What is the recommended evaluation and management approach for acute nausea, including red‑flag assessment, workup, and pharmacologic and non‑pharmacologic treatment options?

Approach to Acute Nausea

Start with dopamine receptor antagonists (metoclopramide 10–20 mg every 6 hours, prochlorperazine 10 mg every 6–8 hours, or haloperidol 0.5–2 mg every 4–6 hours) on a scheduled basis, not PRN, and escalate systematically if symptoms persist beyond 4 weeks by adding a 5-HT3 antagonist like ondansetron rather than switching agents. 1, 2

Red-Flag Assessment and Initial Stabilization

Critical Exclusions Before Treatment

• Rule out mechanical bowel obstruction immediately through clinical examination and imaging if indicated, because antiemetics can mask progressive ileus and gastric distension. 2
• Obtain a urine pregnancy test in all women of reproductive age before initiating any workup, as pregnancy (including hyperemesis gravidarum) is the most common endocrine cause of nausea in this demographic. 2
• Assess for dehydration, altered mental status, and severe metabolic abnormalities that warrant hospitalization and intravenous fluid resuscitation with isotonic crystalloids (lactated Ringer's or normal saline). 2, 3
• Administer thiamine 100 mg IV before glucose-containing fluids in patients with prolonged vomiting to prevent Wernicke encephalopathy. 2

Essential Initial Workup

• Order complete blood count, comprehensive metabolic panel (including electrolytes, glucose, calcium), liver function tests, lipase, and urinalysis to exclude metabolic causes and assess dehydration severity. 2
• Correct hypokalemia and hypomagnesemia aggressively, as these are common after prolonged vomiting and can perpetuate symptoms. 2
• Obtain urine drug screen to assess for cannabis use, particularly in younger patients, as Cannabis Hyperemesis Syndrome requires 6 months of cessation for definitive diagnosis. 2
• Consider testing for hypercalcemia, thyroid-stimulating hormone, and cortisol if clinically indicated by history or physical examination. 2, 4

Cause-Specific Red Flags

• Assess for constipation or fecal impaction as a reversible cause before escalating antiemetic therapy. 1
• Evaluate for CNS pathology (brain metastases, increased intracranial pressure) if headache, focal neurologic signs, or papilledema are present; obtain head CT if suspected. 1, 4
• Review all medications and discontinue non-essential agents that may be emetogenic or constipating. 1, 2
• Rule out hypercalcemia, radiation therapy effects, and chemotherapy-induced nausea in cancer patients. 1

Pharmacologic Management Algorithm

First-Line Therapy (Days 1–28)

Initiate dopamine receptor antagonists on a scheduled (around-the-clock) basis, not PRN, to achieve maximal symptom control. 1, 2

• Metoclopramide 10–20 mg PO/IV every 6 hours is preferred when gastroparesis or gastric stasis is suspected, as it enhances gastric emptying through prokinetic effects. 1, 2
• Prochlorperazine 10 mg PO/IV every 6–8 hours is an effective alternative dopamine antagonist with lower prokinetic activity. 1, 2
• Haloperidol 0.5–2 mg PO/IV every 4–6 hours provides additional anti-dopaminergic effect and may be used when other agents are unsuitable. 1, 2, 5
• Monitor for extrapyramidal symptoms (rigidity, tremor, akathisia), particularly in young males and elderly patients; treat with diphenhydramine 50 mg IV if they develop. 1, 2, 5

Adjunctive First-Line Agents

• Add lorazepam 0.5–1 mg PO/IV every 4–6 hours when anxiety contributes to nausea, but recognize it is ineffective for mechanical obstruction. 1, 2
• Initiate proton pump inhibitor or H2-receptor antagonist if dyspepsia, gastritis, or gastroesophageal reflux is suspected, as patients may confuse heartburn with nausea. 1, 2, 5

Second-Line Therapy (After ≥4 Weeks or Severe Symptoms)

Add a 5-HT3 antagonist without discontinuing the dopamine antagonist, targeting a different emetic pathway rather than replacing one agent with another. 1, 2

• Ondansetron 4–8 mg PO/IV every 8 hours (maximum 16 mg per dose) is the preferred 5-HT3 agent; sublingual tablets improve absorption in actively vomiting patients. 1, 2, 5
• Monitor for QTc prolongation when using ondansetron, especially in combination with other QT-prolonging agents. 2
• Note that ondansetron may increase stool volume/diarrhea and can worsen constipation in elderly patients. 2, 5
• Consider granisetron 1 mg PO twice daily or 34.3 mg transdermal patch weekly as an alternative 5-HT3 antagonist. 5

Third-Line Therapy (48–72 Hours After Second-Line Failure)

• Add dexamethasone 4–10 mg PO/IV twice daily for severe or CNS-related nausea, particularly effective in combination with metoclopramide and ondansetron. 1, 2, 5
• Consider scopolamine (anticholinergic) to further reduce nausea through a different mechanism. 1, 2
• Add meclizine (antihistamine) for vestibular-modulating effects. 1, 2

Fourth-Line / Refractory Management

• Olanzapine 2.5–10 mg PO daily may be introduced for refractory nausea, particularly in cancer-related contexts, with evidence showing 50% nausea-free rates versus 10.5% with placebo (P=0.008). 2, 5
  • Use extreme caution in elderly patients due to FDA boxed warning for increased mortality in dementia-related psychosis; consider 2.5–5 mg doses in this population. 5
  • Avoid concurrent use with metoclopramide, phenothiazines, or haloperidol to prevent additive dopaminergic effects. 5
• Dronabinol 2.5–7.5 mg PO every 4 hours as needed is FDA-approved for refractory nausea unresponsive to conventional antiemetics. 1, 2
• Consider continuous IV or subcutaneous infusion of antiemetics for intractable vomiting. 1, 2
• Employ multiple concurrent agents on alternating schedules when single-agent regimens are insufficient. 2

Route of Administration Considerations

• Use alternative routes (rectal, sublingual, IV, subcutaneous) when oral intake is not feasible due to ongoing vomiting. 1, 2
• Administer antiemetics on a scheduled basis rather than PRN, as prevention is far easier than treating established vomiting. 2

Non-Pharmacologic Management

Fluid and Nutritional Support

• Oral rehydration solution (ORS) is first-line therapy for mild to moderate dehydration (3–9% fluid deficit) in all age groups, even when vomiting is present. 2
• Administer 50–100 mL/kg of reduced-osmolarity ORS over 3–4 hours for rehydration in adults. 2
• Reserve isotonic IV crystalloids for severe dehydration (≥10% deficit), shock, altered mental status, or failure of oral rehydration. 2
• Initiate IV hydration before attempting oral rehydration in patients with ketonemia. 2
• Resume age-appropriate normal diet during or immediately after rehydration; avoid high-sugar fluids (fruit juices, sports drinks, soft drinks). 2
• Recommend small, frequent meals and adequate fluid intake of at least 1.5 L/day. 2

Behavioral Interventions

• Consider guided imagery or hypnosis for anticipatory or anxiety-related nausea. 5

Special Population Considerations

Elderly Patients

• Start with 25–50% dose reduction of dopamine receptor antagonists due to increased sensitivity to side effects. 5
• Initiate lorazepam at 0.25 mg PO/IV every 4–6 hours with gradual tapering when discontinuing; avoid long-term use and never discontinue abruptly. 5
• Reduce ondansetron to maximum 8 mg total daily in severe hepatic impairment. 5
• Monitor closely for sedation, extrapyramidal symptoms, and falls. 5

Pregnancy

• Combined doxylamine/pyridoxine is first-line for nausea and vomiting of pregnancy, as it is not teratogenic and may be effective. 6
• Ondansetron is commonly used for hyperemesis gravidarum, but studies are needed to determine if it is safer and more effective than first-line antiemetics. 6

Cannabis Hyperemesis Syndrome

• Do not stigmatize patients with cannabis use; offer abortive and prophylactic therapy even with ongoing use, as treatments can still be effective. 2
• Definitive diagnosis requires 6 months of cannabis cessation or at least 3 typical cycle lengths without vomiting. 2

Critical Pitfalls to Avoid

• Never use antiemetics in suspected mechanical bowel obstruction, as this can mask progressive ileus and gastric distension. 2
• Do not replace one antiemetic with another; instead, add agents from different drug classes to engage multiple neuroreceptor pathways. 1, 2
• Avoid repeated endoscopy or imaging unless new symptoms develop; one-time EGD or upper GI imaging is sufficient to exclude obstructive lesions. 2
• Do not use antimotility agents (loperamide) in children <18 years with acute diarrhea or in any patient with inflammatory diarrhea or fever. 2
• Recognize that overall response rates to antiemetic therapy range only 23–36% even with optimal regimens, particularly in elderly patients. 5

Reassessment and Follow-Up

• Systematically reassess for non-pharmacologic causes (brain metastases, electrolyte disturbances, tumor infiltration, medications) before escalating therapy. 2
• If nausea persists longer than one week on maximal therapy, reassess the cause and consider opioid rotation if opioid-induced. 1
• Persistently abnormal liver chemistries after symptom resolution warrant evaluation for viral hepatitis, autoimmune hepatitis, or drug-induced liver injury. 2
• A cyclic pattern of vomiting suggests cyclic vomiting syndrome; consider prophylactic amitriptyline 50 mg nightly. 2