A new formulation of ORS for children is warranted.

Abstract

For decades, the World Health Organization (WHO) and the United Nations Children's Fund have recommended a single formulation of glucose-based oral rehydration salts (ORS) to treat or prevent dehydration from diarrhea of any cause and in individuals of any age (1,2). This product has proven safe and effective in worldwide use and has contributed substantially to the global decrease in mortality from diarrheal disease. More recently, solutions of reduced osmolarity (e.g., 75 mEq/L Na, 75 mmol/L glucose) have been investigated, because these solutions preserve the 1:1 molar ratio of sodium to glucose, but present less of an osmolar load to the intestinal tract than does WHO ORS (245 versus 311 mOsm/L). Animal (3) and human studies (4) indicate that solutions of decreased osmolarity are better rehydration fluids. Children receiving decreased osmolarity ORS have been reported to have less vomiting, less stool output, shorter duration of illness, and less need for supplemental intravenous fluid than those treated with standard WHO ORS. Therefore, should the WHO and others modify the ORS formulation that has long proven to be safe and effective? Two large clinical trials and a meta-analysis have recently shed light on this dilemma. In one trial of 300 adult cholera patients (5), subjects who received decreased osmolarity ORS had similar clinical outcomes compared with those who received standard WHO ORS (i.e., stool output, duration of diarrhea, need for unscheduled intravenous therapy, and treatment failures). Patients who received decreased osmolarity ORS had an increased incidence of hyponatremia (serum Na <130 mmol/L) (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.1–4.1), although the mean difference in serum sodium at 24 hours was only 1.2 mEq/L and none of the subjects had symptoms of hyponatremia. In a large multicenter trial of children with acute noncholera diarrhea (6), 675 children from five countries were randomized to receive standard ORS or decreased osmolarity ORS. Although stool output and vomiting did not differ between groups, the use of unscheduled intravenous fluids was greatly decreased in the group that received low-osmolarity ORS (10% versus 15%; OR, 0.6; 95% CI, 0.4–1.0). The occurrence of hyponatremia did not statistically differ between groups (11% in the decreased osmolarity group and 9% in the standard group, OR, 1.3; 95% CI, 0.2–2.2). Finally, a meta-analysis published this summer (7) evaluated the effects of reduced osmolarity ORS in 15 randomized trials of nearly 2,400 patients (including the two trials noted above). Use of decreased osmolarity ORS was associated with less frequent use of unscheduled intravenous fluid (combined OR, 0.61; 95% CI, 0.47–0.81) and less vomiting (combined OR, 0.71; 95% CI, 0.55–0.92). In addition, a statistically significant reduction in stool output was noted. The incidence of hyponatremia in these trials was not significantly elevated in children who received decreased osmolarity ORS (OR, 1.45; 95% CI, 0.93–2.26). Based on these studies, ORS of decreased osmolarity probably is more effective than the WHO ORS in children with noncholera diarrhea and shows no important trend for increased rates of hyponatremia. In adult patients with cholera infection, decreased osmolarity ORS is equally as effective as standard ORS, but its use is associated with increased rates of hyponatremia. However, the clinical significance of these laboratory outcomes is unclear. If a single solution continues to be the goal of WHO and other policy-making bodies, a solution with 75 mEq/L sodium should be adopted. Critics have argued that any change in the composition of ORS to a lower concentration of sodium will increase the risk of hyponatremia among cholera patients (8). Although in cholera, stool sodium losses can be as high as 120 to 150 mEq/L, even the current formulation of WHO ORS contains less sodium than may be required for adequate Na repletion. However, if proper nutritional and fluid repletion occurs during cholera treatment (i.e., a diet containing sodium), ensuing clinically significant negative sodium status seems less likely. This summer, an expert committee convened by WHO and the United Nations Children's Fund suggested that if a solution of decreased osmolarity (and therefore sodium) is used in areas in which cholera infection is common, a postmarketing surveillance study should be performed to assess the occurrence of clinically significant electrolyte abnormalities. In 1992, the European Society of Pediatric Gastroenterology and Nutrition recommended the use of decreased osmolarity ORS “for children in Europe” with acute gastroenteritis because concern was raised that a sodium concentration of 60 mEq/L was unsafe for children in developing countries with higher purging rates and poorer nutritional status (9). Based on the data now available, a solution with 75 mEq/L Na and 75 mmol/L glucose probably is optimal for all children. Should concerns about hyponatremia in adult cholera infections be proven valid, the production and distribution of two ORS solutions (one for children with noncholera infections and the second for cholera) should be considered.