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Acute gastroenteritis in infants and children


WKY Yeung $#<[ Summary
Acute gastroenteritis is a common cause for medical consultations and hospital visits among children less than 5-year-old. Advances in knowledge have led to new concepts in management of gastroenteritis in children. The major advance is the development of oral rehydration fluid, which is effective for the treatment of fluid and electrolyte loss in diarrhoea of any aetiology, in patients of any age with mild to moderate dehydration. Optimal management of acute gastroenteritis include (1) early rehydration using an appropriate glucose-based oral rehydration solution, (2) early refeeding with normal diet with no interruption of breast feeding and (3) judicious use of medications.

result, the direct cost of hospitalisations and outpatient care attributable to acute gastroenteritis is substantial. Although there are no local data about the incidence of acute gastroenteritis in paediatric population, it remains an important and common cause for medical visits and hospitalisations in children. In view of these, a review of the current management of children w i t h acute gastroenteritis is warranted.

Aetiology Among the causes of acute gastroenteritis in children listed in (Table 1), viral agents are the most common, followed by bacterial and parasitic infections. Rotavirus is the most common aetiogical agent responsible for acute gastroenteritis especially in young children during winter.

Pathogenesis and pathophysiology of diarrhoea Acute diarrhoea can be divided into three main types, namely osmotic diarrhoea, secretary diarrhoea and dysentery syndrome (Table 2). In osmotic diarrhoea, the loss of mucosal surface as a result of infection causes malabsorption of carbohydrates, resulting in increase in osmotic load in the gut. In secretary diarrhoea, the bacterial toxins act on the intestinal mucosa, which results in increased levels of cyclic nucleotides that s t i m u l a t e chloride secretion and i n h i b i t sodium absorption. In dysentery, the invasive organisms penetrate the mucosa of the large bowel, producing a marked inflammatory response, which accounts for the pus, blood and mucus seen in the stool. In diarrhoeal diseases, the loss of fluid, electrolytes and bicarbonate in stool may cause dehydration, hypokalaemia and acidosis or even hypovolaemic shock in severe cases.

(2)

HK Pract 1999;21:471-478

Introduction Acute diarrhoea is defined as an increase in the frequency, fluidity and volume of stool of acute onset. Acute diarrhoeal illness remains a major cause of mortality in developing countries and a major cause of morbidity in developed countries. In the United States, acute gastroenteritis accounts for about 10% of hospitalisations among children less than 5 years of age and causes about 300 deaths in children per year. As a

W K Y Yeung, MBBS, DCH. FHKCPaed, FHKAM(Paed)

Senior Medical Officer, Department of Paediatrics, Pamela Youde Nethersole Eastern Hospital. Correspondence to : Dr W K Y Yeung, Department of Paediatrics, Pamela Youde Nethersole Eastern Hospital, 3 Lok Man Road, Chai Wan, Hong Kong.

Assessment of patients Clinicians should be able to assess the degree of dehydration in children with acute diarrhoea, based on the parameters shown in Table 3. In hypernatraemic
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The Hong Kong Practitioner

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1999

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Table 1: Causes of paediatric gastroenteritis Common
Rotavirus Enteric adenovirus

Type of organism Viral

Uncommon
Norwalk virus

Uncertain frequency Calicivirus Astrovirus

Bacterial

Salmonella Shigella Campylobacter jejuni

Yersinia enterocolitica Vibrio cholerae

Escherichia coli Aeromonas hydrophia Plesiomonas shigelloides Clostridium difficile

Parasitic

Giardia lambia

Entamoeba histolytica

Cryptosporidium Blastocystis hominis

Table 2:

Types of acute diarrhoea Osmotic diarrhoea


Secretory diarrhoea Bacterial toxins in intestinal mucosa leads to <t cAMP/cGMP Losses of watery stool Not improve with fasting Stool Na > 70mmol/1 Stool CL >95 mmol/1

Dysentery syndrome
Invasive organisms leads to inflammatory responses in large bowel Fever, abdominal pain, tenesmus and bloody stool Pus, blood and mucus in stool

Mechanism

\U Absorptive Surface leads to ^ Osmotic load Diarrhoea stops when patients fast

2. Clinical Features

3. Stool characteristics

Stool Na < 70 mmol/1 Stool pH <5 Stool reducing substances +ve Stool osmolarity >2x (stool Na + K)

4. Examples

Rotavirus

Vibrio cholera E Coli Shigella Salmonella Aeromonas

Shigella Campylobacter E Coli

dehydration, the physical signs of dehydration are less obvious but the patient may have doughy skin. It is useful to express the severity of dehydration in terms of weight loss as a percentage of total body weight if a recent w e i g h t record is a v a i l a b l e . F u r t h e r m o r e prospective cohort studies in infants between 3 months and 18 months of age showed that decreased skin turgor, dry oral mucosa, sunken eyes and altered neurological status, are the clinical signs that best correlate with the degree of dehydration. 1 The usefulness of capillary refill time is controversial since it is affected by other factors
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like ambient temperature and anaemia. Yet a normal capillary refill time is unlikely with severe dehydration. In addition, the risk of dehydration should be assessed. Studies have identified the following risk factors of dehydration: (1) age < 12 months (2) frequent stools >8 times/day (3) vomiting >2 times/day (4) discontinuation of breast feeding during illness (5) failure to give oral rehydration solution (ORS) (6) severe undernutrition (7) Vibrio cholerae infection. 2
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Table 3: Variable Blood pressure Quality of pulses Heart rate Skin turgor Fontanelle Mucous membrane Eyes Extremities Mental status Urine output Thirst Clinical assessment of severity of dehydration Mild, 3%-5% Normal Normal Normal Normal Normal Slightly dry Normal Warm, normal capillary refill Normal Slightly decreased Slightly increased Moderate, 6%-9% Normal Normal to slightly decreased Increased Decreased Sunken
Dry

Severe, > 10% Normal to reduced Markedly decreased Increased Decreased Sunken
Dry

Sunken orbits Delayed capillary refill Normal to listless < 1 ml/kg/hr Moderately decreased

Deeply sunken orbits Cool, mottled Normal to lethargic or comatose 1 ml/kg/hr Very thirsty or too lethargic to indicate

Laboratory investigations
Most e p i s o d e s o f d e h y d r a t i o n c a u s e d b y gastroenteritis are isonatraemic. Electrolytes levels s h o u l d be measured in m o d e r a t e l y and severely dehydrated children or if hypernatraemic dehydration is suspected when patients have fever, irritability with loss of skin t u r g o r in d i s p r o p o r t i o n to the degree of dehydration.

Treatment of gastroenteritis
There are three important aspects of treatment, namely rehydration, refeeding and use of anti-diarrhoeal agents.

Rehydration using oral rehydration therapy (ORT)


An i m p o r t a n t advance in the m a n a g e m e n t of gastroenteritis is the use of ORT. Controlled clinical trials have confirmed the efficacy of ORS in replacing fluid and electrolyte loss in children with gastroenteritis, with mild to moderate dehydration, regardless of the aetiology of dehydration and the type of dehydration.1-3 ORT is preferred to intravenous fluid replacement because ORT is cheaper and it is convenient for home use. Furthermore, studies have shown that ORS can successfully rehydrate >90% of dehydrated children and is associated with lower complication rate than those on intravenous therapy. ORT is not effective only in the following situations: (1) when the patient is severely dehydrated or in shock, (2) when oral fluid is not tolerated due to severe vomiting or ileus, (3) when the child is unconscious or extremely fatigued, (4) when supervision on oral fluid replacement by reliable parents is not available.
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Stool examination
Gross examination of stool is important in the evaluation of patients with acute diarrhoea as it may reveal the underlying cause such as the greenish slimy stool in Salmonella gastroenteritis or the bloody stool with mucous in dysentery. The red currant jelly stool of intussusception should be recognised as it may present with symptoms and signs m i m i c k i n g acute gastroenteritis. Fresh stool may be sent for microscopic examination for leucocytes u s i n g m e t h y l e n e blue stain when inflammatory colitis is suspected. The stool should be sent for culture and antibiotic sensitivity in bacterial gastroenteritis. Rotavirus gastroenteritis can be diagnosed by detection of antigen using ELIZA test (Rotazyme) in stool. In persistent diarrhoea, stool can be sent for pH study and reducing substances when lactose intolerance is suspected.
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A range of ORS products is currently available (Table 4). They u s u a l l y v a r y in their sodium concentrations with range between 45 to 90mmol/L and their glucose concentrations. A glucose-electrolyte ORS is used because the coupled transport of sodium and glucose is intact in patients with diarrhoea. Yet there is still controversy about the ideal composition of ORS. The classical ORS is the WHO solution, which proved its efficacy more than 30 years ago during cholera epidemics in Bangladesh. It has higher s o d i u m concentrations (90 mmol/L) than the current commercial ORS, which has sodium concentration of 40-60 mmol/L. The ORS with lower sodium concentration has also been shown by studies to be effective in the treatment of dehydration in children with diarrhoea, especially noncholera diarrhoea. They are also more palatable owing to their less salty taste. The European Society for Pediatric Gastroenterology and Nutrition (ESPGAN) r e c o m m e n d s ORS w i t h s o d i u m c o n c e n t r a t i o n of 60 mmol/L for European children. 2 Rice-based or cereal-based ORS have been used in an a t t e m p t to provide ORS s o l u t i o n w i t h reduced osmolarity but improved nutritious value by virtue of the complex carbohydrates. There is no conclusive benefit of these ORS over the conventional glucose-based ORS on the duration and severity of diarrhoea in children with non-cholera diarrhoea.9 However beverages such as cola, apple juices and sports beverages, which have low electrolyte content but high carbohydrate and osmolarity, should be avoided. 1. R e h y d r a t i o n u s i n g ORS should n o r m a l l y be completed over a three to four hour period. (i) In mild dehydration (3-5%), give 30-50 ml/kg oral fluid (ii) In moderate dehydration (5-10%), give 50100 ml/kg oral fluid (iii) In severe dehydration (>10%), give 100150 ml/kg oral fluid (iv) Reassess dehydration immediately after giving the estimated deficit (v) The ORS can be given orally via bottle, cup, spoon or even nasogastric tube, whichever is tolerated by the patient. In severe dehydration with signs of shock, 20 ml/kg boluses of n o r m a l s a l i n e or Ringer's lactate intravenously should be given in one hour period. ORS can be given when peripheral circulation is restored and patient's condition is stable. In h y p e r n a t r a e m i c d e h y d r a t i o n , use ORS to rehydrate over a period of 12 hours, and monitor sodium to avoid rapid reduction. To prevent primary dehydration or recurrence of dehydration, allow unrestricted fluid, and in high risk cases either (a) alternate normal drinks with ORS or (b) give normal drinks and 10 ml/kg ORS after each watery stool.

2.

3.

4.

Nutritional management
Conventional practice among family physicians has been to delay feeding children who have diarrhoea. Some will also recommend diluted milk formula or lactose-free formula to these children. This practice has become obsolete. Studies have shown that early refeeding has the advantages of stimulation of mucosal growth and r e d u c t i o n of the a b n o r m a l increase in i n t e s t i n a l permeability in acute gastroenteritis. 16-17

Recommendations on rehydration
The past practice of advocating gradual rehydration over 24 hours or more is not evidence-based. The current recommendations for fluid management in patients with diarrhoea are as follows: 3

Table 4: Solution

Composition of glucose-electrolyte solutions


CHO, mmol/L Na, mmol/L K, mmol/L Base, mmol/L Osmolarity

Pedialyte (Ross) GES45 (Milupa) Infalyte (Mead Johnson) Rehydrate (Ross) WHO/UNIEF
476

140 160

45 45 50 75 90

20 25 25 20 20

30 25 30 30 30
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250 300 200 310 310


October 1999

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There has been no difference between early feeding and late feeding in the incidences of vomiting or watery stool, while early feeding has the theoretical advantage of improved nutrition. Furthermore, meta-analysis has shown that 80% or more of children with diarrhoea can safely tolerate full strength milk. Lactose free formula (Table 5) is considered if there is persistent diarrhoea after introduction of feeds especially when the stool is acidic and contains more than 0.5% reducing substances. In older children, it is better to avoid fatty foods or foods high in simple sugars such as juices and soft drinks. Clinical experience suggested that certain foods, including complex carbohydrates (rice, wheat, potatoes, bread, and cereals), lean meats, yogurt, fruits and vegetables, are better tolerated.

The current recommendations for refeeding children with acute diarrhoea:2-3 Patients with diarrhoea with no dehydration should be fed age appropriate diet. Patients with diarrhoea and dehydration should be fed age appropriate diet after rehydration. Breast feeding should continue through rehydration and maintenance phases of treatment. Full strength milk can be given for most children as transient lactase deficiency associated with acute gastroenteritis is not clinically significant in more that 80% of paediatric patients. Formula for children with persistent diarrhoea
Unit Kcal
g

Pharmacotherapy Anti-diarrhoeal agents A variety of pharmacological agents have been used in medical practice to treat diarrhoea. These compounds may be c l a s s i f i e d by t h e i r m e c h a n i s m of a c t i o n (Table 6). In general, there is no evidence that they have beneficial effects. On the other hand, indiscriminate use of anti-diarrhoeal drugs in children will give rise to

Table 5:
Nutrient Energy Protein

O-Iac 676
15 (9%) Milk protein 37 (49%) Vegetable oils

Isomil

Nursoy

Prosobee

Pregestimil

*Milupa HN

672
18 ( 1 1 % ) Soy protein isolate 36 (48%) Oils: coconut oleo, oleic

676
18 (11%) Soy protein isolate 36 (48%) Oils: coconut, palm, olein soy, oleic, vegetable 69 (41%) Sucrose 25%, corn syrup solids 75%

676
20(12%) Soy protein isolate
36 (48%) Oils: coconut, palm, olein, soy, oleic, vegetable 66 (39%) glucose polymers

676
19 ( 1 1 % ) Hydro caseinate 38 (49%) Oils: corn, soy, oleic, 55% MCT

570
26 (6%) Milk protein

Fat

12 (19%) Vegetable fat

CHO

73 (43%) Glucose polymers

69(41%) Sucrose, corn syrup solid

69(41%) 80% corn syrup solids modified starch 20%

93 (65%) Glucose, sucrose, fructose, maltose, galactose polysaccharide starch, lactose (1%)

* Milupa HN has lower calories content than normal milk, it should not be used for more than 1 week

Table 6:

Medications used to relieve symptoms in patients with diarrhoea 2. Alteration of secretion Bismuth subsalicylate (Pepto-Bismol) 3. Adsorption of toxins and water Attapulgate (Kaopectate) 4. Alteration of intestinal microflora Lactobacillus (Pro-Bionate, Superdophilus)
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1. Alteration of intestinal motility Opiates Loperamide (Immodium) Diphenoxylate and atropine (Lomotil) Tincture of opium (Paregoric)

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systemically ill. Antibiotics are also indicated in patients with Campylobacter jejuni gastroenteritis, who have systemic or prolonged disease. In Shigella dysentery, antibiotics have been shown to shorten the clinical illness and the duration of pathogen excretion.

Key messages
1. Clinician should be able to assess the severity of dehydration in children with acute diarrhoea. Oral r e h y d r a t i o n therapy is the recommended treatment for mild to moderate dehydration in children with acute gastroenteritis. Most children with acute diarrhoea can be fed breast milk or full strength milk as well as age appropriate diet early after rehydration. Lactose free formula is indicated only if there is persistent diarrhoea after refeeding. Antidiarrhoeal drugs are not recommended to treat diarrhoea in children and antibiotics are only indicated in special situations.

2.

3.

Vaccine
Preventive efforts to reduce the incidence of acute diarrhoea remain the best way to reduce the burden of diarrhoeal disease. Attempts to develop effective vaccines such as cholera vaccine and rotavirus vaccine have not been successful yet. At present, the major preventive measures are promotion of breast feeding, reinforcement of hand washing and food hygiene.

4.

5.

References
high incidence of side effects. Loperamide is notorious for causing unacceptable adverse effects such as lethargy, paralytic ileus, toxic megacolon, respiratory depression and coma. L i f e - t h r e a t e n i n g e v e n t s and serious consequences like loperamide - associated nercotizing enterocolitis, 11 pancreatitis, toxic delirium 1 2 as well as worsening of the course of diarrhoea in patients with shigellosis, antimicrobial associated colitis or diarrhoea caused by Escherichia coli 0157:H7, 13-15 have been reported with use of loperamide. Anticholinergic agents including atropine-diphenoxylate (lomotil) will produce side effects like dry mouth, tachycardia, flushing, urinary retention, coma, respiratory depression and paradoxical hyperexcitability. In addition, peristalsis inhibition by these drugs may result in fluid retention w i t h i n the intestinal tract, exacerbating dehydration and electrolyte imbalance. Treatment with bismuth subsalicylate has the risk of salicylate toxicity and Reye syndrome. Use of adsorbents may have the disadvantage of absorbing the nutrients, enzymes and antibiotics in the intestine. In view of their lack of proved efficacy and the serious adverse side effects, anti-diarrhoeal agents are not recommended for treatment of gastroenteritis in children.
Provisional Committee on Quality improvement, Subcommittee on Acute G a s t r o e n t e r i t i s . Practice P a r a m e t e r : The m a n a g e m e n t of A c u t e Gastroenteritis in Young Children. Paediatrics 1996;97(3):424-433. 2. Murphy MS. Guidelines for managing acute gastroenteritis based on a systematic review of published research. Arch Dis Child 1998:79:279-284. 3. A Synopsis of \he American Academy of Paediatrics Practice Parameter on the Management of Acute Gastroenteritis in Young Children. Paediatrics in Review 1997;18(7):221-223. 4. Dellcrt SF. Diarrhoea Disease: Established pathogens, New pathogens, and Progress in vaccine development. Gastroenterology Clinics of N America 1994:23(4):637-655. 5. Sar A Aca. Electrolyte fluxes in the gut and oral rehydration solutions. Paediatrics Clinics of North America, 1996;43(2):433-447. 6. Gavin N, Merrick N. Davidson B. Efficacy of glucose-based oral rehydration solution. Paediatrics 1998(1);45-5l. 7. Sack B. Current treatment of infectious diarrhoea. Infect Med 1996;13(4): 301-313. 8. Brown KH. Use of Nonhuman milks in the dietary management of young children with acute diarrhoea: A Mela-analysis of Clinical Trials. Paediatrics 1994:93(1): 17-27. 9. Fontaine O, Gore SM, Pierce NF. Diarrhoea treatment: rice-based oral dehydration solution. The Cochrane Library 1998;Issue 4. 10. Walker WA. Paediatric Gastrointestinal Disease: pathophysiology, diagnosis and management 2nd edition. 1996:251-262; 1843-1850. 11. Chow CB, Li SH, Leung NK. Loperamide associated necrotizing enterocolitis. Acta Paediatr Scand. 1986:75:1034-1036. 12. Schwartz RH, Rodriguez WJ. Toxic d e l i r i u m possibly caused by loperamide. J Pediatr 1991:118:656-657. 13. Dupont HL. Hornick RB. Adverse effect of lomotil effect in Shigellosis. JAMA 1973:226:1525-1528. 14. Novak E. Unfavourable effect of lotmotil therapyin linomycin-caused diarrhoea. JAMA 1976;235:1451-1454. 15. Pickering LK. Hemolytic uremic syndrome and enterohemorrhagic E. coli. Pediatr Infect Dis J 1994:13:459-475. 16. Isolauri E, Jurturen M. Wiren S, et al. Intestinal permeability changes in acute gastroenteritis: effects of clinical factors and nutritional management. J Pediatr Gastroenterol Nutr 1989:8:466-473. 17. Levine GM, Deren JJ. Steiger E, et al Role of oral intake in maintainence of gut mass and disarcharidase activity. Gastroenterology 1974;67:972982. The Hong Kong Practitioner VOLUME 21 October 1999 1.

Antimicrobial agents

Most cases of bacterial gastroenteritis are selflimiting and do not require or benefit from antibiotics treatment. In Salmonella gastroenteritis, antibiotic treatment may be indicated in the very young, in immunocompromised patients and in those who are
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