We found that reduced osmolarity rehydration solution was more effective than standard WHO rehydration solution in first line treatment of children with diarrhoea. It reduced the need for unscheduled intravenous infusion, stool output during rehydration, and the number of patients with vomiting during oral rehydration treatment. The reduced osmolarity rehydration solution did not seem to increase the risk of developing hyponatraemia compared with the standard WHO solution, although we cannot exclude this possibility.
We examined trials of oral rehydration salts in children admitted to hospital with dehydration because of diarrhoea. The trials do not provide any direct evidence for or against use of oral rehydration solutions at home to prevent dehydration; nor do they provide any direct evidence that reduced osmolarity solutions are more effective in preventing dehydration in the home. Oral rehydration solutions are widely used to prevent dehydration, and further research is therefore needed in this area.
Choice of primary outcome
We stand by our selection of unscheduled intravenous infusion rather than volume of diarrhoea as the primary outcome.9
Some specialists consider that volume of diarrhoea is more appropriate, probably because it reflects the animal and human perfusion experiments that provide part of the rationale for a reduced osmolarity rehydration solution. Unscheduled intravenous infusion is pragmatic; it provides a measure of failed oral rehydration and has implications for healthcare resources. For these reasons, we preserved this as the primary outcome.
When we reviewed the studies for inclusion, most trials reported unscheduled intravenous infusion in the details of trial implementation. As this was identified as our primary outcome, we sought out these data and presented them as the primary analysis. We believe that the analysis shows a clear effect. Our approach highlights the value of paying careful attention to the protocol for a systematic review before examining the trials and illustrates how non-specialist viewpoints can help obtain practical and useful answers from a meta-analysis.
We intended to examine treatment effects in patients with and without cholera.9
A Cochrane review of rice based rehydration compared with glucose oral rehydration solution showed that rice water was associated with lower stool volumes in cholera patients but not in diarrhoea from other causes.27
The available data were, however, insufficient. Three studies included cholera patients,12,14,21
but separate data for cholera patients were not available. We excluded two studies in patients with cholera because they were in adults.28,29
Any recommendation for rehydration treatment for adults with cholera will need to take into account these and any other trials found through careful systematic searching.
Patients with cholera have severe loss of electrolytes. It is unclear, therefore, whether reduced osmolarity rehydration solution would be more effective than standard WHO rehydration solution in these patients. The reduced osmolarity solution could increase the risk of hyponatraemia and result in adverse clinical events
Our study suggests that reduced osmolarity rehydration solution should replace the WHO solution as the standard treatment for dehydration caused by diarrhoea. Policymakers and clinicians may, however, consider that the risk of hyponatraemia in patients with cholera outweighs the advantages of a reduced osmolarity solution. One option would be to provide standard WHO rehydration solution for people with suspected cholera or in areas where cholera is prevalent. This is likely to be a logistical problem in areas where diarrhoea is common and coexists with cholera. The single formula sachet aids implementation of this lifesaving intervention. Providing different formulations complicates distribution and may impair the effective delivery of any oral rehydration solution to children. If policymakers decide not to use reduced osmolarity solution in areas where cholera is common, they must conduct a randomised controlled trial of the two treatments in children with cholera to determine whether the decision is correct.