What is the next step in managing postprandial nausea with normal CBC, CMP, RUQ ultrasound, lipase, and negative H. pylori test?

Workup for Postprandial Nausea with Normal Initial Testing

Next Diagnostic Step: Upper Endoscopy

Given your negative initial workup, the next step is upper endoscopy (esophagogastroduodenoscopy) to exclude structural causes and confirm functional dyspepsia as the diagnosis. 1

Why Endoscopy Now?

• The British Society of Gastroenterology guidelines emphasize that functional dyspepsia (FD) is a diagnosis of exclusion requiring "no evidence of structural disease (including at upper endoscopy) likely to explain the symptoms" 1
• Your patient has completed appropriate screening tests (CBC, CMP, RUQ ultrasound, lipase, H. pylori), but endoscopy remains necessary to definitively rule out peptic ulcer disease, erosive esophagitis, or gastric malignancy 1
• Approximately 20% of patients with dyspeptic symptoms will have peptic ulcer or erosive esophagitis on endoscopy, while the remaining 80% have functional dyspepsia 1

Age and Alarm Features Matter

• If the patient is above your local age cutoff for gastric cancer risk (typically ≥60 years in Western populations, lower in high-risk areas), endoscopy is mandatory before empiric treatment 1
• Alarm symptoms requiring immediate endoscopy include: unintentional weight loss, progressive dysphagia, persistent vomiting, evidence of GI bleeding, palpable abdominal mass, or family history of upper GI malignancy 1

If Endoscopy is Normal: Functional Dyspepsia Management

Subtype Classification Guides Treatment

Once structural disease is excluded, classify the patient by predominant symptom pattern 1:

Postprandial Distress Syndrome (PDS) - Your patient likely fits here:

• Bothersome postprandial fullness and/or early satiation occurring ≥3 days per week 1
• Postprandial nausea is a supportive feature of PDS 1

Epigastric Pain Syndrome (EPS):

• Bothersome epigastric pain or burning occurring ≥1 day per week 1

First-Line Pharmacologic Treatment

For postprandial nausea with PDS features, start with metoclopramide 5-20 mg three to four times daily before meals: 2, 3, 4

• Metoclopramide is FDA-approved for diabetic gastroparesis and addresses the delayed gastric emptying component common in PDS 3
• It works by stimulating upper GI motility through myenteric 5-HT4 receptor activation and has direct antiemetic effects via D2 and 5-HT3 receptor antagonism 5
• Clinical trials demonstrate significant improvement in nausea, vomiting, postprandial bloating, and early satiety in patients with delayed gastric emptying 4

If epigastric pain is the predominant symptom instead:

• Use full-dose PPI therapy (omeprazole 20 mg once daily) as first-line treatment 1
• The 2022 BSG guidelines note that PPIs are most effective for ulcer-like dyspepsia symptoms 1

Second-Line Options for Persistent Symptoms

Add ondansetron 4-8 mg as needed or scheduled twice daily if nausea persists on metoclopramide: 2

• 5-HT3 antagonists like ondansetron effectively block serotonin receptors in the chemoreceptor trigger zone 2
• Combining metoclopramide (prokinetic) with ondansetron (5-HT3 antagonist) provides synergistic effect through different mechanisms 2

Consider mirtazapine 7.5-30 mg daily for refractory cases: 6

• The American Gastroenterological Association specifically lists mirtazapine for refractory gastroparesis symptoms 6
• Mirtazapine simultaneously addresses nausea, appetite loss, insomnia, and mood disorders—common comorbidities in chronic nausea 6
• Unlike some antiemetics, it does not significantly prolong QT intervals, making it safer in patients with cardiac disease 6

Additional Diagnostic Considerations

Gastric Emptying Study

If symptoms persist despite empiric treatment, order a gastric emptying scintigraphy study: 7, 8

• This test is indicated when gastroparesis is suspected clinically 7
• However, the BSG guidelines note that delayed gastric emptying may be present in FD patients, and the term "FD with or without delayed gastric emptying" may be preferable to gastroparesis 1
• Treatment approach remains similar regardless of emptying study results 1

Rule Out Medication-Induced Causes

• Review all medications for agents that delay gastric emptying: opioids, anticholinergics, GLP-1 agonists, calcium channel blockers 9, 7
• Constipation is present in 50% of patients with chronic nausea and must be addressed 9

Critical Pitfalls to Avoid

• Do not use antiemetics if mechanical bowel obstruction is suspected—rule out structural causes first 2
• Do not rely on H. pylori serology alone—use 13C urea breath test or stool antigen test with ≥90% sensitivity and specificity 1
• Do not restrict diet excessively—the BSG guidelines state there is no evidence for specialized diets in FD, and excessive restriction risks malnutrition 1
• Monitor for QT prolongation if using multiple antiemetics, particularly ondansetron in high-risk patients 2
• Reassess if symptoms persist beyond one week on scheduled antiemetics—consider medication rotation or adding agents from different drug classes 2