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Title: Newer Trends in Management of Acute Diarrhea in Children


1
Newer Trends in Management of Acute Diarrhea in
Children
2
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
3
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
4
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
5
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.

6
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.

7
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.

8
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

9
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
10
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.

11
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

12
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
13
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
14
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
15
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)

16
Antimotility agents
  • Antimotility agents are generally contraindicated
    for children
  • Antimotility agents may reduce diarrheal output
    and cramps, but do not accelerate cure.

17
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)
24
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.

25
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)
26
Racecadotril
  • Antisecretory drug that exerts its antidiarrhoeal
    effects by inhibiting intestinal enkephalinase

27
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
28
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
32
Adsorbents
33
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
34
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
35
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.

36
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
37
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
38
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
39
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
40
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

45
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

46
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

47
Smectite (Diosmec) Indications
  • Indications
  • Symptomatic treatment of acute and chronic
    diarrhea, especially with children.

48
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

49
AGE Adjunct Therapies
  • Dr Rajesh
  • 23/01/2008

50
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.

51
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)

52
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.

53
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

54
  • 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

64
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.

65
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.

66
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.

67
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)

68
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.

69
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
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