8th January 2024

Management of Physical Symptoms Other Than Pain

Respiratory

Dyspnoea

Dyspnoea, or breathlessness, is the subjective experience of breathing discomfort. This encompasses effort of breathing, chest tightness and air hunger. Dyspnoea is complex and occurs due to the interplay of physical, psychological and social factors. It affects patients with both malignant and non-malignant disease and is a common reason for hospital attendance, with figures suggesting up to 25% of accident and emergency (A&E) visits in the UK are due to dyspnoea.

Causes of Dyspnoea

Dyspnoea is often multi-factorial, and thorough assessment should exclude reversible causes, such as infection, anaemia or pulmonary embolus. Consider the speed of onset of breathlessness and its behaviour (Present at rest? Present on minimal exertion? Present on certain activities, or less predictable?)

• Respiratory – COPD, pneumonia, pleural effusion, pulmonary embolus
• Cardiac – Heart failure, arrhythmias
• Musculoskeletal – Respiratory muscle weakness, e.g., motor neuron disease, chest wall deformities
• Systemic – Anaemia, ascites, obesity
• Malignancy-Related – Lung malignancy, airway obstruction by tumour, mesothelioma, side-effects of treatment, including radiation-induced fibrosis or chemotherapy-induced pneumonitis, superior vena cava obstruction (SVCO)
• Psychological – Anxiety, panic disorder

Management of Dyspnoea

Dyspnoea is a distressing and frightening symptom for patients and their families. Explanation of the factors contributing to dyspnoea and what can be done to treat it or ease the symptoms can help with anxiety, and patients should be encouraged to discuss their fears.

Non-Pharmacological:

• Energy Conservation Techniques
  • Sitting upright and leaning forward improves ventilatory capacity
  • Exercise and pulmonary rehabilitation can prevent deconditioning
  • Physiotherapy can help with breathing exercises and techniques to reduce breathlessness
  • Occupational therapy input for home adaptations
• Cognitive Behavioural Strategies
  • Manages anxiety and negative thoughts due to breathlessness
• Breathing Strategies
  • Controlled breathing techniques, e.g., pursed lip breathing
  • Breathing retraining – Improves respiratory muscle strength and sense of control
  • Handheld fan blows air across the face and nose and reduces the sensation of breathlessness

Pharmacological:

• Opioids
  • Reduce breathlessness at rest and end-of-life stage by slowing the ventilatory response to hypoxia and hypercapnia
  • Morphine can be given as regular, low-dose modified release for constant dyspnoea, 10-20mg per day, or as immediate release 2.5-5mg as needed. Subcutaneous morphine should be used if the patient cannot swallow
  • Monitor for side effects, especially nausea and constipation
• Steroids
  • Useful for lymphangitis or airway obstruction due to tumour
  • Dexamethasone 8-16mg given orally in the morning
• Benzodiazepines
  • Relieves anxiety associated with breathlessness
  • Not as effective as opioids for breathlessness
  • Lorazepam is short-acting, and 500mcg 4-6 hourly sublingual PRN can be useful acutely, or longer-acting diazepam 2 or 5mg or clonazepam 0.5-1mg if continuous anxiety
• Oxygen
  • Patients with dyspnoea who are hypoxaemic (SP02 ≤ 92%) may benefit from supplemental oxygen
  • There is a poor relationship between breathlessness, hypoxaemia and response to oxygen therapy

Secretions

Secretions can accumulate in a palliative patient’s oropharynx and cause a rattling or gurgling noise (‘death rattle’). This can occur if clearance of secretions is inadequate, such as impaired cough or swallow when approaching the end of life, or due to sedating medications. There may be increased viscosity of secretions due to dehydration or illness, or being nursed in a supine position means secretions accumulate in the hypopharynx.

Secretions may also be excessive if there is a chest infection or fluid overload resulting in pulmonary oedema, both of which can be difficult to diagnose in the final stage of life.

Management

The noises may be distressing for patients or their families but aren’t usually uncomfortable. Explanation may be adequate to reassure the person and their family.

Non-Pharmacological:

• Positioning
• Gentle oral suctioning

Pharmacological:

• Glycopyronnium bromide
• Hyoscine hydrobromide
• Hyoscine butylbromide – Crosses blood-brain barrier
• Side effects can include sedation, confusion, agitation, dry mouth and confusion, which should be closely monitored
• In a patient approaching end of life, antibiotics may be considered if a patient has large amounts of purulent sputum that is causing distress

References

• • Boland JW, Boland EG Noisy upper respiratory tract secretions: pharmacological management BMJ Supportive & Palliative Care 2020;10:304-305
  • Chin C, Booth S. Managing breathlessness: a palliative care approach. Postgraduate Medical Journal. 2016;92(1089):393-400.
  • Parshall M, Schwartzstein R, Adams L, Banzett R, Manning H, Bourbeau J et al. An Official American Thoracic Society Statement: Update on the Mechanisms, Assessment, and Management of Dyspnea. American Journal of Respiratory and Critical Care Medicine. 2012;185(4):435-452.
  • Watson M, Campbell R, Vallath N, Ward S, Wells J. Oxford Handbook of Palliative Care. 3rd ed. Oxford University Press; 2019.
  • Palliative Care Guidelines Plus [Internet]. Book.pallcare.info. 2021 [cited 3 April 2022]. Available from: https://book.pallcare.info/index.php
  • Palliative care – dyspnoea | Health topics A to Z | CKS | NICE [Internet]. Cks.nice.org.uk. 2022 [cited 3 April 2022]. Available from: https://cks.nice.org.uk/topics/palliative-care-dyspnoea/
  • Palliative care – secretions | Health topics A to Z | CKS | NICE [Internet]. Cks.nice.org.uk. 2022 [cited 18 Aug 2022]. Available from: https://cks.nice.org.uk/topics/palliative-care-secretions/

Neurological Symptoms

Depression

The prevalence of depressive disorder in the UK general population is around 7.5%, but around 15% of palliative patients meet the diagnostic criteria for major depressive disorder, and many others exhibit depressive symptoms. For a diagnosis of depression, at least one of the core symptoms must be present for at least two weeks. Other associated symptoms, as shown below, should also be considered.

Palliative patients have additional risk factors for depression. This is especially true for those who are young, have advanced disease at diagnosis, are socially isolated, have poor symptom control, have had a decline in performance status, have a previous personal or family history of depression, and those with additional life stresses such as a recent bereavement or relationship breakdown.

The associated symptoms used to diagnose depression, as shown above, can be less useful in palliative patients who may have fatigue, appetite changes or sleep disturbances because of their disease or treatment.

Screening tools to help diagnose depression includes the PHQ-9, which is used in primary care. The Hospital Anxiety and Depression (HAD) questionnaire is largely focused on physical symptoms, so it may not be useful in a palliative setting, whilst the Brief Edinburgh Depression Scale (BEDS) has been shown to be more valuable in a palliative context.

Differentials for Depression in Palliative Patients

• Dementia
• Poorly controlled physical symptoms
• Medication side-effects, e.g., steroids, methyldopa, propranolol
• Brain metastases
• Metabolic – hypothyroidism, hypercalcaemia, B12/ folate deficiency

Management of Depression

Non-Pharmacological:

• Adequate symptom control and referral to palliative services if necessary
• Guided self-help programmes
• Cognitive Behavioural Therapy (CBT)
• Counselling

Pharmacological:

There is currently insufficient evidence to recommend one antidepressant over another, so choice should be based on the patient’s previous experience with antidepressants, likelihood of interactions with other medications and consideration of side effects. It is important to remember that antidepressants can take several weeks to work, so if someone is approaching end-of-life, there will be insufficient time for the medication to work.

• SSRIs e.g., sertraline, fluoxetine, citalopram
  • Side effects include nausea, vomiting, anorexia, diarrhoea, increased risk of gastrointestinal (GI) bleeding, insomnia, agitation and increased risk of serotonin syndrome if used with other serotonergic medications
  • Serotonin syndrome is a group of symptoms that can happen with use of serotonergic medications, e.g. SSRIs, MAOIs, St John’s Wort, ecstasy, and amphetamines. Symptoms include confusion, sweating, hyperthermia, hyperreflexia, myoclonus and rigidity. Management is supportive, including IV fluids and benzodiazepines may be used. In more severe cases, serotonin antagonists such as cyproheptadine or chlorpromazine may be necessary
• Mirtazapine
  • Generally, well tolerated and can have beneficial effects on appetite, weight gain and management of insomnia
• Tricyclics, e.g., amitriptyline
  • Antimuscarinics can cause dry mouth, constipation, blurred vision and urinary retention. It can have a role in palliative patients with neuropathic pain but would generally not be started as first line for depression

Pruritus

Pruritis or itch is an unpleasant sensation of the skin or mucous membranes that elicits the urge to rub or scratch the area.

It is not as common in palliative patients as pain or breathlessness but can significantly affect quality of life.

The pathophysiology of pruritus is dependent on the cause and is often independent of histamine, e.g., uraemic pruritus, meaning antihistamines can have a limited role.

Assessment

Palliative patients may have multiple reasons for pruritus, so should be assessed for skin conditions like eczema and contact dermatitis, and infectious causes such as candidiasis or fungal infection should be excluded.

Medications should be reviewed as opioids, Penicillins, and cephalosporins can all contribute to pruritus. If any new medications have been started, drug reaction should be excluded.

Blood tests should be considered, and possible conditions contributing to pruritus are listed below:

• Full blood count – Polycythaemia, leukaemia, lymphoma, multiple myeloma
• Ferritin (If anaemic) – Iron deficiency
• Urea and electrolytes – Uraemia in renal failure
• Liver function tests – hepatic failure, cholestatic jaundice
• Bone profile – Hyperphosphatemia, hypercalcaemia
• Thyroid function – Hyperthyroidism
• HIV test – Pruritus can occur in up to 30% of those with HIV

Management of Pruritus

Conservative

• Ensure skin is not dry
• Soap substitutes and emollients
• Short fingernails
• Psychological support to help break cycle of itching and scratching

Pharmacological and Non-Pharmacological Management by Diagnosis

Sedating antihistamines like chlorphenamine, benzodiazepines or doxepin given at night can help with sleep. Other strategies may be appropriate depending on the cause, as shown in Table 1.

Source: Watson M, Campbell R, Vallath N, Ward S, Wells J. Oxford Handbook of Palliative Care. 3rd ed. Oxford University Press; 2019.

Fatigue

Fatigue is a sustained, subjective feeling of weakness, tiredness, or low energy. It is reported in up to 80% of patients with cancer, and this increases following treatments like radiotherapy. It is also prevalent in people with non-malignant diseases, including COPD, CCF and multiple sclerosis.

In malignancy, inflammatory cytokines can contribute to fatigue, but secondary causes are common and should be excluded.

Causes of Fatigue

• Organ dysfunction – Renal/ cardiac/ hepatic failure
• Hypothyroidism
• Adrenal insufficiency
• Anaemia
• Infection
• Nutrition – Poor diet/ malabsorption
• Sleep pattern
• Physical exertion or deconditioning
• Depression/ anxiety

Management

Non-Pharmacological:

• Diary – Identifying any triggers for symptoms
• Conserving energy – Prioritising tasks, pace activities, schedule tasks for the time with most energy, occupational therapy input
• Physical activity – Exercise can reduce fatigue, and physiotherapy input may be beneficial
• Stress and anxiety management
• Complementary therapy

Pharmacological:

• Dexamethasone 2-4mg OD may improve appetite, nausea, and subjective feelings of weakness but is more appropriate in those with anorexia/cachexia

References

• Radbruch L, Strasser F, Elsner F, Gonçalves JF, Løge J, Kaasa S, Nauck F, Stone P; Research Steering Committee of the European Association for Palliative Care (EAPC). Fatigue in palliative care patients — an EAPC approach. Palliat Med. 2008 Jan;22(1):13-32. doi: 10.1177/0269216307085183. PMID: 18216074.
• Scottish Palliative Care Guidelines. 2022. [online] Available at: <https://www.palliativecareguidelines.scot.nhs.uk/guidelines/symptom-control/weakness-fatigue.aspx> [Accessed 5 April 2022].
• Blanes M, Belinchón I, Portilla J, Betlloch I, Reus S, Sánchez-Payá J. Pruritus in HIV-infected patients in the era of combination antiretroviral therapy: a study of its prevalence and causes. International Journal of STD & AIDS. 2012;23(4):255-257.
• Scottish Palliative Care Guidelines. 2022. [online] Available at: <https://www.palliativecareguidelines.scot.nhs.uk/guidelines/symptom-control/Pruritis.aspx> [Accessed 5 April 2022].
• Arias De La Torre, J. et al. 2021. Prevalence and age patterns of depression in the United Kingdom. A population-based study. Journal of Affective Disorders 279, pp. 164–172.
• 2022. The Management of Depression in Palliative Care EUROPEAN CLINICAL GUIDELINES. [eBook] Available at: <https://www.kcl.ac.uk/cicelysaunders/attachments/depression-guidlines/the-management-of-depression-in-palliative-care.pdf> [Accessed 20 April 2022].
• Scottish Palliative Care Guidelines. 2022. [online] Available at: <https://www.palliativecareguidelines.scot.nhs.uk/guidelines/symptom-control/weakness-fatigue.aspx> [Accessed 5 April 2022].
• Lloyd-Williams M, Shiels C, Dowrick C. The development of the Brief Edinburgh Depression Scale (BEDS) to screen for depression in patients with advanced cancer. J Affect Disord. 2007 Apr;99(1-3):259-64. doi: 10.1016/j.jad.2006.09.015. Epub 2006 Oct 20. PMID: 17055588.
• Volpi-Abadie, Jacqueline et al. “Serotonin syndrome.” The Ochsner journal vol. 13,4 (2013): 533-40.
• Watson M, Campbell R, Vallath N, Ward S, Wells J. Oxford Handbook of Palliative Care. 3rd ed. Oxford University Press; 2019.

Gastrointestinal Symptoms

Nausea and Vomiting

Nausea is an unpleasant sensation of needing to vomit and is often associated with autonomic symptoms such as sweating, pallor, salivation and tachycardia. It is often accompanied by vomiting, which is the forceful ejection of stomach contents through the mouth. Patients generally report that nausea is more debilitating, lasts longer and feels worse than vomiting. There are many possible causes in a palliative patient, so thorough assessment is essential. Nausea and vomiting should be assessed separately. Ask about any triggers or patterns to the nausea and vomiting, as well as relieving factors and associated symptoms. If a patient vomits, does this relieve nausea, or does it persist?

Causes of Nausea and Vomiting

Possible causes of nausea and vomiting in palliative patients are highlighted below in Table 2.

Source: Watson M, Campbell R, Vallath N, Ward S, Wells J. Oxford Handbook of Palliative Care. 3rd ed. Oxford University Press; 2019.

Nausea caused by medication and metabolic disturbances will often present with persistent nausea with minimal relief from vomiting.

If there is delayed gastric emptying, there will be minimal nausea until vomiting is imminent. The patient will typically vomit a large volume, which will temporarily relieve nausea.

Additional symptoms should be considered. If a patient has headache, altered consciousness, and worse symptoms on movement, consider raised intracranial pressure.

Management of Nausea and Vomiting

Reversible causes should be treated, e.g., metabolic disturbance, pain, raised intracranial pressure, tense ascites, constipation and anxiety. Current medication use should be reviewed and adjusted accordingly.

Non-Pharmacological:

Being in a calm environment, away from the sight and smell of food can help. Offer the person regular small portions of food with little odour, instead of large meals.

Relaxation techniques and acupressure bands are helpful for some patients.

Pharmacological:

The choice of antiemetic should be based on the cause of nausea and vomiting, as shown in Table 3. Consider the most appropriate route of administration – patients may struggle to take tablets orally due to nausea, or absorption may be inadequate due to vomiting. Administering parenterally will reduce tablet burden, and giving via continuous subcutaneous infusion (CSCI), i.e., a syringe driver will ensure constant delivery of antiemetic.

Source: Watson M, Campbell R, Vallath N, Ward S, Wells J. Oxford Handbook of Palliative Care. 3rd ed. Oxford University Press; 2019.

Anorexia and Cachexia

Patients with malignancy often suffer from anorexia, or reduced appetite, and cachexia, which is the progressive loss of skeletal muscle and sometimes adipose tissue. Anorexia and cachexia often occur in parallel, and this is termed cancer anorexia-cachexia syndrome (CACS). CACS occurs in 15-40% of patients with cancer, increasing to 80% in those with advanced disease. It is especially common in those with pancreatic and gastric cancers. The resulting malnutrition is associated with reduced survival, as well as reduced benefit from treatments, including chemotherapy and reduced overall quality of life.

Cachexia can be broken down into primary causes, i.e., metabolic changes brought about by the cancer itself and secondary causes, i.e., dietary factors causing reduced oral intake, such as nausea, vomiting, chemotherapy-induced changes in smell and taste, constipation and obstruction from tumours, e.g., oesophageal.

When assessing patients with CACS, it is important to ensure reversible causes of anorexia are excluded and treated, e.g., pain, depression, anxiety, heartburn, ascites, medications, oral pain and biochemical abnormalities, including hypercalcaemia and uraemia.

Management of CACS

Treatment of cancer-associated cachexia is best achieved by removal of the malignancy, but this is unfortunately not always possible.

Involvement of the MDT is essential, with dieticians having a key role.

Non-Pharmacological:

Exploring the concerns of patients and their families around anorexia and explaining that appetite will often decrease can provide some reassurance.

Encourage any oral intake that the patient can manage, irrespective of nutritional or health benefit, and try to discourage carers from talking about food too much. Offer foods that are soft and easy to swallow, such as soup or pudding, or cold, plain foods with little odour.

Nutritional supplements have variable impact on body weight and nutritional intake in CACS, and don’t reverse cachexia but can be enjoyable and provide reassurance for the patient and their family.

Enteral and parenteral nutrition do not reverse cachexia and is not routinely recommended. It can have a role when patients are expected to have inadequate oral intake for several days, e.g., after surgery, and have a life expectancy of over two months.

Pharmacological:

Corticosteroids help in the short-term improvement of appetite and improve nausea and fatigue but do not impact overall nutritional status. They should be prescribed for 1 week and stopped if no benefit is seen during this time.

Progesterones, including megesterol acetate, improve appetite and calorie intake over several weeks, with effects potentially lasting for months. They cause weight gain, but this is due to increased fat mass instead of lean body mass.

Prokinetic drugs such as metoclopramide or domperidone can be used for nausea, gastroparesis, early satiety or delayed gastric emptying.

Constipation

Constipation describes infrequent bowel movements or those that are difficult to pass or result in a sensation of incomplete emptying. Stools are often small, dry and hard. Stool frequency varies between individuals, but constipation is often defined as fewer than three bowel movements per week.

Causes of constipation in palliative patients

Medications:

• Opioids – Up to 90% of patients will require concomitant laxatives
• Iron or calcium supplements
• Antidepressants, including tricyclics like amitriptyline
• Anti-psychotics, including quetiapine and clozapine
• Anti-epileptics including carbamazepine, gabapentin, pregabalin
• Calcium channel blockers
• Diuretics
• Antiemetics – Ondansetron, Cyclizine
• Chemotherapy

Endocrine:

• Diabetes mellitus – Type 1 or 2 resulting in autonomic neuropathy
• Hypothyroidism
• Electrolyte derangement – hypercalcaemia
• Neurological – Depression, multiple sclerosis, Parkinson’s disease, spinal cord injury

Structural:

• Anal fissures
• Haemorrhoids
• Rectal prolapse

Dietary/ Environmental:

• Low fibre diet
• Low-calorie intake
• Dehydration
• Change in lifestyle – going into hospital/ hospice/ residential care
• Poor mobility/ inactivity
• Lack of privacy

Patients with malignancies have several additional risk factors for developing constipation

Malignancy-Related:

• Bowel obstruction from bowel malignancy or extra-luminal compression from abdominal or pelvic tumours
• Cauda equina or compression or infiltration of pelvic or spinal nerves
• Autonomic neuropathy – associated with small-cell lung cancer + carcinoid tumours

Consequences of Constipation

• Pain
• Nausea and vomiting
• Faecal retention which can cause rectal distention and impair sensory and motor function of the rectum
• Faecal impaction
• Bowel obstruction
• Faecal incontinence
• Rectal bleeding or prolapse
• Urinary retention and infection
• Agitation
• Delirium

Management of Constipation

Treatment aims to facilitate comfortable bowel movements, not to achieve a particular frequency. Prevention is key, so patients should be asked about bowel habit and encouraged to stay hydrated, eat foods high in fibre like fruit, vegetables, and whole grains, and to keep active. This can be challenging in palliative patients who are approaching end-of-life as their appetites and mobility will often decline.

Patients should be toileted regularly if mobility is reduced, ensuring adequate privacy.

When assessing somebody with constipation, abdominal and rectal examinations should be done to exclude haemorrhoids, fissures and impacted stool in the rectum.

If starting a patient on the medications listed above, especially opioids, consider a concomitant laxative.

Pharmacological:

Laxatives may be divided based on their mode of action:

• Osmotic laxatives include Laxido, Lactulose, Sodium phosphate and Polyethylene glycol
• Stimulant laxatives include Senna and Bisacodyl
• Bulk-forming laxatives include Ispaghula husk and Methylcellulose
• Faecal softeners and lubricants such as Docusate sodium, arachis oil and glycerol which are often given rectally as suppositories. There is often significant overlap between these categories.

Osmotic and bulk-forming laxatives may be of limited value in palliative patients. Lactulose needs to be taken with large volumes of fluid, which may not be possible in these patients, and bulk-forming laxatives may worsen constipation if not taken with adequate fluid.

Stimulant laxatives should be avoided in those with bowel obstruction

Faecal impaction must be treated initially, and this may require rectal treatment.

Manual evacuation may be required, but this should not be attempted without analgesia and sedation.

Hiccups

Bouts of hiccups (lasting less than 48 hours) are common, but palliative patients may experience persistent (lasting 48 hours to 1 month) or intractable (lasting over 1 month) hiccups. Persistent or intractable hiccups are estimated to affect up to 9% of palliative patients and can have a detrimental effect on sleep, eating, drinking and mood.

The most common cause is gastric stasis and distension, but other causes include:

• Reflux
• Diaphragmatic/ phrenic nerve irritation
• Metabolic disturbance, e.g., uraemia
• Infection
• Hepatomegaly

Management

• Most evidence is based on case-control studies, and there are currently no RCTs for hiccups
•  Non-Pharmacological:
  • Simple measures like holding breath, sipping iced water or pulling knees up to the chest
• Pharmacological:
  • Anti-flatulent peppermint water 10ml BD
  • Prokinetics metoclopramide or domperidone TDS – Not to be used with peppermint water due to opposing effects on gastro-oesophageal sphincter
  • PPI if reflux
  • Muscle relaxants, e.g., baclofen or midazolam, may be initiated by specialists
  • Dexamethasone 4-8mg OD can reduce compression/ irritation if hepatic, mediastinal or cerebral disease

References

• JATOI, A. L., CHARLES L.; 2022. Up To Date. Pathogenesis, clinical features, and assessment of cancer cachexia.
• Scottish Palliative Care Guidelines. 2022. [online] Available at: <https://www.palliativecareguidelines.scot.nhs.uk/guidelines/symptom-control/weakness-fatigue.aspx> [Accessed 5 April 2022].
• MULIAWATI, Y., HAROEN, H. & ROTTY, L. 2012. Cancer anorexia-cachexia syndrome. pathogenesis, 5.
• Candy, B. et al. 2015. Laxatives for the management of constipation in people receiving palliative care. Cochrane Database of Systematic Reviews.
• Cks.nice.org.uk. 2022. Scenario: Adults | Management | Constipation | CKS | NICE. [online] Available at: <https://cks.nice.org.uk/topics/constipation/management/adults/> [Accessed 18 April 2022].
• Scottish Palliative Care Guidelines. 2022. [online] Available at: <https://www.palliativecareguidelines.scot.nhs.uk/guidelines/symptom-control/Constipation.aspx> [Accessed 18 April 2022].
• Watson M, Campbell R, Vallath N, Ward S, Wells J. Oxford Handbook of Palliative Care. 3rd ed. Oxford University Press; 2019.
• Scottish Palliative Care Guidelines. 2022. [online] Available at: <https://www.palliativecareguidelines.scot.nhs.uk/guidelines/symptom-control/Hiccups.aspx> [Accessed 8 August 2022].
• Cks.nice.org.uk. 2022. Palliative care – nausea and vomiting | Health topics A to Z | CKS | NICE. [online] Available at: <https://cks.nice.org.uk/topics/palliative-care-nausea-vomiting/> [Accessed 9 April 2022].