9th January 2024

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].