What is the recommended workup and treatment for a patient with chronic nausea?

Chronic Nausea Workup

Initial Clinical Assessment

Begin by determining if the nausea is truly chronic (≥4 weeks duration) versus acute, as this fundamentally changes your diagnostic and therapeutic approach. 1, 2

Key Historical Elements to Elicit

• Timing patterns: Document whether symptoms are episodic with well periods versus continuous, as episodic patterns suggest cyclic vomiting syndrome (CVS) while continuous symptoms point toward chronic nausea vomiting syndrome 3
• Associated symptoms: Specifically ask about headache, focal neurologic deficits, altered mental status (which mandate immediate neuroimaging), severe abdominal pain, and signs of dehydration 4
• Medication review: Systematically review opioids, antibiotics, NSAIDs, chemotherapy agents, antidepressants, and check blood levels of digoxin, phenytoin, carbamazepine, and tricyclic antidepressants 5, 4
• Comorbid conditions: Screen for migraine headaches (present in 20-30% of CVS patients), anxiety disorders, postural orthostatic tachycardia syndrome, and seizure disorders (3% of CVS) 3
• Relationship to food: Determine if symptoms worsen postprandially (suggests gastroparesis or gastric outlet obstruction) 3, 5

Diagnostic Testing Algorithm

First-Tier Laboratory Studies

• Complete blood count, comprehensive metabolic panel, glucose, liver function tests, lipase, and thyroid-stimulating hormone to identify metabolic, endocrine, or inflammatory causes 4, 6
• Urinalysis and urine pregnancy test in women of childbearing age 6
• Serum calcium to exclude hypercalcemia 3, 5

When to Pursue Advanced Testing

If alarm features are present (neurologic symptoms, severe vomiting, dehydration, severe metabolic abnormalities), proceed immediately with comprehensive workup including imaging. 4

• Esophagogastroduodenoscopy (EGD): Indicated for patients with risk factors for gastric malignancies or alarm symptoms to exclude mechanical obstruction, peptic ulcer disease, or malignancy 6, 7
• Gastric emptying study: Order when gastroparesis is suspected based on postprandial symptom exacerbation, but do not order for acute, isolated nausea 4, 6
• Brain imaging (CT or MRI): Required when headache, focal neurologic deficits, or altered mental status accompany nausea 4, 6
• Abdominal CT: Consider when bowel obstruction, intra-abdominal pathology, or "squashed stomach syndrome" from liver metastases is suspected 3, 5

Testing to Avoid

• Do not pursue imaging or endoscopy for single, self-limited episodes without recurrence or alarm symptoms 4
• Avoid repeated upper endoscopy or imaging for isolated episodes 4
• Do not order gastric emptying studies for acute nausea 4

Differential Diagnosis Framework

Gastrointestinal Causes

• Gastroparesis: Suggested by postprandial fullness and vomiting; confirm with gastric emptying study 6, 7
• Cyclic vomiting syndrome: Episodic pattern with stereotypical episodes lasting <7 days (though 15% last >7 days), separated by well periods of ≥1 week 3
• Gastric outlet obstruction: From intra-abdominal tumor, liver metastases causing "squashed stomach syndrome" 3, 5
• Bowel obstruction: Requires octreotide for symptom management 5

Non-Gastrointestinal Causes

• Medication-induced: Opioids are the most common culprit; consider opioid rotation if nausea persists 3, 5
• CNS pathology: Brain metastases, meningeal involvement, increased intracranial pressure 3, 5
• Metabolic/endocrine: Hypercalcemia, uremia, diabetic ketoacidosis, adrenal insufficiency, hypothyroidism 3, 6
• Vestibular disorders: Consider when nausea is positional 1, 2
• Psychiatric: Anxiety disorders, eating disorders, somatization 3, 6

Special Consideration: Coalescent CVS

A subset of severe CVS patients develop coalescent CVS, characterized by loss of asymptomatic periods and progression to daily nausea with intermittent severe episodes. 3 These patients meet Rome IV criteria for chronic nausea vomiting syndrome but have a clear history of episodic vomiting for years before coalescence. A careful history distinguishing this from primary chronic nausea vomiting syndrome is critical, as management differs. 3

Treatment Approach

First-Line Pharmacologic Management

For chronic non-specific nausea, initiate dopamine receptor antagonists as first-line therapy: 3, 5, 4

• Metoclopramide 10-20 mg every 6 hours (has both central and peripheral effects; recommended as first-line for chronic nausea including opioid-related) 3, 5
• Prochlorperazine 10 mg every 6 hours 3, 5, 4
• Haloperidol 0.5-1 mg every 6-8 hours 3, 5, 4

If nausea persists after 1 week of as-needed dosing, switch to around-the-clock administration for 1 week, then reassess. 3, 5

Second-Line and Adjunctive Agents

When first-line therapy fails, add medications with different mechanisms: 3, 5

• 5-HT3 antagonists: Ondansetron 8 mg daily or twice daily, or granisetron daily 3, 5
• Anticholinergics: Scopolamine transdermal patch 1 mg/3 days 3, 5
• Antihistamines: Meclizine 3, 5
• Corticosteroids: Dexamethasone 2-8 mg (particularly effective for CNS involvement, gastric outlet obstruction, or inflammation) 3, 5

Prophylactic Therapy for Moderate-Severe CVS

For patients with ≥4 episodes per year, each lasting >2 days, requiring ED visits or hospitalizations, initiate prophylactic therapy: 3

• Tricyclic antidepressants (first-line): Amitriptyline starting at 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
• Topiramate (alternative): Start 25 mg daily, titrate by 25 mg weekly to goal of 100-150 mg daily in divided doses; monitor electrolytes and renal function biannually 3

Refractory Nausea Management

For nausea persisting despite maximal medical therapy: 3, 5

• Cannabinoids: Dronabinol or nabilone for chemotherapy-induced or refractory nausea 3, 5
• Opioid rotation: If opioid-induced nausea persists after trials of multiple antiemetics 3, 5
• Continuous IV/subcutaneous infusions: Consider for intractable symptoms 3
• Alternative therapies: Acupuncture, hypnosis, or cognitive behavioral therapy 5

Cause-Specific Interventions

• Constipation/fecal impaction: Aggressive bowel regimen with senna, docusate, magnesium-based products, or bisacodyl 3
• Gastritis/GERD: Proton pump inhibitors plus metoclopramide 3, 5
• Gastric outlet obstruction: Corticosteroids, proton pump inhibitor, metoclopramide, and consider endoscopic stenting 3, 5
• Bowel obstruction: Octreotide 5

Critical Pitfalls to Avoid

• Do not ignore complaints of chronic nausea, as this leads to non-adherence and potential disease progression 8
• Do not empirically order gastric emptying studies or repeat endoscopy without appropriate clinical indications 4
• Do not overlook medication adverse effects, particularly opioids, which cause nausea in up to 50% of patients 3
• Do not miss coalescent CVS by failing to elicit the historical pattern of episodic vomiting that preceded continuous symptoms 3
• Do not delay neuroimaging when neurologic symptoms accompany nausea 4