What are the causes and treatments of nausea?

Causes and Treatments of Nausea

Nausea has multiple causes including chemotherapy, radiotherapy, infection, metabolic disorders, electrolyte disturbances, constipation, gastrointestinal obstruction, cachexia syndrome, metastases (brain, liver, bone), paraneoplasia, and medications (e.g., opioids, antibiotics, antifungals). 1

Common Causes of Nausea

Medical Conditions

• Gastrointestinal disorders:

  • Gastroenteritis
  • Gastroparesis
  • Bowel obstruction
  • Constipation (affects 40-90% of patients with advanced cancer) 2
  • Gastric outlet obstruction

• Metabolic/Endocrine disorders:

  • Hypercalcemia
  • Hypokalemia
  • Uremia
  • Diabetic ketoacidosis
  • Pregnancy
  • Thyroid disorders

• Neurological causes:

  • Increased intracranial pressure
  • Migraine headaches
  • Vestibular disorders
  • Brain metastases

• Cancer-related causes:

  • Chemotherapy-induced (classified as acute, delayed, or anticipatory) 1
  • Radiation-induced (particularly abdominal radiation)
  • Tumor burden (liver, brain metastases)

Medication-Related Causes

• Chemotherapeutic agents (particularly cisplatin, cyclophosphamide, doxorubicin)
• Opioid analgesics
• Antibiotics
• Antifungals
• NSAIDs
• Digoxin, phenytoin, carbamazepine, tricyclic antidepressants 1

Diagnostic Approach

Key Assessment Elements

• Timing of nausea (acute vs. chronic)
• Associated symptoms (vomiting, pain, neurological symptoms)
• Relationship to meals or medications
• Exacerbating/relieving factors
• Recent changes in medication

Alarm Signs Requiring Urgent Evaluation

• Dehydration
• Signs of bowel obstruction
• Severe abdominal pain
• Neurological deficits
• Hematemesis

Treatment Approaches

Non-Pharmacological Management

• Fluid and electrolyte replacement
• Small, frequent meals
• Avoidance of trigger foods
• Behavioral therapies for anticipatory nausea (progressive muscle relaxation, systematic desensitization) 1

Pharmacological Treatment

For Chemotherapy-Induced Nausea and Vomiting

1. Highly emetogenic chemotherapy:

   • Combination of 5-HT3 receptor antagonist (e.g., ondansetron 8-24 mg), dexamethasone (20 mg), and NK-1 receptor antagonist (e.g., aprepitant) 1, 3

2. Moderately emetogenic chemotherapy:

   • 5-HT3 receptor antagonist plus dexamethasone 1

3. For breakthrough or refractory nausea:

   • Add dopamine antagonist (e.g., metoclopramide, prochlorperazine) 1
   • Consider olanzapine 1

For Non-Chemotherapy Related Nausea

1. First-line options:

   • Serotonin (5-HT3) antagonists: Ondansetron 4-8 mg orally every 8 hours 2, 3
   • Dopamine antagonists: Metoclopramide 5-10 mg three times daily (particularly for gastroparesis) 2
   • Antihistamines: For vestibular-related nausea

2. Second-line options:

   • Phenothiazines: Prochlorperazine 10-20 mg 3-4 times daily 1
   • Butyrophenones: Haloperidol for persistent symptoms 1
   • Benzodiazepines: Lorazepam 1-2 mg (particularly for anticipatory nausea) 1

3. For specific causes:

   • Gastroesophageal reflux: Proton pump inhibitors or H2 receptor antagonists 1
   • Gastric outlet obstruction: Corticosteroids, endoscopic stenting, or decompressing G-tube 1
   • Opioid-induced nausea: Consider opioid rotation 1

Special Considerations

• Hepatic impairment: Reduce doses of ondansetron and other medications metabolized by the liver 3
• Mechanical obstruction: Antiemetics will not resolve underlying condition and may mask important symptoms 2
• Drug interactions: Aprepitant affects CYP3A4 metabolism and can interact with many medications 2
• QT prolongation: Monitor ECG when using ondansetron in patients with cardiac risk factors 3

Treatment Algorithm

1. Identify and treat underlying cause when possible
2. For acute nausea: Start with ondansetron 4-8 mg or metoclopramide 10 mg
3. For persistent symptoms: Add or switch to different class of antiemetic
4. For specific causes: Target therapy to underlying mechanism
5. For refractory nausea: Consider combination therapy with agents from different classes

Remember that nausea significantly impacts quality of life, and aggressive management is warranted to improve patient outcomes.