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Guidelines on the management of

2011

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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

THE MANAGEMENT OF ACUTE DIARRHOEA IN CHILDREN 2011

Terms of Reference
Target audience:
This guidelines aim to cater mainly for paediatricians, primary care physicians and other frontline healthcare providers involved in providing care for children.

Format:
This guidelines consist of easy-to-read information with appropriate flow charts. All facts are evidence-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 obtained from the following websites:
College of Paediatrics, Academy of Medicine of Malaysia (AMMCOP) http://www.acadmed.org.my/ Malaysian Paediatric Association (MPA) http://www.mpaweb.org.my/ Mead Johnson Nutrition Malaysia http://www.meadjohnsonasia.com.my/home.aspx

2.

A pocket reference guide which is a summary of the recommendations for the management of acute diarrhoea in children may be obtained from AMMCOP, MPA or Mead Johnson Nutrition Malaysia. A wall poster consisting of a flow chart on the management of acute diarrhoea in children may be obtained from AMMCOP, MPA or Mead Johnson Nutrition Malaysia.

3.

Content:
The committee members have the sole right to determine the content of the suggested guidelines. 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.

Source of funding:
This guidelines was made possible by an unrestricted educational grant from Mead Johnson Nutrition Malaysia.

Disclaimer:
The content / guidelines is based solely on currently available scientific evidence or best clinical practice. Healthcare professionals are expected to utilise the information contained within this guidelines when exercising their clinical judgement. However, this guidelines should not replace the individual responsibility of the user to make decisions appropriate to the circumstances of the individual patient and informed by the current indications and accuracy of the drug they are considering.

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

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Contents
01 Introduction 02 Summary of the Guidelines 03 Scope of the Guidelines 04 Definition of Diarrhoea 05 Clinical Types of Diarrhoeal Diseases 06 Important Causative Agents of Gastroenteritis 07 Assessment of Acute Diarrhoea 08 Management of Childhood Acute Diarrhoea 09 Prevention of Childhood AGE 10 Special Considerations 11 Part I: Algorithm for Managing Acute Gastroenteritis in Children 12 Part II: Algorithm for Managing Acute Gastroenteritis in Children 13 Summary of Established Guidelines References Appendix A Appendix B 1 2 3 3 4 5 7 11 23 25 26 27 28 29 34 35

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THE MANAGEMENT OF ACUTE DIARRHOEA IN CHILDREN 2011

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 in the literature. Over the last few years, there has been publication of a few guidelines on the management of 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 the European 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 of 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 study on the burden of acute diarrhoea in children from Malaysia. However, it was estimated that 1.3% of all medically certified and uncertified deaths (or 69 deaths per year) among children younger than 5 years of age were due to acute gastroenteritis.8 There are four clinical types of diarrhoea, namely acute watery diarrhoea, acute bloody diarrhoea, persistent diarrhoea and diarrhoea with severe malnutrition.1 The main causes of childhood AGE are various enteric viruses and bacteria, although parasites are important in certain specific setting.9 Various studies, based mainly on hospital admission studies, showed that rotavirus is the most common cause of dehydrating diarrhoea in young children requiring hospital care in Malaysia.10-20 Important bacterial pathogens include non-typhoidal Salmonella and E. coli.21 Proper clinical assessment is required to correctly diagnose the condition, in particular the severity of dehydration of the child, to provide the appropriate management. Every child with AGE should be carefully assessed for dehydration and other complications. Criteria for hospital care include moderate-to-severe dehydration, persistent vomiting or worsening 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, no laboratory investigation is necessary. A careful history and detailed physical examination to assess the state of hydration is often all that is necessary. In most instances with uncomplicated AGE, oral rehydration therapy is the treatment of choice 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. Food should 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 and switching to lactose-free, soy or hydrolysate formulae are not recommended. Breastfeeding is the best measure for the prevention of AGE in young infants. Rotavirus is the commonest viral pathogen causing severe dehydrating diarrhoea in the world over. Rotavirus vaccines are not part of the national immunisation schedule in Malaysia. However, it is recommended that vaccination should be considered as part of prevention of 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 episode of AGE, lactose intolerance and food protein allergy (most commonly cow milk or soy protein) complicating AGE, repeated or persistent bacterial or parasitic infections should be excluded. In these cases, consultation with or referral to a specialist with expertise in this area should be considered. 2

THE MANAGEMENT OF ACUTE DIARRHOEA IN CHILDREN 2011

03 Scope of 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 various management 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 Definition of Diarrhoea
Diarrhoea is defined as the passage of unusually loose or watery stools, usually at least 3 times in a 24-hour period. It is the consistency of the stools that is most important, rather than 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 day which should not be considered as diarrhoea.1 The main problem with acute diarrhoea is its ability to cause rapid fluid loss through stools 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 losses associated with untreated diarrhoea are the main causes of morbidity and mortality of childhood AGE. Diarrhoea can also be the initial signs of non-gastrointestinal tract illness, including meningitis, bacterial pneumonia, otitis media, intussusception and urinary tract infection. In addition, vomiting without diarrhoea can be the first symptom of a host of diverse surgical and metabolic conditions as well. 2

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05 Clinical Types of Diarrhoeal Diseases 1

Acute Watery Diarrhoea

Lasts for several hours or days. The main concern is dehydration. Weight loss can also occur if feeding is being withheld for too long.

Acute Bloody Diarrhoea (dysentery)

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.

Persistent diarrhoea

Dened as diarrhoea that lasts 14 days or longer. It may lead to malnutrition and serious infection with or without dehydration.

Diarrhoea with severe malnutrition

A serious condition and warrants special attention to exclude severe systemic infection, dehydration, severe electrolytes imbalance, heart failure, and vitamin and mineral deciencies.

THE MANAGEMENT OF ACUTE DIARRHOEA IN CHILDREN 2011

06 Important Causative Agents of Gastroenteritis


Rotavirus is the main cause of virus-induced gastroenteritis in both developed and developing countries. Other enteric viruses include norovirus, adenovirus, astrovirus and calicivirus.9 In developed countries, enteric viruses are more important than bacterial pathogens in causing childhood diarrhoea.9 In the developing countries, on the other hand, bacterial pathogens, 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 and nature of stools (Table 1): Table 1: Important causative agents of gastroenteritis by age group and nature of stool worldwide 4

Watery 2 years
Rotavirus, astrovirus, calicivirus, enteric adenovirus, enteropathogenic Escherichia coli (EPEC), enterotoxigenic Escherichia coli (ETEC), Vibrio cholerae Enterotoxigenic Escherichia coli (ETEC), rotavirus, Shigella, Vibrio cholerae

2-5 years Mucousy / bloody 2 years 2-5 years

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

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Table 2: Important causative agents of childhood acute gastroenteritis in Malaysia 10, 12, 14, 19, 20, 23
Percentage of aetiological agent (%)
Author Iyngkaran et al 10 Koe et al 12 Lee et al 14 Poo and Lee 19 Tan 20 Kahar-Bador & Lee 23 Number Rota- NoroTested virus virus 300 97 228 288 261 568 19 9 29 30 54 28 9 Adeno- Salmonella Shigella E. Coli a Campylovirus bacter jejuni 4 NT 4 NT NT 2 11 26 10 9 6 6 2 0.4b 0 0.4 10 1 0.4 1 0.4 0 3 0 0 0 No organism 50 59 56 60 39 49

includes enteropathogenic and enterotoxigenic E. coli as a mixed infection NT Not tested


b

In Malaysia, major enteric viruses causing childhood AGE are rotavirus, norovirus, and enteric 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 patients demonstrated severe vomiting and diarrhoea and severe dehydration. As for outpatient, the main causative agent is non-typhoidal Salmonella. Only 10% of the cases are caused by rotavirus.12 However, the above figure was based on only one study in Malaysia which was performed in a private outpatient clinic in Klang Valley with a relatively small number of patients.

THE MANAGEMENT OF ACUTE DIARRHOEA IN CHILDREN 2011

07 Assessment of Acute Diarrhoea 1-5


Aims of assessment
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 other uids 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 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 lling time) Skin turgor (anterior abdominal wall) Inspection of stool (presence of blood or mucous) Classication into severity of dehydration is essential for appropriate uid 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 signicant dehydration are: 4, 25 Prolonged capillary rell time (normal < 2 seconds) Reduced skin turgor Abnormal respiratory pattern

7.1 Assessment:

History

7.2 Assessment:

(see Appendix A)

Physical Examination

7.3 Assessment:

Dehydration

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7.4 Hypernatraemic

Dehydration

This is generally dened 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 inappropriately prepared 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 reect 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 study on 393 children admitted with AGE to a teaching hospital, the incidence of hypernatraemia was 1.2%, while that of hyponatraemia was 1.0%.19

Table 3: Simplified ways of classifying the degree of dehydration


Classication Fluid decit as % of body weight Fluid decit in ml/kg of body weight

No signs of dehydration Some signs of dehydration Severe dehydration

< 3% 3-9% >9%

< 30 ml/kg 30 90 ml/kg > 90 ml/kg


Adapted from: WHO 2005 1

THE MANAGEMENT OF ACUTE DIARRHOEA IN CHILDREN 2011

7.5 Differential

Diagnoses 23

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 Inammatory 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

7.6 Bacterial

or Viral Cause?

Generally, in patients with high fever (>39C), 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 signicant 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 bacterial aetiology overlap considerably.27

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7.7 Diagnostic

Workup 1, 4

In the majority of children with uncomplicated AGE with no signs of dehydration, laboratory investigations are unnecessary.4 It should also be noted that laboratory assessment for severity of dehydration are imprecise. The only laboratory measurement that appears to be useful in decreasing the likelihood of > 5% dehydration is serum bicarbonate (presence of a normal serum bicarbonate).23 Electrolytes should be measured in moderately dehydrated children whose history and physical examination ndings are inconsistent with a straight-forward diarrhoeal illness, and in all severely dehydrated children.4 Electrolytes should also be measured in all children requiring intravenous therapy, and during therapy to monitor the presence of hyperand hyponatraemia, and other electrolyte imbalances.4

7.7.1

Stool:

Routine stool culture is not indicated as it is expensive and does not alter the management in the vast majority of patients 4 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.

Table 4: Indications for stool culture and sensitivity 4


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

7.7.2

Urine:

Specic 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 Urea, Na+, K+, pH, HCO3 Complete blood count if bacterial sepsis is suspected Consider glucose monitoring (girls younger than 5 years with vomiting) ( Ca 2+, Mg2+ in young infants)

7.7.3

Blood:

The incidence of hypoglycaemia in children with AGE has been estimated to be between 1.9 9.2%.30-32 The risk factors for developing hypoglycaemia are female gender, signs of neuroglycopenia, and frequent vomiting.32 10

THE MANAGEMENT OF ACUTE DIARRHOEA IN CHILDREN 2011

08 Management of Childhood Acute Diarrhoea 1-5


Important points to be considered: Identification of children at risk of severe disease or at risk of developing complications 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

Referral for Hospital Care

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 The presence of the following warning signs is helpful in deciding whether the child needs further assessment and possible hospital care: Table 5: Criteria for 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

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8.2

Rehydration in Acute Diarrhoea

General principles: Generally, oral rehydration should be used as first-line therapy for the management of children with AGE.1-5 When oral rehydration is not feasible, enteral rehydration via 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 shorter hospital stay compared with intravenous therapy and is successful in most children.
8.2.1

No signs of dehydration
(< 3%)

If no excessive vomiting, home management is usually sufcient If breastfeeding, continue breastfeeding If formula-fed, continue usual feeding and offer extra water For older children: continue normal diet with extra uids 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 uid if there is persistent vomiting, worsening dehydration despite adequate therapy Resuscitation (normal saline / Ringers lactate) Frequent monitoring Immediate referral to hospital for admission

8.2.2

Some signs of dehydration


(3-9%)

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 WHO ORS 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 of Diarrhoea Before Admission
Cholera
Duration
(h) (mmol/L)

EPEC
K
(mmol/L)

Rotavirus
(mmol/L)

Na 98 83 63 46

(mmol/L)

Na 67 55 44 44

(mmol/L)

Na 53 42 32 34

(mmol/L)

0 12 13 24 25 48 48+

29 37 28 65

37 38 26 37

46 42 28 43

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Adapted from Molla AM et al, 199134

THE MANAGEMENT OF ACUTE DIARRHOEA IN CHILDREN 2011

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 of Various ORS Preparations
(mmol/L)

Na 90 75 56 75 75 90

(mmol/L)

(mmol/L)

Cl

(mmol/L)

HCO3 30 30 20

Glucose
(mmol/L)

Citrate #
(mmol/L)

Osmolality
(mmol/kg)

Standard WHO (1975) Reduced-Osmolality WHO (2002) Ministry of Health ORS Plus (per sachet) Upha E-Lyte (per sachet) Weewa ORS (per sachet)

20 20 20 20 20 21

80 65 56 65 65 81

111 75 137.5 75 75 110 10 10 10

311 245 290 245 245 312

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


(mmol/L)

Na 2 3

(mmol/L)

K 0

(mmol/L)

Cl

(mmol/L)

HCO3 NA 0 0 0 3

Glucose
(mmol/L)

Osmolality
(mmol/kg)

Coca cola Apple juice Chicken broth Tea 100 Plus

NA NA NA NA 20

616 600 900 0 0 NA

618

20 8 0 3.5

250 0 21

260

330

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


NA Not available

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8.3 8.3.1

Special Consideration Hypernatraemic dehydration

Hypernatraemic dehydration is defined as serum sodium concentration of more than 145 mEq/L. Generally patients with hypernatraemic dehydration respond well to oral rehydration therapy.2 Those with severe dehydration should first receive intravenous fluid therapy for resuscitation. The principal of subsequent rehydration should be the use 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 than intravenous fluid because it is less likely to lead to a precipitous increase in intracellular water associated with seizures and raised intracranial pressure. 2

8.4 8.4.1

Adjunctive Therapy for Acute Diarrhoea Antibiotics 1-5

With only a few exceptions, antibiotic therapy should not be given routinely to children with diarrhoea. Such therapy is ineffective and may be harmful.1-5 Majority of gastroenteritis cases in children are viral in origin (rotavirus, norovirus, adenovirus). Thus, antibiotics are only 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 be treated 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

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Table 9: Recommended Antibiotics for Acute Diarrhoea 4

Pathogen Shigellosis
4

Antibiotics Azithromycin Ceftriaxone Trimethoprimsulfamethoxazole

Total daily doses Day 1: 12 mg/kg Day 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

No. of Doses/day 1 1 2

Duration 5 days 2-5 days 5 days

Salmonella Gastroenteritis (in high risk children) A

Amoxicillin Ceftriaxone Trimethoprim -sulfamethoxazole Ciprooxacin

3 1 2 2 2 2 2 1

5 days 2-5 days 5 days 5 days 5 days 5 days 5 days Single dose

Campylobacter dysentery

Erythromycin Azithromycin

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

Cholera

Doxycycline B

Azithromycin

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.

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8.4.2

Anti-emetics

Anti-emetics include drugs such as dimenhydrinate, metoclopromide, domperidone and promethazine. 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 through vomiting.4, 37 Therefore, it is recommended that children with persistent vomiting be given small 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 they can be divided into the following categories: Table 10: Anti-diarrhoeal Agents and Other Therapies Commonly Used in Childhood Acute Diarrhoea, According to Efficacy on Diarrhoea and Safety Profile
No. 1 2 Categories No effect on diarrhoea or not safe in young children Possible effects on diarrhoea but not licensed to be used in young children Uncertain or some effects, but generally safe Safe and licensed in children with useful / positive effects in childhood diarrhoea Examples Loperamide Activated charcoal Kaolin-pectin Cholestyramine Bismuth-salt Diosmectite Certain probiotics Zinc Certain probiotics Racecadotril

3 4

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THE MANAGEMENT OF ACUTE DIARRHOEA IN CHILDREN 2011

8.4.3.1 Anti-motility (intestinal transit inhibitor; opiate agonists) (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 metaanalysis, 8 out of 972 children with loperamide had lethargy/death compared to none 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

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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-controlled trials showed that as compared to placebo, diosmectite significantly reduced the duration of diarrhoea by approximately 22.7 hours, and the chance of a cure on intervention day 3 was significantly increased in diosmectite vs. the control group (RR 1.64, 95% CI: 1.36-1.98).40 A more recent randomised controlled trial showed that diosmectite reduced stool output in children with acute watery diarrhoea, especially those who were rotavirus-positive.41 No side effects 4, 40 Recommendations: Can be considered as an adjunctive therapy 4, 40

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8.4.3.3 Anti-secretory (i) Enkephalinase inhibitors (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 therapy 42, 43

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

Table 11: Recommendation on The Use of Anti-emetics and Anti-diarrhoeal Agents on Childhood Acute Gastroenteritis 4
Agents Anti-emetics Dimenhydrinate, Metoclopromide, Domperidone, Promethazine Anti-motility Loperamide Diphenoxylate HCl Intramural agents Silicates-kaolin / pectin Diosmectite Anti-secretory Racecadotril Recommendation Not recommended

Not recommended Not recommended Not recommended Can be considered as adjunctive Can be considered as adjunctive

Though commonly used, most of the anti-diarrhoeal agents and other therapies have no practical benefits and are never indicated for the treatment of acute diarrhoea in children. In fact, some are harmful to children.1-5

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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 not always consistent. In fact, there is no evidence of efficacy for many available commercial preparations. Products with multiple strains should also have efficacy studies. Adding additional strains to an effective strain may not necessarily have a synergistic effect or increase 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 effect and moderate clinical benefit of selected probiotic strains in the treatment of acute watery 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 strains and some a combination of different strains. The studies also have different aims and measured different end points.

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THE MANAGEMENT OF ACUTE DIARRHOEA IN CHILDREN 2011

Table 12: Summary of Randomised Controlled Trials (RCT) of The Four Commonest Strains on Acute Gastroenteritis in Children
Strain Total number of RCT 10 Efficacy (number of studies) 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) Efficacy (number of studies) 1.2x1010 to 2x1013 CFU 3 to 7 days

Lactobacillus Rhamnosus GG 47-56

Lactobacillus acidophilus 57-62

Reduce duration of diarrhoea (5/6) Reduce by 6.6 to 31 hours Reduce stool frequency (1/6) Reduce duration of diarrhoea (4/5) Reduce by 24 to 38 hours

1x10 9 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) Reduce by 30 to 40 hours

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

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8.5

Nutritional Therapy / Special Infant Formula

Children who require rehydration should continue to be fed. Food should not be withdrawn for longer than 4 6 hours after the onset of rehydration. Breastfeeding should 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 investigated the 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) as compared to those fed with diluted formula, but there was no difference in the duration of diarrhoea. Children fed with undiluted formula resulted in a significant body weight catch-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

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8.5.2

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

The vast majority of young children with acute gastroenteritis can safely continue to receive 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 lactosecontaining formula after AGE, overall, 22% (95% CI 18-27%) of children who consumed lactose had therapeutic failure compared to 12% (95% CI 9% - 15%) in children who did not. 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-free formula.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 cannot be 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 need to switch from a cow milk-based formula to a soy or hydrolysate formula in a baby with acute gastroenteritis.4 There is also no advantage for soy formula over cow milk formula over severity and duration of diarrhoea, duration of hospitalisation, or treatment failure.74, 75 In addition, the incidence of secondary lactose intolerance after AGE in Malaysian infants is generally low, about 3% (see section 10.1).

Recommendations: In the absence of clinical evidence suggestive of lactose intolerance (please refer to 10.2), a routine change to lactose-free formula (either soy-based or cow milk-based) after an episode of acute diarrhoea is not recommended.

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Table 12: Locally Available Soy-based and Lactose-free Formulae (in Alphabetical Order)
Nature Cow milkbased lactose-free Locally available brand Dulac Lactose Free Enfalac A+ LactoFree Mamex Gold Lactose Free

Age range 0 12 months Infancy and beyond Infancy and beyond Infancy and beyond Infancy and beyond Infancy and beyond 0 12 months Infancy and beyond 0 12 months > 12 months 0 6 months 7 months and beyond Infancy and beyond

Manufacturer Danone Dumex Mead Johnson Danone Dumex Nestle Morinaga UP International Abbott Nutrition Mead Johnson Abbott Nutrition Abbott Nutrition Danone Dumex Danone Dumex Pfizer

Nan AL 110 NL33 Novalac AD Similac LF

Soy-based

Enfalac A+ ProSobee Isomil

Isomil Plus Mamex Gold Soya Step 1

Mamex Gold Soya Step 2 Nursoy

8.5.4

Zinc

UNICEF and WHO recommend zinc supplementation (10mg below 6 months of age, 20mg in older 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, with acute 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 insufficient evidence to recommend its use for the treatment of acute gastroenteritis in children.4 Herbal Medicine: There is insufficient evidence to recommend in favour or against the use of herbal medicine for the treatment of acute gastroenteritis in children.4 24

THE MANAGEMENT OF ACUTE DIARRHOEA IN CHILDREN 2011

09 Prevention of Childhood AGE


9.1 General Measures

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 safe drinking water, and an improvement of environmental hygiene.

9.2

Vaccines

Rotavirus is the commonest viral pathogen causing severe dehydrating diarrhoea in the world 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 not available on a routine basis. Rotavirus vaccines are part of routine universal vaccination programme in many countries in the world. First dose of primary vaccination should be given between the age of 6 and 12 weeks, and the full schedule (RotaTeq 3 doses and Rotarix 2 doses) should be completed by the age of 8 months for RotaTeq and 6 months for Rotarix.80 Both have been proven to be very safe and are highly effective in preventing 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 prevention of 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 Rotateq (Pentavalent Rotavirus vaccine)

Dosage PO x 3 doses up to age 32 weeks

Dosing interval 1st dose administered at 6-12 weeks of age. Subsequent 2 doses administered at 4-10 weeks interval. 3rd dose should be completed before 32 weeks of age. 1st dose between 6-14 weeks of age. 2nd dose between 14-24 weeks of age. Interval between 2 doses should not be < 4 weeks.

Rotarix (Monovalent human attenuated Rotavirus vaccine)

PO x 2 doses up to age 24 weeks

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9.3

Probiotics and prebiotics

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 like Bifidobacterium lactis, Streptococcus thermophilus, Saccharomyces boulardii, Lactobacillus rhamnosus are able to reduce the risk of AAD (relative risk [RR] between 0.3 to 0.45).81, 82, 83 A meta-analysis on use the use of probiotics to prevent AAD concluded that 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 prevent AAD in children did not withstand intention-to-treat analysis.85 There are also studies that looked at using probiotics supplements to prevent acute diarrhoea in children or use of formula with added probiotics with or without prebiotics to 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 host by selectively stimulating the growth and/or activity of one or of a limited number of bacteria in the large intestine, thereby improving the health of the host. Not all types of prebiotics are the same or have similar effect. There is very little evidence that prebiotics may be used as a preventive measure to the management of diarrhoea.90, 91

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10 Special Considerations
10.1 Persistent Diarrhoea
Approximately 3-14% of children with acute gastroenteritis developed persistent diarrhoea.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 diarrhoea following AGE in Malaysia. 22, 92

10.2 Lactose Intolerance


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 resolve with the presence of the above clinical features. In children with lactose intolerance without malnutrition, a temporary change to lactose-free formula, either cow milk-based or soy protein-based, is often adequate. A change to either extensively hydrolysed formula or elemental formula is unnecessary. In malnourished children with persistent diarrhoea, consultation with or referral to an appropriate expert is indicated.

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10.3 Cow Milk Protein Allergy


Food protein allergy is a potentially serious complication following acute gastroenteritis. Children suspected with cow milk protein allergy should be referred to a specialist with expertise in this area. Recommendations: In children with lactose intolerance with normal nutritional status, a temporary change to lactose-free formula, either cow milk-based or soy protein-based, is adequate. A change to either extensively hydrolysed formula or elemental formula is not indicated. Soy formula is generally not recommended in infants younger 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 is advisable.

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11 Part I: Algorithm for Managing Acute Gastroenteritis in Children


Child with diarrhoea
(> 3 times in a 24 hour period) 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 status 6. 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: Watery without blood and mucous 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 Inammatory bowel disease

Blood and mucous

Consider the following: 1. Stool hanging drop test for V. cholerae or culture if the diarrhoea is profuse and watery in nature or shy odour, should consider cholera as a possibility 2. Rehydrate as necessary

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 specic 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, signicant 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

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12 Part II: Algorithm for Managing Acute Gastroenteritis in Children


No signs of dehydration
(<3% loss of body weight) Child alert Drinks normally Heart rate, quality of pulse, breathing, eyes and capillary rell 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 rell 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

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 rell 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

No admission if no excessive vomiting

No admission if no excessive vomiting

Immediate referral to hospital for admission

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 uid 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 not recommended Children may continue on lactose containing milk formula Continue normal diet in older children Small and frequent feeds with regular assessment

Resuscitation (normal saline/Ringers lactate) Frequent monitoring

Consider intensive care if not resolved

Unresolved

Stable

Unstable
Hospital referral for admission for IV uid if persistent vomiting/worsening dehydration

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THE MANAGEMENT OF ACUTE DIARRHOEA IN CHILDREN 2011

13 Summary of Established Guidelines


CDC 2003 2 WHO 2005 1 ESPGHAN 2008 4 European Countries, low diarrhoeal morbidity and mortality Yes Do not recommend routine use in otherwise healthy children New South Wales Health 2010 5 Primary case setting in New South Wales, Australia AMMCOP/MPA 2011 Paediatric, primary care and frontline healthcare providers in Malaysia Yes Not routinely indicated. Only required for specific pathogens or defined clinical settings NR NR

Setting

Paediatric practice, with emphasis on US populations Yes Routine use wastes resources & may lead to antimicrobial resistance NR NR

Developing countries or communities with scarce health resources Yes Not routinely indicated. Only in selected clinical situations

ORS Antibiotics

Yes Rarely required. Consult paediatric or infectious specialist NR NR

Antiemetics Antimotility (Loperamide, Imodium) Antimotility (Diphenoxylate HCL; Lomotil) Adsorbants (Smectite) Adsorbants (Kaolin-pectin) Anti-secretory (Racecodotril) Anti-secretory (Bismuth subsalicylate)

NR NR

NR NR

NR

NR

NR

NR

NR

NR

May be recommended NR May be recommended NR

May be considered as an adjunctive NR May be considered as an adjunctive* NR

NR Need more studies NR

NR -

NR -

NR (Not practical, needs to be given frequently) -

NR

Probiotics

Should await further clinical trials

Strain-specific (Lactobacillus GG, S. boulardii)

Some benefits. Can be given when a normal diet is reintroduced -

May be considered as an adjunctive. Should be strainspecific and dose specific. NR

Prebiotics

Should await further clinical trials NR

NR

A switch to lactose-free, soy or hydrolysate

NR

NR

NR

NR

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

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45. Szajewska H, Mrukowicz JZ. Probiotics in the treatment and prevention of acute infectious diarrhea 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, Skrka A, Ruszczyski M, Gieruszczak-Biaek D. Meta-analysis: Lactobacillus GG 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 of Lactobacillus GG in aboriginal children with acute diarrhoeal disease: a randomised clinical trial. J Pediatr Gastroenterol Nutr 2010;50(6):619-24. 48. Misra S, Sabui TK, Pal NK. A randomized controlled trial to evaluate the efficacy of lactobacillus 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 Lactobacillus rhamnosus GG in controlling acute watery diarrhea in Indian children: a randomized controlled trial. J Clin Gastroenterol 2009;43(3):208-13. 50. Basu S, Chatterjee M, Ganguly S, Chandra PK. Efficacy of Lactobacillus rhamnosus GG in acute watery diarrhoea of Indian children: a randomised controlled trial. J Paediatr Child Health 2007;43(12):837-42. Epub 2007 Sep 4. 51. Szymaski H, Pejcz J, Jawie M, Chmielarczyk A, Strus M, Heczko PB. Treatment of acute infectious diarrhoea in infants and children with a mixture of three Lactobacillus rhamnosus strains--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: a multicenter 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 low osmolarity 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. Acta Paediatr 1997;86(5):460-5. 55. Pant AR, Graham SM, Allen SJ, Harikul S, Sabchareon A, Cuevas L, Hart CA. Lactobacillus GG 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 promotes recovery from acute nonbloody diarrhea in Pakistan. Pediatr Infect Dis J 1995;14(2):107-11. 57. Rerksuppaphol S, Rerksuppaphol L. Lactobacillus acidophilus and Bifidobacterium bifidum stored 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 in acute diarrhea. Indian J Pediatr 2005;72(11):935-8. 59. Vivatvakin B, Kowitdamrong E. Randomized control trial of live Lactobacillus acidophilus plus Bifidobacterium infantis in treatment of infantile acute watery diarrhea. J Med Assoc Thai 2006;89 Suppl 3:S126-33. 60. Livin-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 of Lactobacillus acidophilus strain LB against nonrotavirus diarrhea. Pediatrics 2007;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 to oral rehydration therapy in the treatment of acute diarrhea in children. J Pediatr Gastroenterol Nutr 2000;30(1):68-72.

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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 mild acute 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, Tern CG, Araya M. Probiotics in the treatment of acute rotavirus diarrhoea. A randomized, double-blind, controlled trial using two different probiotic preparations in Bolivian children. BMC Infect Dis 2010;10:253. 65. Eren M, Dinleyici EC, Vandenplas Y. Clinical efficacy comparison of Saccharomyces boulardii and yogurt fluid in acute non-bloody diarrhea in children: a randomized, controlled, open label 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 Saccharomyces boulardii and metronidazole compared to metronidazole alone in children with acute bloody 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 treatment of acute watery diarrhea in Myanmar children: a randomized controlled study. Am J Trop Med Hyg 2008;78(2):214-6. 68. Rosenfeldt V, Michaelsen KF, Jakobsen M, Larsen CN, Mller PL, Pedersen P, Tvede M, Weyrehter H, Valerius NH, Paerregaard A. Effect of probiotic Lactobacillus strains in young children hospitalized with acute diarrhea. Pediatr Infect Dis J. 2002;21(5):411-6. 69. Rosenfeldt V, Michaelsen KF, Jakobsen M, Larsen CN, Mller PL,Tvede M, Weyrehter H, Valerius NH, Paerregaard A. Effect of probiotic Lactobacillus strains on acute diarrhea in a cohort of nonhospitalized children attending day-care centers. Pediatr Infect Dis J. 2002;21(5):417-9. 70. Shornikova AV, Casas IA, Isolauri E, Mykknen H, Vesikari T. Lactobacillus reuteri as a therapeutic agent in acute diarrhea in young children. J Pediatr Gastroenterol Nutr. 1997;24(4):399-404. 71. Mauln-Radovn I, Brown KH, Acosta MA, Fernandez-Varela H. Comparison of a ricebased, mixed diet versus a lactose-free, soy-protein isolate formula for young children with acute diarrhea. J Pediatr 1994;125(5 Pt 1): 699-706. 72. Brown KH, Peerson JM, Fontaine O. Use of nonhuman milks in the dietary management of young 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 four feeding 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 Childrens 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.

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80. Vesikari T, Van Damme P, Giaquinto C, et al. European Society for Paediatric Infectious Diseases / European Society for Paediatric Gastroenterology, Hepatology, and Nutrition Evidence-based recommendations for rotavirus vaccination in Europe: Executive summary. J Pediatr Gastroenterol Nutri 2008;46:615-618. 81. Ruszczyski M, Radzikowski A, Szajewska H. Clinical trial: effectiveness of Lactobacillus rhamnosus (strains E/N, Oxy and Pen) in the prevention of antibiotic-associated diarrhoea in children. Aliment Pharmacol Ther 2008;28(1):154-61. Epub 2008 Apr 13. 82. Corra NB, Pret Filho LA, Penna FJ, Lima FM, Nicoli JR. A randomized formula controlled trial of Bifidobacterium lactis and Streptococcus thermophilus for prevention of antibioticassociated diarrhea in infants. J Clin Gastroenterol 2005;39(5):385-9. 83. Kotowska M, Albrecht P, Szajewska H. Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea in children: a randomized double-blind placebo-controlled trial. Aliment Pharmacol Ther 2005;21(5):583-90. 84. Szajewska H, Ruszczyski M, Radzikowski A. Probiotics in the prevention of antibioticassociated 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: a meta-analysis of randomized placebo-controlled trials. CMAJ 2006;175(4):377-83. Erratum in: CMAJ 2006;175(7):777. 86. Binns CW, Lee AH, Harding H, Gracey M, Barclay DV. The CUPDAY Study: prebioticprobiotic 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 with bifidobacterium 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, Pnk A, Meurman JH, Poussa T, Nse L, Saxelin M, Korpela R. Effect of long term consumption of probiotic milk on infections in children attending day care 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 intervention with a mixture of prebiotic oligosaccharides reduces the incidence of allergic manifestations and 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, Cinquetti M, Iacono G, Amarri S, Guarino A. A formula containing galacto- and fructooligosaccharides 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 to severe 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 10 years. 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

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APPENDIX A
Assessment of dehydration in acute diarrhoea
Symptom No signs of dehydration ( < 3% loss of body weight) Well, alert Mild to moderate dehydration ( 3-9% loss of body weight) N, fatigue or restless, irritable Thirsty, eager to drink Normal to increased Normal to decreased Normal, fast Slightly sunken Decreased Dry Recoil in < 2 seconds Prolonged Cool Decreased Severe dehydration ( > 9% loss of body weight)

Mental status Thirst Heart rate Quality of pulse Breathing Eyes Tears Mouth and tongue Skin fold Capillary refill Extremities Urine output

Apathetic, lethargic, unconscious Drinks poorly, unable to drink Tachycardia, with bradycardia in most severe cases Weak, thready, or impalpable Deep Deeply sunken Absent Parched (very dry) Recoil in > 2 seconds Prolonged, minimal Cold, mottled, cyanotic Minimal

Drinks N, might refuse liquids Normal Normal Normal Normal Present Moist Instant recoil Normal Warm Normal to decreased

Adapted from WHO 2005 1, CDC 2003 2

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

APPENDIX B
Anti-Diarrhoeal Drugs
Attributes Reduces secretion Prevents virulence Reduce stool output Shorten duration of diarrhoea Fast acting Constipation as a side effect Systemic side effects Does not interfere with ORS Loperamide Yes No No No Bismuth subsalicylate No No Yes No Smectide Yes Yes Yes Yes Racecadotril Yes No Yes Yes

Yes

No No

Yes No

Yes No

Yes Not tested

Potentially Yes

No Yes

No Yes

Adapted from Edelman et al, 198593 and Salazar-Lindo E. 2010 94

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The full guidelines on the management of acute diarrhoea in children may be obtained from the following websites: College of Paediatrics, Academy of Medicine of Malaysia (AMMCOP)
http://www.acadmed.org.my/

Malaysian Paediatric Association (MPA)


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

Mead Johnson Nutrition Malaysia


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