What to do for 3 weeks of nausea, vomiting, and fatigue?

Management of 3 Weeks of Nausea, Vomiting, and Fatigue

Begin with dopamine receptor antagonist therapy (metoclopramide 10 mg orally three times daily) while simultaneously conducting targeted laboratory evaluation to identify treatable underlying causes. 1

Immediate Diagnostic Workup

Obtain the following laboratory tests to exclude metabolic and systemic causes:

• Complete blood count, comprehensive metabolic panel (including calcium), glucose, liver function tests, lipase, and urinalysis to assess for dehydration, electrolyte disturbances, hypercalcemia, and metabolic abnormalities 1
• Thyroid-stimulating hormone and morning cortisol if clinically indicated to exclude hypothyroidism and Addison's disease 1
• Urine drug screen with specific inquiry about cannabis use, as Cannabis Hyperemesis Syndrome is common in this age group and requires 6 months of cessation for definitive diagnosis 1
• Correct hypokalemia and hypomagnesemia aggressively, as prolonged vomiting causes metabolic alkalosis and electrolyte depletion 1

Critical consideration: Hypercalcemia from vitamin D toxicity or other causes can present with this exact triad of symptoms and requires urgent treatment 2. Hypercalcemia >13 mg/dL warrants intravenous hydration, furosemide, and potentially pamidronate 2.

Initial Imaging

• Obtain one-time esophagogastroduodenoscopy (EGD) or upper GI imaging to exclude obstructive lesions, but avoid repeated endoscopy unless new symptoms develop 1
• Consider brain MRI if personality changes, nystagmus, or neurologic signs are present, as central nervous system pathology can manifest as isolated nausea and vomiting 3

Pharmacologic Management Algorithm

First-Line Therapy (Initiate Immediately)

Metoclopramide 10 mg orally 30 minutes before meals and at bedtime (onset 30-60 minutes orally, duration 1-2 hours), titrated to maximum benefit and tolerance 1, 4. This agent is particularly effective for gastric stasis and promotes gastric emptying 1.

• Administer on a scheduled basis rather than as-needed, as prevention is superior to treating established vomiting 1
• Monitor for extrapyramidal symptoms, especially in young males, and treat with diphenhydramine 50 mg IV if they occur 1, 4

Second-Line Therapy (Add After 4 Weeks if Symptoms Persist)

Add ondansetron 8 mg orally every 8 hours, as it acts on different receptors (5-HT3) than metoclopramide and provides complementary antiemetic coverage 1, 5

• Monitor QTc interval when using ondansetron, particularly with other QT-prolonging medications 1
• Note: Ondansetron may increase stool volume/diarrhea if gastroenteritis is still present 1

Alternative Dopamine Antagonists

If metoclopramide is not tolerated:

• Prochlorperazine 10 mg orally every 6-8 hours 5, 1
• Haloperidol 1 mg orally every 4 hours as needed, which has a different receptor profile 1

Adjunctive Therapies

For Suspected Gastroparesis or Gastritis

• Add proton pump inhibitor (omeprazole 20-40 mg daily) or H2 receptor antagonist, as patients may confuse heartburn with nausea 1
• Continue metoclopramide as it specifically addresses delayed gastric emptying 1

For Refractory Cases

Combine multiple agents from different drug classes simultaneously rather than sequential monotherapy, as no single agent has proven superior for breakthrough emesis 1:

• Dexamethasone 4 mg twice daily for 14 days may be considered for severe fatigue, though evidence for cancer-related fatigue may not fully translate to other causes 5
• Dronabinol 2.5-7.5 mg orally every 4 hours as needed is FDA-approved for refractory nausea 1
• Consider alternating routes (rectal suppositories, sublingual) if oral route fails due to ongoing vomiting 1

Non-Pharmacologic Management

• Ensure fluid intake of at least 1.5 L/day with small, frequent meals 1
• Thiamin supplementation to prevent Wernicke's encephalopathy in patients with persistent vomiting 1
• Moderate-intensity exercise (walking, swimming, cycling) 2-3 times weekly for 30-60 minutes may improve fatigue, though this may be challenging during acute symptoms 5

Critical Pitfalls to Avoid

• Never use antiemetics if mechanical bowel obstruction is suspected, as this masks progressive ileus and gastric distension 1
• Do not stigmatize patients with cannabis use—offer treatment even with ongoing use, as therapies can still be effective 1
• Avoid repeated endoscopy or imaging unless new symptoms develop 1
• Do not use psychostimulants (methylphenidate, modafinil) for fatigue, as their efficacy has not been proven 5

When to Reassess

If nausea persists longer than one week despite optimal antiemetic therapy, reassess the underlying cause and consider opioid rotation if applicable, or escalate to combination therapy 5. If symptoms continue beyond 4 weeks with negative workup, consider functional gastroduodenal disorders such as cyclic vomiting syndrome or chronic idiopathic nausea 6, 7.