Acute Gastroenteritis

Aroona Abdulla

Acute gastroenteritis

AGEPathophysiology, Clinical assessment and InvestigationsAssessment and management of dehydrationOther aspects of managing a child with AGEFollow-up and prevention

ComplicationsDysenteryPersistent diarrhoeaAGE with hypernatraemic dehydration

AGE - Definition

Acute disease of the GIT due to infective cause leading to diarrhoea +/- vomiting of rapid onset

+/- other symptoms including: Nausea, anorexiaFeverAbdominal pain

Diarrhoea = passage of excessively liquid or frequent stools with increased water content. >3 loose stools /dayWide variation in patterns of stool. Diarrhoea a change from the norm

Epidemiology

Worldwide:3-5 billion cases of AGE in children <5 years1.5 million deaths annually (WHO 2004)ORT developed in late 1960’sDeaths from diarrhoea in children <5 years

1979: 4.5 million2002: 1.6 million

WHO: Bulletin of World Health Organization

CausesViruses (about 70%) Rotaviruses Noroviruses (Norwalk-like

viruses) Enteric adenoviruses Caliciviruses Astroviruses Enteroviruses

Protozoa (<10%) Giardia lamblia Entamoeba histolytica Cryptosporidium

Bacteria (10-20%) Shiga toxin producing E. coli Vibrio cholerae Non-typhoid Salmonella spp Salmonella typhi and S

paratyphi Shigella spp Enteropathogenic E. coli Enteroinvasive E. coli Campylobacter jejuni Yersinia enterocolitica Clostridium difficile

Helminths Strongyloides stercoralis

Case 1

8 month old infantLoose stools Vomiting

Case 1- HistoryAge –

For DD (eg. 6 mths – intussusception, lower the age, higher the risk, st in infants < 12mths

Onset and duration: duration risk of dehydration and complicationsConstipation followed by diarrhoea – SalmonellaProtracted diarrhoea – secondary lactose intolerance,

bacterial or protozoan infectionsDiarrhoea –

Watery – Viral, profuse watery – cholera, enterotoxic E. coli Blood and mucus – Shigella, shigatoxin producing E. coli,

Campylobacter and enteroinvasive E. coli Frequency and amount – for assessment of dehydration and

risk (>8/day - risk)

Case 1- HistoryVomiting

Frequency and amount - risk of dehyration (>2/day - risk), need for iv fluid,

DD – meningitis, systemic infections Blood stained vomitus – DHF, Mallory – Weiss Bilious vomiting, projectile vom. – surgical / int. obstruction

FeverHigh fever – shigellosis, enteroinvasive E.coli, campylobacter,

other infections (UTI)High swinging fever - Salmonella typhi/paratyphiPersistent high fever – septicaemia, DF, other infections

Abdominal pain Salmonella, Shigella, enteroinvasive bacteria, (+tenesmus) DD – Sx: intususception in infants, ac. Appendicitis, UTI

Case 1- History

Thirst – for assessment of dehydrationUOP (should be >1ml/kg/hr)

Frequency Last passage of urine

LOC for assessment of dehydrationDD – meningitis, encephalitis in Salmonella spp.

Systemic inquiry – for other infections, and other problems

H/o antibiotic use AB induced diarrhoea, Clostridium difficile

Case 1- History

Feeding historyBottle-feeding and bottle washing / sterilizing

Contact history of diarrhoea in family / householdViral AGE more likely with good hygiene

practices

Hygiene practicesHandwashing, boiling of drinking water

DD – AGE and complicationsInfective AGE – CommonestAcute watery diarrhoea (viral)

>3 stools/dayNo blood in stools

CholeraDiarrhoea with severe dehydration during cholera

outbreakStool culture +ve for Vibrio cholera O1 or O139

Dysentery – blood in the stoolPersistent diarrhoea – lasting > 14 daysDiarrhoea with severe malnutritionDiarrhoea with AB use

DD – less commonOther DD:Other infections

Systemic: septicaemia, meningitis, DF Local: UTI, URTI, hepatitis A

Surgical: intestinal obstruction vomiting, abd pain / crying attacks > diarrhoea pyloric stenosis, intussusception, acute appendicitis, necrotizing enterocolitis, Hirschprung disease

Metabolic Diabetes mellitus/DKA and Inborn errors of metabolism

Other coeliac dis, cows milk protein intolerance, adrenal insuf., Reyes synd

Chronic constipation with overflow incont. – spurious diarrhoea

Pathophysiology

Protective mechanisms of GITacid content of the stomachIgA secreted by the small intestineIgA in breast milk

Limit growth of bac in upper small intestine

predominance of lactobacillus and bifidobacteria in lower GIT

Pathophysiology - Viral

Rotavirus attacks mature enterocytes at the tips of the small intestinal villi killed and shed into lumen

of immature crypt-like cells + shortening of villi (pic)

absorptive and disaccharidase activity+ Ca mediated active secretion of fluids

and electrolytes DIARRHOEA

Pathophysiology - Bacterial Enterotoxic E. coli and Vibrio enterotoxins

promote Cl- mediated active secretion of fluids + electrolytes profuse watery diarrhoea Na – linked co-transport preserved

Enteropathogenic E. coli adhere to the brush border membrane of SI severe mucosal damage May take many weeks to recover

Shigella species and E. coli serotypes O124 and O164 invade colonic mucosa (enteroinvasive) Watery / mucoid diarrhoea and dysentery Blood and pus in stool Pain and tenesmus High fever ( febrile convulsions)

Clostridium difficile prod. cytotoxins direct toxic effect on enterocytes

DehydrationMetabolic disturbances:

Hypernatraemic dehydration lethargy and irritability (particularly marked in hypernatremic

dehydration)rapid correction with i.v. fluids fluid shifts across BBB cerebral

edema convulsions or even death

Hyponatraemia

Loss of HCO3- and K+ in stool, poor tissue perfusion,

Metabolic acidosis hypokalaemia hypoglycemia ketosis renal failure

Complications

may have severe metabolic derangement

Complications

Carbohydrate (lactose, glucose) intolerance milk intolerance

Bloody diarrhea (in Shigella, Salmonella, Campylobacter and E. coli O157)

HUS (E. coli O157)Iatrogenic complications from inappropriate

iv fluidSusceptibility to re-infectionDeath

Case 18 month old baby2 day h/o:

Mod. fever, intermittentLoose watery greenish stools x10 /d, mucus +, no

blood, mod. large amountVomiting 3 times – 1 day, no h’temesis, non-

bilious, food and fluids given, mod. amountUOP fair, passed w stoolsMother is worried because baby is irritable and

not taking anything orally

Case 1Examination:

*Weight – recent weight loss deg. of dehydrationTemperatureLOC and general conditionAssess hydration Abdomen: distension / mass / tendernessNutritional status – malnutritionSystemic examination for other infectionsInspect stools for blood

AssessmentRisk of dehydration age

(highest in infants<12m) frequency of watery stools

(>8/day) vomiting (>2/day) Nutrition

(malnutrition increases risk of complications, esp. electrolyte disturb.)

Pathogen (Vibrio cholerae)

Degree of dehydration *recent weight loss thirst oliguria Clinical examination:

*altered LOC *prolonged “skin-pinch”, *dry oral mucosa, *sunken eyes tears sunken fontanelle CRT –

Sensitivity & specificity, <2sec - v. unlikely in severe

dehydration Haemodynamic status – tachycardia,

peripheral pulses, BP, cold peripheries (vasoconstriction)

tachypnoea

*signs of proved value [I,A] signs of severe dehydration

Assessment of Dehydration (AAP/CDC)Degree Mild Moderate Severe dehydration

Weight loss 3-5% 6-9% >10%

Skin turgor normal (immed) *slow (<2 sec) *v. slow (>2 sec)

Fontanelle normal sunken sunken

Mucous mem. Slightly dry dry dry

Eyes normal *sunken orbits *deeply sunken

Extremities Normal CRT CRT > 2sec cool, mottled

Neuro status normal *normal to listless

*normal to lethargic or comatose

Pulse volume normal slightly mod.

Heart rate normal , (brady in v.sev.)

BP normal normal normal to

UOP slightly < 1ml/kg/hr << 1ml/kg/hr

Thirst slightly *mod. - eager to drink

*very thirsty or too lethargic to indicate

Sources: Adapted from Duggan C, Santosham M, Glass RI. The management of acute diarrhea in children: oral rehydration, maintenance, and nutritional therapy. MMWR 1992;41(No. RR-16):1–20; and World Health Organization. The treatment of diarrhoea: a manual for physicians and othersenior health workers. Geneva, Switzerland: World Health Organization, 1995.

Assessment of Dehydration - WHODegree No or minimal Some dehydration Severe dehydration

Weight loss < 3% - 5% moderate (6-10%) (>10%) +/- shock

Signs < 2 of * 2 or more of * 2 or more of **

Neuro status alert / active *restlessness / irritability

**abnormally sleepy or lethargic

Skin pinch normal (immed) *slow (<2 sec) **v. slow (>2 sec)

Eyes not sunken *sunken **sunken

Thirst normal * - eager to drink ** poorly or not at all

AF normal not sunken sunken

CRT <2 sec > 2sec > 2sec

CVS stable stable circulatory collapse#

RR normal normal tachypnoea, deep br.

# Weak rapid pulse, cool or blue extremities, CRT, or hypotension

Skin pinch test showing laxity with dehydration*Pitfall: Skin pinch may not be elicitable in hypernatremic dehydr.

Child with severe dehydration

Poor GCDrowsySunken eyesChest risen due to

deep breathing in response to acidosis

Case 18 month old baby2 day h/o:

Mod. fever, intermittent Loose watery stools x10 /d, mucus +, no blood, mod. large amount Vomiting 3 times – 1 day, no h’temesis, food and fluids given, mod. amt UOP fair, passed with stools

O/E: T 100F, irritable, feeding vigorously, eyes slightly sunken, no tears seen, tongue dry, skin pinch slightly lax (<2 sec), CRT =2 sec, pulse 140/min, p. pulses good vol, BP 85/ 50mmHg Abdomen soft, CVS, RS: NAD Weight 7.6 kg (5% from 8kg)

Case 1

AssessmentAGE, DD – UTI, Sepsis, Some dehydrationRisk of dehydration +Nutritional status –

Wt for age: 50th cent.

Needs Observation &Rehydration

Investigations - Basic

Stool RE – (if ?bacterial AGE, dysentery or protracted diarrhoea) Pus cells – Shigella, Salmonella spp, enteropathogenic E.coli, RBC – Shigella, enteropathogenic and enteroinvasive E.coli,

Campylobacter, some Salmonella spp. Amoeba – E. hystolytica trophozoites with ingested rbc Giardia lamblia cysts or trophozoites Reducing substances (in protracted diarrhoea with watery

stools and perianal excoriation) lactose intoleranceUrine RE (if ?UTI, esp. in infant < 1yr)WBC counts with DC + platelets (if systemic infection or

DF suspectedCRPElectrolytes – Na, K, Cl

If severe dehydration, high risk of dehydration or vomiting

Further Investigations – complicationsBlood gases for acid base statusUrea, creatinine………………….Stool culture

If bloody diarrhoea / dysentery, HUS, stool pus cells, diarrhoea in immunocompromised, persistent diarrhoea

Blood culture If sepsis +ve clinically or Ix

Hb / PCV / counts / Blood picture If HUS

If surgical cause suspected Abdominal USG – pyloric stenosis, intussusception X-rays – intestinal obstruction

Proctosigmoidoscopy If severe sympt. of colitis or cause of inflammatory

symptoms obscure after lab Ix

If severe dehydration +

Management

Rehydration + replace ongoing lossesORT Iv fluids

AntiemeticsProbioticsNutritional managementZinc supplementationAntibiotics - roleAntidiarrhoeals – role

Physiology of Rehydration

Enterotoxins inhibit GTPase activity cAMP

Cl- secretion Na+ and fluid loss

Preserved reabsorption byNa+ -glucose co-transporter

(SGLT1)Amino acid stimulated Na+

co-transporter

ORS

ORS components New ORS g/L

Old* ORS g/L

ORS compo-nents

New ORS

mmol/L

Old* ORS

mmol/L

Sodium chloride 2.6 3.5 Sodium 75 90

Chloride 65 80

Glucose, anhydrous 13.5 20 Glucose 75 110

Potassium chloride 1.5 1.5 Potassium 20 20

Trisodium citrate, dihydrate

2.9 2.9 Citrate 10 10

Total 20.5 27.9 Total 245 310

*clinical trials Less hyponatremia with Na+ ORS in cholera, but not others

ORS (contd.)Other formulations

Rice-based ORS Shown efficacy in cholera diarrhoeaProvides more glucose for utilizing glucose coupled Na

co-transportProvides amino acids for amino acid coupled NA co-

transportTaste – not palatable, difficult to administer

Home prepared ORT solutionPinch of salt + 2 teaspoons sugar to 1 litre of boiled

cooled waterImportant to prepare ORS following instructions

strictly

Case 22 yr old child2 day h/o:

High gr. fever, continuous Loose watery stools x10 /d, mucus +, no

blood, large amount Vomited 8 times – 1 day, no h’temesis,

taken breastfeeds and fluids, but vomited all

UOP uncertain, ? with stools, last noticed previous night (8hrs)

O/E: T 101F, drowsy, refusing feeds, eyes

sunken, no tears seen, tongue dry, skin pinch (<2 sec),

CRT >2 sec, pulse 150/min, p. pulses vol, cool peripheries

Abdomen soft, RS: NAD CNS: no neck stiff., pupils ER

Case 2

Wt: 10.8 kg No recent weight check

Ix: TLC 25,000 CRP 45mg/dl stool R/E: awaiting

Assessment AGE with sepsis, Severe dehydration – circ. Shock + Risk of further dehydration + complications ?Electrolyte abnorm, metab. Acidosis, glycemia Nutritional status - ?10th cent.

Urgent IVF bolus 100 mL/kg of RL or n. saline

Reassess every 15-30 min+ ORS 5ml/kg/hr as soon as able to take orally

usually after 3-4 hrsAssess after 6 hrs

Still severe dehydration, haemodynamically unstable, no UOP back to C (Resuscitation)

CVS stable, moderate dehydration Go to step B.

C. Resuscitation (Sev. dehyd >10%)

Age 30ml/kg 70ml/kg Total 100ml/kg

Infant <12mths Over 1 hr Over 5 hrs Over 6 hrs

1 – 5 yrs Over ½ hr Over 2½ hrs Over 3 hrs

If vomiting, wait 10 min and restart Antiemetics if repeated vomiting – ondansetron iv or oral

(not in WHO protocol but recent research may be useful)

Reassess hydration after 4 hrs Include weight check Categorize as no, some or severe dehydration Treat as appropriate stage A, B or C

B. Replacement (Some dehyd 3-9%)

Age < 4 mths 4-12 mths 1-2 yrs 2-5 yrs

Weight < 6kg 6 - <10kg 10 - <12kg 12-19kg

ORS (ml)Min. amt

200-400 400-700 700-900 900-1400

Case 2

A. Maintenance - Minimal dehydr. (<3%)

Replace ongoing stool loses with ORSWHO

< 2 yrs – 50-100ml for each loose stool> 2 yrs – 100-200ml for each loose stool

Other protocols 1 mL ORS for each 1gram loose stool or, 10 mL/kg body weight of ORS for each watery or loose

stool, and 2 mL/kg body weight for each episode of emesis.

Other fluids in between ORS – breastfeeds, coconut water, rice cunjee, soup, yogurt

drinksFruit juices, cola and sports drinks are inappropriate

Continue age appropriate feeding

IV Fluids

Indications in Replacement phase: Mod dehydration and unable to retain oral fluids because of

persistent vomitingLOC Ileus Inability to closely supervise or

give ORT

Problems: Fluid overload Electrolytes disturbances occurrence of seizures

AAP - Practice Parameter: The management of Acute gastroenteritis in young children. Pediatrics1996.97(3);424-435.

IV Fluids

Rehydration (algorhythm from BMJ)

BMJ review - Based on WHO

Repletion phase (Mod Dehyd. 6-9%) - AAP

IVF or ORT by NG or oral at 100 mL/kg over 4-6 hrs.Which iv fluid? RLD or DNS, in infants <1yr – n/2+5%D

(½ DNS)Additional ORS to replace ongoing loss of stool*.

1 mL ORS for each 1gram loose stool or, 10 mL/kg body weight of ORS for each watery or loose stool, 2 mL/kg body weight for each episode of emesis.

Hourly reassess:hydration status -calculate continuing stool and emesis losses and add

ongoing losses to replacement.After 4 hrs reassess hydration. If mild dehydration (3-

5%) go to mild dehydration

Repletion phase (mild-mod 3-5%) - AAP

Repletion phase — ORS by mouth or NG (or IVF) at 50 mL/kg over 4 hours. Which iv fluid? RLD or DNS, in infants <1yr – ½ DNS Additional ORS to replace ongoing loss of stool*.

1 mL ORS for each 1gram loose stool or, 10 mL/kg body weight of ORS for each watery or loose stool,

and 2 mL/kg body weight for each episode of emesis.

Reassess hydration and replacement of ongoing losses at least 2 hourly.

After 4 hrs – reassess hydration If no dehydration go to Step A – Maintenance phase

Nutritional Management - DosFeed as early as possibleMilk

Continue breastfeeding - freq Formula need not be diluted when reintroduced

Other fluids -coconut water, rice cunjee, soup, yogurt drinks

Resume normal (solid) diet when appetite returns Yogurt lactobacillus Rice / cereal - complex carbohydrates more glucose and

amino acids fluid reabsorption and stool volume Banana, fruit K+, high energy, fibre stool bulk - solid Vegetables fibre Fish / lean meat (proteins) amino acids help fluid

reabsorption Mix with 1-2 teaspoons of vegetable oil

Nutritional Management – Dont’s

Avoid foods high in fat and sugars Commercial fruit juices, cola and sports drinks are

inappropriate - sugar content, Na

Don’t add sugar or glucose to coconut water Fruit juices should be prepared without adding

sugar as far as possibleAll these can worsen diarrhoea

Pharmacological measures

AntiemeticsProbioticsZincAntibiotics – limited roleAntidiarrhoeals – no role

Antiemetics Ondansetron - useful in reducing vomiting over 8 hrs

vomiting, oral intake, need for iv fluids, hospital admission A/E: diarrhoeal episodes and representation after discharge.

Some other antiemetics suggested:1

Dopamine antagonists – domperidonemetoclopramide - not recommended for use in neonates (in any form). A/E: may increase gut motility

Promethazine (not recommended for children <2 years in any form)A/E: drowsiness and complicates assessment

When to give: during oral replacement / iv replacement

1. Marc Bevan, et al. Proposal for the inclusion of anti-emetic medications (for children) in the who model list of essential medicines. Report - Second Meeting of the Subcommittee of EC on the Selection and Use of Essential Medicines, Geneva, 29 September to 3 October 2008.

2. Elliott EJ, et al. Antiemetics for reducing vomiting related to acute gastroenteritis in children and adolescents. Cochrane Database Syst Rev 2006;(3):CD005506. Evidence-Based Child Health 2006 (in press). Cited in Elizabeth Jane Elliott. Acute gastroenteritis in children. BMJ 2007;334;35-40.

Probiotics

Found to duration of diarrhoea and daily frequency of stools1

Lactobacillus rhamnosus and a mix of L. delbrueckii var bulgaricus, Streptococcus thermophilus, L. acidophilus, and Bifidobacterium bifidum2

Saccharomyces boulardii not shown significant difference 2

1. Allen SJ, Okoko B, Martinez E, Gregorio G, Dans LF. Probiotics for treating infectious diarrhoea. Cochrane Database Syst Rev 2003;(4):CD003048.

2.Canani BC et al. Probiotics for treatment of acute diarrhoea in children: randomised clinical trial of five different preparations. BMJ 2007;335;340;online

Zinc supplementationWHO recommends:

> 6 months: 20 mg /dayfor infants < 6 months: 10 mg /day 1

of zinc suppl. for 10–14 days

Reduce severity and duration of diarrhoea2

Prevents re-infection3

1.WHO/UNICEF Joint statement – Clinical Management of Acute Diarrhoea

2.Bahl, R., et al., ‘Effect of zinc supplementation on clinical course of acute diarrhoea‘ – Report of a Meeting, New Delhi, 7-8 May 2001.Journal of Health, Population and Nutrition, vol. 19, no. 4, December 2001, pp. 338-346.

3.Bhutta Z.A., Black, R.E., Brown K. H., et al., ‘Prevention of diarrhoea and pneumonia by zinc supplementation in children in developing countries: Pooled analysis of randomized controlled trials’, Zinc Investigators’ Collaborative Group, Journal of Paediatrics, vol. 135, no. 6, December 1999, pp. 689-697.

Role of antibiotics

Most AGE do not require nor benefit from ABA/E: AB diarrhoea, prolonged Salmonella excretion

Indicated for AGE complicated by septicaemia with some

bacterial infectionsProtozoal infections – Giardia, Amoebic desenteryEvidence of other systemic or severe local bacterial

infection, eg. UTI, pharyngitis, otitis media, septicaemia, meningitis

WHO 2005. Management of Common illnesses with Limited Resources (Paediatric) - WHO 2005Elizabeth Jane Elliott. Acute gastroenteritis in children. BMJ 2007;334;35-40.

M S Murphy. Guidelines for managing acute gastroenteritis based on a systematic review of published research. Arch. Dis. Child. 1998;79;279-284

Role of antibiotics - Indications

Organism Indication AB

Shigella All ampi, cipro / oflox, ceftrioxone

Vibrio cholerae All doxycyline, tetracycline

Campylobacter Early erythromycin

Salmonella Inf<3mth, typhoid, bacteraemia, localized suppuration

cefotaxime, ceftrioxone, ampicillin, chloramphenicol, cotrim

Clostridium difficile Mod-severe illness metronid, vancoWHO 2005. Management of Common illnesses with Limited Resources (Paediatric) - WHO 2005

Role of antibiotics - IndicationsOrganism Indication AB

E. coli - enterotoxigenic

Severe prolonged illness

cotrimoxazole

E. coli - enteropathogenic

Nursery epidemics, life threatening

cotrimoxazole

E. coli - enteroinvasive

All cotrimoxazole

Aeromonas Dysentery, prolonged diarrhoea

cotrimoxazole

Giardia lamblia If stool Giardia cysts or trophozoites

metronidazole

Entamoeba histolytica

If stool amoebic trophozoites in rbc

metronidazole

WHO 2005. Management of Common illnesses with Limited Resources (Paediatric) - WHO 2005

Role of antidiarrheals

Not recommended Can mask dehydration and ongoing

lossesInadequate evidence on safety

Medicines under research

Racecadotril – antisecretory agentan enkephalinase inhibitorpreserves the antisecretory activity of enkephalinsdoes not slow intestinal transit or promote bacterial

overgrowthPromising as an adjunctive in stool output in clinical

trialsCurrent guidelines do not emphasize use

not required in most cases, may be used only as an adjunct

as mainstay of treatment is rehydration

On discharge advicePrescribe

ORSZinc supplements Probiotics

How to prepare and give ORSContinue to feed

– breastfeeds, fluids and dietary adviceHygeine

– handwashing, avoiding bottle feeds, boiled water for drinking

How to recognize danger signs of dehydration WHO– lethargy/ irritability, thirst, sunken eyes, skin pinch

When to follow-up

Follow-up after discharge

Bring child immediately if:SickLethargic, LOCUnable to drink or breast-feedPoor drinkingUOPDevelops feverBlood in stool

Not improving for 5 days

May need hospital admission

Prevention

Prevention

Intervention area Reduction of diarrhoea frequency

Hygiene 37%

Sanitation 32%

Water supply 25%

Water quality 31%

Multiple 33%

WHO 2006. Ref:

Fewtrell L et al. Water, sanitation, and hygiene interventions to reduce diarrhoea in less developed countries: a systematic review and metaanalysis. The Lancet Infectious Diseases, 2005, 5(1):42–52.

SummaryMainstay of treatment is rehydration – saves livesAntiemetics – useful in reducing vomiting, but may

diarrhoeaProbiotics – useful in diarrhoea duration and freqNutrition – early feeding improves outcome and re-

infection Zinc supplementation - severity and duration of

diarrhoea and re-infectionAntibiotics –

not required and does not benefit in most cases [1A] Indicated for Shigella dysentery and septicaemia

complicating other bacterial AGEAntidiarrhoeals – should not be used

Literature Pocket Book of Hospital Care for Children – Guidelines for the Management of Common

Illnesses with Limited Resources - WHO 2005 Review of Medical Physiology – WF Ganong Nelsons Paediatrics - Forfar & Arneil’s Textbook of Paediatrics – 6th ed Elizabeth Jane Elliott. Acute gastroenteritis in children. BMJ 2007;334;35-40. M S Murphy. Guidelines for managing acute gastroenteritis based on a systematic review

of published research. Arch. Dis. Child. 1998;79;279-284 Practice Parameter: The management of Acute gastroenteritis in young children.

Pediatrics1996.97(3);424-435. Managing Acute Gastroenteritis Among Children - Oral Rehydration, Maintenance, and

Nutritional Therapy. CDC MMWR. November 21, 2003 / Vol. 52 / No. RR-16 WHO/UNICEF Joint statement. Clinical Management of Acute Diarrhoea. May 2004 Allen SJ, Okoko B, Martinez E, Gregorio G, Dans LF. Probiotics for treating infectious

diarrhoea. Cochrane Database Syst Rev 2003;(4):CD003048. Canani BC et al. Probiotics for treatment of acute diarrhoea in children: randomised clinical

trial of five different preparations. BMJ 2007;335;340;online Marc Bevan, Elizabeth Seil, Robin Bell and Jane Robertson. Proposal for the inclusion of

anti-emetic medications (for children) in the WHO model list of essential medicines. Report - Second Meeting of the Subcommittee of the Expert Committee on the Selection and Use of Essential Medicines, Geneva, 29 September to 3 October 2008