What is the best course of treatment for an adult patient with no significant medical history experiencing persistent vomiting?

Management of Persistent Vomiting in Adults

For an adult with no significant medical history experiencing persistent vomiting, initiate dopamine receptor antagonists (metoclopramide, prochlorperazine, or haloperidol) as first-line therapy, titrated to maximum benefit and tolerance, while simultaneously conducting a focused diagnostic workup to identify and treat reversible causes. 1, 2

Initial Diagnostic Evaluation

Obtain the following laboratory tests immediately to exclude metabolic causes and assess severity: 1

• Complete blood count, serum electrolytes (particularly potassium and magnesium), glucose, liver function tests, lipase, and urinalysis 1
• Consider hypercalcemia, thyroid function, and cortisol testing if clinically indicated 1
• Urine drug screen is critical—specifically assess for cannabis use, as Cannabis Hyperemesis Syndrome (CHS) is increasingly common and requires cessation for definitive treatment 1

Perform one-time upper GI imaging or esophagogastroduodenoscopy (EGD) to exclude obstructive lesions, but avoid repeated endoscopy unless new symptoms develop. 1

Stepwise Pharmacologic Management Algorithm

First-Line Therapy (Initiate Immediately)

Start with dopamine receptor antagonists on a scheduled basis rather than PRN, as prevention is far easier than treating established vomiting: 3, 1

• Metoclopramide 10 mg PO/IV three times daily before meals (particularly effective for gastric stasis and can be titrated upward) 1, 2
• Alternative: Prochlorperazine 10 mg PO/IV every 6-8 hours 1
• Alternative: Haloperidol 1 mg PO/IV every 4 hours as needed (different receptor profile than prochlorperazine) 1

Monitor for extrapyramidal symptoms, particularly in young males, and treat with diphenhydramine 50 mg IV if they develop. 1, 2

Second-Line Therapy (Add if Symptoms Persist After 4 Weeks)

Add a 5-HT3 antagonist to the dopamine antagonist rather than replacing it—use agents from different drug classes simultaneously for synergistic effect: 3, 1, 2

• Ondansetron 8 mg PO/IV 2-3 times daily, or 0.15 mg/kg IV over 15 minutes (maximum 16 mg per dose) 1, 2, 4
• Sublingual formulations may improve absorption in actively vomiting patients 2
• Monitor for QTc prolongation, especially when combined with other QT-prolonging agents or in patients with electrolyte abnormalities (hypokalemia, hypomagnesemia) 1, 4

Third-Line Therapy (For Refractory Cases)

If vomiting persists despite dopamine antagonist plus 5-HT3 antagonist, add one or more of the following: 1, 2

• Dexamethasone 10-20 mg IV (combination with ondansetron is superior to either agent alone) 1
• Olanzapine (if not already used prophylactically) 3, 2
• Dronabinol 2.5-7.5 mg PO every 4 hours as needed (FDA-approved cannabinoid for refractory nausea) 1
• Lorazepam or alprazolam for anxiety-related component 3, 2

Consider continuous intravenous or subcutaneous infusion of antiemetics for severe refractory cases. 2

Route of Administration Considerations

The oral route is often not feasible due to ongoing vomiting—use alternative routes: 3, 1, 2

• Intravenous or intramuscular administration for acute management 3, 1
• Rectal suppositories (promethazine, prochlorperazine) 2
• Sublingual tablets (ondansetron, alprazolam) 1, 2
• Administer antiemetics on a scheduled, around-the-clock basis rather than PRN dosing 3, 1

Treatment of Specific Underlying Causes

If Gastroparesis or Gastritis is Suspected:

• Continue metoclopramide as it promotes gastric emptying 1
• Add proton pump inhibitor or H2 receptor antagonist 1, 2

If Metabolic Abnormalities are Identified:

• Correct hypercalcemia and treat dehydration aggressively 1
• Address electrolyte imbalances, particularly hypokalemia and hypomagnesemia, which can cause metabolic alkalosis and worsen QTc prolongation risk 1
• Ensure adequate fluid intake of at least 1.5 L/day 1

If Cannabis Hyperemesis Syndrome is Suspected:

• Definitive diagnosis requires 6 months of cannabis cessation or at least 3 typical cycle lengths without vomiting 1
• Do not stigmatize patients—offer abortive and prophylactic therapy even with ongoing use, as treatments can still be effective 1
• Hot showers may provide temporary relief (though not mentioned in guidelines, this is a characteristic feature)

Supportive Care Measures

Implement the following supportive measures concurrently with pharmacologic therapy: 1

• Ensure adequate hydration and fluid repletion, checking and correcting electrolyte abnormalities simultaneously 3, 1
• Thiamin supplementation to prevent Wernicke's encephalopathy in patients with persistent vomiting 1
• Small, frequent meals and dietary modifications 1

Critical Pitfalls to Avoid

Never use antiemetics in suspected mechanical bowel obstruction, as this can mask progressive ileus and gastric distension—this is a critical safety concern. 1, 2

Avoid repeated endoscopy or imaging unless new symptoms develop. 1

Do not replace one antiemetic with another from the same class—instead, add agents from different drug classes targeting different neuroreceptors for synergistic effect. 3, 1, 2

Monitor for extrapyramidal symptoms with dopamine antagonists, particularly in young males, and have diphenhydramine readily available. 1, 2

In severe hepatic impairment (Child-Pugh score ≥10), do not exceed a total daily ondansetron dose of 8 mg. 4

Reassessment Strategy

Before continuing therapy, reassess for non-gastrointestinal causes if symptoms persist: 3

• Brain metastases or other intracranial pathology 3, 2
• Medication adverse effects 2
• Tumor infiltration of bowel 3
• Other comorbidities 3

If the patient fails to respond to intensified therapy with multiple agents from different classes, consider palliative sedation as a last resort for severe, intractable vomiting. 2