What is the best management approach for an adult patient with no significant past medical history who experiences intermittent vomiting on exertion and has a normal abdominal ultrasound?

Intermittent Vomiting on Exertion with Normal Abdominal Ultrasound

This patient requires a focused diagnostic workup to exclude serious neurological and metabolic causes, followed by empiric treatment with dopamine antagonists if no etiology is identified.

Initial Laboratory Evaluation

The first step is obtaining targeted laboratory studies to exclude metabolic and endocrine causes:

• Complete blood count, comprehensive metabolic panel (including electrolytes, glucose, calcium, liver function tests), lipase, and urinalysis should be obtained immediately 1, 2, 3
• Thyroid function tests and morning cortisol to exclude hypothyroidism and Addison's disease, as these can present with vomiting without other obvious symptoms 1
• Urine drug screen is essential to assess for cannabis use, as Cannabis Hyperemesis Syndrome (CHS) is increasingly common and can present with exertional triggers 1

The normal abdominal ultrasound effectively excludes biliary pathology, liver/kidney abscesses, and most structural abdominal causes 4.

Critical Neurological Consideration

A brainstem lesion must be excluded in any patient with unexplained persistent vomiting, even without other neurological signs or symptoms 5. This is a frequently missed diagnosis with potentially devastating consequences:

• Brain MRI with gadolinium contrast should be performed, particularly focusing on the brainstem and posterior fossa 5
• Brainstem tumors can present with isolated vomiting for months before other neurological manifestations appear 5
• The absence of raised intracranial pressure, headache, or focal neurological signs does not exclude a central cause 5

Consideration of Cyclic Vomiting Syndrome

Given the intermittent nature and exertional trigger, Cyclic Vomiting Syndrome (CVS) should be considered 4, 6:

• CVS is characterized by stereotypical episodes of vomiting separated by symptom-free intervals 4, 6
• Screen for typical comorbidities: migraine headaches, anxiety, depression, autonomic dysfunction, and sleep disorders 4, 6
• The exertional trigger is consistent with CVS, as episodes can be precipitated by physical or emotional stress 6
• Cannabis use history is critical, as heavy cannabis use can both mimic and coexist with CVS 1

Upper Gastrointestinal Evaluation

One-time esophagogastroduodenoscopy (EGD) or upper GI imaging should be performed to exclude obstructive lesions, but repeated endoscopy should be avoided 1:

• This excludes peptic ulcer disease, gastric outlet obstruction, and mucosal pathology 1, 2
• Consider gastric emptying study if gastroparesis is suspected based on postprandial symptom pattern 2, 3

Empiric Pharmacologic Management

If the diagnostic workup is unrevealing, initiate dopamine receptor antagonists as first-line therapy 1, 7, 8:

• Metoclopramide 10 mg three times daily before meals is the preferred initial agent, as it both reduces nausea and promotes gastric emptying 1, 8
• Titrate to maximum benefit and tolerance, up to 20 mg four times daily if needed 8
• Monitor for extrapyramidal symptoms, particularly in young males, though the risk of tardive dyskinesia may be lower than historically estimated 1, 8

If symptoms persist after 4 weeks of dopamine antagonist therapy, add a 5-HT3 antagonist 1, 8:

• Ondansetron 8 mg orally 2-3 times daily or sublingual formulation for better absorption 1, 8
• The combination targets different receptor pathways for synergistic effect 8
• Monitor QTc interval when using ondansetron, especially with other QT-prolonging medications 1

Prophylactic Therapy for Moderate-Severe CVS

If CVS is diagnosed and episodes occur ≥4 times per year, each lasting >2 days, or requiring ED visits/hospitalizations, prophylactic therapy is indicated 4, 6:

• Amitriptyline 25 mg at bedtime, titrated slowly by 10-25 mg increments every 2 weeks to goal dose of 75-150 mg is the first-line prophylactic agent 4, 6
• Slow titration improves tolerability of anticholinergic side effects 4
• Alternative prophylactic agents include topiramate (starting 25 mg daily, goal 100-150 mg daily) or zonisamide (starting 100 mg daily, goal 200-400 mg daily) 4, 6

Abortive Therapy for Acute Episodes

For acute vomiting episodes, combination therapy is most effective 8, 6:

• Sumatriptan 6 mg subcutaneous or 50-100 mg oral plus ondansetron 8 mg 8, 6
• Inducing sedation with promethazine, diphenhydramine, or lorazepam can abort attacks 8
• Most patients require combinations of 2 agents to reliably abort episodes 8

Critical Pitfalls to Avoid

• Never use antiemetics if mechanical bowel obstruction is suspected until surgical evaluation is complete, as this can mask progressive ileus 1, 7
• Do not stigmatize patients with cannabis use—offer treatment even with ongoing use, as therapies can still be effective 1
• Avoid repeated endoscopy or imaging unless new symptoms develop 1
• Do not overlook brainstem pathology simply because neurological examination is normal 5
• Ensure adequate hydration and correct electrolyte abnormalities, particularly hypokalemia and hypomagnesemia, which can perpetuate symptoms 1, 7