What is the best management approach for a patient with persistent vomiting, considering their age, medical history, and potential underlying causes?

Management of Persistent Vomiting

Initiate dopamine receptor antagonists (metoclopramide 10-20 mg every 6 hours, prochlorperazine, or haloperidol) as first-line therapy, titrated to maximum benefit and tolerance, and if vomiting persists after this optimization, add ondansetron 8-16 mg as a 5-HT3 antagonist from a different drug class. 1, 2, 3

Identify and Treat Underlying Causes First

Before initiating antiemetic therapy, systematically evaluate for reversible causes:

• Obtain complete blood count, serum electrolytes, glucose, liver function tests, lipase, and urinalysis to exclude metabolic causes and assess dehydration 2
• Check for hypercalcemia, hypothyroidism, and Addison's disease if clinically suggested 2
• Perform one-time esophagogastroduodenoscopy (EGD) or upper GI imaging to exclude obstructive lesions, but avoid repeated endoscopy 2
• Obtain urine drug screen and detailed cannabis use history, as Cannabis Hyperemesis Syndrome requires 6 months cessation or 3 typical cycle lengths without vomiting for definitive diagnosis 2
• Assess for constipation/fecal impaction, gastroparesis, bowel obstruction, CNS involvement, gastric outlet obstruction, and medication-induced causes 1, 3

Stepwise Pharmacologic Algorithm

First-Line: Dopamine Receptor Antagonists

Start with metoclopramide 10-20 mg every 6 hours, prochlorperazine, or haloperidol, and titrate to maximum benefit and tolerance. 1, 2, 3 These agents target dopamine receptors in the chemoreceptor trigger zone and are the foundation of persistent vomiting management across multiple guidelines. 1, 3

• Metoclopramide is particularly effective for gastroparesis as it promotes gastric emptying 1, 3
• Monitor for extrapyramidal symptoms, especially in young males, and treat with diphenhydramine 50 mg IV if they develop 2
• Administer on a scheduled around-the-clock basis rather than PRN, as prevention is far easier than treating established vomiting 1, 2

Second-Line: Add 5-HT3 Antagonist

If vomiting persists after optimizing dopamine antagonist therapy, add ondansetron 8-16 mg orally 2-3 times daily or 0.15 mg/kg IV (maximum 16 mg per dose). 2, 3, 4 The key principle is adding agents from different drug classes rather than replacing one antiemetic with another, as different neuroreceptors are involved in the emetic response. 3

• Ondansetron is available in sublingual tablet form, which may improve absorption in actively vomiting patients 3
• Monitor for QTc prolongation when using ondansetron, especially in combination with other QT-prolonging agents 2
• The oral route may not be feasible due to ongoing vomiting; consider rectal or intravenous administration 1, 3

Third-Line: Add Corticosteroids and Additional Agents

If symptoms persist, add dexamethasone 4-8 mg three to four times daily, and consider adding anticholinergic agents (scopolamine), antihistamines (meclizine), or cannabinoids. 1, 3

• Dexamethasone combined with ondansetron is superior to either agent alone and represents category 1 evidence 2
• For anxiety-related nausea, add lorazepam as a benzodiazepine 1, 3
• Haloperidol 1 mg IV/PO every 4 hours as needed is an alternative dopamine antagonist with a different receptor profile 2

Fourth-Line: Refractory Cases

For intractable vomiting, consider continuous IV/subcutaneous infusion of antiemetics, olanzapine, or opioid rotation if patient is on opioids. 1, 3

• Dronabinol 2.5-7.5 mg PO every 4 hours as needed is FDA-approved for refractory nausea 2
• Multiple concurrent agents in alternating schedules may be necessary, as no single agent has proven superior for breakthrough emesis 1, 2
• Consider alternative therapies such as acupuncture or palliative sedation as a last resort for severe, intractable vomiting 1, 3

Treatment of Specific Underlying Causes

Gastroparesis or Gastritis

Continue metoclopramide as it promotes gastric emptying, and add proton pump inhibitor or H2 receptor antagonist. 1, 2, 3

Metabolic Abnormalities

Correct hypercalcemia, treat dehydration, and address electrolyte imbalances (particularly hypokalemia and hypomagnesemia) identified on initial laboratory testing. 1, 2, 3

Medication-Induced Vomiting

Discontinue unnecessary medications, check blood levels of necessary medications (digoxin, phenytoin, carbamazepam, tricyclic antidepressants), and treat medication-induced gastropathy with proton pump inhibitor and metoclopramide. 1 If due to opioids, initiate opioid rotation. 1

CNS Involvement

Use corticosteroids (dexamethasone 4-8 mg three to four times daily) and consider palliative radiation therapy. 1

Critical Pitfalls to Avoid

• Never use antiemetics in suspected mechanical bowel obstruction, as this can mask progressive ileus and gastric distension 2, 3
• Do not stigmatize patients with cannabis use; offer abortive and prophylactic therapy even with ongoing use, as treatments can still be effective 2
• Avoid repeated endoscopy or imaging unless new symptoms develop 2
• Ensure adequate hydration and fluid repletion, and assess and correct any electrolyte abnormalities 1, 2
• Consider adding an H2 blocker or proton pump inhibitor if dyspepsia is present, as patients may confuse heartburn with nausea 1, 2