What is the best approach to manage intractable nausea and vomiting?

Management of Intractable Nausea and Vomiting

For intractable nausea and vomiting, initiate dopamine receptor antagonists (metoclopramide, haloperidol, or prochlorperazine) as first-line therapy, then sequentially add 5-HT3 antagonists (ondansetron), corticosteroids (dexamethasone), and consider continuous IV/subcutaneous infusions if symptoms persist despite around-the-clock dosing. 1

Stepwise Pharmacologic Algorithm

First-Line Treatment

• Start with dopamine receptor antagonists titrated to maximum benefit and tolerance 1, 2:
  • Metoclopramide 10-20 mg PO/IV every 6 hours 1
  • Haloperidol 0.5-2 mg PO/IV every 4-6 hours 3
  • Prochlorperazine 10 mg PO/IV every 6-8 hours 1
  • Olanzapine 2.5-5 mg PO daily (especially effective in palliative care) 3
• Use around-the-clock dosing rather than as-needed for persistent symptoms 1
• If anxiety contributes to symptoms, add lorazepam 0.5-1 mg every 4 hours 1, 3

Second-Line Treatment (If Symptoms Persist After 4 Weeks)

• Add a 5-HT3 antagonist rather than replacing the dopamine antagonist—target different receptor pathways for synergistic effect 1, 2:
  • Ondansetron 4-8 mg PO/IV 2-3 times daily 3, 2
  • Granisetron 1 mg PO twice daily or 34.3 mg transdermal patch weekly 3
• Consider adding anticholinergic agents (scopolamine), antihistamines (meclizine), or cannabinoids 1, 2

Third-Line Treatment (For Refractory Symptoms)

• Add corticosteroids: dexamethasone 4-8 mg BID-TID 1
• Consider continuous IV or subcutaneous infusion of antiemetics for intractable symptoms 1
• If patient is on opioids, perform opioid rotation 1

Critical Underlying Causes to Address

Immediately Rule Out or Treat:

• Severe constipation/fecal impaction: This is a reversible cause that must be addressed before escalating antiemetics 1
• Bowel obstruction: Physical exam and abdominal x-ray required; never use antiemetics in mechanical obstruction as this masks progressive ileus 4, 2
• Medication-induced: Discontinue unnecessary medications, check drug levels (digoxin, phenytoin, carbamazepine) 1
• Metabolic abnormalities: Correct hypercalcemia, treat dehydration, address electrolyte imbalances (hypokalemia, hypomagnesemia) 1, 4
• Gastroparesis: Metoclopramide 5-10 mg PO 30 minutes before meals and at bedtime promotes gastric emptying 1, 2
• CNS involvement: Brain metastases or meningeal disease require corticosteroids (dexamethasone 4-8 mg TID-QID) and palliative radiation 1
• Gastric outlet obstruction: Treat with corticosteroids, proton pump inhibitor, and metoclopramide; consider stenting 1

Route of Administration Considerations

When oral route is not feasible due to active vomiting 2, 5:

• Rectal suppositories (prochlorperazine, promethazine) 2, 5
• Subcutaneous or intravenous infusions 1
• Sublingual formulations (ondansetron sublingual tablets) 2

Special Population Adjustments

Elderly Patients:

• Reduce initial doses by 25-50% for all antiemetics 3
• Start lorazepam at 0.25 mg (not 0.5 mg) and taper gradually when discontinuing 3
• Monitor closely for extrapyramidal side effects with dopamine antagonists, especially in elderly patients 3, 4
• Avoid long-term benzodiazepine use due to dependence risk 3

Critical Pitfalls to Avoid

• Never use antiemetics in suspected mechanical bowel obstruction—this can mask progressive ileus and gastric distension 4, 2
• Do not replace one antiemetic with another—instead, add agents targeting different receptor pathways for synergistic effect 1, 2
• Monitor for QTc prolongation when using ondansetron, especially with other QT-prolonging agents 4
• Watch for extrapyramidal symptoms with dopamine antagonists, particularly in young males 4
• Avoid repeated endoscopy or imaging unless new symptoms develop 4
• If nausea persists beyond 1 week despite around-the-clock antiemetics, reassess the underlying cause rather than continuing to escalate doses 1

Last Resort Measures

For severe, intractable symptoms failing all interventions 1, 3:

• Consider alternative therapies (acupuncture) 1
• Palliative sedation may be considered in end-of-life care 1, 3
• Consult or refer to specialized palliative care services 1