Title: Managing AGE Among Children Oral Rehydration, Maintenance, and Nutritional Therapy
1Managing AGE Among ChildrenOral Rehydration,
Maintenance, and Nutritional Therapy
- Chris Longhurst, MD, MS
- Valley Journal Club
- August 15, 2009
2Background
- 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
solutions - These recommendations update the previous report
3Background
- 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.
populations.
4Overview 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
5Diarrhea
6Introduction - 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
mortality - 1.5 billion episodes and 1.5 - 2.5 million deaths
occur annually among children aged
7Introduction - Making Progress
- Worldwide mortality decreased in the 1980s and
1990s - 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)
8Introduction - 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.
9Introduction - 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
10Historical 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
11Historical 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
12Historical 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
13Physiologic 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.
14Physiologic Basis for ORT
15Physiologic 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
199472945--55. - Fontaine O, Gore SM, Pierce NF. Rice-based oral
rehydration solution for treating diarrhoea.
Cochrane Database Syst Rev 20002 CD001264.
16Physiologic 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
management.
17Barriers 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
solution - Ozuah PO, Avner JR, Stein RE. Oral rehydration,
emergency physicians, and practice parameters a
national survey. Pediatrics 2002109259--61
18Barriers 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
199493708--11 - The practice of continued feeding during
diarrheal episodes has been difficult to
establish as accepted standard of care
19Home 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.
20Home 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.
21Home Management of Diarrhea
22Assessment 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
23Assessment 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)
24Assessment 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.
25Assessment 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
26Assessment of Dehydration
27Assessment 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.
28Therapy of AGE
29Therapy of AGE
30Therapy of Minimal Dehydration
- Minimal dehydration (
- Encourage use of ORS
- Nutrition should not be restricted
31Therapy 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
32Therapy 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
rehydration. - Nager AL, Wang VJ. Comparison of nasogastric and
intravenous methods of rehydration in pediatric
patients with acute dehydration. Pediatrics
2002109566--72.
33Therapy 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.
34Management 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
35Management 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
36Management 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
198826032815
37Therapy of AGE
38Overview 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
39Dietary Therapy of AGE
- Breastfed infants should continue nursing on
demand - Formula-fed infants should continue their usual
formula immediately upon rehydration
40Dietary 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.
41Dietary 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.
42Dietary 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
output. - 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
199392241--7.
43Dietary 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
fiber. - 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
2001139578--82.
44Dietary 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.
45Pharmacologic 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.
46Pharmacologic 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
recommended.
47Supplemental 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
diarrhea. - 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.
48Supplemental 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.
49Supplemental 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.
50Supplemental 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
2000721516--22.
51Supplemental 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.
52Functional 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.
53Functional 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.
54Functional 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.
55Functional Foods - Prebiotics
- The oligosaccharides in human milk have been
called the prototypic prebiotic because they
foster growth of lactobacilli in the colon of
neonates. - 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.
56Functional 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.
57Choice of ORS
58Choice 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.
59Choice of ORS
- However, a reduced osmolarity ORS has been
associated with less vomiting, less stool output,
and a reduced need for unscheduled intravenous
infusions. - 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
200132381--5.
60Choice 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.
61Choice 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,
2002. - The composition of available oral rehydration
solutions is distinct from other beverages
frequently used inappropriately for rehydration.
62Choice of ORS
63Barriers 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.
64Barriers 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
65Barriers to ORS
- Among patients, barriers to using ORS and
continued nutrition during diarrheal disease
include - 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
66Future 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
67Conclusions 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.
68Conclusions 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.
69Shilo