What are the recommended treatments for nausea?

Treatment of Nausea

First-line treatment for nausea should be dopamine antagonists (haloperidol, metoclopramide, or prochlorperazine), with ondansetron added as a second agent if symptoms persist despite initial therapy. 1

Initial Assessment and Etiology

Before initiating antiemetic therapy, identify and address reversible causes 1:

• Constipation (especially with opioid use)
• CNS pathology (increased intracranial pressure, metastases)
• Metabolic disturbances (hypercalcemia, electrolyte imbalances, hypoglycemia)
• Medication-related causes (chemotherapy, opioids, other psychoactive drugs)
• Bowel obstruction (requires specific management approach)

First-Line Pharmacologic Treatment

Dopamine Antagonists (Preferred Initial Agents)

Start with medications targeting dopaminergic pathways 1:

• Haloperidol: 0.5-2 mg PO/IV every 6-8 hours 1
• Metoclopramide: 10-20 mg PO/IV every 6-8 hours 1
• Prochlorperazine: 5-10 mg PO/IV every 6-8 hours 1

These agents work by inhibiting receptors in the brain's chemoreceptor trigger zone 1. Studies have not shown newer 5-HT3 medications (like ondansetron) to be superior to older dopaminergic agents 1.

Important Caveats with Dopamine Antagonists

• Monitor for akathisia with metoclopramide and prochlorperazine, which can develop any time within 48 hours post-administration 2
• Slow the infusion rate to reduce akathisia incidence 2
• Treat akathisia with diphenhydramine if it occurs 2
• Risk of extrapyramidal effects, particularly in children 3
• Metoclopramide can prolong QT interval 3

Second-Line Treatment for Refractory Nausea

Adding Serotonin Antagonists

If nausea persists despite dopamine antagonist therapy, add ondansetron (not replace) to target different mechanisms of action 1:

• Ondansetron: 4-8 mg IV/PO every 8 hours 1, 4, 5
• Granisetron: Alternative 5-HT3 antagonist 1

The rationale for adding rather than switching is to achieve synergistic effects by targeting multiple neurotransmitter pathways 1.

Persistent Nausea Management Algorithm

If nausea continues despite first-line and second-line agents 1:

1. Administer antiemetics around-the-clock for 1 week (rather than as-needed dosing)
2. Reassess the underlying cause after 1 week of persistent symptoms
3. Consider alternative agents:
   • Scopolamine: 1.5-3 mg topical every 72 hours (especially for increased secretions) 1
   • Olanzapine: Particularly helpful for bowel obstruction 1
   • Dexamethasone: 2-8 mg PO/IV every 6-8 hours (effective in combination with metoclopramide and ondansetron, especially for bowel obstruction or intracranial hypertension) 1
   • Lorazepam: 0.5-2 mg PO/IV every 6 hours (for anticipatory nausea) 1

Context-Specific Considerations

Opioid-Induced Nausea

• Prophylactic antiemetics are highly recommended for patients with prior history of opioid-induced nausea 1
• First assess for constipation as a contributing factor 1
• Consider opioid rotation if nausea persists beyond 1 week despite antiemetic therapy 1

Bowel Obstruction from Cancer

Octreotide should be utilized specifically for nausea and vomiting due to malignant bowel obstruction 1. This represents a distinct clinical scenario requiring targeted therapy beyond standard antiemetics.

Chemotherapy-Induced Nausea

• Ondansetron is highly effective for chemotherapy-induced nausea and vomiting 4, 5, 3
• Neurokinin antagonists (aprepitant) are also highly effective for this indication 3
• FDA-approved cannabinoids (dronabinol, nabilone) may be considered for refractory chemotherapy-induced nausea 1

Pregnancy-Related Nausea

Metoclopramide and antihistamines are first-line options for nausea and vomiting in pregnancy 3.

Evidence Quality and Clinical Reality

The evidence for antiemetic superiority is surprisingly weak in general ED populations 6, 7. A Cochrane review found no convincing evidence of superiority of any particular drug over placebo for undifferentiated ED nausea 6. One high-quality RCT showed similar reductions in nausea severity for ondansetron, metoclopramide, and placebo in adult ED patients 7.

However, in clinical practice with identifiable causes (opioid-induced, chemotherapy-induced, bowel obstruction), targeted antiemetic therapy demonstrates clear benefit 1. The key is matching the antiemetic mechanism to the suspected etiology.

Safety Profile Comparison

Ondansetron has the most favorable safety profile with no sedation or akathisia risk, making it suitable as a first-line agent when safety is prioritized over mechanism-based selection 2. However, it can prolong QT interval 3.

Promethazine causes more sedation than other agents and has potential for vascular damage with IV administration, limiting its use to situations where sedation is desirable 2.

Droperidol is more effective than prochlorperazine or metoclopramide but carries an FDA black box warning for QT prolongation, limiting use to refractory cases 2.

Nonpharmacologic Measures

Concurrent supportive care is essential 8, 6:

• Fluid and electrolyte replacement
• Small, frequent meals
• Avoidance of trigger foods

Placebo-controlled trials show significant improvement with supportive care alone, suggesting IV fluids may be sufficient for many patients 6, 7.