The question is whether low-osmolarity ORS can achieve even better results by changing its composition. Addition or replacement with amino-acid (glycine/alanine) in ORS showed promise some years back, but has not been shown to be useful. Rice and other cereal based solutions release glucose very slowly, not only increasing the reabsorption of water and electrolyte(3), but reducing the osmotic load as well. If this slower process could translate into reduced stool losses and/or shorten the duration of diarrhea, it would make a good thing even better. This issue is explored here.

There is little doubt that the clinical problem (diarrheal dehydration), population (children, especially those under five years old) and intervention (non-glucose based ORS) are highly relevant in the context of our country; owing to high overall diarrheal disease burden, frequent occurrence of dehydration, ease of administration of ORS, acceptability of oral rehydration among physicians and the community in general, and strong commitment of the Government and international agencies to tackle the problem(4-6). The relevant outcomes of interest are mortality, hospitalization, treatment failure (need for administration of intravenous fluid), duration and/or amount of diarrheal losses, complications related to diarrhea and/or dehydration, adverse events related to ORS and cost of therapy. Thus the clinical question is: "In children with diarrheal dehydration (population), does non-glucose oral rehydration solution (intervention) result in better clinical outcome (outcome) as compared to low osmolarity glucose ORS (comparison)"

An updated Cochrane Library search on 24 April 2009, with the term ‘diarrhea’ yielded 21 Cochrane publications (including 8 protocols for systematic reviews) and 31 other systematic reviews; ‘gastroenteritis’ yielded two Cochrane reviews and 5 other systematic reviews. Among these, one Cochrane review published 10 days back(7) compared polymer-based (rice, wheat etc) ORS against glucose-based ORS in adults and children. The authors reported that polymer-based ORS was superior in terms of reduced need for intravenous infusion, shorter duration of cholera diarrhea, lower stool output and comparable rate of adverse events. However, careful appraisal of the data reveals that the authors reported their findings, combining data of standard (310 mOsm/L) ORS and low osmolarity ORS (<270 mOsm/L) in the control group. Although a sub-group analysis of low-osmolarity ORS trials was done, adult and pediatric data were combined to get the pooled estimate. As standard ORS is no longer the recommended rehydrating solution and combining pediatric with adult data is inappropriate, the conclusions of the Cochrane review cannot be taken at face value.

Therefore, a fresh systematic review was undertaken comparing low-osmolarity glucose ORS versus non-glucose ORS with the same electrolye composition. For this, Pubmed was searched on 25 April 2009 using the terms ‘diarrhea AND systematic review’ (Limits: all child) yielding 352 citations; another search using "oral rehydration" (Limits: randomized controlled trials, all child) yielded 64 citations. A third search beyond the date of the Cochrane review search (September 2008) with the term "ORS" (Limits: All child, randomized controlled trials) yielded 2 citations. Sixteen trials from these searches were considered relevant; from these 13 were excluded. Three trials from the Pubmed search and one additional trial from the Cochrane review comprise current best evidence on the subject. Table I summarises the characteristics of included(8-11) and excluded trials(12-24).

TABLE I



Characteristics of Included and Excluded Randomized Controlled Trials

The four included trials can be regarded as having average methodological quality. All of them used appropriate randomization, though only one reported allocation concealment(11). None of the trials blinded observers or participants; all included around 90% or greater of randomized participants in the analysis.

The results are summarized in Table II. None of the trials examined mortality or hospitalization as an outcome. Non-glucose ORS was comparable to glucose ORS in terms of treatment failure (requirement of intravenous fluid), as well as the frequency of two adverse events viz vomiting and hyponatremia. Hyponatremia was surprisingly frequent in the single trial reporting it; this trial was conducted in children with cholera diarrhea having severe dehydration. This could be a matter of concern for using low osmolarity ORS (either type), if substantiated by other reports. The duration and amount of diarrhea were significantly reduced with non-glucose ORS. However, these statistically significant differences may not have as much clinical significance considering that the duration was shortened by only about 4.5 hours and the amount by less than 25g/kg, i.e 2.5% body weight, although the latter represents approximately 25% decrease compared to glucose ORS. It may be recalled that 5% loss results in mild dehydration in infants and young children (3% in older). Thus, it is difficult to agree with the Cochrane review conclusion that non-glucose ORS is superior, although both solutions can be considered comparable. Owing to limited data, no meaningful sub-group analysis based on age of participants, type of diarrhea, degree of dehydration or type of cereal in non-glucose ORS, could be performed.

Table II



Systematic Review Comparing Low-Osmolarity Non-glucose ORS versus Low-Osmolarity Glucose ORS

All the four included trials were conducted in developing countries including one in India. Diarrhea was defined by the usual clinical definition viz >3 watery stools per day. The clinical setting comprised different age groups, level of dehydration and type of diarrhea, all of which occur in Indian children. Two limitations of the current best evidence are that it is limited in terms of power (small sample size) and the four trials are heterogenous in terms of participants, degree of dehydration and outcomes assessed. Therefore, although the evidence can be extended to our clinical setting, it is unlikely to be the final word on the subject.

Funding: None.

Competing interest: None stated.

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