Nausea and Vomiting

KEYPOINTS

• A distressing symptom present in over 50% of patients with advanced cancer
• There are multiple receptors in the central nervous system, which are involved in the development of nausea. Blocking of these receptors forms the basis of antiemetic medications. These receptors are: dopaminergic, muscarinic, cholinergic, histaminic, and serotonergic
• The choice of antiemetic therapy should be based on what is the presumed underlying cause of the nausea
• Often multiple, concurrent medications from different classes may be required for effective control (e.g. metoclopramide and haloperidol, or prochlorperazine and dexamethasone, etc.)

• In children with life limiting diseases benign causes such as gastroenteritis, reflux and infections such as otitis media should still be ruled out
• Nausea and vomiting may also occur in children due to emotional distress

ASSESSMENT

(see Foreword)

• Examination and investigation can be helpful in determining the underlying cause of the nausea/vomiting
• In addition to a (normally transient) side effect of initiating opioids, other causes of nausea/vomiting include severe constipation and impaction, bowel obstruction (malignant and non-malignant), chemotherapy, radiotherapy, metabolic abnormalities (e.g. hypercalcaemia), infection and other medications

MANAGEMENT

• Management should be “mechanism based” and reflect the most likely underlying cause of the nausea and vomiting
  • For gastric stasis consider a prokinetic such as metoclopramide 10-20 mg q4-6h PO/SC/IV
  • For opioid-induced nausea consider a prokinetic (see above) or a neuroleptic (see below)
  • For metabolic abnormalities or uremia consider a neuroleptic such as haloperidol 0.5-2 mg q6-12h PO/SC/IV, metoclopramide 10-20 mg q4-6h PO/SC/IV or prochlorperazine 10-20 mg q6h PO/IV or 25 mg q6h PR. These act as dopamine receptor antagonists at the chemoreceptor trigger zone (CTZ). Olanzapine 1.25-2.5 mg once daily PO is an atypical neuroleptic which is both a dopamine and 5HT receptor antagonist
  • For gastric irritation consider stopping offending agent and adding an H2 blocker such as ranitidine 150 mg bid PO or a proton pump inhibitor such as omeprazole 20 mg once daily PO
  • For chemotherapy or radiation-induced nausea consider 5HT3 receptor antagonists such as ondansetron 4-8 mg q8-12h PO/IV and/or dexamethasone 4-20 mg qAM PO/IV/SC
  • For motion-induced nausea consider an anti-histamine such as dimenhydrinate 50-100 mg q4-6h PO/IV
  • For infection consider treatment with antibiotics
  • For raised ICP (intracranial pressure) consider dexamethasone 4-20 mg qAM PO/IV/SC
  • For hypercalcaemia consider treatment with hydration and bisphosphonates such as pamidronate 60-90 mg (single dose) IV
  • For constipation see Constipation
  • For bowel obstruction see Malignant Bowel Obstruction
  • For over eating re-educate patient and family to reduce intake

• If no resolution then consider an additional antiemetic agent that targets different receptors (prokinetic, neuroleptic, anti-histamine, 5HT3 receptor antagonist)
• If anxiety is thought to be a contributing factor to the nausea or vomiting then lorazepam 0.5-2 mg q4-6h PO/SC/PR can be effective in control of nausea and vomiting in addition to other medications such as those mentioned above
• If no resolution then consider corticosteroids i.e. dexamethasone 4-20 mg qAM PO/IV/SC
• Medications should be dosed regularly if nausea and vomiting are ongoing symptoms

• Metoclopramide 0.1-0.2 mg/kg/dose q6h PO/SC/IV
• Haloperidol 0.05-0.15 mg/kg/day bid/tid PO/SC/IV
• Ranitidine (if gastritis) 2-4 mg/kg bid PO
• Ondansetron 0.15 mg/kg/dose q8h IV (max 8mg/dose)
• Dexamethasone
  • 2-5 years: 0.5-1 mg bid PO/SC/IV
  • 6-12 years: 1-2 mg bid PO/SC/IV
  • 12 (plus): 2-4 mg bid PO/SC/IV

PITFALLS/CONCERNS

• In the setting of complete bowel obstruction the use of prokinetic agents such as metoclopramide may result in increased pain and cramping and should be discontinued

• Metoclopramide and haloperidol (and other neuroleptics) can cause extra pyramidal reactions in children (as well as adults) and can be used in combination with diphenhydramine which will reduce likelihood of this

PALLIATIVE TIPS

• For intractable nausea and vomiting, a multimodal approach combining antiemetics targeting different receptors is recommended (e.g. haloperidol + dimenhydrinate + dexamethasone)
• Similar to the setting of ongoing pain, ongoing nausea requires regular dosing of antiemetics rather than just prn!

• Distraction and the avoidance of the smell of food and unpleasant odours may be helpful with children

SOURCES/REFERENCES

1. 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 antiemetic regimen. J Pain Symptom Manage 1996;11(3):147-153. http://www.ncbi.nlm.nih.gov/pubmed/8851371
2. Hardy J, Daly S, McQuade B, Albertsson M, Chimontsi-Kypriou V, Stathopoulos P et al. A double-blind, randomised, parallel group, multinational, multicentre study comparing a single dose of Ondansetron 24 mg PO. with placebo and metoclopramide 10 mg tds. PO. in the treatment of opioid induced nausea and emesis in cancer patients. Support Care Cancer 2002;10:231-236. http://www.ncbi.nlm.nih.gov/pubmed/11904788
3. Herndon CM, Jackson KC II, Hallin PA. Management of opioid-induced gastrointestinal effects in patients receiving palliative care. Pharmacotherapy 2002;22(2):240-250. http://www.ncbi.nlm.nih.gov/pubmed/11837561
4. Kovac AL. Prevention and treatment of postoperative nausea and vomiting. Drugs 2000;59(2):213-243. http://www.ncbi.nlm.nih.gov/pubmed/10730546
5. Mercadante S, Portenoy RK. Opioid poorly-responsive cancer pain. Part 3. Clinical strategies to improve opioid responsiveness. J Pain Symptom Manage 2001;21(4):338-354. http://www.ncbi.nlm.nih.gov/pubmed/11312049
6. Ross DD, Alexander MS. Management of common symptoms in terminally ill patients: part I. Fatigue, anorexia, cachexia, nausea and vomiting. Am Fam Physician 2001;64(5):807-814. http://www.ncbi.nlm.nih.gov/pubmed/11563572

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