What is the best approach to managing chronic nausea and vomiting in a patient?

Management of Chronic Nausea and Vomiting

Start metoclopramide 10-20 mg every 6 hours on a scheduled basis (not PRN) as first-line therapy, and if symptoms persist after 4 weeks, add ondansetron 8-16 mg orally 2-3 times daily, followed by dexamethasone 4-8 mg three to four times daily for refractory cases. 1, 2

Initial Diagnostic Workup

Before initiating treatment, obtain specific laboratory tests to identify reversible causes:

• Complete blood count, serum electrolytes, glucose, liver function tests, lipase, and urinalysis to exclude metabolic causes and assess dehydration 1, 2
• Check for hypercalcemia, hypothyroidism, and Addison's disease if clinical features suggest these conditions 1, 2
• Perform one-time esophagogastroduodenoscopy (EGD) or upper GI imaging to exclude obstructive lesions, but avoid repeated endoscopy unless new symptoms develop 2
• Obtain urine drug screen and detailed cannabis use history, as Cannabis Hyperemesis Syndrome requires specific management 2

Pattern Recognition: Episodic vs. Continuous

• Document episode frequency, duration, and symptom-free intervals to distinguish between cyclic vomiting syndrome (episodic with well periods) and continuous symptoms (suggesting metabolic, medication-induced, or coalescent disease) 3
• Consider Cyclic Vomiting Syndrome (CVS) if the patient has stereotypical episodes of acute-onset vomiting lasting <7 days, with at least 3 discrete episodes in a year (2 in the prior 6 months), separated by at least 1 week of baseline health 1
• Classify CVS severity: mild is <4 episodes/year lasting <2 days without ED visits; moderate-severe is ≥4 episodes/year lasting >2 days requiring ED visits or hospitalization 3

Stepwise Pharmacologic Algorithm

First-Line: Dopamine Antagonist (Scheduled Dosing)

• Metoclopramide 10-20 mg every 6 hours on a scheduled around-the-clock basis, not PRN, as prevention is far easier than treating established vomiting 1, 2
• Metoclopramide is particularly effective for gastroparesis as it promotes gastric emptying 1, 2
• Monitor for extrapyramidal symptoms, especially in young males, and treat with diphenhydramine 50 mg IV if they develop 2
• Alternative dopamine antagonists include prochlorperazine or haloperidol, titrated to maximum benefit and tolerance 2

Second-Line: Add 5-HT3 Antagonist (After 4 Weeks)

• If vomiting persists after 4 weeks of optimized dopamine antagonist therapy, add ondansetron 8-16 mg orally 2-3 times daily or 0.15 mg/kg IV (maximum 16 mg per dose) 1, 2
• Ondansetron is available in sublingual tablet form, which may improve absorption in actively vomiting patients 2
• Monitor for QTc prolongation, especially in combination with other QT-prolonging agents 2
• In clinical trials, 66% of patients receiving ondansetron 24 mg once daily completed 24 hours with zero emetic episodes 4

Third-Line: Add Corticosteroids

• If symptoms persist despite dopamine antagonist plus 5-HT3 antagonist, add dexamethasone 4-8 mg three to four times daily 1, 2
• Dexamethasone combined with ondansetron is superior to either agent alone 2
• Consider adding anticholinergic agents (scopolamine), antihistamines (meclizine), or lorazepam for anxiety-related nausea 2

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
• If patient is on opioids, consider opioid rotation or dose reduction as opioids commonly cause gastroparesis 3

Metabolic Abnormalities

• Correct hypercalcemia, treat dehydration, and address electrolyte imbalances, particularly hypokalemia and hypomagnesemia 1, 2

Medication-Induced Vomiting

• Discontinue unnecessary medications and check blood levels of digoxin, phenytoin, carbamazepine, or tricyclic antidepressants 2
• Treat medication-induced gastropathy with proton pump inhibitor and metoclopramide 2

Cyclic Vomiting Syndrome (Moderate-Severe)

• Use tricyclic antidepressants as first-line prophylactic therapy, starting with amitriptyline 25 mg at bedtime, titrate slowly (10-25 mg increments every 2 weeks) to goal of 75-150 mg or 1-1.5 mg/kg at bedtime 1
• Identify and treat comorbid conditions: anxiety (50-60% of CVS patients), depression (20-30%), migraine headaches, and postural orthostatic tachycardia syndrome 1

Critical Pitfalls to Avoid

• Never use antiemetics in suspected mechanical bowel obstruction, as this can mask progressive ileus and gastric distension 1, 2
• Do not stigmatize patients with cannabis use; offer abortive and prophylactic therapy even with ongoing use, as treatments can still be effective 1, 2
• Avoid repeated endoscopy or imaging unless new symptoms develop 2
• Do not dismiss episodic patterns in patients with daily symptoms, as patients with coalescent CVS may have lost their well periods but universally endorse years of prior episodic patterns—a careful history identifies this 3
• Ensure adequate hydration and fluid repletion, and assess and correct any electrolyte abnormalities 2
• Consider adding an H2 blocker or proton pump inhibitor if dyspepsia is present, as patients may confuse heartburn with nausea 2