• Assess the person and, where possible, identify the cause of nausea and vomiting.
• Manage the underlying cause if possible and appropriate.
• Manage any complications of prolonged nausea and vomiting.
• Try simple measures to relieve symptoms.
• Offer a first-line anti-emetic, depending on the cause of nausea and vomiting.
• Review and reconsider the diagnosis if response to treatment is unexpectedly poor or symptoms persist.
• Add in or switch to a second-line anti-emetic if nausea and vomiting persists after 24 hours.
• Seek specialist help if symptoms remain poorly controlled after another 24 hours.
• Consider management of other physical symptoms, and take into account the psychological, social, and spiritual needs of the person and their family. For more information, see the CKS topic on Palliative cancer care - general issues.

• Use the findings from history, examination, and investigations to try to identify the cause of the vomiting and assess the person's clinical state. See Features indicating a 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 illness and the person's prognosis.
• The person's wishes and those of carers and family.
• The cause of the person's nausea or vomiting and whether it is reversible or untreatable.
• The severity of nausea or vomiting and the presence of complications (e.g. dehydration, poor nutrition, 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).

• This recommendation is pragmatic advice, based on expert opinion in palliative care textbooks [Doyle et al, 2004; Regnard and Hockley, 2004].

• Features:
• Nausea: onset, frequency, intensity, relieving and exacerbating factors, relationship to vomiting.
• Vomiting: onset, frequency, quantity, force, colour, timing, and pattern.
• Other symptoms:
• Dyspepsia, heartburn, fullness, early satiety, constipation, diarrhoea, flatus, cough, headache, confusion.
• Treatments:
• Simple measures — what has been tried, and its effectiveness.
• Current medication — recent changes and coinciding symptoms (especially opiates, anticholinergics, digoxin, antibiotics).
• Chemotherapy — timing of last treatment.
• Anti-emetics — current and past use, effectiveness.
• Radiation — area treated and number of treatments received.
• Medical history (e.g. ulcers, bowel surgery).
• Effect on nutrition (e.g. fluid and food intake in the past 24 hours).
• Effect on quality of life.
• For more information, see Features indicating a cause.

• This recommendation is based on palliative care guidelines [Cancer Care Ontario, 2005], palliative care textbooks [Regnard and Hockley, 2004], and palliative care reviews written by experts [Kinley, 2005; Perdue, 2005].

• Perform an examination appropriate for the stage of the person's illness to determine, if possible, the cause of the nausea or vomiting:
• Perform a general examination (e.g. for signs of dehydration, infection, confusion, drowsiness, weakness).
• Assess the condition of the oral cavity (e.g. for signs of candida, tumour, or poor dental condition).
• Examine the abdomen for tenderness, swelling, or distension; signs of intestinal obstruction; or constipation.
• Perform a rectal examination if faecal impaction is suspected.
• Check the fundi for papilloedema if increased intracranial pressure is a possibility (although absence of papilloedema does not exclude intracranial pathology).
• Determine whether anxiety may be contributing to the person's symptoms.

• This recommendation is based on palliative care guidelines [Cancer Care Ontario, 2005], palliative care textbooks [Twycross and Wilcock, 2001; Regnard and Hockley, 2004], and palliative care reviews written by experts [Kinley, 2005; Perdue, 2005].

• 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 and uraemia are among the most useful investigations in all people with nausea or vomiting in a palliative care situation in primary care.
• Other investigations are more appropriately done in secondary care (e.g. abdominal radiography to exclude constipation or intestinal obstruction, ultrasonography to detect ascites), but the primary care team may also be able to arrange these and receive the results.

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

• 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.

• 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 the person with 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 meals are small and palatable.
• Carbohydrate meals are often better tolerated.
• Offer cool, fizzy drinks (citrus flavours are often preferred).
• Consider parenteral hydration if appropriate (in all people but those at the very end of life).
• Consider the use of complementary therapies; relaxation and acupressure bands may be useful to relieve symptoms.
• Consider the use of cognitive behavioural therapy for anticipatory nausea or vomiting.
• In general, avoid nasogastric suction.

• This recommendation is based on palliative care literature from textbooks [Twycross and Wilcock, 2001; Doyle et al, 2004; Regnard and Hockley, 2004] and published journal articles [Wright, 2005; Mannix, 2006]:
• Snacks consisting of a few mouthfuls are less challenging than big meals [Twycross and Wilcock, 2001].
• Cool, fizzy drinks are more palatable than still or hot drinks [Doyle et al, 2004].
• Parenteral hydration, 500–1000 mL/24 hours, may help to reduce persistent nausea [Regnard and Hockley, 2004].
• Nasogastric suction has no role in most causes of nausea and vomiting [Regnard and Hockley, 2004].
• 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 (e.g. 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.

• 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:
• Drugs (e.g. opioids, diuretics, nonsteroidal anti-inflammatory drugs, antibiotics, chemotherapy)
• Metabolic causes (e.g. hypercalcaemia, renal failure, tumour toxins)
• Intracranial disease (e.g. raised intracranial pressure, brainstem/meningeal disease)
• Movement (e.g. vestibular disease, 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 (e.g. the cause was self-limited or has been reversed).

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

[Twycross and Back, 1998]

• 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 nausea and vomiting [Thompson, 2004].

• Review current medication use:
• Discontinue use of any unnecessary medications.
• Check blood levels if appropriate (e.g. digoxin, phenytoin, carbamazepine).
• Chemotherapy-induced nausea and vomiting: seek advice from the specialist who is supervising the person's chemotherapy.
• Chemically induced nausea and vomiting (most drugs, including opioids): give haloperidol, 1.5–10 mg daily:
• Starting dosage: 1.5 mg immediately and at night.
• Usual dosage: 3–5 mg at night or in divided doses.
• Usual maximum dosage in nausea and vomiting: 10 mg/day (at night or in divided doses).
• Gastrointestinal irritation (e.g. due to nonsteroidal anti-inflammatory drugs, some antibiotics, iron supplements): change the drug if possible, and consider gastroprotection.
• Antimuscarinic drugs (e.g. amitriptyline, lofepramine, opioids): treat as for gastric stasis.

• Opioids can induce nausea by several mechanisms:
• If nausea and vomiting starts concurrently with beginning the use of an opioid, it is likely to be chemically induced.
• If constipation is also present, nausea and vomiting may be due to gastric stasis.
• When starting an opioid, prescribe an anti-emetic (e.g. haloperidol or metoclopramide) [Twycross et al, 2002]:
• 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 1 week, in case the person experiences nausea with morphine but has not experienced nausea with a previous opioid.

• These recommendations are consistent with specialist palliative care guidelines for the management of nausea and vomiting [Twycross and Wilcock, 2001; Fife Area Drug & Therapeutics Committee, 2004; Lothian Palliative Care Guidelines Group, 2004a; Regnard and Hockley, 2004; Cancer Care Alliance, 2006a].
• The prevention and management of nausea and vomiting due to cytotoxic drugs is primarily the responsibility of the specialist prescribing those drugs [Fife Area Drug & Therapeutics Committee, 2004; Lothian Palliative Care Guidelines Group, 2004a].

• If hypercalcaemia is present (corrected serum calcium concentration greater than 2.8 mmol/L), arrange 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.
• Metabolic-induced nausea and vomiting: give haloperidol, 1.5–10 mg daily.
• Starting dosage: 1.5 mg immediately and at night.
• Usual dosage: 3–5 mg at night or in divided doses.
• Usual maximum dosage in nausea and vomiting: 10 mg/day (at night or in divided doses).

• These recommendations are consistent with specialist palliative care guidelines for the management of nausea and vomiting [Twycross and Wilcock, 2001; Fife Area Drug & Therapeutics Committee, 2004; Lothian Palliative Care Guidelines Group, 2004a; Regnard and Hockley, 2004; Cancer Care Alliance, 2006a].

• Nausea and vomiting due to intracranial disease: give cyclizine, 25–50 mg every 8 hours and when required (maximum dose 150 mg/24 hours).
• 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:
• A suitable dose might be 8–16 mg daily for up to 7 days, with subsequent reduction to 4–6 mg daily if possible.
• Stop dexamethasone therapy if there is no obvious benefit within 3–5 days, or if it becomes ineffective.

• These recommendations are consistent with specialist palliative care guidelines for the management of nausea and vomiting [Twycross and Wilcock, 2001; Fife Area Drug & Therapeutics Committee, 2004; Lothian Palliative Care Guidelines Group, 2004a; Regnard and Hockley, 2004; Cancer Care Alliance, 2006a].

• Vestibular disturbance (e.g. diseases of the inner ear, motion sickness): give cyclizine, 25–50 mg every 8 hours and when required (maximum dose 150 mg/24 hours).
• Movement may intensify symptoms of abdominal and pelvic tumour. For more details see Managing known cause: Due to an abdominal or pelvic tumour.

• These recommendations are consistent with specialist palliative care guidelines for the management of nausea and vomiting [Twycross and Wilcock, 2001; Fife Area Drug & Therapeutics Committee, 2004; Lothian Palliative Care Guidelines Group, 2004a; Regnard and Hockley, 2004; Cancer Care Alliance, 2006a].

• Seek specialist advice early, as management can be complex.
• A syringe driver may be needed because the oral route is often unreliable.

Peristaltic failure:

• If possible stop drugs which decrease peristalsis (e.g. cyclizine, tricyclic antidepressants, opioids).
• Advise small, frequent meals with avoidance of high-fibre foods.
• If there is no colic: start a prokinetic anti-emetic (e.g. metoclopramide, 30–100 mg/24 hours) via continuous subcutaneous infusion (CSCI).
• If colic develops: stop use of the prokinetic anti-emetic and treat as for mechanical bowel obstruction.

Mechanical bowel 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.
• 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 (e.g. hyoscine butylbromide, 20 mg immediately by subcutaneous injection, then 60–120 mg/24 hours via CSCI).
• Large-volume vomiting: start an antisecretory drug (e.g. hyoscine butylbromide or octreotide):
• If colic is present:
• Hyoscine will reduce secretions and treat colic, but its full antisecretory effect is achieved only 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.

• These recommendations are consistent with specialist palliative care guidelines on the management of bowel obstruction [Lothian Palliative Care Guidelines Group, 2004b] and with specialist palliative care guidelines for the management of nausea and vomiting [Fife Area Drug & Therapeutics Committee, 2004; Lothian Palliative Care Guidelines Group, 2004a].

• Nausea and vomiting because of distension, compression, or disturbance of abdominal or pelvic organs (e.g. bowel or liver): give cyclizine 25–50 mg orally every 8 hours and when required (maximum dose 150 mg/24 hours), or 75–150 mg by subcutaneous infusion over 24 hours.
• If bowel obstruction is suspected: see Managing known cause: Due to bowel obstruction.

• These recommendations are based on specialist palliative care literature and guidelines for the management of nausea and vomiting [Regnard and Hockley, 2004; Cancer Care Alliance, 2006a].
• 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 [Doyle et al, 2004].
• Anti-emetics active at the vomiting centre may therefore help to palliate nausea in this situation [Doyle et al, 2004]; cyclizine acts principally on acetylcholine and histamine type 1 (H₁) receptors in the vomiting centre [Twycross et al, 2002; Mannix, 2006].

• 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 (e.g. cyclizine, hyoscine).

• These recommendations are based on specialist palliative care guidelines for the management of nausea and vomiting [Twycross and Wilcock, 2001; Fife Area Drug & Therapeutics Committee, 2004; Lothian Palliative Care Guidelines Group, 2004a; Regnard and Hockley, 2004; Cancer Care Alliance, 2006a].

• Manage anxiety independently, according to the person's prognosis.
• Consider a benzodiazepine (e.g. lorazepam, 0.5–1 mg sublingually) or levomepromazine (3–6 mg orally or 2.5–6.25 mg by subcutaneous injection). Avoid diazepam.

• These recommendations are based on UK specialist palliative care guidelines on the management of nausea and vomiting [Cancer Care Alliance, 2006a].
• Diazepam is not recommended because it has a long plasma half-life and marked individual variation in metabolism. Concurrent administration with other sedative drugs (including strong opioids), old age, debilitation, or hepatic impairment may lead to excessive sedation.

• Try simple measures to relieve symptoms.
• Review the history, examination, and medication and consider checking blood for renal failure, hypercalcaemia, liver failure, or blood glucose abnormalities.
• If the cause is still uncertain or further investigation is not appropriate:
• Try haloperidol, 1.5–10 mg daily:
• Starting dosage: 1.5 mg immediately and at night.
• Usual dosage: 3–5 mg at night or in divided doses.
• Usual maximum dosage in nausea and vomiting: 10 mg/day (at night or in divided doses).
• Add cyclizine (25–50 mg three times a day) if haloperidol alone is not effective.
• 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.
• 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 (e.g. the cause was self-limited or has been reversed).

• 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 Area Drug & Therapeutics Committee, 2004; Lothian Palliative Care Guidelines Group, 2004a; Regnard and Hockley, 2004; Pan-Glasgow Palliative Care Algorithm Group, 2005; Cancer Care Alliance, 2006a].
• 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.

• Try simple measures to relieve symptoms.
• If current anti-emetic controls symptoms well:
• Continue with the same drug.
• Give the 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 (e.g. replace domperidone with metoclopramide, and prochlorperazine with cyclizine).
• For new or uncontrolled nausea and vomiting:
• If appropriate try to determine the underlying cause of nausea and vomiting and manage accordingly (see Managing 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.

• This recommendation is based on UK specialist palliative care guidelines on nausea and vomiting at the end of life [Cancer Care Alliance, 2006b].

• 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.
• If the cause has been correctly identified, optimize the dose and route of the first-line anti-emetic.
• If nausea and vomiting persist after two to 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 metoclopramide with antimuscarinincs, e.g. hyoscine, cyclizine, or levomepromazine).
• Refer to a specialist palliative care team if symptoms remain uncontrolled after 24 hours.

• 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 [Perdue, 2005].

• These are pragmatic recommendations based on expert opinion from current literature [Twycross and Wilcock, 2001; Perdue, 2005] and from expert reviewers.