Nausea and vomiting in palliative care

Nausea and vomiting are distressing symptoms in patients receiving palliative care for advanced cancer. Effective management can significantly improve the quality of life in these patients. An understanding of the likely causes of these symptoms is required for accurate assessment and treatment, resulting in better symptom control.

Nausea and vomiting are separate entities. Some people experience nausea with little or no vomiting (for example, when associated with chemotherapy or radiotherapy). Bowel obstruction, conversely, may cause profuse vomiting with little or no nausea.¹

How common is nausea and vomiting in palliative care? (Epidemiology)

Nausea and vomiting are common and distressing symptoms amongst patients receiving palliative care.² Establishing the true prevalence of these symptoms is challenging, especially given that patients receiving palliative care are a very heterogeneous group. A 2006 systematic review found that nausea and vomiting perhaps occurs less frequently than expected: pain, breathlessness and fatigue were all more common.³

The review reported a prevalence of 30% in end-stage kidney disease patients, at least 17% of heart failure patients and at least 6% of cancer patients. Nausea was most commonly reported in late-stage AIDS patients (43%). The prevalence increases towards the end of life; one study reported a figure of 71% in the last 1-2 weeks of life.⁴

15-30% of patients given morphine for chronic cancer pain experience long-term nausea.⁵

Causes of nausea and vomiting (aetiology)

A greater understanding of the physiological mechanisms causing nausea and vomiting in the palliative care patient will help to select the most appropriate treatment. The neuroanatomical basis of nausea and vomiting involves:¹

• The vomiting centre (VC) - this is situated in the brainstem and has histamine (H1), acetylcholine (ACh) and 5-hydroxytryptamine 2 (5-HT2) receptors. It processes afferent sensory information, including inputs representing taste, vestibular signals, and visceral sensation, and generates output to the dorsal motor nucleus of the vagus nerve, leading to the act of vomiting.

• The chemoreceptor trigger zone (CTZ) or area postrema - located in an area of the brain that has no blood-brain barrier, which enables various drugs, toxins and metabolites to access the site. It has dopamine (D2) and 5-HT3 receptors.

• The cerebral cortex and limbic system. These higher centres modulate the activity of the vomiting centre. Anxiety, low mood, pain, and loneliness can all reduce the threshold for vomiting. Also, mechanoreceptors in the meninges are sensitive to changes in intracranial pressure.

• The vestibular system - changes in movement or diseases of the ear may stimulate the ACh or H1 receptors, triggering nausea or vomiting.

• Gut and serosal surfaces in the viscera - 5-HT3 receptors in the gut are stimulated by drugs, radiotherapy and bacterial exotoxins. H1 and ACh receptors in the gut and the serosal surfaces of other viscera are stimulated by mechanical distortion.

Blocking the receptors at various sites is the mainstay of the drug management of nausea and vomiting. In cancer patients, it is helpful to group the principal causative pathways into seven syndromes, based on receptor sites, clinical features and treatment.

Assessment of the palliative care patient with nausea and vomiting

An accurate assessment of patients with nausea and vomiting will allow for appropriate management of the patient and better symptom control.

Assessment of the patient may include the following:

History

• Timing of symptoms - after meals (eg, gastric stasis), on movement (eg, vestibular disease), when lying flat (eg, due to meningeal irritation or raised intracranial pressure).

• Food and fluid intake.

• Drugs, including over-the-counter ones and alternative therapies.

• Pain.

• Bowel habit.

• Urinary output.

• Effect on daily life.

Examination

• Assessment of hydration.

• Signs of infection - eg, fever.

• Presence of jaundice.

• Neurological examination, including examination of the optic fundi to exclude papilloedema.

• Rectal examination, if faecal impaction or obstruction are suspected.

• Abdominal examination - tenderness, distension, ascites, masses, hepatomegaly.

Depending on the findings of the history and examination, further investigations may be performed to look for the underlying cause of the symptoms - for example:

• U&Es.

• Serum calcium level.

• LFTs.

• FBC and differential.

• Urine culture.

• Abdominal ultrasound/X-ray.

• Endoscopy.

• CT/MRI scan.

At the end of the assessment it may be possible to categorise the cause into one of the following syndromes. Nausea and vomiting, however, are often multifactorial, especially in advanced cancer. ⁶

Nausea and vomiting in palliative care treatment and management⁶

• The effective management of nausea and vomiting in palliative care requires a multidisciplinary approach with good communication between all members of the team and the patient and their family. Support for the patient should be available at all times and they should be aware of whom to contact in order to help with queries and concerns.

• Simple advice such as the size and type of meal, advice on fluid intake and the timing of medication, may all be helpful.

• Attention to the patient's environment is also very important. Bowls, tissues and fresh drinking water should always be within reach.

• For patients unable to drink, attention to oral hygiene and regular mouth washes are important.

• If nausea and vomiting are preventing other medication such as analgesia from being effective, it may be appropriate to consider other forms of delivery of these medications, such as syringe drivers and patches.

• A review of current medication should be undertaken and drugs likely to be aggravating the situation - eg, non-steroidal anti-inflammatory drugs (NSAIDs) - should be changed or stopped.

• Reversible causes of nausea and vomiting should be corrected first wherever possible:
  

  • Hypercalcaemia may respond to rehydration and the use of bisphosphonates.

  • Uraemia may be corrected by rehydration using intravenous (IV) fluids in some patients.

  • Gastric ulceration or gastritis may respond to treatment with proton pump inhibitors or H₂-receptor antagonists.

  • Infection should be treated with appropriate antibiotics.

  • Constipation may respond to the use of laxatives or enemas.

  • Corticosteroids, such as dexamethasone, may reduce the size of the tumour or reduce oedema surrounding the tumour.

  • Anxiolytics may have a role in some patients in whom anxiety is thought to be playing a part.

Treatment in specific scenarios ^{6 7 8}

For dosing information, refer to the BNF⁷ , NICE CKS⁶ , or palliative care guidelines.⁸

First-line treatment should be tailored according to the identified clinical syndrome and likely receptors to be targeted. A non-oral route may be preferable, particularly if there is vomiting, gastric stasis, or poor GI absorption. IT may be possible to change to an oral preparation if vomiting improves.

Irritation or stretching of the meninges

• Cyclizine (oral, injected, or via syringe driver, as appropriate) is the first line-treatment.

• If the patient has raised intracranial pressure due to a tumour, consider referring for consideration of radiotherapy.

• High-dose dexamethasone may help.

• Levomepromazine is a second-line option. Higher doses of levomepromazine can cause significant adverse effects (postural hypertension, dry mouth, sedation).⁴

Pelvic or abdominal tumour

• Cyclizine is helpful, as it blocks ACh and histamine H1 receptors in the vomiting centre that are triggered by the mechanoreceptors in the abdominal and pelvic viscera.

Malignant bowel obstruction

Management of malignant bowel obstruction can be complex, and early specialist advice may be required.

Functional obstruction(peristalsis failure)⁶

• Preserving bowel motility needs to be balanced with the prevention of colic.

• Stop osmotic and stimulant laxatives.

• If possible, stop other peristalsis-impairing drugs, such as cyclizine, tricyclic antidepressants, or opioids.

• Docusate is minimally stimulating and should be titrated to produce a comfortable stool without colic. Avoid high-fibre foods and advise taking food and fluids at regular intervals and in small amounts.

• A prokinetic anti-emetic such as metoclopramide or domperidone should be given if the patient continues to pass flatus and does not have colic.

• Prokinetics should be stopped if gut colic develops, and treatment should proceed as for mechanical obstruction.

• Prokinetic drugs should not be given with antimuscarinic drugs (eg, cyclizine, hyoscine), as they are competitively blocked by the latter.

Mechanical bowel obstruction⁶

• The first-line treatment is cyclizine, as it blocks the stimulation of the vomiting centre via the vagal afferents, which happens in complete obstruction. If nausea persists, add haloperidol or levomepromazine.

• Ensure reversible constipation is not contributing to the obstruction. If it is, sodium docusate or a macrogol (eg, Movicol®, Laxido®) should be used, alongside enemas or suppositories if required.

• Large-volume vomiting should be treated with an antisecretory drug (such as hyoscine butylbromide or octreotide).

• A nasogastric tube can be used as a temporary measure; these have a role in reducing large volume secretions and decompression. These may be removed as soon as control is achieved with medication.

• Intravenous or subcutaneous fluids may be necessary initially to treat dehydration, which itself can cause distressing symptoms.

• Dexamethasone is a potential adjunct; it may help to reduce bowel wall oedema, as well as having anti-emetic and anti-secretory effects.

• Surgical interventions, which may be considered in refractory cases, include:⁸

• Surgical resection, for single-site obstruction where the patient is fit enough to undergo surgery.

• Stenting, for accessible single-site obstruction where surgery is not suitable.

• A venting gastrostomy, for intractable nausea and vomiting - particularly if there is ongoing need for an NG tube.

Gastric stasis

• Metoclopramide is the first-line drug; domperidone can be used if extrapyramidal side-effects develop. ⁶

• Additional treatments include a proton pump inhibitor or H2 antagonist to reduce gastric secretions, and dexamethasone if hepatomegaly is causing impaired gastric emptying.⁸

Chemically/metabolically-induced nausea

• Haloperidol, metoclopramide, or levomepromazine can be used for drug-induced nausea and vomiting, or metabolic (eg, hypercalcaemia) nausea and vomiting.⁶

• Hypercalcaemia is likely to require hospital admission for intravenous rehydration and bisphosphonates, if appropriate.⁶

• Treatment of chemotherapy-induced nausea and vomiting depends on the chemotherapy agents used. Seek advice from the oncology team managing the chemotherapy⁶ and follow cancer centre guidelines.⁸ Options include granisetron, ondansetron, metoclopramide, dexamethasone and aprepitant.

• A further option occasionally used under specialist care is nabilone, a synthetic cannabinoid with anti-emetic properties, although its use is limited by side-effects such as dizziness and drowsiness. It is particularly useful in patients with nausea and vomiting induced by cytotoxic chemotherapy who are unresponsive to other agents.⁷

• Granisetron, ondansetron and haloperidol are all options for radiotherapy-induced nausea and vomiting.⁸

• Chemotherapy-induced nausea and vomiting in children has been studied in a Cochrane review. This suggested that 5-HT3 antagonists with dexamethasone added were effective, although the risk-benefit profile of additional steroid remained uncertain. Cannabinoids were probably effective but induced more side-effects.⁹

Anxiety-induced nausea

• Anxiety is often generated by lack of information or by failure of communication and may be easily resolved with simple explanation and reassurance. More deep-seated anxiety may require the support of other members of the multidisciplinary team, such as psychologists, Macmillan nurses, or spiritual advisers. Cognitive behavioural therapy may be useful.

• Ensure that all other physical causes of nausea and vomiting have been excluded before attributing the symptoms to anxiety.

• Whilst best avoided in other settings, benzodiazepines are useful anxiolytics in palliative care when prognosis is limited and their addictive potential is less relevant.⁸

  • Lorazepam is short acting, rapidly anxiolytic, and less sedating than diazepam.

  • Diazepam has a long half-life; it may accumulate and lead to oversedation, but can be given once a day.

  • Levomepromazine is another (non-benzodiazepine) alternative.⁶

Motion-induced nausea⁶

• Cyclizine (given via the most appropriate route) is the first-line treatment.

• Hyoscine hydrobromide, cinnarizine, levomepromazine and prochlorperazine are all alternatives.

Nausea and vomiting of uncertain origin

There will be cases where the cause of nausea or vomiting remains uncertain, or where the prognosis does not warrant subjecting the patient to further invasive investigations. Metoclopramide or haloperidol and/or cyclizine are good first-line options. Levomepromazine is a 'broad spectrum' anti-emetic that blocks 5-HT2, histamine H1 and ACh receptors and is useful if these are ineffective; however, sedation may limit titration.⁸