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Home , Cyclizine, Ondansetron

GUIDELINES FOR THE MANAGEMENT OF AND IN PALLIATIVE CARE

27.1 GENERAL PRINCIPLES  Nausea and vomiting are experienced by 50-60% of patients with advanced cancer. 1

 Nausea and vomiting are more common in certain groups of patients i.e. <65 years old, females and certain malignancies e.g. gastric and breast cancer. 1

 Patients with advanced malignancy may develop nausea and vomiting from causes unrelated to the cancer e.g. gall bladder disease or . 1

 Table 27.1 lists some common causes of nausea and vomiting in patients with advanced cancer. 1, 2

1, 2 Table 27.1 Common causes of nausea and vomiting in advanced cancer

Anxiety Gastritis Autonomic neuropathy Hypercalcaemia Biochemical Infection Brainstem / meningeal disease Intestinal obstruction

Constipation Pain

Cough Radiotherapy

Drugs Raised intracranial pressure

Functional obstruction Renal failure

Gastric outlet obstruction Vestibular disturbance

 Anti-emetics are -blocking agents and are effective at different receptor sites (see Figure 27.1). 3

 The choice of anti-emetic will be influenced by the cause of vomiting. They may be administered by a variety of routes. The oral or subcutaneous routes are the preferred options in palliative care. 4

27.2 GUIDELINES

 Table 27.2 lists the pharmacological options for the management of nausea and vomiting in advanced cancer. 3

Table 27.2 Pharmacological options for the management of nausea and vomiting in advanced cancer 1, 2, 3, 5, 6 [Level 4]

Drug name Type of drug Indication for Oral dose Parenteral dose Parenteral dose Notes use (subcutaneously over (subcutaneous stat 24 hours via a syringe doses) driver) Central causes. 50mg tds. 100g-150mg 50mg subcutaneous Dilute with water Movement Maximum prn. include dry mouth, urinary related nausea daily dose is retention and restlessness. Should not be and vomiting. 150mg. co-prescribed with or Bowel . Avoid in severe cardiac obstruction. failure. Should not be mixed with in a CSCI. Intracranial 8mg-16mg od 8mg-16mg Not applicable. Side effects include insomnia, delerium disease. Exact dose and restlessness. If dose≤ 8mg can give as Bowel determined subcutaneous bolus dose. Use separate obstruction. by cause. (See syringe driver as does not mix with other Guidelines on drugs. Use of ) Domperidone Prokinetic Useful in gastric 10mg-20mg n/a n/a Can be given via rectal route. Does not stasis. tds-qds. cross the blood-brain barrier so less likely D2 to give extrapyramidal reactions compared to .

Haloperidol Butyrophenone Chemical causes 1.5mg-5mg 1.5mg-5mg 1.5mg-3mg Risk of . Single (D receptor e.g. . nocte. (maximum 10mg daily) subcutaneously as daily dose usually sufficient because of 2 required. long half life. Parental administration is antagonist) Metabolic (maximum10 NB: Subcutaneous: oral causes. mg daily) more potent therefore consider starting at potency of haloperidol a lower dose. is 2:1. Continued on next page

Table 27.2 (continued) Pharmacological options for the management of nausea and vomiting in advanced cancer 1, 2, 3, 5, 6 [Level 4]

Drug name Type of drug Indication for Oral dose Parenteral dose Parenteral dose Notes use (subcutaneously over (subcutaneous stat 24 hours via a syringe doses) driver) Hyoscine Anti-cholinergic Mechanical 300 micro- 1.2mg-2.4mg 400microgrammes May cause paradoxical agitation. Has Hydrobromide obstruction grams - subcutaneously as central anti-emetic activity. Movement-related hourly required nausea and (sublingual) vomiting Unknown cause 6.25mg- 6.25mg-25g 6.25mg-12.5mg Side effects include dry mouth, sedation (Methotrimeprazine) of vomiting 25mg od subcutaneously as and . Usually used as required Parenteral administration is more potent second line therefore consider starting at a lower dose. therapy due to There is a 6mg tablet available sedative effect. (unlicensed). Benzodiazepine Anxiety 0.5mg-1mg n/a n/a Risk of sedation. Often used during Anticipatory sublingually . nausea as required or bd Metoclopramide Prokinetic. Useful in gastric 10mg-20mg 30mg-120mg 10mg-20mg Reduce dose in severe renal failure. Do not stasis/ tds subcutaneously as use in complete bowel obstruction. May D2 receptor antagonist required cause extrapyramidal reactions at higher doses. Prokinetic effect may be reduced if drugs are co-prescribed. Octreotide Somatostatin Reduction of Not 300microgrammes- 50microgrammes– A long acting depot injection is available. analogue gastrointestinal applicable 600microgrammes 100microgrammes secretions subcutaneously as required

Ondansetron 5HT3 receptor Chemotherapy 4mg-8mg bd 8mg-24mg 4mg subcutaneously Side effects include . antagonist and radiotherapy or tds as required Dilute with saline. induced nausea and vomiting

Figure 27.1 Sites of action of selected anti-emetics 2, 3 [Level 4]

CORTICAL STRUCTURES

Dexamethasone (reduces raised intracranial pressure but probably not anti-emetic at cortex)

VOMITING CENTRE

M 5-HT2 H1 (muscarinic) ()

- Cyclizine - Levomepromazine - Hyoscine hydrobromide

CHEMORECEPTOR VESTIBULAR APPARATUS TRIGGER ZONE H1 M

D2 5-HT3 - Cyclizine () - Hyoscine hydrobromide

- Haloperidol - Metoclopramide - Levomepromazine - VAGAL/SOMATIC AFFERENTS e.g. bowel

D2 5-HT3 M

- Metoclopramide/Domperidone - Levomepromazine - Ondansetron

 Patient assessment should include a full history, examination and investigations where appropriate. 1 [Level 4]

 The history should include details of the volume, content and timing of vomiting. Nausea should be specifically enquired for and rated, along with any diurnal pattern or associated features which may suggest a cause. 1 [Level 4]

 A biochemical profile, including corrected calcium, should be checked in patients with nausea and / or vomiting unless they are in the dying phase. 1 [Level 4]

 Reversible causes should be treated where appropriate. These include: drugs, constipation, hypercalcaemia, cough, anxiety and gastric irritation. 3, 4 [Level 4]

 Non-pharmacological measures which may be useful in the management of nausea and vomiting include: psychological measures, transcutaneous electrical nerve stimulation (TENS), complementary therapies and advice on posture and diet. 1, 3 [Level 4]

 Anti-emetics may be given via the oral route for patients with nausea. However, if nausea is severe or protracted, early use of the parenteral route should be considered. Gastric stasis can cause nausea and oral anti-emetics may be ineffective in this situation. 1,3 [Level 4]

 A continuous subcutaneous infusion (CSCI) via a syringe driver should be considered for:

− Patients who have vomiting lasting more than 24 hours.

11 − Patients who have nausea unresponsive to oral anti-emetics for more than 24 hours. [Level 4]

 Various subcutaneous regimens are suggested in Table 27.3.

 A single stat subcutaneous injection should be given at the same time as setting up the CSCI and breakthrough anti-emetics should always be prescribed. 11 [ Level 4]  If using levomepromazine in a syringe driver, the syringe should be shielded from sunlight. 9 [Level 3]

 In cases of inoperable bowel obstruction, a nasogastric tube or venting gastrostomy may be appropriate for symptom control. (see Guidelines for the Management of Bowel Obstruction). 1,10 [Level 3]

 Autonomic neuropathy is common in advanced disease and may cause gastroparesis. This may contribute to terminal restlessness. Consider using a nasogastric tube to remove gas and liquid from the stomach. This may restore comfort and the tube can then be withdrawn. 11 [Level 4]

 If a nasogastric tube is left in-situ, prescribe cyclizine or levomepromazine to alleviate the nausea caused by pharyngeal stimulation. 11 [Level 4]

Table 27.3 Suggested regimens via CSCI 2, 3, 6, 7, 8 [Level 4]

Aetiology First line Second line Cause unknown Cyclizine 100mg-150mg +/- Levomepromazine 6.25mg – 25mg haloperidol 1.5mg-5mg via CSCI over 24 hours, +/- dexamethasone over 24 hours. 4mg–8mg subcutaneously once daily. Bowel obstruction See Guidelines for the Management See Guidelines for the Management of Bowel Obstruction. of Bowel Obstruction.

Chemical/ 1.5mg-5mg haloperidol injected Discuss with specialist team Metabolic subcutaneously once daily or via CSCI over 24 hours. Gastroparesis Initial stat subcutaneous injection of Discuss with specialist team metoclopramide 10mg, followed by CSCI of metoclopramide 30mg– 60mg over 24 hours.

NB Do not use in complete obstruction.

27.3 STANDARDS

1. Any patient with a history of nausea and vomiting should have a full assessment including a history, clinical examination and appropriate investigations to try and identify a cause for the symptoms. 1 [Grade D] 2. Appropriate anti-emetics should be prescribed on a regular and as required basis. 11 [Grade D]

3. If a patient is vomiting or nauseated for more than 24 hours, anti-emetics should be given via the parenteral route. 11 [Grade D]

4. If combinations of anti-emetics are required, drugs with different but complementary actions should be used. 2, 3 [Grade D]

5. Metoclopramide should not be prescribed if the vomiting is caused by complete intestinal obstruction. 2, 3 [Grade D] 6. Symptoms of nausea and vomiting should be controlled within 72 hours. 11 [Grade D]

27.4 REFERENCES

1. Baines MJ. ABC of palliative care: Nausea and vomiting in intestinal obstruction. Br Med J 1997; 315(7116): 1148-1150.

2. Dickman A, Schneider J, Varga J (eds). The Syringe Driver: Continuous Subcutaneous Infusions in Palliative Care. 2nd edition. Oxford: Oxford University Press; 2005. 3. Twycross R, Wilcock A (editors). Palliative Care Formulary 3rd edition. Nottingham: Palliativedrugs.com Ltd. 2007. p. 1-40

4. Bentley A, Boyd K. Use of clinical pictures in the management of nausea and vomiting: a prospective audit. Palliat Med 2001; 15(3): 247-253.

5. Currow DC, Coughlan M, Fardell B, Cooney NJ. Use of ondansetron in palliative medicine. J Pain Symptom Manage 1997; 3(5): 302-307.

6. Twycross R, Barkby GD, Hallwood PM. Use of levomepromazine in the management of nausea and vomiting. Prog Palliat Care 1997; 5(2): 49-53.

7. Bruera E, Seifert L, Watanabe S, Babul N, Darke A, Harsanyi Z et al. Chronic nausea in advanced cancer patients: A retrospective assessment of a metoclopramide-based anti-emetic regime. J Pain Symptom Manage 1996; 11(3): 147-153.

8. Mannix K. Palliation of nausea and vomiting. In: Hanks GWC, Cherny NI, Calman K, Doyle D (eds). Oxford Textbook of Palliative Medicine. 3rd edition. Oxford: Oxford University Press; 2005: p. 459-467.

9. Davies AN, Mitchell M. Methotrimeprazine and UV light. Palliat Med 1996; 10(3): 264.

10. Brooksbank MA, Game PA, Ashby MA. Palliative venting gastrostomy in malignant intestinal obstruction. Palliat Med 2002; 16(6): 520-526.

11. Merseyside and Cheshire Palliative Care Network Audit Group. Management of Nausea and Vomiting. Expert Consensus. July 2003.

27.5 CONTRIBUTORS

Lead Contributors External Reviewer

Dr L Chapman Dr K Mannix Consultant in Palliative Medicine Consultant in Palliative Medicine Royal Liverpool and Broadgreen University Royal Victoria Infirmary Hospitals NHS Trust Newcastle-upon-Tyne Liverpool

Dr C Usborne Consultant in Palliative Medicine Glan Clwyd District General Hospital NHS Trust Rhyl North Wales

Mr A Dickman Specialist Principal Pharmacist Marie Curie Palliative Care Institute Liverpool