Diarrhoea Master Final 2011

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Guidelines on the management of

2011


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COLLEGE OF PAEDIATRICS, ACADEMY OF MEDICINE OF MALAYSIA | MALAYSIAN PAEDIATRIC ASSOCIATION

Committee Members

The following are members of the Guidelines Committee:

Professor Lee Way Seah (Chair)– Professor of Paediatrics and Consultant Paediatric Gastroenterologist and

Hepatologist, University of Malaya Medical Centre, Kuala Lumpur;President, College of Paediatrics, Academy of Medicine of Malaysia (AMMCOP)

Datuk Dr. Zulkifli Ismail – Consultant Paediatrian and Paediatric Cardiologist, KPJ Selangor Specialist

Hospital, Shah Alam;President Elect, Asia Pacific Pediatric Association (APPA);Past President, Malaysian Paediatric Association (MPA)

Dr. Nur Atiqah Ng Abdullah– Consultant Paediatrician and Paediatric Gastroenterologist,

Pantai Hospital, Bukit Pantai, Kuala Lumpur

Dr. Oon Meng Kar – Consultant Paediatrician, Klinik Kanak-kanak Oon, Cheras, Kuala Lumpur

Dr. Chai Pei Fan – Consultant Paediatrician and Paediatric Gastroenterologist and Hepatologist,

Pantai Hospital, Bukit Pantai, Kuala Lumpur

©2011 College of Paediatrics, Academy of Medicine of Malaysia and Malaysian Paediatric Association


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THE MANAGEMENT OF ACUTE DIARRHOEA IN CHILDREN 2011

Terms o Reerence

Target audience:

This guidelines aim to cater mainly for paediatricians, primary care physicians and otherfrontline healthcare providers involved in providing care for children.

Format:

This guidelines consist of easy-to-read information with appropriate flow charts. All facts areevidence-based as far as possible. Where evidence is not currently available, the combined and

consensus opinion of the members with adequate consultation with senior colleagues prevailed.

1. The full guidelines on the management of acute diarrhoea in children may be obtainedfrom the following websites:

• CollegeofPaediatrics,AcademyofMedicineofMalaysia(AMMCOP)

http://www.acadmed.org.my/

• MalaysianPaediatricAssociation(MPA)

http://www.mpaweb.org.my/

• MeadJohnsonNutritionMalaysia

http://www.meadjohnsonasia.com.my/home.aspx

2. A pocket reference guide which is a summary of the recommendations for themanagement of acute diarrhoea in children may be obtained from AMMCOP, MPA orMead Johnson Nutrition Malaysia.

3. A wall poster consisting of a flow chart on the management of acute diarrhoea inchildren may be obtained from AMMCOP, MPA or Mead Johnson Nutrition Malaysia.

Content:

The committee members have the sole right to determine the content of the suggestedguidelines. The sponsor did not influence any part of the content at any time.

Disclosure:

No conflict of interest declared by any of the committee members.

Sourceoffunding:

This guidelines was made possible by an unrestricted educational grant from Mead JohnsonNutrition Malaysia.

Disclaimer:

The content / guidelines is based solely on currently available scientific evidence or best clinicalpractice. Healthcare professionals are expected to utilise the information contained withinthis guidelines when exercising their clinical judgement. However, this guidelines shouldnot replace the individual responsibility of the user to make decisions appropriate to thecircumstances of the individual patient and informed by the current indications and accuracyof the drug they are considering.

Copyrightownership:Copyright of the document remains with the College of Paediatrics, Academy of Medicine ofMalaysia (AMMCOP) and Malaysian Paediatric Association (MPA). No part of this publicationmay be reproduced in any form without the prior written permission of the authors.


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Contents

01 Introduction 1

02 Summary o the Guidelines 2

03 Scope o the Guidelines 3

04 Defnition o Diarrhoea 3

05 Clinical Types o Diarrhoeal Diseases 4

06 Important Causative Agents o Gastroenteritis 5

07 Assessment o Acute Diarrhoea 7

08 Management o Childhood Acute Diarrhoea 11

09 Prevention o Childhood AGE 23

10 Special Considerations 25

11 Part I: Algorithm or Managing Acute Gastroenteritis in Children 26

12 Par t II: Algorithm or Managing Acute Gastroenteritis in Children 27

13 Summary o Established Guidelines 28

Reerences 29

Appendix A 34

Appendix B 35




01 Introduction

The first Guidelines on Childhood Acute Gastroenteritis (AGE) in Malaysia were published

in 2001 by the College of Paediatrics, Academy of Medicine of Malaysia (AMMCOP).Since then there has been a proliferation of publications and new findings in this area inthe literature.

Over the last few years, there has been publication of a few guidelines on the managementof childhood AGE. The new WHO Guidelines on the ‘Treatment of Diarrhoea’ (2005)caters mainly for the need of developing countries with a limited health care resources,1

while other guidelines such as those from the Center for Disease Control (CDC) and theEuropean Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN)cater mainly for North America and the European countries, respectively.2-5 Therefore

there is an urgent need to have a local guidelines catering to the specific need for Malaysia.


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02 Summary o the Guidelines

Acute diarrhoea is the second most important cause of childhood mortality worldwide. 6

It is estimated that each year, approximately 1.9 million children younger than 5 years

of age dies of acute diarrhoea.7 At present, there is no detailed epidemiological studyon the burden of acute diarrhoea in children from Malaysia. However, it was estimatedthat 1.3% of all medically certified and uncertified deaths (or 69 deaths per year) amongchildren younger than 5 years of age were due to acute gastroenteritis.8

There are four clinical types of diarrhoea, namely acute watery diarrhoea, acute bloodydiarrhoea, persistent diarrhoea and diarrhoea with severe malnutrition.1 The maincauses of childhood AGE are various enteric viruses and bacteria, although parasites areimportant in certain specific setting.9 Various studies, based mainly on hospital admissionstudies, showed that rotavirus is the most common cause of dehydrating diarrhoea in

young children requiring hospital care in Malaysia.10-20 Important bacterial pathogensinclude non-typhoidal Salmonella and E. coli .21

Proper clinical assessment is required to correctly diagnose the condition, in particularthe severity of dehydration of the child, to provide the appropriate management. Everychild with AGE should be carefully assessed for dehydration and other complications.Criteria for hospital care include moderate-to-severe dehydration, persistent vomiting orworsening diarrhoea even in the absence of dehydration, uncertainty about diagnosis,presence of unfavourable socio-economic factors, or presence of other complications.

In most cases of uncomplicated acute diarrhoea with no significant dehydration, nolaboratory investigation is necessary. A careful history and detailed physical examinationto assess the state of hydration is often all that is necessary.

In most instances with uncomplicated AGE, oral rehydration therapy is the treatment ofchoice and is sufficient in a majority of cases. Drug therapy is unnecessary in most cases,and may even be contraindicated or dangerous.

Children who require rehydration should continue to be breastfed or formula-fed. Foodshould not be withdrawn for longer than 4 – 6 hours after the onset of rehydration. For

children who are formula-fed; formula dilution, gradual reintroduction of feeding andswitching to lactose-free, soy or hydrolysate formulae are not recommended.

Breastfeeding is the best measure for the prevention of AGE in young infants. Rotavirusis the commonest viral pathogen causing severe dehydrating diarrhoea in the worldover. Rotavirus vaccines are not part of the national immunisation schedule in Malaysia.However, it is recommended that vaccination should be considered as part of preventionof rotavirus diarrhoea. Currently there are two rotavirus vaccines available in Malaysia.Both are safe and highly effective in preventing severe dehydrating diarrhoea. 22

When the duration of diarrhoea persists for more than 14 days following an episodeof AGE, lactose intolerance and food protein allergy (most commonly cow milk or soyprotein) complicating AGE, repeated or persistent bacterial or parasitic infections shouldbe excluded. In these cases, consultation with or referral to a specialist with expertise inthis area should be considered.




03 Scope o the Guidelines

The present guidelines are intended to be used in the following settings in Malaysia:

• Primary care settings (out-patient clinic, emergency room)• In-patient care

The guidelines focus mainly on acute diarrhoea in children. It will include variousmanagement aspects including office management of AGE such as:

• Clinical assessment• Rehydration management• Drugs (antibiotics, anti-diarrhoeal, and anti-emetics)

• Probiotics and prebiotics• Nutrition management (manipulation of feeding practices, special formulae)• Vaccines (rotavirus vaccines)

04 Defnition o Diarrhoea

Diarrhoea is defined as the passage of unusually loose or watery stools, usually at least 3times in a 24-hour period. It is the consistency of the stools that is most important, ratherthan the frequency. Frequent passing of formed stools is not considered as diarrhoea.Similarly, breastfed babies pass loose, 'pasty' stools sometimes up to 6 to 7 times a daywhich should not be considered as diarrhoea.1

The main problem with acute diarrhoea is its ability to cause rapid fluid loss throughstools in addition to electrolytes loss. The volume of fluid loss can vary from 5ml/kg

body weight/day to≥

200 ml/kg body weight/day. Dehydration and electrolyte lossesassociated with untreated diarrhoea are the main causes of morbidity and mortality ofchildhood AGE.

Diarrhoea can also be the initial signs of non-gastrointestinal tract illness, includingmeningitis, bacterial pneumonia, otitis media, intussusception and urinary tract infection.In addition, vomiting without diarrhoea can be the first symptom of a host of diversesurgical and metabolic conditions as well.2




05 Clinical Types o Diarrhoeal Diseases 1

Acute Watery Diarrhoea

Acute Bloody Diarrhoea

(dysentery)

Persistent diarrhoea

Diarrhoea with

severe malnutrition

Lasts for several hours or days. The main concern

is dehydration. Weight loss can also occur if

feeding is being withheld for too long.

Should be considered when blood and mucous are

present in the stools. The main dangers are damage

to the intestinal mucosa, sepsis and malnutrition.

Dehydration, although not as common as in acute

watery diarrhoea, may also occur.

Defined as diarrhoea that lasts 14 days or longer.

It may lead to malnutrition and serious infection

with or without dehydration.

A serious condition and warrants special attention to

exclude severe systemic infection, dehydration, severe

electrolytes imbalance, heart failure, and vitamin andmineral deficiencies.




06 Important Causative Agents o Gastroenteritis

Rotavirus is the main cause of virus-induced gastroenteritis in both developed and

developing countries. Other enteric viruses include norovirus, adenovirus, astrovirus andcalicivirus.9

In developed countries, enteric viruses are more important than bacterial pathogens incausing childhood diarrhoea.9 In the developing countries, on the other hand, bacterialpathogens, such as E. coli , non-typhoidal Salmonella, Shigella species, and Campylobacter species are important pathogens, in addition to enteric viruses.9

Developed Countries Developing Countries

Rotavirus

Unknown

Parasites

Bacteria

Adenovirus

Astrovirus

Calicivirus

Other Bacteria

Toxigenic

Escherichia coli

Adapted from Estes MK and Kapikian AZ . In: Fields Virology. 5th ed. Philadelphia: Lippincott, Williams, and Wilkins; 2007:Page 1917-19749

It is also useful to classify important aetiological agents according to age group andnature of stools (Table 1):

Table 1: Important causative agents o gastroenteritis by age group and natureo stool worldwide 4

Rotavirus, astrovirus, calicivirus, enteric adenovirus,enteropathogenic Escherichia coli (EPEC), enterotoxigenicEscherichia coli (ETEC), Vibrio cholerae

≤ 2 years

Enterotoxigenic Escherichia coli (ETEC), rotavirus, Shigella,Vibrio cholerae

2-5 years

Watery

Shigella, shiga-toxin producing Escherichia coli (STEC),

Campylobacter jejuni

≤ 2 years

Shigella, shiga-toxin producing Escherichia coli (STEC),non-typhoidal Salmonella, E. histolytica

2-5 years

Mucousy / bloody




Table 2: Important causative agents o childhood acute gastroenteritis

in Malaysia 10, 12, 14, 19, 20, 23

a includes enteropathogenic and enterotoxigenic E. coli b as a mixed infection

NT Not tested

In Malaysia, major enteric viruses causing childhood AGE are rotavirus, norovirus, andenteric adenovirus (Table 2). For bacterial gastroenteritis, the most important causative

agent is the non-typhoidal Salmonella, followed by Campylobacter , Shigella and E.coli .21

Among the hospitalised children, 40 to 50% of cases are caused by rotavirus and patientsdemonstrated severe vomiting and diarrhoea and severe dehydration.

As for outpatient, the main causative agent is non-typhoidal Salmonella. Only 10% ofthe cases are caused by rotavirus.12 However, the above figure was based on only onestudy in Malaysia which was performed in a private outpatient clinic in Klang Valley witha relatively small number of patients.

Author

Iyngkaran et al 10

Koe et al 12

Lee et al 14

Poo and Lee19

Tan 20

Kahar-Bador& Lee 23

Number

Tested

300

97

228

288

261

568

Rota-

virus

19

9

29

30

54

28

Noro-

virus

9

Adeno-

virus

4

NT

4

NT

NT

2

Salmonella

11

26

10

9

6

Shigella

6

2

0.4b

0

0.4

E. Coli a

10

1

0.4

1

0.4

Campylo-

bacter jejuni

0

3

0

0

0

No

organism

50

59

56

60

39

49

Percentage of aetiological agent (%)




07 Assessment o Acute Diarrhoea 1-5

• Identify the presence of, the degree of, and type

of dehydration• Identify the aetiological agent, if indicated and possible

• Identify co-morbidity and complications

• To assess nutritional status

• To ascertain the most appropriate mode of treatment

The following aspects should be covered:

• Assess the onset, frequency, quantity and character

of both vomiting (presence of bile, blood) and diarrhoea

(presence of blood or mucous)

• Recent oral intake (including breast milk and otherfluids and food)

• Urine output

• Weight before illness (if available)

• Associated symptoms (fever, change in mental status)

• Past medical history (underlying medical problems,

history of other recent infections, medications, immune

compromised states)

• Social history

7.1 Assessment:

History

The following aspects should be covered:

• Accurate body weight• Vital signs (temperature, heart rate, respiratory rate,

blood pressure)

• General conditions

• Eyes: sunken eyes, presence / absence of tears

• Mucous membrane – moist or dry

• Respiratory pattern

• Bowel sounds

• Extremities (perfusion, capillary filling time)

• Skin turgor (anterior abdominal wall)

• Inspection of stool (presence of blood or mucous)

7.2 Assessment:

Physical Examination(see Appendix A)

Classification into severity of dehydration is essential for

appropriate fluid management. The best measure of

dehydration is by the percentage loss of body weight.1

However, the actual weight is often not available. It

should also be emphasised that clinical signs for

dehydration are imprecise.4, 24 Therefore, repeated

assessment is often necessary.

Most useful signs for significant dehydration are: 4, 25

• Prolonged capillary refill time (normal < 2 seconds)

• Reduced skin turgor

• Abnormal respiratory pattern

7.3 Assessment:

Dehydration

Aims of assessment




Table 3: Simplied ways o classiying the degree o dehydration

This is generally defined as a serum sodium concentration

of ≥ 150 mmol/L. Important causes of hypernatraemic

dehydration in childhood acute diarrhoea include young

infants who were predominantly breastfed and were given

inadequate breastfeeding, or given inappropriatelyprepared infant formula. Very little evidence-based

guidelines on this condition have been published recently.

An excellent review on this topic can be found elsewhere.26

Signs and symptoms of hypernatremia largely reflect

central nervous system dysfunction and are prominent

when the increase in the serum sodium concentration is

large or occurs rapidly (i.e., over a period of hours).

Common symptoms in infants include:26

• hyperpnoea

• muscle weakness

• restlessness

• a characteristic high-pitched cry

• insomnia

• lethargy

• and even coma

• convulsions are typically absent except in cases of

inadvertent sodium loading or aggressive rehydration

Hypernatraemic dehydration complicating AGE is

uncommon nowadays. In a one-year prospective studyon 393 children admitted with AGE to a teaching hospital,

the incidence of hypernatraemia was 1.2%, while that of

hyponatraemia was 1.0%.19

7.4 HypernatraemicDehydration

Classification

No signs of dehydration

Some signs of dehydration

Severe dehydration

Fluid deficit as % of body weight

< 3%

3-9%

>9%

Fluid deficit in ml/kg of body weight

< 30 ml/kg

30 – 90 ml/kg

> 90 ml/kg

Adapted from: WHO 2005 1




Generally, in patients with high fever (>39°C), overt

faecal blood, abdominal pain, central nervous

system involvement such as irritability, apathy,

seizures or coma suggest bacterial aetiology.27, 28

Patients presenting with more significant vomiting

and respiratory symptoms suggest viral aetiology.29

Rotavirus causes more severe vomiting and

dehydration. However, it should be emphasised

that the clinical features of both viral and bacterialaetiology overlap considerably.27

7.6Bacterial or Viral Cause?

It is always useful to keep in mind the possibility

that the diagnosis of AGE may be incorrect. Although

gastroenteritis consists of the triad of vomiting, diarrhoea

and fever, other conditions can present with the above

symptoms as well. These include:• Acute appendicitis

• Strangulated hernia

• Intussusception or other causes of bowel obstruction

• Urinary tract infection

• Meningitis and other types of sepsis

• Any cause of raised intracranial pressure

• Diabetic ketoacidosis

• Inborn error of metabolism

• Haemolytic uraemic syndrome

• Inflammatory bowel disease

Always consider another diagnosis in the presence

of any of the following warning signs:23

• Abdominal distension

• Bile-stained vomiting

• Blood in vomitus or stool

(in appropriate clinical setting)

• Severe abdominal pain

• Vomiting in the absence of diarrhoea

• Headache

7.5DifferentialDiagnoses 23




In the majority of children with uncomplicated AGE withno signs of dehydration, laboratory investigations areunnecessary.4

It should also be noted that laboratory assessment for

severity of dehydration are imprecise. The onlylaboratory measurement that appears to be useful indecreasing the likelihood of > 5% dehydration is serumbicarbonate (presence of a normal serum bicarbonate).23 Electrolytes should be measured in moderatelydehydrated children whose history and physicalexamination findings are inconsistent with astraight-forward diarrhoeal illness, and in all severelydehydrated children.4 Electrolytes should also bemeasured in all children requiring intravenous therapy,and during therapy to monitor the presence of hyper-and hyponatraemia, and other electrolyte imbalances.4

• Routine stool culture is not indicated as it is expensiveand does not alter the management in the vast majorityof patients4

• Stools culture is mandatory if profuse watery stools(cholera), blood and mucous in stool (bacterial dysentery)

• Virus – usually not indicated• Parasites – only if clinically indicated• Reducing substances (only in watery stool)

Indications for stool culture are shown in Table 4.

• Bloody diarrhoea (consider dysentery)• Severe watery stools (consider cholera)• Severe and prolonged diarrhoea• Immune-compromised child

7.7 DiagnosticWorkup 1, 4

7.7.1 Stool:

• Specific gravity – may be helpful in the monitoring of

response to therapy in children with severe

dehydration undergoing rehydration therapy

• Urine microscopy – should not be performed

routinely because of possibility of contamination

of urine samples during acute diarrhoea

7.7.2 Urine:

• Urea, Na+, K+, pH, HCO3-

• Complete blood count– if bacterial sepsis is suspected

• Consider glucose monitoring (girls younger

than 5 years with vomiting)

• (± Ca2+, Mg2+ in young infants)

7.7.3 Blood:

Table 4: Indications or stool culture and sensitivity 4

The incidence of hypoglycaemia in children with AGE has been estimated to be between1.9 – 9.2%.30-32 The risk factors for developing hypoglycaemia are female gender, signs ofneuroglycopenia, and frequent vomiting.32




08 Management o Childhood Acute Diarrhoea 1-5

Important points to be considered:

• Identification of children at risk of severe disease or at risk of developingcomplications

• Prevention / correction of dehydration and electrolyte imbalance• Prevention and treatment of complications such as invasive disease, severe

electrolyte imbalance, metabolic and other complications, malnutrition• Drug(s) treatment, which may have a supplementary role• Provision of adequate and appropriate nutrition

8.1 ReferralforHospitalCare

In the majority of cases of uncomplicated childhood AGE with no significant dehydration,outpatient assessment and subsequent home management is all that is necessary.1, 4, 5 Thepresence of the following warning signs is helpful in deciding whether the child needsfurther assessment and possible hospital care:

Table 5: Criteria or Hospital Care 4

• Severe dehydration (> 9% of body weight), shock• Neurological abnormalities (lethargy, seizures, etc.)• Persistent or bilious vomiting (even if no dehydration)• Treatment failure with oral rehydration salts (ORS)• Presence of systemic illness (high fever, toxic looking)• Underlying medical conditions (heart failure, significant

neurodevelopment disabilities)• Caregivers unable to provide adequate care at home or

other social/logistic concerns• Suspected surgical condition, uncertain about diagnosis• Uncertain about degree of dehydration (obese children)

However, it should be emphasised that at present, there are no established,

evidence-based criteria for the hospital admission of childhood AGE.4




8.2 RehydrationinAcuteDiarrhoea

Generalprinciples: Generally, oral rehydration should be used as first-line therapy for themanagement of children with AGE.1-5 When oral rehydration is not feasible, enteral rehydrationvia the naso-gastric route is as effective if not better than intravenous rehydration.1-5, 33 Oral

or enteral rehydration is associated with significantly fewer major complications and a shorterhospital stay compared with intravenous therapy and is successful in most children.

• If no excessive vomiting, home management is

usually sufficient

• If breastfeeding, continue breastfeeding

• If formula-fed, continue usual feeding and offer

extra water

• For older children: continue normal diet with extra fluids

8.2.1 No signs ofdehydration(< 3%)

• If no excessive vomiting and in the absence of

adverse social circumstances, may still consider

outpatient therapy

• ORS 30-90ml/kg within 2-3 hours

• After every diarrhoea episode: ORS 10ml/kg

• Small and frequent feeds with regular assessment

• Hospital referral for admission for IV fluid if there is

persistent vomiting, worsening dehydration despite

adequate therapy

8.2.2 Some signs ofdehydration(3-9%)

• Resuscitation (normal saline / Ringer’s lactate)

• Frequent monitoring

• Immediate referral to hospital for admission

8.2.3 Severe dehydration(> 9%)

8.2.4 Selection of oral rehydration salts (ORS) Table 6 shows the electrolyte content of stool samples obtained from patients with cholera,rotavirus and enteropathogenic Escherichia coli. It is more appropriate to use the original WHOORS in situations where cholera is likely. In other situations, a reduced osmolality ORS is preferred.

Table 6: Mean Stool Na+ and K+ (mmol/L) According to Duration o Diarrhoea

Beore Admission

Adapted from Molla AM et al, 1991 34

Duration(h)

0 – 12

13 – 24

25 – 48

48+

Na(mmol/L)

98

83

63

46

K(mmol/L)

29

37

28

65

EPEC

Na(mmol/L)

67

55

44

44

K(mmol/L)

37

38

26

37

Rotavirus

Na(mmol/L)

53

42

32

34

K(mmol/L)

46

42

28

43

Cholera




Table 7 shows the electrolyte content of various ORS preparations available in Malaysia.Fluids that are not suitable as substitute for ORS include 100 Plus (Table 8).

Table 7: Electrolytes Composition, Osmolality o Various ORS Preparations

Adapted from Santosham M, 1997 35 ; Lee WS, 2009 36

# 1 molecule of citrate is metabolised into 3 molecules of bicarbonate in the body.

Table 8: Fluids Not Appropriate to be Used in Rehydration Therapy

Adapted from Santosham M, 1997 35 ; Lee WS, 2009 36

NA Not available

Standard WHO (1975)

Reduced-Osmolality WHO (2002)

Ministry of Health

ORS Plus (per sachet)

Upha E-Lyte (per sachet)

Weewa ORS (per sachet)

Na(mmol/L)

90

75

56

75

75

90

K(mmol/L)

20

20

20

20

20

21

Cl(mmol/L)

80

65

56

65

65

81

HCO3

(mmol/L)

30

30

20

Glucose(mmol/L)

111

75

137.5

75

75

110

Citrate #

(mmol/L)

10

10

10

Osmolality(mmol/kg)

311

245

290

245

245

312

Coca cola

Apple juice

Chicken broth

Tea

100 Plus

Na(mmol/L)

2

3

250

0

21

K(mmol/L)

0

20

8

0

3.5

Cl(mmol/L)

NA

NA

NA

NA

20

HCO3

(mmol/L)

NA

0

0

0

3

Glucose(mmol/L)

616

600 – 900

0

0

NA

Osmolality(mmol/kg)

618

260

330




8.3 SpecialConsideration

8.3.1 Hypernatraemic dehydration

Hypernatraemic dehydration is defined as serum sodium concentration of more than145 mEq/L. Generally patients with hypernatraemic dehydration respond well to oralrehydration therapy.2 Those with severe dehydration should first receive intravenousfluid therapy for resuscitation. The principal of subsequent rehydration should be theuse of isotonic solution (normal saline) administered at a slower rate, i.e. over 48 hours.Subsequent rehydration can also be achieved with ORS. ORS might be safer thanintravenous fluid because it is less likely to lead to a precipitous increase in intracellularwater associated with seizures and raised intracranial pressure.2

8.4 AdjunctiveTherapyforAcuteDiarrhoea

8.4.1 Antibiotics 1-5

With only a few exceptions, antibiotic therapy should not be given routinely to childrenwith diarrhoea. Such therapy is ineffective and may be harmful.1-5 Majority of gastroenteritiscases in children are viral in origin (rotavirus, norovirus, adenovirus). Thus, antibiotics areonly needed for specific pathogens or defined clinical settings.

Recommendations:

Antibiotics are indicated in the following situations:

• Shigella dysentery - in cases presenting as bloody diarrhoea, these should betreated with an antimicrobial effective for Shigella

• When cholera is suspected• When diarrhoea is associated with another acute infection such as pneumonia

and urinary tract infection• May be indicated for Salmonella gastroenteritis in very young babies

(< 3 months), immune-compromised, immuno-suppressed, systemically ill,achlorhydia




Table 9: Recommended Antibiotics or Acute Diarrhoea 4

Pathogen

Shigellosis 4

Salmonella

Gastroenteritis

(in high risk children) A

Campylobacter

dysentery

Cholera

Antibiotics

Azithromycin

Ceftriaxone

Trimethoprim-

sulfamethoxazole

Amoxicillin

Ceftriaxone

Trimethoprim

-sulfamethoxazole

Ciprofloxacin

Erythromycin

Azithromycin

Doxycycline B

Azithromycin

Total daily doses

Day 1: 12 mg/kgDay 2-5: 6 mg/kg

50 mg/kg

10/50 mg/kg

( TM/SMZ )

40-50 mg/kg

50 mg/kg

10/50 mg/kg

5-10 mg/kg PO

4-7 mg/kg IV

30-50 mg/kg

4-7 mg/kg IV

>8 kg: 4.4 mg/kg

(300 mg as a single

dose in adult)

Day 1: 12 mg/kg

Day 2-5: 6 mg/kg

No. of Doses/day

1

1

2

3

1

2

2

2

2

2

1

1

Duration

5 days

2-5 days

5 days

5 days

2-5 days

5 days

5 days

5 days

5 days

5 days

Single dose

3 days

Note:

A: High risk children include those with underlying immune deficiency, anatomical and functional asplenia, corticosteroid or

immunosuppressive therapy, inflammatory bowel disease, achlorhydria, and neonates and young infants.4

B: World Health Organization (WHO) does not recommend the use of doxycycline in children with cholera.




8.4.2 Anti-emetics

Anti-emetics include drugs such as dimenhydrinate, metoclopromide, domperidone andpromethazine. These may cause sedation that can interfere with oral rehydration therapy.

Due to this reason, anti-emetics are not routinely indicated in children with diarrhoea.

1-5

In addition, anti-emetics may decrease vomiting but increase frequency of diarrhoea.This will lead to retention of fluid and toxin that would have been eliminated throughvomiting.4, 37 Therefore, it is recommended that children with persistent vomiting be givensmall frequent feeds.

Recommendations:

• Not recommended

8.4.3 Anti-diarrhoeal agents and other therapies

Anti-diarrhoeal agents are generally not indicated in childhood AGE.

Various anti-diarrhoeal agents and other therapies are available in the market, and theycan be divided into the following categories:

Table 10: Anti-diarrhoeal Agents and Other Therapies Commonly Used in Childhood

Acute Diarrhoea, According to Efcacy on Diarrhoea and Saety Prole

No. Categories Examples

1 No e ect on diarrhoea or not sae in young children Loperamide

Activated charcoal

2 Possible eects on diarrhoea but not licensed to be

used in young children

Kaolin-pectin

CholestyramineBismuth-salt

3 Uncertain or some eects, but generally sae Diosmectite

Certain probiotics

4 Sae and licensed in children with useul / positive

eects in childhood diarrhoea

Zinc

Certain probiotics

Racecadotril




8.4.3.1 Anti-motility(intestinaltransitinhibitor;opiateagonists)

(i) Loperamide (Imodium® )

• decrease frequency and duration of diarrhoea but have serious side effects(lethargy and death) especially in young children (< 3 years).38 In this meta-analysis, 8 out of 972 children with loperamide had lethargy/death compared tonone from the placebo group.38

Recommendations:

• Not recommended 38

(ii) Diphenoxylate HCl (Lomotil ® )

• anti-peristaltic, mask water loss, prolong intestinal transit time• increases direct contact between intestinal epithelium and noxious agents• usage in Shigella – invasive illness, prolonged fever, prolonged excretion of

Shigella• has narrow therapeutic range, hence risk of overdose and severe side effects

Recommendations:

• Not recommended




8.4.3.2 Intraluminal agents(adsorbents,bulk-forming,etc.)

(i) Silicates - kaolin/pectin39

• binds microorganisms or their products• increase stool consistency but not losses of water and electrolytes• not very effective• may decrease intestinal nutrient or drug absorption

Recommendations:

• Not recommended 39

(i) Silicates – diosmectite (Smecta® )

• binds selected bacterial pathogens and rotavirus• restore integrity of damaged intestinal epithelium• reduce stool output and duration of diarrhoea• shown to be effective in rotavirus diarrhoea• maybe used as adjunctive to ORS• A meta-analysis published in 2006 showed that diosmectite is a useful adjunctive

therapy to childhood acute gastroenteritis.40

A total of six randomised-controlledtrials showed that as compared to placebo, diosmectite significantly reduced theduration of diarrhoea by approximately 22.7 hours, and the chance of a cureon intervention day 3 was significantly increased in diosmectite vs. the controlgroup (RR 1.64, 95% CI: 1.36-1.98).40 A more recent randomised controlledtrial showed that diosmectite reduced stool output in children with acute waterydiarrhoea, especially those who were rotavirus-positive.41

• No side effects 4, 40

Recommendations:• Can be considered as an adjunctive therapy4, 40




8.4.3.3 Anti-secretory

(i) Enkephalinaseinhibitors(racecadotril*)

• enkephalinase-inhibitor, preserving endogenous enkephalinase• significantly reduces stool output (~50%) by 48 hour• well tolerated• no side effects42, 43

One of the major drawbacks on racecadotril is that most randomised-controlled trials

previously were mainly industry-sponsored.42, 43

Recommendations:

• Can be considered as an adjunctive therapy42, 43

* Not commercially available in Malaysia at the time of publication of this guideline.

Table 11: Recommendation on The Use o Anti-emetics and Anti-diarrhoeal Agents on

Childhood Acute Gastroenteritis 4

Agents Recom

Anti-emetics

Dimenhydrinate, Metoclopromide,

Domperidone, Promethazine

Not recommended

Anti-motility

Loperamide

Diphenoxylate HCl

Not recommended

Not recommended

Intramural agents

Silicates-kaolin / pectin

Diosmectite

Not recommended

Can be considered as adjunctive Anti-secretory

Racecadotril

Can be considered as adjunctive

Though commonly used, most of the anti-diarrhoeal agents and other therapies have nopractical benefits and are never indicated for the treatment of acute diarrhoea in children.In fact, some are harmful to children.1-5




8.4.4 Probiotics and prebiotics

Certain strains of probiotics may be an effective adjunct to the management of diarrhoea.4

The effects of probiotics are strain-specific and dose specific. Not all probiotics are

equivalent in terms of efficacy and the efficacy of a specific strain cannot be generalised.Even the most studied strain like Lactobacillus GG show efficacy results that are notalways consistent. In fact, there is no evidence of efficacy for many available commercialpreparations. Products with multiple strains should also have efficacy studies. Addingadditional strains to an effective strain may not necessarily have a synergistic effect orincrease in efficacy.

Recommendations:

• probiotic strain or strains with proven efficacy and in appropriate doses• commercial probiotic products with viability studies

Several meta-analyses and systemic reviews have shown a statistically significant effectand moderate clinical benefit of selected probiotic strains in the treatment of acutewatery diarrhoea.44, 45, 46

The most studied probiotic strains are Lactobacillus GG, lactobacillus acidophilus and Saccharomyces boulardii . The designs of the studies are different, using different strainsand some a combination of different strains. The studies also have different aims andmeasured different end points.




Table 12: Summary o Randomised Controlled Trials (RCT) o The Four Commonest

Strains on Acute Gastroenteritis in Children

Strain Total

numbero RCT

Efcacy

(number o studies)

Efcacy

(number o studies)

Lactobacillus

Rhamnosus GG 47-56

10 • Reduce duration of diarrhoea (5/10)

• Reduce by 8 to 37 hours

• Reduce stool frequency (5/10)

• Effective only for rotavirus positive

patients (2/10)

1.2x1010 to 2x1013 CFU

3 to 7 days

Lactobacillus

acidophilus 57-62


• Reduce by 6.6 to 31 hours

• Reduce stool frequency (1/6)

1x109 to 6x109 CFU

3 to 5 days

Saccharomyces

boulardii 63-67



3 x 109 CFU

5 to 6 days

Lactobacillus

reuteri 68, 69, 70

3* • Reduce duration of diarrhoea (2/3)


1x1010 CFU

5 days

* 2 studies with added Lactobacillus rhamnosus

Currently there is no role for prebiotics in the treatment of AGE.

Recommendations:

• Not recommended




8.5 NutritionalTherapy/SpecialInfantFormula

Children who require rehydration should continue to be fed. Food should not bewithdrawn for longer than 4 – 6 hours after the onset of rehydration. Breastfeedingshould be continued during acute gastroenteritis. For children who are formula-fed,

formula dilution and gradual reintroduction of feeding are not recommended.3, 4, 71, 72

8.5.1 Undiluted vs. diluted formula

A meta-analysis (1994) identified 16 studies (9 randomised controlled trials) that investigatedthe practice of diluting formula 2- to 6-fold for periods ranging from 1 to 6 days.72

Children given undiluted formula has a slight increase in stool frequency (p = 0.046) ascompared to those fed with diluted formula, but there was no difference in the durationof diarrhoea. Children fed with undiluted formula resulted in a significant body weightcatch-up (p = 0.002) as compared to those fed with diluted formula.72

Recommendations:

• In children who are on infant formula, no dilution of formula is recommended




8.5.2 Soy-based or cow milk-based lactose-free formula

The vast majority of young children with acute gastroenteritis can safely continue toreceive lactose-containing milk formula because the number of treatment failures is

negligible compared to children with acute diarrhoea on a lactose-free diet.4, 71, 72, 73

In a meta-analysis on randomised controlled trials comparing lactose-free versus lactose-containing formula after AGE, overall, 22% (95% CI 18-27%) of children who consumedlactose had therapeutic failure compared to 12% (95% CI 9% - 15%) in children who didnot. However, the results were widely heterogeneous.72

However, only 4 out of 14 trials provided information on stool frequency and outputs.Lactose-containing formula caused marginally greater stool outputs than lactose-freeformula.72 Nine trials reported data on the duration of diarrhoea after the initiation of

therapy. Pooled results were widely heterogeneous.72

The effects on weight gain cannotbe reliably assessed as very few studies reported data on weight gain.72

Thus, there is at present no sufficient, evidence-based data to support the routine needto switch from a cow milk-based formula to a soy or hydrolysate formula in a baby withacute gastroenteritis.4

There is also no advantage for soy formula over cow milk formula over severity andduration of diarrhoea, duration of hospitalisation, or treatment failure.74, 75

In addition, the incidence of secondary lactose intolerance after AGE in Malaysian infantsis generally low, about 3% (see section 10.1).

Recommendations:

• In the absence of clinical evidence suggestive of lactose intolerance (pleaserefer to 10.2), a routine change to lactose-free formula (either soy-based orcow milk-based) after an episode of acute diarrhoea is not recommended.




Table 12: Locally Available Soy-based and Lactose-ree Formulae (in Alphabetical Order)

Nature Locally available brand Age range Manuacturer

Cow milk-based

lactose-ree

• Dulac® Lactose Free

• Enfalac A+ LactoFree®

• Mamex® Gold Lactose Free

• Nan AL 110

• NL33

• Novalac AD

• Similac® LF

0 – 12 months

Inancy and beyond

Inancy and beyond

Inancy and beyond

Inancy and beyond

Inancy and beyond

0 – 12 months

Danone Dumex

Mead Johnson

Danone Dumex

Nestle

Morinaga

UP International

Abbott Nutrition

Soy-based • Enfalac A+ ProSobee®

• Isomil®

• Isomil® Plus

• Mamex® Gold Soya Step 1

• Mamex® Gold Soya Step 2

• Nursoy®

Inancy and beyond

0 – 12 months

> 12 months

0 – 6 months

7 months and beyond

Inancy and beyond

Mead Johnson

Abbott Nutrition

Abbott Nutrition

Danone Dumex

Danone Dumex

Pfzer

8.5.4 Zinc

UNICEF and WHO recommend zinc supplementation (10mg below 6 months of age, 20mg inolder infants and children for 10-14 days) as a universal treatment for children with diarrhoea.76 There is no proven benefit of the use of zinc in children without severe malnutrition, withacute gastroenteritis.77 Thus, zinc should only be given to malnourished children.4

Recommendations:

• Zinc can be considered to be given to malnourished children with acute diarrhoea

8.5.5 Others

Homeopathy: Although homeopathy continues to be widely used, there is insufficientevidence to recommend its use for the treatment of acute gastroenteritis in children.4

HerbalMedicine: There is insufficient evidence to recommend in favour or against theuse of herbal medicine for the treatment of acute gastroenteritis in children.4




09 Prevention o Childhood AGE

9.1 GeneralMeasures

General measures of preventing childhood AGE are effective in certain circumstances. 4

The best measure is the promotion of breastfeeding, while others include the use of safedrinking water, and an improvement of environmental hygiene.

9.2 Vaccines

Rotavirus is the commonest viral pathogen causing severe dehydrating diarrhoea in theworld over. Two rotavirus vaccines, RotaTeq® and Rotarix®, both safe and highly efficacious,are available in Malaysia.78, 79 Vaccines for other enteric pathogens are currently notavailable on a routine basis. Rotavirus vaccines are part of routine universal vaccinationprogramme in many countries in the world. First dose of primary vaccination shouldbe given between the age of 6 and 12 weeks, and the full schedule (RotaTeq® 3 dosesand Rotarix® 2 doses) should be completed by the age of 8 months for RotaTeq ® and 6months for Rotarix®.80 Both have been proven to be very safe and are highly effective inpreventing severe dehydrating diarrhoea.80

Rotavirus vaccines are not part of the National Immunisation Program (NIP) in Malaysia.

However, it is recommended that vaccination should be considered as part of preventionof rotavirus diarrhoea.

Recommendations:

• Rotavirus vaccine should be considered as a part of prevention of rotavirus

diarrhoea in Malaysian children.

Table 13: Rotavirus Vaccines Available in Malaysia

Drug Dosage Dosing interval

Rotateq®

(Pentavalent

Rotavirus vaccine)

PO x 3 doses

up to age 32 weeks

1st dose administered at 6-12 weeks o age.

Subsequent 2 doses administered at 4-10

weeks’ interval. 3rd dose should be completed

beore 32 weeks o age.

Rotarix®

(Monovalent

human attenuatedRotavirus vaccine)

PO x 2 doses

up to age 24 weeks

1st dose between 6-14 weeks o age. 2nd dose

between 14-24 weeks o age. Interval between

2 doses should not be < 4 weeks.




9.3 Probioticsandprebiotics

There are studies on the use of probiotics in preventing antibiotic associated diarrhoea(AAD) in children and adults. Studies in children have shown certain strains likeBifidobacterium lactis, Streptococcus thermophilus, Saccharomyces boulardii ,

Lactobacillus rhamnosus are able to reduce the risk of AAD (relative risk [RR] between 0.3to 0.45).81, 82, 83 A meta-analysis on use the use of probiotics to prevent AAD concludedthat treating 7 children at risk of developing AAD will only prevent 1 case of AAD. 84 Another meta-analysis noted that the potential protective effects of probiotics to preventAAD in children did not withstand intention-to-treat analysis.85

There are also studies that looked at using probiotics supplements to prevent acutediarrhoea in children or use of formula with added probiotics with or without prebioticsto prevent acute diarrhoea in children.86, 87 Not all studies showed beneficial effects.88, 89

Prebiotics are defined as non-digestible food compounds that beneficially affect the hostby selectively stimulating the growth and/or activity of one or of a limited number ofbacteria in the large intestine, thereby improving the health of the host. Not all types ofprebiotics are the same or have similar effect. There is very little evidence that prebioticsmay be used as a preventive measure to the management of diarrhoea.90, 91




10 Special Considerations

10.1 PersistentDiarrhoea

Approximately 3-14% of children with acute gastroenteritis developed persistentdiarrhoea.22, 92

In Malaysia, approximately 3% of children with AGE developed persistent diarrhoea(duration > 14 days).22, 92 Bacterial infections, lactose intolerance and food protein allergy(cow milk and soy protein) are the three most important causes of persistent diarrhoeafollowing AGE in Malaysia.22, 92

10.2 LactoseIntolerance

Clinical features of lactose intolerance include:92

• Abdominal pain• Nausea• Persistent diarrhoea• Watery stools• Abdominal distension• ± Perianal excoriation

Secondary lactose intolerance should be suspected when acute diarrhoea fails to resolvewith the presence of the above clinical features.

In children with lactose intolerance without malnutrition, a temporary change tolactose-free formula, either cow milk-based or soy protein-based, is often adequate. Achange to either extensively hydrolysed formula or elemental formula is unnecessary.In malnourished children with persistent diarrhoea, consultation with or referral to anappropriate expert is indicated.




10.3 CowMilkProteinAllergy

Food protein allergy is a potentially serious complication following acute gastroenteritis.Children suspected with cow milk protein allergy should be referred to a specialist withexpertise in this area.

Recommendations:

• In children with lactose intolerance with normal nutritional status, a temporarychange to lactose-free formula, either cow milk-based or soy protein-based,is adequate. A change to either extensively hydrolysed formula or elementalformula is not indicated. Soy formula is generally not recommended in infantsyounger than 6 months of age.

• In a malnourished child with persistent diarrhoea, consultation with or referral

to a specialist with expertise in this area is advisable.• In a child with persistent diarrhoea where food protein allergy is suspected,

consultation with or referral to a specialist with special expertise in this area isadvisable.




11 Part I: Algorithm or Managing Acute

Gastroenteritis in Children

Child with diarrhoea(> 3 times in a 24 hour period)

Watery without

blood and mucous

Do the following:

1. History and physical examination

2. Assess presence, degree and type of dehydration

3. Assess if stools are watery and if blood and mucous

are present

4. It should be emphasised that by just inspecting the

appearance of the stool, it is impossible to differentiate

with certainty viral from bacterial gastroenteritis

5. Assess nutritional status6. Consider other diagnoses in the presence of warning signsa

7. Always consider differential diagnosesb

a. Warning signs:

• Abdominal distension

• Bile-stained vomiting

• Blood in vomitus or stool

• Severe abdominal pain

• Vomiting in the absence

of diarrhoea

• Headache

b. Differential diagnoses:

• Acute appendicitis

• Strangulated hernia

• Intussusception or

other causes of bowel

obstruction

• Urinary tract infection

• Meningitis and other

types of sepsis

• Any cause of raisedintracranial pressure

• Diabetic ketoacidosis

• Inborn error of metabolism

• Haemolytic uraemic

syndrome

• Inflammatory bowel

disease

Consider the following:

1. Stool hanging drop test

for V. cholerae or cultureif the diarrhoea is profuse

and watery in nature or

fishy odour, should

consider cholera as

a possibility

2. Rehydrate as necessary

Blood and mucous

Consider the following:

1. Exclude bacterial pathogens

2. Stool studies for dysentery(Shigella, Campylobacter

jejuni , STEC, non-typhoidal

Salmonella, E. histolytica )

3. Treatment with antibiotic for

the specific pathogen

(see Guideline above)

4. Rehydrate as necessary

Criteria for hospital admission:

• severe dehydration (> 9% of body weight), shock

• neurological abnormalities (lethargy, seizures, etc.)

• persistent or bilious vomiting (even if no dehydration)

• treatment failure with oral rehydration salts (ORS)

• presence of systemic illness (high fever, toxic looking)

• underlying medical conditions (heart failure, significant

neurodevelopment disabilities)

• caregivers unable to provide adequate care at home or

other social/logistic concerns

• suspected surgical condition, uncertain about diagnosis

• uncertain about degree of dehydration (obese children)

Continue and refer to part II: Algorithm for Managing

Acute Gastroenteritis in Children




12 Part II: Algorithm or Managing Acute

Gastroenteritis in Children

Stable

Unstable

Unresolved

No signs of dehydration(<3% loss of body weight)

• Child alert

• Drinks normally

• Heart rate, quality of pulse,

breathing, eyes and capillary

refill are normal

• Tears present and mouth

and tongue are moist

• Instant recoil in skin fold

• Warm extremities

• Normal to decreased

urine output

Some signs of dehydration(3-9% loss of body weight)

• Child normal, fatigued,

restless or irritable

• Thirsty and eager to drink

• Heart rate normal to

increased, quality of pulse

normal to decreased,

breathing normal to fast,

eyes slightly sunken and

capillary refill prolonged

• Tears decreased and mouth

and tongue are dry• Skin fold recoil in

< 2 seconds

• Cool extremities

• Decreased urine output

• If patient has 2 or more

signs of the above, there is

some dehydration

• Breastfeed or milk

feed normally

• Formula dilution not

recommended

• Children may continue

on lactose containing

milk formula

• Continue normal diet in

older children

• Encourage lots of fluid intake

• Offer ORS

Advise to seek medical

attention if persist more than

14 days. Consider lactose

intolerance and

food protein allergy

• Trial of ORS 30-90 ml/kg

(75 ml/kg for moderate

cases) within 4 to 6 hours

• Every diarrhoea episode:

ORS 10 ml/kg

• If ORS by mouth is

refused/inadequate, try

spoon feeding or ORS by

nasogastric /oralgastric

tube feeding

• Breastfeed or milk feed

normally

• Formula dilution notrecommended

• Children may continue

on lactose containing

milk formula

• Continue normal diet in

older children

• Small and frequent feeds

with regular assessment

Hospital referral for admissionfor IV fluid if persistent

vomiting/worsening dehydration

Severe dehydration(>9% loss of body weight)

• Child apathetic, lethargic,

unconscious

• Drinks poorly and unable

to drink

• Tachycardia with

bradycardia in most severe

cases, quality of pulse weak

and thready or impalpable,

breathing deep, eyes deeply

sunken and capillary refill

prolonged and minimal• Tears absent and mouth and

tongue are parched

• Skin fold recoil in

> 2 seconds

• Cold, mottled and cyanotic

extremities

• Minimal urine output

• Resuscitation

(normal saline/Ringer’s lactate)

• Frequent monitoring

Consider intensive care

if not resolved

No admission

if no excessive vomiting

No admission

if no excessive vomiting

Immediate referral to hospital

for admission




13 Summary o Established Guidelines

CDC 20032 WHO 20051 ESPGHAN20084

New SouthWales Health

20105

AMMCOP/MPA2011

Setting Paediatricpractice, withemphasison USpopulations

Developingcountries orcommunitieswith scarcehealthresources

EuropeanCountries,low diarrhoealmorbidity andmortality

Primary casesetting in NewSouth Wales, Australia

Paediatric,primary careand rontlinehealthcareproviders inMalaysia

ORS Yes Yes Yes Yes Yes

Antibiotics Routineuse wastesresources &may lead to

antimicrobialresistance

Not routinelyindicated. Onlyin selectedclinical

situations

Do notrecommendroutine use inotherwise healthy

children

Rarelyrequired.Consultpaediatric

or inectiousspecialist

Not routinelyindicated.Only requiredor specifc

pathogens ordefned clinicalsettings

Antiemetics NR NR NR NR NR

Antimotility(Loperamide,Imodium)

NR NR NR NR NR

Antimotility(DiphenoxylateHCL; Lomotil)

NR NR NR NR NR

Adsorbants(Smectite)

- NR May berecommended

- May beconsidered as anadjunctive

Adsorbants(Kaolin-pectin)

NR NR NR NR NR

Anti-secretory(Racecodotril)

Need morestudies

- May berecommended

- May beconsidered as anadjunctive*

Anti-secretory(Bismuthsubsalicylate)

NR NR (Notpractical,needs tobe givenfrequently)

NR NR NR

Probiotics Should awaiturther clinicaltrials

- Strain-specifc(LactobacillusGG, S. boulardii )

Some benefts.Can be givenwhen anormal diet isreintroduced

May beconsidered asan adjunctive.Should be strain-specifc anddose specifc.

Prebiotics Shouldawait urtherclinical trials

- NR - NR

A switch tolactose-ree, soyor hydrolysate

NR NR NR NR NR

NR Not recommended

* Not commercially available in Malaysia at the time of publication of this guideline.




Reerences

1. World Health Organization. The Treatment of Diarrhoea – A Manual for Physicians andother Senior Health Workers. World Health Organization, 2005.

2. Center for Disease Control (CDC). Managing Acute Gastroenteritis among Children - OralRehydration, Maintenance, and Nutritional Therapy. MMWR 2003.3. Armon K, Stephenson T, MacFaul R, et al . An evidence and consensus based guideline for

acute diarrhoea management. Arch Dis Child 2001;85:132-142.4. Guarino A, Albano F, Ashkenazi S, Gendrel D, Hoekstra JH, Shamir R, Szajewska

H. ESPGHAN/ ESPID Evidence-Based Guidelines for the Management of AcuteGastroenteritis in Children in Europe Expert Working Group. European Society forPaediatric Gastroenterology, Hepatology, and Nutrition/European Society for PaediatricInfectious Diseases evidence-based guidelines for the management of acute gastroenteritisin children in Europe: executive summary. J Pediatr Gastroenterol Nutr 2008;46(5):619-21.

5. Policy Directive of New South Wales Health: Children and Infants with Gastroenteritis –Acute Management. (www.health.nsw.gov.au/policies/) (accessed 8 March, 2011).

6. Murray CJ, Lopez AD. Global mortality, disability, and the contribution of risk factors:Global Burden of Disease Study. Lancet 1997;349(9063):1436-42.

7. Boschi-Pinto C, Velebit L, Shibuya K. Estimating child mortality due to diarrhoea indeveloping countries. Bull World Health Organ 2008;86(9):710-7.

8. Hsu VP, Abdul Rahman H, Wong SL, et al. Estimates of the burden of rotavirus disease inMalaysia. J Infect Dis 2005;192(Suppl. 1):S80–6.

9. Estes MK and Kapikian AZ. Rotaviruses. In: Knipe DM, Howley PM, Griffin DE, et al ., editors. Fields virology . 5th Edition. Philadelphia: Lippincott, Williams & Wilkins; 2007:1917-74.

10. Iyngkaran N, Abidin Z, Lam SK, Puthucheary SD. Acute gastroenteritis in Malaysian children:

aetiological and therapeutic considerations. Med J Malaysia 1980;34:403-8.11. Yap KL, Sabil D, Muthu PA. Human rotavirus infection in Malaysia. III. A one year survey on

the prevalence of rotavirus enteritis in children. Southeast Asian J Trop Med Public Health 1983;14(4):467-9.

12. Koe SL, Tay LK, Puthucheary SD, Lam SK. Infectious agents causing diarrhoea in Malaysianchildren. Malaysian J Child Health 1991;13:29-33.

13. Yap KL, Yasmin AM, Wong YH, et al . A one year community-based study on the incidenceof diarrhoea and rotavirus infection in urban and suburban Malaysian children. Med J Malaysia 1992;47:303-308.

14. Lee WS, Lee SP, Boey CCM. Admission to Hospital with Gastroenteritis in Malaysia.Singapore Paediatr J 1997;39:185-190.

15. Lee WS, Veerasingam PD, Goh AY, Chua KB. Hospitalization of childhood rotavirusinfection from Kuala Lumpur, Malaysia. J Paediatr Child Health 2003;39:518-22.

16. Hung LC, Wong SL, Chan LG, Rosli R, Ng AN, Bresee JS. Epidemiology and straincharacterization of rotavirus diarrhea in Malaysia. Int J Infect Dis 2006;10:470-4.

17. Lee WS, Rajasekaran G, Pee S, Karunakaran R, Hassan HH, Puthucheary SD. Rotavirus andother enteropathogens in childhood acute diarrhoea: a study of two centres in Malaysia. J Paediatr Child Health 2006;42:509-14.

18. Lee WS, Poo MI, Nagaraj S. Estimates of economic burden of providing inpatient care inchildhood rotavirus gastroenteritis from Malaysia. J Paediatr Child Health 2007;43:818-25.

19. Poo MI, Lee WS. Admission to Hospital with Childhood Acute Gastroenteritis in Kuala

Lumpur, Malaysia. Med J Malaysia 2007;62:189-194.20. Tan A. Rotavirus infection in paediatric community-acquired acute gastroenteritis:

a retrospective cross- sectional study in a private hospital in Malaysia. Malaysian J Pediatr Child Health 2007;15:7-15.




21. Lee WS, Puthucheary SD. Bacterial enteropathogens isolated in children with acutegastroenteritis in Kuala Lumpur – a changing trend. Med J Malaysia 2002;57:24-30.

22. Lee WS, CCM Boey. Chronic diarrhoea in infants and young children: causes, clinicalfeatures and outcome. J Paediatr Child Health 1999;35:260-3.

23. Kahar-Bador M, Lu KS, Ngeow YF, Lee WS. The Prevalence and Epidemiology of Viral

Enteropathogens in Childhood Acute Gastroenteritis in Kuala Lumpur, Malaysia. AbstractPresented at the 14th ASEAN Paediatric Congress 2011, Singapore 15-17 April, 2011.

24. Duggan C, Refat M, Hashem M, Wolff M, Fayad I, Santosham M. How valid are clinicalsigns of dehydration in infants? J Pediatr Gastroenterol Nutr 1996;22:56-61.

25. Steiner MJ, DeWalt DA, Byerley JS. Is this child dehydrated? JAMA 2004;291:2746-54.26. Adrogue H, Madias N. Hypernatraemia. New Engl J Med 2000;342:1493-1499.27. Finkelstein JA, Schwartz JS, Torrey S, Fleisher GR. Common clinical features as predictors of

bacterial diarrhea in infants. Am J Emerg Med 1989;7:469-73.28. Koopman JS, Turkish VJ, Monto AS, Gouvea V, Srivastava S, Isaacson RE. Patterns and

etiology of diarrhea in three clinical settings. Am J Epidemiol 1984;119:114-23.29. Jonas A, Yahav J, Soudry A. Clinical features of viral and bacterial gastroenteritis in

hospitalized children. Isr J Med Sci 1982;18:753-9.30. Daral TS, Singh HP, Sachdev HP, et al. Acute dehydrating diarrhoea. Clinical profiles in

neonates and young children. Indian Pediatr 1985;22:333-8.31. Bennish ML, Azad AK, Rahman O, et al. Hypoglycaemia during diarrhea in childhood.

Prevalence, pathophysiology, and outcome. N Engl Med J 1990;322:1357-63.32. Glyn-Jones R. Blood sugar in infantile gastro-enteritis. S Afri Med J 1975;49:1474-633. Fonseca BK, Holgate A, Craig JC. Enteral vs. intravenous rehydration therapy for children

with gastroenteritis: a meta-analysis of randomized controlled trials. Arch Pediatr Adolesc Med 2004;158:483-90.

34. Molla AM, Bari A, Greenough WB 3rd. Food based oral rehydration therapy for improved

management diarrheal disease. Indian J Pediatr 1991;58:745-5535. Santosham M, Keenan EM, Tulloch J, Broun D, Glass R. Oral rehydration therapy for

diarrhea: an example of reverse transfer of technology. Pediatrics 1997;100:E10.36. Ng YJ, Lo YL, Lee WS. Pre-admission therapy for childhood acute diarrhoea--a hospital-

based study. J Clin Pharm Ther 2009;34:55-60.37. Alhashimi D, Al-Hashimi H, Fedorowicz Z. Antiemetics for reducing vomiting related to

acute gastroenteritis in children and adolescents. Cochrane Database Syst Rev 2009;(2):CD005506.

38. Li ST, Grossman DC, Cummings P. Loperamide therapy for acute diarrhea in children:systematic review and meta-analysis. PLoS Med 2007;4(3):e98.

39. Watkinson M. A lack of therapeutic response to kaolin in acute childhood diarrhoeatreated with glucose electrolyte solution. J Trop Pediatr 1982;28(6):306-7.

40. Szajewska H, Dziechciarz P, Mrukowicz J. Meta-analysis: Smectite in the treatment of acuteinfectious diarrhoea in children. Aliment Pharmacol Ther 2006;23(2):217-27.

41. Dupont C, Lee JKF, Garnier P, et al. Oral diosmectite reduces stool output and diarrheaduration in children with acute watery diarrhea. Clin Gastroenterol Hepatol 2009;7:456-462.

42. Salazar-Lindo E, Santisteban-Ponce J, Chea-Woo E, Gutierrez M. Racecadotril in thetreatment of acute watery diarrhea in children. N Engl J Med 2000;343(7):463-7.

43. Cézard JP, Duhamel JF, Meyer M, Pharaon I, Bellaiche M, Maurage C, Ginies JL, Vaillant JM,Girardet JP, Lamireau T, Poujol A, Morali A, Sarles J, Olives JP, Whately-Smith C, Audrain S,Lecomte JM. Efficacy and tolerability of racecadotril in acute diarrhea in children.

Gastroenterology 2001;120: 799-805.44. Szajewska H, Skórka A, Dylag M. Meta-analysis: Saccharomyces boulardii for treating acute

diarrhoea in children. Aliment Pharmacol Ther 2007;25(3):257-64.




45. Szajewska H, Mrukowicz JZ. Probiotics in the treatment and prevention of acute infectiousdiarrhea in infants and children: a systematic review of published randomized, double-blind,placebo-controlled trials. J Pediatr Gastroenterol Nutr 2001;33 Suppl 2:S17-25.

46. Szajewska H, Skórka A, Ruszczyński M, Gieruszczak-Biańek D. Meta-analysis: LactobacillusGG for treating acute diarrhoea in children. Aliment Pharmacol Ther 2007;25(8):871-81.

47. Ritchie BK, Brewster DR, Tran CD, Davidson GP, McNeil Y, Butler RN. Efficacy ofLactobacillus GG in aboriginal children with acute diarrhoeal disease: a randomised clinicaltrial. J Pediatr Gastroenterol Nutr 2010;50(6):619-24.

48. Misra S, Sabui TK, Pal NK. A randomized controlled trial to evaluate the efficacy oflactobacillus GG in infantile diarrhea. J Pediatr 2009;155(1):129-32.

49. Basu S, Paul DK, Ganguly S, Chatterjee M, Chandra PK. Efficacy of high-dose Lactobacillusrhamnosus GG in controlling acute watery diarrhea in Indian children: a randomizedcontrolled trial. J Clin Gastroenterol 2009;43(3):208-13.

50. Basu S, Chatterjee M, Ganguly S, Chandra PK. Efficacy of Lactobacillus rhamnosus GG inacute watery diarrhoea of Indian children: a randomised controlled trial. J Paediatr Child Health 2007;43(12):837-42. Epub 2007 Sep 4.

51. Szymański H, Pejcz J, Jawień M, Chmielarczyk A, Strus M, Heczko PB. Treatment of acuteinfectious diarrhoea in infants and children with a mixture of three Lactobacillus rhamnosusstrains--a randomized, double-blind, placebo-controlled trial. Aliment Pharmacol Ther 2006;23(2):247-53.

52. Guandalini S, Pensabene L, Zikri MA, Dias JA, Casali LG, Hoekstra H, Kolacek S, Massar K,Micetic-Turk D, Papadopoulou A, de Sousa JS, Sandhu B, Szajewska H, Weizman Z.Lactobacillus GG administered in oral rehydration solution to children with acute diarrhea: amulticenter European trial. J Pediatr Gastroenterol Nutr 2000;30(1):54-60.

53. Rautanen T, Isolauri E, Salo E, Vesikari T. Management of acute diarrhoea with lowosmolarity oral rehydration solutions and Lactobacillus strain GG. Arch Dis Child

1998;79(2):157-60.54. Shornikova AV, Isolauri E, Burkanova L, Lukovnikova S, Vesikari T. A trial in the Karelian

Republic of oral rehydration and Lactobacillus GG for treatment of acute diarrhoea. ActaPaediatr 1997;86(5):460-5.

55. Pant AR, Graham SM, Allen SJ, Harikul S, Sabchareon A, Cuevas L, Hart CA. LactobacillusGG and acute diarrhoea in young children in the tropics. J Trop Pediatr 1996;42(3):162-5.

56. Raza S, Graham SM, Allen SJ, Sultana S, Cuevas L, Hart CA. Lactobacillus GG promotesrecovery from acute nonbloody diarrhea in Pakistan. Pediatr Infect Dis J 1995;14(2):107-11.

57. Rerksuppaphol S, Rerksuppaphol L. Lactobacillus acidophilus and Bifidobacterium bifidumstored at ambient temperature are effective in the treatment of acute diarrhoea. Ann Trop

Paediatr 2010;30(4):299-304.58. Khanna V, Alam S, Malik A, Malik A. Efficacy of tyndalized Lactobacillus acidophilus inacute diarrhea. Indian J Pediatr 2005;72(11):935-8.

59. Vivatvakin B, Kowitdamrong E. Randomized control trial of live Lactobacillus acidophilusplus Bifidobacterium infantis in treatment of infantile acute watery diarrhea. J Med Assoc Thai 2006;89 Suppl 3:S126-33.

60. Liévin-Le Moal V, Sarrazin-Davila LE, Servin AL. An experimental study and a randomized,double-blind, placebo-controlled clinical trial to evaluate the antisecretory activity ofLactobacillus acidophilus strain LB against nonrotavirus diarrhea. Pediatrics2007;120(4):e795-803. Epub 2007 Sep 3.

61. Simakachorn N, Pichaipat V, Rithipornpaisarn P, Kongkaew C, Tongpradit P, Varavithya W.

Clinical evaluation of the addition of lyophilized, heat-killed Lactobacillus acidophilus LB tooral rehydration therapy in the treatment of acute diarrhea in children. J Pediatr Gastroenterol Nutr 2000;30(1):68-72.




62. Salazar-Lindo E, Figueroa-Quintanilla D, Caciano MI, Reto-Valiente V, Chauviere G, Colin P;Lacteol Study Group. Effectiveness and safety of Lactobacillus LB in the treatment of mildacute diarrhea in children. J Pediatr Gastroenterol Nutr . 2007;44(5):571-6.

63. Villarruel G, Rubio DM, Lopez F, Cintioni J, Gurevech R, Romero G, Vandenplas Y.Saccharomyces boulardii in acute childhood diarrhoea: a randomized, placebo-controlled

study. Acta Paediatr 2007;96(4):538-41. Epub 2007 Feb 14.64. Grandy G, Medina M, Soria R, Terán CG, Araya M. Probiotics in the treatment of acute

rotavirus diarrhoea. A randomized, double-blind, controlled trial using two differentprobiotic preparations in Bolivian children. BMC Infect Dis 2010;10:253.

65. Eren M, Dinleyici EC, Vandenplas Y. Clinical efficacy comparison of Saccharomyces boulardiiand yogurt fluid in acute non-bloody diarrhea in children: a randomized, controlled, openlabel study. Am J Trop Med Hyg 2010;82(3):488-91.

66. Dinleyici EC, Eren M, Yargic ZA, Dogan N, Vandenplas Y.Clinical efficacy of Saccharomycesboulardii and metronidazole compared to metronidazole alone in children with acutebloody diarrhea caused by amebiasis: a prospective, randomized, open label study. Am J Trop Med Hyg 2008;80(6):953-5.

67. Htwe K, Yee KS, Tin M, Vandenplas Y. Effect of Saccharomyces boulardii in the treatmentof acute watery diarrhea in Myanmar children: a randomized controlled study. Am J TropMed Hyg 2008;78(2):214-6.

68. Rosenfeldt V, Michaelsen KF, Jakobsen M, Larsen CN, Møller PL, Pedersen P, Tvede M,Weyrehter H, Valerius NH, Paerregaard A. Effect of probiotic Lactobacillus strains in youngchildren hospitalized with acute diarrhea. Pediatr Infect Dis J. 2002;21(5):411-6.

69. Rosenfeldt V, Michaelsen KF, Jakobsen M, Larsen CN, Møller PL,Tvede M, Weyrehter H,Valerius NH, Paerregaard A. Effect of probiotic Lactobacillus strains on acute diarrhea in acohort of nonhospitalized children attending day-care centers. Pediatr Infect Dis J. 2002;21(5):417-9.

70. Shornikova AV, Casas IA, Isolauri E, Mykkänen H, Vesikari T. Lactobacillus reuteri as atherapeutic agent in acute diarrhea in young children. J Pediatr Gastroenterol Nutr. 1997;24(4):399-404.

71. Maulén-Radován I, Brown KH, Acosta MA, Fernandez-Varela H. Comparison of a rice-based, mixed diet versus a lactose-free, soy-protein isolate formula for young children with acutediarrhea. J Pediatr 1994;125(5 Pt 1): 699-706.

72. Brown KH, Peerson JM, Fontaine O. Use of nonhuman milks in the dietary management ofyoung children with acute diarrhoea: a meta-analysis of clinical trials. Pediatrics 1994;93:17-27.

73. Sandhu BK. Rationale for early feeding in childhood gastroenteritis. J Pediatr Gastroenterol Nutri 2001;33:S13-S16.

74. Conway SP, Ireson A. Acute gastroenteritis in well nourished infants: comparison of fourfeeding regimens. Arch Dis Child 1989;64(1):87-91.75. Lifshitz F, FagundesNeto U, Garcia Olivo CA, Cordano A, Friedman S. Refeeding of infants

with acute diarrheal disease. J Pediatr 1991;118(4 Pt 2): S99-108.76. WHO/UNICEF Joint Statement: Clinical Management of Acute Diarrhoea. New York, NY,

and Geneva, Switzerland: The United Nations Children’s Fund / WHO: 2004.77. Boran P, Tukuc G, Vagas E, et al . Impact of zinc supplementation in children with acute

diarrhoea in Turkey. Arch Dis Child 2006;91:296-9.78. Vesikari T, Matson DO, Dennehy P, et al . Safety and efficacy of a pentavalent human–

bovine (WC3) reassortant rotavirus vaccine. N Engl J Med 2006;354:23-33.79. Ruiz-Palacios GM, Perez-Schael I, Velazquez FR, et al . Safety and efficacy of an attenuated

vaccine against severe rotavirus gastroenteritis. N Engl J Med 2006;354:11-22.




80. Vesikari T, Van Damme P, Giaquinto C, et al. European Society for Paediatric InfectiousDiseases / European Society for Paediatric Gastroenterology, Hepatology, and NutritionEvidence-based recommendations for rotavirus vaccination in Europe: Executive summary.

J Pediatr Gastroenterol Nutri 2008;46:615-618.81. Ruszczyński M, Radzikowski A, Szajewska H. Clinical trial: effectiveness of Lactobacillus

rhamnosus (strains E/N, Oxy and Pen) in the prevention of antibiotic-associated diarrhoea inchildren. Aliment Pharmacol Ther 2008;28(1):154-61. Epub 2008 Apr 13.

82. Corrêa NB, Péret Filho LA, Penna FJ, Lima FM, Nicoli JR. A randomized formula controlledtrial of Bifidobacterium lactis and Streptococcus thermophilus for prevention of antibiotic-associated diarrhea in infants. J Clin Gastroenterol 2005;39(5):385-9.

83. Kotowska M, Albrecht P, Szajewska H. Saccharomyces boulardii in the prevention ofantibiotic-associated diarrhoea in children: a randomized double-blind placebo-controlledtrial. Aliment Pharmacol Ther 2005;21(5):583-90.

84. Szajewska H, Ruszczyński M, Radzikowski A. Probiotics in the prevention of antibiotic-associated diarrhea in children: a meta-analysis of randomized controlled trials. J Pediatr 2006;149(3):367-372.

85. Johnston BC, Supina AL, Vohra S. Probiotics for pediatric antibiotic-associated diarrhea: ameta-analysis of randomized placebo-controlled trials. CMAJ 2006;175(4):377-83. Erratumin: CMAJ 2006;175(7):777.

86. Binns CW, Lee AH, Harding H, Gracey M, Barclay DV. The CUPDAY Study: prebiotic-probiotic milk product in 1-3-year-old children attending childcare centres. Acta Paediatr 2007;96(11):1646-50.

87. Chouraqui JP, Van Egroo LD, Fichot MC. Acidified milk formula supplemented withbifidobacterium lactis: impact on infant diarrhea in residential care settings. J Pediatr Gastroenterol Nutr 2004;38(3):288-92.

88. Sazawal S, Dhingra U, Hiremath G, Sarkar A, Dhingra P, Dutta A, Verma P, Menon VP,

Black RE. Prebiotic and probiotic fortified milk in prevention of morbidities among children:community-based, randomized, double-blind, controlled trial. PLoS One 2010;5(8):e12164.

89. Hatakka K, Savilahti E, Pönkä A, Meurman JH, Poussa T, Näse L, Saxelin M, Korpela R.Effect of long term consumption of probiotic milk on infections in children attending daycare centres: double blind, randomised trial. BMJ 2001;322(7298):1327.

90. Arslanoglu S, Moro GE, Schmitt J, Tandoi L, Rizzardi S, Boehm G. Early dietary interventionwith a mixture of prebiotic oligosaccharides reduces the incidence of allergic manifestationsand infections during the first two years of life. J Nutr 2008;138(6):1091-5.

91. Bruzzese E, Volpicelli M, Squeglia V, Bruzzese D, Salvini F, Bisceglia M, Lionetti P, CinquettiM, Iacono G, Amarri S, Guarino A. A formula containing galacto- and fructo-oligosaccharides prevents intestinal and extra-intestinal infections: an observational study.Clin Nutr 2009;28(2):156-61. Epub 2009 Feb 23.

92. Lee WS, Gan CS, Chai PF, Harun F. Outcome of nutritional intervention in moderate tosevere malnutrition following persistent diarrhoea – a hospital-based study. Med J Malaysia 2008:63;229-236.

93. Edelman R. Prevention and treatment of infectious diarrhoea. Speculations on the next 10years. Am J Med 1985;78:99-106

94. Salazar-Lindo E. Acute infectious diarrhoea in children - The role of drug treatment.European Gastroenterology & Hepatology Review 2010;6: in press




APPENDIX A

Assessment o dehydration in acute diarrhoea

Symptom No signs o

dehydration

(< 3% loss o

body weight)

Mild to moderate

dehydration

(3-9% loss o

body weight)

Severe dehydration

(> 9% loss o body weight)

Mental status Well, alert N, atigue or restless,

irritable

Apathetic, lethargic,

unconscious

Thirst Drinks N, might

refuse liquids

Thirsty, eager to

drink

Drinks poorly, unable to drink

Heart rate Normal Normal to increased Tachycardia, with bradycardia

in most severe cases

Quality o

pulse

Normal Normal to

decreased

Weak, thready, or impalpable

Breathing Normal Normal, ast Deep

Eyes Normal Slightly sunken Deeply sunken

Tears Present Decreased Absent

Mouth and

tongue

Moist Dry Parched (very dry)

Skin old Instant recoil Recoil in < 2

seconds

Recoil in > 2 seconds

Capillary refll Normal Prolonged Prolonged, minimal

Extremities Warm Cool Cold, mottled, cyanotic

Urine output Normal to

decreased

Decreased Minimal

Adapted from WHO 2005 1 , CDC 20032




APPENDIX B

Anti-Diarrhoeal Drugs

Attributes Loperamide Bismuth

subsalicylate

Smectide Racecadotril

Reduces

secretion

Yes No Yes Yes

Prevents

virulence

No No Yes No

Reduce stool

output

No Yes Yes Yes

Shorten

duration o

diarrhoea

No No Yes Yes

Fast acting - No Yes Yes

Constipation

as a side

eect

Yes No No No

Systemic

side eects

Yes Potentially No No

Does not

interere

with ORS

Not tested Yes Yes Yes

Adapted from Edelman et al, 1985 93 and Salazar-Lindo E. 201094



The sponsor of this educational material was not involved in thedevelopment of this publication and in no way influenced its content.

The fullguidelines on the management of acute diarrhoea in childrenmay be obtained from the following websites:

•CollegeofPaediatrics,AcademyofMedicineofMalaysia(AMMCOP) http://www.acadmed.org.my/

•MalaysianPaediatricAssociation(MPA) http://www.mpaweb.org.my/

•MeadJohnsonNutritionMalaysia http://www.meadjohnsonasia.com.my/home.aspx

©2011 College of Paediatrics, Academy of Medicine of Malaysia and Malaysian Paediatric Association

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Diarrhoea Master Final 2011