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Persistent Diarrhea

Persistent Diarrhea. Dr. Shrish Bhatnagar Consultant Paediatric Gastroenterologist Eras’ Lucknow Medical College & Vivekananda Polyclinic and Institute of Medical Sciences, Lucknow. WHO Definition. Diarrhea Duration >/= 14 days acute in onset following infective etiology.

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Persistent Diarrhea

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  1. Persistent Diarrhea Dr. ShrishBhatnagar Consultant Paediatric Gastroenterologist Eras’ Lucknow Medical College & Vivekananda Polyclinic and Institute of Medical Sciences, Lucknow.

  2. WHO Definition Diarrhea • Duration >/= 14 days • acute in onset • following infective etiology Definition excludes specific conditions like celiac disease, tropical sprue, or other congenital, biochemical or metabolic disorders Bulletin of the World Health Organization, 1988, 66:709–717.

  3. Burden of disease 80% associated with malnutrition WHO CDD Programme; Indian J Med Res 1996;

  4. Causes of Persistent diarrhea Secondary Lactose intolerance Fungal Super-infection Diarrhea compounded by Primary malnutrition……Enteropathy UTI SEPSIS SIBO Antibiotic- associated diarrhea

  5. Natural history of diarrhea Majority subsides in 4-6 weeks If persistent beyond >6-8 weeks (small proportion) Think of other causes Ind J Gastroenterol 1993;12:111-115

  6. Further prolongation of diarrhea(>6-8 weeks) Think of • Cow’s milk ± soya allergy • Immunodeficiency • Celiac disease • Lymphangiectasia • Cystic fibrosis • Anatomical causes Refer to a specialist at the earliest

  7. Risk factors of disease • Age <1 year • Malnutrition • Impaired immunity • Multiple antibiotics • Early introduction of animal milk • Occurrence of recent diarrheal episode • Reduced intake of breast milk

  8. Risk factors of death • 6 months of age or less • Severe dehydration • Use of total parenteral nutrition • Systemic infection: most important WHO Bulletin 1996

  9. Stool Pathogens • Shigella • Salmonella • E.coli (Enteropathogenic and enteroaggregative) • Giardialamblia • Cryptosporidium • Entamebahistiolytica Ind J Gastroenterol 1993;12:111-115 Isolation in stool : 55-70% Interpretation difficult: excreted in healthy

  10. Management

  11. Principles

  12. Prolonged Diarrhea Malnutrition Food allergies (soy, bovine) Compromised immunity Persisting infections Small bowel mucosal injury Superadded infections (fungal) Villous atrophy Loss of brush border enzymes Antibiotics Effects: Secondary lactose intolerance Malabsorption Hypoalbuminemia Bacterial overgrowth

  13. Vicious cycle Break!

  14. Step 1: Resuscitation • Fluid resuscitation: • ORS or • Ringer lactate (I.V.) • Correction of electrolytes • Correction of hypoglycemia

  15. Step 2: Identify infections • Look for infections quickly: • Respiratory, UTI, Sepsis • Examine perineum and oral cavity • TLC and DLC • Blood and urine culture • Chest X-Ray Start appropriate antimicrobials

  16. Stool examination • No role of routine stool culture and isolation of pathogen • Stool for fungus: budding yeasts and hyphae • Stool for C. difficiletoxin in a clinical setting: Antibiotic associated diarrhea • Stool for opportunistic infections if immunodeficiency is suspected: 3 consecutive fresh samples

  17. Indications for antibiotics • Blood in stools: Shigella • Systemic infections • Severe malnutrition • Concomitant UTI • <4mo age group No Role of empirical Nitazoxanide for Cryptosporidium Insufficient data to recommend the use of any kind of antibiotic in persistent diarrhoea of unknown cause or non-specific cause BMC Infectious Diseases 2009,

  18. Case I: 4 mo girl VPIMS Ofloxacin , racecadotril, probiotics Top fed Bottle feeding Intt. fever (1000F) 10 days Acute onset, watery 15 times/day for 7 days dehydration Persistent diarrhea 2 weeks 5-6 times/day, small quantities Catheterized

  19. Further course… • Urine exmn: 15 WBC/ hpf • Urine culture: E.coli • USG-KUB: normal H/O fever Catheterization Suspect UTI • Sensitive antibiotics (3rd gen cephalosporin) for 7 days • Afebrile • Formed stools • MCU/ DMSA scan at follow-up (8 weeks): normal

  20. Case II: 9mo boy ELMCH No fever or urinary symptoms Top fed Bottle feeding Acute onset, watery 15 times/day for 7 days Persistent diarrhea 2 weeks 5-6 times/day, small quantities Cefixime 3 days Ofloxacin 5 d Norfloxacin-metranidazole 7 d

  21. Examination • Oral thrush + • Soft abdomen • No hepatosplenomegaly • Other systems normal Perianalerythema + Satellite lesions around flexures, scrotum and penis Curdy white lesions

  22. Diagnosis Fungal diarrhea (super-infection) • Stool • Budding yeast cells and hyphae ++ • Opportunistic infections: no organism • C. difficile antigen: negative

  23. Management Oral fluconazole 6mg/kg for 10 days Oral Clotrimazole paint Supplements Diarrhea resolved in 3 days No recurrence

  24. Step 3: Lactose intolerance Lactose Load in diet Glucose + Galactose Absorbed Lactase Unabsorbed lactose Acidic Osmotic stool Colon Hydrogen + Lactic acid

  25. Case III: 11 mo boy SPARSH Explosive stools On cow’s milk Acute onset, watery diarrhea for 5 days Persistent diarrhea 3 weeks 10-14 times/day, explosive Ofloxacin 7 days

  26. Examination • Soft abdomen • No hepatosplenomegaly • Other systems normal Perianalerythema (widespread) Minimal lesion on scrotum

  27. Step 4: Dietary therapy Cornerstone of management

  28. Diet algorithm Diet A: Low lactose diet failure Diet B: Lactose-free diet Diet C: Monosaccharide based diet ? failure May use Green banana diet Hydrolysed or amino acid formulae (Elemental diet) Needs to be revisited in current era failure Total parenteral nutrition

  29. Green banana formulation Basis of use Amylase resistant starch (ARS) Not digested in human intestine Delivered to colon Increase salt, water absorption Provide energy Trophic effect Colonic Bacteria Short chain fatty acids Gastroenterology 2001;121:554-60

  30. Step 5: Nutritional supplements • Multivitamins: Twice RDA for 2-4 weeks • Iron: after cessation of the diarrhea • Folic acid: 1 mg/day for 2 weeks • Vitamin A: as per protocol • Potassium: 2-3 mEq/kg/day for 2 weeks • Magnesium sulphate: 0.2 mL/kg/d IM for 2-3d • Zinc: Can be given. No major role

  31. Step 6: Monitoring the response • Successful treatment: • Diarrhoea: passive (<2 stools/day x 2 consec. days) • Adequate food intake • Documented weight gain • Target: Weight on day 7 > weight at admission • Weight gain should be documented on at least 3 successive days • Regular follow up

  32. How long should we give Diet A or B? • Minimum 7 days trial each before failure is declared • If lactose intolerance: Lactose-free diet for at least 21 days

  33. Additional drugs Antimotility drugs: Never • Antisecretory (racecadotril): • No role in persisted diarrhea • Probiotics (Lactobacilli, S. boulardii): • weak benefit

  34. Case IV: 16 mo boy Sparsh No fever or urinary symptoms Top fed Bottle feeding Acute onset, watery 15 times/day for 7 days Loose stools , occasional abdominal pain & bloating X 14 days Cefixime 3 days Ofloxacin 5 d Norfloxacin-metranidazole 7 d

  35. Further course… Lactulose hydrogen breath test which showed a rise in hydrogen suggestive of “Small intestinal bacterial overgrowth’’. All Investigation Normal Suspect SIBO • Substantially under-diagnosed & misdiagnosed entity • Frequently implicated as a cause of prolonged diarrhea & abdominal pain. • Characterised by an increased number and/or abnormal type of bacteria in the small intestine.

  36. SIBO-Pathophysiology 9

  37. Summing up:- Infectious diarrhoea can predispose to SIBO and SIBO inturn can lead to prolongation of the diarrhoea. Infectious diarrhoea Persistent diarrhea SIBO Source : Giannattasio, Antonietta, Alfredo Guarino, and Andrea Lo Vecchio. “Management of Children with Prolonged Diarrhea.” F1000Research 5 (2016): F1000 Faculty Rev–206. PMC. Web. 10 May 2016.

  38. SIBO-Diagnosis 9 • Physical examination provides non specific findings. • Laboratory investigations • Complete blood count – anemia may be present • Low serum Vit. B12 • Low serum prealbumin • Microbial investigation of jejunal aspirate obtained by endoscopy (gold standard but has low reproducibility & difficulty in identifying culture resistant organisms) • Hydrogen & methane breath analysis by chromatography following oral glucose /lactulose (most commonly used test): Early single peak following oral glucose or double peak after lactulose indicates a positive test.

  39. SIBO-Treatment 9 • Correction of the underlying cause (dietary/medical/surgical) • Nutritional support in patients with weight loss & nutritional deficiency. - Supplementation of vitamin B12 , fat-soluble vitamins, calcium, Folic Acid - Exclusion of lactose from diet. - Reduction of simple sugars - Energy needs conveyed by administering fat & medium chain triacylglyceroles 3) Antibiotics (mainstay of treatment) : A number of antibiotics have been tried for SIBO. Rifaximin appears promising.

  40. Rifaximin-Dosing Dosing as per body weight • Dosage for adults and children older than 12 years is 10 to 15 mg/kg/day • Younger children a daily dose of 20 to 30 mg/kg/day (Treatment duration 7days) • Still not approved for <2 Years of age Prescribing Information- Rifaximin A Review of its Antibacterial Activity, Pharmacokinetic Properties and Therapeutic Potential in Conditions Mediated by Gastrointestinal Bacteria Jane C. Gillis  Rex N. Brogden March 1995, Volume 49, Issue 3, pp 467-484 First online: 24 October 2012

  41. Rifaximin Pharmacokinetics & Safety profile • Unabsorbed from gut ->enables inhibition of enteric pathogens. • < 0.4% detected in blood & urine. • Undetected in bile, breast milk • Excreted unchanged in feces. • Half life – 6 hrs • No significant drug interactions. • Excellent safety profile. • Caution advocated in liver disease. • Safety in pregnancy not evaluated.

  42. Rifaximin efficay & safety in children • Rifaximin being a non absorbable antibiotic with excellent tolerability in adults promises an ideal drug for use in children with Travelers Diarrhea & SIBO. • A meta-analysis of studies of Rifaximin in children was conducted by Fabio Capello et al. 11 Search Methods: All available publications related to use of rifaximin in children included Results: Higher number of healed patients in the rifaximin groups at the end of the studies, with a reduction of the mean number of stool/day (-2,021; p<0,001); more formed stool (OR 4,31; p=0,001); a shorter Recovery Time when compared to control groups. The microbiological tests performed after treatment have shown the persistence of 54% of the potentially most dangerous pathogenic bacteria in the children treated with diet and rehydration alone, in comparison with 11.2% in children treated with rifaximin . (chi square 7.4; p= 0.02). Conclusions: Use of rifaximin for bacterial diarrhea in children over 2 years may be fully justified in selected circumstances as in case of travelers' diarrhea, recurrent or relapsing diarrhea known or supposed to be caused by non-invasive Bacterial over growth

  43. Summary Persistent diarrhea > 14 days Infections, malnutrition form vicious cycle UTI, Fungal Infection ,Secondary lactose intolerance, SIBO are cause for prolongation Home Based Dietary Management with correction of prolongation factor is the main stay of treatment Rifaximin has a role in SIBO in children

  44. Preparation of green banana diet Raw, green banana Remove skin Take pulp, blend Homogenized 100 g Cook in boiling water For 7-10 minutes + Oil 25 g Glucose 20 g Nacl 01 g ± Egg white 80 g Rice 10 g powder Cook in one liter water + Feed Calories: 54/100ml

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