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;