What is the treatment for non-infectious diarrhea?

Treatment of Non-Infectious Diarrhea

The cornerstone of treating non-infectious diarrhea is adequate fluid and electrolyte replacement, with oral rehydration solution (ORS) as first-line therapy for mild to moderate dehydration, followed by symptomatic management with antimotility agents in appropriate patients and addressing the underlying cause. 1

Immediate Management: Rehydration

Oral Rehydration Therapy

• Reduced osmolarity ORS is the first-line treatment for mild to moderate dehydration in all age groups with non-infectious diarrhea. 1
• Continue ORS until clinical dehydration is corrected, then switch to maintenance fluids to replace ongoing losses. 1
• Nasogastric administration of ORS may be used in patients with moderate dehydration who cannot tolerate oral intake or are too weak to drink adequately. 1

Intravenous Rehydration

• Use isotonic IV fluids (lactated Ringer's or normal saline) for severe dehydration, shock, altered mental status, or ileus. 1
• Continue IV rehydration until pulse, perfusion, and mental status normalize, then transition to ORS for remaining deficit replacement. 1

Nutritional Support

• Resume age-appropriate usual diet immediately after rehydration is completed. 1
• Continue breastfeeding throughout the diarrheal episode in infants. 1
• Monitor for signs of malnutrition or catabolic state and supplement enteral or parenteral electrolytes, carbohydrates, lipids, amino acids, and vitamins as indicated. 1

Symptomatic Treatment

Antimotility Agents

• Loperamide may be given to immunocompetent adults with non-infectious watery diarrhea once adequately hydrated. 1
• Loperamide is contraindicated in children <18 years of age with acute diarrhea. 1
• Avoid loperamide in inflammatory diarrhea, diarrhea with fever, or when toxic megacolon is a concern. 1
• FDA-approved loperamide is indicated for chronic diarrhea in adults associated with inflammatory bowel disease and for reducing ileostomy discharge volume. 2

Critical Pitfall: Never exceed recommended loperamide doses due to risk of cardiac arrhythmias, QT prolongation, and sudden death. 2

Antiemetic Agents

• Ondansetron may be given to children >4 years of age and adolescents with vomiting to facilitate oral rehydration tolerance. 1
• Antiemetics are not a substitute for fluid and electrolyte therapy but can be considered once the patient is adequately hydrated. 1

Probiotics

• Probiotic preparations may be offered to reduce symptom severity and duration in immunocompetent adults and children with non-infectious diarrhea. 1

Specific Etiologies of Non-Infectious Diarrhea

Paraneoplastic Diarrhea

• Consider VIP-secreting tumors (causing watery diarrhea, hypokalemia, hypochlorhydria), carcinoid tumors (serotonin-producing), or other hormone-secreting tumors (glucagonoma, gastrinoma, somatostatinoma). 1
• Treatment targets the underlying malignancy and hormone excess.

Inflammatory Bowel Disease (IBD)

• Consider IBD as an underlying etiology in patients with symptoms lasting ≥14 days without identified infectious source. 1
• Specific IBD therapy should be initiated based on disease severity and extent.

Irritable Bowel Syndrome (IBS)

• Consider IBS in patients with persistent symptoms ≥14 days without identified cause. 1
• For IBS with diarrhea (IBS-D), options include low-FODMAP diet, 5-HT3 receptor antagonists (alosetron), rifaximin, or low-dose tricyclic antidepressants. 3
• Alosetron is FDA-approved for severe diarrhea-predominant IBS in women, providing relief of pain, urgency, and bowel frequency. 4

Drug-Induced and Other Causes

• Cholestyramine may be used for bile acid diarrhea. 3
• Lactose intolerance should be considered in non-responders to initial therapy. 1

Reassessment for Persistent Symptoms

• Perform clinical and laboratory reevaluation in patients not responding to initial therapy, including consideration of non-infectious conditions like lactose intolerance. 1
• Reassess fluid and electrolyte balance, nutritional status, and treatment approach in patients with persistent symptoms. 1
• Repeat testing for the same pathogen should be avoided to prevent false-positive results. 1

Key Clinical Pitfalls

• Never withhold fluid replacement while pursuing symptomatic treatment—rehydration is always the priority. 1
• Avoid loperamide in children, inflammatory conditions, or when exceeding recommended doses. 1, 2
• Do not assume infectious etiology without workup in chronic diarrhea (≥14 days)—non-infectious causes predominate. 1
• Monitor cancer patients closely for paraneoplastic syndromes and maintain nutritional support. 1