The Committee reviewed an application submitted by the Department of Child and Adolescent Health, WHO, to change the formula of oral rehydration salts (ORS). The current formula, which provides a solution containing 90mEq/l of sodium with an osmolarity of 311mOsm/l, has proven effective, without apparent adverse effects, in worldwide use, and has contributed substantially to the dramatic global reduction in mortality from diarrhoeal disease.

The Committee was informed that, over the past 20 years, numerous studies have been undertaken with a view to developing an "improved" ORS formulation. The goal has been a product that is at least as safe and as effective as the standard ORS solution for preventing or treating dehydration from all types of diarrhoea but which would, in addition, reduce stool frequency or have other important clinical benefits. One approach that was adopted involved decreasing the osmolarity of the standard ORS solution to avoid possible adverse effects of hypertonicity on net fluid absorption. This was achieved by reducing the solution's glucose and salt (NaCl) concentrations.

Studies evaluating this approach were reviewed at a consultative technical meeting held in New York in July 2001; as a result, technical recommendations were made to WHO and UNICEF regarding the efficacy and safety of a reduced-osmolarity ORS solution in children with acute non-cholera diarrhoea, and in adults and children with cholera (29). The studies showed that the efficacy of ORS treatment in children with acute non-cholera diarrhoea is improved by reducing the sodium concentration to 75mEq/l, the glucose concentration to 75mmol/l, and the total osmolarity to 245mOsm/l. Compared with the established ORS solution, the need for unscheduled supplemental intravenous therapy is reduced by 33% (NNT = 20). In addition, a combined analysis of the studies reviewed at the New York meeting and other studies involving reduced-osmolarity ORS solutions of differing composition (osmolarity 210-268mOsm/l, sodium 50-75mEq/ l), reported a reduction in stool output of about 20% and a decrease in the incidence of vomiting of about 30%. The 245mOsm/l solution also appeared to be as safe, and at least as effective, as the standard ORS solution for use in children with cholera (29).

The application also mentioned the fact that the reduced-osmolarity ORS solution containing 75mEq/l sodium, 75mmol/l glucose (total osmolarity = 245mOsm/l) has been shown to be as effective as standard ORS in treating adults with cholera, but is associated with an increased incidence of transient, asymptomatic hyponatraemia. Thus, the reduced osmolarity ORS may be used in place of the standard ORS solution for treating adults with cholera, but careful monitoring is advised for significant hyponatraemia.

In its discussions, the Committee noted that the new reduced-osmolarity ORS formulation has already been officially released by WHO and its partners during the United Nations General Assembly Special Session on Children that was held in New York, and that UNICEF, USAID and MSF are supporting this application. The Committee further noted that WHO and UNICEF have recently published criteria for acceptable ORS formulations (29). These criteria are summarized in Table 1.

The Committee concluded that the evidence supporting the superiority of the new reduced osmolarity ORS solution for the treatment of acute non-cholera diarrhoea in children was convincing, with a 5% absolute risk reduction (NNT = 20) in the need for unplanned intravenous infusions, and on this basis recommended that the formula for ORS in the Model List (section 17.7.1 Oral hydration) be changed to 75mEq/l sodium (sodium chloride 2.6g/l) and 75mmol/l (13.5g/l) glucose. The Committee also recommended the addition of the following footnote:

In cases of cholera a higher concentration of sodium may be required.

Table 1
Recommended composition of oral rehydration salts^a

^a The listed criteria specify the desired characteristics of the solution after it has been prepared according to the instructions on the packet.

Source: reference 30.