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Oral rehydration solution containing a mixture of non-digestible carbohydrates in the treatment of acute diarrhea: a multicenter randomized placebo controlled study on behalf of the ESPGHAN working group on intestinal infections.

OBJECTIVE: A randomized, double-blind, placebo-controlled multicenter study to evaluate efficacy and safety of a mixture of non-digestible carbohydrates (NDC) as an adjunct to oral rehydration therapy in treatment of acute infectious diarrhea in children with mild to moderate dehydration. METHODS: 144 boys aged 1 to 36 months with diarrhea defined as three or more watery stools per day for >1 day but <5 days with mild or moderate dehydration (World Health Organization criteria) were randomly assigned to receive hypotonic oral rehydration solution (ORS) (Na 60 mmol/L, glucose 111 mmol/L) with or without a mixture of NDC (soy polysaccharide 25%, alpha-cellulose 9%, gum arabic 19%, fructooligosaccharides 18.5%, inulin 21.5%, resistant starch 7%). RESULTS: Intention-to-treat analysis did not show significant differences in mean 48 hour stool volume (ESPGHAN-ORS with NDC versus ESPGHAN-ORS, 140 +/- 124 g/kg versus 143 +/- 114 g/kg; P = 0.41). Duration of diarrhea after randomization was similar in both groups (82 +/- 39 hours versus 97 +/- 76 hours, P = 0.24). There were no significant differences in the duration of hospital stay (111 +/- 44 hours versus 126 +/- 78 hours; P = 0.3). Unscheduled intravenous rehydration was similar in both groups (21.4% versus 16.2%, P = 0.42). CONCLUSION: In boys with acute non-cholera diarrhea with mild to moderate dehydration a mixture of non-digestible carbohydrates was ineffective as an adjunct to oral rehydration therapy.

Acute Disease↗

Control study of oral rehydration solution (ORS)/ORS + dioctahedral smectite in hospitalized Thai infants with acute secretory diarrhea.

Dioctahedral smectite, a non systemic antidiarrheal agent, is mucoprotective and absorbs enterotoxins and rotavirus as demonstrated in animal models. Smectite has been successfully used in various countries in children and adults with acute diarrhea. This study was to assess the efficiency of smectite associated with rehydration in infants with acute secretory diarrhea. Sixty-two hospitalized Thai infants, aged 1-24 months, with acute secretory diarrhea were randomly divided into 2 groups receiving (1) oral rehydration solution (ORS) (30 cases), (2) ORS and Smectite (3.6 g/day) (32 cases). Both groups were comparable for age, weight, nutritional status and duration of symptoms before treatment. All 62 infants received lactose free formula and chicken rice soup as the standard diet. Stool frequency, weight change and duration of diarrhea were recorded. The mean duration of diarrhea was 84.7 +/- 48.5 hours in group 1, and 43.3 +/- 25.1 hours in group 2 (p = 0.005). The number of infants with diarrhea was significantly lower in group 2 on Day 1 (p < 0.01) and Day 3 (p = 0.001); furthermore 27% of infants in group 1 and 3% in group 2 had still diarrhea on Day 5. The stool frequency and weight changes were not statistically different in the two groups. No major side effects were observed except two cases of vomiting and hardened stools. It is concluded that (1) Smectite shortens the course of acute secretory diarrhea in Thai infants; (2) smectite may reduce the occurrence of prolonged diarrhea; furthermore (3) in our study dioctahedral smectite was found to be safe in children aged 1 to 24 months.

Chi-Square Distribution↗

Partially hydrolyzed guar gum-supplemented oral rehydration solution in the treatment of acute diarrhea in children.

BACKGROUND: Partially hydrolyzed guar gum (Benefiber; Novartis Nutrition, Minneapolis, MN, U.S.A.) is fermented by colonic bacteria liberating short-chain fatty acids (SCFAs), which accelerate colonic absorption of salt and water. The purpose of this study was to evaluate the effect of Benefiber (BF)-supplemented World Health Organization Oral Rehydration Solution (WHO ORS) in the treatment of acute noncholera diarrhea in children. METHODS: A double-blind, randomized, controlled clinical trial was performed at ICDDR,B in 150 male children aged 4 to 18 months who had watery diarrhea of less than 48 hours' duration. After admission, children were assigned to receive either WHO ORS or BF-supplemented WHO ORS until recovery. Major outcome measures, such as duration of diarrhea and amount of stool output, were compared between the treatment groups. RESULTS: Patients receiving BF-supplemented WHO ORS had significantly reduced duration of diarrhea compared with the control group (mean +/- SD, 74 +/- 37 vs. 90 +/- 50 hours, P = 0.03). Survival analysis for duration of diarrhea also showed a reduction the BF-supplemented WHO ORS-treated group (P = 0.025, log rank test). There was also less stool output daily from days 2 through 7 in the patients treated with BF-supplemented WHO ORS compared with that in the children treated with WHO ORS; the reduction was significant on day 7 only. CONCLUSION: Benefiber added to standard WHO ORS substantially reduces the duration of diarrhea and modestly reduced stool output in acute noncholera diarrhea in young children, indicating its potential as a new antidiarrheal therapy for acute diarrhea in children.

Acute Disease↗

Water and electrolyte absorption from hypotonic oral rehydration solution in rat small intestine and colon.

BACKGROUND: The authors evaluated and compared the efficacy of hypotonic oral rehydration solutions (ORS), isotonic ion solutions, and distilled water to elucidate the relation between net water absorption and osmolality, or between electrolyte absorption and their ion concentrations in rat small intestine and colon. METHODS: Water and electrolyte absorption from two hypotonic ORS (Solita-T granules No. 2 [STG2]; sodium 60 mEq/L, osmolality 249 mOsm/L, Solita-T granules No. 3 [STG3]; sodium 35 mEq/L, osmolality 199 mOsm/L), two isotonic ion solutions (Aqualight [AL]; sodium 30 mEq/L, osmolality 290 mOsm/L, Pocarisweat [PS]; sodium 21 mEq/L, osmolality 300 mOsm/L), and distilled water, were evaluated by an in vivo perfusion technique with the small intestine and colon of anesthetized rats. RESULTS: In the small intestine and colon, two hypotonic ORS significantly promoted net water absorption much greater than did two isotonic ion solutions (P < 0.05). Net sodium absorption from two hypotonic ORS was significantly greater than that from two isotonic ion solutions (P < 0.05). Sodium absorption from all solutions was greater in the colon than in the small intestine. Distilled water did not contribute to give net water absorption in the small intestine, but in the colon, it caused almost equivalent net water absorption to that by two hypotonic ORS. The largest amount of sodium secretion from the small intestine and colon was induced by distilled water. CONCLUSIONS: These data indicate that low osmolality is a crucial factor to facilitate water absorption, and the electrolytes, sodium and chloride, can effectively be salvaged in the colon.

Animals↗

Clinical experience in Mexico with a new oral rehydration solution with lower osmolality.

A clinical trial was conducted to compare the safety and efficacy of a new oral rehydration solution (ORS) with that of the ORS recommended by the World Health Organization (WHO). One hundred thirty infants with dehydration due to acute diarrhea were randomized into two groups: 68 infants received the WHO ORS containing sodium and glucose in a concentration of 90 and 111 mmol/L, respectively, and an osmolality of 311 mosm/kg (ORS-90); 62 infants received an ORS containing sodium and glucose in a concentration of 60 and 90 mmol/L, respectively, with an osmolality of 240 mosm/kg (ORS-60). Treatment failure was noted in seven infants (10.3%) in the ORS-90 group; the causes of failure were high stool output (three cases), persistent vomiting (three cases), and ileus (one case). Only one patient in the ORS-60 group (1.6%) was considered a failure because of high stool output. No significant differences were noted in the serum sodium levels in either group of patients, both in relation to the natremia seen on admittance or that seen after rehydration. A trend was observed toward correction of hypernatremia or hyponatremia with both types of ORS. A similar situation was observed with respect to the variations seen in serum potassium levels. The results from this study suggest that there may be clinical advantages of using an ORS with concentrations of sodium and glucose and a total osmolality lower than that of ORS-90, because of the lower incidence of treatment failures.

Diarrhea↗

Studies of water and electrolyte movement for oral rehydration solutions (rice- and glucose-based) across a normal and secreting gut using a dual isotope tracer technique in a rat perfusion model.

AIMS: To establish a model to measure bidirectional flow of water from a glucose oral rehydration to solution (G-ORS) and a newly developed rice-based oral rehydration solution (R-ORS) using a dual isotope tracer technique in a rat perfusion model. To measure net water, sodium and potassium absorption from the ORS. METHOD: In vivo steady-state perfusion studies were carried out in normal and secreting (induced by cholera toxin) rat small intestine (n = 11 in each group). To determine bidirectional flow of water from the ORS the animals were initially with tritium, and deuterium was added to the perfusion solution. Sequential perfusate and blood samples were collected after attainment of steady-state conditions and analysed for water and electrolyte content. RESULTS: There was significant increase in net water absorption from the R-ORS compared to the G-ORS in both the normal (P < 0.02) and secreting intestine (P < 0.05). Water efflux was significantly reduced in the R-ORS group compared to the G-ORS group in both the normal (P < 0.01) and the secreting intestine (P < 0.01). There was an increase in sodium absorption in the R-ORS group compared to the G-ORS. The G-ORS produced a significantly greater blood glucose level at 75 min compared to the R-ORS (P < 0.03) in the secreting intestine. CONCLUSIONS: This study demonstrates the improved water absorption from a rice-based ORS in both the normal and secreting intestine. Evidence that the absorption of water may be influenced by the osmolality of the ORS was also demonstrated.

Absorption↗

Composition and contamination of oral rehydration solutions prepared with well water by village mothers in Burma.

A field study was carried out at Htaukkyant village in Burma to assess whether village mothers could use condensed milk tins to measure one litre of water with reasonable accuracy for the preparation of oral rehydration solutions (ORS) and whether the extent of bacterial contamination of well water was serious and if this affected the bicarbonate content of the ORS solution. Empty condensed milk tins have a fairly uniform volume around 330 ml and using three condensed milk tins full of water mothers made up one litre quite consistently. Mothers also proved capable of preparing ORS solution by dissolving one packet of oral rehydration salt (ORS) in three condensed milk tins full of water to obtain solutions which contained acceptable and safe concentrations of sodium and potassium. Contamination of well water with faecal coliforms was present. Both storing water in domestic vessels and boiling water reduced the coliform count. Storing could be a good way of reducing the risk of infection if repeated contamination from dipping in to the water could be avoided. The counts on coliforms and faecal coliforms in ORS both increased by about 1 log per day over the first and second 24 hours after the preparation with contaminated well water. Despite this the bicarbonate content of ORS remained stable. In the absence of boiled water, ORS solution can be made using the cleanest available water and using it within 24 hours.

Bicarbonates↗

Negative findings for use of coconut water as an oral rehydration solution in childhood diarrhea.

This study reports the chemical composition of coconut water during its maturation. Composition was measured at 5, 6, 7, 8, 9, 10, 11 and 12 months maturation. Concentrations of sodium and glucose, and the osmolality values showed great variation throughout maturation. The concentration of sodium remained constant between the 5th and 7th months (mean 2.9 mEq/l), but increased after the 8th month (mean 12.5 mEq/l). The concentration of glucose remained constant between the 5th and 8th months (mean 3392.4 mg%), but abruptly decreased after the 9th month (mean 820 mg%). Osmolality followed the variation of the glucose concentration averaging 377.3 mOsm/l up to the 8th month, then decreasing to 310.3 mOsm/l after the 9th month. This study showed great variability in coconut water composition during maturation of the fruit. In no instance did the coconut water contain sodium and glucose concentrations of potential value as an oral rehydration solution.

Chlorides↗

Oral rehydration solution containing 90 millimol sodium is safe and useful in treating diarrhoea in severely malnourished children.

The safety and efficacy of standard oral glucose-electrolyte solution, containing 90 mmol of sodium per litre, was evaluated in the treatment of dehydrating diarrhoea among severely malnourished (marasmic) children. A total of 81 male children aged between 6 and 48 months were studied; 41 were in the malnourished group (study group: less than 60% of Harvard Standard weight-for-age) and 40 were in the well-nourished group (control group: 80% or more Harvard Standard weight-for-age). Children of both groups could be rehydrated with standard oral rehydration solution (ORS) without encountering any clinical or biochemical complications. The results of this study lend support to the World Health Organization's concept of a unified formula of ORS for the treatment of all cases of acute diarrhoea, including severely malnourished children.

Child, Preschool↗

Impact of rice based oral rehydration solution on stool output and duration of diarrhoea: meta-analysis of 13 clinical trials.

OBJECTIVE: To define the benefit of rice oral rehydration salts solution in relation to the glucose based World Health Organisation oral rehydration salts solution for treating and preventing dehydration in patients with severe dehydrating diarrhoea. DESIGN: Meta-analysis using data from 13 available randomised trials that compared these two formulations. SUBJECTS: The studies compared 1367 patients with cholera, severe cholera-like diarrhoea, or acute non-cholera diarrhoea. 668 received the standard WHO solution and 699 the rice based solution. INTERVENTION: Each trial report was reviewed to determine patient eligibility, the number of patients who were randomised and the number of these excluded from analysis, details of the randomisation procedure, and the precise timing of the outcome measurements. MAIN OUTCOME MEASURES: Stool output during the first 24 hours; weighted estimates of the difference in mean stool output between treatments. RESULTS: The rice solution significantly reduced the rate of stool output during the first 24 hours by 36% (95% confidence interval 28 to 44%) in adults with cholera and by 32% (19 to 45%) in children with cholera. The rate of stool loss in infants and children with acute non-cholera diarrhoea was reduced by only 18% (6 to 30%). CONCLUSIONS: The benefit of rice oral rehydration salts solution for patients with cholera is sufficiently great to warrant its use in such patients. The benefit is considerably smaller for children with acute, noncholera diarrhoea and should be more precisely defined before its practical value can be judged.

Bicarbonates↗

Controlled clinical trial on the efficacy of rice powder-based oral rehydration solution on the outcome of acute diarrhea in infants.

We report a controlled clinical trial of rice powder-based oral rehydration solution (ORS) versus glucose ORS on the outcome of acute diarrhea in infants. The rice ORS group (n = 30) received ORS containing 50 g rice powder instead of standard WHO solution (20 g glucose, n = 30). Formula-fed male infants were enrolled to enable calculation of milk intake and excretion of urine. Patient allocation to either group depended on the method of random permuted blocks. Both groups were comparable regarding age (4-18 months), duration of diarrhea, number of bowel movements or vomiting per 24 h, rectal temperature, dehydration score, and nutritional status. Results revealed that the rice ORS group had a shorter duration of diarrhea (28.4 +/- 5.1 vs 34.3 +/- 2.3 h) and greater mean weight gain in the first 24 h as percentage of recovery weight (5.7 +/- 0.5% vs 4.1 +/- 0.6%). Furthermore, the mean amount of ORS intake, mean stool output, and mean number of episodes of vomiting were lower in the rice-ORS group as compared with the glucose ORS group. All differences were statistically significant. Due to its observed superiority and low cost, the widespread use of rice ORS should be considered for treatment of acute diarrhea.

Clinical Trials as Topic↗

Oral rehydration solution safely used in breast-fed children without additional water.

Sixty-four children of age 3 months to 2 years were treated for diarrhoea in a rural treatment centre with oral rehydration solution (90 mmol/l Na+); plain water was not supplied during rehydration. All children continued breast-feeding during the therapy. Serum sodium levels after 24 h of intake indicated that 61 children had serum sodium level below 148 mmol/l and three were above (range 150-151). None of the children developed clinical signs or symptoms of hypernatremia. The use of additional water may not be necessary during rehydration therapy of breast-fed children.

Breast Feeding↗

Effects of administration of water versus an isotonic oral rehydration solution (ORS) at rest and changes during exercise and recovery.

The administration of 41 of an isotonic, plasma-like oral rehydration solution (ORS) with an osmotic skeleton and 41 of water (water; no osmotic skeleton), were evaluated in five thoroughbred horses. Solutions were administered by nasogastric tube 4 h after feeding. Uptake of deuterium, concentrations of plasma sodium, potassium, chloride, glucose, total protein and packed cell volume, pH, PCO2, HCO3-, total CO2, actual base excess, standard base excess, plasma volume and weight loss were assessed both at rest, and during and after exercise on a treadmill. Each horse underwent four experimental sessions (water-resting; ORS-resting; water-exercise; ORS-exercise). There was an indication of uptake of both water and ORS by 10 min post-administration. Based on the appearance of deuterium in plasma, there was no significant difference in the rate of uptake of water or ORS at rest, although there was a trend for the uptake of ORS to be slower than water during the exercise session. The mean decrease in total protein (TP, 3.0 g l-1) and the increase in plasma volume (PV, 4.6 ml kg-1) after administration of ORS at rest was greater (P < 0.05) than that of water (TP, 1.3 g l-1 and PV, -1.2 ml kg-1). There was no significant difference in TP or PV following administration of water or ORS during the exercise treatment. Exercise had little effect on plasma sodium concentration. The results confirmed that administration of 41 of isotonic, plasma-like ORS provided a much more distinct and durable contribution to the maintenance of plasma volume and circulation than administration of an equal amount of water at rest. Subsequent exercise may, however, mask some of the effects observed at rest.

Acid-Base Equilibrium↗

Comparison of two oral rehydration solutions in eutrophic infants with moderate acute diarrhea: results of an interim analysis.

A randomized, multicenter clinical trial comparing two oral rehydration solutions (ORS) with different sugar content and total osmolality was carried out in France. Solution A had 168 mmol/L of sugar and a total osmolarity of 326 mosm/kg; solution D had 90 mmol/L of sugar and a total osmolarity of 240 mosm/kg. Weight gain, stool output, and biologic variables were analyzed. This interim analysis included 49 infants (27 in group A and 22 in group D). Patients in both groups gained weight without any significant difference between the two ORS. Between admission and day 4, the overall number of stools and the number of liquid stools decreased. Laboratory values were within the normal range on admission and remained unchanged. The weight increase during the first 24 hours and the reduced frequency of stools was similar in both groups.

Acute Disease↗

Comparison of two oral rehydration solutions in children with gastroenteritis in Australia.

An open-label inpatient study is in progress to compare the efficacy and safety of two oral rehydration solutions in children and infants with acute diarrhea and mild to moderate dehydration. One solution (ORS-60) contains 60 mmol/L of sodium and 1.8% glucose, with a total osmolality of 240 mosm/kg; the other (ORS-26) contains 26 mmol/L of sodium, 2.7% glucose, and 3.6% sucrose, with a total osmolality of 340 mosm/kg. An outcome analysis of 28 children with gastroenteritis indicated that ORS-60 (n = 13) reduced stool volume during the first eight hours after admission to a significantly greater (P less than 0.05) extent than did ORS-26 (n = 15). Diarrhea had ceased by 24 hours in 64% of ORS-60 patients but in only 31% of ORS-26 patients, and the patients' clinical condition was improved at eight hours in 84% of ORS-60 patients versus 60% of ORS-26 patients. Differences between treatments in degree of dehydration at each follow-up point, total duration of diarrhea, and duration of hospital stay were not detected. No adverse drug reactions occurred. Four patients received intravenous rehydration therapy, but none was considered a treatment failure. We conclude that the lower osmolar solution, ORS-60, conferred earlier recovery and reduced continuing fluid losses in the management of gastroenteritis.

Australia↗

Efficacy of mung bean (lentil) and pop rice based rehydration solutions in comparison with the standard glucose electrolyte solution.

Children with acute diarrhea and moderate dehydration between 3 months and 5 years of age were randomly assigned to receive treatment with standard WHO oral rehydration solution (ORS) (n = 33) and two other solutions in which the 20 g/L glucose was substituted by 50 g/L of pop rice (n = 31) and 60 g/L of mung bean (lentil) powder (n = 29). Satisfactory oral rehydration, as assessed clinically and by changes in PCV and total serum solids (TSS), was achieved in 90.9% with WHO ORS, 96.8% with pop rice, and 96.6% in the mung bean ORS treated group (p greater than 0.05). The purging rates (ml/kg/h) until recovery were 2.49 +/- 1.5 (pop rice); 2.91 +/- 2.0 (WHO), and 3.41 +/- 1.7 in the mung bean group (p greater than 0.05). The percentage of patients recovering from diarrhea within the 72 h study period was 58.0 (pop rice), 48.4 (WHO), and 44.8 for mung bean group (p greater than 0.05). Though differences in stool volumes and duration in the three groups were not statistically different, there was a trend toward improvement in efficacy with the pop rice ORS in several parameters: greater weight gain, higher percentage decline in TSS, higher urine output despite lower ORS intake, and lower purging rates. The intake of semisolids in the 24-72 h study period was also higher in the pop rice group as compared to the other two groups (p less than 0.05). The number of breast feeds and intake of artificial milk was however similar in all groups (p greater than 0.05).

Breast Feeding↗

Improving the palatability of oral rehydration solutions has implications for salt and water transport: a study in animal models.

It is believed that improving the taste of oral rehydration solutions (ORSs) might lead to greater patient acceptability. A pilot trial showed that replacing glucose with sucrose and increasing the citrate concentration at the expense of chloride improves palatability. However, the transport implications of such modifications are not known. Three hypotonic experimental ORSs (Suc/cit-ORS, 211 mosmol/kg; Suc/Cl-ORS, 224 mosmol/kg; and Glu-ORS, 224 mosmol/kg) were compared with a standard European ORS (Euro-ORS, 265 mosmol/kg) by in vivo perfusion of entire rat small intestine in normal adult rats and rotavirus-infected neonates. All ORSs were of identical sodium, potassium, chloride, and citrate content except that in the Suc/cit-ORS, chloride was removed in favor of increased citrate, and the chloride concentration in Euro-ORS was higher than in the others. Suc/cit-ORS and Suc/Cl-ORS had glucose partially replaced by sucrose while Glu-ORS and Euro-ORS contained only glucose. In normal small intestine, water absorption was greater from Glu-ORS than Suc/cit-ORS or Euro-ORS, although water absorption was similar from Suc/cit-ORS and Suc/Cl-ORS. In the rotavirus model, Glu-ORS produced more water absorption than Euro-ORS or either sucrose ORS. In both models, Suc/cit-ORS caused sodium and chloride secretion. Glucose absorption was similar from all ORSs. These findings indicate that attempts to improve ORS palatability by adding sucrose or increasing citrate at the expense of chloride would incur a significant penalty in terms of salt and water absorption.

Animals↗

Practices of preparation of oral rehydration solution among mothers reporting to the drug distribution centres in Delhi, India, 1992.

A study to assess the ability for preparing oral rehydration solution (ORS) correctly among the recipients of ORS packets from the Government of India service outlets was carried out in Delhi during July to August, 1992. One centre from each of the municipal zones of Delhi was selected randomly. Four hundred mothers with a child having diarrhoea reporting to the nearest centre were studied using a standardized questionnaire adopted from the WHO household survey schedule. Two paramedical personnel from each of the centres who were responsible for distribution of ORS were also interviewed regarding their knowledge of preparation of ORS. Results indicate that only 10.8% of mothers prepared the ORS correctly and that the majority (83%) of the paramedicals involved in ORS distribution had correct knowledge about its preparation. Communication methods directed at the mothers regarding the preparation of ORS should be stepped up in these communities.

Child, Preschool↗