What is the workup for a patient with recurrent nausea and vomiting, normal abdominal computed tomography (CT) scans, and normal laboratory work?

Workup for Recurrent Nausea and Vomiting with Normal Abdominal CT and Labs

The most critical next step is to perform upper endoscopy to exclude mechanical obstruction, peptic ulcer disease, or malignancy, followed by gastric emptying scintigraphy if gastroparesis is suspected, while simultaneously screening for cyclic vomiting syndrome (CVS) and cannabinoid hyperemesis syndrome (CHS) based on symptom pattern and cannabis use history. 1, 2, 3

Immediate Diagnostic Priorities

Pattern Recognition: Episodic vs. Continuous Symptoms

• If symptoms occur in stereotypical episodes (acute-onset vomiting lasting <7 days, at least 3 discrete episodes in the past year with 2 in the prior 6 months, separated by ≥1 week of baseline health), strongly suspect CVS 1, 2, 3
• Look for prodromal symptoms including impending sense of doom, panic, fatigue, mental fog, restlessness, anxiety, headache, bowel urgency, diaphoresis, or flushing—present in 65% of CVS patients 1, 3
• Screen for personal or family history of migraine, present in 20-30% of CVS patients 1, 2

Cannabis Use Assessment (Critical First Step)

• Screen all patients for cannabis use patterns before proceeding with diagnosis—use >4 times weekly for >1 year suggests cannabinoid hyperemesis syndrome rather than CVS 1, 2, 3
• CHS requires 6 months of cannabis cessation (or at least 3 typical cycle lengths) to retrospectively differentiate from CVS 2, 3
• Hot water bathing is NOT pathognomonic for CHS—it occurs in 48% of CVS patients who don't use cannabis 2

Essential Laboratory Workup

Basic Metabolic Panel

• Complete blood count, serum electrolytes, glucose, liver function tests, lipase, and urinalysis to identify metabolic causes, dehydration, and electrolyte abnormalities 3, 4
• Prolonged vomiting causes hypokalemia, hypochloremia, and metabolic alkalosis that must be corrected 3
• Check for hypercalcemia, hypothyroidism, and adrenal insufficiency if clinically indicated 2, 3

Pregnancy Testing

• Urine pregnancy testing in women of childbearing age 3, 4

Structural and Functional Gastrointestinal Evaluation

Upper Endoscopy (First-Line Imaging)

• Perform one-time esophagogastroduodenoscopy to exclude obstructive lesions, peptic ulcer disease, or malignancy—this is mandatory if symptoms persist >7 days 1, 2, 3, 4
• Avoid repeated endoscopy or imaging studies unless new symptoms develop 3

Gastric Emptying Study

• Perform gastric emptying scintigraphy (2-4 hour study) if gastroparesis is suspected based on postprandial symptom exacerbation or early satiety 2, 3
• Gastroparesis is a leading cause of chronic vomiting and requires this specific test for diagnosis 2
• Do not order gastric emptying scans routinely in CVS, as few patients have delayed emptying and results during an episode are uninterpretable 3

Upper GI Series Consideration

• If bilious vomiting is present, this represents a surgical emergency requiring immediate fluoroscopy upper GI series to rule out malrotation with volvulus 5, 2
• Malrotation with volvulus can present at any age and requires urgent evaluation 2

Neurologic Evaluation (If Indicated)

Red Flag Symptoms Requiring Head CT

• Perform head CT if increased intracranial pressure is suspected, indicated by headache pattern changes, visual disturbances, or other neurologic signs 2, 4
• Increased intracranial pressure from tumor, trauma, or hydrocephalus typically causes other neurologic signs 2

Medication and Toxin Review

• Review all medications for potential causes: opioids (cause nausea in 10-50% of patients), antibiotics, recent anesthesia 2, 6
• Consider toxin exposure and metabolic abnormalities 4

Psychiatric Comorbidity Screening

• Screen all patients for anxiety, depression, and panic disorder—present in 50-60% of CVS patients 1, 2, 3
• Treating underlying anxiety can decrease CVS episode frequency 1, 3
• Consider rumination syndrome in the differential 2

Diagnostic Algorithm Summary

Step 1: Screen for cannabis use patterns (>4 times weekly for >1 year suggests CHS) 1, 2, 3

Step 2: Obtain basic labs (CBC, CMP, LFTs, lipase, urinalysis, pregnancy test) 3, 4

Step 3: Perform upper endoscopy to exclude mechanical obstruction, peptic ulcer disease, or malignancy 1, 2, 3

Step 4: If gastroparesis suspected, obtain gastric emptying scintigraphy 2, 3

Step 5: If episodic pattern with prodromal symptoms, diagnose CVS and initiate treatment 1, 3

Step 6: Screen for psychiatric comorbidities and treat accordingly 1, 3

Critical Pitfalls to Avoid

• Never use antiemetics if mechanical bowel obstruction is suspected 3
• Do not perform repeated endoscopy or imaging unless new symptoms develop 3
• Bilious vomiting is a surgical emergency until proven otherwise 2
• Do not stigmatize patients using cannabis—offer treatment regardless of ongoing use while encouraging cessation 3
• Provide thiamin supplementation to prevent Wernicke's encephalopathy in patients with persistent vomiting 3

Initial Therapeutic Approach (If CVS Diagnosed)

• For moderate-severe CVS (≥4 episodes/year lasting >2 days), initiate amitriptyline 25 mg at bedtime, titrating to 75-150 mg nightly with baseline ECG monitoring 1, 3
• Educate patients to recognize prodromal symptoms and take abortive medications immediately: sumatriptan 20 mg intranasal spray and ondansetron 8 mg sublingual 1, 3
• Implement lifestyle modifications: regular sleep schedule, avoiding prolonged fasting, stress management techniques, identifying and avoiding individual triggers 1, 3