Clinical Topic A-Z Clinical Speciality

Palliative cancer care - nausea & vomiting

Palliative cancer care - nausea & vomiting
D010166Palliative Care
D009325Nausea
GastrointestinalPalliative care
2012-09-01Last revised in September 2012

Palliative cancer care - nausea & vomiting - Summary

Nausea is an unpleasant sensation of the need to vomit, which is often accompanied by autonomic symptoms (for example pallor, cold sweat, salivation, and tachycardia).

Vomiting (emesis) is the forceful ejection of stomach contents through the mouth.

There are many causes of nausea and vomiting in people in palliative care, including:

Drugs (e.g. opioids and cytotoxic drugs).

Metabolic causes (e.g. hypercalcaemia and renal failure).

Gastric stasis (due to drugs, ascites, hepatomegaly, peptic ulcer, or gastritis).

Vestibular disturbance (from opioids, gut distortion, or gastroparesis).

Anxiety (for example before chemotherapy).

Nausea and vomiting may cause various complications, including dehydration and electrolyte imbalance, decreased nutrition, and decreased quality of life.

When assessing a person to determine the cause of nausea and vomiting:

Findings from their history, examination, and investigations should be reviewed to try to identify the cause of the nausea and vomiting, and assess the person's clinical state. If appropriate, blood tests should be considered to exclude hypercalcaemia or renal failure.

A decision should be made on whether to treat the cause of nausea and vomiting, or whether the emphasis should be on the treatment of symptoms.

Several factors, including the stage of the person’s illness, their prognosis, the severity of their symptoms, and the wishes of the person and their family should be taken into account.

Simple measures may help relieve nausea and vomiting in palliative care. They include:

Ensuring access to a large bowl, tissues, and water.

Eating snacks consisting of a few mouthfuls rather than large meals.

Drinking cool fizzy drinks rather than still or hot drinks.

Relaxation techniques and acupressure bands.

Parenteral hydration, if appropriate (except in people at the end of life).

Cognitive behavioural therapy (for anticipatory nausea or vomiting).

The underlying cause of nausea and vomiting should be managed, if possible and appropriate. Anti-emetics should be chosen according to the cause, if known. For example:

For chemically and metabolically-induced nausea and vomiting, haloperidol should be used.

For gastric stasis, metoclopramide should be used.

For movement-related nausea and vomiting, cyclizine should be used.

For anxiety related nausea and vomiting, a benzodiazepine should be considered.

Anti-emetics should be:

Given via the most appropriate route.

Prescribed regularly and as required.

Reviewed every 24 hours.

Continued unless symptoms have resolved.

If a single first-line anti-emetic does not relieve nausea and vomiting:

The cause of nausea and vomiting should be re-assessed.

The anti-emetic dose should be optimized and/or the route of administration re-assessed.

If symptoms persist after 2 or 3 doses of optimal first-line anti-emetic, a different anti-emetic or a combination of anti-emetics with complementary action should be tried.

If symptoms still persist after 24 hours, the person should be referred to a specialist palliative care team.

If the cause is uncertain, or further investigation is not appropriate:

Haloperidol should be tried. Cyclizine should be added if haloperidol is ineffective.

If symptoms persist, levomepromazine or dexamethasone can be considered after seeking specialist advice.

Have I got the right topic?

192months3060monthsBoth

This CKS topic covers the assessment and management of nausea and vomiting in people in palliative care.

This CKS topic does not cover the management of nausea and vomiting due to radiotherapy or cytotoxic chemotherapy, as this is a specialist area.

There are separate CKS topics on Palliative cancer care - constipation, Palliative cancer care - cough, Palliative cancer care - dyspnoea, Palliative cancer care - general issues, Palliative cancer care - malignant ulcer, Palliative cancer care - oral, Palliative cancer care - pain, and Palliative cancer care - secretions.

The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary healthcare.

How up-to-date is this topic?

How up-to-date is this topic?

Changes

Last revised in September 2012

June 2013 — minor update. The 2013 QOF options for local implementation have been added to this topic [BMA and NHS Employers, 2013].

September 2012 — reviewed. A literature search was conducted in August 2012 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of this topic.

No major changes to recommendations have been made.

Previous changes

March 2012 — minor update. The 2012/2013 QOF indicators have been added to this topic [BMA and NHS Employers, 2012]. Issued in April 2012.

January 2012 — minor update. McNeil Products Ltd, in collaboration with the Medicines and Healthcare products Regulatory Agency (MHRA), has published new safety data regarding the association of domperidone with an increased risk of serious ventricular arrhythmias or sudden cardiac death [McNeil Products Ltd and Winthrop Pharmaceuticals UK Ltd, 2011]. This topic has been updated to reflect their advice on dosing, adverse effects, and drug interactions. Issued in February 2012.

May 2011 — minor update. The 2011/2012 QOF indicators have been added to this topic [BMA and NHS Employers, 2011]. Issued in June 2011.

February 2011 — topic structure revised to ensure consistency across CKS topics — no changes to clinical recommendations have been made.

July to October 2007 — converted from CKS guidance to CKS topic structure. The evidence-base has been reviewed in detail and recommendations are more clearly justified and transparently linked to the supporting evidence.

A section has been added covering the management of nausea and vomiting at the end of life. The emphasis of this CKS topic is on the treatment of nausea and vomiting in a palliative care situation; malignant bowel obstruction has been included, but in less detail than previously.

January 2006 — minor update. Prescriptions for diamorphine updated to reflect the change in handwriting requirements for controlled drug prescriptions. Issued in February 2006.

October 2005 — minor technical update. Issued in November 2005.

March 2004 — written in March 2004. Validated in June 2004 and issued in July 2004.

Update

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 August 2012.

HTAs (Health Technology Assessments)

No new HTAs since 1 August 2012.

Economic appraisals

No new economic appraisals relevant to England since 1 August 2012.

Systematic reviews and meta-analyses

Systematic reviews published since the last revision of this topic:

Darvill, E., Dorman, S. and Perkins, P. (2013) Levomepromazine for nausea and vomiting in palliative care (Cochrane Review). The Cochrane Library. Issue 4. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Primary evidence

No new high quality randomized controlled trials since 1 August 2012.

New policies

No new national policies or guidelines since 1 August 2012.

New safety alerts

No new safety alerts since 1 August 2012.

Changes in product availability

No changes in product availability since 1 August 2012.

Goals and outcome measures

Goals

To alleviate the symptoms of nausea and vomiting in a manner that most enhances the person's quality of life

QOF indicators

Table 1 . Indicators related to palliative care in the Quality and Outcomes Framework of the General Medical Services contract.
Indicator Points Payment stages
PC001 The contractor establishes and maintains a register of all patients in need of palliative care/support irrespective of age 3
PC002 The contractor has regular (at least 3 monthly) multidisciplinary case review meetings where all patients on the palliative care register are discussed 3
Data from: [BMA and NHS Employers, 2013]

Background information

Definition

What are nausea and vomiting?

Nausea is an unpleasant sensation of the need to vomit, which is often accompanied by autonomic symptoms (for example pallor, cold sweat, salivation, and tachycardia) [Kinley, 2005; Twycross et al, 2009].

Retching is a strong, involuntary effort to vomit, which usually occurs in the presence of nausea. It involves movement of the diaphragm and abdominal muscles against a closed glottis [Kinley, 2005; Twycross et al, 2009].

Vomiting (emesis) is the forceful ejection of stomach contents through the mouth. The diaphragm and abdominal muscles contract and increase intra-abdominal pressure, compressing the stomach. The stomach, oesophageal sphincter, and pylorus relax, allowing reverse peristalsis and forcing the stomach contents upwards [Kinley, 2005; Perdue, 2005; Twycross et al, 2009].

The vomiting process can be triggered by:

The chemoreceptor trigger zone (CTZ) which is situated in the brain, in the floor of the fourth ventricle, in the area postrema.

The CTZ lies partly outside the blood-brain barrier, allowing exposure to water-soluble chemicals in the blood and cerebrospinal fluid (for example toxins, biochemical products, and drugs) which stimulate its chemoreceptors [Perdue, 2005; Mannix, 2006].

The vomiting centre which is situated in the brainstem and coordinates the vomiting process.

The vomiting centre receives nerve signals from the CTZ, the vestibular apparatus, higher cortical centres (for example fear, pain, memory), and other pathways (for example from liver capsule stretch by metastatic disease, peritoneal distortion from lymphadenopathy, or bowel dilatation due to obstruction or constipation). Impulses are sent from the vomiting centre to the pharynx, larynx, diaphragm, intercostal muscles, and gut, causing nausea, salivation, pallor, sweating, retching, protective glottis closure, and vomiting [Perdue, 2005; Mannix, 2006].

Prevalence of nausea and vomiting in palliative care

How common are nausea and vomiting in palliative care?

Despite major advances in anti-emetic drugs in the past 20 years, there has been very little change in the incidence and severity of nausea and vomiting in people receiving palliative cancer care [Mannix, 2010].

Nausea and vomiting occur in 50–70% of people with advanced cancer [Kinley, 2005; Mannix, 2010; Regnard and Dean, 2010].

Causes of nausea and vomiting in palliative care

What are the causes of nausea and vomiting in palliative cancer care?

There are many causes of nausea and vomiting in people with cancer. These can be grouped according to the mechanism leading to nausea and vomiting and the receptors involved [Mannix, 2010]. Table 1 lists the possible causes of nausea and vomiting in people receiving palliative cancer care.

In some people there may be more than one cause of nausea and vomiting, stimulating symptoms via more than one pathway [Mannix, 2010; Hamling, 2011]. Occasionally the cause of nausea and vomiting may be unknown (see Scenario: Unknown cause).

Nausea and vomiting may also have causes that are not directly related to the underlying cancer. For example [Kinley, 2005]:

Systemic infection.

Motion sickness.

Alcohol intake.

Table 1 . Causes of nausea and vomiting in people receiving palliative cancer care.
Causes Mechanism leading to nausea and vomiting
Chemical Drugs (for example opioids, cytotoxics, and antibiotics) Metabolic (for example organ failure and hypercalcaemia) Toxins (for example food poisoning and ischaemic bowel) Chemicals and toxins stimulate receptors in the chemoreceptor trigger zone Cytotoxic drugs cause vagal receptor stimulation, resulting in stimulation of the vomiting centre
Gastrointestinal stretch or irritation Drugs (for example nonsteroidal anti-inflammatory drugs, iron supplements, antibiotics, and cytotoxics) Constipation Intestinal obstruction Liver metastases Retroperitoneal cancer Mechanoreceptors in the gut stimulate the vagus nerve which acts on the vomiting centre
Gastric stasis Drugs (for example anticholinergics, opioids, and tricyclics) Ascites Hepatomegaly Peptic ulcer Gastritis (caused by stress, drugs, or radiotherapy) Autonomic failure Gastric receptors stimulate the vagus nerve which acts on the vomiting centre
Increased intracranial pressure Intracranial tumour or bleeding Cerebral oedema Meningeal tumour Skull metastases Cerebral histamine receptors may be stimulated Meningeal mechanoreceptors stimulate the vomiting centre
Movement-associated Opioids Gut distortion Gastroparesis Opioids induce sensitivity of vestibular nerves Gut mechanoreceptors stimulate the vagus nerve, which acts on the vomiting centre
Anxiety-related Anxiety Anticipatory vomiting (for example before cytotoxic drugs) Cerebral cortex is stimulated, resulting in stimulation of the vomiting centre
Data from: [Mannix, 2010]

Complications of nausea and vomiting

What are the complications of nausea and vomiting?

Complications of nausea and vomiting include:

Dehydration and electrolyte imbalance (metabolic alkalosis in severe vomiting).

Decreased nutrition leading to nutritional deficiencies.

Aspiration pneumonia.

Oesophageal tears.

Decreased ability to self care.

Decreased quality of life.

[Thompson, 2004; Perdue, 2005]

Management

Management

Scenario: Assessment : covers the assessment of nausea and vomiting in palliative care and identification of an underlying cause, where possible.

Scenario: Known cause : covers management of nausea and vomiting in palliative care when the cause is known. This scenario also covers treatment options when first-line anti-emetics have not worked.

Scenario: Unknown cause : covers management of nausea and vomiting in palliative care when the cause is not known. This scenario also covers treatment options when first-line anti-emetics have not worked.

Scenario: End of life : covers the identification of people at the end of life and the management of nausea and vomiting in this group.

Scenario: Assessment

Scenario: Assessment of nausea and vomiting in palliative care

192months3060monthsBoth

Assessment to determine the cause

How should I assess the person and determine the cause of nausea and vomiting?

Use findings from the history, examination, and investigations to try and identify the cause of the nausea and vomiting, and assess the person's clinical state. See Features indicating a cause for help diagnosing the underlying cause.

Consider whether treatment of the cause is appropriate, or whether the emphasis should be on treatment of symptoms.

Take the following factors into account:

The stage of the illness and the person's prognosis.

The person's wishes and those of their carers and family.

The cause of the person's nausea or vomiting and whether it is reversible or treatable.

The severity of nausea or vomiting and the presence of complications (for example dehydration, poor nutrition, or diminished quality of life).

The urgency with which treatment is required.

The input of the multidisciplinary team (for more information, see the CKS topic on Palliative cancer care - general issues).

Features indicating a cause

What features of nausea and vomiting may suggest a cause?

Patterns of symptoms can be indicative of the cause of nausea and vomiting. See Table 1.

There may be more than one cause of nausea and vomiting in people with cancer.

Table 1 . Features of nausea and vomiting of different causes.
Features of nausea and vomiting Cause
Large-volume of vomitus, infrequent vomiting, relief of symptoms after vomiting, oesophageal reflux, epigastric fullness, early satiation, hiccups. Succussion splash in some people. Gastric stasis
Symptoms similar to gastric stasis, but also forceful vomiting and rapid dehydration. Gastric outflow obstruction
Symptoms similar to gastric stasis, but low-volume vomiting. 'Squashed stomach syndrome' (reduction in gastric cavity by tumour or external compression)
Vomiting soon after eating or drinking, vomitus consisting of what has just been swallowed, sensation of food sticking. Oesophageal blockage
Intermittent nausea (often relieved by vomiting), worsening nausea and/or feculent vomiting as obstruction progresses, abdominal pain (may be colicky), abdominal distention (may be absent if high obstruction). Bowel obstruction
Effortless vomiting, often in the morning, which may be associated with headache (diurnal) and papilloedema; nausea (may be diurnal). Neurological signs and photophobia may be absent. Increased intracranial pressure
Nausea and/or sudden vomiting on movement (for example turning in bed). Motion-associated emesis
Nausea present in waves — may be triggered by a previously experienced stimulus and may be relieved by distraction. Anxiety-related nausea
Constant nausea, variable vomiting. Chemically induced nausea
Information from: [Mannix, 2010; Regnard and Dean, 2010]

Basis for recommendation

Basis for recommendation

These recommendations are pragmatic advice, based on expert opinion in palliative care textbooks [Mannix, 2010; Regnard and Dean, 2010].

What to ask about nausea and vomiting

What should I ask about the nausea and vomiting?

Ask about:

Features of:

Nausea: onset, frequency, intensity, relieving and exacerbating factors, and relationship to vomiting.

Vomiting: onset, frequency, quantity, force, colour, timing, and pattern.

Other symptoms such as:

Dyspepsia, heartburn, fullness, early satiety, constipation, diarrhoea, flatus, cough, headache, or confusion.

Treatment history, including:

Simple measures — what has been tried and its effectiveness.

Current medication — recent changes and coinciding symptoms (especially with opiates, anticholinergics, digoxin, and antibiotics).

Chemotherapy — regimen and timing of last treatment.

Anti-emetics — current and past use, and effectiveness.

Radiation — area treated and number of treatments received.

Medical history (for example ulcers or bowel surgery).

Effect on nutrition (for example fluid and food intake in the past 24 hours).

Effect on quality of life.

For more information, see Features indicating a cause.

Basis for recommendation

Basis for recommendation

These recommendations are based on a palliative care textbook [Regnard and Dean, 2010] and palliative care reviews written by experts [Kinley, 2005; Perdue, 2005].

What to look for on examination

What should I look for on examination?

Perform an appropriate examination for the stage of the person's illness to determine, if possible, the cause of the nausea or vomiting:

Perform a general examination (for example look for signs of dehydration, infection, confusion, drowsiness, or weakness).

Assess the condition of the oral cavity (for example look for signs of candida, tumour, or poor dental condition).

Examine the abdomen for tenderness, swelling, or distension; signs of intestinal obstruction; or constipation.

If faecal impaction is suspected, perform a rectal examination.

If increased intracranial pressure is a possibility, check the fundi for papilloedema (although absence of papilloedema does not exclude intracranial pathology).

Determine whether anxiety could be contributing to the person's symptoms.

Basis for recommendation

Basis for recommendation

These recommendations are based on palliative care textbooks [Twycross et al, 2009; Regnard and Dean, 2010] and palliative care reviews written by experts [Kinley, 2005; Perdue, 2005].

How to investigate

How should I investigate nausea and vomiting in palliative care?

With the person and their carers and family, determine what investigations are appropriate for the person's stage of illness:

The choice of diagnostic tests should be based on the stage of disease, the person's prognosis, the risk-to-benefit ratio of the investigation, and the wishes of the person and their family.

Blood tests to exclude hypercalcaemia or uraemia are among the most useful investigations to do in primary care for all people with nausea or vomiting in a palliative care situation.

Other investigations are more appropriately done in secondary care (for example abdominal radiography to exclude constipation and ultrasonography to detect ascites), but the primary care team may also be able to arrange these and receive the results.

Basis for recommendation

Basis for recommendation

This recommendation is pragmatic advice, based on a review article written by a specialist nurse in palliative care [Kinley, 2005].

Scenario: Known cause

Scenario: Known cause of nausea and vomiting in palliative care

192months3060monthsBoth

Managing known cause

How should I manage nausea and vomiting of known cause?

Manage the underlying cause or correct reversible causes if possible and appropriate.

Try simple measures to relieve symptoms.

Choose an anti-emetic according to the cause of nausea and vomiting such as:

Drugs (for example opioids, diuretics, nonsteroidal anti-inflammatory drugs, or antibiotics).

Metabolic causes (for example hypercalcaemia, renal failure, or tumour toxins)

Intracranial disease (for example raised intracranial pressure or brainstem/meningeal disease)

Movement (for example vestibular disease or tumour at the base of the skull)

Bowel obstruction

Abdominal or pelvic tumour

Gastric stasis

Anxiety

Ascertain the most appropriate route of administration of the anti-emetic.

Prescribe anti-emetics regularly and as required.

Review the effectiveness of anti-emetic treatment every 24 hours.

Continue use of anti-emetics unless nausea and vomiting has resolved (for example the cause was self-limited or has been reversed).

Antiemetics and receptor affinity

Anti-emetics and receptor affinity

Anti-emetics vary in their affinities for the receptors involved in the causes of nausea and vomiting (see Table 1).

Table 1 . Anti-emetics: receptor site affinities.
Anti-emetic Dopamine D2 antagonist Histamine H1 antagonist Acetylcholine antagonist 5-HT2 antagonist
Metoclopramide* ++
Domperidone† ++
Cyclizine ++ ++
Hyoscine +++
Haloperidol +++
Levomepromazine ++ +++ ++ +++
– none or insignificant; + slight; ++ moderate; +++ marked. * Metoclopramide in higher doses >= 100 mg, demonstrates 5-HT3-receptor antagonism. † Domperidone does not cross the blood brain barrier so the risk of extrapyramidal adverse effects (such as tremors, slurred speech, and dystonia) is negligible.
Information from: [Twycross and Wilcock, 2011]

Basis for recommendation

Basis for recommendation

Nausea and vomiting can be controlled in up to 70% of people in palliative care by using anti-emetics appropriate to the receptor site that is thought to contribute to the nausea and vomiting [Thompson, 2004; Mannix, 2006; Glare et al, 2011; Hamling, 2011].

Simple measures

What simple measures may help nausea and vomiting in palliative care?

Make sure the person has access to a large bowl, tissues, and water.

The sight and smell of food or drink may provoke nausea:

Provide a calm environment away from where food is usually prepared or consumed.

If the person is usually responsible for cooking, make alternative arrangements.

Make sure that meals are small and palatable — snacks consisting of a few mouthfuls are less challenging than big meals.

Carbohydrate meals are often better tolerated.

Offer cool, fizzy drinks (citrus flavours are often preferred) — these are more palatable than still or hot drinks.

Consider parenteral hydration, if appropriate (in all people but those at the very end of life). Parenteral hydration, 500–1000 mL/24 hours, may help to reduce persistent nausea.

Consider the use of complementary therapies; relaxation and acupressure bands may be useful to relieve symptoms.

Consider cognitive behavioural therapy for anticipatory nausea or vomiting.

In general, avoid nasogastric suction. It has no role in the management of most causes of nausea and vomiting.

Basis for recommendation

Basis for recommendation

These recommendations are based on palliative care literature from textbooks [Twycross et al, 2009; Mannix, 2010; Regnard and Dean, 2010] and published journal articles [Wright, 2005; Mannix, 2006].

Evidence from a small observational study (n = 54) of hospice patients suggested that acupressure has benefit in controlling nausea and vomiting [Wright, 2005]. Although the study had methodological weaknesses which limit the findings, the risk of this technique is probably low; acupressure bands are safe and easy to administer [Ernst et al, 2006].

CKS could not find studies relating to acupuncture or relaxation for people experiencing nausea and vomiting in general palliative care; the trials and reviews that were found related to chemotherapy-related nausea and vomiting (treatment of which is not covered in this CKS topic) and people experiencing nausea and vomiting who were not receiving palliative care (for example motion sickness, pregnancy, or post-operative nausea and vomiting):

A review provides positive evidence that relaxation is effective for preventing nausea before, during, and after chemotherapy, and is usually a low-risk intervention [Ernst et al, 2006]. In view of this, CKS extrapolated this evidence to recommend consideration of relaxation therapies for people receiving palliative care, since this may provide benefit with little chance of harm.

A paper written by a consultant in palliative care medicine suggests that although studies in the palliative care setting are lacking, case reports suggest that acupuncture can be helpful [Mannix, 2006]. In the absence of stronger evidence relating to the general palliative care population, and considering the potential (albeit rare) adverse effects of acupuncture, CKS could not extrapolate this tentatively positive evidence on acupuncture for chemotherapy-induced nausea [Ernst et al, 2006] to make a recommendation.

Expert opinion in a textbook suggests that nasogastric suction has no role in the management of most causes of nausea and vomiting but may be useful in [Regnard and Dean, 2010]:

Gastric outflow or duodenal obstruction — to reduce high volume of vomiting.

Gastric atony ('floppy stomach') — a nasogastric tube can be passed easily and removed after all the fluid and air has been aspirated.

Faecal vomiting.

Drug-induced nausea and vomiting

How should I treat drug-induced nausea and vomiting?

Review current medication use:

Discontinue use of any unnecessary medications.

Check blood levels if appropriate (for example with digoxin, phenytoin, and carbamazepine).

For chemotherapy-induced nausea and vomiting: seek advice from the specialist who is supervising the person's chemotherapy.

For chemically induced nausea and vomiting (most drugs, including opioids): give haloperidol via the most appropriate route of administration.

Usual oral dose: 1.5 mg at night or twice daily, titrate up to a maximum dose of 10 mg daily (some experts suggest a lower starting dose of 0.5 mg).

As-required dose: oral, 1.5mg; subcutaneous injection, 1.25–2.5 mg.

Syringe driver dose per 24 hours: 2.5–10 mg.

To manage gastrointestinal irritation (for example due to nonsteroidal anti-inflammatory drugs, some antibiotics, or iron supplements): change the drug if possible, or consider gastroprotection.

To manage nausea and vomiting caused by antimuscarinic drugs (for example amitriptyline, lofepramine, or opioids): treat as for gastric stasis.

Basis for recommendation

Basis for recommendation

These recommendations are consistent with specialist palliative care guidelines for the management of nausea and vomiting [Fife Palliative Care Guidelines Group, 2008; Lothian Palliative Care Guidelines Group, 2010] and on palliative care literature from textbooks [Regnard and Dean, 2010; Twycross and Wilcock, 2011].

The prevention and management of nausea and vomiting due to cytotoxic drugs is primarily the responsibility of the specialist prescribing those drugs [Fife Palliative Care Guidelines Group, 2008; Lothian Palliative Care Guidelines Group, 2010].

Drugs such as opioids, cytotoxics, and some antibiotics cause nausea and vomiting by stimulating dopamine type 2 (D2) receptors in the chemoreceptor trigger zone (CTZ) [Mannix, 2010; Twycross and Wilcock, 2011]. Haloperidol is the anti-emetic of choice because it is the most potent antagonist of D2 receptors in the CTZ [Lothian Palliative Care Guidelines Group, 2010; Mannix, 2010].

Haloperidol is a centrally acting anti-emetic, useful for nausea and vomiting induced by drugs, toxins, and metabolites [North of England Cancer Network, 2012].

The recommended anti-emetic doses are consistent with specialist palliative care guidelines for the management of nausea and vomiting [Fife Palliative Care Guidelines Group, 2008; Lothian Palliative Care Guidelines Group, 2010], palliative care literature from a textbook [Twycross and Wilcock, 2011], and the British National Formulary [BNF 63, 2012].

Expert opinion from specialist palliative care guidelines [Lothian Palliative Care Guidelines Group, 2010; North of England Cancer Network, 2012] and from CKS expert reviewers is that a lower starting dose of haloperidol (that is 0.5 mg instead of 1.5 mg) should be used for managing nausea and vomiting in a palliative care situation.

Metabolic causes of nausea and vomiting

How should I treat nausea and vomiting due to metabolic causes?

If hypercalcaemia is present (corrected serum calcium concentration greater than 2.8 mmol/L), arrange hospital admission, if appropriate.

Management of hypercalcaemia usually involves admission for intravenous rehydration and bisphosphonates.

Correction of hypercalcaemia may not always be appropriate in people near the end of life.

For more information, see the Scenario: Known cancer in the CKS topic on Hypercalcaemia.

To manage metabolic causes of nausea and vomiting: give haloperidol via the most appropriate route of administration.

Usual oral dose: 1.5 mg at night or twice daily, titrate up to a maximum dose of 10 mg daily (some experts suggest a lower starting dose of 0.5 mg).

As-required dose: oral, 1.5mg; subcutaneous injection, 1.25–2.5 mg.

Syringe driver dose per 24 hours: 2.5–10 mg.

Basis for recommendation

Basis for recommendation

These recommendations are consistent with specialist palliative care guidelines for the management of nausea and vomiting [Fife Palliative Care Guidelines Group, 2008; Lothian Palliative Care Guidelines Group, 2010] and on palliative care literature from textbooks [Regnard and Dean, 2010; Twycross and Wilcock, 2011].

Metabolic causes of nausea and vomiting, for example organ failure and hypercalcaemia, cause nausea and vomiting by stimulating dopamine type 2 (D2) receptors on the chemoreceptor trigger zone (CTZ) [Mannix, 2010; Twycross and Wilcock, 2011]. Nausea can be controlled by using a central dopamine antagonist such as haloperidol [Mannix, 2010].

Haloperidol is the most potent antagonist of D2 receptors on the CTZ [Mannix, 2010] and is useful for relieving nausea and vomiting associated with stimulation of the D2 receptors on the CTZ [Lothian Palliative Care Guidelines Group, 2010].

Haloperidol is a centrally acting anti-emetic useful for nausea and vomiting induced by drugs, toxins, and metabolites [North of England Cancer Network, 2012].

The recommended anti-emetic doses are consistent with specialist palliative care guidelines for the management of nausea and vomiting [Fife Palliative Care Guidelines Group, 2008; Lothian Palliative Care Guidelines Group, 2010], palliative care literature from a textbook [Twycross and Wilcock, 2011], and the British National Formulary [BNF 63, 2012].

Expert opinion from specialist palliative care guidelines [Lothian Palliative Care Guidelines Group, 2010; North of England Cancer Network, 2012] and from expert reviewers of this CKS topic is that a lower starting dose of haloperidol (that is 0.5 mg instead of 1.5 mg) should be used for managing nausea and vomiting in a palliative care situation.

Intracranial disease-related nausea and vomiting

How should I treat nausea and vomiting due to intracranial disease?

For nausea and vomiting due to intracranial disease: give cyclizine via the most appropriate route of administration.

Usual oral dose: 25–50 mg every 8 hours up to a maximum dose of 150 mg daily.

Immediate/as-required dose: oral and subcutaneous injection, 25–50 mg every 8 hours.

Syringe driver dose per 24 hours: 50–150 mg.

If intracranial pressure is raised:

Consider referral for radiotherapy for all people with raised intracranial pressure due to a tumour.

Consider adding high-dose dexamethasone to cyclizine:

A suitable dose might be 8–16 mg daily for up to 7 days. If dexamethasone has been given for longer than 5 days, or there is a risk of recurrent severe symptoms, or repeated courses of dexamethasone have been given, dexamethasone should be reduced by 2 mg daily every 5–7 days.

Stop dexamethasone therapy if there is no obvious benefit within 3–7 days, or if it becomes ineffective.

Basis for recommendation

Basis for recommendation

These recommendations are consistent with specialist palliative care guidelines for the management of nausea and vomiting [Fife Palliative Care Guidelines Group, 2008; Lothian Palliative Care Guidelines Group, 2010] and on palliative care literature from textbooks [Regnard and Dean, 2010; Twycross and Wilcock, 2011].

In intracranial disease, meningeal mechanoreceptors stimulate the histamine type 1 (H1) receptors in the vomiting centre [Mannix, 2010; Twycross and Wilcock, 2011].

Cyclizine is an antihistaminic, anticholinergic anti-emetic [North of England Cancer Network, 2012] which acts principally on H1 receptors in the vomiting centre [Lothian Palliative Care Guidelines Group, 2010; Mannix, 2010; Twycross and Wilcock, 2011].

Cyclizine is useful for managing nausea and vomiting caused by raised intracranial pressure [BNF 63, 2012].

The recommended anti-emetic doses are consistent with specialist palliative care guidelines for the management of nausea and vomiting [Fife Palliative Care Guidelines Group, 2008; Lothian Palliative Care Guidelines Group, 2010], palliative care literature from a textbook [Twycross and Wilcock, 2011], and the British National Formulary [BNF 63, 2012].

The recommendation to add dexamethasone to cyclizine for raised intracranial pressure is consistent with specialist palliative care guidelines for the management of nausea and vomiting [Fife Palliative Care Guidelines Group, 2008; Lothian Palliative Care Guidelines Group, 2010] and on palliative care literature from textbooks [Regnard and Dean, 2010; Twycross and Wilcock, 2011].

The recommended dose, duration of treatment, and dose adjustment of dexamethasone are based on specialist palliative care guidelines for the management of nausea and vomiting [Fife Palliative Care Guidelines Group, 2008; North of England Cancer Network, 2012].

Movement-related nausea and vomiting

How should I treat movement-related nausea and vomiting?

For vestibular disturbance (for example diseases of the inner ear and motion sickness): give cyclizine via the most appropriate route of administration.

Usual oral dose: 25–50 mg every 8 hours up to a maximum dose of 150 mg daily.

As-required dose: oral and subcutaneous injection, 25–50 mg every 8 hours.

Syringe driver dose/24 hours: 50–150 mg.

Be aware that movement may intensify symptoms of abdominal and pelvic tumour. For more details see Nausea and vomiting related to an abdominal or pelvic tumour.

Basis for recommendation

Basis for recommendation

These recommendations are consistent with specialist palliative care guidelines for the management of nausea and vomiting [Fife Palliative Care Guidelines Group, 2008; Lothian Palliative Care Guidelines Group, 2010] and on palliative care literature from textbooks [Regnard and Dean, 2010; Twycross and Wilcock, 2011].

Movement-associated nausea and vomiting may be caused by opioids, gut distortion, or gastroparesis [Mannix, 2010].

Cyclizine is an antihistaminic, anticholinergic anti-emetic [North of England Cancer Network, 2012]. It acts principally on histamine (H1) receptors in the vomiting centre; however, it also acts on H1 receptors on vestibular afferents [Lothian Palliative Care Guidelines Group, 2010; Mannix, 2010; Twycross and Wilcock, 2011].

Cyclizine is useful for managing nausea and vomiting caused by motion sickness [BNF 63, 2012].

The recommended anti-emetic doses are consistent with specialist palliative care guidelines for the management of nausea and vomiting [Fife Palliative Care Guidelines Group, 2008; Lothian Palliative Care Guidelines Group, 2010], palliative care literature from a textbook [Twycross and Wilcock, 2011], and the British National Formulary [BNF 63, 2012].

Bowel obstruction-related nausea and vomiting

How should I treat nausea and vomiting due to bowel obstruction?

Bowel obstruction may be due to peristaltic failure or mechanical obstruction. When managing nausea and vomiting due to bowel obstruction:

If necessary, seek specialist advice early as management can be complex.

A syringe driver may be needed because the oral route is often unreliable.

To manage bowel obstruction due to peristaltic failure:

If possible, stop drugs which decrease peristalsis (for example cyclizine, tricyclic antidepressants, or opioids).

If there is no colic: start a prokinetic anti-emetic (for example metoclopramide, 30–100 mg/24 hours) via continuous subcutaneous infusion (CSCI).

If colic develops: stop the prokinetic anti-emetic and treat as for mechanical obstruction.

To manage bowel obstruction due to mechanical obstruction:

Exclude constipation, or treat if present:

To relieve and prevent constipation, docusate or Movicol® should be titrated to produce a comfortable stool without colic. For more information, see the CKS topic on Palliative cancer care - constipation.

Treat nausea with cyclizine, 50–150 mg/24 hours via CSCI:

If nausea persists, add haloperidol, 2.5–10 mg/24 hours or as a single night-time dose, or levomepromazine, 5–25 mg/24 hours or as a single night-time dose.

Avoid prokinetics.

Treat colic with an antimuscarinic drug (for example hyoscine butylbromide, 20 mg immediately by subcutaneous injection, then 60–100 mg/24 hours via CSCI).

Manage large-volume vomiting with an antisecretory drug (for example hyoscine butylbromide or octreotide).

Hyoscine will reduce secretions and treat colic, but its full antisecretory effect is achieved after about 3 days.

If large volume vomiting persists, consider using octreotide if a more rapid or profound antisecretory effect is required. This may require admission, depending on the experience of the primary healthcare professional and the availability of octreotide in the community.

Basis for recommendation

Basis for recommendation

These recommendations are consistent with specialist palliative care guidelines for the management of nausea and vomiting [Fife Palliative Care Guidelines Group, 2008; Lothian Palliative Care Guidelines Group, 2010; North of England Cancer Network, 2012] and on palliative care literature from textbooks [Mannix, 2010; Regnard and Dean, 2010; Twycross and Wilcock, 2011].

Peristaltic failure

Bowel obstruction due to peristaltic failure may be due to autonomic neuropathy or a wide spread intra-abdominal cancer [Lothian Palliative Care Guidelines Group, 2010]. Mechanoreceptors in the gut stimulate the vagus nerve which acts on the vomiting centre [Mannix, 2010].

Peristaltic failure is characterized by partial obstruction, reduced bowel sounds, and the absence of colic [Lothian Palliative Care Guidelines Group, 2010].

Prokinetic anti-emetics (such as metoclopramide) are useful for managing nausea and vomiting due to peristaltic failure because they act predominantly in the gut to antagonize dopamine type 2 (D2) receptors. Prokinetics also stimulate serotonin type 4 (5HT4) receptors in the gut, and the subsequent release of acetylcholine appears to play an important role in restoring normal peristalsis [Mannix, 2010]. Cyclizine is not recommended because its anticholinergic properties will further decrease peristalsis.

Bowel obstruction

Cyclizine is useful for managing vagally-mediated nausea and vomiting caused by mechanical bowel obstruction [BNF 63, 2012]. Haloperidol is useful with cyclizine in bowel obstruction if nausea persists with cyclizine alone [North of England Cancer Network, 2012].

Levomepromazine is a broad-spectrum anti-emetic useful for mechanical obstruction, and for persistent nausea and vomiting uncontrolled by other anti-emetics. It should be give at night because of the risk of sedation and hypotension (even at low dose) [Twycross et al, 2009; North of England Cancer Network, 2012].

Prokinetic anti-emetics should be avoided in people with bowel obstruction as they may induce colic [Mannix, 2010; North of England Cancer Network, 2012].

Hyoscine butylbromide is used for managing bowel colic (it reduces gastrointestinal motility) and excessive gastrointestinal secretions (it reduces the volume of vomit in obstruction) [BNF 63, 2012].

Octreotide, a somatostatin analogue, is a useful adjunct in managing complete mechanical bowel obstruction. It stimulates water and electrolyte absorption and inhibits water secretion in the small bowel [BNF 63, 2012]. It is fast acting; however, its cost limits its use.

The recommended doses of anti-emetics are consistent with the British National Formulary [BNF 63, 2012] and the Palliative Care Formulary [Twycross and Wilcock, 2011].

Nausea and vomiting related to an abdominal or pelvic tumour

How should I treat nausea and vomiting due to an abdominal or pelvic tumour?

To manage nausea and vomiting due to distension, compression, or disturbance of abdominal or pelvic organs (for example bowel or liver): give cyclizine via the most appropriate route of administration.

Usual oral dose: 25–50 mg every 8 hours up to a maximum dose of 150 mg daily.

As-required dose: oral and subcutaneous injection, 25–50 mg every 8 hours.

Syringe driver dose per 24 hours: 50–150 mg.

If bowel obstruction is suspected: see Bowel obstruction-related nausea and vomiting.

Basis for recommendation

Basis for recommendation

These recommendations are consistent with specialist palliative care guidelines for the management of nausea and vomiting [Fife Palliative Care Guidelines Group, 2008; Lothian Palliative Care Guidelines Group, 2010; North of England Cancer Network, 2012] and on palliative care literature from textbooks [Mannix, 2010; Regnard and Dean, 2010; Twycross and Wilcock, 2011].

Vomiting commonly occurs in advanced intra-abdominal, retroperitoneal or pelvic malignancy because mechanoreceptors in the bowel wall or capsules of organs are stimulated by stretch or distortion by a tumour, stimulating the vomiting centre via the vagus and splanchnic nerves [Mannix, 2010].

Anti-emetics active at the vomiting centre may therefore help to palliate nausea in this situation [Mannix, 2010]; cyclizine acts on acetylcholine and histamine type 1 (H1) receptors in the vomiting centre [Mannix, 2006; Twycross and Wilcock, 2011].

The recommended anti-emetic doses are consistent with specialist palliative care guidelines for the management of nausea and vomiting [Fife Palliative Care Guidelines Group, 2008; Lothian Palliative Care Guidelines Group, 2010], palliative care literature from a textbook [Twycross and Wilcock, 2011], and the British National Formulary [BNF 63, 2012].

Gastric stasis-related nausea and vomiting

How should I treat nausea and vomiting due to gastric stasis?

For manage nausea and vomiting due to gastric stasis: give metoclopramide.

Unless gastric stasis is mild, start metoclopramide parenterally (10–20 mg every 8 hours by subcutaneous injection or 30–100 mg/24 hours via continuous subcutaneous infusion).

If extrapyramidal effects are a problem with metoclopramide, use domperidone (30–60 mg rectally every 4–8 hours).

Do not give prokinetics concurrently with drugs with antimuscarinic activity (for example cyclizine and hyoscine).

Basis for recommendation

Basis for recommendation

These recommendations are consistent with specialist palliative care guidelines for the management of nausea and vomiting [Fife Palliative Care Guidelines Group, 2008; Lothian Palliative Care Guidelines Group, 2010; North of England Cancer Network, 2012] and on palliative care literature from textbooks [Mannix, 2010; Regnard and Dean, 2010; Twycross and Wilcock, 2011].

In gastric stasis, gastric receptors stimulate the vagus nerve which acts on the vomiting centre. Prokinetic anti-emetics (such as metoclopramide) are useful for managing nausea and vomiting due to gastric stasis because they act predominantly in the gut to antagonize dopamine type 2 (D2) receptors [Mannix, 2010].

Unlike metoclopramide, domperidone does not cross the blood brain barrier so the risk of extra-pyramidal adverse effects are less [Mannix, 2010; BNF 63, 2012].

Prokinetics should not be used concurrently with drugs with antimuscarinic activity (for example cyclizine and hyoscine) because antimuscarinic drugs competitively block the action of prokinetics [Lothian Palliative Care Guidelines Group, 2010; Twycross and Wilcock, 2011].

The recommended anti-emetic doses are consistent with specialist palliative care guidelines for the management of nausea and vomiting [Fife Palliative Care Guidelines Group, 2008; Lothian Palliative Care Guidelines Group, 2010], palliative care literature from a textbook [Twycross and Wilcock, 2011], and the British National Formulary [BNF 63, 2012].

Anxiety-related nausea and vomiting

How should I treat anxiety-related nausea and vomiting?

Manage anxiety independently, according to the person's prognosis.

Consider a benzodiazepine (for example lorazepam, 0.5–1 mg sublingually) or levomepromazine (3–6 mg orally or 2.5–6.25 mg by subcutaneous injection).

Basis for recommendation

Basis for recommendation

These recommendations are based on UK specialist palliative care guidelines on the management of nausea and vomiting [North of England Cancer Network, 2012] and on palliative care literature from textbooks [Mannix, 2010]

Expert opinion is divided as to whether diazepam should be used in this situation. Whilst some experts recommend diazepam because it has a long half-life, thus preventing as required use of anxiolytics [Breitbart et al, 2010; Mannix, 2010], others advise that diazepam is avoided to prevent toxic accumulation due to impaired metabolism in debilitated people [Breitbart et al, 2010]. In addition, concurrent administration of diazepam with other sedative drugs (including strong opioids) may lead to excessive sedation.

Action if first-line anti-emetic fails

What should I do if a first-line anti-emetic has not worked?

If a single first-line anti-emetic does not relieve nausea and vomiting:

Confirm that the cause of nausea and vomiting has been correctly identified.

Optimize the dose of the first-line anti-emetic.

Consider the need for an alternative route of administration.

If nausea and vomiting persist after two or three doses of optimal first-line anti-emetic:

Change to an anti-emetic with a different action, or combine anti-emetics with complementary action.

Do not combine prokinetics (metoclopramide or domperidone) with antimuscarinics (for example hyoscine, cyclizine, or levomepromazine).

About one third of people with advanced cancer who experience nausea and vomiting will require more than one anti-emetic to control their nausea and vomiting.

Refer to a specialist palliative care team if symptoms remain uncontrolled after 24 hours.

Basis for recommendation

Basis for recommendation

These are pragmatic recommendations based on expert opinion from current literature [Perdue, 2005; Twycross et al, 2009; Ang et al, 2010; Lothian Palliative Care Guidelines Group, 2010; Twycross and Wilcock, 2011] and from CKS expert reviewers.

Prokinetics should not be used concurrently with drugs with antimuscarinic activity (for example cyclizine, hyoscine) because antimuscarinic drugs competitively block the action of prokinetics [Lothian Palliative Care Guidelines Group, 2010; Twycross and Wilcock, 2011].

Scenario: Unknown cause

Scenario: Unknown cause of nausea and vomiting in palliative care

192months3060monthsBoth

Simple measures

What simple measures may help nausea and vomiting in palliative care?

Make sure the person has access to a large bowl, tissues, and water.

The sight and smell of food or drink may provoke nausea:

Provide a calm environment away from where food is usually prepared or consumed.

If the person is usually responsible for cooking, make alternative arrangements.

Make sure that meals are small and palatable — snacks consisting of a few mouthfuls are less challenging than big meals.

Carbohydrate meals are often better tolerated.

Offer cool, fizzy drinks (citrus flavours are often preferred) — these are more palatable than still or hot drinks.

Consider parenteral hydration, if appropriate (in all people but those at the very end of life). Parenteral hydration, 500–1000 mL/24 hours, may help to reduce persistent nausea.

Consider the use of complementary therapies; relaxation and acupressure bands may be useful to relieve symptoms.

Consider cognitive behavioural therapy for anticipatory nausea or vomiting.

In general, avoid nasogastric suction. It has no role in the management of most causes of nausea and vomiting.

Basis for recommendation

Basis for recommendation

These recommendations are based on palliative care literature from textbooks [Twycross et al, 2009; Mannix, 2010; Regnard and Dean, 2010] and published journal articles [Wright, 2005; Mannix, 2006].

Evidence from a small observational study (n = 54) of hospice patients suggested that acupressure has benefit in controlling nausea and vomiting [Wright, 2005]. Although the study had methodological weaknesses which limit the findings, the risk of this technique is probably low; acupressure bands are safe and easy to administer [Ernst et al, 2006].

CKS could not find studies relating to acupuncture or relaxation for people experiencing nausea and vomiting in general palliative care; the trials and reviews that were found related to chemotherapy-related nausea and vomiting (treatment of which is not covered in this CKS topic) and people experiencing nausea and vomiting who were not receiving palliative care (for example motion sickness, pregnancy, post-operative).

A review provides positive evidence that relaxation is effective for preventing nausea before, during, and after chemotherapy and is usually a low-risk intervention [Ernst et al, 2006]. In view of this, CKS extrapolated this evidence to recommend consideration of relaxation therapies for people receiving palliative care, since this may provide benefit with little chance of harm.

A paper written by a consultant in palliative care medicine suggests that although studies in the palliative care setting are lacking, case reports suggest that acupuncture can be helpful [Mannix, 2006]. In the absence of stronger evidence relating to the general palliative care population and considering the potential (albeit rare) adverse effects of acupuncture, CKS could not extrapolate this tentatively positive evidence on acupuncture for chemotherapy-induced nausea [Ernst et al, 2006] to make a recommendation.

Expert opinion in a textbook suggests that nasogastric suction has no role in the management of most causes of nausea and vomiting but may be useful in [Regnard and Dean, 2010]:

Gastric outflow or duodenal obstruction — to reduce high volume of vomiting.

Gastric atony ('floppy stomach') — a nasogastric tube can be passed easily and removed after all the fluid and air has been aspirated.

Faecal vomiting.

Managing unknown cause

How should I manage nausea and vomiting of unknown cause?

Try simple measures to relieve symptoms.

Review the person's history, examination results, and medication(s), and consider checking blood for signs of renal failure, hypercalcaemia, liver failure, or blood glucose abnormalities.

If the cause is still uncertain or further investigation is not appropriate:

Try haloperidol.

Usual oral dose: 1.5 mg at night or twice daily and titrate up to a maximum of 10 mg daily (some experts suggest a lower starting dose of 0.5 mg).

As-required dose: oral, 1.5 mg; subcutaneous injection,1.25–2.5 mg.

Syringe driver dose per 24 hours: 2.5–10 mg.

If haloperidol alone is not effective, add cyclizine.

Usual oral dose: 25–50 mg every 8 hours up to a maximum dose of 150 mg daily.

As-required dose for oral and subcutaneous injection:1.5 mg.

Syringe driver dose per 24 hours: 50–150 mg.

If still ineffective, change to levomepromazine or consider a trial of dexamethasone (seek specialist advice first).

Ascertain the most appropriate route of administration of the anti-emetic(s).

Prescribe anti-emetics regularly and as required.

Review the effectiveness of anti-emetic treatment every 24 hours.

Continue anti-emetics unless nausea and vomiting has resolved.

Basis for recommendation

Basis for recommendation

These recommendations are consistent with specialist palliative care guidelines for the management of nausea and vomiting [Fife Palliative Care Guidelines Group, 2008; Lothian Palliative Care Guidelines Group, 2010; North of England Cancer Network, 2012] and on palliative care literature from textbooks [Regnard and Dean, 2010; Twycross and Wilcock, 2011].

With appropriate history, examination, and investigation (where appropriate) it is unusual not to have some indication of the cause of the nausea and vomiting. Specialist palliative care guidelines for the management of nausea and vomiting recommend levomepromazine as the anti-emetic of choice for nausea and vomiting of unknown or multiple causes because of its broad spectrum of activity [Fife Palliative Care Guidelines Group, 2008; Lothian Palliative Care Guidelines Group, 2010; Regnard and Dean, 2010].

CKS expert reviewers, however, consider levomepromazine too sedating to be recommended as first choice. An initial trial of haloperidol is recommended because the unknown causes are often metabolic, biochemical, or drug-related.

Haloperidol is a centrally acting anti-emetic useful for nausea and vomiting induced by drugs, toxins, and metabolites [North of England Cancer Network, 2012].

The recommended anti-emetic doses are consistent with specialist palliative care guidelines for the management of nausea and vomiting [Fife Palliative Care Guidelines Group, 2008; Lothian Palliative Care Guidelines Group, 2010], palliative care literature from a textbook [Twycross and Wilcock, 2011], and the British National Formulary [BNF 63, 2012].

Expert opinion from specialist palliative care guidelines and CKS expert reviewers is that a lower starting dose of haloperidol (that is 0.5 mg instead of 1.5 mg) should be used [Lothian Palliative Care Guidelines Group, 2010; North of England Cancer Network, 2012].

Action if first-line anti-emetic fails

What should I do if a first-line anti-emetic has not worked?

If a single first-line anti-emetic does not relieve nausea and vomiting:

Optimize the dose of the first-line anti-emetic.

Consider the need for an alternative route of administration.

If nausea and vomiting persist after two or three doses of optimal first-line anti-emetic:

Change to an anti-emetic with a different action, or combine anti-emetics with complementary action.

Do not combine prokinetics (metoclopramide or domperidone) with antimuscarinics (for example hyoscine, cyclizine, or levomepromazine).

About one third of people with advanced cancer who experience nausea and vomiting will require more than one anti-emetic to control their nausea and vomiting.

Refer to a specialist palliative care team if symptoms remain uncontrolled after 24 hours.

Basis for recommendation

Basis for recommendation

These are pragmatic recommendations based on expert opinion from current literature [Perdue, 2005; Lothian Palliative Care Guidelines Group, 2010; Twycross and Wilcock, 2011] and from CKS expert reviewers.

Prokinetics should not be used concurrently with drugs with antimuscarinic activity (for example cyclizine and hyoscine) because antimuscarinic drugs competitively block the action of prokinetics [Lothian Palliative Care Guidelines Group, 2010; Twycross and Wilcock, 2011].

Scenario: End of life

Scenario: Nausea and vomiting at the end of life in palliative care

192months3060monthsBoth

How to recognize the terminal phase

How should I recognize the terminal phase?

The terminal phase may last hours to several days.

It is essential to recognize the signs of dying in order to appropriately care for people at the end of life.

People are likely to be in the terminal phase of their illness when they:

Deteriorate day by day, or faster, because of their underlying condition.

Become progressively weak and fatigued without an apparent cause (for example hypercalcaemia).

Express a realization that they are dying or report seeing a person that has already died.

Have reduced cognition, and are drowsy, lethargic, or comatose.

Are delirious, characterized by increased restlessness, confusion, and agitation.

Are bed-bound.

Take little food or fluid and have difficulty taking oral medication.

Are peripherally cyanosed and cold.

Have apnoea (whether awake or asleep) or an altered breathing pattern.

For further details, see the CKS topic on Palliative cancer care - general issues.

Basis for recommendation

Basis for recommendation

The definition of the terminal phase in terms of timescale is based on a prospective study of 100 terminally ill cancer patients [Morita et al, 1998].

Other information is based on expert opinion from palliative care resources that were developed from clinical experience [Regnard and Dean, 2010; ICSI, 2011].

Simple measures

What simple measures may help nausea and vomiting in palliative care?

Make sure the person has access to a large bowl, tissues, and water.

The sight and smell of food or drink may provoke nausea:

Provide a calm environment away from where food is usually prepared or consumed.

If the person is usually responsible for cooking, make alternative arrangements.

Make sure that meals are small and palatable — snacks consisting of a few mouthfuls are less challenging than big meals.

Carbohydrate meals are often better tolerated.

Offer cool, fizzy drinks (citrus flavours are often preferred) — these are more palatable than still or hot drinks.

Consider the use of complementary therapies; relaxation and acupressure bands may be useful to relieve symptoms.

Consider cognitive behavioural therapy for anticipatory nausea or vomiting.

In general, avoid nasogastric suction. It has no role in the management of most causes of nausea and vomiting.

Basis for recommendation

Basis for recommendation

These recommendations are based on palliative care literature from textbooks [Twycross et al, 2009; Mannix, 2010; Regnard and Dean, 2010] and published journal articles [Wright, 2005; Mannix, 2006].

Evidence from a small observational study (n = 54) of hospice patients suggested that acupressure has benefit in controlling nausea and vomiting [Wright, 2005]. Although the study had methodological weaknesses which limit the findings, the risk of this technique is probably low; acupressure bands are safe and easy to administer [Ernst et al, 2006].

CKS could not find studies relating to acupuncture or relaxation for people experiencing nausea and vomiting in general palliative care; the trials and reviews that were found related to chemotherapy-related nausea and vomiting (treatment of which is not covered in this CKS topic) and people experiencing nausea and vomiting who were not receiving palliative care (for example motion sickness, pregnancy, post-operative):

A review provides positive evidence that relaxation is effective for preventing nausea before, during, and after chemotherapy, and is usually a low-risk intervention [Ernst et al, 2006]. In view of this, CKS extrapolated this evidence to recommend consideration of relaxation therapies for people receiving palliative care, since this may provide benefit with little chance of harm.

A paper written by a consultant in palliative care medicine suggests that although studies in the palliative care setting are lacking, case reports suggest that acupuncture can be helpful [Mannix, 2006]. In the absence of stronger evidence relating to the general palliative care population and considering the potential (albeit rare) adverse effects of acupuncture, CKS could not extrapolate this tentatively positive evidence on acupuncture for chemotherapy-induced nausea [Ernst et al, 2006] to make a recommendation.

Expert opinion in a textbook suggests that nasogastric suction has no role in the management of most causes of nausea and vomiting but may be useful in [Regnard and Dean, 2010]:

Gastric outflow or duodenal obstruction — to reduce high volume of vomiting.

Gastric atony ('floppy stomach') — a nasogastric tube can be passed easily and removed after all the fluid and air has been aspirated.

Faecal vomiting.

Management at end of life

How should I manage nausea and vomiting at the end of life?

Try simple measures to relieve symptoms.

If an anti-emetic already controls symptoms well:

Continue with the same drug.

Give the same drug by syringe driver if the person becomes unable to take oral medication. If an injectable form is not available, use a drug with a similar mode of action.

For new or uncontrolled nausea and vomiting:

If appropriate, try to determine the underlying cause of nausea and vomiting and manage accordingly. See Scenario: Known cause.

Otherwise give levomepromazine 6.25 mg once daily by subcutaneous injection. Repeat the dose after 1 hour if needed.

If a repeat dose is needed, start levomepromazine by continuous subcutaneous injection (CSCI):

Start at a dose of 12.5 mg in 24 hours by CSCI, plus a 6.25 mg subcutaneous injection as needed.

If one or more extra doses are needed, increase the dose to 25 mg in 24 hours.

If symptoms remain uncontrolled, contact the local palliative care team for advice.

Review the effectiveness of anti-emetic treatment every 24 hours.

For more information on recognizing the terminal phase and issues relating to caring for a person and their family at this time, see the CKS topic on Palliative cancer care - general issues.

Basis for recommendation

Basis for recommendation

These recommendations are based on the UK specialist palliative care guidelines on nausea and vomiting at the end of life [North of England Cancer Network, 2012].

Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (http://medicines.org.uk/emc), or the British National Formulary (BNF) (www.bnf.org).

Prescribing an anti-emetic

Prescribing an anti-emetic

Route of administration

What route of administration should I use?

Oral administration is the route of choice. However, this may not be appropriate for people:

Who cannot swallow.

With compromised absorption.

Who have persistent nausea and vomiting.

In whom swallowing causes them to vomit.

With gastric stasis or bowel obstruction.

If the oral route is not appropriate, give anti-emetics parenterally (subcutaneously or intravenously) or rectally. The intramuscular route is not recommended as people with advanced cancer tend to be cachectic.

If the person has continuous or severe nausea or frequent vomiting, continuous subcutaneous infusion via a syringe driver is the route of choice.

Continuous subcutaneous infusion (via a syringe driver) is used for drug delivery if the person cannot take medicines by mouth (for example because of persistent nausea and vomiting, dysphagia, severe weakness, poor oral absorption, or coma).

Use only drugs that are known to be safe and effective by the subcutaneous route. These include metoclopramide, haloperidol, cyclizine, hyoscine butylbromide, and levomepromazine.

Use water for injection as the diluent when mixing drugs in a syringe driver (except for octreotide).

Use sodium chloride as the diluent for octreotide and consider a second syringe driver if octreotide is to be co-administered with other drugs.

Before mixing drugs, check their compatibility.

Always follow local palliative care guidelines or seek advice from local palliative care services or hospital pharmacy drug information services before mixing drugs in a syringe driver.

Data are most often available on combinations of two drugs in a syringe driver, although some combinations of three or four drugs are compatible.

If you cannot contact the appropriate authorities for further guidance, see www.palliativedrugs.com/syringe-driver-database-introduction.html (registration required).

Do not use solutions that are discoloured or have precipitated.

Basis for recommendation

These recommendations are consistent with specialist palliative care guidelines for the management of nausea and vomiting [Perdue, 2005; Fife Palliative Care Guidelines Group, 2008] and palliative care literature from a textbook [Twycross and Wilcock, 2011].

Anti-emetics in conjunction with opioids

How should I prescribe an anti-emetic in conjunction with an opioid?

When starting an opioid, prescribe an anti-emetic (for example haloperidol or metoclopramide):

Regularly for the first week, to prevent opioid-induced nausea and vomiting if the person has experienced nausea with a previous opioid, or

On standby, for use on an as-required basis for one week, in case the person experiences nausea with morphine but has not experienced nausea with a previous opioid.

Basis for recommendation

This recommendation is based on palliative care literature from a textbook [Twycross and Wilcock, 2011] and published journal articles [Mannix, 2006; Laugsand et al, 2011].

Nausea at introduction of opioids occurs in about 30% of people; however, tolerance to nausea occurs within 2 weeks of starting the opioid [Mannix, 2006].

Evidence from a review article suggests that the risk of opioid-induced nausea and vomiting in people with advanced cancer may be reduced by changing the opioid or its route of administration. However, the authors concluded that the evidence was too limited to prioritize between symptomatic treatment of the nausea and vomiting and adjustment of the opioid treatment [Laugsand et al, 2011].

Prescribing a prokinetic

Prescribing a prokinetic

Prokinetics (metoclopramide and domperidone) should not be given concurrently with drugs with antimuscarinic activity (for example cyclizine, hyoscine) because antimuscarinic drugs competitively block the action of prokinetics.

Prokinetics are useful for nausea and vomiting induced by gastric stasis, for example due to hepatomegaly, opioids, or functional/partial obstruction.

Metoclopramide:

Is generally given orally three to four times a day. It can also be given as a subcutaneous injection or infusion.

Can induce acute dystonic reactions involving facial and skeletal muscle spasms and oculogyric crises.

These reactions are more common in younger people (particularly girls and young women), elderly people, and people who are also taking other drugs known to cause extrapyramidal effects. They generally occur within a few days of starting treatment and subside within 24 hours of stopping metoclopramide.

Injection of procyclidine, 5–10 mg intravenously or intramuscularly, will abort a dystonic attack.

Can also cause drowsiness, restlessness, and diarrhoea.

Domperidone:

Can be given orally or rectally.

Is not as effective as metoclopramide, but it is less likely to cause central adverse effects (such as sedation and dystonic reactions) because it does not readily cross the blood-brain barrier.

May be associated with an increased risk of ventricular tachyarrythmias and sudden cardiac death; these risks may be higher in people aged over 60 years and people taking more than 30 mg of domperidone daily. When prescribing domperidone:

The lowest effective dose should be prescribed.

The person should be advised to seek prompt medical attention if symptoms such as syncope or tachyarrhythmias arise during treatment.

Should be avoided in people who are taking medication that prolongs the QT interval such as ketoconazole and erythromycin.

Should be prescribed with caution in people aged over 60 years and people who have existing prolongation of cardiac conduction intervals (particularly the QTc interval), electrolyte disturbance, and an underlying cardiac disease (such as congestive heart failure).

Basis for recommendation

These recommendations are based mainly on palliative care literature from textbooks [Mannix, 2010; Twycross and Wilcock, 2011] and the British National Formulary [BNF 63, 2012].

Advice on safe prescribing of domperidone

The Medicines and Healthcare products Regulatory Agency (MHRA) in collaboration with McNeil Products Ltd. and Winthrop Pharmaceuticals, have issued new information regarding the cardiac risks associated with domperidone following the publication of two epidemiological studies. The studies showed that domperidone may be associated with an increased risk of serious ventricular arrhythmias and sudden cardiac death, especially in people aged over 60 years and in people who receive a daily oral dose of over 30 mg. However, the benefits of domperidone still outweigh the risks [McNeil Products Ltd and Winthrop Pharmaceuticals UK Ltd, 2011].

Prescribing haloperidol

Prescribing haloperidol

Haloperidol is usually given orally, once or twice a day, to treat chemically or metabolically induced vomiting. This is an off-label indication for haloperidol tablets and oral solution.

At the low doses used in palliative care, adverse effects (for example dystonias, dyskinesia, and akathisia) are unusual.

Basis for recommendation

This information is based on palliative care literature from a textbook [Twycross and Wilcock, 2011] and the British National Formulary [BNF 63, 2012].

Prescribing levomepromazine

Prescribing levomepromazine

Levomepromazine is a first-generation antipsychotic drug which acts predominantly by blocking dopamine type 2 (D2) receptors in the brain. It is usually used as a second- or third-line anti-emetic because of its sedative effect.

Levomepromazine may be given orally but is generally given by the subcutaneous route. It is usually given once a day but some people may benefit from divided daily doses (twice or three times a day) or from continuous subcutaneous infusion.

When converting from the oral route to the subcutaneous route, the oral dose should be divided by two to get the equivalent subcutaneous dose.

Levomepromazine 6 mg tablets are an unlicensed preparation and are available on a named-patient basis only. They can be ordered directly from the manufacturer (but this can take up to 48 hours) or they may be available through the local palliative care team or hospice.

If the 6 mg tablets are not available, experts suggest using a quarter of a 25 mg tablet (that is 6.25 mg).

Adverse effects include sedation (particularly at doses of 25 mg or more in 24 hours), dose-dependent postural hypotension, and antimuscarinic adverse effects (dry mouth, sedation, and blurred vision). Doses less than 12.5 mg daily do not usually cause problems.

Basis for recommendation

This information is based mainly on palliative care literature from a textbook [Twycross and Wilcock, 2011] and the British National Formulary [BNF 63, 2012].

The information on converting from oral to the subcutaneous route is based on a specialist palliative care guideline on the management of nausea and vomiting [Lothian Palliative Care Guidelines Group, 2010].

The recommendation to quarter a 25 mg tablet if 6 mg tablets are unavailable is based on expert opinion in a palliative and end of life care guideline [North of England Cancer Network, 2012] and on palliative care literature from a textbook [Twycross and Wilcock, 2011].

Prescribing cyclizine

Prescribing cyclizine

Cyclizine is useful for managing vagally-mediated nausea and vomiting caused by mechanical bowel obstruction, raised intracranial pressure, and movement disorders.

Cyclizine can be given two to three times a day by mouth, subcutaneously, or intravenously; or by continuous subcutaneous infusion. Subcutaneous administration may cause skin irritation at the injection site.

Drowsiness and antimuscarinic adverse effects (dry mouth and blurred vision) are common.

Basis for recommendation

This information is based on palliative care literature from a textbook [Twycross and Wilcock, 2011] and the British National Formulary [BNF 63, 2012].

Prescribing dexamethasone

Prescribing dexamethasone

Dexamethasone is generally given as a single dose in the morning but may be given via a syringe driver when appropriate.

If large doses cannot be taken at once because of nausea, the dose may be divided and given in the morning and at lunchtime. If possible, oral or subcutaneous dexamethasone should be taken no later than 16.00 hours, to avoid night-time restlessness.

Adverse effects of oral corticosteroids include:

Oral candidiasis — regular mouth care is essential to reduce the risk of oral candidiasis.

Gastrointestinal adverse effects — dyspepsia and indigestion are common. The risk of serious gastrointestinal complications (for example peptic ulcer or silent perforation) is markedly increased in people who are also taking nonsteroidal anti-inflammatory drugs (NSAIDs).

Gastrointestinal prophylaxis with a proton pump inhibitor or misoprostol should be considered for people receiving concurrent NSAIDs or those with a history of peptic ulcer disease.

Dexamethasone should only be used in people with active peptic ulcer disease if the benefits are likely to outweigh the risks.

Stopping use of dexamethasone in the terminal phase lacks expert consensus:

If the oral route is no longer available, dexamethasone can be given as a single slow subcutaneous dose, once a day.

If treatment is not given the person may become agitated and distressed because of corticosteroid withdrawal. The onset of withdrawal symptoms is highly variable, depending on the risk of adrenal suppression, the length of time that the person lives after their last treatment, and their degree of physical stress; it is highly unlikely within the first 24 hours.

The clinician must balance the disadvantages of intrusive treatment of a dying person against the risks of not providing treatment.

Basis for recommendation

These recommendations are based on palliative care literature from a textbook [Twycross and Wilcock, 2011].

The information on dyspepsia and indigestion are based on a published review article [Piper et al, 1991] and the British National Formulary [BNF 63, 2012].

Prescribing hyoscine butylbromide

Prescribing hyoscine butylbromide

Hyoscine butylbromide must not be confused with hyoscine hydrobromide, which is used in lower doses.

Hyoscine butylbromide is poorly absorbed orally. For the management of nausea and vomiting it should be given as a subcutaneous bolus dose or by continuous subcutaneous infusion.

Unlike hyoscine hydrobromide, hyoscine butylbromide does not cross the blood–brain barrier and therefore does not cause drowsiness or have a central anti-emetic action.

Antimuscarinics should be avoided in people with paralytic ileus or symptomatic acid reflux, as they relax the lower oesophageal sphincter.

Antimuscarinics should be used with caution in people with:

Angle-closure glaucoma — antimuscarinics may precipitate glaucoma in these people, particularly the elderly.

Bladder outflow obstruction (prostatism).

Conditions predisposing to tachycardia (including hyperthyroidism, cardiac insufficiency, and cardiac surgery).

Pyrexia — use in pyrexia or hot weather may lead to heatstroke.

Basis for recommendation

These recommendations are based on palliative care literature from a textbook and the British National Formulary [Twycross and Wilcock, 2011; BNF 63, 2012].

Evidence

Evidence

Search strategy

Scope of search

A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on primary care management of palliative cancer care - nausea and vomiting, with additional searches for evidence in the following areas:

Anxiety related nausea and vomiting in palliative cancer care

Search dates

2007 - August 2012.

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline and these were adapted for other databases. Further details are available on request.

exp Palliative Care/, exp Terminal Care/, exp Terminally Ill/, palliat$.tw., (terminal adj care).tw., (palliative or cancer or terminal or end of life).tw.

exp Nausea/, exp Vomiting/, (nausea$ or vomit$).tw., emesis.tw.

exp Anxiety/, exp Anxiety Disorders/, (anxiety or anxious$).tw., (anticipation or anticipatory).tw., exp Vomiting, Anticipatory/

Table 1 . Key to search terms.
Search commands Explanation
/ indicates a MeSh subject heading with all subheadings selected
.tw indicates a search for a term in the title or abstract
exp indicates that the MeSH subject heading was exploded to include the narrower, more specific terms beneath it in the MeSH tree
$ indicates that the search term was truncated (e.g. wart$ searches for wart and warts)
Sources of guidelines

National Institute for Health and Care Excellence (NICE)

Scottish Intercollegiate Guidelines Network (SIGN)

Royal College of Physicians

Royal College of General Practitioners

Royal College of Nursing

NICE Evidence

Health Protection Agency

World Health Organization

National Guidelines Clearinghouse

Guidelines International Network

TRIP database

GAIN

NHS Scotland National Patient Pathways

New Zealand Guidelines Group

Agency for Healthcare Research and Quality

Institute for Clinical Systems Improvement

National Health and Medical Research Council (Australia)

Royal Australian College of General Practitioners

British Columbia Medical Association

Canadian Medical Association

Alberta Medical Association

University of Michigan Medical School

Michigan Quality Improvement Consortium

Singapore Ministry of Health

National Resource for Infection Control

Patient UK Guideline links

UK Ambulance Service Clinical Practice Guidelines

RefHELP NHS Lothian Referral Guidelines

Medline (with guideline filter)

Driver and Vehicle Licensing Agency

NHS Health at Work (occupational health practice)

Sources of systematic reviews and meta-analyses

The Cochrane Library :

Systematic reviews

Protocols

Database of Abstracts of Reviews of Effects

Medline (with systematic review filter)

EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

NIHR Health Technology Assessment programme

The Cochrane Library :

NHS Economic Evaluations

Health Technology Assessments

Canadian Agency for Drugs and Technologies in Health

International Network of Agencies for Health Technology Assessment

Sources of randomized controlled trials

The Cochrane Library :

Central Register of Controlled Trials

Medline (with randomized controlled trial filter)

EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

Bandolier

Drug & Therapeutics Bulletin

TRIP database

Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

Department of Health

Health Management Information Consortium (HMIC)

Patient experiences

Healthtalkonline

BMJ - Patient Journeys

Patient.co.uk - Patient Support Groups

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

British National Formulary (BNF)

electronic Medicines Compendium (eMC)

European Medicines Agency (EMEA)

LactMed

Medicines and Healthcare products Regulatory Agency (MHRA)

REPROTOX

Scottish Medicines Consortium

Stockley's Drug Interactions

TERIS

TOXBASE

Micromedex

UK Medicines Information

References

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BMA and NHS Employers (2012) Quality and outcomes framework for 2012/13. Guidance for PCOs and practices. ..BMA and NHS Employers.www.bma.org.uk [Free Full-text]

BMA and NHS Employers (2013) Summary of QOF changes for 2013/14 in England. ..British Medical Association and NHS Employers.www.nhsemployers.org [Free Full-text]

BNF 63 (2012) British National Formulary. 63rd edn. London: British Medical Association and Royal Pharmaceutical Society of Great Britain.

Breitbart, W., Chochinov, H.M. and Passik, S.D. (2010) Psychiatric symptoms in palliative medicine. In: Hanks, G., Cherny, N.I., Christakis, N.A. et al. (Eds.) Oxford textbook of palliative medicine. 4th edn. Oxford: Oxford University Press. 1453-1482.

Ernst, E., Pittler, M.H. and Wider, B. (Eds.) (2006) Nausea and vomiting. In: The desktop guide to complementary and alternative medicine: an evidence-based approach. 2nd edn. London: Mosby Elsevier. 214-224.

Fife Palliative Care Guidelines Group (2008) Guidelines for the management of nausea/vomiting in palliative care. ..Fife Area Drug & Therapeutics Committee.www.fifeadtc.scot.nhs.uk

Glare, P., Miller, J., Nikolova, T. and Tickoo, R. (2011) Treating nausea and vomiting in palliative care: a review. Clinical Interventions in Aging 6, 243-259. [Abstract] [Free Full-text]

Hamling, K. (2011) The management of nausea and vomiting in advanced cancer. International Journal of Palliative Nursing 17(7), 321-327. [Abstract]

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Lothian Palliative Care Guidelines Group (2010) Nausea/vomiting in palliative care. ..NHS Scotland.www.scan.scot.nhs.uk [Free Full-text]

Mannix, K. (2006) Palliation of nausea and vomiting in malignancy. Clinical Medicine 6(2), 144-147.

Mannix, K.A. (2010) Palliation of nausea and vomiting. In: Hanks, G., Cherny, N.I., Christakis, N.A. et al. (Eds.) Oxford textbook of palliative medicine. 4th edn. Oxford: Oxford University Press. 801-812.

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Morita, T., Ichiki, T., Tsunoda, J. et al. (1998) A prospective study on the dying process in terminally ill cancer patients. American Journal of Hospice & Palliative Care 15(4), 217-222. [Abstract]

North of England Cancer Network (2012) Palliative and end of life care guidelines for cancer and non-cancer patients. .3rd edn.North of England Cancer Network.www.cancernorth.nhs.uk [Free Full-text]

Perdue, C. (2005) Understanding nausea and vomiting in advanced cancer. Nursing Times 101(4), 32-35. [Abstract]

Piper, J.M., Ray, W.A., Daugherty, J.R. and Griffin, M.R. (1991) Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs. Annals of Internal Medicine 114(9), 735-740. [Abstract]

Regnard, C. and Dean, M. (2010) A guide to symptom relief in palliative care. 6th edn. Oxford: Radcliffe Publishing.

Thompson, I. (2004) The management of nausea and vomiting in palliative care. Nursing Standard 19(8), 46-53. [Abstract]

Twycross, R. and Wilcock, A. (Eds.) (2011) Palliative care formulary. 4th edn. Nottingham: Palliativedrugs.com Ltd.

Twycross, R., Wilcock, A. and Stark Toller, C. (Eds.) (2009) Symptom management in advanced cancer. 4th edn. Nottingham: Palliativedrugs.com Ltd.

Wright, L.D. (2005) The use of motion sickness bands to control nausea and vomiting in a group of hospice patients. American Journal of Hospice & Palliative Care 22(1), 49-53. [Abstract]