2 Research recommendations
The Guideline Development Group has made the following recommendations for research, based on its review of evidence, to improve NICE guidance and patient care in the future. The Guideline Development Group's full set of research recommendations is detailed in the full guideline (see section 5).
In children with gastroenteritis, what is the predictive value of clinical symptoms and signs in assessing the severity of dehydration, using post-rehydration weight gain as the reference standard, in primary and secondary care settings?
Evidence from a systematic review suggests that some symptoms and signs (for example, prolonged capillary refill time, abnormal skin turgor and abnormal respiratory pattern) are associated with dehydration, measured using the accepted 'gold standard' of the difference between pre-hydration and post-hydration weight. However, 10 of the 13 included studies were not blinded and had ill-defined selection criteria. Moreover, all these studies were conducted in secondary care where children with more severe dehydration are managed.
Most children with gastroenteritis can and should be managed in the community but there is a lack of evidence to help primary care healthcare professionals correctly identify children with more severe dehydration. Symptoms and signs that researchers may wish to investigate include overall appearance, irritability/lethargy, urine output, sunken eyes, absence of tears, changes in skin colour or warmth of extremities, dry mucous membranes, depressed fontanelle, heart rate, respiratory rate and effort, character of peripheral pulses, capillary refill time, skin turgor and blood pressure.
In children who do not tolerate oral rehydration therapy, is ORS solution administration via nasogastric tube cost effective, safe and acceptable in treating dehydration compared with intravenous fluid therapy?
Oral rehydration therapy is normally preferable to intravenous fluid therapy for rehydration in children with gastroenteritis. However, some children may not tolerate oral rehydration therapy, either because they are unable to drink ORS solution in adequate quantities or because they persistently vomit. In such cases, ORS solution could be administered via a nasogastric tube, rather than changing to intravenous fluid therapy. This overcomes the problem of ORS solution refusal. Continuous infusion of ORS solution via a nasogastric tube might reduce the risk of vomiting. A well-conducted randomised controlled trial is needed to assess the cost effectiveness, safety and acceptability of rehydration using nasogastric tube administration of ORS solution compared with intravenous fluid therapy.
In children who require intravenous fluid therapy for the treatment of dehydration, is rapid rehydration safe and cost effective compared with the common practice of rehydration over 24 hours?
Most children with clinical dehydration should be treated with oral rehydration therapy, but some require intravenous fluid therapy because they are shocked or they cannot tolerate oral rehydration therapy. Rehydration with oral rehydration therapy is usually carried out over a period of 4 hours. Rehydration with intravenous fluid therapy has traditionally been undertaken slowly – typically over 24 hours. The National Patient Safety Agency has advised that intravenous fluid deficit replacement should be over 24 hours or longer. Consequently, children will remain dehydrated and in hospital for a prolonged period. The WHO recommends that intravenous rehydration should be completed in 3–6 hours. Many experts now support rapid intravenous rehydration, suggesting that it allows oral fluids to be starter earlier and can shorten the duration of hospital treatment. Randomised controlled trials are needed urgently to examine the safety and cost effectiveness of rapid intravenous rehydration regimens compared with slow intravenous rehydration.
In children with persistent vomiting caused by gastroenteritis, is oral ondansetron cost effective and safe compared with placebo therapy?
Several randomised controlled trials have shown that in children with persistent vomiting during oral rehydration therapy, administration of oral ondansetron, an anti-emetic agent, can increase the likelihood of successful oral rehydration. However, in two of these there was evidence suggesting that diarrhoea was more pronounced in those given ondansetron than in those in the placebo groups. In one, in children given ondansetron, the number of stools passed during the rehydration phase was significantly greater, and in the other the number of stools passed in the first and second 24-hour period after rehydration was significantly greater. In those studies, diarrhoea was not a primary outcome, and it was reported as an adverse event. The reliability of the finding was therefore somewhat uncertain. If ondansetron does worsen diarrhoea it would be crucially important to determine the clinical significance of this effect, for example in relation to the risk of dehydration recurring or re-admission to hospital. If ondansetron is shown to be both effective and safe in secondary care then studies should also be undertaken to evaluate its use in primary care.
Are probiotics effective and safe compared with a placebo in the treatment of children with gastroenteritis in the UK? Which specific probiotic is most effective and in what specific treatment regimen?
The available studies of probiotic therapy frequently report benefits, particularly in terms of reduced duration of diarrhoea or stool frequency. However, most of the published studies have methodological limitations. Moreover, there is great variation in the specific probiotics evaluated and in the treatment regimens used. Many of these studies were conducted in developing countries where the response to probiotic therapy may differ. Good-quality randomised controlled trials should be conducted in the UK to evaluate the effectiveness and safety of specific probiotics, using clearly defined treatment regimens and outcome measures.
 Steiner MJ, DeWalt DA, Byerley JS (2004) Is this child dehydrated? JAMA: the Journal of the American Medical Association. 291(22):2746–54.
 Hay AD, Heron J, Ness A; the ALSPAC study team (2005) The prevalence of symptoms and consultations in pre-school children in the Avon Longitudinal Study of Parents and Children (ALSPAC): a prospective cohort study. Family Practice. 22(4):367–74.
 Reducing the risk of hyponatraemia when administering intravenous infusions to children. National Patient Safety Agency, Alert no. 22, Ref: NPSA/2007/22, Issued: 28 Mar 2007
 World Health Organization (2005) The treatment of diarrhoea: a manual for physicians and other senior health workers