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Jacqueline Dalby-Payne and Elizabeth Elliott What are the effects of treatments for acute gastroenteritis? . . . . . . . . . . . . . . . . . . . . . .2 Enteral (oral or gastric) rehydration solutions (as effective as intravenous fluids). . . . . .2 Probiotics (Lactobacillus) as an adjuvant to Lactose free feeds (may reduce duration of diarrhoea) . . . . . . . . . . . . . . . . . . . . . .3 Loperamide (reduces duration of diarrhoea, but risk of adverse effects). . . . . . . . . . .4 Clear fluids (other than oral rehydration solutions) . . . . . . . . . . . . . . . . . . . . . .5 • Gastroenteritis in children worldwide is usually caused by rotavirus, which leads to considerable Bacterial causes of gastroenteritis are more common in resource poor countries.
• Enteral rehydration solutions containing sugar or food plus electrolytes are as effective as intravenous fluids at correcting dehydration and reducing the duration of hospital stay, and may have fewer major Experimental models have shown that clear fluids, including fruit juices and carbonated drinks, are low in electrolytes, and often high in sugar, and can worsen diarrhoea.
Lactose free feeds may reduce the duration of diarrhoea in children with mild to severe dehydration compared with feeds containing lactose, but studies have shown conflicting results.
• Loperamide can reduce the duration of diarrhoea in children with mild to moderate dehydration compared with placebo, but studies have shown conflicting results, and adverse effects have been Acute gastroenteritis results from infection of the gastrointestinal tract, most commonly with a virus.
It is characterised by rapid onset of diarrhoea with or without vomiting, nausea, fever, and abdominal pain.1 In children, the symptoms and signs can be non-specific.2 Diarrhoea is defined as the frequent passage of unformed, liquid stools.3 Regardless of the cause, the mainstay of management of acute gastroenteritis is provision of adequate fluids to prevent and treat dehydration. In this review, we examine the benefits and harms of different treatments for gastroenteritis, irrespective of its cause.
Worldwide, about 3–5 billion cases of acute gastroenteritis occur each year in children under 5 years, resulting in nearly 2 million deaths.4,5 In the UK, acute gastroenteritis accounts for 204/1000 general practitioner consultations in children under 5 years.6 Gastroenteritis leads to hospital admission in 7/1000 children under 5 years each year in the UK,6 and 13/1000 in the USA.7 In Australia, gastroenteritis accounts for 6% of all hospital admissions in children under 15 years.8 In resource rich countries, acute gastroenteritis is predominantly caused by viruses (87%), of which rotavirus is the most common.8–12 Bacteria, predominantly Campylobacter, Salmonella, Shigella, and Escherichia coli, cause most of the remaining cases. In resource poor countries, where bacterial pathogens are more frequent, rotavirus is also a major cause of gastroenteritis.
Acute gastroenteritis is usually self limiting, but if untreated it can result in morbidity and mortality secondary to water loss, and electrolyte and acid–base disturbance. Acute diarrhoea causes 4 million deaths each year in children under 5 years in Asia (excluding China), Africa, and Latin America, and more than 80% of deaths occur in children under 2 years of age.13 Although death is uncommon in developed countries, dehydration secondary to gastroenteritis is a significant cause of morbidity and To reduce the duration of diarrhoea, quantity of stool output, and duration of hospital stay; to prevent INTERVENTION and treat dehydration; to promote weight gain after rehydration; to prevent persistent diarrhoea associated with lactose intoleranceẦ.
Total stool volume; duration of diarrhoea (time until permanent cessation); failure rate of oral rehydration treatment (as defined by individual RCTs); weight gain after rehydration; length of hospital BMJ Clinical Evidence search and appraisal August 2006. The following databases were used to identify studies for this review: Medline 1966 to August 2006, Embase 1980 to August 2006, and The Cochrane Database of Systematic Reviews 2006, Issue 3. Additional searches were carried out using these websites: NHS Centre for Reviews and Dissemination (CRD), Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA), Turning Research into Practice (TRIP), and National Institute for Health and Clinical Excellence (NICE) clinical guidelines. Abstracts of the studies retrieved were assessed independently by two information specialists using predeter- mined criteria to identify relevant studies. Study design criteria for inclusion in this review were: published systematic reviews and RCTs in any language, at least single blinded, and containing more than 20 children aged 0–12 years, of whom more than 80% were followed up. There was no minimum length of follow up required to include studies. We excluded all studies described as “open”, “open label”, or not blinded. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are continually added to the What are the effects of treatments for acute gastroenteritis? One systematic review, which included studies in children with mild to severe dehydration, found that enteral (oral or nasogastric) rehydration reduced hospital stay compared with intravenous rehydration, and found no significant difference between treatments in weight gain or duration of diarrhoea. Enteral rehydration reduced major adverse events (death or seizure) compared with intravenous rehydration; this was largely based on the results of one large RCT in children with severe gastroenteritis. A second systematic review found that oral rehydration failed in one out of every 25 children treated (failure is defined as the need for intravenous fluids), but this was minimised by the use of low osmolarity solutions. There were no significant differences in weight gain, electrolyte disturbance, or duration of diarrhoea in the enteral and intravenous groups. Hospital stay and phlebitis were significantly less common, and paralytic ileus more common in those children treated with We found three systematic reviews.14–16 Of the three systematic reviews, we report results from the two that reported the most relevant outcomes.15,16 The third review14 focused on the outcome of treatment failure, which is defined variably in different studies and can be difficult to define with intravenous therapy. The first review (search date 2003) found that enteral rehydration significantly reduced the duration of hospital stay compared with intravenous rehydration (hospital stay: 3 RCTs, 161 children; WMD –0.88 days, 95% CI –1.45 days to –0.32 days).15 However, it found no significant difference between enteral and intravenous rehydration in weight gain or duration of diarrhoea (weight gain: 5 RCTs, 276 children, WMD –26 g, 95% CI –60.8 g to + 9.7 g; duration of diarrhoea: 8 RCTs, 946 children, WMD –6.39 hours, 95% CI –13.73 hours to + 0.94 hours).15 Subgroup analysis found that, compared with intravenous rehydra- tion, nasogastric rehydration significantly reduced the duration of diarrhoea, whereas oral rehydration did not (duration of diarrhoea with nasogastric rehydration: 2 RCTs, 494 children, WMD –17.77 hours, 95% CI –27.55 hours to –7.99 hours; duration of diar- rhoea with oral rehydration: 5 RCTs, 415 children, WMD + 1.76 hours, 95% CI –0.91 hours to + 4.42 hours). The results for nasogastric rehydration were heavily influenced by one large study (470 participants) in children with severe gastroenteritis.
Results for weight gain in the first review excluded one RCT in a population of under-nourished children. Inclusion of this study in meta-analyses resulted in significant heterogeneity. Analysis of major adverse events (death or seizure) was strongly weighted by a large RCT conducted in a developing community in 1985 in children with severe gastroenteritis, exclusion of which rendered the results not significant.15 The second review (search date 2006, including children up to 18 years of age with acute gastroenteritis) found that the hospital stay was shorter for those treated with oral rehydration (6 RCTs, 526 children; WMD –1.2 days, 95% CI –2.38 to –0.02 days), but there was no significant difference in weight gain (6 RCTs, 369 children; WMD –26.33 g, 95% CI –206.92 g to + 154.26 g) or duration of diarrhoea (8 RCTs, 960 children; WMD –5.90 hours, 95% CI –12.70 hours to + 0.89 hours). The risk of failure to rehydrate was higher for oral rehydration than for intravenous rehydration (18 RCTs, 1811 children, 4.9% for oral rehydration v 1.3% for intravenous rehydration; RD 4%, 95% CI 1% to 7%), but the definitions of failure varied. The RCTs included in the systematic reviews were of variable quality and many did not report sufficient information about randomisation, blinding, and allocation concealment to enable quality assessment of included tri- als.15,16 RCTs in both systematic reviews discussed included children with a wide age range, variable degrees of dehydration, and different socioeconomic backgrounds; they also included different modes of oral therapy (by mouth or nasogastric tube).
The first systematic review found significantly fewer major adverse events (death or seizure) with enteral rehydration than with intravenous rehydration (16 RCTs, 1545 children; AR for death or seizure: 5/886 [0.6%] with enteral v 15/659 [2.3%] with intravenous; RR 0.36, 95% CI 0.14 to 0.89).15 Oral rehydration had a failure rate (need to convert to intravenous rehydration) of 4%, and nasogastric rehydration had a failure rate of 3.3%. The review did not report on minor adverse events. The second systematic review found that only three of the 17 trials reported deaths, with all reported deaths occurring in low to middle income countries.17 They found that phlebitis was more common in those given intravenous rehydration (NNT 50, 95% CI 25 to 100). Paralytic ileus was more common in those treated with oral rehydration (NNT 33, 95% CI 20 to Clinical guide: There is evidence from systematic reviews that enteral and intravenous rehydration are equally effective for the management of mild to moderate dehydration.
It is accepted practice in resource rich communities that children who are shocked or severely dehydrated require intravenous fluids.
One systematic review of weak RCTs and three of five subsequent RCTs found that lactose free feeds reduced the duration of diarrhoea in children with mild to severe dehydration compared with feeds containing lactose. The two remaining subsequent RCTs found no significant difference between lactose free and lactose-containing feeds in duration of We found one systematic review (search date not reported)18 and five subsequent RCTs19–23 comparing feeds containing lactose versus lactose free feed (see table 1, p 7).
The review was limited by flaws in its methods (see comment below). It found that feeds containing lactose significantly increased “treatment failure” compared with lactose free feeds (13 RCTs, 873 children with mild to severe dehydration; treatment failure rate: 89/399 [22%] with lactose v 56/474 [12%] with lactose free; RR 2.1, 95% CI 1.6 to 2.7).18 However, the definition of treatment failure varied among trials and included increasing severity or persistence of diarrhoea or recurrence of dehydration. The review found that lactose free feeds significantly reduced the mean duration of diarrhoea compared with feeds containing lactose (9 RCTs, 826 children with mild or no dehydration receiving oral rehydration treatment; 92 hours with lactose v 88 hours with lactose free; P = 0.001). When the three RCTs that included children given additional solid food were excluded, the review found that lactose free feeds also significantly reduced the duration of diarrhoea compared with feeds containing lactose (6 RCTs, 604 children; 95 hours with lactose v 82 hours with lactose free; P < 0.001). Children receiving lactose free feeds had significantly reduced stool frequency compared with children receiving feeds containing lactose (4 RCTs, 387 children; 4.0 stool movements/ day with lactose v 3.5 stool movements/day with lactose free; P < 0.004). Total stool volume was greater in children who received feeds containing lactose (4 RCTs, 209 children; P = 0.002). Differences in weight gain during treatment could not be assessed, because of the use of solid food in two studies, and considerable heteroge- neity among studies. Although the systematic review stated criteria for inclusion and exclusion of RCTs, only published studies were included, and the method of determining RCT quality was not reported.18 There was considerable heterogeneity among studies, which limits the validity of the meta-analyses. Lactose free feeds were superior to feeds containing lactose for decreasing the duration of diarrhoea. Differences for other outcomes, although statistically significant, were not clinically important. Of the five subsequent RCTs, three found that lactose free feeds significantly reduced the duration of diarrhoea compared with feeds containing lactose (see table 1, p 7).19,22,23 The other two RCTs found no significant difference.20,21 The results of other outcomes are The RCT assessing adverse effects reported none in the treatment or control groups.21 A protocol on “Lactose avoidance for acute diarrhoea in children less than five years” has been published in the Cochrane Library.23 Clinical guide: There is evidence that lactose free feeds can decrease the duration of diarrhoea compared with lactose-containing feeds, but the existing systematic review is limited by weaknesses in the methods used.
Routine use of lactose free feeds is currently not recommended. We await the results of the Cochane Review that is under way.
Two RCTs found that, in children with mild to moderate dehydration, loperamide reduced the duration of diarrhoea compared with placebo. Another RCT found no significant difference between loperamide and placebo in the duration of diarrhoea. We found insufficient evidence to assess the risk of adverse effects.
We found no systematic review. We found five RCTs in children with acute diarrhoea (701 children, most with mild to moderate dehydration; see table 2, p 8).24–28 Of the three RCTs assessing the duration of diarrhoea, two24,26 found that loperamide significantly reduced the duration of diarrhoea compared with placebo (largest RCT, 315 children; risk of having diarrhoea at 24 hours: 36/100 [36%] with loperamide v 112/203 [55%] with placebo; RR 0.83, 95% CI 0.73 to 0.94).24 Another RCT found no significant difference.25 The results of other outcomes are included in table 2, p 8.
Four RCTs reported no adverse effects from loperamide.24–26,28 One RCT found more mild abdominal distension, excessive sleep, and lethargy in children taking loperamide compared with placebo (3/16 [19%] with loperamide 0.8 mg/kg v 1/18 [6%] with loperamide 0.4 mg/kg v 0/18 [0%] with placebo; RR loperamide v placebo 4.90, 95% CI 0.28 to 86.00).27 Adverse effects caused one child to withdraw from the trial. We found one evidence-based guideline that identified case studies reporting adverse effects including lethargy, intestinal ileus, respiratory depression, and coma, especially We found insufficient evidence to estimate accurately the risk of adverse effects of loperamide in children. Clinical guide: Although loperamide can decrease the duration of diarrhoea, it is not recommended for young children because of the risk of adverse CLEAR FLUIDS (OTHER THAN ORAL REHYDRATION SOLUTIONS) We found no systematic reviews or RCTs comparing “clear fluids” (water, carbonated drinks, and translucent fruit juices) versus oral rehydration solutions for treatment of acute We found no systematic review or RCTs of “clear fluids” compared with oral rehydration solutions (In this review, oral rehydration solutions are defined as solutions containing sugar (e.g. glucose) or food (e.g. rice) plus electrolytes (e.g. sodium, potassium), and are designed to be used to prevent or treat dehydration.
Fruit juices and carbonated drinks are low in sodium and potassium, and usually have a high sugar content (hence osmolarity), which can exacerbate diarrhoea and lead to Clinical guide: In experimental models, scientifically formulated oral rehydration solutions have been proven to promote greater water and solute absorption compared with clear fluids, which are often high in sugar, and contain minimal sodium. Oral rehydration solutions are accepted as the preferred option for the prevention and treatment of dehydration in gastroenteritis.
GLOSSARYLactose intolerance Malabsorption of lactose can occur for a short period after acute gastroenteritis because of mucosal damage and temporary lactase deficiency.
Substantive changesEnteral rehydration solutions One systematic review added.16 Benefits and harms sections enhanced; categorisation unchanged (Beneficial).
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Discipline of Paediatrics and Child Health Competing interests: EE is co-author for one review (reference 1) and one study referenced in this review (reference 8). JDP declares that she has no competing interests.
76 diarrhoea moderate (2 60 diarrhoea 52 diarrhoea moderate (1 200 diarrhoea 315 diarrhoea moderate months 50 diarrhoea 100 diarrhoea moderate years) 53 diarrhoea years) 185 gastroenteritis moderate months). reported;

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