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Managing AGE Among Children Oral Rehydration, Maintenance, and Nutritional Therapy


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Title: Managing AGE Among Children Oral Rehydration, Maintenance, and Nutritional Therapy

Managing AGE Among Children Oral Rehydration,
Maintenance, and Nutritional Therapy
  • Chris Longhurst, MD, MS
  • Valley Journal Club
  • August 15, 2009

  • In 1992, CDC prepared the first national
    guidelines for managing childhood diarrhea
  • Since the last recommendations were published in
    MMWR, new data have emerged regarding diarrhea
    treatment and the value of more effective oral
  • These recommendations update the previous report

  • Developed by specialists in managing
    gastroenteritis in consultation with CDC and
    external consultants.
  • Relevant literature was identified through an
    extensive MEDLINE search by using related terms.
  • Articles were then reviewed for their relevance
    to pediatric practice, with emphasis on U.S.

Overview I
  • Introduction
  • Background
  • Epidemiology
  • Historical perspective
  • Physiologic Basis for Using ORT
  • Fluid therapy
  • Home Management of Acute Diarrhea
  • Therapy Based on Degree of Dehydration
  • Clinical Management in the Hospital

Introduction - Burden of Disease
  • United States of America
  • 1.5 million outpatient visits
  • 200,000 hospitalizations
  • 300 deaths/year
  • 1 billion/year in total costs to society for
    rotavirus diarrhea alone!
  • Worldwide
  • Diarrhea is leading cause of morbidity and
  • 1.5 billion episodes and 1.5 - 2.5 million deaths
    occur annually among children aged

Introduction - Making Progress
  • Worldwide mortality decreased in the 1980s and
  • In 1982, 5 million deaths/year occurred
  • In 1992, deaths declined to 3 million/year
  • A substantial portion of the decrease in
    mortality is attributable to worldwide campaigns
    to treat acute diarrhea with oral rehydration
    therapy (ORT)

Introduction - ORT
  • Represents a case of reverse technology transfer,
    because protocols originally implemented to
    benefit patients in developing countries have
    changed the standard of care in industrialized
    countries as well.
  • Santosham M, Keenan EM, Tulloch J, Broun D, Glass
    R. Oral rehydration therapy for diarrhea an
    example of reverse transfer of technology.
    Pediatrics 1997100E10.

Introduction - ORT
  • Two phases of treatment
  • Rehydration phase, in which water and
    electrolytes are administered as oral rehydration
    solution (ORS) to replace existing losses
  • Maintenance phase, which includes both
    replacement of ongoing fluid and electrolyte
    losses and adequate dietary intake

Historical Use of IVF
  • Early attempts at treating dehydration resulting
    from diarrhea were described in the 1830s during
    epidemics of cholera
  • Latta T. Malignant cholera treatment by copious
    injection of aqueous and saline fluids into the
    veins. Lancet 18322274
  • Use of IV fluid did not become widespread until
    100 years later

Historical Use of ORT
  • In the 1940s, oral solutions were developed and
    the effect of potassium replacement in reducing
    mortality was recognized, which led to
    substantial decreases in case fatality rates
  • Studies published in 1968 from Dhaka and Calcutta
    demonstrated the effectiveness of ORS for cholera
    patients, including those with high stool output
  • Nalin DR, Cash RA, Islam R, Molla M, Phillips RA.
    Oral maintenance therapy for cholera in adults.
    Lancet 19682370-3

Historical Use of ORT
  • In 1971, oral electrolyte solutions were tested
    through the large-scale treatment of refugees
  • Mahalanabis D, Choudhuri AB, Bagchi N,
    Bhattacharya AK, Simpson TW. Oral fluid therapy
    of cholera among Bangladesh refugees. Johns
    Hopkins Med J 1973132197--205
  • The resulting success hastened development of the
    first WHO guidelines for ORT and the production
    of standard packets of oral rehydration salts
  • ORT is now accepted as the standard of care for
    the clinically efficacious and cost-effective
    management of acute gastroenteritis

Physiologic Basis for ORT
  • Although three principle mechanisms of sodium
    absorption have been described, the mechanism
    essential to the efficacy of ORS is the coupled
    transport of sodium and glucose molecules at the
    intestinal brush border.
  • Curran PF. Na, Cl, and water transport by rat
    ileum in vitro. J Gen Physiol 1960431137--48.
  • This mechanism remains intact, even in patients
    with severe diarrhea.

Physiologic Basis for ORT
Physiologic Basis for ORT
  • ORS in which additional co-transporters of Na
    (e.g., amino acids or cereals) were added has
    demonstrated promising results, but larger trials
    have not confirmed their efficacy.
  • Bhan MK, Mahalanabis D, Fontaine O, Pierce NF.
    Clinical trials of improved oral rehydration salt
    formulations a review. Bull World Health Organ
  • Fontaine O, Gore SM, Pierce NF. Rice-based oral
    rehydration solution for treating diarrhoea.
    Cochrane Database Syst Rev 20002 CD001264.

Physiologic Basis for ORT
  • Osmolarity is important!
  • Solutions with a high concentration of
    co-transporters increase the risk from hypertonic
    solutions that decrease rather than improve
    sodium and water transport into the bloodstream.
  • However, solutions of lower osmolarity, but that
    maintain the 11 glucose to sodium ratio, perform
    optimally as oral solutions for diarrhea

Barriers to ORT
  • The full benefits have not been realized in
    countries with developed market economies
  • Many reasons, including
  • ingrained use of intravenous (IV) therapy
  • reduced appeal of a technologically simple
  • Ozuah PO, Avner JR, Stein RE. Oral rehydration,
    emergency physicians, and practice parameters a
    national survey. Pediatrics 2002109259--61

Barriers to ORT
  • Especially true in America
  • Approximately 30 of practicing pediatricians
    withhold ORT for children with vomiting or
    moderate dehydration
  • Reis EC, Goepp JG, Katz S, Santosham M. Barriers
    to use of oral rehydration therapy. Pediatrics
  • The practice of continued feeding during
    diarrheal episodes has been difficult to
    establish as accepted standard of care

Home Management of Diarrhea
  • Therapy should begin at home as long as
    caregivers are instructed properly regarding
    signs of dehydration or are able to determine
    when children appear markedly ill or appear not
    to be responding to treatment.

Home Management of Diarrhea
  • Treatment with ORS is simple and enables
    management of uncomplicated cases at home,
    regardless of etiologic agent.
  • Early administration of ORS leads to fewer
    office, clinic, and ED visits and to potentially
    fewer hospitalizations and deaths.
  • Duggan C, Lasche J, McCarty M, et al. Oral
    rehydration solution for acute diarrhea prevents
    subsequent unscheduled follow-up visits.
    Pediatrics 1999104e29.

Home Management of Diarrhea
Assessment of Dehydration
  • Dehydration and electrolyte losses associated
    with untreated diarrhea cause the primary
    morbidity of acute gastroenteritis
  • Goal of assessment is to
  • provide a starting point for treatment
  • conservatively determine which patients can
    safely be sent home for therapy, which ones
    should remain for observation during therapy, and
    which ones should immediately receive more
    intensive therapy

Assessment of Dehydration
  • Prior guidelines, including CDC's 1992
    recommendations and the American Academy of
    Pediatrics (AAP) 1996 guidelines, divide patients
    with dehydration into subgroups for
  • mild (3-5 fluid deficit)
  • moderate (6-9 fluid deficit)
  • severe (10 fluid deficit, shock, or near shock)

Assessment of Dehydration
  • Studies that have evaluated the correlation of
    clinical signs of dehydration with post-treatment
    weight gain indicate that the first signs of
    dehydration might not be evident until 3-4,
    with more numerous clinical signs evident at 5
    and signs indicating severe dehydration not
    evident until fluid loss reaches 9-10.
  • Duggan C, Refat M, Hashem M, Wolff M, Fayad I,
    Santosham M. How valid are clinical signs of
    dehydration in infants? J Pediatr Gastroenterol
    Nutr 19962256--61.

Assessment of Dehydration
  • Because of this threshold effect, these updated
    recommendations group together patients with mild
    to moderate dehydration over a relatively wide
    range of fluid loss (i.e., from 3-9)
  • Nevertheless, the goal of assessment is the same
  • to provide a starting point for treatment
  • to conservatively determine which patients can
    safely be sent home for therapy, which ones
    should remain for observation during therapy, and
    which ones should immediately receive more
    intensive therapy

Assessment of Dehydration
Assessment of Dehydration
  • Supplementary laboratory studies, including serum
    electrolytes, to assess patients with acute
    diarrhea are usually unnecessary.
  • Teach SJ, Yates EW, Feld LG. Laboratory
    predictors of fluid deficit in acutely dehydrated
    children. Clin Pediatr (Phila) 199736395--400.
  • Stool cultures are indicated in cases of
    dysentery (bloody diarrhea) but are not usually
    indicated in acute, watery diarrhea for the
    immunocompetent patient.

Therapy of AGE
Therapy of AGE
Therapy of Minimal Dehydration
  • Minimal dehydration (
  • Encourage use of ORS
  • Nutrition should not be restricted

Therapy of Mod. Dehydration
  • Mild to moderate (3-9 loss of body wt)
  • ORS 50-100 cc/kg over 2-4 hrs
  • Small, frequent feedings
  • A randomized trial of ORS versus IV rehydration
    demonstrated shorter stays in EDs and improved
    parental satisfaction with oral rehydration
  • Atherly-John YC, Cunningham SJ, Crain EF. A
    randomized trial of oral vs intravenous
    rehydration in a pediatric emergency department.
    Arch Pediatr Adolesc Med 20021561240--3

Therapy of Mod. Dehydration
  • Nasogastric (NG) feeding allows continuous
    administration of fluid at a slow, steady rate,
    particularly for patients with persistent
    vomiting or oral ulcers.
  • Rapid rehydration by nasogastric fluid can be
    well-tolerated, more cost-effective, and
    associated with fewer complications than IV
  • Nager AL, Wang VJ. Comparison of nasogastric and
    intravenous methods of rehydration in pediatric
    patients with acute dehydration. Pediatrics

Therapy of Severe Dehydration
  • Severe dehydration constitutes a medical
    emergency requiring immediate IV rehydration.
  • As soon as the severely dehydrated patient's
    level of consciousness returns to normal, therapy
    can usually be changed to the oral route, with
    the patient taking by mouth the remaining
    estimated deficit.

Management in the Hospital
  • When is hospitalization indicated?
  • caregivers cannot provide adequate care at home
  • substantial difficulties exist in administrating
    ORT, including intractable vomiting, ORS refusal,
    or inadequate ORS intake
  • concern exists for other possible illnesses
    complicating the clinical course
  • ORS treatment fails, including worsening diarrhea
    or dehydration despite adequate volumes

Management in the Hospital
  • When is hospitalization indicated?
  • severe dehydration (9 of body weight) exists
  • social or logistical concerns exist that might
    prevent return evaluation, if necessary
  • such factors as young age, unusual irritability
    or drowsiness, progressive course of symptoms, or
    uncertainty of diagnosis exist that might
    indicate a need for close observation

Management in the Hospital
  • Risk factors for suboptimal outcomes
  • Prematurity
  • Young maternal age
  • Black race
  • Rural residence
  • Ho MS, Glass RI, Pinsky PF. Diarrheal deaths in
    American children. Are they preventable? JAMA

Therapy of AGE
Overview II
  • Other therapies
  • Dietary Therapy during AGE
  • Pharmacologic Therapy of AGE
  • Supplemental Zinc Therapy
  • Functional Foods
  • Choice of ORS
  • New solutions
  • Barriers to ORT
  • Limitations of ORT
  • Conclusion

Dietary Therapy of AGE
  • Breastfed infants should continue nursing on
  • Formula-fed infants should continue their usual
    formula immediately upon rehydration

Dietary Therapy of AGE
  • A meta-analysis of clinical trials indicates no
    advantage of lactose-free formulas over
    lactose-containing formulas for the majority of
    infants, although certain infants with
    malnutrition or severe dehydration recover more
    quickly when given lactose-free formula.
  • Brown KH, Peerson J, Fontaine O. Use of nonhuman
    milks in the dietary management of young children
    with acute diarrhea a meta-analysis of clinical
    trials. Pediatrics 19949317--27.

Dietary Therapy of AGE
  • Although medical practice has often favored
    beginning feedings with diluted (e.g., half- or
    quarter-strength) formula, controlled clinical
    trials have demonstrated that this practice is
    unnecessary and is associated with prolonged
    symptoms and delayed nutritional recovery.
  • Santosham M, Foster S, Reid R, et al. Role of
    soy-based, lactose-free formula during treatment
    of acute diarrhea. Pediatrics 198576292--8.
  • Brown KH, Gastanaduy AS, Saavedra JM, et al.
    Effect of continued oral feeding on clinical and
    nutritional outcomes of acute diarrhea in
    children. J Pediatr 1988112191--200.

Dietary Therapy of AGE
  • Formulas containing soy fiber have been marketed
    to physicians and consumers in the United States,
    and added soy fiber has been reported to reduce
    liquid stools without changing overall stool
  • Brown KH, Perez F, Peerson J, et al. Effect of
    dietary fiber (soy polysaccharide) on the
    severity, duration, and nutritional outcome of
    acute, watery diarrhea in children. Pediatrics

Dietary Therapy of AGE
  • A reduction in the duration of antibiotic-associat
    ed diarrhea has been demonstrated among older
    infants and toddlers fed formula with added soy
  • Burks AW, Vanderhoof JA, Mehra S, Ostrom KM,
    Baggs G. Randomized clinical trial of soy formula
    with and without added fiber in
    antibiotic-induced diarrhea. J Pediatr

Dietary Therapy of AGE
  • The BRAT diet is unnecessarily restrictive and,
    similar to juice-centered diets, can provide
    suboptimal nutrition for the patient's
    nourishment and recovering gut.
  • Severe malnutrition can occur after
    gastroenteritis if prolonged gut rest or clear
    fluids are prescribed.
  • Baker SS, Davis AM. Hypocaloric oral therapy
    during an episode of diarrhea and vomiting can
    lead to severe malnutrition. J Pediatr
    Gastroenterol Nutr 1998271--5.

Pharmacologic Therapy
  • Because viruses are the predominant cause of
    acute diarrhea in developed countries, the
    routine use of antimicrobial agents for treating
    diarrhea is not indicated.
  • Nonspecific antidiarrheal agents, antimotility
    agents, antisecretory drugs, and toxin binders
    (e.g., cholestyramine), are commonly used among
    older children but none of these drugs address
    the underlying causes of diarrhea, specifically
    increased secretion by intestinal crypt cells.

Pharmacologic Therapy
  • Reliance on pharmacologic agents shifts the
    therapeutic focus away from appropriate fluid,
    electrolyte, and nutritional therapy, can result
    in adverse events, and can add unnecessarily to
    the economic cost of illness.
  • Because acute diarrhea is a common illness,
    cost-effective analyses should be undertaken
    before routine pharmacologic therapy is

Supplemental Zinc Therapy
  • Multiple reports have linked diarrhea and
    abnormal zinc status, including increased stool
    zinc loss, negative zinc balance, and reduced
    tissue levels of zinc.
  • In India, zinc supplementation was associated
    with a decrease in both the mean number of watery
    stools per day and the number of days with watery
  • Sazawal S, Black RE, Bhan MK, Bhandari N, Sinha
    A, Jalla S. Zinc supplementation in young
    children with acute diarrhea in India. N Engl J
    Med 1995333839--44.

Supplemental Zinc Therapy
  • Prophylactic zinc supplementation in India has
    been associated with a substantially reduced
    incidence of severe and prolonged diarrhea, two
    key determinants of malnutrition and
    diarrhea-related mortality.
  • Bhandari N, Bahl R, Taneja S, et al. Substantial
    reduction in severe diarrheal morbidity by daily
    zinc supplementation in young north Indian
    children. Pediatrics 2002109e86.

Supplemental Zinc Therapy
  • In Peru, zinc administration was associated with
    a reduction in duration of persistent diarrhea.
  • Penny ME, Peerson JM, Marin RM, et al.
    Randomized, community-based trial of the effect
    of zinc supplementation, with and without other
    micronutrients, on the duration of persistent
    childhood diarrhea in Lima, Peru. J Pediatr
    1999135(2 Pt 1)208--17.

Supplemental Zinc Therapy
  • In developing countries, zinc supplementation was
    beneficial for treating children with acute
    diarrhea and as a prophylactic supplement for
    decreasing the incidence of diarrheal disease.
  • Bhutta ZA, Black RE, Brown KH, et al. Prevention
    of diarrhea by zinc supplementation in children
    in developing countries pooled analysis of
    randomized controlled trials. Zinc Investigators'
    Collaborative Group. J Pediatr 1999135689--97.
  • Bhutta ZA, Bird SM, Black RE, et al. Therapeutic
    effects of oral zinc in acute diarrhea in
    children in developing countries pooled analysis
    of randomized controlled trials. Am J Clin Nutr

Supplemental Zinc Therapy
  • A number of trials have supported zinc
    supplementation as an effective agent in treating
    and preventing diarrheal disease.
  • Further research is needed to identify the
    mechanism of action of zinc and to determine its
    optimal delivery to the neediest populations.

Functional Foods - Definitions
  • Functional foods can be defined as foods that
    have an effect on physiologic processes separate
    from their established nutritional function.
  • Probiotics are live microorganisms in fermented
    foods that promote optimal health by establishing
    an improved balance in intestinal microflora.
  • Prebiotics are complex carbohydrates used to
    preferentially stimulate the growth of
    health-promoting intestinal flora.

Functional Foods - Probiotics
  • Reviews have evaluated studies of probiotic use
    in preventing or reducing the severity or
    duration of diarrheal illnesses among children.
  • Vanderhoof JA, Young RJ. Use of probiotics in
    childhood gastrointestinal disorders. J Pediatr
    Gastroenterol Nutr 199827323--32.
  • One meta-analysis concludes that Lactobacillus
    species are both safe and effective as treatment
    for children with infectious diarrhea.
  • Szajewska H, Kotowska M, Mrukowicz JZ, Armanska
    M, Mikolajczyk W. Efficacy of Lactobacillus GG in
    prevention of nosocomial diarrhea in infants. J
    Pediatr 2001138361--5.

Functional Foods - Probiotics
  • A positive recommendation emerges from a
    meta-analysis of probiotic use in
    antibiotic-associated diarrhea.
  • D'Souza AL, Rajkumar C, Cooke J, Bulpitt CJ.
    Probiotics in prevention of antibiotic associated
    diarrhoea meta-analysis. BMJ 20023241361--6.

Functional Foods - Prebiotics
  • The oligosaccharides in human milk have been
    called the prototypic prebiotic because they
    foster growth of lactobacilli in the colon of
  • Dai D, Walker WA. Protective nutrients and
    bacterial colonization in the immature human gut.
    Adv Pediatr 199946353--82.
  • Early data linked higher intake of breast milk
    oligosaccharides with a lowered incidence of
    acute diarrhea.
  • Morrow A, Ruiz-Palacios G, Altaye M, et al. Human
    milk oligosaccharides are associated with
    protection against diarrhea in breast-fed
    infants. Ped Res 200353167A.

Functional Foods - Prebiotics
  • Two randomized trials of prebiotic supplemented
    infant cereal did not demonstrate a reduced
    incidence of diarrheal disease among infants and
    children living in an urban economically
    depressed area.
  • Duggan C, Penny ME, Hibberd P, et al.
    Oligofructose-supplemented infant cereal 2
    randomized, blinded, community-based trials in
    Peruvian infants. Am J Clin Nutr 200377937--42.
  • Specific recommendations regarding their use
    should await further well-controlled human trials.

Choice of ORS
Choice of ORS
  • In 1975, WHO and the United Nations Children's
    Fund (UNICEF) agreed to promote a single ORS
    (WHO-ORS) containing (in mmol/L) sodium 90,
    potassium 20, chloride 80, base 30, and glucose
    111 (2) for use among diverse populations.
  • This composition was selected to allow for a
    single solution to be used for treatment of
    diarrhea caused by different infectious agents.
  • WHO-ORS has been demonstrated during 25 years of
    use to be safe and effective for children and
    adults with all types of infectious diarrhea.

Choice of ORS
  • However, a reduced osmolarity ORS has been
    associated with less vomiting, less stool output,
    and a reduced need for unscheduled intravenous
  • Subsequent clinical research, documented in
    multiple controlled trials and summarized in a
    meta-analysis, has supported adoption of a lower
    osmolarity ORS.
  • Hahn S, Kim Y, Garner P. Reduced osmolarity oral
    rehydration solution for treating dehydration due
    to diarrhoea in children systematic review. BMJ

Choice of ORS
  • On the basis of those and other findings, UNICEF
    and WHO organized a consultation on oral
    rehydration that recommended a reduced osmolarity
    solution for global use.
  • World Health Organization. Reduced osmolarity
    oral rehydration salts (ORS) formulation. New
    York, NY UNICEF House, 2001.

Choice of ORS
  • In May 2002, WHO announced a new ORS formulation
    consistent with these recommendations, with 75
    mEq/L sodium, 75 mmol/L glucose, and total
    osmolarity of 245 mOsm/L.
  • World Health Organization. Oral rehydration salts
    (ORS) a new reduced osmolarity formulation.
    Geneva, Switzerland World Health Organization,
  • The composition of available oral rehydration
    solutions is distinct from other beverages
    frequently used inappropriately for rehydration.

Choice of ORS
Barriers to ORS
  • An informal survey of hospital Internet sites
    revealed outdated recommendations for treating
    diarrhea that include nonstandard fluids.
  • A case report of one child whose care was
    compromised by following advice obtained from a
    prominent pediatric hospital's Internet site
    highlights the continued gap between knowledge
    and practice and the ongoing need to disseminate
    accurate information regarding oral rehydration.
  • Crocco AG, Villasis-Keever M, Jadad AR. Two
    wrongs don't make a right harm aggravated by
    inaccurate information on the Internet.
    Pediatrics 2002109522--3.

Barriers to ORS
  • The advice on the Internet site specified
  • Give clear fluids every 2 to 3 hours. These may
    include Pedialyte (Abbott Laboratories, Abbott
    Park, IL), flat cola, ginger ale, tea with sugar,
    Kool Aid (Kraft Foods, East Hanover, NJ), or
    Jello (Kraft Foods, East Hanover, NJ)
  • Stop all regular foods and fluids
  • For children drinking regular milk, give no milk
    or milk products for 1 week

Barriers to ORS
  • Among patients, barriers to using ORS and
    continued nutrition during diarrheal disease
  • cultural practices
  • lack of parental knowledge
  • lack of training of medical professionals
  • cost of commercially available ORS
  • Among physicians, preference for IV hydration,
    even where evidence indicates improved results
    from oral rehydration remains a major barrier

Future Possibilities for ORS
  • Potential future additives to ORS include
  • substances capable of liberating short-chain
    fatty acids and partially hydrolyzed guar gum
  • probiotics
  • prebiotics
  • zinc
  • protein polymers / amino acids

Conclusions I
  • Treatment of acute diarrhea can rely upon the
    simple and effective therapy of oral rehydration.
  • The critical co-principle of early resumption of
    feeding of children immediately upon rehydration
    has also gained wide acceptance.
  • Recent advances include recognition for the role
    of zinc supplementation in reducing disease
    severity and occurrence, and development of an
    oral rehydration solution of lower osmolarity for
    global use.

Conclusions II
  • ORT is suitable for use among children throughout
    the world.
  • If the principles of therapy outlined in this
    report are accepted by all levels of the medical
    community and if education of parents includes
    teaching them to begin ORT at home, numerous
    deaths and unnecessary clinic visits and
    hospitalizations can be avoided.