Table of Contents

HK J Paediatr (New Series)
Vol 8. No. 3, 2003

HK J Paediatr (New Series) 2003;8:203-236

Clinical Guideline

Guidelines for the Management of Acute Diarrhoea in Young Children

EAS Nelson, WK Ko, E Kwan, SF Leung, KH Poon, CB Chow, WK Sin, YK Wong, CY Yeung


These guidelines are not intended for the management of acute diarrhoea in neonates.

Disclaimer

These guidelines have been developed by the Hong Kong College of Paediatricians and the authors, according to the state of medical knowledge at the time of compilation. These guidelines are for general guidance only and are designed to provide information to assist decision making. Paediatricians should use their up-to-date medical knowledge, clinical data of the patients and their own clinical judgement in applying the recommendations in this document to the management of individual patients.

Explanatory Notes on Level of Evidence and Grading System on Recommendation

The definition of types of evidence and grading recommendations originate from the US Agency for Health Care Policy and Research (AHCPR) and are also recommended and used by the Royal College of Paediatrics and Child Health.

Levels of evidence
Level Type of evidence (based on AHCPR 1992)
Ia Evidence obtained from meta-analysis of randomised controlled trials
Ib Evidence obtained from at least one randomised controlled trial
IIa Evidence obtained from at least one well-designed controlled study without randomisation
IIb Evidence obtained from at least one other type of well-designed quasi-experimental study
III Evidence obtained from well-designed non-experimental descriptive studies, such as comparative studies, correlation studies and case control studies
IV Evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities

 

Grading of recommendations
Grade Type of recommendation (based on AHCPR 1994)
A (Levels Ia, Ib) Requires at least one randomised control trial as part of the body of literature of overall good quality and consistency addressing the specific recommendation
B (Levels IIa, IIb, III) Requires availability of well-conducted clinical studies but no randomised clinical trials on the topic of recommendation
C (Level IV) Requires evidence from expert committee reports or opinions and/or clinical experience of respected authorities. Indicates absence of directly applicable studies of good quality

Evidence is graded upon the methodological qualities. Guidelines normally contain many different recommendation based upon different levels of evidence. It is important that users are aware of the level of evidence on which each guideline recommendation is based. The link between guideline recommendation and the supporting evidence should be made explicit. Separating the strength of the recommendation from the level of evidence helps in situations where extrapolation is required to take the evidence of a methodologically strong study and apply it to the target population. Gradings of recommendation in addition to level of evidence allow more flexibility for future revision. Currently, there are discussions on taking account of relevant high quality non-RCTs and qualitative research and to incorporate them into appropriate grading system.

Key Recommendations

Assessment

  • Signs for assessment of dehydration should be used collectively.

Signs and symptoms No signs of dehydration Mild to Moderate dehydration Severe signs of dehydration
INITIAL ASSESSMENT
General condition Well, alert Restless, irritable, floppy Lethargic or unconscious
Eyes Normal Sunken Very sunken
Tears Present Absent Absent
Mucous membrane Moist Dry Very dry
Thirst Drinks normally, not thirsty Thirsty, drinks eagerly Drinks poorly or not able to drink
Skin turgor (Pinch) Goes back quickly Goes back slowly Goes back very slowly >2s
ADDITIONAL INDICATORS
Extremities Warm normal capillary refill Delayed capillary refill Cool, mottled, pale
Capillary refill >2s
Respiration Normal Deep Deep and rapid
Heart rate Normal Increased Increased (bradycardia in severe cases)
Blood pressure Normal Normal Normal to reduced
Urine output Normal Reduced (<1 mL/kg/h) None for many hours
(<<1 mL/kg/h)
Fontanelle if open Normal Sunken Sunken
  • Children with diarrhoea who have signs of dehydration, signs of toxaemia, young age of less than 3 months, or blood in the stool should be considered for hospital admission.

Oral Rehydration Therapy

  • Oral Rehydration Therapy (ORT) is the preferred treatment of mild to moderate dehydration in children with acute diarrhoea.

  • Hypotonic ORS is preferred in developed countries.

  • ORT should be under medical supervision and can usually be completed over four hours.

  • ORT can successfully rehydrate most children even with vomiting.

  • In hypernatraemic dehydration, ORT is safer than intravenous rehydration provided child is able to drink.

Nutrition Therapy

  • Breastfeeding should continue through rehydration and maintenance phases of treatment.

  • Dehydrated infants and children should be fed age-appropriate diets as soon as they are rehydrated.

  • Gradual reintroduction of milk-based formulas or cow's milk is not routinely required.

  • Lactose free or lactose-reduced formulas are not routinely required.

Drug Therapy

  • Antibiotics are not recommended for uncomplicated diarrhoea.

  • Probiotics (Lactobacillus) are safe and effective and can be recommended for the treatment of children with acute infectious diarrhoea.

  • Antidiarrhoeal drugs are not routinely recommended for acute diarrhoea in children.

Recommendations for Management of Acute Diarrhoea in Young Children

Assessment

  • Assessment determines treatment modality and monitors treatment response. (Level IIa Evidence, Grade B Recommendation)

  • Reliable signs for assessment of dehydration include: (Level IIa Evidence, Grade B Recommendation)

Signs and symptoms No signs of dehydration Mild to moderate dehydration Severe signs of dehydration
INITIAL ASSESSMENT
General condition Well, alert Restless, irritable, floppy Lethargic or unconscious
Eyes Normal Sunken Very sunken
Tears Present Absent Absent
Mucous membrane Moist Dry (inaccurate in mouth Very dry
      breather)
Thirst Drinks normally, not thirsty Thirsty, drinks eagerly Drinks poorly or not able to drink
Skin turgor (Pinch) Goes back quickly Goes back slowly Goes back very slowly > 2 s
ADDITIONAL INDICATORS
Extremities Warm normal capillary refill Delayed capillary refill Cool, mottled, pale
Capillary refill >2 s
       
Respiration Normal Deep Deep and rapid
Heart rate Normal Increased Increased (bradycardia in severe cases)
Pulse volume Normal Normal or slightly decreased Moderately decreased
Blood pressure Normal Normal Normal to reduced
Urine output Normal Reduced (<1 mL/kg/h) None for many hours
(<<1 mL/kg/h)
Fontanelle if open Normal Sunken Sunken
  • Conventional clinical signs of dehydration are valid and reliable when used collectively, but individually lack sensitivity and specificity. (Level IIa Evidence, Grade B Recommendation)

  • Children with diarrhoea who have signs of dehydration, signs of toxaemia, young age of less than 3 months, or blood in the stool should be considered for hospital admission. (Level IV Evidence, Grade C Recommendation)

Investigation

  • Plasma or serum biochemistry tests are indicated for patients with severe dehydration and probably also for those patients with some signs of dehydration who require intravenous fluid replacement. (Level IV Evidence, Grade C Recommendation)

  • Stool culture should be considered for patients who have blood in the diarrhoeal stool, persistent fever or signs of toxicity. (Level IV Evidence, Grade C Recommendation)

  • Stool for rotavirus antigen testing is not routinely required as it should not alter management. However it is useful for diagnostic purposes. (Level IV Evidence, Grade C Recommendation)

Oral Rehydration Therapy

  • Oral Rehydration Therapy (ORT) is the preferred treatment of mild to moderate dehydration in children with acute diarrhoea. (Level Ia Evidence, Grade A Recommendation) Children who are very ill, lethargic, drink poorly, with shock or near shock should be treated initially with IV solutions, details of which are not discussed in this guideline. When the child's condition has stabilised and mental status is satisfactory, ORT

  • may be instituted. (Level IV Evidence, Grade C Recommendation) ORT should not be given to children with intestinal ileus until bowel sounds are audible, (Level IV Evidence, Grade C Recommendation) or in the presence of glucose malabsorption i.e. patients with dramatic increase in stool output with ORT and glucose or reducing substances in the stool. (Level IV Evidence, Grade C Recommendation)

  • Standard WHO-ORS, hypotonic ORS and rice-based ORS are all effective for the treatment of dehydration. (Level Ia Evidence, Grade A Recommendation) However hypotonic ORS with reduced sodium (50-75 mmol/L) and glucose (75-111 mmol/L) concentration and low osmolarity (200-250 mmol/L) is preferred in developed countries where mainly non-cholera diarrhoea occurs. (Level IV Evidence, Grade C Recommendation) Compared to WHO-ORS, hypotonic ORS may decrease stool output and shorten duration of diarrhoea, without increased risk of hyponatraemia. (Level Ia Evidence, Grade A Recommendation) Rice-based ORS does not have beneficial effects over the WHO-ORS in the treatment of dehydration due to non-cholera diarrhoea, especially when food is given immediately after rehydration. (Level Ia Evidence, Grade A Recommendation)

  • Oral rehydration can usually be completed over four hours. (Level IV Evidence, Grade C Recommendation)
    - NO signs of dehydration give maintenance therapy
    - Mild-moderate dehydration give 50-75 ml/kg ORS

    Rehydration should be carried out under medical supervision and regular and frequent assessment of hydration status is essential. (Level IV Evidence, Grade C Recommendation) ORT may fail in children with continuing rapid stool loss (>10-20 ml/kg/hour), insufficient intake of ORS or frequent, severe vomiting. (Level IV Evidence, Grade C Recommendation) If the child still has signs of dehydration at the end of four hours, appropriate rehydration therapy should be instituted accordingly.

  • Maintenance fluids can be given as breast milk, formula, or other fluids appropriate for age, offered ad libitum. (Level IV Evidence, Grade C Recommendation) More fluids than usual should be offered to prevent dehydration. (Level IV Evidence, Grade C Recommendation) Drinks sweetened with sugar (e.g. soft drinks, sweetened juices) should be avoided as they may cause osmotic diarrhoea and hypernatraemia. (Level IV Evidence, Grade C Recommendation)

  • Ongoing losses can be replaced by normal diets given ad libitum in children with mild diarrhoea and NO signs of dehydration. (Level IV Evidence, Grade C Recommendation) In high risk cases with persistent profuse diarrhoea or vomiting, ongoing losses should be replaced with extra feeds of low-sodium ORS (40-60 mmol/L of sodium). (Level IV Evidence, Grade C Recommendation) When high-sodium ORS (>60 mmol/L) is used to replace ongoing losses after rehydration, other low-sodium fluids (e.g. breast milk, formula, or water) should be given in alternate feeds. (Level IV Evidence, Grade C Recommendation) The following guide may be useful for caregivers to replace ongoing losses (stool and vomitus) during both rehydration and maintenance therapy: (Level IV Evidence, Grade C Recommendation)

    Each watery or loose stool:  
    <2 years of age: 50-100 ml
    (1/4 to 1/2 a large cup)
    2-10 years:

    100-200 ml
    (1/2 to 1 large cup)

    OR 10 ml/kg
    Each episode of emesis: 2 ml/kg

  • Families should be advised to seek further medical advice should the child: (Level IV Evidence, Grade C Recommendation)

    • Starts to pass many watery stools
    • Has repeated vomiting
    • Becomes very thirsty
    • Is eating or drinking poorly
    • Develops a fever
    • Has blood in the stool
    • Deteriorates in any other way

     

  • ORT can successfully rehydrate most children even with vomiting. (Level Ia Evidence, Grade A Recommendation) Small volumes of ORS (5-10 ml) should be administered every 1-2 minutes, with a gradual increase in the amount consumed. (Level IV Evidence, Grade C Recommendation) Continuous, slow infusion of ORS via a nasogastric tube may be an alternative in non-comatose patients and those without ileus. (Level III Evidence, Grade B Recommendation)

  • In hypernatraemic dehydration ORT is safer than intravenous rehydration. (Level Ib Evidence, Grade A Recommendation) Provided the child's neurological status is stable and the child is able to drink, use "Slow ORT", aiming to complete rehydration over 12 hours and monitoring serum sodium to avoid a rapid reduction. (Level III Evidence, Grade B Recommendation)

Nutrition Therapy

  • Breastfeeding should continue through rehydration and maintenance phases of treatment. (Level Ib Evidence, Grade A Recommendation)

  • Exclusive breastfeeding should be promoted to reduce the severity of acute diarrhoea in infants during the first six months of life. (Level IIa Evidence, Grade B Recommendation)

  • Children who are not dehydrated should continue to be fed age-appropriate diets. (Level Ia Evidence, Grade A Recommendation)

  • Dehydrated infants and children should be fed age-appropriate diets as soon as they are rehydrated (usually within 4 hours). (Level Ia Evidence, Grade A Recommendation)

  • Gradual reintroduction of milk-based formulas or cow's milk is not routinely required. (Level Ia Evidence, Grade A Recommendation)

  • Lactose free or lactose-reduced formulas are not routinely required. (Level Ia Evidence, Grade A Recommendation) These formulas may be considered if there is no improvement in the stool consistency after several days or if reducing substances are identified in the stool. (Level IV Evidence, Grade C Recommendation)

  • Complex carbohydrates (e.g. rice, wheat, potatoes, bread and cereals), lean meat, yoghurt, fruits, and vegetables are better tolerated and more preferred than foods which are sugary (e.g. tea, juices and soft drinks) or fatty. (Level IV Evidence, Grade C Recommendation)

Drug Therapy

Antibiotics

  • Antibiotics are not recommended for uncomplicated diarrhoea. (Level III Evidence, Grade B Recommendation)

  • Most cases of Salmonella gastroenteritis do not require antibiotic therapy as symptoms are not improved by antibiotics (Level Ib Evidence, Grade A Recommendation)

  • Parenteral antibiotics, e.g. third generation cephalosporins may be required for young infants (<3 months), any ill or septic looking patient and immunocompromised children with Salmonella gastroenteritis who have a higher risk of complications. (Level IV Evidence, Grade C Recommendation)

  • Campylobacter gastroenteritis is usually self-limiting and antibiotic may only be of value if given early. Antibiotic may be indicated for children in institutional settings to shorten bacterial excretion. (Level IV Evidence, Grade C Recommendation)

  • Shigellosis is highly infectious and notifiable. Antibiotic may shorten the infectious period but the disease is often self-limiting and hence antibiotic is used in ill patients or those who are still symptomatic when the pathogen is detected. (Level IV Evidence, Grade C Recommendation)

  • Antibiotics are not usually required for diarrhoeagenic E. Coli, Yersinia enterocolitica, Vibrio parahaemolyticus, Aeromonas spp., Plesiomonas spp. Oral metronidazole or vancomycin is indicated for severe Clostridium difficile associated diarrhoea. Metronidazole is helpful for giardia lamblia. (Level IV Evidence, Grade C Recommendation)

Probiotics

  • Probiotics (Lactobacillus) are safe and effective and can be recommended for the treatment of children with acute infectious diarrhoea. (Level Ia Evidence, Grade A Recommendation)

Antidiarrhoeal agents

  • Antidiarrhoeal agents are not routinely recommended for acute diarrhoea in children. (Level IV Evidence, Grade C Recommendation)

  • These agents should not be used in children with fever, toxaemia or blood in the stool. (Level IV Evidence, Grade C Recommendation)

  • Users of these agents as adjunctive therapy should pay attention to precautions and possible risks. Attention to the appropriate dosage and proper education of parents are prudent. (Level IV Evidence, Grade C Recommendation)

Background

Acute diarrhoea is a very significant cause of morbidity amongst hospitalised children in Hong Kong. Less data is available for ambulatory children. Approximately 12% of all paediatric medical admissions to Hospital Authority Hospitals for the two-year period July 1997 to June 1999 were due to acute diarrhoea (Table 1). Approximately 10% of these admissions were due to rotavirus and 11% to Salmonella. However these percentages are believed to underestimate the true burden of these pathogens.1 A prospective study over a one year period at one hospital in Hong Kong showed that approximately one third of diarrhoeal admissions were due to rotavirus, one third to bacteria (majority Salmonella) and the remaining one third had no specific organism identified.2 Pathogenic E. Coli were not a common cause of acute diarrhoea in this population.2 Shigella was uncommon and tended to cause disease in older children, whereas Salmonella mainly affected the younger infants. The economic importance of rotavirus infection in Hong Kong has been highlighted, although the impact of other causes of viral diarrhoea are less well quantified.1,3 A number of Hong Kong studies have looked at rotavirus gastroenteritis in hospital and community settings (Table 2). In community settings rotavirus is responsible for a smaller proportion of children assessed with diarrhoea.

Table 1 Diarrhoea-associated hospitalisations by reported diagnosis among 106,919 children aged 1-59 months, Hong Kong Hospital Authority Hospitals from 1 July 1997 to 30 June 1999
ICD codes Primary diagnosis** n (%)
Presumed infectious 009.0-009.3 5753 (46.7)
Presumed non-infectious 558.9, 787.91 3358 (27.3)
Viral* 008.6-008.8 183 (1.5)
Rotavirus 008.61 1270 (10.3)
Cholera 001-001.9 1 (0)
Salmonella 002-003.9 1347 (10.9)
Shigella 004-004.9 66 (0.5)
Food poisoning 005-005.9 38 (0.3)
E. Coli & others 008-008.5 241 (2.0)
Total diarrhoea   12257 (12.2%)
All other diseases   94662 (87.8%)
(*Excludes rotavirus;**Primary diagnosis code only)

 

Table 2 Review of previous Hong Kong studies assessing rotavirus disease burden
  Year Duration (mo) n % rotavirus
Active surveillance studies
Prince of Wales Hospital2 94-95 12 388 35
Queen Mary Hospital4 82-85 30 2228 30
Queen Mary Hospital5 83-85 30 2246 24
Queen Mary Hospital6 83-84 12 899 28.5
Passive surveillance and laboratory data
Prince of Wales Hospital1 87-96 120 7945 28*
Community and laboratory studies
Kwun Tong Community7 84-86 36 637 11#
Prince of Wales Hospital8 84-90 80 3267 34**
Government Virus Laboratory3 87-92 72 27618 14##
*2213 laboratory reports were positive for rotavirus in children under five years during a period when 7,945 children of this age were admitted with a diagnosis of diarrhoea. However only 14% of the diarrhoea admissions were classified as viral diarrhoea indicating under-reporting in the patient discharge diagnosis; #Community study;**Laboratory based study of positive isolates; ##16.7% of stools specimens were positive for viruses and 84.4% of viral isolates were rotavirus (all ages).

Evidence for Recommendations

Assessment

Recommendation:

  • Assessment determines treatment modality and monitors treatment response. (Level IIa Evidence, Grade B Recommendation)
  • Reliable signs for assessment of dehydration include: (Level IIa Evidence, Grade B Recommendation)
Signs and symptoms No signs of dehydration Mild to moderate dehydration Severe signs of dehydration
INITIAL ASSESSMENT
General condition Well, alert Restless, irritable, floppy Lethargic or unconscious
Eyes Normal Sunken Very sunken
Tears Present Absent Absent
Mucous membrane Moist Dry (inaccurate in mouth breather) Very dry
Thirst Drinks normally, not thirsty Thirsty, drinks eagerly Drinks poorly or not able to drink
Skin turgor (Pinch) Goes back quickly Goes back slowly Goes back very slowly >2 s
ADDITIONAL INDICATORS
Extremities Warm normal capillary refill Delayed capillary refill Cool, mottled, pale
      Capillary refill >2 s
Respiration Normal Deep Deep and rapid
Heart rate Normal Increased Increased (bradycardia in severe cases)
Pulse volume Normal Normal or slightly decreased Moderately decreased
Blood pressure Normal Normal Normal to reduced
Urine output Normal Reduced (<1 mL/kg/h) None for many hours
(<<1 mL/kg/h)
Fontanelle if open Normal Sunken Sunken
  • Conventional clinical signs of dehydration are valid and reliable when used collectively, but individually lack sensitivity and specificity. (Level IIa Evidence, Grade B Recommendation)

  • Children with diarrhoea who have signs of dehydration, signs of toxaemia, young age of <3 months, or blood in the stool should be considered for hospital admission. (Level IV Evidence, Grade C Recommendation)

Evidence:

A number of guidelines for the clinical assessment of dehydration have been proposed (Tables 3a-3d). The gold standard for diagnosis of dehydration is measurement of acute weight loss. However as the patient's true pre-illness weight is rarely known in the acute care setting, an estimate of the fluid deficit is mainly based on clinical assessment. Assessment of dehydration is used to determine the treatment modality and to monitor the response to treatment.9 (Level IIa Evidence, Grade B Recommendation) Weight after rehydration was found to be similar to pre-illness weight and the clinical signs used to assess dehydration were correlated with the actual dehydration.9 (Level IIa Evidence, Grade B Recommendation) 3-4% is the level at which dehydration becomes clinically apparent, rather than 5% as is normally stated. Decreased peripheral perfusion, deep acidotic breathing and decreased skin turgor were found to be reliable signs,10 together with circulatory collapse and capillary refill time >= 2 seconds showing severe dehydration >= 9%.11 (Level IIa Evidence, Grade B Recommendation) Although actual weight losses of <3%, 3-8% and >= 9% better reflects the clinical findings of no signs of dehydration, mild to moderate dehydration and severe dehydration respectively, the weight loss classification of <5%, 5-10% and >10% is still widely used in clinical practice.

Conventionally used clinical signs of dehydration are valid and reliable when used collectively. However, when used individually parameters lack sensitivity and specificity (Table 4). (Level IIb Evidence, Grade B Recommendation)

The sensitivity of individual conventional clinical signs of dehydration ranged from 0.35 to 0.85. The specificity of these signs ranged from 0.53 to 0.97.9

Table 3a Clinical assessment of severity of dehydration (WHO) (http://www.who.int/chd/publications/cdd/textrev4.htm)
Signs and symptoms None or mild Moderate Severe
Condition Well, alert Restless, irritable, floppy Lethargic or unconscious
Eyes Normal Sunken Very sunken
Tears Present Absent Absent
Mouth and tongue Moist Dry Very dry
Thirst Drinks normally, not thirsty Thirsty, drinks eagerly Drinks poorly or not able to drink
Skin turgor (Pinch) Goes back quickly Goes back slowly Goes back very slowly >2 s

 

Table 3b Clinical assessment of severity of dehydration12,13
No dehydration Mild-moderate dehydration Severe dehydration
<3% weight loss 3-8% weight loss >= 9% weight loss
NO SIGNS
  • Dry mucous membrane (inaccurate in mouth breather)
  • Sunken eyes (and minimal or no tears)
  • Diminished skin turgor (pinch test >1 sec.)
  • Altered neurological state (drowsiness, irritability)
  • Deep (acidotic) breathing
Signs from the mild-moderate group
PLUS
  • Decreased peripheral circulation (cool/mottled/paleperipheries; capillary refill time >2 sec.)
  • Circulatory collapse

 

Table 3c Clinical assessment of severity of dehydration9
Signs and symptoms None or mild Moderate Severe
General Condition      

Infants

Thirsty, alert, restless Lethargic or drowsy Limp, cold cyanotic extremities, maybe comatose

Older children

Alert, postural dizziness Apprehensive, cold cyanotic extremities, muscle cramps
Radial pulse Normal Thready or weak Feeble or impalpable
Respiration Normal Deep Deep and rapid
Skin turgor (Pinch) Retracts immediately Retracts slowly Retracts very slowly >2 s
Eyes Normal Sunken Very sunken
Tears Present Absent Absent
Mucous membrane Moist Dry Very dry
Urine output Normal Reduced None for many hours

 

Table 3d Clinical assessment of severity of dehydration (AAP)14
Signs and symptoms Mild (3-5%) Moderate (6-9%) Severe (>= 10%)
Blood pressure Normal Normal Normal to reduced
Pulse volume Normal Normal or slightly decreased Moderately decreased
Heart rate Normal Increased Increased (bradycardia in severe cases)
Skin turgor (Pinch) Normal Decreased Decreased
Fontanelle Normal Sunken Sunken
Mucous membrane Slightly dry Dry Dry
Eyes Normal Sunken orbits Deeply sunken orbits
Extremities Warm normal capillary refill Delayed capillary refill Cool mottled
Mental status Normal Normal to listless Normal to lethargic or comatose
Urine output Slightly decreased <1 mL/kg/h <<1 mL/kg/h
Thirst Slightly increased Moderately increased Very thirsty or too lethargic to indicate

 

Table 4 Diagnostic performance of 10 individual clinical findings
  Sensitivity Specificity
Decreased skin elasticity 0.35 0.97
Capillary refill >2 seconds 0.48 0.96
General appearance (ill-appearing, irritable, apathetic) 0.59 0.91
Absent tears 0.67 0.89
Abnormal respiration 0.43 0.86
Dry mucous membrane 0.80 0.78
Sunken eyes 0.60 0.84
Abnormal radial pulse 0.43 0.86
Tachycardia (heart rate >150) 0.46 0.79
Decreased urine output 0.85 0.53

Suggestions for Admission

Delphi consensus agreement was used to determine the recommendations for admission of children who present to hospital with diarrhoea in the United Kingdom.13 Factors considered included level of hydration, presence of risk factors and assessment of the caregiver. However the extent to which these recommendations can be applied to children managed in community settings is less clear.

Investigations

Recommendation:

  • Plasma or serum biochemistry tests are indicated for patients with severe dehydration and probably also for those patients with some signs of dehydration who require intravenous fluid replacement. (Level IV Evidence, Grade C Recommendation)

  • Stool culture should be considered for patients who have blood in the diarrhoeal stool, persistent fever or signs of toxicity. (Level IV Evidence, Grade C Recommendation)

  • Stool for rotavirus antigen testing is not routinely required, as it should not alter management. However it is useful for diagnostic purposes. (Level IV Evidence, Grade C Recommendation)

Evidence:

There is limited evidence for cost-effectiveness of investigations in acute diarrhoea, especially for the local setting. Recommendations are based on consensus. The following investigations may be useful in patients with acute diarrhoea:

  • Plasma/serum biochemistry
    (e.g. Na, K, HCO3, urea, pH)
  • Full blood counts
  • Blood culture
  • Stool bacterial culture
  • Stool lactoferrin, occult blood and leucocytes
  • Stool viral antigens, viral EM, viral culture
  • Stool parasites
  • Stool biochemistry for carbohydrate intolerance (pH, reducing substance and osmotic gap)

The value of plasma/serum electrolytes and urea level is obvious in the situation of severe dehydration. For lesser degrees of dehydration, the need for investigations is less clear cut and should be individualised. It has been suggested that electrolyte, urea/creatinine and bicarbonate levels should be checked in moderately dehydrated children whose histories or physical findings (e.g. "doughy" feel to skin) are inconsistent with straight-forward diarrhoeal episodes and in all severely dehydrated children.13,14

The band neutrophil counts, if raised, may help identify patient with bacterial gastroenteritis.15 Blood culture is needed whenever patient appears toxic or ill. It is useful when managing cases of Salmonella gastroenteritis because of its propensity for deep invasion, especially for infants <3 months and in immuno-compromised patients.16

As stool bacterial yield on culture is low, especially in developed countries, a more selective approach to stool culture is recommended.17 In one recent study in U.S.A., for example, only 7 out of 250 (2.8%) stools in paediatric patients admitted to hospital for diarrhoea were positive on culture.15 Local experience suggests that the proportion of positive stool cultures may be up to 30% in hospitalised patients.2 If stool culture is needed in a patient, one specimen suffices. In a local study, the first specimens already picked up the bacterial pathogen in 95% of cases.18 A recent guideline suggested that stool be sent for microscopy, culture, sensitivity, and virology when there is a history suggestive of food poisoning, recent travel abroad or blood in the stool, with or without mucus. A stool should also be sent if the child is systemically unwell, or has severe or prolonged diarrhoea.13

Screening tests, including stool lactoferrin, occult blood and leucocytes, were studied for usefulness in assisting selective stool culture when these tests are positive. In terms of sensitivity with the least false positivity, stool lactoferrin is the best, followed by stool occult blood and finally stool leucocytes.19 However, stool lactoferrin is not currently available locally. As the positive or negative predictive values would depend on the local prevalence of various bacterial pathogens, the result of overseas studies may not be directly applicable locally. Therefore the usefulness of these test on top of clinical judgement is unclear.

Retrospective analysis showed that viruses (rotavirus, adenovirus, astrovirus, Norwalk-like virus and calicivirus taken together) were present only in <20% of stools from infants and children less than five during the period from 1987 to 1992.3 However, a more recent study suggests that approximately one third of children hospitalised with acute diarrhoea will have rotavirus.2 Cost and epidemiological considerations will determine whether stool specimens should be tested for viruses.

Stool parasites are uncommonly detected in Hong Kong children with diarrhoea.2 This is generally the case in developed countries where general hygienic standards are good.17 Giardiasis should be considered when the child passes loose offensive frothy stools and in such situations fresh stools should be sent for immediate examination. Examining stools for parasites may be considered for children arriving from regions where the prevalence of infection is higher. As special detection method may be needed for some parasites, e.g. cryptosporidium, adequate communication with the laboratory is prudent when parasites are considered.

Oral Rehydration Therapy

Safety and Efficacy of Oral Rehydration Therapy

Recommendation

  • Oral Rehydration Therapy (ORT) is the preferred treatment of mild to moderate dehydration in children with acute diarrhoea. (Level Ia Evidence, Grade A Recommendation) Children who are very ill, lethargic, drink poorly, with shock or near shock should be treated initially with IV solutions. When the child's condition has stabilised and mental status is satisfactory, ORT may be instituted. (Level IV Evidence, Grade C Recommendation) ORT should not be given to children with intestinal ileus until bowel sounds are audible, (Level IV Evidence, Grade C Recommendation) or in the presence of glucose malabsorption i.e. patients with dramatic increase in stool output with ORT and glucose or reducing substances in the stool. (Level IV Evidence, Grade C Recommendation)

Evidence

Replacement of fluid and electrolyte losses is the critical central element of effective treatment of acute diarrhoea. The discovery of coupled co-transport of sodium and glucose provides the scientific basis for ORT as an alternative to intravenous (IV) therapy. This co-transport mechanism works in an approximately equimolar ratio and remains intact even during copious secretory diarrhoea.20

In 1975, the World Health Organisation (WHO) and the United Nations Children's Fund (UNICEF) agreed to promote a single solution (WHO-ORS) containing (in mmol/L): sodium 90, potassium 20, chloride 80, base 30 and glucose 111 (2%). Recently, the bicarbonate component of the WHO-ORS has been replaced with citrate because of its longer shelf-life. The standard WHO oral rehydration solution (ORS) can successfully rehydrate more than 90% of children with dehydration due to acute diarrhoea.21 However, ORT does not reduce the rate of stool loss or the duration of diarrhoea, which are the main concerns of parents.22

In randomised controlled trials in which ORT was compared with standard intravenous therapy, both in developed23-25 and developing26 countries, ORT was as effective as IV therapy in rehydrating children. In addition ORT was found to be more rapid in correcting dehydration and acidosis,24 while being safer and with none of the complications associated with intravenous therapy.23,26

In a meta-analysis of the efficacy of glucose-based ORT in developed countries among well-nourished young children with acute diarrhoea, 6 randomised-control trials comparing ORT with intravenous rehydration treatment and 7 randomised-control trials comparing ORSs with different sodium contents were included.21 The overall failure rate was 3.6% (95% CI, 1.4-5.8%) while the failure rate for those with or without IV arms were 5.7% (95% CI, 1.8-9.6%) and 3.0% (95% CI, 0.6-5.4%) respectively. Failure rates broken down by sodium content of the ORS failed to show a statistically significant difference. Iatrogenic hypernatraemia or hyponatraemia was only reported in 2 studies - hyponatraemia in 10 cases and hypernatraemia in 3 cases. When sodium content of ORS was divided into high (90 mmol/L), medium (50-75 mmol/L) and low (26-45 mmol/L), the number of cases of iatrogenic hyponatraemia was 1, 9 and 6 from the respective groups. One case of iatrogenic hypernatraemia occurred in each of the group. Therefore children rehydrated with medium to low sodium solutions may be at a slightly higher risk of mild iatrogenic hyponatraemia. When other outcome parameters including duration of diarrhoea, length of hospitalisation and weight gain at discharge were considered, there was a tendency favouring ORT over IV rehydration. There was little difference among these outcomes of ORSs with different concentration of sodium.

Composition of ORS

Recommendation

  • Standard WHO-ORS, hypotonic ORS and rice-based ORS are all effective for the treatment of dehydration. (Level Ia Evidence, Grade A Recommendation) However hypotonic ORS with reduced sodium (50-75 mmol/L) and glucose (75-111 mmol/L) concentration and low osmolarity (200 -250 mmol/L) is preferred in developed countries where mainly non-cholera diarrhoea occurs. (Level IV Evidence, Grade C Recommendation) Compared to WHO-ORS, hypotonic ORS may decrease stool output and shorten duration of diarrhoea, without increased risk of hyponatraemia. (Level Ia Evidence, Grade A Recommendation) Rice-based ORS does not have beneficial effects over the WHO-ORS in the treatment of dehydration due to non-cholera diarrhoea, especially when food is given immediately after rehydration. (Level Ia Evidence, Grade A Recommendation)

Evidence

Despite the proven efficacy and safety of the WHO-ORS, there is concern over the risk of hypernatraemia in developed countries where children are well-nourished and mostly suffering from non-cholera diarrhoea with lower sodium loss in stool, especially in infants less than 3 months of age.27 WHO actually recommended the use of complete WHO-ORS for initial rehydration only. During maintenance therapy, the addition of free water to the WHO-ORS in a ratio of 1:2 was recommended to give a sodium concentration of 60 mmol/L.28

Currently, WHO recommends using solutions with a glucose-to-sodium ratio of less than 1.4:1,29 whereas the American Academy of Pediatrics recommends a ratio of less than 2:1.30 The inability of the WHO-ORS to reduce stool volume may be due to its slight hypertonicity, combined with incomplete absorption of glucose in some children, resulting in osmotic diarrhoea. In addition, perfusion studies in animals and humans have also shown that osmolarity rather than sodium concentration and the sodium-glucose ratio, may be the most critical determinant of intestinal absorption of an ORS solution.31,32 From these studies, it was concluded that optimal water absorption could be obtained by using a hypotonic solution with a sodium concentration of 50-60 mmol/L and a glucose concentration of 50-100 mmol/L. In randomised controlled trials, oral rehydration solutions containing 50-60 mmol/L sodium are safe and effective treatment for the dehydration and electrolyte abnormalities associated with acute diarrhoea of varied aetiology and in all age groups including neonates, eliminating the need for additional free water for maintenance therapy.23,27 Mild and asymptomatic hyponatraemia was observed in some children. In 1992, the European Society of Paediatric Gastroenterology and Nutrition (ESPGN) recommended an ORS solution containing 60 mmol/L sodium, 74-111 mmol/L glucose and an osmolarity between 200-250 mmol/L for European children (Table 5).33 Very similar recommendations were made for United Kingdom children.13

Table 5 Oral rehydration solutions in Hong Kong
Product Na K Cl HCO3 Citrate Glucose Other constituent Rice Osmolarity Flavour Form
ESPGAN guideline 60 20 60 - 10 74-111 - - 200-250 - -
G.E.S. 45 45 25 45 25 - 160 - - 300 - Sachet
ORS 90 20 80 - 10 111 - - 311 Orange Sachet
Pedialyte (plain) 45 20 35 - 10 139 - - 249 - Liquid
Pedialyte (flavoured) 45 20 35 - 10 111 Fructose:5 - 250 Fruit Liquid
WHO-ORS B 90 20 80 30   111 - - 331 - Sachet
WHO-ORS C 90 20 80 - 10 111 - - 311 - Sachet
New WHO-ORS 75 20 65 - 10 75 - - 245 - Sachet
QMH Rice ORS 60 20 50 - 10 - - 50 280 - Liquid
Dioralyte 60 20 60 - 10 90 - - 240 - Sachet
Glucolyte 60 20 50 0 10 100 Gluconate 5 - 248 Regular, orange, apple Sachet
Units : Electrolytes, citrate, glucose (mmol/L); Osmolarity (mosml/L); Fructose, rice (g/L)

In a few clinical trials comparing low sodium ORSs with WHO-ORS, stool output, fluid intake and treatment failures were reduced in children treated with hypotonic ORS without an increased risk of hyponatraemia (Tables of Evidence - Table C2). Studies that compared other high osmolarity ORSs with low osmolarity ORSs are shown in Tables of Evidence - Table C3.

In a multicentre evaluation of reduced-osmolarity ORS in developing countries, standard ORS with osmolarity of 311 mmol/L was compared to reduced-osmolarity ORS of 224 mmol/L (sodium 60 mmol/L, glucose 84 mmol/L) in the rehydration of mild to moderate dehydration in non-cholera diarrhoea.34 Treatment with reduced-osmolarity ORS resulted in decreased stool output (39%), decreased ORS intake (18%), decreased duration of diarrhoea (22%) and increased urine output. The risk of developing or worsening hyponatraemia was not increased in children given the reduced-osmolarity ORS. A significant reduction in the need for unscheduled intravenous therapy of up to 33% was demonstrated in another recent multicentre, randomised, double-blind study in 5 countries including Bangladesh, Brazil, India, Peru and Vietnam. In this study, a reduced-osmolarity ORS (75 mmol/L sodium, 20 mmol/L potassium, 65 mmol/L chloride, 10 mmol/L citrate,

75 mmol/L glucose and osmolarity 245 mosmol/L) was compared with the standard WHO-ORS in 675 children. However, there was no significant difference in terms of stool output, duration of diarrhoea and percentage with vomiting. The risk of hyponatraemia at 24 hours was not significantly different but can be up to doubling the number when compared with the WHO group.35

In a recent systemic review of the effect of reduced osmolarity ORS in children, the results in 15 randomised controlled studies including 2397 children were analysed. Standard WHO-ORS was compared with reduced-osmolarity ORS (osmolarity <270 mosmol/L). Reduced-osmolarity ORS was associated with a 35% reduction in unscheduled intravenous therapy, a 20% reduction in stool output and a 30% reduction in vomiting, with no difference in the incidence of hyponatraemia.36 Very similar results were shown in the systemic review of the Cochrane Library of reduced osmolarity ORS for treating dehydration caused by acute diarrhoea in children.37 Based on this evidence, WHO has recently announced the use of a new formula for ORS with sodium 75 mmol/L, glucose 75 mmol/L and total osmolarity of 245 mosmol/L on 8 May 2002.38

The substitution of cereal for glucose in ORS is one of the many efforts to improve the WHO-ORS. The apparent superiority of rice-based ORS has been attributed to its capacity to release more glucose from rice starch than is present in glucose-based ORS, facilitating greater coupled transport with sodium while maintaining low osmolarity.39 In addition to glucose polymers, cereal also provides amino acids and short chain peptides that have all been demonstrated to enhance sodium and water reabsorption without incurring an osmotic penalty in the gut.40 Many clinical trials have been conducted with conflicting results.41 Most studies were characterised by highly heterogeneous patient groupings with different causes of diarrhoea. In addition, the quantity and quality of the maintenance diet often were not standardised, measured, or described adequately. Since early feeding reduces the severity, duration and nutritional consequences of diarrhoea, variations in diet may account for the differences in results.42 Details of randomised controlled trials comparing rice-based ORS with WHO-ORS were shown in Tables of Evidence ?Table C4. In a meta-analysis of 13 randomised clinical trials involving more than 1300 children and adults, the efficacy of rice-based ORS (containing 50-80 g/L rice powder) was compared with that of WHO-ORS. Rice-based ORS resulted in a significant reduction in stool output in the first 24 hours and reduction of duration of diarrhoea in adults and children with cholera, but not in children with non-cholera diarrhoea.22 The authors concluded that "the benefit of rice-based ORS for children with acute, non-cholera diarrhoea should be more precisely defined before its practical value can be judged". In order to define more precisely the benefit of rice-based ORS for children with non-cholera diarrhoea, the meta-analysis was updated in 1996 by the addition of 9 trials in children with non-cholera diarrhoea. Rice-based ORS only caused a small and non-significant reduction in stool output.43 The authors concluded that "rice-based ORS does not reduce stool output when compared with standard ORS in children with acute, non-cholera diarrhoea, especially when food is given immediately after rehydration". Similar results and conclusions were obtained in the systematic review of the Cochrane Library to assess the effects of rice-based ORS compared with WHO-ORS on reduction of stool output and duration of diarrhoea.44

Rehydration Regimen

Recommendation

  • Oral rehydration should usually be completed over four hours. (Level IV Evidence, Grade C Recommendation)

    • NO signs of dehydration give maintenance therapy
    • Mild-moderate dehydration give 50-75 ml/kg ORS

    Rehydration should be carried out under medical supervision and regular and frequent assessment of hydration status is essential. (Level IV Evidence, Grade C Recommendation) ORT may fail in children with continuing rapid stool loss (>10-20 ml/kg/hour), insufficient intake of ORS or frequent, severe vomiting. (Level IV Evidence, Grade C Recommendation) If the child still has signs of dehydration at the end of four hours, appropriate rehydration therapy should be instituted accordingly.

  • Maintenance fluids can be given as breast milk, formula, or other fluids appropriate for age, offered ad libitum. (Level IV Evidence, Grade C Recommendation) More fluids than usual should be offered to prevent dehydration. (Level IV Evidence, Grade C Recommendation) Drinks sweetened with sugar (e.g. soft drinks, sweetened juices) should be avoided as they may cause osmotic diarrhoea and hypernatraemia. (Level IV Evidence, Grade C Recommendation)

  • Ongoing losses can be replaced by normal diets given ad libitum in children with mild diarrhoea and NO signs of dehydration. (Level IV Evidence, Grade C Recommendation) In high risk cases with persistent profuse diarrhoea or vomiting, ongoing losses should be replaced with extra feeds of low-sodium ORS (40- 60 mmol/L of sodium). (Level IV Evidence, Grade C Recommendation) When high-sodium ORS (>60 mmol/L) is used to replace ongoing losses after rehydration, other low-sodium fluids (e.g. breast milk, formula, or water) should be given in alternate feeds. (Level IV Evidence, Grade C Recommendation) The following guide may be useful for caregivers to replace ongoing losses (stool and vomitus) during both rehydration and maintenance therapy: (Level IV Evidence, Grade C Recommendation)

Each watery or loose stool:  
<2 years of age: 50-100 ml (1/4 to 1/2 a large cup)
2-10 years: 100-200 ml (1/2 to 1 large cup)
OR 10 ml/kg
Each episode of emesis: 2 ml/kg
  • Families should be advised to seek further medical advice should the child: (Level IV Evidence, Grade C Recommendation)

    • Starts to pass many watery stools
    • Has repeated vomiting
    • Becomes very thirsty
    • Is eating or drinking poorly
    • Develops a fever
    • Has blood in the stool
    • Deteriorates in any other way

Evidence

In the past many regimes aimed at gradual rehydration over 24 hours, but this approach was not evidence-based. Most authorities now recommend rapid rehydration over three to four hours.42,45,46

Management guidelines for the treatment of acute diarrhoea have been published by the WHO,47 the Centers for Disease Control and Prevention,42 and the American Academy of Paediatrics.14 A recent evidence and consensus based guideline has been published in the United Kingdom,13 and there is also a review article by Murphy.48 In essence, the objectives of treatment are to prevent dehydration, treat dehydration and to prevent nutritional damage.

Vomiting

Recommendation
  • ORT can successfully rehydrate most children even with vomiting. (Level Ia Evidence, Grade A Recommendation) Small volumes of ORS (5-10 ml) should be administered every 1-2 minutes, with a gradual increase in the amount consumed. (Level IV Evidence, Grade C Recommendation) Continuous, slow infusion of ORS via a nasogastric tube may be an alternative in non-comatose patients and those without ileus. (Level III Evidence, Grade B Recommendation)

Evidence

Greater than 90% of children who have vomiting and dehydration can be successfully rehydrated with ORT25,49,50 when small volumes of ORS (5-10 mL) are administered every 1-2 minutes, with a gradual increase in the amount consumed. Continuous, slow nasogastric infusion through a feeding tube is another option in a child with frequent vomiting.13,42

Hypernatraemic Dehydration

Recommendation

  • In hypernatraemic dehydration ORT is safer than intravenous rehydration. (Level Ib Evidence, Grade A Recommendation) Provided the child's neurological status is stable and the child is able to drink, use "Slow ORT", aiming to complete rehydration over 12 hours and monitoring serum sodium to avoid a rapid reduction. (Level III Evidence, Grade B Recommendation)

Evidence

In cases of hypernatraemia (serum sodium >150 mmol/L), "slow ORT" with fluid replacement over 12 hours has been recommended to reduce the risk of seizures.51 None of 34 infants with hypernatraemic dehydration suffered seizures when rehydration was treated with WHO-ORS over 12 hours.51 In another controlled trial of IV therapy versus ORT, 6% of hypernatraemic patients treated with ORT developed seizures compared with 25% in the group given intravenous treatment.26

Nutrition Therapy

Recommendation

  • reastfeeding should continue through rehydration and maintenance phases of treatment. (Level Ib Evidence, Grade A Recommendation)

  • Exclusive breastfeeding should be promoted to reduce the severity of acute diarrhoea in infants during the first six months of life. (Level IIa Evidence, Grade B Recommendation)

  • Children who are not dehydrated should continue to be fed age-appropriate diets. (Level Ia Evidence, Grade A Recommendation)

  • Dehydrated infants and children should be fed age-appropriate diets as soon as they are rehydrated (usually within 4 hours). (Level Ia Evidence, Grade A Recommendation)

  • Gradual reintroduction of milk-based formulas or cow's milk is not routinely required. (Level Ia Evidence, Grade A Recommendation)

  • Lactose free or lactose-reduced formulas are not routinely required. (Level Ia Evidence, Grade A Recommendation) They may be considered if there is no improvement in the stool consistency after several days or if reducing substances are identified in the stool. (Level IV Evidence, Grade C Recommendation)

  • Complex carbohydrates (e.g. rice, wheat, potatoes, bread and cereals), lean meat, yoghurt, fruits, and vegetables are better tolerated and more preferred than foods which are sugary (e.g. tea, juices and soft drinks) or fatty. (Level IV Evidence, Grade C Recommendation)

Evidence

Although there has been a common belief that bowel rest would hasten the recovery of the bowel and decrease the severity and duration of the diarrhoea, there is evidence to the contrary. Early feeding may in fact decrease intestinal permeability changes induced by infection.52 (Level IIb Evidence, Grade B Recommendation) Animal studies suggest it may also facilitate enterocyte healing and help maintain disaccharidase activity.53 (Level IIb Evidence, Grade B Recommendation)

Evidence based guidelines on managing acute diarrhoea recommend that breastfeeding should continue through rehydration and maintenance phases of treatment of acute diarrhoea.48,54 (Level Ib Evidence, Grade A Recommendation) The ESPGAN working group on acute diarrhoea recommended that at all times, breastfeeding should be continued.55 (Level IV Evidence, Grade C Recommendation) It is noted that if a baby is being breast-fed at the time of a diarrhoeal episode, the progress of that episode is milder, particularly if breastfeeding is continued.56-58 (Level IV Evidence, Grade C Recommendation) Discontinuation of breastfeeding during diarrhoea significantly increases the risk of dehydration.59 (Level IIa Evidence, Grade B Recommendation)

Clinical studies with a variety of early feeding regimens have demonstrated unrestricted diets do not worsen the course or symptoms of mild diarrhoea and can decrease stool output compared with oral rehydration therapy (ORT) or intravenous therapy alone.54,58,60-66 (Level Ib Evidence, Grade A Recommendation) When used with ORT, early feeding can reduce stool output as much as cereal-based ORT can.67,68 (Level Ib Evidence, Grade A Recommendation) Meta-analysis on the studies from developed countries shows that early refeeding reduces the duration of diarrhoea by 0.43 days (95% CI, -0.74 to -0.12), and improves nutrition.14,63-65 (Level Ia Evidence, Grade A Recommendation) Currently early refeeding is recommended by the European Society of Paediatric Gastroenterology and Nutrition, the American Academy of Pediatrics and in a recent evidence and consensus based review.13,14,55 (Level IV Evidence, Grade C Recommendation)

Lactose intolerance should be suspected in the presence of frothy watery acidic stools and with associated excoriation of the buttocks. Although transient lactase deficiency is common, particularly after rotavirus gastroenteritis, most children with decreased lactase levels do not have clinical features of malabsorption.42 (Level IV Evidence, Grade C Recommendation) Clinically significant lactose intolerance secondary to acute diarrhoea is apparently uncommon in Europe.69 (Level IIb Evidence, Grade B Recommendation) This has also been our experience on hospitalised children with acute diarrhoea in Hong Kong. (Level IV Evidence, Grade C Recommendation) A meta-analysis of clinical trials has indicated that lactose free diet is rarely necessary after acute diarrhoea.70 (Level Ia Evidence, Grade A Recommendation) If children are followed up to identify the few in whom signs of malabsorption develop, a regular age-appropriate diet, including full-strength milk, can be safely used for refeeding.

The question of which foods are best for refeeding has been an issue of continuing study. Although agreement is not universal, controlled clinical trials suggest that certain foods, including complex carbohydrates (rice, wheat, potatoes, bread, and cereals), lean meat, yoghurt, fruits, and vegetables, are better tolerated.60,67,68,71 (Level Ib Evidence, Grade A Recommendation) Fatty foods or foods high in simple sugars (including tea, juices, and soft drinks) should be avoided.13,42 (Level IV Evidence, Grade C Recommendation)

Drug Therapy

Antibiotic Use

Recommendation

  • Antibiotics are not recommended for uncomplicated diarrhoea. (Level III Evidence, Grade B Recommendation)
  • Most cases of Salmonella gastroenteritis do not require antibiotic therapy as symptoms are not improved by antibiotics. (Level Ib Evidence, Grade A Recommendation)
  • Parenteral antibiotics, e.g. third generation cephalosporins may be required for young infants (<3 months), any ill or septic looking patient and immunocompromised children with Salmonella gastroenteritis who have a higher risk of complications. (Level IV Evidence, Grade C Recommendation)
  • Campylobacter gastroenteritis is usually self-limiting and antibiotic may only be of value if given early. Antibiotic may be indicated for children in institutional settings to shorten bacterial excretion. (Level IV Evidence, Grade C Recommendation)
  • Shigellosis is highly infectious and notifiable. Antibiotic may shorten the infectious period but the disease is often self-limiting and hence antibiotic is used in ill patients or those who are still symptomatic when the pathogen is detected. (Level IV Evidence, Grade C Recommendation)
  • Antibiotics are not usually required for diarrhoeagenic E. Coli, Yersinia enterocolitica, Vibrio para-haemolyticus, Aeromonas spp., Plesiomonas spp. Oral metronidazole or vancomycin is indicated for severe Clostridium difficile associated diarrhoea. Metronidazole is helpful for giardia lamblia. (Level IV Evidence, Grade C Recommendation)

Evidence

Salmonella

Salmonellosis is very common in Hong Kong. Randomised control trials have shown that antibiotic treatments, even with higher generation cephalosporins or macrolides, did not shorten the duration of diarrhoea or fever.72 Antibiotics are not indicated, except for extra-intestinal involvement, immunocompromised patients, very ill children, or infants younger than 3 months old.16 Ampicillin, cefotaxime or ceftriaxone parenterally are useful in such situations.16,73 Although local sensitivity patterns indicate that co-trimoxazole and chloramphenicol may also be effective,74 they are seldom used as empirical therapy because of their potential side effects, especially in young infants.

Campylobacter

Campylobacter gastroenteritis is usually mild and self-limited. The benefit of antibiotic is questionable for the individual unless it is given within the first few days of the illness. However it shortens the period of bacterial shedding and hence may be useful for institutional children or nursery infants to reduce cross-infection.75 Campylobacter spp. are sensitive to erythromycin and chloramphenicol.74

Shigella

Antibiotic therapy for shigellosis is controversial. Antibiotic is probably not needed in mild diarrhoea as the disease is often self-limited but it should be considered in severely ill patients and those who are still symptomatic when the stool culture is positive. It may shorten bacterial excretion.75 The haemolytic uraemic syndrome (HUS) was associated with the use of antibiotics in shigella gastroenteritis. However, the risk of HUS may in fact be reduced if patients were given an appropriate antibiotic early. It is postulated that the inappropriate antibiotics, to which the bacteria are resistant, would allow the disease to progress or may even enhance the disease severity.76 Nalidixic acid and ceftriaxone are usually effective.74,75

E. Coli

Diarrhoeagenic E. Coli are not a significant clinical problem locally.77 Data on the use of antibiotics is limited.78,79 There are six types: ETEC - Enterotoxigenic (traveller's diarrhoea and watery diarrhoea in weaning children); EPEC - Enteropathogenic (persistent watery diarrhoea in young children) where non-absorbable oral antibiotics, e.g., aminoglycosides, have been shown to be effective; EHEC - Enterohaemorrhagic (haemorrhagic colitis and HUS) where use of antibiotics is controversial; EIEC - Enteroinvasive (less severe invasive colitis); EAEC - Enteroaggregative (mucoid secretory acute or persistent diarrhoea); DAEC - Diffuse-adherent.

Other Bacteria

Yersinia enterocolitica, Vibrio parahaemolyticus, Aeromonas spp., and Plesiomonas spp. gastroenteritis are usually mild. Use of antibiotics is not necessary in general.75 Staphylococcus aureus toxin causes vomiting and diarrhoea. Use of antibiotic is not indicated. Enteral symptoms caused by Bacillus cereus usually resolve within a day and do not require antibiotic.75 Oral metronidazole or vancomycin is indicated for severe Clostridium difficile associated diarrhoea. A second course of these antibiotics and/or probiotics may be helpful to treat relapse, which may be up to 40%.75,80

Parasites

Giardia lamblia and Entamoeba histolytica very occasionally cause diarrhoea. Metronidazole is helpful.81,82

Probiotics

Recommendation

  • Probiotics (Lactobacillus) are safe and effective and can be recommended for the treatment of children with acute infectious diarrhoea. (Level Ia Evidence, Grade A Recommendation)

Evidence

Microflora of the large intestine normally ferment residual carbohydrate and produce short chain fatty acids (SCFAs). This reduces the luminal pH and discourages intestinal pathogens. The SCFAs also enhance colonic water absorption. In acute diarrhoea, as intestinal microflora is altered, production of SCFAs is reduced and there is increased water loss.14 Given these theoretical advantages, probiotics have been tried on acute infectious diarrhoea.83 Among the probiotics, Lactobacillus spp. and Saccharomyces boulardii are more widely studied and used clinically. Still the number of studies for treatment of acute diarrhoea is small. The evidence that Lactobacillus spp. alter the course of diarrhoea is not consistently demonstrated.14 Saccharomyces boulardii is a non-pathogenic yeast and was found to be effective in the treatment of diarrhoea associated with Clostridium difficile.84 One randomised placebo-controlled study demonstrated its efficacy in shortening the duration of acute childhood diarrhoea.85 A recent meta-analysis suggests that Lactobacillus is safe and effective as treatment for children with acute infectious diarrhoea.86 Issues of cost effectiveness need further investigation to better delineate the role of probiotics in management of acute diarrhoea (Table 6).

Table 6 List of Probiotics in Drugdex and Martindale from HALIS search and MIMS (Hong Kong)
Brand names Micro-organisms
Bacid Lactobacillus
Bioflor* Saccharomyces boulardii
DDS-Acidophilus L. acidophilus
Enpac Lactobacillus
Infloran Berna* Bifidobacterium infantis,
Lactobacillus acidophilus
Lacteol fort* L. acidophilus (killed)
Lactinex L. acidophilus + L. bulgaris
Shin-Biofermin S* Bifidobacterium bifidum,
Lactobacillus acidophilus,
Streptococcus fecalis
*available in Hong Kong

Antidiarrhoeal Agents

Recommendation

  • Antidiarrhoeal drugs are not routinely recommended for acute diarrhoea in children. (Level IV Evidence, Grade C Recommendation)

  • These agents should not be used in children with fever, toxaemia or blood in the stool. (Level IV Evidence, Grade C Recommendation)

  • Users of these agents as adjunctive therapy should pay attention to precautions and possible risks. Attention to the appropriate dosage and proper education of parents are prudent. (Level IV Evidence, Grade C Recommendation)

Evidence

Anti-motility Drugs

Examples of these drugs include loperamide, diphenoxylate + atropine, difenoxin & atropine, paregoric. These drugs act rapidly by producing segmental contractions of the intestine, thereby reducing peristalsis, diarrhoea and pain. They may also inhibit intestinal secretion. Side effects include dizziness, dry mouth, drowsiness, constipation & vomiting. They should be avoided in patients with high fever, toxaemia, or bloody mucoid stools.87 They are usually not necessary for the management of acute diarrhoea as it is usually self-limiting. Most are not approved for children less than 2 or 3 years of age.88 In certain circumstances, they may be used as an adjunctive treatment to oral rehydration therapy. These drugs should only be prescribed to children of appropriate age group and with the recommended dosage. Parents should be routinely reminded the directions of dosing and the possible side effects.

Results of clinical trials on loperamide are too conflicting to allow any conclusion about the risk benefit ratio. Seven placebo-controlled trials with loperamide were identified and four showed either an antidiarrhoeal effect or better weight gain in the loperamide group,87,89-91 while the other studies found no benefit.92-94 However, side effects were associated with loperamide use, especially with the higher dose of 0.4-0.8 mg/kg/day.91 The most recent study that demonstrated benefit with minimal side effects used a dose of 0.14-0.28 mg/kg/day in children 2 years or more.87

Loperamide is approved by U.S. Food and Drug Administration for treating acute diarrhoea only in patients at or above 2 years old. Diluted syrup form may be safer than concentrated drops as the chance of overdose for the latter preparation is probably higher. The risk of inadvertent overdose is a concern.95 The American Academy of Pediatrics does not recommend loperamide to treat acute diarrhoea in children based on strong committee consensus and limited scientific evidence that the risks of adverse effects outweigh the limited benefits.14

Loperamide has often been used by paediatricians locally as reported in a recent retrospective questionnaire survey.96 The Private Practising Paediatricians Study Group recommended the following dosage for loperamide: ?.1 mg/kg/dose three times a day as required. The diluted preparation rather than loperamide drops were recommended and only limited doses per visit should be given.96

Adsorbents

Examples of these drugs include smectite, kaolin-pectin, attapulgite. These theoretically act by adsorbing bacterial toxins and binding water to improve stool consistency. They may also adsorb nutrients, enzymes and medications in the intestine.88 Although a few controlled studies have shown possible benefit,97-101 most medical authorities still do not think the evidence is convincing enough for recommending their routine use.14,82,102 Passage of a formed stool does not imply therapeutic success because water content can remain high in such "formed" stools. Such cosmetic changes may give patients or their families a false sense of security, causing a delay in seeking more effective treatment. Therefore careful explanation to parents is needed when prescribing these drugs.

Anti-secretory Drugs

Examples of these drugs include bismuth-subsalicylate and racecadotril. Bismuth subsalicylate has been used as adjunctive therapy for acute diarrhoea. The mechanism of action is uncertain. It may act by inhibiting intestinal secretion. It was shown to reduce the frequency of unformed stools and decreased stool weight. No side effect was reported with the dosage of 100-150 mg/kg/day.103,104 However, the beneficial effects have been modest. As systemic absorption was noted, Reye syndrome is a theoretical risk.105 Racecadotril (synonyms: acetorphan, ecatorfate) inhibits enkephalinase to exert its anti-secretory effect by prolonging the action of endogenous enkephalins. It has a potential application in acute diarrhoea but studies are too few for any recommendation at present.106,107

In summary, all of the above drugs are not routinely needed because of lack of convincing clinical benefit while hydration therapy is well established. However individualised use as adjunctive therapy is sometimes useful while paying attention to the possible risk and precautions.14,82

Tables of Evidence

Table A Assessment of dehydration
Authors Study design N Treatment Results/Comments
(Gorelick et al, 1997)9
Philadelphia
Prospective cohort 1 m-5 yr 186 Evaluated for 10 clinical signs before treatment
Fluid deficit determined from serial weight gain after treatment
Capillary refill >2 seconds, absent tears, dry mucus membrane, and general appearance predict dehydration, indicate a deficit of at least 5%.
(Mackenzie et al, 1989)10
Australia
Prospective cohort <4 yr 102 Evaluated for presence of any or obvious sign of dehydration according to hospital guideline The mean estimated dehydration was 6.6% and the mean true dehydration was 3.4%.
3-4% is the level at which dehydration becomes clinically apparent, rather than 5% as usually stated.
Decreased skin turgor is the earliest sign of dehydration. Signs that pointed to dehydration >4% are: acidotic breathing, decreased peripheral perfusion, decreased skin turgor.
(Duggan et al, 1996)11
Egypt
Prospective cohort 3-18 m 135 Clinical assessment of signs according to two guidelines: Santosham & Fortin and Parent Patients classified as having mild, moderate and severe dehydration were found to have ~4%, ~5% and ~10% gain in percent weight respectively.
Abnormal skinfold is most significantly correlated with degree of dehydration followed by neurological status, weak pulse, sunken eyes, dry mucous membranes, deep breathing, weak pulse and cold extremities.

Acknowledgements

The provisional working draft of this document was prepared by a Task Force on Management Guidelines for Gastroenteritis convened by the Hong Kong Society of Paediatric Gastroenterology, Hepatology and Nutrition (Ip Kin-Sing, Lau CY David, Leung CW Paul, Leung Ying-Kit, Nelson EAS, Ng Chi-Hang, Poon Kin-Hung, Tse Kong, Yiu Wai-Lim, Yeung KY Wilson). The participation of the Task Force in this project is greatly appreciated. Many thanks also go to Li Kai-Ming of the Hong Kong College of Emergency Medicine, Tsang CY Luke of the Education and Training Centre in Family Medicine, Department of Health, Cheng Chun-Fai of the Private Practising Paediatricians Study Group and Chik Ki-Wai, Fung Lai-Wah, Sin Ngai-Chuen, Wong Hiu-Lei of the Prince of Wales Hospital for their assistance in reviewing the document during the drafting process.

Table B Investigations
Authors Study Design N Results/Comments
(Anonymous, 1996)14 Expert committee opinions 93 ref Electrolyte levels should be checked in moderately or severely dehydrated children as well as those on intravenous drip. Knowledge of electrolyte levels is especially important in hypernatraemic dehydration.
(Meropol et al, 1997)15
U.S.A.
Retrospective descriptive study 250 hospital admissions;
3-18 years old
Band neutrophil count of 0.1x109/L is 100% sensitive but not specific in picking up patient with positive stool bacterial cultures. (positive predictive value 9%, negative predictive value 100%) Only 7 of 250 (2.8%) admitted patients have positive stool bacterial culture.
(Geme et al, 1988)16 Consensus opinions and non-systematic review 32 ref The need of a blood culture for young infant with diarrhoea follows the principles as for other acute infectious illnesses. However, if Salmonella is suspected for epidemiological reasons, blood culture is needed even if the infant is not very ill as Salmonella bacteraemia is frequent and clinical severity of illness is a poor predictor for bacteraemia in infants with Salmonella gastroenteritis. Immunocompromised children are more likely to have extra-intestinal Salmonella infections.
(Gastanaduy & Begue, 1999)17 Non-systematic review 42 ref In developed countries, percentage of positive bacterial stool cultures and parasite detection are as follows: - Salmonella sp.: 2-4; Campylobacter sp.: 1-7; Shigella sp.: 1-3; Enterotoxigenic E. coli:1-4; Aeromonas sp.: <1; Vibrio sp.: rare; Giardia lamblia: 0-8; Cryptosporidium parvum: 1-3; Entamoeba histolytica: rare.
(Biswas et al, 1996a)2
Hong Kong
Prospective case-control study 388 hospitalised children with diarrhoea: birth-15 years old (95% are <5 years old); 306 control children Bacterial stool cultures were positive in 30% of diarrhoea patients versus 5.6% of controls.
Rotavirus was detected in 130 cases with diarrhoea (34%). Giardia lamblia cysts were found in 1 case only (0.3%).
(Kwan et al, 1999)18
Hong Kong
Retrospective descriptive study 2800 stools from 1135 hospitalised children Excluded immunodeficiency, routine stool surveillance and rectal swabs. 21.7% of patients yielded bacterial pathogens; 95.1% of cases werepicked up by the first stool specimen; a second and third specimen increased the yield to 98.4% and 99.1% respectively.
(Huicho et al, 1996)19
Various overseas studies analysed
Meta-analysis 2603 ref identified, 81 was relevant and 25 were fit for analysis Among the faecal screening tests, faecal lactoferrin was the most accurate index test for inflammatory bacterial diarrhoea; faecal occult blood produced intermediate performance while faecal leukocytes was the poorest index test.
(Chan et al, 1994)3
Hong Kong
Retrospective descriptive study Database of Virus Unit of Department of Health 1987-1992 For children 0-5 years old with acute diarrhoea, of 24466 stool specimens received, 4086 (16.7%) yielded viruses that might cause gastroenteritis:Rotavirus: 3462; Adenovirus: 386; Astrovirus: 151; Norwalk-like: 71; Calicivirus: 16.

 

Table C (1) Randomised, controlled trials of ORT and IV rehydration in developed countries (Level I)
Authors Study design n Treatment Results/Comments
(Santosham et al, 1982)23
U.S.A. & Panama
RCT 52 in US, 94 in Panama 98 ORT(50 GpA,
48 GpB)
48 IV
ORSA - WHO-ORS
ORSB - Na 50, Cl 40, osmolarity 251
Rehydrate over 12 h
Dilute soya formula when diarrhoea stopped
Rotavirus main pathogen 97/98 ORT successful (from Gp A).
All patients with electrolyte disturbances were successfully treated.
All 6 with hypernatraemia successfully rehydrated with ORT alone (4 Gp A, 2 Gp B).
(Bhargava et al, 1984)27
India
RCT
Birth to 3 m
22 ORSA
22 ORSB
21 IV
ORSA - WHO-ORS
ORSB - Na 60, Cl 50, osmolarity 270
Rehydrate over 8 h Full feeding when diarrhoea
stopped
44/44 ORT successful
Dehydration, acidosis, electrolyte disturbances corrected with equal efficacy in all 3 groups
(Sharifi et al, 1985)26
Iran
RCT 236 ORT
234 IV
Rehydration ORS: Na 80, HCO 35, Cl 65, G 70, osmolarity 270, at 40 ml/kg/hr via NGT
Maintenance ORS: Na 40, K30, G1 30, HCO 25, Cl 45, osmolarity 270
Refeed small amount of normal diet within 24 h
235/236 ORT successful.
ORT associated with lower incidence of convulsion in hypernatraemic patients, lower incidence of iatrogenic electrolyte disturbances, shorter duration of diarrhoea, greater weight gain and more rapid correction of hypokalaemia & acidosis.
(Tamer et al, 1985)24
U.S.A.
RCT 47 ORT
50 IV
ORS with Na 75, K75 for 6 h followed by ORS with Na 50, K50
Dilute soya formula after rehydration
44/47 ORT successful.
ORT associated with faster correction of acidosis and sustained rise in potassium.
(Listernick et al, 1986)49
U.S.A.
RCT
Outpatient
15 ORT
14 IV
ORS : Na 60, K 20, Cl 50, citrate 30, G 111, fructose 28; 20 ml/kg 1st hour, then ad lib 1/2 strength lactose-free formula after 24 h Rotavirus main pathogen.
History of vomiting in 100%.
13/15 successfully rehydrated with ORS.
2 failed - persistent vomiting and UTI.
No difference in electrolytes.
(Vesikari et al, 1987)25
Finland
RCT 22 ORT
15 IV
Rapid IV (12 hours) versus ORT
ORS : Na 60, K 20, Cl 50, HCO330, G 144, rehydrated over 6 h Normal diet after 12 hours
Rotavirus main pathogens.
2 in ORT required IV supplements.
Correction of dehydration, metabolic acidosis and sodium deficit at equal rates.
Duration of diarrhoea shorter in ORT.
Better reintroduction of feeding in ORT.
(Mackenzie & Barnes, 1991)50
Australia
RCT Stratified by age 52 ORT
52 IV
ORS : Na 50, K 20, Cl 40, citrate 10, G 111
Rehydrated over 6 h orally/ nasogastric tube
IV : deficit replaced over 24 h
No solid during rehydration
Rotavirus main pathogen. 3.8% failure rate in ORT group. Higher percentage with vomiting.
No difference in number of stool passed in first 24 h. None had electrolytes and acid base disturbances.
(Issenman & Leung, 1993)108
Canada
RCT 42 ORS : Na 75 and 45 Successful in 82% for ORT and 78% for IV.
RCT - Randomised controlled trial
All concentrations given in mmol/L.

 

Table C (2) Randomised, controlled trials comparing WHO-ORS with hypotonic ORS (Level I)
Authors Study design n Treatment protocol Results/Comments
(Bhargava et al, 1984)27
India
RCT
Birth to 3 m 3 cells with IV arm
22 (WHO)
22 (HORS)
21 (IV)
HORS (Na 60, Cl 50, osmolarity 270)
Rehydrate over 8 h Full feeding when diarrhoea stopped
Dehydration, acidosis, electrolyte disturbances corrected with equal efficacy.
HORS associated with lower mean Na, less patients with hypernatraemia, irritability & convulsion.
(el Mougi et al, 1994)109
Egypt
RCT
3 cells with IV arm
20 (HORS)
21 (WHO)
20 (IV)
HORS (Na 60, Cl 75, K 13, Cl 53, citrate 6.6, osmolarity 210). Plain water allowed after rehydration for WHO group.
Normal diet after 4-6 h
HORS associated with lower fluid intake, lower stool output and a trend towards shorter duration of diarrhoea versus WHO-ORS.
Serum sodium decreased by 2.9 mmol/L but within normal range.
(Mahalanabis et al, 1995)110
Bangladesh
RCT 30 (HORS)
30 (WHO)
HORS (Na 67, G 89, Cl 66, citrate 7, osmolarity 249).
Rotavirus and E. Coli main pathogens. 30% undernourished
HORS associated with lower ORS intake and lower stool output in non-rotavirus group.
No difference in electrolytes.
(Santosham et al, 1996)111
Egypt
RCT 94 (HORS)
96 (WHO)
HORS (Na 75, G 75, Cl 65, osmolarity 245)
Pre-cooked rice vegetable mixture after rehydration (<12 h)
HORS associated with lower stool output (36%) and lower risk of vomiting during rehydration and lower risk of treatment failure.
No difference during maintenance phase.
Ris of development or worsening of hyponatraemia not increased in HORS
(Valentiner-Branth et al, 1999)112
West Africa
RCT
Community based
344 (HORS)
361 (WHO)
HORS (Na 60, G 84, Cl 50, osmolarity 224)
E. Coli main pathogens
HORS as efficacious in terms of duration of diarrhoea and stool output.
HORS associated with shorter duration of diarrhoea and lower stool output in Non-breast-fed toddlers
(CHOICE Study Group, 2001)35
5 countries
Multicentre in
RCT 341 (HORS)
334 (WHO)
HORS (Na 75, G 75, osmolarity 245) 33% reduction in unscheduled IV therapy
RCT - Randomised controlled trials, HORS - Hypotonic ORS, WHO - WHO-ORS
All concentrations given in mmol/L. Electrolytes concentration same as WHO-ORS unless otherwise specified

 

Table C (3) Clinical trials comparing High osmolarity ORS with low osmolarity ORS
Authors Study design n Treatment Results / comments
(Rautanen et al, 1993)113
Finland
Non-randomised
Open trial
103 (HORS)
135 (SORS)
HORS (Na 60, G 84, Cl 50, osmolarity 224)
SORS (Na 60, Cl 50, G 144, HCO 30, osmolarity 304).
Rehydrate over 6-8 h orally/ nasogastric tubes (2x deficit).
Normal diet after rehydration.
Rotavirus in >75% of cases
HORS associated with lower stool output, shorter duration of diarrhoea and hospitalisation and less ORS intake.
Requirement for IV supplementation not different.
(Rautanen et al, 1997)114
Finland
RCT 35 (HORS)
35 (SORS)
Same as 1
Rehydration over 6-8 h = 4/3 vol of deficit
Normal feeding after rehydration
Rotavirus in 57%
HORS associated with lower stool output and lower ORS intake. No difference in weight gain, electrolyte balance, recovery from acidosis and requirement for IV therapy.
Subgroup analysis for rotavirus infection showed similar beneficial effect of HORS.
RCT - Randomised controlled trial, HORS - Hypotonic ORS, SORS - Standard ORS
Electrolyte concentrations same as WHO-ORS unless otherwise specified

 

Table C (4) Rice-based ORS versus WHO-ORS (Level I)
Authors Study design n Treatment Results/Comments
(Patra et al, 1982)115
India
RT, unblinded 3 m-5 yr
Failure excluded
26 (RORS)
26 (WHO)
RORS - pop rice-based 50 g
Fed ad lib
Cholera and rotavirus main pathogens. RORS associated with lower stool output and ORS intake and shorter duration of diarrhoea.
(Molla et al, 1985)116
Bangladesh
RT, unblinded
157 adults and
185 children
84 (RORS)
101 (WHO)
RORS - 80 g, osmolarity 288 75% severe dehydration, 75% cholera infection.
RORS associated with lower stool output, lower ORS intake and lower failure rate.
(Alam et al, 1987)117
Bangladesh
RT, unblinded
3-cell study
1-8 yr
Failure excluded
24 (RORS)
24 (WORS)
24 (WHO)
RORS- 50 g rice powder
WORS - 50 g wheat powder, osmolarity 280. IV for 1-2 h
Normal diet after rehydration
Cholera main pathogen. RORS and WORS associated with lower stool output and ORS intake. Same failure rates, same duration of diarrhoea. No difference in non-cholera subgroup.
(Bhan et al, 1987)118
New Delhi
RT, unblinded
3-cell study
3 m-5 yr
31 (RORS)
29 (LORS)
33 (WHO)
RORS - 50 g pop rice powder
LORS - 60 g Mung bean powder
Rehydrate over 8 h
1/2 milk after 8 h
cereal after 24 h
Rotavirus and E. Coli main pathogens. No difference in failure rates, purging rates, duration of diarrhoea, changes in electrolytes and presence of reducing substances. RORS associated with higher urine output and intake of solid foods.
(Dutta et al, 1988)119
Calcutta
RT, unblinded
3-cell study
4 m-4 yr
35 (RORS)
37 (PRORS)
33 (WHO)
RORS - 30 g rice powder
(RORS) and 50 g pop rice powder (PRORS)
1/2 milk and BF after 6 h
Cholera, E. Coli and rotavirus main pathogens
No difference in stool output, duration of diarrhoea, ORS intake and weight gain.
(el Mougi et al, 1988)120
Egypt
RT, unblinded
4-18 m
30 (RORS)
30 (WHO)
RORS - 50 g rice powder
1/2 milk after 6 h for 24 h, then FS milk
Stool cultures not done.
Children mildly malnourished.
RORS associated with better weight gain, shorter duration of diarrhoea, lower ORS intake and stool output and less episodes of vomiting Same failure rates.
(Mohan et al, 1988)121
New Delhi
RT, unblinded
Failure excluded
26 (RORS)
24 (WHO)
RORS - 50 g rice powder
1/2 milk and normal diet after 8 h
80% had vomiting. Failure rate same. RORS associated with decreased stool frequency in 1st 24 h.
(Molla et al, 1989)122
Bangladesh
RT, unblinded
<5 yr
47 (RORS)
46 (WHO)
RORS - 50 g rice-flour based
Normal diet after 24 h
Cholera proven cases only. RORS associated with lower ORS intake and stool output in 1st 24 h only.
(Fayad et al, 1993)67
Egypt
RT, unblinded
3-18 m
219 (RORS)
222 (WHO)
RORS - pre-cooked rice-based 50 g
Weaning diet after rehydration (4-12 h)
No differences in rehydration phase in stool volume, ORS intake, weight gain and duration of rehydration.
WHO-ORS associated with lower stool volumes and ORS intake and shorter duration of diarrhoea after initiation of feeding. Failure rates same. Duration of diarrhoea on admission longer in WHO group by 1 day.
(Islam et al, 1994)123
Pakistan
RT, unblinded 27 (RORS)
25 (WHO)
RORS - 50 g rice powder, osmolarity 288
Infants <6 months old
Normal diet after 6 h
(1/2 S milk)
E. Coli most common pathogen.
Success rate: RORS 70%, WHO 72%.
RORS associated with lower stool output and ORS intake from 6-48 h, no difference in duration of diarrhoea and presence of glucose intolerance.
(Maulen-Radovan et al, 1994)124
Mexico
RT, unblinded 49 (RORS)
48 (WHO)
RORS - pre-cooked rice-based
50gInfants <6 months old. Low-protein milk and FS milk after 6 h for infants below or above 4 m
Rotavirus and E.Coli main pathogens.
No difference in stool output, ORS intake, duration of diarrhoea, presence of reducing substances in stool.
(Guiraldes et al, 1995)125
Chile
RT, unblinded
3-18 m
51 (RORS)
49 (WHO)
RORS - pre-cooked rice powder 50 g, osmolarity 260.
ORS only 1st 4 h, then plain water added next 2 h, normal diet after 6 h
Rotavirus and E. Coli main pathogens.
No differences in stool output, duration of diarrhoea, carbohydrate malabsorption and failure rates.
(Dutta et al, 2000)126
Calcutta
RT,
2-10 yr, boys
19 (HORS)
19 (RORS)
20 (WHO)
HORS - Na 70, K 20, G 16.2,
RORS - Na 70, K 20, rice 50
All cholera. All patients given IV therapy for first 6-8 h and treated with tetracycline for 3 days. Duration of diarrhoea, stool output and ORS requirement all significantly less in rice-ORS.
(Zaman et al, 2001)127
Bangladesh
RT, unblinded
5-15 yr, boys
85 (RORS)
82 (WHO)
RORS - Packaged proprietary form of rice syrup 40 g, Na 90, osmolarity 270 88% had cholera, all given antibiotics and early feeding.
Stool output decreased by 20% in rice-ORS in first 8 h only.
RORS - Rice-based ORS, PRORS - Pop rice powder ORS, LORS - Lentil based ORS, WORS - Wheat-based ORS, WHO - WHO-ORS, HORS - Hypotonic glucose ORS, RT - Randomised trials, Yr - years, m - months
Rice concentration - in g/L
Other concentrations given in mmol/L
RORS - same electrolyte concentrations as WHO-ORS unless otherwise specified

 

Table D Nutrition therapy
Authors Study design n Treatment Results/Comments
(Alarcon et al, 1991)60
Developing country
RCT 29:28:28 Soy formula, wheat-peas, potato-milk Latter two locally available diets were as effective as commercial soy formula.
(Anonymous, 1996)14 Review/Meta 93 ref   AAP guidelines on management of acute gastroenteritis in young children.
(Brown et al, 1988)61
Developing country
RCT 31:29:34:34 4 lactose free groups Malnourished. Therapeutic success similar in 4 groups (lactose free). Continued early oral feeding improved nutritional results.
(Brown et al, 1991)71
Developing country
RCT 28:30:29:29 Milk-noodles and milk Two noodle-milk groups better than two milk groups.
(Brown & Lake, 1991)58 Review 49 ref   Continue feeding during diarrhoea; excess complications in small subgroup with exclusive nonhuman milk; discuss methodological problems.
(Brown et al, 1994)70 Meta 43 ref   Vast majority of young children with acute diarrhoea successfully managed on undiluted nonhuman milks. Routine use of lactose-free milk is unnecessary.
(Duggan et al, 1992)42 Review     CDC guidelines on management of acute gastroenteritis.
(Faruque et al, 1992)59
Developed country
Case-control 285:728   Withdrawal of breastfeeding during diarrhoea 5x increase risk of dehydration.
(Fayad et al, 1993)67
Developing country
RCT 222:210 G-ORS and R-ORS G-ORS resulted in lower stool volumes than R-ORS after early introduction of rice diet.
(Fox et al, 1990)62
Developing country
RCT 32:30 Gradual versus abrupt refeeding Gradual refeeding versus abrupt refeeding in infants under 6 months. No difference but 42% had diarrhoea recurrence responding to lactose-free formula.
(Golding et al, 1997)56 Review 61 ref   Focus on breastfeeding and protection against gastroenteritis.
(Hjelt et al, 1989)63
Developed country
RCT 25:27 Gradual versus rapid refeeding with full-strength lactose-limited milk. Higher stool frequency and energy intake in rapid group.
(Isolauri & Vesikari, 1985)64
Developed country
RCT 11:42:39 IV fluids, WHO ORS or low osmolality ORS groups, also randomised to receive cholestyramine or placebo, and randomised to rapid or slow feeding schedule Rapid feeding group did better.
(Isolauri et al, 1989)52
Developed country
Comparative 50 (41) Grouping (parents preadmission treatment):
A (n=12) fasted;
B (n=17) oral fluids;
C (n=12) fluids + food
 
(Khin et al, 1985)54
Developing country
RCT 26:26 Breastfeeding continued or not Continued breastfeeding group during diarrhoea passed fewer stools of smaller volume and recovered quicker.
(Lembcke & Brown, 1992)57 Review 29 ref   Continue breastfeeding (2 ref); also feeding in most cases; exclusive non-human milk may increase complications.
(Levine et al, 1974)53 Animal 6/7   IV alimentation versus oral - effect on gut mucosa.
(Margolis et al, 1990) Developed country65 RCT 21:35 Unrestricted diet versus graded refeeding Children with mild diarrhoea on unrestricted diet recovered sooner than infants given graded refeeding.
(Murphy, 1998)48 Review 70 ref   Guidelines based on systematic review.
(Rees & Brook, 1979)66
Developed country
RCT 16:16:14 Full-strength (FS), clear fluids (CF) + FS or CF + graded refeeding More vomiting in FS but no need to change treatment.
(Sandhu et al, 1997)69
Developed country
RCT 134:96 Early and late feeding groups in multicentre study  
(Santosham et al, 1990)68
Developing country
RCT 50x4 G-ORS/Soy Formula, G-ORS/Rice Formula, R-ORS/SF, G-ORS/rice  
(Walker-Smith et al, 1997)55 Review 14 ref   ESPGAN recommendations for feeding in childhood gastroenteritis.

 

Table E Antibiotic use
Authors Study design n Treatment Results/Comments
(Nelson et al, 1980)128
U.S.A.
Prospective randomised double-blind placebo control study Paediatric patients:-
Ampicillin group: n=15
Amoxicillin group: n=15
Placebo group: n=14
Ampicillin or amoxicillin
100 mg/kg/day in 4 divided doses x 5 days or placebo x 5 days
No difference in duration of diarrhoea among the 3 groups. Bacteriologic relapse was higher in antibiotic group (p=0.003).
(Chiu et al, 1999)72
Taiwan
Prospective randomised control study 42 children >6 months old with uncomplicated
Salmonella gastroenteritis, equally divided among 3 groups
Oral macrolide and third generation cephalosporin therapy were studied:
A: Azithromycin 10 mg/kg/day once daily x 5 days; B: Cefixime 10 mg/kg/day bd. x 5 days; C: No antibiotic
Duration of fever, diarrhoea and Salmonella carriage were similar in the three groups.
(Aserkoff & Bennett, 1969)129
U.S.A.
Cohort study at an outbreak of Salmonella typhimurium Antibiotic treated: n=185
No antibiotic: n=87
All were symptomatic adults
Ampicillin 1 g daily x 3 days or Chloramphenicol 1 g daily x 3 days 65.4% and 27.0% of antibiotic treated patients still carried Salmonella 12 and 31 days respectively after exposure compared to corresponding figures of 42.5% and 11.5% for those not given antibiotics.
(Geme et al, 1988)16 Consensus opinions and non-systematic review 32 ref Discussion on investigations and antibiotic treatment for infants with Salmonella gastroenteritis in developed country (U.S.A.) Antibiotic therapy is not needed in children with uncomplicated Salmonella gastroenteritis in general. Bacteraemia and extraintestinal complication is more likely in young infants, especially those < 3 months old. Any infant with Salmonella gastroenteritis should have a blood culture done. If Salmonella bacteraemia is documented or if the infant is ill, he should be treated with cefotaxime or ceftriaxone. Immunocompromised patients should receive antibiotics even if they do not appear ill.
(Anonymous, 2000)130 Expert committee opinions and non-systematic review Not listed Discussion on treatment of infections for developed country (U.S.A.) Treatment of individual infectious diarrhoea is discussed.
(Pickering & Matson, 1995)73 Expert opinions and non-systematic review 197 ref Treatment modality for infectious diarrhoea in children Antibiotic choices and dosages for various bacterial and parasitic causes of diarrhoea are discussed.
Of note is dosage intervals for cefotaxime, ceftriaxone and ampicillin in treating Salmonella bacteraemia are every 6, 12 and 4 hours respectively.
(Cohen & Laney, 1999)75 Expert opinions and non-systematic review 249 ref   Antibiotic therapy for various bacterial pathogens were discussed. For Campylobacter gastroenteritis, bacterial excretion may be up to 7 weeks; this may be shortened by antibiotic therapy. Antibiotic may also shorten symptomatic period if given within 4 days of the illness. Antibiotics neither reduce symptoms nor shorten bacterial excretion period for Yersinia gastroenteritis. Antibiotic is recommended only if patient has severe disease and underlying illness. Similarly, antibiotic is advised for severe cases of gastroenteritis due to Vibrio parahaemolyticus, Aeromonas and Plesiomonas.
(Butler et al, 1987)76
Bangladesh
Retrospective case control study 30 children of haemolytic-uraemic syndrome (HUS) and 30 age-matched control subjects; all had Shigella dysenteriae 1 isolated Antibiotic treatment was started empirically for all patients on the first day of admission 14 cases of HUS group vs. 6 of control group had received antimicrobial therapy before admission (p<0.05); inappropriate antibiotic use in first 2 days after admission was found in 17 cases in HUS group vs. 7 in control group (p<0.05).
(Nataro & Kaper, 1998)78
Non-systematic review 719 ref Not applicable It was a comprehensive review on diarrhoeagenic E. Coli. Both the microbiological and clinical aspects were covered.
(Wong et al, 2000)79
U.S.A.
Prospective cohort study N=71 History of treatment, both antibiotic or non-antibiotic, were reviewed for each patient Children with E. Coli O157:H7 were studied. Antibiotics increased the risk of HUS: HUS occurred in 5 of 9 children (56%) who were given antibiotics versus 5 of 62 (8%) who did not receive antibiotics (p<0.001).
(Vanderhoof & Young, 1998)84 Non-systematic review 121 ref Probiotic therapy for children Use of probiotics for Clostridium difficile associated diarrhoea was discussed.
(Pruksananonda & Powell, 1989)80
U.S.A.
Case report and non-systematic review N=2 (4 months and 1 year old respectively) Cholestyramine therapy x 7 weeks was effective for relapse of Clostridium difficile associated diarrhoea Cholestyramine was efficacious in the two cases.
(Heresi & Cleary, 1997)81 Expert opinions and non-systematic review 10 ref (for reader) Treatment of giardiasis Quinacrine, furazolidone and metronidazole were listed as effective therapy but FDA only approved the first two for children since it consider the safety of metronidazole in children being uncertain in view of its mutagenic effect in animals.
(WHO, 1990)82 Expert opinions and non-systematic review   Treatment of giardiasis and amoebiasis Metronidazole is listed as drug of choice for both conditions; alternatives for giardiasis are tinidazole, ornidazole and quinacrine; alternative therapy for amoebiasis is dehydroemetine hydrochloride.

 

Table F (1) Drug therapy: Loperamide
Authors Study design n Treatment Results/Comments
(Motala et al, 1990)91 Placebo-controlled 30 infants (male, 6 wk-12 m), 30 control Loperamide 0.8 mg/kg/day Subjects: shorter duration of diarrhoea (2.5 vs 6 days) Lower daily stool output (gm/dg/day)
No difference in rotavirus GE 4 drowsiness, 1 ileus, 1 persistent severe vomiting, doubts regarding safety.
(Bowie et al, 1995)92 Double-blind Placebo-controlled 91 infants & young children, 94 control acute dehydrating diarrhoea   No difference between groups for duration of rehydration or no. of treatment failures. Use of loperamide not recommended.
(Anonymous, 1984)89 Double-blindPlacebo-controlled Multicentre 315 young children 0.4 mg/kg/day,
0.8 mg/kg/day
or placebo
Larger proportion of children in Loperamide groups gained wt than in placebo (wt on admission & 3 days later) 1 abdominal distension.
(Karrar et al, 1987)90 Double-blind Placebo-controlled 53 young children 0.4 mg/kg/day,
0.8 mg/kg/day
or placebo
Recovery rate p<0.05
Fastest: 0.8 mg/kg/day
Slowest: placebo gp
Wt gain (on admission & 3 days later)
Loperamide gps > placebo p<0.05
1 excessive lethargy & sleepy
(Ghisolfi et al, 1987)93 Double-blind Placebo-controlled 63 infants
1-32 m
Loperamide
0.16-0.2 mg/kg/day
No significant decrease in no. of stools or more rapid recovery from diarrhoea. No mention of side effect.
(Owens et al, 1981)94 Double-blind Placebo-controlled 50 subjects
1 m-4 yr
Loperamide 0.2 mg/kg/day No significant difference in duration of diarrhoea. No side effect.
(Kaplan et al, 1999)87 Multicentre randomised controlled-placebo 130 subjects
2-11 yr (87 subjects 2-6 yr)
128 controls
Loperamide 0.14-0.28 mg/kg/day Shorter time to last unformed stool (p=0.0017)
Median time 26.8 h to 18.5 h
Higher rating of efficacy & acceptability.
Adverse events in 15% Loperamide group, 7% in placebo p=0.048 e.g. vomiting, nausea, fever, somnolence.
(PPPSG, 2000)96 Retrospective questionnaire survey 26 paediatricians 25/26 used loperamide for gastroenteritis in patients above 3 months old. 72% found it "usually useful" and 28% "sometimes useful" in reducing diarrhoea. A dose of 0.1 mg/kg or less given 2-4 times daily [0.2-0.4 mg/kg/day] was most commonly employed. 62% of respondents did not encounter side effects with loperamide. Of 20 cases with side effects recalled by the doctors, 14 had abdominal distension or ileus, and 1 had respiratory depression (attributed to gross overdose by mother). No fatality reported.

 

Table F (2) Drug therapy: Bismuth subsalicylate
Authors Study design n Treatment Results/Comments
(Figueroa-Quintanilla et al, 1993)103 Randomised placebo-controlled 275 male infants & young children (mean age 13.5m) Bismuth subsalicylate 100-150 mg/kg/day Lower stool output, p=0.015
Lower intake of ORS, p=0.013
Shorter duration of hospitalisation, p=0.005.
Bismuth & Salicylate blood level well below toxic level.
(Soriano-Brucher et al, 1991)104 Double-blindPlacebo-controlled 123 children
4-28 months
Bismuth subsalicylate
100 mg/kg/day
Significant decrease in stool freq. & stool wt
Decrease in disease duration (6.9 vs. 8.5 days)
Decrease IV fluid requirement.
Increase clearance of pathogenic E. Coli but not rotavirus No side effect. Bismuth & Salicylate level well below toxic level.

 

Table F (3) Drug therapy: Smectite and attapulgite
Authors Study design n Treatment Results/Comments
(Madkour et al, 1993)100 Double-blind Placebo-controlled 90 boys
(3-24 m)
Smectite 1.5 gm in 50 ml water QID x 3 days Shorter duration of diarrhoea. Fewer stools Amount of liquid stools not significantly reduced. Higher wt gain.
(Vivatvakin et al, 1992)101 Randomised placebo-controlled 62 children
(1-24 m)
Smectite 3.6 gm/day Shorter duration of diarrhoea (8.4 vs. 4.3 days), p=0.005. Stool frequency and weight changes no significant differences. No side effects.
(Gilbert et al, 1991)99   56 (2-24 m) Smectite, Loperamide or placebo Diarrhoea resolved faster under Smectite than placebo
Similar between Smectite & Loperamide. Smectite was well tolerated.
(Charritat et al, 1992)97 Placebo-controlled multicentre study 113 children (mean age 28 m) Attapulgite 1st & 2nd normal formed stools were passed one day earlier in subjects (p=0.01 & 0.002) resumption of normal diet earlier (4.4 vs 5.1 days). Well tolerated.

 

Table F (4) Drug therapy: Probiotics
Authors Study design n Treatment Results/Comments
(Van Niel et al, 2002)86 Meta-analysis 9 RCTs with a total of 391 cases and 374 controls Lactobacillus Duration of diarrhoea reduced by 0.7 days (95% CI: 0.3-1.2 days) and diarrhoea frequency reduced by 1.6 stools on Day 2 of treatment (95% CI: 0.7-2.6 fewer stools).

References

1. Chan PK, Tam JS, Nelson EA, et al. Rotavirus infection in Hong Kong: epidemiology and estimates of disease burden. Epidemiol Infect 1998;120:321-5.

2. Biswas R, Lyon DJ, Nelson EA, Lau D, Lewindon PJ. Aetiology of acute diarrhoea in hospitalized children in Hong Kong. Trop Med Int Health 1996;1:679-83.

3. Chan PK, Lim WL, Wong MF, Kwok CSY. Viral gastroenteritis in Hong Kong. J Hong Kong Med Assoc 1994;46:195-9.

4. Lam BC, Tam J, Ng MH, Yeung CY. Nosocomial gastroenteritis in paediatric patients. J Hosp Infect 1989;14:351-5.

5. Yam WC, Lung ML, Yeung CY, Tam JS, Ng MH. Escherichia coli associated with childhood diarrheas. J Clin Microbiol 1987;25:2145-9.

6. Tam JS, Kum WW, Lam B, Yeung CY, Ng MH. Molecular epidemiology of human rotavirus infection in children in Hong Kong. J Clin Microbio 1986;23:660-4.

7. Zheng BJ, Lo SK, Tam JS, Lo M, Yeung CY, Ng MH. Prospective study of community-acquired rotavirus infection. J Clin Microbiol 1989;27:2083-90.

8. Ling JM, Cheng AF. Infectious diarrhoea in Hong Kong. J Trop Med Hyg 1993;96:107-12.

9. Gorelick MH, Shaw KN, Murphy KO. Validity and reliability of clinical signs in the diagnosis of dehydration in children. Pediatrics 1997;99:E6.

10. Mackenzie A, Barnes G, Shann F. Clinical signs of dehydration in children. Lancet 1989;2:605-7.

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

12. Armon K, Elliott E. Acute gastroenteritis. In: Moyer V, Elliott E, Davis RL, et al., editors. Evidence based pediatrics and child health. BMJ 2000:273-86.

13. Armon K, Stephenson T, MacFaul R, Eccleston P, Werneke U. An evidence and consensus based guideline for acute diarrhoea management. Arch Dis Child 2001;85:132-42.

14. Practice parameter: the management of acute gastroenteritis in young children. American Academy of Pediatrics, Provisional Committee on Quality Improvement, Subcommittee on Acute Gastroenteritis. Pediatrics 1996;97:424-35.

15. Meropol SB, Luberti AA, De Jong AR. Yield from stool testing of pediatric inpatients. Arch Pediatr Adolesc Med 1997;151:142-5.

16. Geme JW 3rd, Hodes HL, Marcy SM, et al. Consensus: management of Salmonella infection in the first year of life. Pediatr Infect Dis J 1988;7:615-21.

17. Gastanaduy AS, Begue RE. Acute gastroenteritis. Clin Pediatr (Phila) 1999;38:1-12.

18. Kwan E, Poon G, Tse C, Wong M, Chiu S, Seto WH. How many stool cultures are good enough? Hong Kong: Queen Mary Hospital Quality Improvement Forum, 1999:47.

19. Huicho L, Campos M, Rivera J, Guerrant RL. Fecal screening tests in the approach to acute infectious diarrhea: a scientific overview. Pediatr Infect Dis J 1996;15:486-94.

20. Hirschhorn N, Kinzie JL, Sachar DB, et al. Decrease in net stool output in cholera during intestinal perfusion with glucose-containing solutions. N Engl J Med 1968;279:176-81.

21. Gavin N, Merrick N, Davidson B. Efficacy of glucose-based oral rehydration therapy. Pediatrics 1996;98:45-51.

22. Gore SM, Fontaine O, Pierce NF. Impact of rice based oral rehydration solution on stool output and duration of diarrhoea: meta-analysis of 13 clinical trials. BMJ 1992;304:287-91.

23. Santosham M, Daum RS, Dillman L, et al. Oral rehydration therapy of infantile diarrhea: a controlled study of well-nourished children hospitalized in the United States and Panama. N Engl J Med 1982;306:1070-6.

24. Tamer AM, Friedman LB, Maxwell SR, Cynamon HA, Perez HN, Cleveland WW. Oral rehydration of infants in a large urban U.S. medical center [published erratum appears in J Pediatr 1986;108:160]. J Pediatr 1985;107:14-9.

25. Vesikari T, Isolauri E, Baer M. A comparative trial of rapid oral and intravenous rehydration in acute diarrhoea. Acta Paediatr Scand 1987;76:300-5.

26. Sharifi J, Ghavami F, Nowrouzi Z, et al. Oral versus intravenous rehydration therapy in severe gastroenteritis. Arch Dis Child 1985;60:856-60.

27. Bhargava SK, Sachdev HP, Das Gupta B, Daral TS, Singh HP, Mohan M. Oral rehydration of neonates and young infants with dehydrating diarrhea: comparison of low and standard sodium content in oral rehydration solutions. J Pediatr Gastroenterol Nutr 1984;3:500-5.

28. WHO. A manual for the treatment of acute diarrhoea - for use by physicians and other senior health workers. Geneva: World Health Organization, 1984.

29. WHO. Oral rehydration therapy for treatment of diarrhoea in the home. Geneva: World Health Organization: Diarrhoeal Disease Control Programme, 1986.

30. Mauer AM, Dweck HS, Finberg L, et al. American Academy of Pediatrics Committee on Nutrition: Use of oral fluid therapy and posttreatment feeding following enteritis in children in a developed country. Pediatrics 1985;75:358-61.

31. Farthing MJ. Disease-related animal models for optimising oral rehydration solution composition. Acta Paediatr Scand Suppl 1989;364:23-30.

32. Hunt JB, Thillainayagam AV, Salim AF, Carnaby S, Elliott EJ, Farthing MJ. Water and solute absorption from a new hypotonic oral rehydration solution: evaluation in human and animal perfusion models. Gut 1992;33:1652-9.

33. Recommendations for composition of oral rehydration solutions for the children of Europe. Report of an ESPGAN Working Group. J Pediatr Gastroenterol Nutr 1992;14:113-5.

34. Multicentre evaluation of reduced-osmolarity oral rehydration salts solution. International Study Group on Reduced-osmolarity ORS solutions. Lancet 1995;345:282-5.

35. CHOICE Study Group. Multicenter, randomized, double-blind clinical trial to evaluate the efficacy and safety of a reduced osmolarity oral rehydration salts solution in children with acute watery diarrhea. Pediatrics 2001;107:613-8.

36. Hahn S, Kim Y, Garner P. Reduced osmolarity oral rehydration solution for treating dehydration due to diarrhoea in children: systematic review. BMJ 2001;323:81-5.

37. Hahn S, Kim S, Garner P. Reduced osmolarity oral rehydration solution for treating dehydration caused by acute diarrhoea in children. Cochrane Database Syst Rev 2002;(1):CD002847.

38. WHO. New formula for oral rehydration salts will save millions of lives. Geneva: World Health Organization, 2002.

39. Carpenter CC, Greenough WB, Pierce NF. Oral-rehydration therapy--the role of polymeric substrates. N Engl J Med 1988;319:1346-8.

40. Thillainayagam AV, Carnaby S, Dias JA, Clark ML, Farthing MJ. Evidence of a dominant role for low osmolality in the efficacy of cereal based oral rehydration solutions: studies in a model of secretory diarrhoea. Gut 1993;34:920-5.

41. Khin-Maung-U, Greenough WB 3rd. Cereal-based oral rehydration therapy. I. Clinical studies. J Pediatr 1991;118(4 Pt 2):S72-9.

42. Duggan C, Santosham M, Glass RI. The management of acute diarrhea in children: oral rehydration, maintenance, and nutritional therapy. Centers for Disease Control and Prevention. MMWR Recomm Rep 1992;41(RR-16):1-20.

43. Gore SM, Fontaine O, Pierce NF. Efficacy of rice-based oral rehydration. Lancet 1996;348:193-4.

44. Fontaine O, Gore SM, Pierce NF. Rice-based oral rehydration solution for treating diarrhoea. Cochrane Database Syst Rev 2000;(2):CD001264.

45. Goepp JG, Katz SA. Oral rehydration therapy. Am Fam Physician 1993;47:843-51.

46. Meyers A. Fluid and electrolyte therapy for children. Curr Opin Pediatr 1994;6:303-9.

47. WHO. The treatment of diarrhoea. A manual for physicians and other senior health workers. Geneva: World Health Organization, 1995.

48. Murphy MS. Guidelines for managing acute gastroenteritis based on a systematic review of published research. Arch Dis Child 1998;79:279-84.

49. Listernick R, Zieserl E, Davis AT. Outpatient oral rehydration in the United States. Am J Dis Child 1986;140:211-5.

50. Mackenzie A, Barnes G. Randomised controlled trial comparing oral and intravenous rehydration therapy in children with diarrhoea. BMJ 1991;303:393-6.

51. Pizarro D, Posada G, Levine MM. Hypernatremic diarrheal dehydration treated with "slow" (12-hour) oral rehydration therapy: a preliminary report. J Pediatr 1984;104:316-9.

52. Isolauri E, Juntunen M, Wiren S, Vuorinen P, Koivula T. Intestinal permeability changes in acute gastroenteritis: effects of clinical factors and nutritional management. J Pediatr Gastroenterol Nutr 1989;8:466-73.

53. Levine GM, Deren JJ, Steiger E, Zinno R. Role of oral intake in maintenance of gut mass and disaccharide activity. Gastroenterology 1974;67:975-82.

54. Khin MU, Nyunt-Nyunt-Wai, Myo-Khin, Mu-Mu-Khin, Tin U, Thane-Toe. Effect on clinical outcome of breast feeding during acute diarrhoea. Br Med J (Clin Res Ed) 1985;290:587-9.

55. Walker-Smith JA, Sandhu BK, Isolauri E, et al. Guidelines prepared by the ESPGAN Working Group on Acute Diarrhoea. Recommendations for feeding in childhood gastroenteritis. European Society of Pediatric Gastroenterology and Nutrition. J Pediatr Gastroenterol Nutr 1997;24:619-20.

56. Golding J, Emmett PM, Rogers IS. Gastroenteritis, diarrhoea and breast feeding. Early Hum Dev 1997;49 Suppl:S83-103.

57. Lembcke JL, Brown KH. Effect of milk-containing diets on the severity and duration of childhood diarrhea. Acta Paediatr Suppl 1992;381:87-92.

58. Brown KH, Lake A. Appropriate use of human and non-human milk for the dietary management of children with diarrhoea. J Diarrhoeal Dis Res 1991;9:168-85.

59. Faruque AS, Mahalanabis D, Islam A, Hoque SS, Hasnat A. Breast feeding and oral rehydration at home during diarrhoea to prevent dehydration. Arch Dis Child 1992;67:1027-9.

60. Alarcon P, Montoya R, Perez F, Dongo JW, Peerson JM, Brown KH. Clinical trial of home available, mixed diets versus a lactose-free, soy-protein formula for the dietary management of acute childhood diarrhea. J Pediatr Gastroenterol Nutr 1991;12:224-32.

61. Brown KH, Gastanaduy AS, Saavedra JM, et al. Effect of continued oral feeding on clinical and nutritional outcomes of acute diarrhea in children. J Pediatr 1988;112:191-200.

62. Fox R, Leen CL, Dunbar EM, Ellis ME, Mandal BK. Acute gastroenteritis in infants under 6 months old. Arch Dis Child 1990;65:936-8.

63. Hjelt K, Paerregaard A, Petersen W, Christiansen L, Krasilnikoff PA. Rapid versus gradual refeeding in acute gastroenteritis in childhood: energy intake and weight gain. J Pediatr Gastroenterol Nutr 1989;8:75-80.

64. Isolauri E, Vesikari T. Oral rehydration, rapid feeding, and cholestyramine for treatment of acute diarrhea. J Pediatr Gastroenterol Nutr 1985;4:366-74.

65. Margolis PA, Litteer T, Hare N, Pichichero M. Effects of unrestricted diet on mild infantile diarrhea. A practice-based study. Am J Dis Child 1990;144:162-4.

66. Rees L, Brook CG. Gradual reintroduction of full-strength milk after acute gastroenteritis in children. Lancet 1979;1:770-1.

67. Fayad IM, Hashem M, Duggan C, et al. Comparative efficacy of rice-based and glucose-based oral rehydration salts plus early reintroduction of food. Lancet 1993;342:772-5.

68. Santosham M, Fayad IM, Hashem M, Goepp JG, Refat M, Sack RB. A comparison of rice-based oral rehydration solution and "early feeding" for the treatment of acute diarrhea in infants. J Pediatr 1990;116:868-75.

69. Sandhu BK, Isolauri E, Walker-Smith JA, et al. A multicentre study on behalf of the European Society of Paediatric Gastroenterology and Nutrition Working Group on Acute Diarrhoea. Early feeding in childhood gastroenteritis. J Pediatr Gastroenterol Nutr 1997;24:522-7.

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

71. Brown KH, Perez F, Gastanaduy AS. Clinical trial of modified whole milk, lactose-hydrolyzed whole milk, or cereal-milk mixtures for the dietary management of acute childhood diarrhea. J Pediatr Gastroenterol Nutr 1991;12:340-50.

72. Chiu CH, Lin TY, Ou JT. A clinical trial comparing oral azithromycin, cefixime and no antibiotics in the treatment of acute uncomplicated Salmonella enteritis in children. J Paediatr Child Health 1999;35:372-4.

73. Pickering LK, Matson DO. Therapy for diarrheal illness in children. In: Blaser MJ, Smith P, Ravdin J, Greenberg HB, Guerrant RL, eds. Infections of the Gastrointestinal Tract. New York: Raven Press, 1995:1401-5.

74. Department of Health. Public Health & Epidemiology Bulletin. Hong Kong: Department of Hong Kong, 1999:19.

75. Cohen MB, Laney DW, Jr. Infectious diarrhea. Pediatric gastrointestinal diseases. Wylie and Hyams, 1999:348-370.

76. Butler T, Islam MR, Azad MA, Jones PK. Risk factors for development of hemolytic uremic syndrome during shigellosis. J Pediatr 1987;110:894-7.

77. Biswas R, Nelson EA, Lewindon PJ, Lyon DJ, Sullivan PB, Echeverria P. Molecular epidemiology of Escherichia coli diarrhea in children in Hong Kong. J Clin Microbiol 1996;34:3233-4.

78. Nataro JP, Kaper JB. Diarrheagenic Escherichia coli. Clin Microbiol Rev 1998;11:142-201.

79. Wong CS, Jelacic S, Habeeb RL, Watkins SL, Tarr PI. The risk of the hemolytic-uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 infections. N Engl J Med 2000;342:1930-6.

80. Pruksananonda P, Powell KR. Multiple relapses of Clostridium difficile-associated diarrhea responding to an extended course of cholestyramine. Pediatr Infect Dis J 1989;8:175-8.

81. Heresi G, Cleary TG. Giardia. Pediatr Rev 1997;18:243-7.

82. WHO. The rational use of drugs in the management of acute diarrhoea in children. Geneva: World Health Organization, 1990.

83. Macfarlane GT, Cummings JH. Probiotics and prebiotics: can regulating the activities of intestinal bacteria benefit health? BMJ 1999;318:999-1003.

84. Vanderhoof JA, Young RJ. Use of probiotics in childhood gastrointestinal disorders. J Pediatr Gastroenterol Nutr 1998;27:323-32.

85. Cetina-Sauri G, Sierra-Basto G. Therapeutic evaluation of Saccharomyces Boulardii in children with acute diarrhoea. Annales de Pediatrie 1994;41:397-400.

86. Van Niel CW, Feudtner C, Garrison MM, Christakis DA. Lactobacillus therapy for acute infectious diarrhea in children: a meta-analysis. Pediatrics 2002;109:678-84.

87. Kaplan MA, Prior MJ, McKonly KI, DuPont HL, Temple AR, Nelson EB. A multicenter randomized controlled trial of a liquid loperamide product versus placebo in the treatment of acute diarrhea in children. Clin Pediatr (Phila) 1999;38:579-91.

88. Pickering LK. Therapy for acute infectious diarrhea in children. J Pediatr 1991;118(4 Pt 2):S118-28.

89. Loperamide in acute diarrhoea in childhood: results of a double blind, placebo controlled multicentre clinical trial. Diarrhoeal Diseases Study Group (UK). Br Med J (Clin Res Ed) 1984;289:1263-7.

90. Karrar ZA, Abdulla MA, Moody JB, Macfarlane SB, Al Bwardy M, Hendrickse RG. Loperamide in acute diarrhoea in childhood: results of a double blind, placebo controlled clinical trial. Ann Trop Paediatr 1987;7:122-7.

91. Motala C, Hill ID, Mann MD, Bowie MD. Effect of loperamide on stool output and duration of acute infectious diarrhea in infants. J Pediatr 1990;117:467-71.

92. Bowie MD, Hill ID, Mann MD. Loperamide for treatment of acute diarrhoea in infants and young children. A double-blind placebo-controlled trial. S Afr Med J 1995;85:885-7.

93. Ghisolfi J, Baudoin C, Charlet JP, Olives JP, Ghisolfi A, Thouvenot JP. Effects of loperamide on fecal electrolyte excretion in acute diarrhea in infants. Arch Fr Pediatr 1987;44:483-7.

94. Owens JR, Broadhead R, Hendrickse RG, Jaswal OP, Gangal RN. Loperamide in the treatment of acute gastroenteritis in early childhood. Report of a two centre, double-blind, controlled clinical trial. Ann Trop Paediatr 1981;1:135-41.

95. Litovitz T, Clancy C, Korberly B, Temple AR, Mann KV. Surveillance of loperamide ingestions: an analysis of 216 poison center reports. J Toxicol Clin Toxicol 1997;35:11-9.

96. PPPSG. Survey on the usage of loperamide among paediatricians. Hong Kong: The Private Practising Paediatricians Study Group, 2000.

97. Charritat JL, Corbineau D, Guth S, Meunier M, Pernin P, Pflieger H. Therapeutic evaluation of Mormoiron attapulgite in acute diarrheas of infants and children. A multicenter study in controlled liberal practice versus placebo in 113 patients. Ann Pediatr (Paris) 1992;39:326-32.

98. Dupont C, Moreno JL, Barau E, Bargaoui K, Thiane E, Plique O. Effect of diosmectite on intestinal permeability changes in acute diarrhea: a double-blind placebo-controlled trial. J Pediatr Gastroenterol Nutr 1992;14:413-9.

99. Gilbert B, Lienhardt A, Palomera S, Barberis L, Borreda D. The efficacy of smectite in acute infantile diarrhea, compared to a placebo and loperamide. Ann Pediatr (Paris) 1991;38:633-6.

100. Madkour AA, Madina EM, el-Azzouni OE, Amer MA, el-Walili TM, Abbass T. Smectite in acute diarrhea in children: a double-blind placebo-controlled clinical trial. J Pediatr Gastroenterol Nutr 1993;17:176-81.

101. Vivatvakin B, Jongpipatvanich S, Harikul S, Eksaengri P, Lortholary O. Control study of oral rehydration solution (ORS)/ORS + dioctahedral smectite in hospitalized Thai infants with acute secretory diarrhea. Southeast Asian J Trop Med Public Health 1992;23:414-9.

102. Ashorn M, Maki M, Ruuska T, et al. Upper gastrointestinal endoscopy in recurrent abdominal pain of childhood. J Pediatr Gastroenterol Nutr 1993;16:273-7.

103. Figueroa-Quintanilla D, Salazar-Lindo E, Sack RB, et al. A controlled trial of bismuth subsalicylate in infants with acute watery diarrheal disease. N Engl J Med 1993;328:1653-8.

104. Soriano-Brucher H, Avendano P, O'Ryan M, et al. Bismuth subsalicylate in the treatment of acute diarrhea in children: a clinical study. Pediatrics 1991;87:18-27.

105. Pickering LK, Feldman S, Ericsson CD, Cleary TG. Absorption of salicylate and bismuth from a bismuth subsalicylate--containing compound (Pepto-Bismol). J Pediatr 1981;99:654-6.

106. Cezard J, Duhamel J, Meyer M, et al. Efficacy and tolerance of acetorphan in infant acute diarrhoea. A multicentre double blind study. Gastroenterology 1996;110:A795.

107. Turck D, Berard H, Fretault N, Lecomte JM. Comparison of racecadotril and loperamide in children with acute diarrhoea. Aliment Pharmacol Ther 1999;13 Suppl 6:27-32.

108. Issenman RM, Leung AK. Oral and intravenous rehydration of children. Can Fam Physician. 1993;39:2129-36.

109. el-Mougi M, el-Akkad N, Hendawi A, et al. Is a low-osmolarity ORS solution more efficacious than standard WHO ORS solution? J Pediatr Gastroenterol Nutr 1994;19:83-6.

110. Mahalanabis D, Faruque AS, Hoque SS, Faruque SM. Hypotonic oral rehydration solution in acute diarrhoea: a controlled clinical trial. Acta Paediatr 1995;84:289-93.

111. Santosham M, Fayad I, Abu Zikri M, et al. A double-blind clinical trial comparing World Health Organization oral rehydration solution with a reduced osmolarity solution containing equal amounts of sodium and glucose. J Pediatr 1996;128:45-51.

112. Valentiner-Branth P, Steinsland H, Gjessing HK, et al. Community-based randomized controlled trial of reduced osmolarity oral rehydration solution in acute childhood diarrhea. Pediatr Infect Dis J 1999;18:789-95.

113. Rautanen T, el-Radhi S, Vesikari T. Clinical experience with a hypotonic oral rehydration solution in acute diarrhoea. Acta Paediatr 1993;82:52-4.

114. Rautanen T, Kurki S, Vesikari T. Randomised double blind study of hypotonic oral rehydration solution in diarrhoea. Arch Dis Child 1997;76:272-4.

115. Patra FC, Mahalanabis D, Jalan KN, Sen A, Banerjee P. Is oral rice electrolyte solution superior to glucose electrolyte solution in infantile diarrhoea? Arch Dis Child 1982;57:910-2.

116. Molla AM, Ahmed SM, Greenough WB 3rd. Rice-based oral rehydration solution decreases the stool volume in acute diarrhoea. Bull World Health Organ 1985;63:751-6.

117. Alam AN, Sarker SA, Molla AM, Rahaman MM, Greenough WB 3rd. Hydrolysed wheat based oral rehydration solution for acute diarrhoea. Arch Dis Child 1987;62:440-4.

118. Bhan MK, Ghai OP, Khoshoo V, et al. Efficacy of mung bean (lentil) and pop rice based rehydration solutions in comparison with the standard glucose electrolyte solution. J Pediatr Gastroenterol Nutr 1987;6:392-9.

119. Dutta P, Dutta D, Bhattacharya SK, et al. Comparative efficacy of three different oral rehydration solutions for the treatment of dehydrating diarrhoea in children. Indian J Med Res 1988;87:229-33.

120. el-Mougi M, Hegazi E, Galal O, et al. Controlled clinical trial on the efficacy of rice powder-based oral rehydration solution on the outcome of acute diarrhea in infants. J Pediatr Gastroenterol Nutr 1988;7:572-6.

121. Mohan M, Antony TJ, Malik S, Mathur M. Rice powder oral rehydration solution as an alternative to glucose electrolyte solution. Indian J Med Res 1988;87:234-9.

122. Molla AM, Molla A, Nath SK, Khatun M. Food-based oral rehydration salt solution for acute childhood diarrhoea. Lancet 1989;2:429-31.

123. Islam A, Molla AM, Ahmed MA, et al. Is rice based oral rehydration therapy effective in young infants? Arch Dis Child 1994;71:19-23.

124. Maulen-Radovan I, Fernandez-Varela H, Acosta-Bastidas M, Frenk S. Safety and efficacy of a rice-based oral rehydration salt solution in the treatment of diarrhea in infants less than 6 months of age. J Pediatr Gastroenterol Nutr 1994;19:78-82.

125. Guiraldes E, Trivino X, Figueroa G, et al. Comparison of an oral rice-based electrolyte solution and a glucose-based electrolyte solution in hospitalized infants with diarrheal dehydration. J Pediatr Gastroenterol Nutr 1995;20:417-24.

126. Dutta D, Bhattacharya MK, Deb AK, et al. Evaluation of oral hypo-osmolar glucose-based and rice-based oral rehydration solutions in the treatment of cholera in children. Acta Paediatr 2000;89:787-90.

127. Zaman K, Yunus M, Rahman A, Chowdhury HR, Sack DA. Efficacy of a packaged rice oral rehydration solution among children with cholera and cholera-like illness. Acta Paediatr 2001;90:505-10.

128. Nelson JD, Kusmiesz H, Jackson LH, Woodman E. Treatment of Salmonella gastroenteritis with ampicillin, amoxicillin, or placebo. Pediatrics 1980;65:1125-30.

129. Aserkoff B, Bennett JV. Effect of antibiotic therapy in acute salmonellosis on the fecal excretion of salmonellae. N Engl J Med 1969;281:636-40.

130. Anonymous. Red Book 2000. American Academy of Pediatrics, 2000.

 
 

This web site is sponsored by Johnson & Johnson (HK) Ltd.
©2022 Hong Kong Journal of Paediatrics. All rights reserved. Developed and maintained by Medcom Ltd.