Nausea and Vomitting during Chemotherapy

Submitted by Elizabeth Culvewrwell, Clinical Education CEL. Originally printed in June 2008 IVNNZ Inc. Newsletter

Nausea and Vomiting during Chemotherapy  - A Literature Review 

Elizabeth Culverwell

 Nausea and vomiting is a distressing event experienced by patients within the hospital and community setting. This review outlines the mechanism, medical and psychological problems and subsequent management principles for patients receiving Chemotherapy.

Nausea and Vomiting

To manage this debilitating side effect of chemotherapy, is first to understand it.

Vomiting is a protective mechanism that removes ‘poisons' from the stomach. Chemotherapy agents are essentially ‘poisons'. Gastro intestinal receptors and the chemo receptor trigger zone (CTZ) work as detectors in the presents of ‘poisons' in the gut, blood and cerebrospinal fluid. Once stimulated the signal is relayed to the vomiting centre in the brain stem and leads to nausea and vomiting. (Nursing in Haematology and Oncology. Royal College of Nursing)

Nausea and vomiting gives rise to a number of other medical problems such as dehydration; electrolyte imbalances; weight loss; malnourishment; epigastric pain; oesophageal bleeding; hiccups and the development of anticipatory nausea and vomiting. Depression often follows with low morale a contributing factor to general apathy, fear and isolation. Inadequate anti-emetic management makes the patient's experience even more distressing especially when experiencing persistent delayed nausea. (Roila et al 1988-99)

This is a very distressing side effect of nausea and vomiting following aggressive emetogenic chemotherapy regimes. (Coates at al 1983)

Anti-emetic medications are available to assist in the management of this all too often debilitating side effect. Yet twenty four years on (from Coates et al 1983 ref) and despite advances in anti-emetic medication a significant number of our patients are still affected.

It is a recognised fact that Persistent Delayed Nausea (PDN) is more difficult to manage and whilst vomiting brings relief, persistent nausea is often the more distressing of the two. (Osoba et al 1997)

Categories

Nausea and vomiting caused by cytotoxic therapy falls into three categories:

• Immediate - occurs within the first 30 -120 minutes
• Acute - within the first 24 hours
• Delayed - begins after the first 24 hours, although onset can be delayed for up to 3-5 days. It has become more obvious as more effective drug combination régimes were developed to control nausea and vomiting. PDN has emerged as a more significant problem and can be seen in patients receiving Cyclophosphamide or Ifosfamide. It is believed to have a separate mechanism from acute nausea and vomiting with suggestions that gastritis, tissue damage electrolyte fluctuations or effects on Central /Peripheral Nervous Systems. Early prophylactic therapy using steroid/dopamine antagonist combination is the most effective.

 Others

• Anticipatory nausea and vomiting although not drug induced is a fourth syndrome
• Break though nausea and vomiting.  (A scheduled régime of conventional anti-emetics is possibly more effective than using intermittent or PRN 5-HT3 antagonists.)

Classification Anti-emetic Medications

Site of Action

Antimemetics used in the Bone Marrow Transplant Unit

Ondansetron

• 5-HT3 antagonist - highly effective, low side effects. Combined with steroids significantly better than either agent alone. Not a complete solution. ? appropriate second line therapy for treatment failures
• has its greatest protective effect in the initial 24 hrs and possibly the initial 16-18hrs

 Metoclopramide

• most commonly used anti-emetic. Complicated by reactions e.g. restlessness, sedation, hypotension, diarrhea. Used for mild-moderate nausea and/or breakthrough nausea/vomiting

Dexamethasone

• effect mechanism is unknown but is an important component to drug régimes
• enhances the efficacy of Ondansetron
• as a single agent appears to be equal to or more effective than 5-HT3 antagonists for delayed nausea/vomiting

Scopolamine

• blocks muscarinic receptors and is useful as an adjunct in delayed nausea or for prolonged mild nausea

 Lorazapam

• inhibits vomiting centre. Has a mild anti-emetic activity, but highly effective in preventing anticipatory nausea and vomiting

Droperidol

• anti-emetic activity against moderate to highly emetogenic chemo. Optimum response is seen when used as part of a multi drug régime

Promethazine

• effective against mild to moderate nausea or vomiting
• has little impact on emesis from highly emetogenic chemo.

Category of Emetogenic Potential of Chemotherapy Drugs & appropriate Anti-emetics

General Principles for managing Nausea and Vomiting

• Prophylaxis is better than treatment of actual vomiting
• Antiemetic régimes should be individualize for each patient
• If no nausea for 24 hrs consider switch to PRN
• Titrate dose to patient tolerance
• Combined régimes provide optimum control
• Avoid using agents from same pharmacologic category
• Effective prophylaxis  in the first cycle can minimize anticipatory nausea and vomiting
• Use Scopolamine or Lorazapam if anticipatory nausea and vomiting develop
• If it's not broken - don't fix it!
• For high -moderate emetogenic regimes  a steroid & serotonin blocker combination is recommended i.e. Dexamethasone & Ondansetron
• Delayed reactions are not uncommon 1-7 days post chemotherapy
• Antihistamines & anticholinergics are best used in combination with more effective drugs or as a second or third line therapy
• Serotonin antagonists are most effective in scheduled prophylactic régimes than as PRN
• Serotonin antagonists have little effect in stopping nausea and vomiting once it has begun. Dopamine blocker such as Domperidone may be more effective
• Serotonin antagonists i.e. Ondansetron, have a ‘ceiling dose' above which there is little or no anti-emetic effect

References:

1. Andrykowski et al(1992) Development of anticipatory nausea: a prospective analysis. Journal of Consulting Clinical Psychology
2. Coates et al (1983) On the receiving end- patient perception of side effects of chemotherapy. European Journal of Clinical Oncology 19: 203-208
3. Drug Information handbook for Oncology. 6th Edition Management of Nausea and Vomiting.
4. Nursing in Haematology and Oncology - Royal College of Nursing. Balliere Tindall publishers
5. Osoa et al(1997) Determinants of post chemotherapy nausea and vomiting in patients with cancer. Journal of Clinical Oncology 15(1):116-123
6. Roila et al(1989)Protection from vomiting in Cisplatin-treated patients Journal of Clinical Oncology 7:1693-1700