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

Management of Chronic Nausea and Vomiting

Start with metoclopramide 10-20 mg every 6 hours on a scheduled basis, not PRN, as prevention is far easier than treating established vomiting; if symptoms persist after 4 weeks, add ondansetron 8-16 mg orally 2-3 times daily, and for refractory cases, add dexamethasone 4-8 mg three to four times daily. 1, 2

Initial Diagnostic Workup

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

• Order 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
• 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 1
• Perform one-time esophagogastroduodenoscopy (EGD) or upper GI imaging to exclude obstructive lesions, but avoid repeated endoscopy unless new symptoms develop 1, 2

Pattern Recognition: Episodic vs. Continuous Symptoms

The temporal pattern fundamentally changes your diagnostic and therapeutic approach:

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, consider CVS 3:

• Mild CVS (<4 episodes/year, each <2 days, no ED visits): Offer abortive therapy only 3
• Moderate-severe CVS (≥4 episodes/year, each >2 days, requiring ED visits): Offer both prophylactic and abortive therapy 3

For prophylactic therapy in moderate-severe CVS, use tricyclic antidepressants as first-line:

• Start 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 3
• Monitor for somnolence, dry mouth, blurred vision, constipation, weight gain, and prolonged QTc on ECG 3

For abortive therapy during CVS episodes, use combination treatment:

• Sumatriptan via nasal spray (head-forward position) or subcutaneous injection 3
• Plus ondansetron sublingual tablet for better absorption during active vomiting 3
• Plus promethazine or benzodiazepines to induce sedation, which is an effective abortive strategy 3
• Alprazolam is available in sublingual and rectal forms, which may be particularly advantageous 3

Coalescent CVS

If the patient has lost well periods but endorses years of prior episodic patterns, this represents coalescent CVS and requires prophylactic therapy similar to moderate-severe CVS 3, 4

Continuous Symptoms

If symptoms are continuous without episodic patterns, proceed with the stepwise pharmacologic algorithm below.

Stepwise Pharmacologic Algorithm for Continuous Symptoms

First-Line: Dopamine Antagonist

Start metoclopramide 10-20 mg every 6 hours on a scheduled around-the-clock basis (not PRN), as it promotes gastric emptying and is particularly effective for gastroparesis 1, 2:

• Monitor for extrapyramidal symptoms, especially in young males, and treat with diphenhydramine 50 mg IV if they develop 1, 2
• Alternative dopamine antagonists include prochlorperazine or haloperidol 1, 2
• Titrate to maximum benefit and tolerance 1

Second-Line: Add 5-HT3 Antagonist

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 3, 1
• Monitor for QTc prolongation, especially when combined with other QT-prolonging agents 1, 2

Third-Line: Add Corticosteroids and Additional Agents

If symptoms persist despite dopamine antagonist plus 5-HT3 antagonist, add dexamethasone 4-8 mg three to four times daily 1:

• Dexamethasone combined with ondansetron is superior to either agent alone and represents category 1 evidence 1, 2
• Consider adding anticholinergic agents (scopolamine), antihistamines (meclizine), or cannabinoids 1
• Add lorazepam as a benzodiazepine for anxiety-related nausea 1

Treatment of Specific Underlying Causes

Gastroparesis or Gastritis

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

Metabolic Abnormalities

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

Medication-Induced Vomiting

• Discontinue unnecessary medications 1
• Check blood levels of digoxin, phenytoin, carbamazepine, or tricyclic antidepressants 1, 4
• Treat medication-induced gastropathy with proton pump inhibitor and metoclopramide 1
• For opioid-induced symptoms, consider opioid rotation or dose reduction 4

Constipation or Fecal Impaction

• Screen for and treat constipation, as this can cause nausea and vomiting 1, 4

Comorbid Conditions That Guide Management

Identify and treat anxiety, depression, migraine headaches, and postural orthostatic tachycardia syndrome, as these are present in 50-60%, 20-30%, and a substantial subgroup of CVS patients respectively 3:

• Improving anxiety may decrease the frequency of CVS episodes and improve inter-episodic nausea 3
• Treating postural orthostatic tachycardia syndrome may improve overall functional status 3

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 1, 2
• Ensure adequate hydration and fluid repletion, and assess and correct any electrolyte abnormalities 1
• Consider adding an H2 blocker or proton pump inhibitor if dyspepsia is present, as patients may confuse heartburn with nausea 1, 2
• Do not dismiss episodic patterns in patients with daily symptoms, as coalescent CVS patients may have lost their well periods but universally endorse years of prior episodic patterns 4

Administration Strategies

Administer antiemetics on a scheduled around-the-clock basis rather than PRN, as prevention is far easier than treating established vomiting 1, 2:

• Consider alternating routes (IV, rectal, or sublingual) if the oral route is not feasible due to ongoing vomiting 2
• Use agents from different drug classes simultaneously rather than sequential monotherapy, as no single agent has proven superior for breakthrough emesis 2