A double-blind clinical trial comparing World Health Organization oral rehydration solution with a reduced osmolarity solution containing equal amounts of sodium and glucose. Alanine- and glucose-based hypo-osmolar oral rehydration solution in infants with persistent diarrhoea: a controlled trial. Hypotonic oral rehydration solution in acute diarrhoea: a controlled clinical trial. Oral rehydration of neonates and young infants with dehydrating diarrhea: comparison of low and standard sodium content in oral rehydration solutions. Hypo-osmolar sucrose oral rehydration solutions in acute diarrhoea: a pilot study. Is a low-osmolarity ORS solution more efficacious than standard WHO ORS solution? Multicenter, randomized, double-blind clinical trial to evaluate the efficacy and safety of a reduced osmolarity oral rehydration salts solution in children with acute watery diarrhea. [Comparative study of 2 oral rehydration solutions containing 60 or 90 mmol/L of sodium and with different osmolalities]. Hypo-osmolar oral rehydration salts solution in dehydrating persistent diarrhoea in children: double-blind, randomized, controlled clinical trial. Multicentre evaluation of reduced-osmolarity oral rehydration salts solution. International Study Group on Reduced-osmolarity ORS solutions.
To compare the safety and efficacy of an oral rehydration solution (ORS) containing 75 mmol/L of sodium and glucose each with the standard World Health Organization (WHO) ORS among Egyptian children with acute diarrhea.
                One hundred ninety boys, aged 1 to 24 months, who were admitted to the hospital with acute diarrhea and signs of dehydration were randomly assigned to receive either standard ORS (311 mmol/L) or a reduced osmolarity ORS (245 mmol/L). Intake and output were measured every 3 hours.
                In the group treated with reduced osmolarity ORS, the mean stool output during the rehydration phase was 36% lower (95% confidence interval, 1%, 100%) than in those treated with WHO ORS. The relative risk of vomiting during the rehydration phase was significantly lower in children treated with reduced osmolarity ORS (relative risk, 2.4; 95% confidence interval, 1.2, 4.8). During the maintenance phase, stool output, mean intake of food and ORS, duration of diarrhea, and weight gain were similar in the treatment groups. The relative risk of treatment failure (need for unscheduled administration of intravenous fluids) was significantly increased in children receiving standard WHO ORS (relative risk, 7.9; 95% confidence interval, 1.1, 60.9). The mean serum sodium concentration at 24 hours was significantly lower in children receiving the reduced osmolarity ORS solution (134 +/- 6 mEq/L) than in children receiving the standard WHO ORS (138 +/- 7 mEq/L) (p < 0.001). The relative risk of the development or worsening of hyponatremia was not increased in children given the reduced osmolarity ORS, and urine output was similar in the treatment groups.
                The reduced osmolarity ORS has beneficial effects on the clinical course of acute diarrhea in children by reducing stool output, and the proportion of children with vomiting during the rehydration phase, and by reducing the need for supplemental intravenous therapy. These results provide support for the use of a reduced osmolarity ORS in children with acute noncholera diarrhea. To evaluate the efficacy of a hypo-osmolar and a standard (World Health Organization) oral rehydration salt (ORS) solution in persistent diarrhoea, a randomized controlled clinical trial was conducted in 55 children. After a 1-day observation period the children were assigned to one of three solutions: standard ORS (WHO-ORS) (osmolality 311 mosmol/l), hypo-osmolar ORS containing L-alanine and glucose (osmolality 255 mosmol/l) and i.v. polyelectrolyte solutions (osmolality 293 mosmol/l) for ongoing replacement of stool loss for the next 4 days. Excellent acceptability of ORS (101-160 ml/kg body weight/day) by the children was observed. There were no significant differences in the total intake of solutions and food, and frequency of stools among the groups. Stool outputs were significantly less in infants receiving hypo-osmolar ORS than in those receiving WHO-ORS for 0-24 h (p = 0.04), 0-48 h (p = 0.01), 0-72 h (p = 0.04) and 0-96 h (p = 0.03). The results indicate a sufficient scope of ORS practice in persistent diarrhoea. Furthermore, we found that a hypo-osmolar ORS containing L-alanine and glucose is as efficacious as an iv solution and more effective than WHO-ORS for replacement of ongoing stool loss in persistent diarrhoea. In a controlled trial, a hypotonic oral rehydration solution (ORS) (Na+67, K+20, Cl-66, citrate 7, glucose 89 mmol/l osmolality 249 mosmol/kg) was compared with a standard WHO-ORS (Na+90, K+20, Cl-80, citrate 10, glucose 111 mmol/l, osmolality 311 mosmol/kg) in 60 children aged 5-24 months with acute watery diarrhoea. In the hypotonic ORS group, stool frequency, proportion of children who vomited, ORS requirements and purging rate over 24-48 h were reduced by 33% (p = 0.01), 30% (p = 0.02), 21% (p = 0.067) and 21% (p = 0.03), respectively. The proportion of children who vomited and the purging rate over 48 h were reduced by 23% (p = 0.03) and 10% (p = 0.097), respectively. Serum electrolytes after 48 h were comparable. The beneficial effect of hypotonic ORS was most marked in, and largely contributed by, the subgroup negative for rotavirus. Oral rehydration among infants aged 0-3 months has not been adequately investigated. A controlled, randomized study was thus conducted in 65 young infants hospitalized with acute noncholera dehydrating diarrhea. The study was designed to compare the efficacy and safety of the standard WHO oral glucose-electrolyte solution containing 90 mmol of sodium per liter (Group A: 22 infants) with that of an oral glucose-electrolyte solution containing 60 mmol of sodium per liter (Group B: 22 infants) and with standard intravenous therapy (Group C: 21 infants). Among the 44 infants in Groups A and B, none required intravenous therapy. Dehydration, acidosis, and initial hyponatremia or hypokalemia were corrected with equal efficacy in all the three groups. In the critical first 8 h, the mean sodium absorption was significantly higher (p less than 0.01) in Group A. This resulted in hypernatremia (50%), periorbital edema (50%), mild pedal edema (27%), excessive irritability, and convulsions (4.5%). The mean serum sodium levels at 8, 24, and even 48 h were significantly higher (p less than 0.05) than those in Groups B and C. It is concluded that glucose-electrolyte oral solution containing 60 mmol of sodium per liter is as safe and effective as intravenous rehydration for the treatment of noncholera neonatal and early infantile diarrhea, while the standard WHO solution carries a significant risk of hypernatremia under similar conditions. Based on studies showing improved absorption of hypo-osmolar oral rehydration solutions (ORS) with reduced glucose and sodium concentration, a hypo-osmolar ORS with sucrose replacing glucose (sodium 60, potassium 15, chloride 60, citrate 5, sucrose 58 mmol l-1, calculated osmolality 198 mOsm kg-1) was compared with mildly hyperosmolar glucose ORS (WHO) in 46 children aged 6-30 months with acute diarrhoea and dehydration. In the hypo-osmolar sucrose ORS group (n = 18) faecal output was less by 30% during the initial 24 and 48 h compared with controls, suggesting better absorption. Sucrose may be a suitable alternative to glucose in an absorption-efficient hypo-osmolar ORS. The clinical efficacy of a diluted oral rehydration salts (ORS) solution was compared in a pilot study with that of intravenous (i.v.) therapy and of standard World Health Organization (WHO)/United Nations Childrens Fund (UNICEF) ORS solution in children with acute diarrhea. Sixty-one boys aged 3 to 24 months, admitted to hospital with acute diarrhea and signs of dehydration, were randomly assigned to groups receiving standard ORS solution, diluted ORS solution, or i.v. therapy. In children treated with standard ORS solution and small amounts of plain water, the total fluid intake was 25-39% greater, the stool output was 58-77% greater (p < 0.01), and the duration of diarrhea was 30-55% greater than in the other treatment groups. Intake of plain water, taken separately or added to the ORS solution, was greater in children given diluted ORS solution (73 +/- 23 ml/kg) than in those given standard ORS solution (21 +/- 32 ml/kg) (p < 0.001). The mean serum sodium concentration increased by 2.2 mEq/L in children given standard ORS solution, whereas it decreased by 2.9 mEq/L in those given diluted ORS solution. This study shows that some children develop worsening diarrhea and increasing serum sodium concentrations when treated with standard ORS solution and given only small amounts of plain water. This is probably caused by the slight hypertonicity of standard ORS solution combined with transient partial glucose malabsorption. This can be avoided if water, breast milk, or another low-solute drink is given liberally during maintenance therapy with ORS solution, as recommended by the WHO. To compare the efficacy of a reduced osmolarity oral rehydration salts (ORS) solution (75 mmol/L of sodium [Na], 20 mmol/L of potassium [K], 65 mmol/L of chloride, 10 mmol/L of citrate, and 75 mmol/L of glucose; osmolarity, 245 mosm/L) with that of the standard World Health Organization (WHO) ORS solution.
                A multicenter, double-blind, randomized, controlled clinical trial conducted in children with acute diarrhea in 5 developing countries to measure mean stool output in the 24 hours after randomization, proportion of children who required unscheduled intravenous therapy, proportion of children who vomited in the first 24 hours, and diarrhea duration after randomization.
                A total of 675 children who ranged in age from 1 to 24 months and who had acute diarrhea and dehydration were enrolled in the trial; 341 were randomized to receive reduced osmolarity ORS solution, and 334 were randomized to receive the WHO ORS solution. The mean (SE) stool output (g/kg) in the first 24 hours (reduced osmolarity ORS solution vs WHO ORS solution = 114 [4] vs 125 [5]) and during the total study period (reduced osmolarity ORS solution vs WHO ORS solution = 320 [18] vs 331 [18]) were comparable. The proportion of children who vomited in the first 24 hours (reduced osmolarity ORS solution vs WHO ORS solution = 58% vs 62%) and the diarrhea duration in the 2 treatment groups, compared by log rank test, were similar. The proportion of children who required unscheduled intravenous therapy was significantly lower in children who received reduced osmolarity ORS solution (10%) as compared with those who received the WHO ORS solution (15%; odds ratio = 0.6, 95% confidence interval = 0.4-1.0). There was no significant difference in the incidence of hyponatremia (serum Na <130 mmol/L) at 24 hours between the 2 treatment groups (11% in reduced osmolarity ORS solution group vs 9% in the WHO ORS solution group; odds ratio = 1.3; 95% confidence interval = 0.8-2.2). The frequency of patients with serum Na <125 mmol/L at 24 hours was 13 of 341 (4%) in children who were treated with reduced osmolarity ORS solution versus 7 of 334 (2%) in children who received the WHO ORS solution.
                Treatment with reduced osmolarity ORS solution was associated with a 33% reduction in the need for unscheduled intravenous therapy and had no apparent effect on stool output and illness duration when compared with treatment with the standard WHO ORS solution. Children with acute diarrhea, therefore, may benefit from a reduced osmolarity ORS solution. The results of trials that examine the efficacy and safety of reduced osmolarity ORS solution in adult patients with cholera have to be taken into consideration before consensus on composition of oral rehydration formulation can be reached. A total of 186 infants, suffering from acute diarrhea were studied and divided into two groups: 84 children were placed in group A and given the ORS recommended by the World Health Organization which contains sodium and glucose at concentrations of 60 and 90 mmol/L respectively and an osmolality of 311 mOsm/kg (mmol/kg) (ORS-90). Group B included 82 children who received an ORS containing sodium and glucose at concentrations of 60 and 90 mmol/L respectively and with an osmolality of 240 mOsm/kg (mmol/kg) (ORS-60). Seven belonging to group A (8.3%) required intravenous rehydration due to the severity of the diarrhea (three cases), persistent vomiting (three cases) and paralytic ileus (one case), while only two cases belonging to group B (2.5%) required intravenous rehydration due to severe losses through feces (one case) and another due to paralytic ileus (one case). No differences were observed due to the variations in sodium concentrations among either of the groups of patients, whether that be in the natremias when admitted or once rehydrated, with a general tendency towards the correction of the hypernatremia or hyponatremia seen during admittance with both types of ORS. A similar situation was observed with the variations in serum potassium. The results obtained from this study show the different advantages of using an ORS with lesser sodium and glucose concentrations as well as minor osmolality with those from using the solution recommended by the World Health Organization, when a lesser index of failures is observed in the treatment of children with acute diarrhea with oral rehydration therapy. Yet before widely recommending its' use, it should be demonstrated that the new ORS induces lesser losses through feces during the rehydrating period in children dehydrated due to acute diarrhea. A double-blind, randomized, controlled trial was conducted to compare the clinical efficacy of hypo-osmolar oral rehydration salts (ORS) solution (224 mmol/L) and standard ORS solution (311 mmol/L) in children with persistent diarrhoea who were prone to develop dehydration. Initially, 95 children aged between 3 and 24 mo were included in the study for overnight observation. Of these, 70 children who passed stool more than 2 g/kg/h were finally enrolled in the study and were randomly assigned either standard ORS or hypo-osmolar ORS. After decoding the identity of ORS, it was observed that 37 children were in the standard ORS group and 33 in the hypo-osmolar ORS group. Clinical parameters and microbiological findings of stool samples were comparable in the two groups at the time of enrolment. Total stool output (2.5+/-1.1 vs 3.2+/-1.6 kg; p = 0.04), duration of diarrhoea (114.8+/-38.3 vs 145.4+/-40.0 h; p = 0.002), total intake of ORS (5.4+/-1.6 vs 7.8+/-1.8 l; p = 0.002) and total fluid intake (7.9+/-2.6 vs 10.0+/-4.1 l, p = 0.01) were significantly less in the hypo-osmolar ORS group compared to the standard ORS group. However, the percentage of weight gain on recovery in the hypo-osmolar group was less compared to that of the standard ORS group, though the difference was statistically insignificant. Thirty-five (95%) children in the standard ORS and 33 (100%) children in the hypo-osmolar group recovered within 10 d of initiation of therapy and modified dietary management.
                Our findings suggest that hypo-osmolar ORS has beneficial effects on the clinical course of dehydrating persistent diarrhoea. In developed countries, use of oral rehydration salts (ORS) solution with osmolarity lower than that of plasma has been recommended because of the risk of hypernatraemia. We compared the clinical efficacy of reduced-osmolarity ORS and standard ORS solutions in children with acute diarrhoea in four developing countries. 447 boys aged 1-24 months, admitted to hospitals in four countries with acute diarrhoea and signs of dehydration, were randomly assigned either standard ORS (311 mmol/L) or reduced-osmolarity ORS (224 mmol/L) solution. Total stool output was 39% greater (95% CI 11-75), total ORS intake 18% greater (3-33), and duration of diarrhoea 22% longer (2-45) in the standard ORS group than in the reduced-osmolarity ORS group. The risk of requiring intravenous infusion after completion of the initial oral rehydration was greater in children given standard ORS solution than in those given reduced-osmolarity ORS solution in three of the four countries (all-country relative risk 1.4 [0.9-2.4]). This relative risk was significantly increased only in non-breastfed children (2.0 [1.0-3.8], p < 0.05). In breastfed children, the relative risk of requiring intravenous infusion was not affected by the ORS solution (0.9 [0.4-2.0]). The mean sodium concentration 24 h after admission was significantly lower in the reduced-osmolarity ORS group than in the standard ORS group (135 [134-136] vs 138 [136-139] mmol/L, p < 0.01). Reduced-osmolarity ORS solution has beneficial effects on the clinical course of acute diarrhoea. Our findings support the use of reduced-osmolarity ORS solution in children with acute non-cholera diarrhoea in developing countries. Further studies are needed to find the best formulation and whether such a solution would be satisfactory for the treatment of cholera.
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.