5th January 2024

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

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

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
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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 

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

• Back I, Watson M, Armstrong P, et al. Palliative Care Adult Network Guidelines. [Internet]. 2021 [cited 2023 Jul 16]. Available from: https://book.pallcare.info/index.php
• Blundon EG, Gallagher RE, Ward LM. Electrophysiological evidence of preserved hearing at the end of life. Scientific Reports. 2020;10(1). DOI: 10.1038/s41598-020-67234-9. Available from: https://www.nature.com/articles/s41598-020-67234-9
• BMJ Best Practice. Palliative Care [Internet]. [cited 2023 Jul 16]. Available from: https://bestpractice.bmj.com/topics/en-gb/1020/details
• British National Formulary (BNF). Constipation: Treatment Summaries [Internet]. [cited 2023 Jul 16]. Available from: https://bnf.nice.org.uk/treatment-summaries/constipation/
• British National Formulary (BNF). Prescribing in Palliative Care [Internet]. [cited 2023 Jul 16]. Available from: https://bnf.nice.org.uk/medicines-guidance/prescribing-in-palliative-care/
• Clinical Knowledge Summaries (CKS). Hiccups – Management [Internet]. [cited 2023 Jul 16]. Available from: https://cks.nice.org.uk/topics/hiccups/management/management/
• Clinical Knowledge Summaries (CKS). Noisy Respiratory Secretions at the End of Life [Internet]. In: Palliative Care – Secretions. [cited 2023 Jul 16]. Available from: https://cks.nice.org.uk/topics/palliative-care-secretions/management/noisy-respiratory-secretions-at-the-end-of-life/
• Clinical Knowledge Summaries (CKS). Palliative Care – Constipation [Internet]. [cited 2023 Jul 16]. Available from: https://cks.nice.org.uk/topics/palliative-care-constipation/
• Clinical Knowledge Summaries (CKS). Palliative Care – Cough [Internet]. [cited 2023 Jul 16]. Available from: https://cks.nice.org.uk/topics/palliative-care-cough/
• Clinical Knowledge Summaries (CKS). Palliative Care – Nausea and Vomiting [Internet]. [cited 2023 Jul 16]. Available from: https://cks.nice.org.uk/topics/palliative-care-nausea-vomiting/
• Darmani NA, Zhao W, Ahmad B, et al. The cellular mechanisms of the antiemetic action of dexamethasone and related glucocorticoids against vomiting. Eur J Pharmacol. 2014 Jan 5;722:48-54. doi: 10.1016/j.ejphar.2013.10.008. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0014299913007486?via%3Dihub
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• National Institute for Health and Care Excellence. Care of Dying Adults in the Last Days of Life. NICE Guideline [NG31]. London: National Institute for Health and Care Excellence. Available from: https://www.nice.org.uk/guidance/ng31
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• Scottish Palliative Care Guidelines. Bowel Obstruction [Internet]. [cited 2023 Jul 16]. Available from: https://www.palliativecareguidelines.scot.nhs.uk/guidelines/symptom-control/bowel-obstruction.aspx
• Scottish Palliative Care Guidelines. Care in the Last Days of Life [Internet]. [cited 2023 Jul 16]. Available from: https://www.palliativecareguidelines.scot.nhs.uk/guidelines/end-of-life-care/care-in-the-last-days-of-life.aspx
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• UpToDate. Palliative Care for Patients with End-Stage Liver Disease [Internet]. [cited 2023 Jul 16]. Available from: https://www.uptodate.com/contents/palliative-care-for-patients-with-end-stage-liver-disease#H502395891
• Whited L, Graham DD. Abnormal Respirations. [Updated 2023 Mar 9]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470309/