Overview of palliative medicine

Palliative medicine is a comprehensive, interdisciplinary approach to medical care that aims to relieve suffering and provide optimal quality of life in patients with serious or life-threatening illnesses. It is often provided in conjunction with life-prolonging therapy. Crucial components of palliative medicine include symptom relief, assistance in the organization of nursing and social services, and psychological support of patients and their families. As a consequence, palliative care teams are typically multidisciplinary: Palliative care specialists identify needs and coordinate care, oncologists (or other specialists) manage the underlying disease, primary care providers address symptom relief, pain specialists treat advanced pain, and mental health providers and chaplains administer psychological and spiritual support. The palliative care team addresses symptoms including pain, breathlessness, nausea, constipation, and delirium, and provides end-of-life comfort care. Palliative care has been shown to decrease symptom intensity, improve quality of life, decrease hospital admissions, and help bereaved family members adapt to their loss. If a patient desires or meets the criteria for palliative care referral, it should be initiated as quickly as possible.

• Key elements of palliative care
  • Symptom relief, particularly sufficient analgesia
  • Assistance in the organization of adequate, needs-based care
  • Support regarding social services
  • Psychological support of patients and their families
• Members of a palliative care team
  • Physicians (including palliative care specialists)
  • Nurses
  • Social workers
  • Psychologists
  • Chaplains
  • Pharmacists

Palliative medicine is not synonymous with end-of-life care. It is often used to improve a patient's quality of life even as life-prolonging therapy continues.

References:^[1]

General approach ^[2][3][4]

• Consider enrolling patients with cancer or other high-morbidity illness in a palliative care program.
• Frequently reassess the patient's symptoms.
• If new symptoms arise or current symptoms change, consider investigating the etiology of the change in addition to managing symptoms.
  • Discuss the risk-benefit profile and confirm goals of care with patients and caregivers prior to initiating management of a new or newly exacerbated complication.
  • Adjust approach to eliminate diagnostic and therapeutic procedures that are too invasive, painful, or have other side effects that are not aligned with the patient's preferences or wishes.
• Involve associated healthcare professionals (e.g., dietitians, physical therapists, and occupational therapists) to help anticipate and prevent complications.
• See also “Principles of cancer care.”

Overview of symptom management ^[1][5][6]

Address reversible underlying causes of symptoms as long as the investigations and treatment required are consistent with the patient's care plan and wishes.

Pain is an unpleasant experience with sensory and emotional components that may occur with our without actual or potential tissue damage. ^[11]

Approach

• Address multifactorial components of pain.
  • Nociceptive pain: caused by damage or potential damage to tissue (excluding neural tissue)
  • Neuropathic pain: caused by damage to a somatosensory nerve
  • Nociplastic pain: caused by altered nociception despite there being no underlying tissue damage
  • Mixed pain: the simultaneous or concurrent presence of nociceptive, neuropathic, and/or nociplastic pain in one area of the body ^[12]
  • Emotional pain: a term used to describe both mental suffering and the impact of emotions on the experience of pain
  • Total pain: the combination of physical, social, spiritual, and psychological/emotional pain components ^[13]
• Maximize nonpharmacological therapy to either complement or replace pharmacotherapy.
• Use the WHO analgesic ladder to structure treatment. ^[14][15]
• Consider the following causes of pain in patients with cancer:
  • Disorders associated with the tumor (e.g., thrombosis, paraneoplastic syndrome)
  • Therapy: postoperative pain, side effects of radiotherapy or chemotherapy (e.g., mucositis, polyneuropathies, stomach ulcer associated with NSAIDs)
  • Tumor effects: infiltration of soft tissue and bones; compression of nerves, lymphatic vessels, or blood vessels; cerebral edema

Nonpharmacological therapy ^[3][4]

• Spiritual and social services: e.g., chaplains, spiritual advisors, and social workers
• Physical interventions: e.g., physical therapy, acupuncture, massage, transcutaneous electrical nerve stimulation
• Mental health interventions: e.g., depression and anxiety treatment, relaxation therapy, cognitive behavioral therapy

Nonopioid pharmacotherapy ^[3][14][16]

• First-line agents: acetaminophen and NSAIDs
• Neuropathic pain: Consider adding gabapentinoids and antidepressants. ^[17]
• Metastatic bone pain
  • Consider adding bisphosphonates and denosumab. ^[16]
  • Consult radiation oncology for external beam radiotherapy.

Although acetaminophen should be trialed as a first-line analgesic, many patients do not experience significant pain relief with acetaminophen alone. Consider escalation to opioid therapy early. ^[23]

Opioid therapy ^[23]

Most patients require a combination of regularly scheduled slow-release opioids and fast-acting doses as needed for breakthrough pain.

• Treat severe pain first with parenteral therapy.
• Transition to oral medications once the pain is controlled.
• Consider administering preemptive doses before painful procedures, e.g., dressing changes, bed baths.
• Consider continuous opioid infusions to provide sufficient pain relief in terminally ill patients (see “Management of imminently dying patients").
• Consider extended-release formulations in patients whose pain is not controlled with as-needed dosing or those requiring ≥ 4 as-needed doses per day.

Consider starting opioid treatment with lower doses of potent opioids instead of higher doses of weak opioids. ^[16][24]

Starting dosages

• Use short-acting agents (e.g., oral morphine, oxycodone, and hydromorphone) for initial doses.
  • Peak: 1–1.5 hours
  • Duration: 2–4 hours
• Increase dose only after steady state is reached, i.e., at 4–5 drug half-lives or ∼ 24 hours for short-acting agents.

The dosing interval for most immediate-release narcotics should be 4 hours, unless the patient has significant renal or hepatic dysfunction.

Refractory pain ^[23][30]

Cancer pain, in particular, may be refractory to standard medical therapy. The following treatments may be considered under specialist supervision:

• Continuous narcotic infusions
• Radiation therapy: particularly helpful for bony metastases
• Drainage of malignant effusions
• Regional nerve blocks or epidural
• Intrathecal or epidural analgesia
• Neurolytic blocks
• Corticosteroids
• Ketamine

Many medications are used off-label or with off-label dosage regimens in palliative care. The recommendations in the following section are consistent with those of palliative care experts.^[8][31][32]

Breathlessness (dyspnea) ^[2][31][33]

• Background
  • Breathlessness/dyspnea is common in palliative care patients. ^[3][8]
  • This symptom manifests uniquely in these patients, as it often:
    • Is not easily attributable to an organic disease process
    • Responds poorly to standard medical therapies, e.g., bronchodilators, diuretics
• Approach: Tailor to the individual's palliative care plan.
  • Identify and treat reversible causes and provide respiratory support in accordance with the patient's wishes.
  • Optimize nonpharmacological therapy.
  • Offer palliative pharmacotherapy as a symptomatic treatment for patients with irreversible breathlessness.
  • Continue previously prescribed treatments if tolerated, e.g., bronchodilators.
  • Discuss more invasive symptomatic therapy, e.g, bronchoscopic stenting, on an individual basis.
• Treatment of potentially reversible causes
  • Pneumonia: e.g., antibiotics
  • Malignant pleural effusion: e.g., therapeutic thoracentesis, indwelling pleural catheter
  • Large volume ascites: e.g., paracentesis
  • Pulmonary edema: e.g., diuretics, antihypertensive, NIPPV
  • Malignant bronchial obstruction: e.g., endobronchial stent
• Respiratory support as symptom control
  • Administer oxygen therapy to hypoxic patients titrated to SpO₂ > 90%.
  • Consider NIPPV in select patients.
• Nonpharmacological therapy ^[4]
  • Provide a fan (handheld or for room air circulation).
  • Utilize body posture aids (work of breathing is reduced in the upright position).
  • Maintain a cool ambient temperature.
  • Involve respiratory therapists to educate patients about breathing techniques. ^[34]
  • Treat anxiety, e.g., with relaxation therapy (see “Palliative anxiolysis”)
• Palliative pharmacotherapy for breathlessness ^{[8][31][35][36]}
  • Low-dose opioids: Start with a low dose and titrate to effect. ^[3][37]
    • Patients with acute dyspnea
      • Ambulatory: PO short-acting morphine
      • Hospitalized: IV morphine
    • Patients with chronic dyspnea: PO extended-release morphine
  • Benzodiazepines (second line) ^[4]
    • Consider in patients with refractory anxiety.
    • Sample agent: lorazepam

Use benzodiazepines with caution, as concurrent administration with opioids increases the risk of respiratory depression. ^[8]

Consider and address reversible causes of breathlessness in accordance with the patient's wishes and care plan prior to initiating palliative pharmacotherapy.

Nausea and vomiting (N/V)

• Approach ^[38]
  • Symptoms related to cancer treatment (e.g., chemotherapy, radiotherapy): Consult oncology and consider treatment for CINV. ^[39]
  • Symptoms unrelated to cancer: See “Nausea and vomiting” for broad differential diagnosis.
  • Identify and treat underlying causes in accordance with the patient's wishes and care plan.
  • Begin immediate symptomatic treatment of nausea and vomiting while working up underlying causes. ^[4]
• Treatment of potentially reversible causes
  • Drug-induced (e.g., opioid side effects, cannabinoid hyperemesis syndrome): Reduce dose or replace the offending agent. ^[40]
  • Electrolyte abnormalites: e.g., hypercalcemia treatment, hyponatremia treatment, electrolyte repletion
  • Treatment of organ dysfunction: uremia (AKI or CKD), acute hepatic failure
  • Treatment of gastroparesis
  • Treatment of paralytic ileus or gastroparesis
  • Bowel obstruction treatment: nonoperative management of bowel obstruction, endoscopic intervention, or surgery
  • ICP management
• Nonpharmacological therapy ^[4]
  • Dietary modification (e.g., smaller and more frequent meals)
  • Ice chips and cool liquids
  • IV hydration
  • P6 acupressure wristband or acupuncture therapy
  • Aromatherapy
  • Cognitive-behavioral therapy or hypnosis
• Pharmacological therapy: ^[2]
  • Start with a dopamine receptor antagonist, e.g., metoclopramide, and titrate to maximum tolerance.
  • Add an additional drug class if needed.
    • Serotonin (5HT3) antagonist (e.g., ondansetron): for postoperative N/V
    • Antihistamine (e.g., meclizine) or anticholinergic (e.g., scopolamine patch): for vestibular N/V
    • Corticosteroid (e.g., dexamethasone): for meningeal irritation, ↑ ICP-related N/V, or malignant bowel obstruction
  • Consider benzodiazepines for N/V triggered by anxiety (see “Palliative anxiolysis”).
  • Change to sublingual, rectal, or parenteral dosing if N/V interferes with PO medication administration.
  • See “Antiemetics” for dosages.

Constipation ^[38][41]

• Background
  • Occurs in up to 90% of palliative care patients. ^[41]
  • Consequences include:
    • Pain
    • Nausea and vomiting
    • Bowel obstruction
    • Urinary retention
    • Delirium
• Assessment: Consider standardizing the severity of subjective symptoms with patient reporting tools. ^[41]
• Management
  • Address common underlying causes in palliative care, e.g.:
    • Reduce or replace offending medication, e.g., anticholinergics, opioids.
    • Manage bowel obstruction.
    • Address electrolyte abnormalities (e.g., hypercalcemia and hypokalemia).
    • Optimize diet and fluid intake.
  • Provide symptomatic treatment of constipation: See “Overview of laxatives” for details on agents and doses. ^[2]
    • Use stimulant laxatives (e.g., bisacodyl, senna) as first-line for treatment and prevention combined with a stool softener (e.g., docusate).
    • Consider adding osmotic laxatives if stimulant laxatives are ineffective.
    • Provide treatment for fecal impaction, if present.
    • For laxative-refractory opioid-induced constipation, consider targeted therapy, e.g., methylnaltrexone, naloxegol.
  • Avoid treatments for complications that can worsen underlying constipation.

Exercise caution in patients with neutropenia, thrombocytopenia, or bowel obstruction who require enemas and suppositories to avoid iatrogenic bacteremia, hemorrhage, or bowel perforation. ^[41]

Delirium ^[2][32]

• Background: Occurs in up to 90% of patients receiving palliative care. ^[3]
• Etiologies in palliative medicine include:
  • Medications (e.g., opioids, steroids, antiemetics, benzodiazepines)
  • Pain
  • Distended bowel or bladder
  • Metabolic causes (e.g., hypercalcemia, hyponatremia, hypomagnesemia, dehydration)
  • Disruption of the sleep-wake cycle
  • CNS pathology (e.g., brain metastases)
• Assessment: See “Confusion assessment method” and “Symptom-based diagnostic workup of delirium.”

Management of delirium in palliative care ^[42][43]

See also “Delirium management” for a general approach to therapy in nonpalliative patients.

• All patients
  • Address underlying causes in accordance with the patient's care plan, especially pain and constipation (see also “Delirium etiology”).
  • Initiate nonpharmacological supportive measures to prevent and reduce symptoms of delirium (see “Delirium prevention”).
  • Perform medication reconciliation and minimize polypharmacy.
  • Discontinue offending agents commonly encountered in palliative care: e.g., glucocorticoids, anticholinergic medications, benzodiazepines.
• Suspected opioid-induced neurotoxicity: Consider opioid rotation by replacing high-risk opioids with low-risk opioids to reduce delirium symptoms.
  • High-risk opioids: meperidine, morphine, and hydromorphone
  • Low-risk opioids: fentanyl and methadone
• Consider pharmacotherapy depending on symptoms severity.
  • Mild symptoms: Begin with oral antipsychotics.
    • First-line: haloperidol
    • Alternatives
      • Risperidone
      • Olanzapine
      • Quetiapine fumarate
  • Severe symptoms: Consider switching to parenteral antipsychotics.
    • First-line: haloperidol
    • Alternatives
      • Olanzapine
      • Bedbound patients: chlorpromazine
  • Refractory symptoms: Add a benzodiazepine to antipsychotics. ^[32]
    • First-line: lorazepam
    • Alternative: midazolam

Anxiety ^[3]

• Anxiety and depression are very common in palliative care and inadequate treatment can worsen nausea, pain, and depression and decrease the patient's quality of life.
• Consider early treatment with antidepressants or anxiolytics.
• Palliative anxiolysis: Benzodiazepines are first-line in most patients.
  • Short-acting
    • Lorazepam
    • Alprazolam
  • Long-acting
    • Clonazepam
    • Diazepam

General principles ^[2][44]

Patient comfort and psychosocial support for caregivers are the primary concerns.

• Educate the family members and patient about the dying process.
• Offer consultation for spiritual support.
• Discuss end-of-life care, including what resuscitation efforts the patient desires, with the patient and family.
• Ensure that all care providers are aware of the patient's and family's wishes regarding end-of-life care and are willing to participate.

CPR is only appropriate if the cause of death is reversible. CPR will be ineffective for a patient who is in the imminent phase of death. This should be communicated early to the patient and the family.

Recognizing imminent death ^[45]

There can be great uncertainty in making a diagnosis of imminent death. Maintain a low threshold to consult a palliative care specialist and focus attention on patient and caregiver needs rather than diagnostic accuracy. ^[46]

• Early symptoms include:
  • Increased time spent sleeping
  • Loss of interest in food and drink
  • Delirium
  • Difficulty mobilizing (patients become bedbound)
• Late symptoms include:
  • Mottled extremities
  • Noisy terminal respiratory secretions ^[47]
  • Irregular breathing, including periods of apnea
  • Coma
  • Terminal agitation: includes symptoms of cognitive decline, restlessness, altered affect, and/or hallucinations
    • May be part of an unrecognized acute delirium
    • Often distressing to both the patient and the family

Nonpharmacological management

• Discontinue diagnostic testing and unnecessary monitoring.
• Provide positioning support to maximize comfort. Use a pressure-relieving mattress, if available.
• Provide adequate mouth care, e.g.: ^[48][49]
  • Regular moistening of the oral mucosa
  • Artificial saliva
  • Assisted oral care
  • Single-dose fluconazole
  • Analgesics
• Consider respiratory physiotherapy for terminal respiratory secretions. ^[10]
• Consider deactivation of implanted cardiac devices.
• Stop routine medications (e.g., statins) and treatments (e.g., chemotherapy, dialysis) that do not contribute to symptom relief.

Pharmacotherapy

• Continue existing symptom control medications.
• In patients unable to swallow, change medications to nonoral routes.
• Patients may require continuous infusions as end-of-life symptoms worsen.

Management of terminal respiratory secretions ^[2]

Consider the following anticholinergic medications to reduce the production of mucus and saliva:

• Glycopyrrolate
• Atropine
• Hyoscyamine
• Scopolamine

Palliative sedation ^[50][51]

• Background
  • Palliative sedation treats patient discomfort by reducing the level of the patient's consciousness.
  • The use of palliative sedation is controversial, as it requires the use of sedating drugs in doses that can cause respiratory depression, potentially hastening death. ^[52][53][54]
  • Most major palliative care societies support palliative sedation as an exceptional option, to be used only after all other attempts as controlling refractory pain, agitation, and breathlessness have failed.
  • The decision to start palliative sedation should only be made after consultation with the patient or their advocates and the treating team under the guidance of a palliative care physician and/or a medical ethicist.
  • Always follow local institutional policies and national guidance, as the acceptability and legality of palliative sedation vary between countries and cultures. ^[55]
• Initiating palliative sedation
  • Indications: refractory symptoms, terminal agitation, or perceived patient discomfort
  • Consider only after identifying and treating any reversible causes of agitation (see “Management of delirium in palliative care”).
  • Consult palliative care to confirm the symptoms are truly refractory and to discuss the appropriateness of palliative sedation.
  • Discuss the plan in detail with the patient and their family.
    • Clarify that treatment will induce patient unconsciousness and has the potential to hasten death.
    • Obtain explicit permission from the family.
• Medications
  • First line: midazolam
  • Alternatives
    • Lorazepam
    • Propofol infusion (Verify the institutional policy before starting.)

Adequate management of end-of-life symptoms may involve large enough doses of medication to cause respiratory depression; while there is a risk this may hasten death, this is considered an acceptable compromise according to the principle of double effect. ^[56][57]

The health care system measures the outcome (quality of results) of medical treatment and its influence on the current and future health of patients and their quality of life.

• Features of outcome measurement in palliative medicine
  • General outcome measurements assess, for instance, the physical and psychological aspects of an illness.
  • Specific outcome measurements focus on the evaluation of symptoms, clinical situations, or patient populations.
• Common outcome measurements in palliative medicine
  • Numeric rating scale (NRS) and visual analog scale (VAS)
    • One-dimensional scales that are based on self-reported data: NRS scale 0–10, VAS scale 0–100
    • E.g., report of pain level, level of respiratory distress, nausea, quality of life, satisfaction, stress
  • Tools to assess functional performance of individuals receiving palliative care: Karnofsky performance status scale, palliative performance status (PPS), Eastern Cooperative Oncology Group (ECOG) performance status

Definition

• Type of palliative care specifically given to patients at the end of life

Principles

• Preserve the dignity of patients during the final stages of life.
• Provide maximum comfort to the patient.
• Ensure pain relief (including administration of opioids, anxiolytics, or sedatives).
• Prioritize positive effects over potential negative effects (e.g., pain relief over the risk of respiratory depression), according to the ethical principle of double effect.

Who is eligible for hospice care?

• Estimated life expectancy < 6 months
• Patients are usually on Medicare, Medicaid, or private insurance plans.
• The patient (and family) has made the decision to stop curative or life-preserving treatment in order to maximize quality of life.

Not all treatment should be withdrawn. Antibiotics, for example, can still be given if the patient develops an infection.

Facilities

• Patients can receive hospice care at home, in a skilled nursing facility, or at a hospital.
  • Home hospice services may consist of regular nursing visits, assistance with activities of daily living (e.g., cooking, cleaning, bathing, etc.), or support for home medical equipment (e.g., hospital beds, walkers, bedside commodes, etc.).
  • Hospice care in a hospital or nursing facility may be indicated if the patient's pain or symptoms require more specialized care.
• Services are available 24 hours a day, 7 days a week.

Deprescribing medications ^[58][59][60]

• General considerations
  • To improve the quality of life in patients who are receiving end-of-life care, medications should be evaluated, and any nonessential or inappropriate drugs should be discontinued.
  • High-risk medications (e.g., sedatives, opioids, anticholinergics) may be continued because their short-term benefits outweigh their long-term risks.
• Considerations for deprescribing
  • Drug interactions
  • Potential adverse events
  • Treatment burden
• Drugs considered for deprescribing: medications indicated for primary or secondary prevention and/or with no short-term benefits
  • Antihypertensives
  • Statins
  • Aspirin
  • Chronic proton pump inhibitors
  • Short-acting insulins and oral hypoglycemics
  • Antiresorptive medications for osteoporosis

• Communication
  • Full information for the parents/legal guardians regarding the diagnosis, treatment options and goals, and prognosis with and without therapy
  • Disclosure to the child: should be adapted according to the age and developmental level
    • Preschoolers (< 6 years): often cannot conceptualize death; provide a clear explanation of their situation with parental presence
    • Elementary schoolers: often begin understanding death and their own situation; allow participation in medical decisions when appropriate
    • Adolescents: often have a full understanding of death; allow participation in decision-making, respect privacy and autonomy
  • Consider the values and preferences of the family.
• Decision making and ethics
  • Parents/legal guardians are the legal medical decision-makers.
  • Parental consent must be obtained in the pediatric setting (see “Informed consent” in “Principles of medical law and ethics”).
  • Assent from the minor with an appropriate developmental level should also be obtained
  • Consider previously agreed upon DNR orders or advance directives.
  • Encourage exchange with parents in similar situations and facilitate contact with support groups.
  • Ethics committees can aid parental decision making.
• Psychosocial support
  • Facilitate psychosocial and/or spiritual support for the child patient and his/her family.
  • Address implications of the condition (e.g., disability and death).
  • Consider the personal wishes of the child (e.g., make-a-wish grants, family activities).
  • Facilitate contact to grief and bereavement support for family, e.g., counseling services, support groups.
• Symptom management
  • Pharmacological management of symptoms (see “Symptoms and symptom control” above)
  • Nonpharmacological measures include massages, physical therapy, acupuncture, behavioral/cognitive techniques (e.g., play therapy, music therapy, art therapy, guided meditations).

References: ^[61]