Background Most diarrhoeal deaths can be prevented through the prevention and treatment of dehydration. Oral rehydration solution (ORS) and recommended home fluids (RHFs) have been recommended since 1970s and 1980s to prevent and treat diarrhoeal dehydration. We sought to estimate the effects of these interventions on diarrhoea mortality in children aged <5 years.

Methods We conducted a systematic review to identify studies evaluating the efficacy and effectiveness of ORS and RHFs and abstracted study characteristics and outcome measures into standardized tables. We categorized the evidence by intervention and outcome, conducted meta-analyses for all outcomes with two or more data points and graded the quality of the evidence supporting each outcome. The CHERG Rules for Evidence Review were used to estimate the effectiveness of ORS and RHFs against diarrhoea mortality.

Results We identified 205 papers for abstraction, of which 157 were included in the meta-analyses of ORS outcomes and 12 were included in the meta-analyses of RHF outcomes. We estimated that ORS may prevent 93% of diarrhoea deaths.

Conclusions ORS is effective against diarrhoea mortality in home, community and facility settings; however, there is insufficient evidence to estimate the effectiveness of RHFs against diarrhoea mortality.

The effect of oral rehydration solution and recommended home fluids on diarrhoea mortality

Severe acute malnutrition (SAM) arises as a consequence of a sudden period of food shortage and is associated with loss of a person’s body fat and wasting of their skeletal muscle. Many of those affected are already undernourished and are often susceptible to disease. Infants and young children are the most vulnerable as they require extra nutrition for growth and development, have comparatively limited energy reserves and depend on others. Undernutrition can have drastic and wide-ranging consequences for the child’s development and survival in the short and long term. Despite efforts made to treat SAM through different interventions and programmes, it continues to cause unacceptably high levels of mortality and morbidity. Uncertainty remains as to the most effective methods to treat severe acute malnutrition in young children. Objectives To evaluate the effectiveness of interventions to treat infants and children aged Data sources Eight databases (MEDLINE, EMBASE, MEDLINE In-Process & Other Non-Indexed Citations, CAB Abstracts Ovid, Bioline, Centre for Reviews and Dissemination, EconLit EBSCO and The Cochrane Library) were searched to 2010. Bibliographies of included articles and grey literature sources were also searched. The project expert advisory group was asked to identify additional published and unpublished references. Review methods Prior to the systematic review, a Delphi process involving international experts prioritised the research questions. Searches were conducted and two reviewers independently screened titles and abstracts for eligibility. Inclusion criteria were applied to the full texts of retrieved papers by one reviewer and checked independently by a second. Included studies were mapped to the research questions. Data extraction and quality assessment were undertaken by one reviewer and checked by a second reviewer. Differences in opinion were resolved through discussion at each stage. Studies were synthesised through a narrative review with tabulation of the results. Results A total of 8954 records were screened, 224 full-text articles were retrieved, and 74 articles (describing 68 studies) met the inclusion criteria and were mapped. No evidence focused on treatment of children with SAM who were human immunodeficiency virus sero-positive, and no good-quality or adequately reported studies assessed treatments for SAM among infants Limitations The systematic review focused on key questions prioritised through a Delphi study and, as a consequence, did not encompass all elements in the management of SAM. In focusing on evidence from controlled studies with the most rigorous designs that were published in the English language, the systematic review may have excluded other forms of evidence. The systematic review identified several limitations in the evidence base for assessing the effectiveness of interventions for treating young children with severe acute malnutrition, including a lack of studies assessing the different interventions; limited details of study methods used; short follow-up post intervention or discharge; and heterogeneity in participants, interventions, settings, and outcome measures affecting generalisability. Conclusions For many of the most highly ranked questions evidence was lacking or inconclusive. More research is needed on a range of topic areas concerning the treatment of infants and children with SAM. Further research is required on most aspects of the management of SAM in children Funding The National Institute for Health Research Technology Assessment programme.

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The Effectiveness of Interventions to Treat Severe Acute Malnutrition in Young Children: A Systematic Review

Background Oral rehydration solution (ORS) has reduced childhood deaths from diarrhoea in many countries. Recent studies suggest that the currently recommended formulation of ORS recommended by the World Health Organization (WHO) may not be optimal, and solutions that contain lower concentrations of sodium and glucose may be more effective. Objectives To compare reduced osmolarity ORS with WHO standard ORS in children with acute diarrhoea. Search strategy The Cochrane Collaboration Trials Register (on The Cochrane Library, Issue 2, 2001), MEDLINE (1966 to June 2001), EMBASE (1988 to May 2001), and Current Contents (June 2001) were searched. Additional trials were identified by hand searching. Content experts were contacted. Selection criteria Randomized controlled trials comparing reduced osmolarity ORS with the WHO standard ORS formulation. The primary outcome was unscheduled intravenous fluid infusion. Secondary outcomes were measures of clinical illness. Data collection and analysis Two reviewers extracted data. We tested for heterogeneity using the Chi-square statistic, conducted sensitivity analysis by allocation concealment, and the regression approach to assess funnel plot asymmetry from selective trial publication. Main results The primary outcome, unscheduled intravenous fluid infusion, was reported in 11 trials. In a meta-analysis of 8 trials, reduced osmolarity ORS was associated with fewer unscheduled intravenous fluid infusions compared with WHO standard ORS (Mantel Haenzel odds ratio 0.59, 95% confidence interval 0.45 to 0.79) with no evidence for heterogeneity between trials. No unscheduled intravenous fluid infusion therapy was required in any participant in three trials. Eleven trials reported stool output, and data suggested less stool output in the reduced osmolarity ORS group. Vomiting was less frequent in the reduced osmolarity group in the six trials reporting this. Six trials sought hyponatraemia, with events in three studies, but no obvious difference between the two arms. Reviewer's conclusions In children admitted to hospital with diarrhoea, reduced osmolarity ORS when compared to WHO standard ORS is associated with fewer unscheduled intravenous fluid infusions, lower stool volume post randomization, and less vomiting. No additional risk of developing hyponatraemia when compared with WHO standard ORS was detected.

Reduced osmolarity oral rehydration solution for treating dehydration caused by acute diarrhoea in children

Excerpt This study was designed to develop an oral solution that could reduce the need for intravenous fluids for replacement of stool water and electrolyte losses in cholera. Cholera patients in s...

Oral Maintenance Therapy for Cholera in Adults.

BACKGROUND/AIM: The aim of this study was to investigate epithelial cell turnover in childhood enteropathy to establish whether common disease related mechanisms operate. Levels of epithelial cell proliferation were measured in children with food intolerance (cows' milk protein intolerance and coeliac disease), and after infection with Giardia lamblia, Cryptosporidium, and enteropathogenic Escherichia coli. METHODS: Comparative measures of epithelial cell proliferation were performed by recording mitotic activity and MIB-1 immunoreactivity in proximal small intestinal biopsy specimens. RESULTS/CONCLUSIONS: A hyperplastic crypt response was evident in all of the disease states examined and was particularly pronounced in coeliac disease and in infection with enteropathogenic E coli, where mitotic and MIB-1 labelling indices were significantly raised above control values. In contrast with coeliac disease, increased crypt cell production rates in enteropathogenic E coli infection were also due to an expansion of the crypt proliferation compartment, without a comparable increase in crypt cell numbers. Crypt hyperplasia is therefore a common tissue response to mucosal damage in food allergy and infection, although disease specific mechanisms are evident.

https://gut.bmj.com/content/gutjnl/39/2/185.full.pdf

Epithelial cell proliferation in childhood enteropathies.

The effect of oral rehydration therapy was studied in malnourished infants with acute diarrhea and the course of their water and electroltye homeostasis was compared with that in infants in a normal nutritional state who were treated in the same way for acute diarrhea. The clinical studies were performed in the Department of Pediatrics Capa University of Istanbul Turkey from March 1983 to March 1984. The subjects were 14 malnourished infants ranging in age from 2-15 months. All the patients were hydrated orally. The blood creatinine values were higher in the malnourished group than in the well-nourished group of 16 infants. The average values for urine osmolality were significantly lower than those previously observed in the well-nourished infants. Urine osmolality decreased significantly during rehydration and was only 218+50.3 mosm/kg 36 hours after starting rehydration. The malnourished infants received slightly more oral rehydration solution (ORS) during the first 12 hours than did the well-nourished infants in an earlier study. The average volumes of the stools were about the same in both groups but the urine output was lower in the malnourished infants than in the well-nourished ones. The difference between intake and output as well as the average weight gain after 36 hours was signicantly higher in the malnourished infants than in the well-nourished ones. 18 and 36 hours after admission the serum sodium level was within the normal range in all patients. Sodium intake considerably exceeded sodium output during the entire rehydration period. The stool sodium output was not significantly lower in the well-nourished infants. The percentage of filtered sodium that is not reabsorbed in the renal tubules was low on admission. It increased during rehydration but the increase was less rapid than in the well-nourished infants. The urinary potassium sodium quotient was high on admission but it decreased during rehydration. The decrease was at a slower rate than in the well-nourished group. The study results show that malnourished infants can be successfully rehydrated with a solution that has a sodium concentration of 60 mmol/l and that they do not develop abnormal serum sodium levels.

Oral rehydration therapy in malnourished infants with infectious diarrhoea.

A 4-month-old male infant with severe hyponatremic dehydration due to an enteropathogenic E. coli O125: B15-induced diarrhoea had continued very high stool fluid output with a very elevated sodium concentration after hospitalization and the institution of oral rehydration therapy (ORT). Thirty-six hours after start of ORT intravenous therapy was required. The results of studies of fluid and salt homeostasis in this patient have been compared with those obtained in 3 other patients who had acute diarrhoea of the same severity but caused by another strain of enteropathogenic E. coli (O111:B14) and who were successfully treated with ORT. On ORT the patient with treatment failure had a stool volume which was almost 8 times larger and a stool sodium output which was about 5 times higher than in the successfully treated patients. During the 36-hour-period of ORT fluid losses were about the same as the fluid intake. The results as regards urinary fractional sodium excretion and the urinary potassium/sodium quotient indicate that the severe sodium depletion which was present on admission in the unsuccessfully treated patient persisted during ORT. The reason for ORT failure may be that the infectious E. coli strain had bacilli-adherent qualities that cause damage of microvilli.

Unsuccessful oral rehydration therapy in an infant with enteropathogenic E. coli diarrhoea. Studies of fluid and electrolyte homeostasis

The clinical response and changes in water and salt homeostasis were studied during oral rehydration therapy (ORT) with a solution containing 90 mmol sodium per 1 (ORS90) in 9 infants less than 2 months old (range 2-60 days). Two infants were still dehydrated 36 hours after starting ORT and were excluded from the study. Fluid was retained more rapidly and also to a larger extent than in infants of the same age treated with a solution with a sodium concentration of 60 mmol/l (ORS60). The stool sodium output was higher than that found previously in infants of the same age treated with ORS60. We conclude that during ORT the gut plays an active role in the regulation of salt homeostasis. When the sodium intake is high the percentage of sodium remaining unabsorbed is higher than when the intake is low. This mechanism reduces the risk of hypernatremia in young infants treated with ORS90. The study thus demonstrates that ORS90 is effective and also seems to be safe in the treatment of neonates and young infants with dehydration secondary to diarrhoea if fluid intake is kept around 200 ml/kg/day during the rehydration period.

Salt and water homeostasis during oral rehydration therapy in neonates and young infants with acute diarrhoea. II. Rehydration with a solution containing 90 mmol sodium per litre (ORS90).

R. Zetterström

Papers

Oral rehydration therapy in malnourished infants with infectious diarrhoea.

Unsuccessful oral rehydration therapy in an infant with enteropathogenic E. coli diarrhoea. Studies of fluid and electrolyte homeostasis

Salt and water homeostasis during oral rehydration therapy in neonates and young infants with acute diarrhoea. II. Rehydration with a solution containing 90 mmol sodium per litre (ORS90).