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Palliative care is specialised medical care for people with serious illness that focuses on achieving the best quality of life for both the patient and their family or carers.[1][2] Palliative care provides patients with relief from the symptoms, pain, and stress of a serious illness - whatever the diagnosis. Palliative care uses an interdisciplinary approach; the interdisciplinary team consists of doctors, nurses, and other specialists to provide support as needed. Palliative care is appropriate at any age and at any stage in a serious illness, and can be given alongside disease-directed or curative treatment.
Hospice is a philosophy of care that focuses on the palliative care needs of patients and their families or carers, 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 principles and basic skill sets 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 serious illness with anticipated life expectancy of 6 months or less.
Palliative care addresses the physical, psychological, social, and spiritual issues of a patient's disease process. It may be defined as patient- and family-centred care that optimises 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. 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 the existing medical care. Outpatient palliative care has been shown to improve quality of life, improve symptom control, decrease accident and emergency department visits and hospital admissions, improve survival, and lower medical costs.[3]
The 2015 to 2017 estimated life expectancy at birth in the UK is 79.2 years for males and 82.9 years for females, similar to those for the European Union as a whole and for the US.[4] Advancements in public health and technology have modified the leading causes of death to be the end result of chronic illnesses. In England and Wales over 230,000 people develop cancer each year, and cancer accounts for one quarter of all deaths.[5] In the US, the leading causes of death in 2017 were heart disease, cancer, unintentional injuries, and chronic lower respiratory diseases. Globally, the leading causes of death in 2015 were heart disease, stroke, lower respiratory tract infections, and chronic obstructive pulmonary disease.[6]
The older population is growing at a rate faster than that of the world's total population.[7] 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.[8] The ageing population poses unique socio-economic consequences worldwide. A new challenge, as outlined by the United Nations, will be "to ensure that persons everywhere are able to age with security and dignity and to 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 multi-centre 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.[10] Despite >50% of patients dying in hospital, 49% to 100% of patients and 63% of carers state that home is the preferred place of death.[10][11] 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.[10] Families of patients who have died have rated the quality of end-of-life care to be lower in 2011-2013 relative to 2000.[12] Routine palliative care-led support and information team meetings in the intensive care unit (ICU) setting may not be helpful regarding symptoms of depression and anxiety in families of patients with chronic critical illness.[13]
The 2014 Institute of Medicine 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 emphasises 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 5 areas:
Delivery of person-centred, 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 utilisation.[15][16][17][18][19][20][21][22][23] Avoidance of intensive care admission is also pertinent if in keeping with the goals of the patient and their family.[24] There is also emerging evidence for the role of palliative care for surgical patients.[25] 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.[26] Home palliative care services decrease symptom burden and increase the chance of dying at home for patients with cancer.[27][28][29]
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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.[30] Initiating palliative care earlier on in cancer care has also been shown to improve survival.[31][32] 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.[33][34]
In the UK, the Gold Standards Framework (GSF) was developed to support general practitioners and district nurses in delivering quality palliative care.[35] The GSF focuses around the '7 Cs' of communication, coordination, control of symptoms, continuity, continued learning, carer support, and care of the dying.
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).[36] Not only were physicians over-optimistic, but they also over-estimated survival by a factor of 5.3. Factors that decreased prognostic accuracy were less-experienced physicians and longer duration of doctor-patient relationship. Over-optimistic 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 over-optimistic survival prospects.[37][38] 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.[39] In the cancer population, some studies have shown that asking "Would I be surprised if this patient died in the next year?" identifies patients who are at greatly increased risk of 1-year mortality; however, one systematic review found that the surprise question was a poor to modest predictive tool for death.[40][41][42]
Prognosis is often communicated by providing a time range that encompasses average life expectancy (i.e., hours-days, days-weeks, weeks-months, months-years).[43] 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.[44] These include:
Palliative Performance Scale (PPS): initial PPS score on admission to a hospice palliative care unit predicts survival, including for patients admitted to hospital with palliative care consults.[45][46] PPS is significantly associated with hazard of death in ambulatory cancer patients.[47]
Palliative Prognostic Score (PaP): PaP scores of patients admitted to hospital with palliative care consults predict survival, including for patients admitted to hospital with exclusively non-cancer diagnoses seen by a palliative care service.[48][49]
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 hospital.[50]
CARING criteria: 5 prognostic indicators (cancer as the primary diagnosis, 2 or more admissions to hospital in the past year for a chronic illness, residence in a nursing facility, ICU admission with multi-organ failure, 2 or more non-cancer hospice guidelines) identified on hospital admission predict risk of death in 1 year.[51][52]
Prognostigram: patient-specific prognostic tool for adult cancer patients that generates patient-unique survival curves.[53] Washington University in St Louis: Prognostigram Opens in new window
Determining a patient's goals of care (value-based priorities) is the key principle underlying palliative medicine.[54] An 8-step protocol to elicit goals of care is a helpful tool for this process.[55][56]
Create the environment
Secure a place where you can sit down, have privacy, and minimise interruptions. It is essential to be able to listen to the patient throughout the palliative care process. Depending on an individual patient's circumstances and choice, discussion may be with the patient alone or in the company of selected people such as partner, other family member, or carer.
All discussion should proceed at a pace tailored towards a patient's own needs. For some patients goals of care can be established in one discussion. Others may require subsequent conversations.
Explore the patient’s story
Facilitate the patient and family in verbalising the patient’s story ('non-medical'), to learn more about their values and priorities in life. Discuss what brings the greatest value, meaning, and joy to the patient's life.
Determine what the patient and family know
Clarify up front 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, worries, and support systems are
As you unweave the patient’s story, enquire about the hopes, worries, and concerns of the patient and family. Enquire as to where the patient’s inner strengths arise from, and about the patient’s and family’s support systems.
Offer realistic goals and discuss options to achieve those goals
Set goals before determining the treatment plan. 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. 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, summarise, document, communicate, and follow through
Establish a plan for the next steps (e.g., where you go from here). Summarise 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.[57]
The Royal College of Physician’s ‘Talking about dying report’ seeks to offer advice and support for any doctor on holding conversations with patients much earlier after the diagnosis of a progressive or terminal condition, including frailty.[58]
A comprehensive palliative care assessment enables an individualised care plan to be prepared.[59] A key part of the assessment is to prioritise the patient's and family's concerns and problems. However, it should be recognised 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) Opens in new window Alberta Health Services: Edmonton Symptom Assessment System Revised Opens in new window
Assessment should include the following:
History of illness
Review the patient's disease course, including the primary illness and pertinent secondary diagnoses. Summarise the previous treatments and patient's response.
Physical symptoms
Physical assessment is best organised by symptoms and functional activities, rather than by organ system. The physical examination 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
Enquire 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
Enquire about personal meaning and value of the patient's life and illness, faith, religious denomination, and desired pastor services.
Practical needs
Determine carer, dependent, domestic, and residential needs, and how these 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.
Patients with advanced illness can be categorised 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.[60] While simplistic (and with the caveat that not all patients will conform to a specific trajectory), these remain useful models to consider for patients with such illness.
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.[61]
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.
Pain
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-localised pain that is stabbing, throbbing, or aching. Visceral pain involves organs, is not well localised, 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.[62]
Pain can be assessed using the following scales: Numerical Analogue Scale, Visual Analogue Scale, Verbal Descriptive Scale, Face Scale, FLACC (Face, Legs, Activity, Cry, and Consolability) Scale, Modified FLACC Tool, and PABS (Pain Attitudes And Beliefs) Scale.[63]
Dyspnoea
This can arise from multiple aetiologies, including COPD, asthma, pneumonia, pleural or pericardial effusions, pulmonary oedema, pulmonary embolism, anaemia, ascites, acidosis, hypoxia, hypercapnia, and anxiety.[64] Dyspnoea is observed in 21% to 90% of patients with cancer.[65]
Dyspnoea can be assessed using the following scales: Borg Scale, Functional Dyspnoea Scale, Number Counting, and Visual Analogue Scale.
Constipation
This may be caused by medications (e.g., opioids, anticholinergics, iron, antihypertensives), metabolic abnormalities (e.g., hypercalcaemia, hypothyroidism), gastrointestinal aetiologies (e.g., bowel obstruction, tumour, anal fissures, haemorrhoids), neurological 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).[64] Constipation occurs in 35% to 65% of patients with cancer[62] and 15% to 90% of patients with opioid-induced constipation for non-cancer pain.[66]
Constipation can be assessed using either the Modified Constipation Assessment Scale or the Patient Assessment of Constipation Tool.
Depression
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 behaviour, 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), physiological 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).[64] Between 14% and 31% of patients with advanced disease have depression.[67]
Depression can be assessed using the following: Beck Depression Inventory, Geriatric Depression Scale, Zung Depression Scale, Cornell Scale for Depression in Dementia, Hospital Anxiety and Depression Scale.[68][69] [ Geriatric Depression Scale Opens in new window ]
Specific questions to the patient may also be used. For example, "During the last month, have you been bothered by feeling down, depressed, or hopeless?", "During the last month, have you been bothered by having little interest or pleasure in doing things?", or "Are you depressed?"[39][69]
Anxiety
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.[70]
Anxiety can be assessed using the Hamilton Anxiety Rating Scale.
Fatigue
This can be exacerbated by medications (e.g., chemotherapy, corticosteroids, interferon, anticholinergics, sedative-hypnotics, opioids, antihistamines), anaemia, infection, hypercalcaemia, hyponatraemia, hypothyroidism, pain, depression, deconditioning, and sleep disruption.[71] Between 74% and 91% of patients with cancer are found to be fatigued.[62][71][72]
Fatigue may be assessed using the Multidimensional Assessment of Fatigue Scale, Multidimensional Fatigue Inventory, Fatigue Symptom Inventory, Visual Analogue Scale, Fatigue Severity Scale, or Numerical Analogue Scale.[73]
Anorexia
This 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.[62][74]
Anorexia may be assessed using the Functional Assessment Anorexia/Cachexia Therapy Scale (FAACT).
Delirium
This is usually due to multifactor aetiologies, including medications (e.g., analgesics, anticholinergics, antihistamines, sedative-hypnotics), pain, or other symptoms, metabolic abnormalities (e.g., hypercalcaemia, hyponatraemia, hypernatraemia, uraemia), environmental factors (e.g., excessive stimuli, unfamiliar environment), and physiological factors (e.g., dehydration, infection, urinary retention, constipation, hypoxia, and hypercarbia).[64][75][76] Delirium is observed in 60% of patients with cancer.[62] Delirium in the ICU is identified in nearly one third of patients, associated with longer lengths of stay, increased mortality, and cognitive impairment after discharge.[77]
Delirium may be assessed using the Confusion Assessment Method, Confusion Assessment Method for the Intensive Care Unit, Delirium Assessment Scale, or Delirium Rating Scale. There is a need for improved recognition and assessment of delirium.[78]
Nausea
This may be caused by medications (e.g., opioids, chemotherapy, iron, digitalis, non-steroidal anti-inflammatory drugs [NSAIDs]), constipation, obstruction, pain, direct tumour effects, metabolic abnormalities (e.g., uraemia, hypercalcaemia), infection, and increased intracranial pressure.[64] Nausea is observed in 6% to 68% of patients with cancer.[62][79]
Nausea may be assessed using the Visual Analogue 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.
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. There are patients who are seriously ill, deteriorating, and in whom death is likely but not certain. 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. It is important to consider the need for continuation of preventive drugs among older patients with advanced cancer because these drugs are unlikely to achieve their clinical benefit during the patients' remaining lifespan and deprescribing strategies may be warranted.[80]
Pain is an unpleasant sensory and emotional experience that simply is "whatever the patient says it is".[81][82] Pain is the most common reason patients seek health care.[83] 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.[84] There is some evidence that opioids are also effective for non-cancer pain.[85][86][87] Opioids are more effective than placebo for nociceptive and neuropathic pain.[88][89][90]
Potentially reversible causes of pain should be identified.
Non-pharmacological interventions for pain include:[81][91][92][93][94][95][96][97][98][99][100]
Patient and family education
Self-help techniques
Cognitive-behavioural coping strategies
Music therapy
Complementary therapies (e.g., massage therapy, reflexology, acupuncture)
Physical exercise/therapy
Counselling
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.[89][98][101][102] Approximately 71% to 100% of patients can achieve pain control by following the WHO ladder guidelines.[89] The ladder starts with the use of non-opioid 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)".[89][98][102]
Opioid analgesics
No one opioid has been shown to have superior analgesic efficacy.[103][104][105][106] However, morphine is the preferred drug for moderate to severe pain, owing to its familiarity, low cost, and having been studied the most.[98][102][107][108][109] 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.[98][101][110] 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 formulae for approximately 48 hours.[89] 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.[110] Sustained-release preparations can be titrated up after a minimum of 48 to 72 hours.[111]
The optimal dose of opioid is the dose that controls the patient's pain with the least amount of adverse effects.[101][112]
Immediate-release opioids are used for breakthrough pain dosing.[110] Approximately 5% to 15% of the total 24-hour opioid requirement is used for the breakthrough dose.[110] 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.
Most opioids are primarily cleared by the kidneys.[110] The active metabolite of morphine, morphine-6-glucuronide, can accumulate in renal failure and lead to over-sedation with respiratory depression.[98] Hydromorphone and fentanyl are safer choices in renal failure.
Patients prescribed opioids for chronic pain should be assessed for risk of misuse, abuse, and diversion.[113]
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.[91][102][114]
Opioids can be delivered by almost any route. The oral route is preferred when possible. Other routes include sublingual, intravenous, subcutaneous, rectal, transdermal, inhaled, intrathecal, and epidural.
Complications of opioid therapy
Constipation: prevention and treatment of opioid-induced constipation is with laxatives (e.g., stimulant laxatives). Patients on scheduled opioids should receive scheduled laxatives.[101][102][115][116]
Nausea and vomiting: tolerance to opioid-induced nausea usually develops within 3 to 7 days.[101] Anti-emetics, especially antidopaminergic anti-emetics, are effective for opioid-induced nausea.[101][102][110]
Delirium: opioid rotation or lowering the dose of opioids with the use of adjuvant analgesics may improve symptoms of delirium. Low-dose haloperidol on an as-needed basis may be effective in the pharmacological management of opioid-induced delirium.
Sedation: tolerance to opioid-induced sedation usually develops within 3 to 7 days.[101] Psychostimulants (e.g., methylphenidate) can be used to counteract persistent opioid-induced sedation.[101][102][110]
Pruritus: low doses of antihistamines can be used to counteract opioid-induced pruritus.[110]
Hyperalgesia: opioid-induced hyperalgesia occurs when a patient paradoxically becomes more sensitive to pain, usually seen with high-dose opioid therapy.[117]
Allodynia: pain evoked by stimuli that are not normally painful (e.g., the touch of a bed sheet).[117] 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 neuro-adaptive changes of the nervous system leading to a pro-nociceptive up-regulation.[112][117] Lowering the opioid dose by rotating opioids or using adjuvant analgesics can improve these symptoms.[118][119]
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.[98][101]
Myoclonus: low-dose benzodiazepines can be used to treat myoclonus due to opioids.[101]
Dry mouth: preventative measures for dry mouth include good oral hygiene, sugar-free chewing gum, ice chips, and saliva substitute.
Urinary hesitancy or retention: usually relieved by itself, but intermittent straight catheterisations or a temporary Foley's catheter may be necessary in more extreme cases.
Some patients are reluctant to use opioid therapy because they or their family are frightened that it will hasten death or that the patient will become an addict.
Non-opioid analgesics
Broad classes of adjuvant analgesics include NSAIDs, antidepressants, anticonvulsants, corticosteroids, and local anaesthetics.[91][98][101][115]
NSAIDs are effective in treating pain from soft-tissue inflammation, bone metastasis, and serositis, and postoperative pain.[98][101]
Corticosteroids, such as dexamethasone or methylprednisolone, may be effective in treating pain from soft-tissue inflammation, visceral distension, nerve compression, increased intracranial pressure, and bone metastasis.
First-line therapy for neuropathic pain is gabapentin, pregabalin, and serotonin-noradrenaline reuptake inhibitors (SNRIs).[90] Tricyclic antidepressants (TCAs) are considered to be first-line therapy as well; however, they are limited by their adverse-effect profile.[98] Nortriptyline and desipramine are favoured 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.[120] Duloxetine is effective in treating chemotherapy-induced peripheral neuropathy.[121] Topical agents and botulinum toxin type A are recommended for peripheral neuropathic pain only.[90]
Pain from bone metastasis can be treated with NSAIDs, corticosteroids, bisphosphonates, radiotherapy, and radio-isotopes (e.g., strontium 89).[101][122][123][124][125][126][127][128] Neither calcitonin nor pregabalin has been shown to decrease bone pain compared with placebo.[129][130] Multiple-fraction 30 Gy radiotherapy and single-fraction radiotherapy had similar improvements in pain control.[127][131] Adding strontium 89 to radiotherapy has been shown to improve pain control.[122] Single-fraction (8 Gy) radiotherapy should be considered and is recommended as the standard of care, rather than multi-fraction radiotherapy regimens, for the palliation of painful bone metastasis and/or for the prevention of morbidity.[128][132][133] A response rate of about 45% can be expected in patients who receive palliative radiotherapy for painful bone metastasis in the last 12 weeks of life, which is lower than that found in patients with a longer life expectancy.[132]
There is strong evidence to treat cancer pain with NSAIDs, opioids, radionuclides, and radiotherapy.[134][135] There is less consistent evidence in the literature for the treatment of bone cancer pain with bisphosphonates. There is no evidence that specifically addresses pain management in advanced heart failure or dementia.
Adjuvant analgesics
Medications with a primary purpose other than treating pain but which also have analgesic properties.[136] They may be used alone or in combination with opioids to treat pain. Adjuvants are particularly useful in the management of neuropathic pain.[81][137] 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 radiotherapy and/or palliative chemotherapy may be used to decrease pain in selected patients with cancer.[98][115]
Evidence-based complementary therapy (e.g., acupuncture, reflexology, or acupressure for general or musculoskeletal pain; massage therapy for patients experiencing pain in palliative or hospice care settings) may be considered alongside conventional pain treatment as part of a holistic approach to pain management.[100]
Potentially reversible causes of dyspnoea should be identified.[138]
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, optimising patient body position, and considering placing the patient near a window can all lessen the sensation of dyspnoea.[39][64][97][115][138]
First-line therapy for symptomatic control of dyspnoea is opioids.[39][65][134][135][138][139][140] Opioids decrease dyspnoea given by the oral or parenteral route.[65][141][142][143] Nebulised opioids are either no more effective than placebo or are equivalent to the oral or subcutaneous route.[65][134][135][139][141][142][143][144] [
]
Evidence is strong for the use of opioids in treating dyspnoea for patients with COPD and weak for patients with cancer, and no evidence has addressed dyspnoea management in patients with advanced heart failure.[134][135][145][146]Oxygen therapy can reverse hypoxaemia but not necessarily dyspnoea. Giving oxygen to cancer patients with and without hypoxaemia improved oxygen saturations, with no significant difference in dyspnoea when oxygen versus air was given.[147] Supplemental oxygen did not provide additional symptomatic relief compared with room air for patients with refractory dyspnoea due to life-limiting illness.[148] In non-hypoxaemic cancer patients, there was no significant difference between supplemental oxygen and air in decreasing dyspnoea during exercise.[149] The evidence to support the use of oxygen therapy for dyspnoea in cancer patients is weak.[134][135] However, there is strong evidence to support the use of oxygen therapy for dyspnoea during exercise in patients with COPD.[134][135][150] Simply having air blowing across the face can improve the sensation of dyspnoea.[26]
For patients with COPD, there is strong evidence to support the use of beta-agonists to treat dyspnoea and the use of pulmonary rehabilitation to treat dyspnoea during exercise.[134][135]
In patients with cancer who have lung involvement, dexamethasone may improve dyspnoea.[151]
The use of anxiolytics in the treatment of dyspnoea is not well established. Alprazolam did not improve dyspnoea in COPD patients at rest or with exertion.[152] There is no overall beneficial effect of benzodiazepines for the relief of dyspnoea in patients with advanced cancer and COPD.[153] However, adding midazolam to morphine in end-stage cancer patients with life expectancy of <1 week and severe dyspnoea improved reports of dyspnoea.[154]
In a Cochrane review (that is currently being updated) of non-pharmacological 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.[155] There was a low strength of evidence to support the use of acupuncture/acupressure.[155]
The most common adverse effects of opioid therapy for dyspnoea 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 dyspnoea with opioids.[156][157]
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.[158] 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 minimised or stopped, 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.[64][116][159]
Laxatives accelerate laxation and are categorised into bulk-forming, osmotic, stimulant, lubricating, and detergent laxatives. No one laxative regimen has been shown to be superior to another.[160] However, the use of bulk-forming laxatives in palliative care is usually not recommended because they may exacerbate constipation in patients who are dehydrated or less mobile.[39][161][162]
Opioid-induced constipation is treated frequently with a stimulant laxative, such as senna, with or without a stool softener as an adjunct.[39][159][163] One low-quality study of constipation in cancer patients admitted to hospital revealed that adding docusate to a senna protocol was less effective in inducing laxation than senna alone.[164] One randomised, controlled trial in hospice patients found no significant benefit of adding docusate to senna.[165] There is inadequate evidence assessing the effectiveness of docusate in laxation, and, indeed, the use of docusate is not recommended by consensus recommendations for patients with advanced, progressive illness.[116][166]
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.[158] 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, and should be considered for opioid-induced constipation for patients who have failed to respond to optimal laxative therapy.[102][116][160][167][168][169][170]
Suppositories, such as bisacodyl, and enemas, such as a liquid paraffin enema followed by a large-volume enema, can be used for more refractory constipation.
Adverse effects of laxatives include bloating, abdominal cramping, nausea, and diarrhoea.
Depression is a general term with different subtypes involving a low mood state accompanied by various somatic, psychological, and cognitive symptoms.[67] 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.[39][171][172][173] 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.[39]
Identify potentially reversible causes of depression.
Non-pharmacological interventions include the use of cognitive therapies, behavioural therapies, psychotherapy, an interdisciplinary team approach, massage, aromatherapy, and music therapy.[39][64][96][174][175][176][177]
Antidepressants and psychostimulants are first-line medications for the treatment of depression in advanced illness.[39][67][173][178] However, evidence supporting the efficacy of antidepressants over placebo in cancer patients is weak.[179] [
]
There is no evidence for the superiority of treatment interventions in treating depressive disorders in patients with cancer and advanced illness.[177][180][181] Psychostimulants (e.g., methylphenidate) reduce symptoms of depression in the short term, and are recommended for patients with life expectancies of weeks or less.[39][173][181][182] Selective serotonin-reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) have been shown to improve depressive symptoms in patients with a life-limiting illness.[183] For patients with longer life expectancies, SSRIs or serotonin-noradrenaline reuptake inhibitors (SNRIs) are recommended.[39] TCAs are considered second-line owing to the increased adverse-effect profile.
There is strong evidence to support the treatment of depression in cancer at the end of life with TCAs, SSRIs, or psychosocial interventions.[134][135] 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.[71] Adverse effects of SSRIs and SNRIs include gastrointestinal intolerance, anxiety, headaches, anorexia, sexual dysfunction, hyponatraemia, serotonin syndrome, and bleeding risk.[181] Adverse effects of TCAs include confusion, sedation, dry mouth, ileus, blurred vision, urinary retention, constipation, hyponatraemia, 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.[184][185]
Identify potentially reversible causes of anxiety.
Non-pharmacological interventions include cognitive therapies, behavioural therapies, psychotherapy, interdisciplinary team approach, music therapy, reflexology, massage, and aromatherapy.[70][95][96][97]
There is insufficient evidence regarding the effectiveness of pharmacotherapy for anxiety in palliative care.[177][186][187] First-line medications are short-acting benzodiazepines.[39] 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: generalised weakness, easy fatigability, and mental fatigue.[71]
Identify potentially reversible causes of fatigue.
Non-pharmacological interventions include coping strategies, music therapy, massage, acupuncture, reflexology, cognitive therapies, behavioural therapies, psychotherapy, and an interdisciplinary-team approach.[71][174][188][189][190][191][192][193][194] Yoga and physical activity/exercise should be considered as appropriate per health.[194] Exercise and psychological interventions are more effective than pharmacological therapies for cancer-related fatigue.[193]
Drug therapies for fatigue have had limited benefits. The most commonly used medications for fatigue are psychostimulants and corticosteroids.[71] Methylphenidate has shown improvement in fatigue in patients with cancer and with AIDS.[71][72][195][196][197] Long-acting methylphenidate did not improve fatigue in cancer patients overall, but benefit was shown in a subset of patients with advanced cancer.[198] Guidelines recommend considering methylphenidate for patients with cancer-related fatigue.[194] Corticosteroids (e.g., dexamethasone and methylprednisolone) may reduce fatigue temporarily in patients with cancer, and can be considered for short-term use in patients with advanced cancer.[71][72][194][197][199]
Haematopoietic growth factors (e.g., erythropoietin) can improve fatigue in anaemic cancer patients undergoing chemotherapy.[195]
Evidence is inconclusive for the efficacy of amantadine and modafinil in multiple sclerosis, and for carnitine, donepezil, and modafinil in cancer-related fatigue.[194][197]
Secondary agents with limited to no evidence in improving fatigue include progestational steroids, paroxetine, and testosterone.[72][195]
Adverse effects of psychostimulants include restlessness, loss of appetite, hypertension, tachyarrhythmias, and seizures.[71] Adverse effects of corticosteroids include gastrointestinal intolerance, oedema, anxiety, steroid psychosis, hyperglycaemia, 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.[74]
Identify potentially reversible causes of anorexia.
Non-pharmacological 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.[74] 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.[74][200] The use of megestrol in older nursing home patients has been associated with increased mortality without a significant increase in weight.[201] The corticosteroids methylprednisolone, prednisolone, and dexamethasone increase appetite temporarily in patients with cancer.[74][202]
There are insufficient data to support the use of the following medications in the anorexia-cachexia syndrome: cannabinoids, eicosapentaenoic acid, metoclopramide, cyproheptadine, pentoxifylline, melatonin, erythropoietin, androgenic steroids, ghrelin, interferon, NSAIDs, and thalidomide.[71][74][189][203]
There is no strong evidence to support the use of enteral nutrition in non-surgical cancer therapy.[72][204][205] There is some evidence that net harm can be caused by the use of parenteral nutrition in cancer patients undergoing chemotherapy and radiotherapy.[72][204]
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.[39]
There is insufficient evidence to determine whether medically assisted hydration improves clinical outcomes or lengthens survival in palliative care patients.[206]
In one randomised, controlled trial of hospice patients with advanced cancer, parenteral hydration did not improve symptoms, quality of life, or survival.[207]
There is no evidence that artificial nutrition and hydration improves clinical outcomes in patients with advanced dementia.[39][208][209][210]
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.[211]
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.[211]
Adverse effects of progestins include lower-extremity oedema, venous thromboembolic disease, male impotence, and gastrointestinal intolerance.[200] Adverse effects of corticosteroids include gastrointestinal intolerance, oedema, anxiety, steroid psychosis, hyperglycaemia, 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 disorganised thinking or altered level of consciousness.[212][213]
Identify potentially reversible causes of delirium.
Medications are the most common cause of delirium in patients admitted to hospital.[64] Discontinue all non-essential medications, encourage gentle reorientation, familiarise the environment, minimise excessive environmental stimuli, optimise the sleep-wake cycle, avoid sleep deprivation, and use sensory aids (e.g., glasses, hearing aids, dentures) to minimise the risk of delirium.[64][214]
Multi-component interventions, a series of non-pharmacological strategies, can significantly reduce the risk of incident delirium among hospitalised older patients.[177]
Treat underlying pain or other symptoms because these may be contributing frequently to delirium.[75][76]
There is a lack of strong evidence to support the use of antipsychotics to improve severity or shorten duration of delirium in hospitalised non-ICU patients; however, the general consensus of delirium management is low-dose, as-needed haloperidol for hyperactive delirium as first-line medication therapy when pharmacological therapy is desired.[39][213][215][216][217] In one trial, the use of scheduled haloperidol or risperidone worsened delirium scores, and patients receiving haloperidol had increased risk of death compared with placebo.[218] Limited reporting in studies has not supported increased adverse drug events, including extrapyramidal symptoms, nor reduced mortality with antipsychotics compared to non-antipsychotic drug regimens for delirium in hospitalised non-ICU patients.[219] [
]
The atypical antipsychotics have been associated with increased risk for death in delirium-complicating dementia.[213][220] Conventional antipsychotics are at least as likely as atypical antipsychotics to increase the risk of death in older patients.[221] One small study in patients with advanced acquired immunodeficiency syndrome revealed that haloperidol and chlorpromazine are equally effective in managing delirium.[215] 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.[222]
Terminal agitated delirium that is refractory to the above standard therapies is addressed under the Palliative Sedation section.
Patients with advanced cancer experiencing hypoactive delirium may benefit from methylphenidate.[223]
Adverse effects of antipsychotics include extra-pyramidal 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.[224] Adverse effects of benzodiazepines include paradoxical agitation, sedation, and respiratory depression.
Nausea is the subjective, unpleasant sensation of needing to vomit.[162][225] Vomiting is a neuromuscular reflex that results in the forceful expulsion of gastric contents through the mouth. The vomiting centre in the medulla of the brain is thought unlikely to exist as a discrete structure. An area of loosely organised neurons in the medulla is believed to coordinate the emetic reflex and has been termed the central pattern generator.[225]
There are 4 main pathophysiological 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).[162]
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.[163] The neurotransmitters serotonin (5-HT 3), dopamine, and substance P seem to be particularly important in mediating chemotherapy-induced nausea.[225] Opioid-induced nausea is mediated largely by dopamine.[163]
Identify potentially reversible causes of nausea.
Non-pharmacological interventions include minimising or discontinuing offending medications; using distraction, visualisation, relaxation techniques, and/or music therapy; offering small, frequent meals with bland food; controlling pain; and addressing accompanying social, psychological, and spiritual issues.[64][96]
Choice of anti-emetic treatment for nausea due to chemotherapeutic agents should be based on the emetic risk of the chemotherapy and individual patient factors. Combination therapy with a serotonin receptor antagonist (e.g., ondansetron), dexamethasone, and a substance P/neurokinin-1 receptor antagonist (e.g., aprepitant) is a recommended option for acute nausea from chemotherapeutic agents of high and moderate emetic risk.[226] The addition of olanzapine may improve symptoms and quality of life, and is recommended for patients having therapy with high emetic risk.[226][227][228][229] [
]
Nausea from opioids or multiple aetiologies is best treated by targeting the dopamine (D2) receptor with medications, such as metoclopramide or prochlorperazine.[102][163][230][231]
Refractory nausea should be treated with multiple agents that target different neurotransmitter receptors scheduled around the clock.
Cannabinoids may be helpful in chemotherapy-induced nausea; however, adverse effects may be more prevalent compared with other anti-emetics.[232]
Corticosteroids may have an anti-emetic effect in advanced cancer when this is not chemotherapy-related; however, data supporting efficacy is lacking.[233]
Topical lorazepam/diphenhydramine/haloperidol gel (known as ABH gel) has not been shown to be effective for nausea.[234][235][236]
Adverse effects of serotonin receptor antagonists include headache, constipation, fatigue, and dry mouth.[163] Dopamine receptor antagonists can be associated with extra-pyramidal symptoms and akathisia. Anticholinergics and antihistamines can lead to confusion, sedation, dry mouth, ileus, constipation, blurred vision, and urinary retention. Excessive use of cannabinoids can cause cannabinoid hyperemesis syndrome.[226]
Advance-care planning is the process by which patients communicate and document treatment preferences and guide their medical care through periods of decisional incapacity.[237] Advance directives are tools meant to facilitate end-of-life decision making based on patients' goals of care.[238] 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 physician.[239] Over 70% of seriously ill patients have never discussed advance directives with their physician.[240] Less than half of seriously ill patients with cancer admitted to hospital have an advance directive.[241] The multicentre SUPPORT study revealed that only 47% of physicians knew when their patients preferred DNAR status.[10]
End-of-life wishes are more likely to be honoured with advance care planning in older patients.[242][243] Patients who completed an advance directive spent fewer days in hospital in the last year of life and had lower hospital costs.[244] 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.[245] In addition, family members of a patient who died had lower levels of stress, anxiety, depression, and post-traumatic stress disorder when the patient had advance care planning.[245] 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 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, normally effective when the patient becomes incapacitated.
Medical proxy decision maker
Documents a decision maker to make future medical decisions under the substituted judgement standard effective when the patient becomes incapacitated and does not have an MDPOA. In the US, 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.
Guardianship
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)[246]
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 honoured.[21][245][247][248][249][250][251]
POLST is not used in the UK.
Tools to facilitate advance-care planning discussions:[252][253][254][255]
Despite aggressive, high-quality palliative symptom management, some patients develop symptoms that are refractory to standard therapies. Palliative sedation therapy (PST) can relieve such refractory symptoms, which cause intractable suffering at the very end of life.
Palliative sedation therapy is a procedure in which sedative medications are given to reduce consciousness in a terminally ill patient, to relieve intolerable suffering from refractory symptoms.[256][257][258][259]
Sedation is used as an option for symptom control, titrated carefully to the cessation of symptoms and not for the purpose of euthanasia.[258][259] 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.[256][257][258][259]
Professional consensus supports the use of palliative sedation therapy for refractory symptoms when the following three situations are met: 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; and when the patient (or surrogate if the patient lacks decision-making capacity) has given informed consent.[256][258][259]
The most frequent reasons for providing palliative sedation therapy are delirium (55%), dyspnoea (27%), pain (18%), and nausea/vomiting (4%).[258][259] Using palliative sedation therapy for the relief of psychological and existential suffering alone is controversial and not accepted widely in practice.[256][257][258][259]
Palliative sedation therapy 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.[260] 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).[257][258][260] 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.[256]
Medications used for palliative sedation therapy include anxiolytic sedatives (e.g., midazolam, lorazepam), sedating neuroleptics (e.g., chlorpromazine), barbiturates (e.g., phenobarbital), and general anaesthetics (e.g., propofol).[258] Midazolam is the most frequently used sedative for palliative sedation therapy and has the additional benefit of anxiolytic, antiepileptic, muscle-relaxant, and amnestic properties.[258][260][261][262] 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).[258] There is no evidence that giving sedation proportionally shortens life.[258][261][263]
Palliative sedation therapy is different ethically from physician-assisted death (PAD), medical aid in dying (MAID), and euthanasia. In PAD, the physician provides the means for death and the patient performs the act.[259][264] 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.[256][257][258][259][260] In palliative sedation therapy, the intent is to relieve the patient's suffering, with death resulting from the underlying disease process. The aim of palliative sedation therapy is not to hasten death.
Evidence-based guidelines with recommendations for clinical care in the palliative care setting are available.
National Institute for Health and Care Excellence (NICE). Supportive and palliative care for adults with cancer.[5] Includes recommendations on:
patient and carer involvement
psychological, social and spiritual support services
general and specialist palliative care services
rehabilitation services
complementary therapy services
services for families and carers
workforce development.
Scottish Palliative Care Guidelines. End of life care.[265] Includes recommendations on:
care in the last days of life
rapid transfer home in the last days of life
severe uncontrolled distress
syringe pumps.
National Institute for Health and Care Excellence (NICE). End of life care for infants, children and young people with life-limiting conditions: planning and management.[266] Recommendations regarding:
advance care planning
emotional and psychological support and interventions
managing distressing symptoms, such as pain, agitation, seizures or respiratory distress
hydration and nutrition
recognising that a child or young person is likely to die within hours or days
care and support for parents, carers and healthcare professionals after the death of a child or young person
care at home.
National Institute for Health and Care Excellence (NICE). Palliative care for adults: strong opioids for pain relief.[267] This guideline includes recommendations on:
communication
starting strong opioids and titrating the dose
first-line maintenance treatment
first-line treatment using transdermal patches or subcutaneous delivery, if oral opioids are not suitable
first-line treatment for breakthrough pain in patients who can take oral opioids
managing constipation, nausea and drowsiness.
European Society for Medical Oncology. ESMO Clinical Practice Guidelines on palliative care: supportive and palliative care.[268]
Guidelines on the management of a variety of clinical issues in palliative care in palliative care, e.g., constipation in advanced cancer, delirium in adult cancer patients and diarrhoea in adult cancer patients.
European Society for Medical Oncology. ESMO Clinical Practice Guidelines on palliative care: advanced care planning.[269]
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.
European Society for Medical Oncology. Care of the adult cancer patient at the end of life.[270] Includes recommendations on:
Communication, shared decision making and preparation of patient and family
Nursing considerations
Prognostic factors
Rationalising treatments, routes of drug administration, nutrition and hydration, medication and intervention review
Management of cancer-related fatigue, pain, nausea and vomiting, breathlessness, noisy respiration, delirium and intractable symptoms
Management of psychological issues and spiritual distress
Bereavement care.
National Institute for Health and Care Excellence (NICE). Care of dying adults in the last days of life.[271] The guideline includes recommendations on:
Recognising when people are entering the last few days of life
Communicating and shared decision-making
Clinically assisted hydration
Medicines for managing pain, breathlessness, nausea and vomiting, anxiety, delirium, agitation, and noisy respiratory secretions
Anticipatory prescribing for people who are likely to need symptom control in the last days of life.
Guidelines are also available from Australia/New Zealand, and European groups.[272][273]
Similar guidance is also available in the US and Canada.[274][275][276] American Academy of Hospice and Palliative Medicine Opens in new window National Consensus Project for Quality Palliative Care Opens in new window
Assessment of bereavement needs in specialist palliative care has been reviewed.[277]
Evidence-based interventions to improve the palliative care of pain, dyspnoea, and depression at the end of life: a clinical-practice guideline from the American College of Physicians; 2008.[134]
Strong recommendations with moderate quality of evidence (in patients with serious illness at the end of life)
Clinicians should regularly assess patients for pain, dyspnoea, and depression.
Clinicians should use therapies of demonstrated effectiveness to manage pain. Management includes NSAIDs, opioids, and bisphosphonates in patients with cancer.
Clinicians should use therapies of demonstrated effectiveness to manage dyspnoea. Management includes opioids for dyspnoea and oxygen for short-term relief of hypoxaemia.
Clinicians should use therapies of demonstrated effectiveness to manage depression. Management includes tricyclic antidepressants, selective serotonin-reuptake inhibitors (SSRIs), 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.
Institute for Clinical Systems Improvement. Palliative care; 2013.[39]
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 non-physical 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.[278]
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.
The National Comprehensive Cancer Network has produced a range of guidelines relevant to end-of-life care:[91][194][226][279][280][281]
Palliative care
Adult cancer pain
Antiemesis
Cancer-related fatigue
Distress management
Survivorship.
American College of Chest Physicians. Palliative and end-of-life care for patients with cardiopulmonary diseases: American College of Chest Physicians position statement; 2005.[85]
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 carer.
American Thoracic Society. An official American Thoracic Society clinical policy statement: palliative care for patients with respiratory diseases and critical illnesses; 2008:[282]
The American Thoracic Society (ATS) strongly endorses the integration of palliative care throughout a patient's illness trajectory and individualised 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 and their family or carers.
American Thoracic Society, American Academy of Hospice and Palliative Medicine, Center to Advance Palliative Care, Hospice and Palliative Nurses Association, and Social Work Hospice and Palliative Care Network. An official policy statement: palliative care early in the care continuum among patients with serious respiratory illness.[283]
Palliative care in serious respiratory illness should begin with primary palliative care delivered by pulmonary and critical care clinicians, and should be complemented by secondary or specialist palliative care expertise when necessary.
Comprehensive primary palliative care training of pulmonary critical care clinicians is essential.
A framework for early palliative care in serious respiratory illness is provided.
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:[284]
Knowledge and competence in end-of-life care is an emerging and necessary skill for critical-care physicians. Family-centred care is the basis for comprehensive end-of-life care in the ICU. The emphasis is on standards for decision making, resolving conflict, and communicating 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 Consensus Project for Quality Palliative Care. Clinical practice guidelines for quality palliative care, fourth edition; 2018.[285]
The purpose of these guidelines is to promote access to quality palliative care, foster consistent standards and criteria, and encourage continuity of palliative care across settings.
Palliative care is a person- and family-centered approach to care, providing people living with serious illness relief from the symptoms and stress of an illness.
The focus is on what is most important to the patient, family, and carer(s), assessing their goals and preferences and determining how best to achieve them.
Through early integration into the care plan for the seriously ill, palliative care improves quality of life for the patient and the family.[286]
Palliative care principles and practices can be delivered by any clinician caring for the seriously ill, and in any setting. All clinicians are encouraged to acquire core skills and knowledge regarding palliative care and refer to palliative care specialists as needed.
Since palliative care is not setting-specific, palliative care principles and practices are applicable throughout the course of a serious illness.
American Society of Clinical Oncology. Statement: Toward individualized care for patients with advanced cancer; 2011.[33]
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 individualised care achieved through an earlier and more thorough assessment of patient's options, goals, and preferences.
Palliative care for patients with cancer: American Society of Clinical Oncology guideline update[287]
Patients with advanced cancer should receive dedicated palliative care services, early in the disease course, concurrent with active treatment.
Palliative care should be delivered through interdisciplinary palliative care teams available in both outpatient and inpatient settings.
Essential components of palliative care may include:
Rapport and relationship building with patients and family carers;
Symptom, distress, and functional status management;
Exploration of understanding and education about illness and prognosis;
Clarification of treatment goals;
Assessment and support of coping and spiritual needs;
Assistance with medical decision-making;
Coordination with other care providers; and
Provision of referrals to other care providers as indicated.
Providers may refer carers of patients with cancer to palliative care services for additional support.
A complementary ASCO guideline outlines stratified recommendations for resource-constrained settings.[288]
American Society of Clinical Oncology. Management of chronic pain in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline 2016[113]
Clinicians should conduct an initial comprehensive pain assessment, and screen for pain at every encounter.
New-onset pain should be assessed, treated, and monitored.
The aim should be to enhance comfort and function, minimise adverse events, and ensure safety.
For patients with complex care needs, clinicians should determine the need to involve other health professionals to provide comprehensive pain management.
Systemic non-opioid analgesics and adjuvant analgesics may be prescribed to improve pain and function in patients without contraindications.
A trial of opioids may be prescribed in select patients who do not respond to more conservative management.
Clinicians should incorporate universal precautions to minimise abuse, addiction, and adverse consequences.
Use of opioids for adults with pain from cancer or cancer treatment: American Society of Clinical Oncology clinical practice guideline[289]
Opioids should be offered to patients with moderate to severe pain related to cancer or cancer treatment, unless contraindicated.
Opioids should be started at the lowest possible dose to achieve acceptable pain relief and patient goals, with early assessment and frequent titration to establish an effective dose.
For patients with a substance use disorder, clinicians should collaborate with a palliative care, pain, and/or substance use disorder specialist to determine the optimal approach.
Adverse effects should be monitored closely; strategies for management of adverse effects are provided.
Management of anxiety and depression in adult survivors of cancer: American Society of Clinical Oncology guideline update[290]
All cancer patients should be offered education about depression and anxiety.
A stepped-care model for treatment is recommended.
Non-pharmacological interventions are recommended as first-line treatment for moderate or severe symptoms of depression or anxiety.
Pharmacological interventions can be used if preferred by the patient, if non-pharmacological interventions are unavailable, or as a second-line option.
Society for Integrative Oncology and American Society of Clinical Oncology. Integrative medicine for pain management in oncology guideline[100]
Evidence-based complementary therapy may be considered alongside conventional pain treatment as part of a holistic approach to pain management.
Acupuncture, reflexology, or acupressure may be of benefit for general or musculoskeletal pain; massage therapy may help provide short-term pain relief in palliative or hospice care settings.
Management of fatigue in adult survivors of cancer: American Society of Clinical Oncology-Society for Integrative Oncology[291]
Exercise (aerobic, resistance, or a combination), cognitive behavioural therapy (CBT; with or without hypnosis), mindfulness-based programmes (e.g., mindfulness-based stress reduction), and tai chi or qigong can be recommended to reduce the severity of fatigue in adults undergoing cancer treatment.
Psychoeducation may be recommended, as may American ginseng, to reduce the severity of fatigue in adults undergoing cancer treatment.
National Association of Neonatal Nurses. Palliative and end-of-life care for newborns and infants. Position statement 3063; 2015.[292]
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 ICU.
Neonatal ICUs should have a relationship with a local hospice or palliative care programme to offer seamless continuity of care.
American Academy of Pediatrics. Palliative and end-of-life care for children and adolescents. Clinical report.[293]
Advanced care planning should begin early soon after serious diagnosis and revisited as the goals of care evolve.
Clinicians should consider both family and patient treatment goals and preferences, using shared decision making for end of life care. Families should be provided with straightforward anticipatory guidance about the end of life.
Location for child's or adolescent's final days or hours should be discussed with the patient and family.
American Heart Association. Palliative care across the life span for children with heart disease. Scientific statement.[294]
Early and ongoing primary palliative care is recommended for patients with complex congenital heart disease or paediatric acquired heart disease with the potential for future heart failure.
Includes advice on managing symptoms, triggers for specialty palliative care, advance care planning, and considerations at the end of life.
Discusses palliative care training in paediatric cardiology; diversity, equality, and inclusion considerations; and future research priorities.
American Society for Radiation Oncology. Palliative radiotherapy for bone metastases: an ASTRO evidence-based guideline; 2017.[128]
External-beam radiotherapy is the mainstay for the treatment of painful, uncomplicated bone metastases.
Single-fraction radiotherapy produces equivalent responses to pain and/or the prevention of morbidity compared with multiple-fraction radiotherapy regimens, with no difference in rates of long-term side effects.
Single-fraction radiotherapy optimises patient and carer 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 radiotherapy.
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.[295]
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 physiological 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.
A variety of tools are also available to assist in assessing patient needs from the International Association for Hospice and Palliative Care. International Association for Hospice & Palliative Care Opens in new window
Disease-specific position statements are available for certain illnesses, including:[296][297][298][299][300]
Cancer: Multinational Association of Supportive Care in Cancer; 2010
Lung cancer: The American College of Chest Physicians; 2013
Melanoma: Australian Cancer Network Melanoma Guidelines Revision Working Party; 2008
Heart failure: The Royal Australian College of General Practitioners; 2010
Stroke: American Heart Association; 2014.
The Cochrane Collaboration has produced a systematic review on end-of-life care pathways, with insufficient data at present to make recommendations.[301]
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