What is the differential diagnosis and initial management approach for a patient presenting with nausea?

Differential Diagnosis for Nausea

The differential diagnosis for nausea is extensive and must systematically evaluate gastrointestinal, neurologic, metabolic/endocrine, medication-related, and psychogenic causes, with the initial approach determined by whether symptoms are acute (≤7 days) or chronic (≥4 weeks). 1, 2, 3

Acute Nausea (≤7 days)

Most Common Causes

• Gastrointestinal infections and food poisoning are the most common causes of acute nausea and vomiting 4
• Medication adverse effects should always be suspected first—review all medications including over-the-counter drugs, supplements, and recent additions 2, 3
• Early pregnancy must be considered in all women of reproductive age 3, 4
• Acute migraine headaches with associated photophobia, phonophobia, or aura 3
• Vestibular disturbances including benign positional vertigo, labyrinthitis 3

Life-Threatening Causes Requiring Immediate Evaluation

• Acute coronary syndrome—particularly in patients with cardiac risk factors 2
• Increased intracranial pressure—look for headache, altered mental status, focal neurologic deficits 2, 3
• Bowel obstruction—assess for abdominal distention, absent bowel sounds, colicky pain 1
• Acute metabolic derangements—hypercalcemia, diabetic ketoacidosis, uremia 2, 3

Chronic Nausea (≥4 weeks)

Gastrointestinal Causes with Delayed Gastric Emptying

• Gastroparesis (20-40% of diabetic patients, particularly those with long-standing type 1 diabetes and other complications; 25-40% of functional dyspepsia patients) 1
  • Diabetic gastroparesis represents vagal neuropathy; hyperglycemia itself causes antral hypomotility 1
  • Idiopathic gastroparesis may follow viral infection 1
  • Postsurgical gastroparesis after gastric or vagal surgery 1
• Cyclic vomiting syndrome (prevalence ~2% in US adults, more common in women) 1
  • Stereotypical episodes of acute-onset vomiting lasting <7 days 1
  • At least 3 discrete episodes per year with 2 in prior 6 months, separated by ≥1 week of baseline health 1
  • Prodromal symptoms in ~65% (median 1 hour before vomiting): sense of doom, panic, inability to communicate 1
  • Associated constitutional symptoms: fatigue, mental fog, restlessness, anxiety, headache, bowel urgency, diaphoresis, flushing 1
  • Personal or family history of migraine headaches is supportive 1

Gastrointestinal Causes with Normal Gastric Emptying

• Functional dyspepsia (affects ~20% of US general population) 1
• Chronic intestinal pseudo-obstruction 5
• Rumination syndrome 5

Neurologic Causes

• Central nervous system pathology—tumors, increased intracranial pressure, posterior fossa lesions 1
• Vestibular disorders—Ménière's disease, chronic labyrinthitis 3, 5
• Migraine-associated nausea 3, 5

Metabolic and Endocrine Causes

• Diabetic complications—particularly with poor glycemic control 1
• Chronic kidney disease and uremia 3, 5
• Hypercalcemia 1, 3
• Adrenal insufficiency 3, 5
• Thyroid disorders 3, 5

Medication and Toxin-Related

• Opioid-induced nausea (occurs in 10-50% of patients receiving opioids) 1
• Chemotherapy-induced nausea and vomiting 1
• Radiation therapy-induced nausea 1
• Chronic alcohol use 3, 5
• Cannabis hyperemesis syndrome 5

Psychogenic Causes

• Anxiety disorders and panic attacks 2, 3
• Depression 3, 5
• Eating disorders including bulimia 1, 3

Initial Management Approach

For Acute Nausea

In the absence of alarm symptoms (severe abdominal pain, hematemesis, altered mental status, severe dehydration, focal neurologic deficits), treat symptomatically without extensive evaluation. 3, 4

Pharmacologic Management

• Ondansetron (5-HT3 antagonist) is the preferred initial agent, with sublingual formulation potentially improving absorption in actively vomiting patients 6, 7

  • Dosing: 4-8 mg orally/sublingual 7
  • Caution: Avoid in congenital long QT syndrome; monitor ECG in patients with electrolyte abnormalities, heart failure, or bradyarrhythmias 7
  • Caution: Risk of serotonin syndrome, especially with concomitant SSRIs, SNRIs, MAOIs, tramadol 7

• Alternative antiemetics if ondansetron fails or is contraindicated 6:

  • Promethazine 12.5-25 mg IV/IM/rectal 6
  • Prochlorperazine 10 mg IV/IM or 25 mg rectal suppository 1, 6
  • Metoclopramide 10 mg IV/IM 1, 6

• For refractory vomiting, combination therapy 6:

  • Benzodiazepine (lorazepam 0.5-1 mg IV or alprazolam 0.25-0.5 mg sublingual) PLUS haloperidol 0.5-2 mg IV 6
  • Monitor for QT prolongation with haloperidol 6

Fluid and Electrolyte Management

• Oral rehydration with small, frequent sips of electrolyte-rich fluids (sports drinks) for patients tolerating oral intake 6
• IV fluid therapy with normal saline or lactated Ringer's for those who cannot tolerate oral intake 6
• For moderate-severe dehydration: 500-1000 mL bolus followed by maintenance rate; add dextrose if prolonged fasting or hypoglycemia concern 6

For Chronic Nausea

When symptoms are chronic or moderate-severe, testing for underlying cause should be performed before empirical antiemetic therapy. 2, 3

Diagnostic Evaluation

• Gastric emptying scintigraphy is the best accepted method to diagnose gastroparesis 1

  • Must be performed for at least 2 hours (shorter durations are inaccurate); 4-hour testing increases yield 1
  • Radioisotope must be cooked into solid portion of meal 1

• Upper endoscopy to exclude mechanical obstruction, peptic ulcer disease, malignancy 1, 5

• Laboratory evaluation: Complete metabolic panel, calcium, thyroid function, pregnancy test, hemoglobin A1c 3, 5

• Consider antroduodenal manometry if gastroparesis suspected but scintigraphy normal—provides information about gastric-duodenal motor coordination 1

Special Considerations for Cyclic Vomiting Syndrome

• Abortive therapy during prodromal phase (highest probability of success) 1, 6:
  • Sumatriptan (nasal spray or subcutaneous) + ondansetron + benzodiazepine 6
  • Sedation with promethazine or lorazepam 6
  • Quiet, dark environment 6
  • IV dextrose-containing fluids are essential 6

Critical Pitfalls to Avoid

• Do not assume ondansetron can mask progressive ileus or gastric distension—it does not stimulate peristalsis and should not replace nasogastric suction in post-surgical or high-risk patients 7

• Do not give prophylactic antiemetics in radiation exposure cases—vomiting onset helps determine radiation dose 6

• Do not overlook medication review—this is the most frequently missed reversible cause 2, 3

• Do not confuse vomiting with regurgitation, rumination, or bulimia—careful history is essential 1

• Do not perform gastric emptying studies <2 hours duration—they are inaccurate 1

• Clinicians significantly underestimate rates of nausea—use direct patient-reported outcome measures throughout therapy 1