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4th January 2024

Overview of Palliative Medicine

What is Palliative Care?

Palliative care encompasses a large range of services offered to people with conditions that are deemed to be life-limiting. It is holistic in nature and includes symptom control, psychosocial and spiritual care, both to patients and their loved ones. It, therefore, benefits from a strong multidisciplinary team approach. Life-threatening illnesses that benefit from palliative care include malignancy, frailty, neurological diseases and end-stage organ failure.

Palliative care can start at the beginning of a patient’s diagnosis of a life-threatening condition and can continue until the end of their life, sometimes extending beyond their death for bereavement care of loved ones. Varying terms can describe different aspects of palliative care, as highlighted in the definitions below.

Definitions

  • End-of-life care: Care of individuals in their last 12 months of life
  • Terminal care: Care of individuals in their last few weeks of life
  • Bereavement care: Care of individuals and their loved ones during their illness and after death

References

Pain

Pain is a common symptom in end-of-life care. There are many pharmacological and non-pharmacological management options.

Types of Pain

Pain at the end of life can be broadly categorised into nociceptive or neuropathic pain. Nociceptive pain can be somatic, emanating from skin, soft tissue or bones, or visceral, originating from internal organs. Neuropathic pain emerges from damage to the peripheral or central nervous system. It can be described as a burning, shooting or shocking sensation. Pain is also heavily influenced by psychosocial and spiritual components, and for this reason, a holistic approach to pain management is vital at the end of life. It is important to understand the aetiology of pain in order to help guide appropriate management.

Assessing Pain

Pain can be continuous or intermittent at the end of life. It may be a background pain, best treated with long-acting analgesics, or breakthrough pain, indicating the need for PRN (as required) immediate-release analgesia. Pain can also be incidental, where a clear precipitant can be established. Examples of precipitants include certain movements, the changing of dressings or coughing. Pain may also be due to ‘end-of-dose failure’ when long-acting analgesics wear off sooner than expected. End-of-dose failure is not a breakthrough pain but instead indicates a failure of adequate management of the background pain. Pain can be assessed with history taking, the monitoring of medication charts for frequent use of PRNs, as well as numerical or visual tools.

MRCP Part 1 - Assessing Pain

Source: Created by Dr Tasneem Wadee. Watson M, Campbell R, Vallath N, Ward S, Wells J, editors. Oxford Handbook of Palliative Care. 3rd ed. Oxford: Oxford University Press; 2019. p. 249, 274, 296-297, 306-309

WHO Analgesic Ladder

In 1986, the World Health Organisation (WHO) created a ladder for cancer pain management. It set out three stages of pain: mild, mild-moderate and moderate-severe. Options for pain management were recommended, with mild pain being treated with non-opioids, mild-moderate with weak opioids and moderate-severe with strong opioids. Adjuvant medications were recommended for use alongside every stage.

No single opioid has been proven to be more efficacious than the others. In common practice, morphine is the first opioid medication of choice. In renal disease, oxycodone may be used instead (or alfentanil, following specialist advice).

The mainstay of management in constant background pain, according to WHO, is that analgesia should be given “by the mouth” (orally), “by the clock” (at regular intervals) and “by the ladder” (using the WHO analgesic ladder in a stepwise manner).

Morphine Titration

When commencing morphine, the total dose taken in the first 24 hours can be used to calculate the total morphine requirement. Morphine may be titrated using 4-hourly immediate-release preparations or a mixture of modified-release preparations (starting at 2mg – 5mg) with immediate-release opioid breakthrough doses. Choice of medication is dependent on the patient’s preference, co-morbidities, age, severity of pain and their level of monitoring. Morphine should not be up-titrated by more than 33-50% every 24 hours.

Breakthrough doses are one-tenth to one-sixth of the 24-hour dose and can be given every 2-4 hours or up to one hourly if needed. If more than 3 doses are taken in 24 hours, this indicates the need to assess the patient’s pain and consider further up-titrating the dose of morphine or the use of a different analgesic.

Opioid Dose Equivalence

If patients become unable to swallow, oral preparations of morphine can be switched to the subcutaneous route and are often given through a syringe driver.

From To Calculation
Oral codeine Oral morphine Divide by 10
Oral tramadol Oral morphine Divide by 10
Oral morphine Subcutaneous morphine Divide by 2
Oral morphine Intravenous or subcutaneous diamorphine Divide by 3
Oral morphine Oral oxycodone Divide by 2
Oral oxycodone Subcutaneous oxycodone Divide by 2

Source: adapted from Scottish Palliative Care Guidelines. Choosing and Changing Opioids [Internet]. [cited 2023 Jul 16]. Available from: https://www.palliativecareguidelines.scot.nhs.uk/guidelines/pain/choosing-and-changing-opioids.aspx

Common Opioid Adverse Effects

Drowsiness

Drowsiness is a common but transient adverse effect when starting or increasing a dose of opioid medications. It usually settles after 2-3 days, and if it doesn’t, reducing the dose may be indicated.

Nausea and Vomiting

This is also a transient issue that usually passes after the first week. Ongoing symptoms can be managed with an antiemetic.

Constipation

Constipation is an ongoing and common adverse effect of opioids. NICE suggests co-prescribing a stimulant and softener laxative to help manage this effect. In cases resistant to usual constipation management, naloxegol may be indicated. Naloxegol is a peripherally-acting opioid receptor antagonist that can manage constipation without altering opioid pain management.

Dry Mouth

Many common medications have anticholinergic activity that can also lead to dry mouth. It is worth considering de-prescribing medications appropriately to help alleviate this issue. Non-pharmacological management in the form of ice lollies, boiled sweets and small sips of fluid can all help manage dry mouth.

Opioid Toxicity

Features of Opioid Toxicity

  • Hallucinations
  • Confusion
  • Extreme drowsiness
  • Myoclonus
  • Respiratory depression

Interestingly, opioids can increase the end tidal volume, so a reduction in respiratory rate does not always correlate with a decrease in oxygen saturation. Features of opioid toxicity requiring immediate reversal in the palliative patient are a respiratory rate of 8 or less, abnormal oxygen saturations, or any signs of cyanosis. In the palliative care setting, naloxone is not indicated for use in drowsiness that is not life-threatening.

Naloxone

If opioid reversal is indicated, 400 micrograms of the reversal agent naloxone should be diluted and given as a slow IV bolus at 80 micrograms at a time. It is rare that the full dose will need to be used.

Naloxone should be used cautiously to help prevent immediate return of pain. When too high a dose is given in patients who are established on opioids, it can also lead to significant acute withdrawal reactions that can cause life-threatening tachycardia, arrhythmia, hypertension and arrest.

Non-Opioid Medications

Neuropathic Agents

It is important to first assess the patient to ascertain if there is a treatable cause of neuropathic pain. This could include nerve compression from bone or soft tissue disease that could be managed with corticosteroids, radiotherapy, or surgery. First-line management of neuropathic pain is with either a tricyclic antidepressant, pregabalin or gabapentin.

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

NSAIDs can be used to treat inflammatory pain from soft tissue, as well as bone pain. Examples include non-selective NSAIDs that inhibit COX-1 and COX-2, such as ibuprofen, naproxen and diclofenac, or COX-2 specific medications, such as celecoxib.

Corticosteroids

Corticosteroids include dexamethasone and methylprednisolone and can be used to manage inflammation, oedema and compression-associated pain. They are used in the management of raised intracranial pressure, bone pain, nerve compression and liver capsule pain.

It is important to be aware that steroids have a large side effect profile. They are a potential cause of new-onset agitation or delirium in the palliative patient. Some side effects, such as insomnia and increased appetite, can be used to the patient’s advantage, and steroids may be prescribed solely if a patient wishes to be more alert or to eat more.

Muscle Relaxants

Muscle spasm can be a cause of significant pain at the end of life. This can be treated with muscle relaxants such as benzodiazepines or baclofen. Non-pharmacological management, such as heat pads, massage or transcutaneous electrical nerve stimulation (TENS), may also be used.

Non-Pharmacological Management of Pain

Nerve Blocks

Local nerve blocks can be used to help manage pain and can reduce the need for large opioid doses. Examples include coeliac plexus blocks for upper abdominal pain and saddle blocks for perineal or perianal pain. Spinal or epidural nerve blocks may also be used for difficult-to-manage pain.

Radiotherapy

Radiotherapy can be used to manage localised bone pain alongside analgesia, steroids and bisphosphonates. This can be completed as a single fraction, requiring one visit, or in multiple fractions, requiring multiple visits. The patient’s prognosis and personal choice should be taken into account when deciding between single and multiple-fraction radiotherapy.

Surgery

This can include prophylactic fixation of long bones with lytic metastases, vertebroplasties for unstable vertebral fractures and debulking of tumours causing problems due to compression.

Complementary, Psychosocial and Spiritual Care

Pain can be significantly affected by psychosocial and spiritual components. A multidisciplinary team approach and a holistic view of managing pain can help to reduce medication use and allow for an individual approach to pain management. Psychosocial management strategies include, but are not limited to:

  • Heat pads
  • Cool pads
  • Occupational therapy
  • Complementary therapy
    • Acupuncture
    • Reflexology
    • Massage
  • Creative therapies
  • Psychological therapies
    • Hypnotherapy
    • Meditation
    • Counselling
    • CBT
  • Patient and family education

References

Recognising the Dying Patient

Determining whether a patient has entered the dying phase can sometimes be difficult. Signs that can be indicative of a patient entering the terminal phase of their illness include:

  • Agitation
  • Low conscious level
  • Fatigue
  • Social withdrawal
  • Deteriorating mobility
  • Low appetite
  • Abnormal breathing patterns
  • Noisy secretions
  • Mottled skin

It is important to gather information on patients’ physical, emotional, social and spiritual needs and understand their goals, wishes and feelings about their future. This can help guide individualised and appropriate care when patients enter the dying stage.

Anticipatory Prescribing

Some medications are commonly prescribed towards the end of life. These help manage common end-of-life signs and symptoms, such as agitation and anxiety, breathlessness, nausea and vomiting, respiratory secretions and pain. They may also be prescribed for specific scenarios, such as catastrophic haemorrhage or seizure. Medication type, dose and route should be decided upon based on each individual patient, taking into account their preferences, level of arousal and their ability to swallow safely. In the last few days of life, medicines may be administered subcutaneously and continuous medication can be given via a syringe driver.

Respiratory

Breathing at the End of Life

When approaching the end of life, patients’ breathing may become laboured. Cheyne-Stokes breathing pattern may be seen; this is a pattern of crescendo-decrescendo respirations followed by a period of apnoea. Agonal breathing may also be observed as slow, shallow, irregular respirations.

Due to an inability to cough or swallow effectively, a build-up of secretions in the respiratory system can lead to noisy, rattling breathing. The secretions do not usually distress the patient but can be significantly distressing to their loved ones. They can be managed with simple education of the patient’s loved ones, positioning the patient differently or an anticholinergic such as glycopyrronium bromide, hyoscine butylbromide or hyoscine hydrobromide. One of these pharmacological options will usually be prescribed as an anticipatory medication at the end of life.

Dyspnoea

Breathlessness is a common issue in palliative medicine, affecting over half of patients at the end of life. It is not always associated with lung or pleural pathology. The management of breathlessness depends on the cause and the individual patient. Multiple causes may be identified. Management may be a mixture of pharmacological, non-pharmacological and interventional procedures.

Anticipatory prescribing for terminal breathlessness is usually in the form of PRN subcutaneous doses of morphine sulphate (2mg – 5mg) or midazolam for breathlessness associated with anxiety and distress (2mg – 5mg).

Causes of Dyspnoea

End of Life Cancer Related Organ Failure Psychosocial Other
  • Pain
  • Weakness
  • Lung or oropharyngeal cancers (airway obstruction may be treated with steroids or stenting)
  • Malignant pleural effusion (may be treated with pleural aspiration)
  • Malignant ascites (may be treated with diuretics and/or paracentesis)
  • COPD
  • Heart failure
  • Liver failure
  • Ascites
  • Anxiety
  • PE
  • Infection
  • Anaemia
  • Medications

Source: Created by Dr Tasneem Wadee. Adapted from Back I, Watson M, Armstrong P, et al. Palliative Care Adult Network Guidelines. Dyspnoea/Breathlessness. [Internet]. 2021 [cited 2023 Jul 16]. Available from: https://book.pallcare.info/index.php

Non-Pharmacological Management of Dyspnoea

  • Handheld fan
  • Breathing exercises
  • Positioning
  • Pulmonary rehabilitation
  • Complementary therapy
  • Physiotherapy
  • Anxiety reduction strategies

Cough

Cough may be due to effects of cancer in the lungs or airways, as well as end-stage COPD and heart failure. There are also causes that can potentially be reversed, such as asthma, infection and reflux.

Treatment of the causative issue, such as aspirations of pleural effusions, radiotherapy for tumour masses and antibiotics for infection, may all be appropriate interventions. Symptom control can be in the form of a cough suppressant, such as a simple linctus, codeine or morphine. Humidified air, nebulised saline and mucolytics can all help to encourage expectoration.

Gastrointestinal

Nausea and Vomiting

Nausea and vomiting are common issues at the end of life, affecting over half of patients with cancer and just under half of those with end-stage heart or renal failure.

Understanding the aetiology of nausea and vomiting allows for more successful management by targeting specific neurotransmitters and other causes with suitable pharmacological and non-pharmacological techniques. Patients may need more than one medication to treat their nausea and vomiting, alongside complementary and psychosocial management. Anticipatory medications at the end of life usually include a subcutaneous PRN antiemetic, usually in the form of levomepromazine or haloperidol.

Pathophysiology of Nausea and Vomiting

A number of neurotransmitters are involved in nausea and vomiting. The vomiting centre, which is located in the brainstem, triggers the vomiting reflex. It receives input from the gastrointestinal system, the chemoreceptor trigger zone, the vestibular system and the cerebral cortex. The cerebral cortex is stimulated by pressure receptors, memory and emotions such as fear and pain.

  • Chemoreceptor Trigger Zone
    • Serotonin
    • Dopamine
    • Acetylcholine
    • Histamine
  • Gastrointestinal System
    • Serotonin
    • Acetylcholine
  • Vestibular Apparatus
    • Histamine
    • Acetylcholine

Causes of Nausea and Vomiting

Medication and Radiotherapy Gastrointestinal Organ Failure Biochemical and Metabolic Brain
  • Opioids
  • Chemotherapy
  • Radiotherapy
  • Gastric stasis (may be due to autonomic dysfunction or medications)
  • Ascites and hepatomegaly
  • Bowel obstruction (can cause pain, colic, nausea, vomiting and constipation. Partial obstruction may be treated with stenting or dexamethasone.)
  • End-stage liver disease (accumulation of toxins, biochemical disturbances, gastric stasis and ascites)
  • End-stage renal failure (accumulation of toxins and biochemical disturbances)
  • Hypercalcaemia
  • Uraemia
  • Adrenal insufficiency
  • Raised intracranial pressure (RICP)
  • Vestibular disturbance
  • Anticipatory nausea and vomiting

Source: Adapted from Back I, Watson M, Armstrong P, et al. Palliative Care Adult Network Guidelines. Nausea and Vomiting. [Internet]. 2021 [cited 2023 Jul 16]. Available from: https://book.pallcare.info/index.php?tid=2

Pharmacological Management of Nausea and Vomiting

Antiemetic Receptor Site To be Aware
Cyclizine Histamine and acetylcholine antagonist Vestibular system and vomiting centre Can be given alongside dexamethasone for RICP
Haloperidol Dopamine (D2) antagonist Central Good for biochemical causes, opioid-induced nausea and vomiting and renal failure
Levomepromazine Serotonin (5HT2), dopamine, acetylcholine and histamine antagonist Central Broad spectrum agent that can be used in difficult-to-manage nausea and vomiting
Metoclopramide Dopamine (D2) antagonist centrally and peripherally

Serotonin (5HT4) antagonist (gut)

 Chemoreceptor trigger zone and gut Prokinetic – avoid in mechanical bowel obstruction.

Can cause acute dystonic reactions and extrapyramidal side effects.

Concomitant antimuscarinic use will antagonise the antiemetic effects.
Domperidone Dopamine (D2) antagonist Gut Prokinetic – avoid in mechanical bowel obstruction
Ondansetron Serotonin (5HT3) antagonist Central and gut
Hyoscine Hydrobromide Acetylcholine antagonist Vestibular system and vomiting centre Used first-line for nausea and vomiting associated with bowel obstruction. If there has been no benefit after 24 hours, a switch should be made to Octreotide, a somatostatin analogue.
Aprepitant Neurokinin-1 receptor antagonist Central Used for chemotherapy-related nausea and vomiting
Nabilone Cannabinoid receptor agonist Central and peripheral Synthetic cannabinoid used as an adjunct in intractable nausea and vomiting, where conventional medications have been optimised
Dexamethasone Glucocorticoid receptors Not clearly understood Used for chemotherapy-associated, RICP-associated or refractory nausea and vomiting

Source: Adapted from Back I, Watson M, Armstrong P, et al. Palliative Care Adult Network Guidelines. Nausea and Vomiting. [Internet]. 2021 [cited 2023 Jul 16]. Available from: https://book.pallcare.info/index.php?tid=2

Non-Pharmacological Management of Nausea and Vomiting

  • Small meals
  • Avoid hot beverages
  • Relaxation techniques
  • CBT for anticipatory nausea and vomiting

Constipation

Constipation is a common issue in palliative care. It affects around 80% of patients with cancer.

Causes

  • Medications such as opioids and anticholinergics
  • Biochemical disturbances such as hypercalcaemia and hypokalaemia
  • Neurological conditions, including spinal cord compression
  • Tumour-related, for example, bowel obstruction
  • The dying process
    • Decreased activity
    • Low dietary intake
    • Decreased hydration

Management

Non-pharmacological management options do exist(such as increasing mobility, maintaining diet and hydration and stopping culprit medications), but in patients nearing the end of their lives, this may be neither achievable nor appropriate.

Laxatives Commonly Used in Palliative Care 

Classification Mechanism of Action Examples
Stimulant Laxatives Increases motility of the GI tract (and can, therefore, cause cramping) Bisacodyl

Senna

Glycerol – lubricant and a rectal stimulant
Faecal Softeners Causes fluid to penetrate the faeces Docusate sodium – also has stimulant properties

Arachis oil
Osmotic Laxatives Increases the volume of water in the large bowel Lactulose

Macrogols

Source: Created by Dr Tasneem Wadee. British National Formulary (BNF). Constipation: Treatment Summaries [Internet]. [cited 2023 Jul 16]. Available from: https://bnf.nice.org.uk/treatment-summaries/constipation/

Stepwise Pharmacological Management of Constipation in Palliative Care

  1. Start with a stimulant laxative
    • Up-titrate to most effective and tolerated dose
  2. If still not controlled, add an osmotic or softening laxative
    • Up-titrate to most effective and tolerated dose
  3. If the above combination does not work, and the rectum is full, treat according to whether stool in the rectum is soft or hard
    • Soft stool: bisacodyl suppository
    • Hard stool: glycerol suppository
    • Very hard stool: Arachis oil enema (contraindicated in nut allergy)

Phosphate enemas and bulk-forming laxatives should be avoided in this subset of patients. Phosphate enemas can lead to electrolyte disturbances, and bulk-forming laxatives without adequate hydration can lead to worsening of constipation and even bowel obstruction.

Hiccups

Ongoing hiccups can be distressing for patients. They are most commonly due to gastric stasis and distention but can also be due to reflux, irritation of the diaphragm or phrenic nerve, hepatic disease or metabolic disturbances. They usually cease spontaneously.

Peppermint water, antacids or proton pump inhibitors may be used as first-line pharmacological management. Prokinetic medications, such as domperidone or metoclopramide, are also options.

Intractable hiccups that do not settle with the above management can be treated with haloperidol, baclofen, levomepromazine or nifedipine, all under the recommendation of a specialist.

Neurological

Decreased Alertness

It is common for people in the terminal stages of life to be less easily rousable and spend more time sleeping. There is evidence to suggest that people can still hear even if they are not rousable, and loved ones can therefore be encouraged to continue talking to the patient.

Terminal Agitation

Agitation and restlessness may occur in the terminal phase. It is important to explore possible reversible causes, if appropriate, such as pain, constipation, a full bladder or metabolic disturbances. If no reversible cause can be identified, agitation can be managed with midazolam, haloperidol or levomepromazine. Midazolam may be prescribed as a subcutaneous PRN medication for agitation or anxiety at the very end of life.

References

Allied Teams Involved in End-of-Life Care

The palliative care team consists of medical professionals, allied health professionals and social care workers, both in the community and inpatient settings. The patient and their loved ones remain at the heart of the team, who work together to allow for individualised care at the end of life. Below is a non-exhaustive list of members of the multidisciplinary team in palliative care:

  • Doctors
    • Hospital
    • Hospice
    • GP
  • Nurses
    • Hospital
    • Hospice
    • Macmillan nurses: specialist cancer nurses working both in the hospital and the community to support patients and their loved ones
    • District nurses: provide complex care in the community to patients with long-term conditions
  • Carers
  • Pharmacists
  • Speech and Language Therapists: can help with swallowing as well as communication, for example, in neurological conditions and oropharyngeal cancers
  • Dieticians: complete nutritional assessments, assess suitability for supplements and help to support tube feeding
  • Physiotherapists
  • Occupational therapists
  • Complementary therapists can provide alternative therapies such as acupuncture, massages, Reiki and aromatherapy
  • Psychologists and counsellors: both for patients and for their loved ones if required
  • Faith and spiritual leaders

Place of Care

Patients can be cared for in a number of places at the end of their life. This location depends on their own preferences and care needs. Their own home, hospices, hospitals, care homes, and nursing homes are all available options.

Religious and Spiritual Care

Spirituality describes a person’s quest to find meaning in their life. This can be in the form of faith but can also be expressed in people who do not follow a religion.

It is important to assess patients’ spiritual needs during their illness. This can be done at any point from diagnosis right through to the terminal stage. Assessing spiritual needs allows for individualised support to be given, including access to religious and spiritual caregivers.

Delivering spiritual care in the palliative setting may include listening to the patient’s experience, respecting and protecting their identity and dignity, and discussing thoughts around life, death and meaning. Spiritual care can also allow for the provision of religious rituals at the end of life.

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