How should I evaluate and manage a 31‑year‑old man with persistent, debilitating nausea that confines him to home?

Evaluation and Management of Debilitating Persistent Nausea in a 31-Year-Old Male

Begin with immediate laboratory evaluation including complete blood count, comprehensive metabolic panel, liver function tests, lipase, urinalysis, urine pregnancy test (if applicable), urine drug screen (specifically for cannabis), and thiamine level, while simultaneously initiating intravenous hydration and first-line dopamine antagonist therapy. 1

Immediate Stabilization (First 1–2 Hours)

• Administer isotonic intravenous crystalloids (lactated Ringer's or normal saline) immediately for severe dehydration, as the patient's inability to move without assistance indicates at least moderate-to-severe volume depletion. 1
• Give thiamine 100 mg IV before any glucose-containing fluids to prevent Wernicke's encephalopathy, which is critical in any patient with prolonged vomiting. 1
• Correct electrolyte abnormalities, particularly hypokalemia and hypomagnesemia, which are common after persistent vomiting and can perpetuate symptoms. 1, 2

Critical Initial Diagnostic Workup

Laboratory Testing (Obtain Within First Hour)

• Complete blood count to assess for leukopenia (which with elevated CRP suggests systemic infection, hematologic malignancy, or drug/toxin effect rather than simple gastroenteritis). 1
• Comprehensive metabolic panel to exclude hypercalcemia, hypoglycemia, uremia, and Addison's disease. 1
• Liver function tests and lipase to identify hepatobiliary or pancreatic causes. 1
• Thyroid-stimulating hormone if clinically indicated by other symptoms. 1
• Urine drug screen with specific attention to cannabis use—Cannabis Hyperemesis Syndrome (CHS) is a critical diagnosis in this age group and requires heavy cannabis use history. 1

Cannabis Hyperemesis Syndrome: High-Priority Consideration

• Directly ask about cannabis use patterns, as CHS is common in young adults and presents with debilitating cyclic nausea and vomiting. 1
• CHS requires 6 months of complete cannabis cessation for definitive diagnosis, but clinical suspicion should guide immediate counseling. 1
• Do not stigmatize or withhold treatment even if cannabis use is ongoing—abortive and prophylactic therapies remain effective. 1

Imaging Studies

• Obtain one-time esophagogastroduodenoscopy (EGD) or upper GI imaging to exclude obstructive lesions, but avoid repeated endoscopy unless new symptoms develop. 1

First-Line Pharmacologic Management (Initiate Immediately)

Dopamine Antagonists (First-Line)

• Start metoclopramide 10 mg IV/PO every 6–8 hours, which is particularly effective for gastroparesis and promotes gastric emptying. 1, 2
• Alternative first-line option: prochlorperazine 10 mg IV/PO every 6–8 hours if metoclopramide is contraindicated or not tolerated. 1, 2
• Haloperidol 0.5–2 mg IV/PO every 4–6 hours is another first-line dopamine antagonist with a different receptor profile. 1, 2
• Monitor closely for extrapyramidal symptoms, particularly in young males who are at higher risk; treat with diphenhydramine 50 mg IV if they develop. 1

Route of Administration

• Use IV or rectal routes initially given the severity of symptoms and likely inability to tolerate oral medications. 2
• Consider sublingual ondansetron tablets or rectal suppositories (promethazine, prochlorperazine) if oral route fails. 2

Second-Line Therapy (If Symptoms Persist After 4 Weeks or Are Severe)

Add 5-HT3 Antagonist

• Add ondansetron 8 mg IV/PO every 8 hours to the dopamine antagonist rather than replacing it, as combination therapy targeting different receptors is superior to sequential monotherapy. 1, 2
• Monitor for QTc prolongation, especially when combining ondansetron with other QT-prolonging agents. 1
• Note that ondansetron may increase stool volume/diarrhea if gastroenteritis is present. 1

Adjunctive Therapies

• Add dexamethasone 10–20 mg IV if symptoms are severe or refractory, as the combination with ondansetron is superior to either agent alone (category 1 evidence). 1
• Consider adding a proton pump inhibitor or H2 receptor antagonist if dyspepsia or gastritis is suspected, as patients may confuse heartburn with nausea. 1, 2

Refractory Symptoms (48–72 Hours Without Adequate Control)

Advanced Combination Therapy

• Administer antiemetics on a scheduled basis rather than PRN, as prevention is far easier than treating established vomiting. 1
• Use multiple concurrent agents from different drug classes in alternating schedules rather than sequential monotherapy. 1, 2
• Consider continuous IV or subcutaneous infusion of antiemetics for intractable symptoms. 1, 2

Additional Pharmacologic Options

• Dronabinol 2.5–7.5 mg PO every 4 hours as needed is FDA-approved for refractory nausea unresponsive to conventional antiemetics. 1
• Olanzapine 2.5–5 mg PO daily may be added, particularly in palliative care settings or for refractory symptoms. 2, 3
• Lorazepam 0.5–1 mg IV/PO every 4–6 hours if anxiety is contributing to symptoms. 1, 2

Supportive Care Measures

• Ensure adequate fluid intake of at least 1.5 L/day once oral intake is tolerated. 1
• Recommend small, frequent meals and avoidance of high-sugar fluids (fruit juices, sports drinks, soft drinks). 1
• Continue thiamin supplementation throughout treatment to prevent Wernicke's encephalopathy. 1

Critical Pitfalls to Avoid

• Never use antiemetics if mechanical bowel obstruction is suspected, as this can mask progressive ileus and gastric distension. 1, 2
• Do not perform repeated endoscopy or imaging unless new symptoms develop. 1
• Avoid replacing one antiemetic with another—instead, add agents from different drug classes to target multiple emetic pathways. 1, 2
• Monitor for tardive dyskinesia with long-term metoclopramide use, though risk may be lower than previously estimated. 2

Follow-Up and Reassessment

• If a cyclic pattern of vomiting emerges, consider cyclic vomiting syndrome and initiate prophylactic amitriptyline 50 mg nightly. 1
• Persistently abnormal liver chemistries after symptom resolution warrant evaluation for viral hepatitis, autoimmune hepatitis, or drug-induced liver injury. 1
• Ongoing leukopenia requires hematology consultation to exclude primary bone marrow pathology. 1