What are the causes and treatment options for severe nausea?

Severe Nausea: Causes and Treatment

Severe nausea requires immediate evaluation for specific underlying causes including medications (especially opioids), constipation, central nervous system pathology, gastrointestinal disorders, metabolic derangements (hypercalcemia), chemotherapy/radiation effects, and vestibular disturbances, followed by targeted antiemetic therapy starting with dopamine receptor antagonists. 1

Primary Causes to Evaluate First

Medication-Induced Nausea

• Review all current medications immediately, with particular attention to opioids, which are among the most common culprits of severe nausea 1
• Antipsychotic medications with opioid agonist properties (like lurasidone) stimulate the chemoreceptor trigger zone, directly causing nausea 2
• Any newly started medication within the past several weeks should be considered a potential cause 3

Critical Medical Conditions

• Check for hypercalcemia, which commonly presents with severe nausea and requires urgent correction 1
• Evaluate for central nervous system pathology including increased intracranial pressure, meningitis, or posterior fossa lesions 1
• Assess for bowel obstruction or gastric outlet obstruction, particularly in cancer patients 1
• Rule out acute metabolic derangements including uremia, diabetic ketoacidosis, and adrenal insufficiency 4, 3

Gastrointestinal Disorders

• Gastritis and gastroesophageal reflux disease are frequent causes requiring proton pump inhibitors or H2 receptor antagonists 1
• Gastroparesis (delayed gastric emptying) should be considered when symptoms persist chronically 5
• Constipation is an often-overlooked but common trigger that must be addressed 1

Other Common Causes

• Acute vestibular disturbances cause severe nausea with associated vertigo 4, 3
• Migraine headaches frequently present with severe nausea as a primary symptom 4
• Early pregnancy must be excluded in women of childbearing age 4, 3

Treatment Algorithm

First-Line Antiemetic Therapy

• Begin with dopamine receptor antagonists as the initial pharmacologic approach: 1
  • Prochlorperazine 10 mg orally every 6 hours as needed 1
  • Metoclopramide 10-20 mg orally every 6 hours 1
  • Haloperidol 0.5-1 mg orally every 6-8 hours 1
  • Olanzapine 2.5-5 mg orally 1

Prophylactic Treatment for High-Risk Patients

• For patients with prior history of medication-induced nausea (especially opioid-induced), start prophylactic antiemetics before symptoms develop 2, 1
• Phenothiazines like prochlorperazine can be used prophylactically at the same dosing 2

Persistent Nausea Management

• If nausea continues despite as-needed antiemetics, switch to scheduled around-the-clock dosing for one full week, then transition back to as-needed 1

• Add medications with different mechanisms of action for synergistic effect: 1

  • Serotonin (5-HT3) receptor antagonists: ondansetron 8 mg orally once or twice daily, or granisetron daily 1
  • Anticholinergic agents: scopolamine transdermal patch 1 mg/3 days 1
  • Antihistamines: meclizine 1
  • Corticosteroids: dexamethasone 2-8 mg orally or IV 1

• Combining metoclopramide with ondansetron provides synergistic relief for persistent nausea 2

Refractory Nausea Approach

• Reassess the underlying cause and severity before escalating therapy 1
• Consider cannabinoids (dronabinol, nabilone) for chemotherapy-induced nausea refractory to standard therapies 1
• For persistent opioid-induced nausea, attempt opioid rotation after trials of multiple antiemetics have failed 1
• Alternative therapies including acupuncture, hypnosis, or cognitive behavioral therapy may provide benefit 1

Cause-Specific Interventions

• For gastric outlet obstruction: corticosteroids, endoscopic stenting, or decompressing G-tube placement 1
• For bowel obstruction in cancer patients: octreotide administration 1
• For gastritis/GERD: proton pump inhibitors or H2 receptor antagonists 1

Critical Pitfalls to Avoid

• Never dismiss nausea complaints, as this leads to medication non-adherence and potential disease relapse, particularly in patients on psychiatric medications 2
• Do not assume nausea is benign without evaluating for serious underlying causes—symptoms alone poorly predict functional versus pathological illness 6
• Avoid extensive testing for acute nausea of mild severity; empirical antiemetic trials are appropriate 4
• For chronic nausea (≥4 weeks), testing for underlying causes is mandatory rather than indefinite symptomatic treatment 4, 5
• Recognize that nausea may be confused with other symptoms or conditions, requiring careful clinical assessment 2