What is the appropriate evaluation and management for an adult with persistent vomiting and no known contraindications?

Management of Persistent Vomiting in Adults

Begin with immediate intravenous fluid resuscitation using isotonic crystalloids (lactated Ringer's or normal saline) to correct dehydration and electrolyte abnormalities, then initiate first-line dopamine antagonist therapy (metoclopramide 10 mg IV/PO every 6-8 hours or prochlorperazine 10 mg IV/PO every 6-8 hours), escalating systematically to combination antiemetic therapy if symptoms persist beyond 24-48 hours. 1, 2

Immediate Assessment and Stabilization (First 1-2 Hours)

Critical Diagnostic Priorities

• Obtain urine pregnancy test immediately in any woman of reproductive age—pregnancy (including hyperemesis gravidarum) is the most common endocrine cause of persistent vomiting in this population 2
• Administer thiamine 100 mg IV before any glucose-containing fluids to prevent Wernicke's encephalopathy in patients with prolonged vomiting 2
• Order complete blood count, comprehensive metabolic panel (electrolytes, glucose, calcium, renal and liver function), lipase, and urinalysis to exclude metabolic causes and assess severity of dehydration 2
• Consider urine drug screen to assess for cannabis hyperemesis syndrome, particularly in younger adults with heavy cannabis use 2

Fluid and Electrolyte Correction

• Administer 20 mL/kg boluses of isotonic IV crystalloids (lactated Ringer's or normal saline) repeatedly until pulse, perfusion, and mental status normalize 2
• Correct hypokalemia and hypomagnesemia aggressively—these are the most common electrolyte disturbances after prolonged vomiting and must be addressed before antiemetic therapy will be fully effective 1, 2
• Monitor for metabolic alkalosis with hypochloremia, which develops from loss of gastric acid 2

First-Line Pharmacologic Management (0-24 Hours)

Dopamine Antagonists as Initial Therapy

Metoclopramide 10 mg IV/PO every 6-8 hours is the preferred first-line agent because it both blocks dopamine receptors in the chemoreceptor trigger zone and promotes gastric emptying, making it particularly effective when gastroparesis is suspected 1, 2, 3, 4

Alternative first-line dopamine antagonists include:

• Prochlorperazine 10 mg IV/PO every 6-8 hours 2
• Haloperidol 0.5-2 mg IV/PO every 4-6 hours for additional anti-dopaminergic effect 1, 2

Monitor for extrapyramidal side effects (acute dystonia, akathisia), particularly in young males; treat with diphenhydramine 50 mg IV if they develop 2, 3

Adjunctive Therapy for Anxiety Component

• Add lorazepam 0.5-1 mg PO/IV every 4-6 hours as needed if anxiety is contributing to the vomiting cycle 1, 2, 3
• Use cautiously and avoid long-term benzodiazepine therapy due to dependence risk 1

Second-Line Escalation (24-48 Hours Without Adequate Control)

Add 5-HT3 Antagonist to Dopamine Antagonist

If vomiting persists after 24-48 hours of dopamine antagonist therapy, add ondansetron 4-8 mg IV/PO every 8 hours—this provides complementary antiemetic coverage by blocking serotonin receptors involved in emesis 1, 2, 3

Critical safety consideration: Monitor for QTc prolongation when combining ondansetron with haloperidol or other QT-prolonging agents; obtain baseline and follow-up ECGs in high-risk patients 1, 2

Key principle: Add agents from different drug classes rather than replacing the initial antiemetic, as different neuroreceptors mediate the emetic response and combination therapy is superior to sequential monotherapy 2, 3

Third-Line Management (48-72 Hours of Refractory Symptoms)

Corticosteroids for Severe or Central Vomiting

• Dexamethasone 4-8 mg IV/PO twice daily is indicated for severe nausea or when central nervous system pathology is suspected 2, 3
• Particularly effective when combined with ondansetron 3

Alternative Routes and Formulations

When oral administration fails due to ongoing vomiting:

• Ondansetron sublingual tablets (8 mg) for improved absorption 3
• Prochlorperazine or promethazine rectal suppositories 3
• Continuous IV or subcutaneous infusion of antiemetics via syringe driver for intractable symptoms 1, 2

Cause-Specific Considerations

Cannabis Hyperemesis Syndrome

• Suspect in patients with heavy cannabis use and stereotypical episodes of vomiting 2
• Do not withhold abortive and prophylactic therapy even with ongoing cannabis use—treatments can still be effective, and stigmatizing patients is counterproductive 2
• Definitive diagnosis requires 6 months of cannabis cessation 5

Cyclic Vomiting Syndrome

• Recognize prodromal symptoms (impending doom, anxiety, mental fog) that precede vomiting episodes by approximately 1 hour 5
• Most patients require combination therapy (typically sumatriptan plus ondansetron) to reliably abort attacks 3
• Inducing sedation with promethazine, diphenhydramine, or benzodiazepines is often an effective abortive strategy 3
• Consider prophylactic amitriptyline 50 mg nightly for recurrent episodes 2

Gastroparesis

• Continue metoclopramide as it is the mainstay of gastroparesis therapy due to its prokinetic effects 2, 4
• Add proton pump inhibitor or H2 receptor antagonist if gastritis or reflux is suspected 1, 2, 3

Refractory Cases (>72 Hours)

Advanced Antiemetic Options

• Olanzapine 2.5-5 mg PO daily has shown superior efficacy compared to metoclopramide for breakthrough vomiting in some studies 1, 3
• Dronabinol 2.5-7.5 mg PO every 4 hours as needed is FDA-approved for refractory nausea unresponsive to conventional antiemetics 2, 3
• Continuous subcutaneous or IV infusion of antiemetics should be considered 1, 2

Scheduled Rather Than PRN Dosing

Administer antiemetics on a scheduled basis rather than as-needed—prevention of vomiting is far easier than treating established emesis 3

Critical Pitfalls to Avoid

Absolute Contraindications

Never use antiemetics in suspected mechanical bowel obstruction—this can mask progressive ileus and gastric distension, delaying surgical intervention 2, 3

If bilious vomiting is present:

• Stop all oral intake immediately 6
• Place nasogastric tube for gastric decompression 6
• Obtain urgent surgical consultation and imaging 6

Diagnostic Errors

• Avoid repeated endoscopy or imaging studies unless new symptoms develop—one-time upper GI evaluation is sufficient to exclude obstructive lesions 2
• Do not overlook pregnancy testing in women of reproductive age—this is the single most critical initial omission 2
• Recognize that leukopenia with elevated CRP is atypical for viral gastroenteritis and should raise suspicion for systemic infection, hematologic malignancy, or drug/toxin effect 2

Supportive Care Throughout Treatment

Hydration and Nutrition

• Ensure adequate fluid intake of at least 1.5 L/day once oral intake is tolerated 5, 3
• Provide small, frequent meals rather than large meals 5
• Continue thiamin supplementation when vomiting persists >2-3 weeks to prevent neurological complications 5

Monitoring Parameters

• Reassess hydration status and electrolytes every 12-24 hours until stable 2
• Monitor for signs of Wernicke's encephalopathy (confusion, ataxia, ophthalmoplegia) in patients with prolonged vomiting 5, 2
• Evaluate for surgical complications (anastomotic stricture, bowel obstruction, gastric ulcers) if vomiting persists despite appropriate medical therapy 5