of double effect, which states that it is acceptable to use medications in the setting of terminal illness that may foreseeably, but unintentionally, hasten the moment of death when the intent is to relieve suffering. [241] The principle distinguishes between the intention with which an action is performed and the consequence it may produce, distinguishing between an intended (good) effect and an unintended (bad) effect of an intervention. The nature of the intervention must be good or morally neutral; the intent is the good effect, even though the bad effect may be foreseen; the good effect is not brought about as a means of the bad effect; and the good effect must outweigh the bad effect (principle of proportionality). [238] [239] [241] Under the principle of proportionality, the risk of causing harm must be related directly to the danger and immediacy of the patient's clinical situation and expected benefit of the intervention. [237]

  • Medications used for PST include anxiolytic sedatives (e.g., midazolam, lorazepam), sedating neuroleptics (e.g., chlorpromazine, levomepromazine), barbiturates (e.g., phenobarbital), and general anesthetics (e.g., propofol). [239] Midazolam is the most frequently used sedative for PST and has the additional benefit of anxiolytic, antiepileptic, muscle-relaxant, and amnestic properties. [239] [241] [242] [243] [244] The dose of sedative should be titrated individually to the relief of the symptom. Deep, continuous sedation is not always necessary for symptom relief. Sedatives may be given intermittently (potentially providing periods of alertness) or continuously (providing constant sedation). [239] There is no evidence that giving sedation proportionally shortens life. [239] [242] [245]

Physician-assisted death (PAD) and euthanasia

  • In PAD, the physician provides the means for death and the patient performs the act. [240] [246] In euthanasia, the physician performs the act that results in death. PAD and euthanasia are not supported by the principle of double effect or the principle of proportionality. [237] [238] [239] [240] [241]

    In PST, the intent is to relieve the patient's suffering, with death resulting from the underlying disease process. The aim of PST is not to hasten death. In PAD and euthanasia, the intent is to cause the patient's death, with death used as the means to relieve suffering. In 1997, the US Supreme Court distinguished PST from PAD as a legally acceptable practice through its rulings in Vacco v. Quill and Washington v. Glucksberg. [237] [241]

    On October 27, 1997, the state of Oregon approved the Death with Dignity Act. [247] This Act permits terminally ill Oregonians to end their lives through the voluntary self-administration of lethal medications, specifically prescribed by a physician for that sole purpose. PAD is currently legal in the states of Oregon, Washington, Montana, Vermont, New Mexico, and California. Euthanasia is not legal in any state.


Several professional bodies have produced evidence-based guidelines with recommendations for clinical care in the palliative care setting. Furthermore, information is available from specialty bodies. [American Academy of Hospice and Palliative Medicine] [National Consensus Project for Quality Palliative Care] [248] [249] [250] [251] [252] [253] [254] [255] [256]

National Consensus Project for Quality Palliative Care. Clinical practice guidelines for quality palliative care; 2004. [257]

  • Palliative care services aim to support patients of all ages with debilitating and life-threatening illness and their families through the full course of illness, regardless of its duration, until cure or until death and through the bereavement period.

  • Palliative care is delivered through skilled and interdisciplinary attention to pain and other distressing symptoms; emotional, spiritual, and practical support; assistance with complex medical decision making; and coordination across the continuum of healthcare settings.

  • The goal is to help the patient and family achieve the best possible quality of life in accordance with their values, needs, and preferences.

National Consensus Project for Quality Palliative Care. Clinical practice guidelines for quality palliative care, third edition; 2013. [258]

  • This revision places an emphasis on continuity, consistency, and quality of care.

National Quality Forum. A national framework and preferred practices for palliative and hospice care quality; 2006. [259]

  • Consensus report that provides a framework for palliative and hospice care upon which a quality measures and reporting system should be built.

  • Discusses the 38 preferred practices designed to improve and standardize the clinical practice of palliative and hospice care.

  • The preferred practices are in line with the Institute of Medicine's 6 dimensions of quality (safe, effective, timely, patient-centered, efficient, and equitable), and encompass 8 domains of quality care:

    • Structures and processes of care

    • Physical aspects of care

    • Psychological and psychiatric aspects of care

    • Social aspects of care

    • Spiritual, religious, and existential aspects of care

    • Cultural aspects of care

    • Care of the imminently dying patient

    • Ethical and legal aspects of care.

Institute for Clinical Systems Improvement. Palliative care; 2013. [32]

  • Palliative care planning should begin early in the care of patients with progressive, debilitating illness.

  • Healthcare providers should initiate palliative care discussions with their patients.

  • Healthcare providers should clarify and document patients' goals of care and advance directives.

  • Physical and nonphysical suffering is common in this patient population.

  • Addressing suffering depends on the quality of communication with patients and families. Establishing realistic goals of care and providing realistic hope are essential to providing good-quality care. [260]

  • Palliative care can be delivered simultaneously with aggressive interventions and an increased focus on symptom management.

  • Healthcare providers play an important role in the grief and bereavement processes.

AAHPM Choosing Wisely Task Force. Five things physicians and patients should question in hospice and palliative medicine; 2013. [261]

  • Do not recommend percutaneous feeding tubes in patients with advanced dementia; instead, offer oral-assisted feeding.

  • Do not delay palliative care for a patient with serious illness who has physical, psychological, social, or spiritual distress because he or she is pursuing disease-directed treatment.

  • Do not leave an ICD activated when it is inconsistent with the patient/family goals of care.

  • Do not recommend more than a single fraction of palliative radiation for an uncomplicated painful bone metastasis.

  • Do not use topical lorazepam, diphenhydramine, and haloperidol ("ABH") gel for nausea.

The Scottish Palliative Care Guidelines. End of life care; 2014. [262]

  • Consensus guidelines on the management of adult patients with life-limiting illness.

  • Reviews pain and symptom management, palliative emergencies, end-of-life care, medicine information, and patient information.

The National Comprehensive Cancer Network has produced a range of guidelines relevant to palliative care:

American Society of Clinical Oncology. Statement: Toward individualized care for patients with advanced cancer; 2011. [26]

  • Supports tailoring care to the diverse physical, psychological, social, and spiritual effects of cancer for the individual patient.

  • Advocates improved communication with and decision making for patients with advanced cancer.

  • The paradigm of advanced cancer care should focus on individualized care achieved through an earlier and more thorough assessment of patient's options, goals, and preferences.

American Society for Radiation Oncology. Palliative radiotherapy for bone metastases: an ASTRO evidence-based guideline; 2011. [119]

  • External-beam radiation therapy is the mainstay for the treatment of painful, uncomplicated bone metastases.

  • Single-fraction radiation therapy produces equivalent responses to pain and/or the prevention of morbidity compared with multiple-fraction radiation therapy regimens, with no difference in rates of long-term side effects.

  • Single-fraction radiation therapy optimizes patient and caregiver convenience at the expense of higher repeat treatment rates.

  • The use of surgery, radionuclides, bisphosphonates, or kyphoplasty/vertebroplasty does not obviate the need for external-beam radiation therapy.

European Society for Medical Oncology. Clinical Practice Guidelines on palliative care: advanced care planning; 2014. [268]

  • Topics of advance care planning: do not resuscitate or allow natural death legal orders, medical treatment, symptom management, end-of-life decisions.

  • Discussing advance care planning: establish an appropriate setting, discuss the topic, respond to emotion, establish and implement the plan.

  • Complete advance care planning-specific documents; review and update regularly.

  • Legal and ethical considerations.

Evidence-based interventions to improve the palliative care of pain, dyspnea, and depression at the end of life: a clinical-practice guideline from the American College of Physicians; 2008. [126]

  • Strong recommendations with moderate quality of evidence (in patients with serious illness at the end of life):

    • Clinicians should regularly assess patients for pain, dyspnea, and depression.

    • Clinicians should use therapies of demonstrated effectiveness to manage pain. Management includes nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and bisphosphonates in patients with cancer.

    • Clinicians should use therapies of demonstrated effectiveness to manage dyspnea. Management includes opioids for dyspnea and oxygen for short-term relief of hypoxemia.

    • Clinicians should use therapies of demonstrated effectiveness to manage depression. Management includes tricyclic antidepressants, selective serotonin-reuptake inhibitors, or psychosocial intervention for patients with cancer.

  • Strong recommendations with low-quality evidence:

    • For all patients with serious illness, clinicians should ensure that advance-care planning occurs, including the completion of advance directives.

American College of Chest Physicians. Palliative and end-of-life care for patients with cardiopulmonary diseases: American College of Chest Physicians position statement; 2005. [72]

  • The American College of Chest Physicians strongly supports palliative and end-of-life care as an integral part of cardiopulmonary medicine for patients with acute devastating or chronically progressive pulmonary or cardiac disease. This care should be delivered through an interdisciplinary approach.

  • The focus of palliative and end-of-life care for patients with cardiopulmonary disease is to provide support for the patient and family, care of the patient, and responsibility of the professional caregiver.

American Thoracic Society. An official American Thoracic Society clinical policy statement: palliative care for patients with respiratory diseases and critical illnesses; 2008. [269]

  • The American Thoracic Society (ATS) strongly endorses the integration of palliative care throughout a patient's illness trajectory and individualized therapy based on the patient's goals of care.

  • The ATS recommends that clinicians obtain basic competencies in palliative care and should consult palliative care specialists when managing palliative care situations that are beyond the clinician's level of competence.

  • The ATS supports hospice care as an effective interdisciplinary system to provide palliative care to the patient unit.

American College of Critical Care Medicine. Recommendations for end-of-life care in the intensive-care unit: a consensus statement by the American College of Critical Care Medicine; 2008. [270]

  • Knowledge and competence in end-of-life care is an emerging and necessary skill for critical-care physicians. Family-centered care is the basis for comprehensive end-of-life care in the ICU. The emphasis is on standards for decision making, resolution of conflict, and communication with families.

  • ICU physicians should be competent in the different aspects of withdrawing life-sustaining therapies, including an understanding of the underlying ethical principles, the practical aspects of the procedure, and medications for symptom management.

  • After the death of the patient, end-of-life skills continue with death notification, organ donation, and bereavement needs of the family and interdisciplinary team.

National Association of Neonatal Nurses. Position statement 3051: palliative care for newborns and infants; 2010. [271]

  • Palliative care should be offered at any period in which the infant's life may be limited.

  • Education on palliative care should be provided to parents in the neonatal intensive care unit.

  • Neonatal intensive care units should have a relationship with a local hospice or palliative care program to offer seamless continuity of care.

American Thoracic Society, American Association for Critical Care Nurses, American College of Chest Physicians, European Society for Intensive Care Medicine, and Society of Critical Care Medicine. An official ATS/AACN/ACCP/ESICM/SCCM policy statement: responding to requests for potentially inappropriate treatments in intensive care units; 2015. [272]

  • Organisations should implement strategies to prevent intractable treatment conflicts, including proactive communication and early involvement of expert consultants.

  • The term "potentially inappropriate" should be used, rather than "futile," to describe treatments that have at least some chance of accomplishing the effect sought by the patient, but for which clinicians believe that competing ethical considerations justify not providing them.

  • The term "futile" should be restricted to the rare situations in which surrogates request interventions that simply cannot accomplish their intended physiologic goal. Clinicians should not provide futile interventions.

  • Clinicians should explain and advocate for the treatment plan they believe is appropriate.

  • Conflicts regarding potentially inappropriate treatments that remain intractable despite intensive communication and negotiation should be managed by a fair process of conflict resolution; this process should include hospital review, attempts to find a willing provider at another institution, and opportunity for external review of decisions.

  • When time pressures make it infeasible to complete all steps of the conflict resolution process and clinicians have a high degree of certainty that the requested treatment is outside accepted practice, they should seek procedural oversight to the extent allowed by the clinical situation and need not provide the requested treatment.

  • The medical profession should lead public engagement efforts and advocate for policies and legislation about when life-prolonging technologies should not be used.

Disease-specific position statements are available for certain illnesses, including:

  • Cancer: Multinational Association of Supportive Care in Cancer; 2010 [273]

  • Lung cancer: American College of Chest Physicians; 2013 [274]

  • Melanoma: Australian Cancer Network Melanoma Guidelines Revision Working Party; 2008 [275]

  • Heart failure: Royal Australian College of General Practitioners; 2010 [276]

  • Stroke: American Heart Association/ American Stroke Association; 2014 [277]

The Cochrane Collaboration has produced a systematic review on end-of-life care pathways, with insufficient data at present to make recommendations. [255]

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