Nausea and vomiting

PHYSICAL PROBLEMS

 what is the likely mechanism?  what are the likely receptors involved? It is important to remember that there may be more than one mechanism involved and to take account of this in the management of the symptoms. One other key feature of management involves identifying potentially reversible causes of nausea and vomiting. Assessment of patients with advanced disease will involve a careful history focusing particularly on drugs (especially newly introduced drugs, including recent chemotherapy), the timing of vomiting, the presence of gastric discomfort and dyspepsia, recent bowel movements (constipation or obstruction), and neurological symptoms, especially headache or confusion. A careful examination should focus on and include:  an examination of the mouth and pharynx (oropharyngeal thrush)  palpation for hepatomegaly or other intra-abdominal masses  noting any distension and listening for bowel sounds  a rectal examination (this will usually be indicated)  a neurological examination (if there is any suspicion of vestibular or cerebral involvement, this might look for focal neurological signs and test vestibular function). A limited number of investigations might be useful:  full blood count (consider if infection likely or recent chemotherapy)  urea and electrolytes (dehydration)  calcium  liver function  plain abdominal films (faecal loading in constipation or fluid levels in intestinal obstruction). A contrast-enhanced computed tomography (CT) scan of the head would be indicated if there is a suspicion of raised intracranial pressure or vestibular involvement. A CT scan of abdomen and pelvis may delineate progressive disease, obstructive tumours or lymphadenopathy and should be considered where appropriate. Common, potentially reversible causes of emesis in patients with advanced disease are:  drugs (e.g. opioids, anticholinergics) e stop the drug where possible  metabolic (e.g. hypercalcaemia) e reverse the metabolic abnormality (uraemia, hypercalcaemia)  fear/anxiety e reassurance; anxiolytics; cognitive behavioural therapy  gastric irritation e stop irritants (e.g. non-steroidal antiinflammatory drugs); prescribe a proton pump inhibitor (e.g. omeprazole 20 mg once daily)  cough e suppress with opiates; consider radiotherapy if directly tumour-related (e.g. mediastinal lymphadenopathy)  constipation e aperients; enemata  oropharyngeal thrush e antifungal medication.

Nausea and vomiting Paul W Keeley

Abstract Nausea and vomiting are common problems in palliative care, occurring in 40e70% of patients with advanced incurable disease. They may be disease- or treatment-related, and require a holistic approach to their management. Careful assessment of the problem, with a focused history and a limited range of key investigations, is essential to effective management. Knowledge of the likely receptors involved in this complex phenomenon is vital to ensure the proper pharmacological measures are employed. Although many of the drugs used have been available for many years, newer agents have improved the management of some types of nausea and vomiting (especially surgery-, chemotherapy- and radiotherapyrelated emesis). Non-pharmacological measures, including stenting, laser and venting gastrostomy, can be considered in selected patients.

Keywords emesis; nausea; palliative care; vomiting

Nausea and vomiting are common in patients with cancer and other chronic diseases. They may occur because of several factors, both disease-related and treatment-related. The evidence base for treatment-related causes of nausea and vomiting (chemotherapy and radiotherapy) is much greater and more robust than for disease-related causes.1,2 Nausea and vomiting occur in 40e70% of people with cancer1,2 and are also common in other chronic conditions such as hepatitis C3 and inflammatory bowel disease.4 Nausea and vomiting become more common as disease progresses. Nausea and vomiting are complex neurological and physical phenomena involving a range of areas of the central nervous system and gastrointestinal tract. In palliative and supportive care, nausea may be due to chemotherapy, especially platinumbased chemotherapy,5 other drugs (opioids, antibiotics),6 or radiotherapy.7 It may also have disease-related causes, for example metabolic (hypercalcaemia, uraemia),8 intracranial (raised intracranial pressure, VIIIth nerve tumours), gastrointestinal (gastric outflow obstruction, hepatomegaly constipation, bowel obstruction, or ileus), or psychogenic (anticipatory nausea and vomiting, anxiety, or fear).9 In many cases, nausea will respond to treatment of the underlying cause, for example nausea resulting from metabolic disturbance such as hypercalcaemia. Nausea resulting from emetogenic drugs, such as opioids, may resolve if the drug is switched.

Assessment There are two critical clinical questions that should inform any assessment of nausea and vomiting in patients with advanced incurable disease:

Management Pharmacological management The key to successful pharmacological management is identifying the likely mechanism or mechanisms in order to block the relevant receptor. Table 1 gives a summary of features and the relevant receptors involved.

Paul W Keeley MBChB MRCGP is a Consultant in Palliative Medicine at the Glasgow Royal Infirmary, Glasgow, UK. Competing interests: none declared.

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PHYSICAL PROBLEMS

Anti-emetic drugs by class, dose, effect and indication Anti-emetic

Class

Dose (per 24 h)

Main site of action/receptor

Indication

Metoclopramide

Prokinetic

30e80 mg

Gut stasis

Cyclizine

Antihistamine

150 mg

Increases peristalsis in upper gut Dopamine Vestibular and vomiting centres Acetylcholine

Haloperidol

Butyrophenone

1.5e10 mg

Levomepromazine

Phenothiazines

12.5e50 mg

Ondansetron

5-HT3 receptor antagonist

8e16 mg

Blocks 5-HT3 receptors at cTZ and in gut

Granisetron

5-HT3 receptor antagonist

1e2 mg

Blocks 5-HT3 receptors at cTZ and in gut

Dexamethasone

Corticosteroid

8e16 mg

Reduces inflammatory oedema, has an ill-defined non-specific central anti-emetic effect

Hyoscine butylbromide

Anticholinergic

60e300 mg

Octreotide

Somatostatin analogue

250e750 mg

Reduces gastrointestinal secretions and motility Acetylcholine Reduces gut secretions

Blocks dopamine receptors at chemoreceptor trigger zone (cTZ) Dopamine Blocks dopamine and serotonin Receptors at cTZ

Intestinal obstruction Vestibular causes (middle ear infection/VIII tumours) Chemical/drug causes Hiccup Most causes e useful as a second-line, broad-spectrum anti-emetic Nausea and vomiting related to chemotherapy, radiotherapy and surgery Nausea and vomiting related to chemotherapy, radiotherapy and surgery Adjunct in raised intracranial pressure and chemotherapy-related nausea and vomiting; helpful adjunct where cause is unclear Intestinal obstruction

Intestinal obstruction

Table 1

Commonly used anti-emetics Metoclopramide: is a prokinetic anti-emetic D2-receptor antagonist and 5-HT4 receptor agonist. Its indications include nausea and vomiting, particularly in gastrointestinal disorders (e.g. gastric stasis). Adverse effects of this drug include extrapyramidal effects, restlessness, depression and, rarely, neuroleptic malignant syndrome.

high. Indications include nausea and vomiting. Caution should be taken in patients with parkinsonism, hypotension, epilepsy, hypothyroidism, and myasthenia gravis. Undesirable effects include sedation and postural hypotension. Non-pharmacological measures There are some specific clinical pictures where consideration should be given to non-pharmacological measures.

Haloperidol: is a D2-receptor dopamine antagonist. Indications are metabolic and drug causes of nausea and vomiting. It should be used carefully in patients with Parkinson’s disease as it may increase the sedative effects of other drugs. Adverse effects can include extrapyramidal effects, tardive dyskinesia with chronic use, hypothermia, sedation, hypotension and, rarely, neuroleptic malignant syndrome.

Upper gut tumours: may require endoscopy with stenting or laser treatment for obstructive tumours; intractable, antiemeticresistant vomiting at the end of life may warrant venting gastrostomy. Lower gut tumours: ovarian and other pelvic tumours may respond to chemo- or radiotherapy; nasogastric tubing should be considered where appropriate. Alternatively, in selected patients, colostomy may bypass the obstruction if there is a reasonable prognosis.

Ondansetron, granisetron and tropisetron: are 5-HT3 receptor antagonists. Indications include surgery-, chemotherapy- and radiotherapy-related nausea and undesirable effects include constipation, flushing and hiccup.

Raised intracranial pressure: may respond to radiotherapy of the tumour. Other important environmental measures include avoidance of food smells or unpleasant odours, diversion, and relaxation. Some patients report benefit from acupuncture although there is little robust evidence to support its widespread use. A

Levomepromazine: is a broad-spectrum anti-emetic that is widely used as a second- or third-line agent in patients who fail to respond to other anti-emetics. It is a potent D2-receptor antagonist, and has activity across most receptors except 5-HT3. Its broad-spectrum activity means the incidence of sedation is

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REFERENCES 1 Grond S, Zech D, Diefenbach C, et al. Prevalence and pattern of symptoms in patients with cancer pain: a prospective evaluation of 1635 cancer patients referred to a pain clinic. J Pain Symptom Manage 1994; 9: 372e82. 2 Fainsinger R, Miller MJ, Bruera E, et al. Symptom control during the last week of life on a palliative care unit. J Palliat Care 1991; 7: 5e11. 3 Riley 3rd TR, Chinchilli VM, Shoemaker M, et al. Is nausea associated with chronic hepatitis C infection? Am J Gastroenterol 2001; 96: 3356e60. 4 Greenstein AJ, Geller SA, Dreiling DA, et al. Crohn’s disease of the colon. IV. Clinical features of Crohn’s (ileo) colitis. Am J Gastroenterol 1975; 64: 191e9. 5 Grunberg SM, Deuson RR, Mavros P, et al. Incidence of chemotherapyinduced nausea and emesis after modern antiemetics. Cancer 2004; 100: 2261e8. 6 Campora E, Merlini L, Pace M, et al. The incidence of narcotic-induced emesis. J Pain Symptom Manage 1991; 6: 428e30. 7 Feyer CP, Titlbach OJ, Wilkinson J, et al. Gastrointestinal reactions in radiotherapy. Supp Care Cancer 1996; 4: 249. 8 Bajorunas DR. Clinical manifestations of cancer-related hypercalcemia. Semin Oncol 1990; 17: 16e25. 9 Fallowfield LJ. Behavioural interventions and psychological aspects of care during chemotherapy. Eur J Cancer 1992; 28A: s39e41.

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Practice points C

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Unless, or until, the cause of the vomiting can be treated, give anti-emetics regularly rather than as required If emesis limits drug absorption there is little point in giving drugs orally and a continuous subcutaneous infusion (CSCI) of drug is to be preferred Some anti-emetics can be given as suppositories and this is a useful alternative to CSCIs Prokinetic drugs may cause a worsening of colic and emesis if there is an intestinal obstruction Carefully selected patients may be suitable for corrective surgery: venting gastrostomy or bypass for upper gastrointestinal (GI) obstruction; palliative colostomy for lower GI obstruction Even where surgical approaches are precluded by poor performance status or other considerations, palliative endoscopic procedures such as stenting or laser treatment of obstructive tumours may give effective relief There is some evidence that dexamethasone can act as a useful adjunct to conventional anti-emetic drugs where the cause of nausea is unknown

Ó 2011 Published by Elsevier Ltd.