Newer Trends in Management of Acute Diarrhea in Children

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Newer Trends in Management of Acute Diarrhea in
Children
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Diarrhea India

• Diarrhea is a major killer disease in under five
  (U5) children in India and thus an important
  public health problem
• Upto a third of total pediatric admissions are
  due to diarrheal diseases
• Upto 17 of all deaths in indoor pediatric
  patients are diarrhea related
• Acute watery diarrhea was most common (58.9),
  followed by dysentery (24.2) and persistent
  diarrhea (16.9)

Indian Pediatrics 255 Volume 41__march 17, 2004
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Goals in management of Diarrhea

• Much attention has been given over the last
  decade to acute diarrhea and its management but
  it has not made much impact on the scenario

1. Indian Pediatrics 255 Volume 41__march 17, 2004
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Goals in management of Diarrhea

• Potential goals in the management of diarrhea are
  
• Correction of dehydration and electrolyte
  imbalance,
• Reduction of stool output, prevention of
  recurrence,
• Prevention of malnutrition related complications,
  
• Improvement of mucosal barrier
• Maximization of nutrient availability2

Ooty Pedicon 2005, http//www.pediatriconcall.com/
fordoctor/Conference_abstracts
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WHO classification of Diarrhea

• Acute watery diarrhea
• Starts acutely
• Not associated with blood or mucus
• Lasts for less than 14 days.
• May be associated with fever and vomiting.
• Main causative agents are Rotavirus,
  enterotoxigenic, E.Coli, Shigella and Vibrio
  cholerae.

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WHO classification of Diarrhea

• Acute bloody diarrhea/dysentery
• With visible blood in stools
• Occurs due to infection with Shigella,
  enteroinvasive E.Coli Salmonella or
  Camphylobacter jejuni.
• E. histolytica is rare cause of dysentery in
  young children.
• Dysentery is generally associated with more
  complications, lasts longer and has a higher risk
  of death.

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WHO classification of Diarrhea

• Persistent diarrhea
• Persists for more than 2 weeks after an apparent
  episode of infectious gastroenteritis
• Risk factors for persistent diarrhea are low
  birth weight, absence of breast-feeding
  concurrent medical illness, malnutrition blood or
  mucus in stools and prior antibiotic use.

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Types of Diarrhea

• A. Watery Diarrhea
• a. Secretory Diarrhea (e.g cholera )
• Stool Sodium high (60-120 meq/L)
• b. Osmotic Diarrhea (osmotic loss of
  free water)
• (e.g Coeliac disease)
• Stool Sodium low (30-40 meq/L)
• Results from damage to intestinal microvilli
• B. Inflammatory Diarrhea (Infection,
  autoimmune disease)
• Stool with pus or blood present
• C. Fatty diarrhea (Malabsorption)
• Large greasy, frothy pale stools with
  foul odor
• D. Infectious Diarrhea

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Causes of diarrhea in a child

• Viruses - Rotavirus, enteric adenovirus,
  Astrovirus etc.
• Bacteria - E.Coli, Shigella, Salmonella,
  Vibrio cholerae, Campylobacter jejuni, Yersinia
• Parasites - E.histolytica, Giardia lamblia,
  Cryptosporidium etc
• Dietary causes - overfeeding, underfeeding, food
  allergy, food poisoning etc
• Misc. causes - antibiotic associated,
  malabsorption, anatomic defects of the GIT,
  thyrotoxicosis,laxative abuse and rarely lactase
  deficiency

Common causes
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Predisposing factors for diarrhea

• Poor sanitation, contamination of food and
  drinking water, use of bottle-feeding, failure to
  wash hands after defecation and failure to breast
  feed exclusively for the first 4-6 months of
  life.
• Newborns, young infants and malnourished children
  are at risk for diarrhea because of their
  immature immunological system, especially if they
  are not breast-fed.

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Diarrhea Mechanism

• Active transport of Na back into the gut
• Passive flow of Water, Cl and HCO3.
• Water dilutes toxins and cause intestinal
  distension triggers contractions

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Acute Diarrhea Medical evaluation

• Age
• Premature birth, history of chronic medical
  conditions or concurrent illness
• Fever gt100.4F for age lt3 months or gt102.2F for
  age gt3 months
• Visible blood in stool
• High output diarrhea, including frequent
  substantial volumes of stool
• Persistent vomiting
• Signs consistent with dehydration (e.g., sunken
  eyes or decreased tears, dry mucous membranes, or
  decreased urine output)
• Change in mental status (e.g., irritability,
  apathy, or lethargy)
• Suboptimal response to ORS or inability to
  administer ORS

www.bt.cdc.gov/disasters
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Management of Diarrhea in children

• ORS in small, frequent volumes
• For rapid realimentation, an age-appropriate,
  unrestricted diet is recommended as soon as
  dehydration is corrected
• For breastfed infants, nursing should be
  continued
• Additional ORS, for ongoing diarrheal losses
• No routine laboratory tests or medications are
  recommended
• Except, if a patient is living in conditions that
  are crowded or otherwise conducive to outbreaks
  of GI disease
• Care-takers should be counseled for hand hygiene
  practices

www.bt.cdc.gov/disasters
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Management of Diarrhea in children

• Use of antimicrobials - on a patient-by-patient
  basis
• Even when a bacterial cause is suspected,
  antimicrobial therapy is NOT usually indicated
  among children because most cases of acute
  diarrhea are self-limited and their duration is
  not shortened by the use of antimicrobial agents.
  Exceptions to these rules may involve
• Premature infants, children who are
  immunecompromised or have underlying disorders)
  or Suspicion of sepsis
• In the context of an outbreak of shigellosis,
  cryptosporidiosis, or giardiasis.
• Anti-emetics antimotility agents should be
  avoided

www.bt.cdc.gov/disasters
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Management of Diarrhea in children

• Anti-diarrheal drugs
• Antimotility or Antiperistaltics drugs
• loperamide, diphenoxylate, codeine, tincture
  opium and other opiates
• Anticholinergics
• atropine, hyoscine, hyoscyamine and dicyclomine
• Probiotics
• Racecadotril
• Adsorbents
• activated charcoal, kaolin, pectin, dioctahedral
  smectite, attapulgite (anhydrous aluminum
  silicate)

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Antimotility agents

• Antimotility agents are generally contraindicated
  for children
• Antimotility agents may reduce diarrheal output
  and cramps, but do not accelerate cure.

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Anticholinergic agents

• AMERICAN ACADEMY OF PEDIATRICS
• Management of Acute Gastroenteritis in Young
  Children
• Not recommended in the mgt of diarrhea in
  children
• Causes dry mouth
• May alter the clinical evaluation of dehydration
• Infants and young children are especially
  susceptible to the toxic effects of
  anticholinergic drugs.
• Coma, respiratory depression, and paradoxical
  hyperexcitability have been reported

Pediatrics Volume 97 Number 3 March 1996
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Probiotics rationale
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Probiotics Cochrane analysis
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Comparison 01 Probiotic versus control, Outcome
03 Mean duration of diarrhoea (hours)
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Probiotics Cochrane analysis

• Authors conclusions
• Probiotics appear to be a useful adjunct to
  rehydration therapy in treating acute, infectious
  diarrhoea in adults and children. More research
  is needed to inform the use of particular
  probiotic regimens in specific patient groups.

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Probiotics

• Beneficial effects seem to be
• Moderate
• Strain dose dependent
• Significant in watery diarrhea and viral
  gastroenteritis, but non-existent in invasive,
  bacterial diarrhea
• More evident when treatment with probiotics is
  initiated early in the course of disease.

Szajewska, Pediatric Drugs, Volume 7, Number 2,
2005 , pp. 111-122(12)
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Racecadotril

• Antisecretory drug that exerts its antidiarrhoeal
  effects by inhibiting intestinal enkephalinase

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Racecadotril

• An antisecretory drug - effective against acute
  pediatric diarrhea due to rotavirus negative and
  rotavirus-positive infections1
• Reduces the incidence and duration of acute
  diarrhoea stool output compared with placebo in
  adults1

1. Drug Ther Perspect 17(8)1-5, 2001
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Aliment Pharmacol Ther. 2007 Sep 1526 (6)807-13
17767464 Systematic review racecadotril in the
treatment of acute diarrhoea in children. H
Szajewska , M Ruszczynski , A Chmielewska , J
Wieczorek

• Only randomized-controlled trials were included.
  Results Three randomized-controlled trials (471
  participants) met the inclusion criteria.
• The duration of diarrhoea was significantly
  reduced in the three trials reporting this
  outcome.
• Achievement of a cure by day 5 was similar in
  both groups. Adverse effects were similar in both
  groups.
• Conclusions some evidence in favour of the use
  of racecadotril over placebo or no intervention,
  to reduce the stool output and duration of
  diarrhoea in children with acute gastroenteritis.
  However, more data in out-patients are needed.
  The safety as well as the cost-effectiveness of
  the therapy should be explored, before routine
  therapy with racecadotril is recommended

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WHO Racecadotril

• 2 trials in children, both pharmaceutical
  industry sponsored. No independent trials.
• Indian Association of Paediatrics (IAP)
  Guidelines 2006 on Management of acute diarrhea
  has not recommended use of Racecadotril. The
  committee has gone through the existing
  literature in detail before coming to this
  decision.
• No studies are given to support safety (study
  sample number is small). Unable to comment on
  concerns of adverse effects as the data are not
  adequate
• No adequate evidence of efficacy for the proposed
  use.
• No evidence of efficacy in diverse settings
  and/or populations

mednet3.who.int/EMl/expcom/CHILDREN/Reviewers/Race
cadotril_rev1.pdf
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Adsorbents
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Kaolin Pectin

• In 1992, the FDA banned the use of pectin in
  over-the-counter products, due to insufficient
  data about its safety and efficacy.
• In 1999, WHO recommended withdrawal of
  combination of Pectin Kaolin because of Lack of
  evidence of efficacy in the management of
  diarrhoea

1. WHO, 1999 2. http//uuhsc.utah.edu/pharmacy/al
erts/31.html
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Dioctahedral Smectite (BMJ 2006)

• Dioctahedral smectite is a natural adsorbent clay
• Adsorbs viruses, bacteria, and bacterial toxins,
  thus protecting the intestinal mucosa
• Most studies consistently showed the efficacy of
  smectite in reducing the duration of diarrhoea
• With ORS, shortens duration of diarrhoea by
  2050
• No significant side effects were observed.
• Considering the safety, tolerance and
  antidiarrhoeal activity of smectite, it is worth
  a try in treatment of acute diarrhoea in
  children.

Zui-Shen Yen, Emerg. Med. J. 20062365-66
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Dioctahedral Smectite

• Alimentary Pharmacology Therapeutics
• Volume 23 Issue 2 Page 217-227, January 2006
• Meta-analysis Smectite in the treatment of acute
• infectious diarrhoea in children
• Conclusions
• Smectite may be a useful adjunct to rehydration
• therapy in treating acute paediatric
  gastroenteritis.

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Smectite in Mgt of Acute Diarrhea (Eur J
Gastroenterol Hepatol)

• Increases intestinal barrier function
• Effective against infectious diarrhea in children
  
• Duration of diarrhoea was significantly shorter
  42.3 /- 24.7 h
• No impact on adsorption of electrolytes
• Useful in acute gastroenteritis alongwith ORS

Eur J Gastroenterol Hepatol. 2002 Apr14(4)419-24
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Rehydration Vs Rehydration with smectite in
acute diarrhea

• 32 infants (control Rehyd O/I) 34 infants
  (DSRehyd.)
• Stool were positive for either Salmonella,
  Shigella, Campylobacter, enterotoxigenic E. coli,
  Plesiomonas sp. Rotavirus
• 72 hours after therapy, 71 infants were cured in
  DS group Vs 34 in control grp
• 5 days after beginning of treatment, only 12 in
  DS group had diarrhea Vs 34 in control group.
• The acceptability of DS was considered to be good
  in 88.
• No major side effect was observed.

Southeast Asian J Trop Med Public Health. 1994
Mar25(1)157-62
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Smectite in acute diarrhea in children (J
Pediatr Gastroenterol Nutr.)

• Significantly shorter duration of diarrhea (54
  /- 16 hrs)
• Significantly fewer stools
• 2.6 /- 0.8 on 2nd day
• 1.9 /- 0.7 on 3rd day

J Pediatr Gastroenterol Nutr. 1993
Aug17(2)176-81
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Smectite in Diarrhea predominant IBS (J
Gastroenterol Hepatol , 2007)

• Efficacy of dioctahedral smectite in treating
• patients of diarrhea-predominant irritable bowel
• syndrome.
• Conclusion-
• Drug well tolerated during the 8-week period.
• DS seems acceptable to treat D-IBS patients,
  particularly for pain-related symptoms.

J Gastroenterol Hepatol , 2007
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Smectite in Radiation induced Diarrhea

• Therapy trends in the prevention of radiation
• induced diarrhea after pelvic and abdominal
• irradiation
• Results of a tricenter study
• Conclusion-
• The prophylactic application of Smectite is able
  to
• reduce the diarrhea from the beginning of
  radiotherapy
• or at least to reduce the pathological frequency
  of stool
• and therefore to increase the quality of life.

Strahlenther Onkol. 1995 Jan171(1)49-53.
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Smectite (Diosmec)

• Natural adsorbent clay formed of fine sheets of
  aluminomagnesium silicate
• Non-systemic gastrointestinal tract
  muco-protective agent
• Interacts with mucus molecules, to strengthen the
  mucosal barrier and protect the apical pole of
  the enterocytes and tight junctions against
  bacteria and toxin present within the lumen
• It has also been shown to have a specific binding
  action for rotavirus, one of the main causes of
  diarrhoea in children

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Smectite (Diosmec) Effect

• Adsorbs toxins bacteria and rotavirus
• Has a direct effect on the physical properties of
  the gastric mucus and mucolysis induced by
  bacteria
• It may also repair mucosal integrity

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Smectite (Diosmec) Benefits

• Significantly shortens duration and reduces
  frequency of diarrhea in children and adults
• Reduces the costs of treating gastroenteritis
• Is presented in powder form, provides fast onset
  of action
• Alleviates painful symptoms caused by abnormal
  bowel motions
• Has high safety profile with no systemic side
  effects

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Smectite (Diosmec) Indications

• Indications
• Symptomatic treatment of acute and chronic
  diarrhea, especially with children.

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Smectite (Diosmec) Dosage

• Children less than 1year
• 1 sachet per day diluted with 50 ml water and
  distributed during the day.
• It may be mixed with other liquid food too
  (broth, juice etc.),
• Children with 1-2 years
• 1-2 envelopes per day,
• Children over 2 years
• 2-3 envelopes per day.
• The drug is administrated after meals if
  oesophagitis and before meals in other cases

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AGE Adjunct Therapies

• Dr Rajesh
• 23/01/2008

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Gastroenteritis

• Defined as- Inflammation of the mucous membrane
  of both the stomach and intestine, usually
  causing nausea, vomiting, and diarrhea.
• Acute gastroenteritis usually causes profuse
  watery diarrhea, often c nausea and vomiting, but
  without localized findings.
• Between cramps, the abdomen is completely
  relaxed.

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Infantile Gastroenteritis-

• An endemic viral infection of young children
• (6 mo-12 yrs)
• is especially widespread during winter,
• caused by strains of rotavirus
• the incubation period is 2-4 days,
• with symptoms lasting 3-5 days,
• including abd. pain, diarrhea, fever, and
  vomiting.
• Tx Fluids (PO vs. IV)

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Gastroenteritis

• Invasive Infection The organism enters the
  mucosal cells, destroys them, causing diarrhea
  usually with blood in the stool.
• Enterotoxic syndromes The organisms do not
  invade the mucosa, but produce enterotoxins of
  which act as chemical mediators causing
  hypersecretion of the fluid. Little damage to
  the tissue is done.

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Gastroenteritis Key Symptoms

• Viral
• Abdominal cramps (1)
• Vomiting
• Profuse watery stools
• Myalgias
• Fever
• Headaches
• Arthralgias

• Bacterial Dysentery
• Small volume stools
• Fever
• Tenesmus
• Bloody mucoid stools
• Suprapubic pain relieved by BM

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• Antimotility agents
• Antisecretory agents
• Adsorbents
• Probiotics

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Meta-analysis ondansetron for vomiting in acute
gastroenteritis in children.Szajewska H,
Gieruszczak-Bialek D, Dylag M.Aliment Pharmacol
Ther. 2007 Oct 126

• Four RCTs involving 490 patients
• Ondansetron compared with the control
  significantly increased the chance for vomiting
  cessation soon after drug administration
  relative risk (RR) 1.3, 95 confidence interval
  (CI) 1.2-1.5, number needed to treat (NNT) 5,
• Ondansetron significantly reduced the risk of
  intravenous rehydration
• CONCLUSIONS Despite some clinical benefits,
  there is insufficient evidence to recommend the
  routine use of ondansetron for vomiting during
  acute gastroenteritis in children

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Rotarix - Efficacy

• After 2 doses
•  95.8 protection against severe
  gastro-enteritis.
•  87.1 against any rotavirus gastro-enteritis.
• 100 protection against hospitalisation due to
  rotavirus gastro-enteritis.
•  91.8 protection against gastroenteritis
  requiring medical attention.

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Epidemic Gastroenteritis-

• An epidemic, highly communicable but rather mild
  disease of sudden onset,
• caused by the epidemic gastroenteritis virus
  (especially Norwalk agent),
• with an incubation period of 16-48 hrs
• and a duration of 1-2 days,
• affects all age groups
• infection is associated with some fever, abd.
  cramps, nausea, vomiting, diarrhea, and headache,
  
• one or another of which may be predominant.

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Gastroenteritis

• Acute symptoms may follow a wide variety of
  infectious chemical agents
• Ingestion may occur as a result of person to
  person contact, more commonly via water or food
• The majority of food borne illnesses are caused
  by staphylococcus aureus from contaminated food
  being allowed to stand, producing endotoxins.
• Salmonella Clostridium follow staph poisoning
  as most common. They are found in meats.

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Gastroenteritis (cont.)

• Laboratory
• Stool Culture
• Hemoccult of stool
• Fecal leukocytes
• CBC If WBC count is elevated increased
  likelyhood of bacterial infection.
• (If eosinophils present r/o parasitic infection).
• If C. Difficile is suspected request cytotoxin of
  stool
• Treatment
• With the exception of Giardiasis, amebiasis, C.
  difficile, salmonellosis, shigellosis,
  practically all only need fluid replacement,
  glucose, and electrolyte control (IV NS,
  pedialyte)

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Gastroenteritis (cont.)

• Incubation period
• Chemical poisons onset immediate after ingestion
  of food like Ciguatera or scromboid (scrombotoxin
  found in fish)
• Staphylococcal food poisoning onset within hrs
  after eating contaminated food
• Salmonella Shigella infection onset usually
  within 24-48 hrs (bacillary dysentery)
• Giardiasis infection onset of symptoms after one
  week with recurrent diarrhea.

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Gastroenteritis (cont.)

• Incubation period (cont.)
• Clostridium difficile Antimicrobial use within
  the last 2 weeks
• Botulism Associated Neurological symptoms after
  eating canned food. Symptoms within 24 hrs.
• A h/o homosexuality r/o AIDS, Shigella,
  Campylobacter jejuni, Salmonella, protozoalike
  Entamoeba, cryptosproidia, candida, giardiasis,
  and many others