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A comparative study of glycine fortified oral rehydration solution with standard WHO oral rehydration solution.

The safety, efficacy and acceptability of glycine-fortified oral rehydration solution (ORS) was compared with that of standard WHO-ORS in a controlled randomized trial. Fifty male infants with acute, watery, non-cholera diarrhea were studied. Glycine-fortified ORS at a concentration of 111 mmol/L (8.4 g/L) was used. The electrolyte and glucose concentrations of both the solutions was identical. The proportion of successfully treated patients was 92%. There were two failures in each group. Both solutions were found to be equally safe in correcting and maintaining the hydration status and in correcting hyponatremia and hypokalemia. The acceptability and efficiency of the solutions were also comparable. Addition of glycine does not add to the efficacy of conventional WHO-ORS, therefore offering no additional advantage but adds to the cost of production.

Administration, Oral

Water and solute absorption from a new hypotonic oral rehydration solution: evaluation in human and animal perfusion models.

Controversy continues regarding the optimal composition of glucose electrolyte oral rehydration solutions for the treatment of acute diarrhoea. Four perfusion models (normal human jejunum, normal rat small intestine, cholera toxin treated secreting rat small intestine and rotavirus infected rat small intestine) have been developed and used to compare the efficacy of a hypotonic oral rehydration solution with standard United Kingdom British National formulary and developing world oral rehydration solutions (WHO). Despite obvious physiological and pathophysiological differences between these models there was general congruence in the water and solute absorption profiles of the different oral rehydration solutions. Hypotonic oral rehydration solution promoted significantly greater water absorption than other oral rehydration solutions in all rat models (p < 0.001) but apparently increased water absorption failed to achieve significance in human jejunum. British National Formulary-oral rehydration solution was unable to reverse net water secretion in both rotavirus and cholera toxin models. Net sodium absorption from hypotonic and WHO-oral rehydration solutions was significantly greater than from the low sodium British National Formulary-oral rehydration solutions (p < 0.001) except in the rotavirus model when absorption was similar to hypotonic-oral rehydration solutions. These findings show that there is agreement in the apparent efficacy of oral rehydration solutions in these animal and human perfusion models, and that improved water absorption with adequate sodium absorption may be achieved by reducing oral rehydration solution osmolality.

Adolescent

[Importance of oral rehydration in acute infantile diarrhea. Comparison of 2 rehydration solutions].

Oral rehydration therapy has gained worldwide acceptance as the standard treatment for acute diarrhoeal diseases in infants and children. Besides the high sodium glucose-electrolyte solution based on the WHO/UNICEF recommendations, many diverse formulations of oral rehydration solutions (ORS) have withstood the trial of prolonged clinical use, their main differences concerning the concentration of sodium, the choice of the glycidic component, the use of bicarbonate as buffer or its substitution with acetate or citrate. It was recently hypothesized that glucose polymers-containing ORS markedly improve the intestinal sodium/glucose cotransport by delivering glucose at its critical site on the luminal villous membrane and therefore diminish stool output and duration of the diarrhoea. To investigate this hypothesis, the efficacies of two marketed ORS (table I), one containing sucrose and maltodextrin (solution A) and the other containing glucose (solution B) were compared. The study group comprised 13 infants and toddlers, 1 to 18 months old, who presented with acute diarrhea; 5 were males and 8 females; 7 were randomly allocated to receive solution A (Group A), 6 solution B (Group B). There were no significant differences between the groups in age, sex, causation of diarrhea or severity of dehydration before receiving ORS. Both groups showed a satisfactory response to 24 hours of treatment with either ORS, but a significantly lower stool output (number and global weight of stools) and higher blood glucose and bicarbonate levels were detected in group A (table II).(ABSTRACT TRUNCATED AT 250 WORDS)

Diarrhea, Infantile

Comparison of rat and human intestinal perfusion models for assessing efficacy of oral rehydration solutions.

The optimal composition for oral rehydration solutions remains controversial. Animal models have been used to assess the efficacy of new formulations but the relevance of these studies to the handling of oral rehydration solutions in human intestine during diarrhoeal disease states remains uncertain. Using steady state perfusion techniques we have compared water and solute transport from a variety of oral rehydration solutions in both the entire rat small intestine and in the human jejunum. Overall the pattern of water, sodium and glucose absorption was similar from the three oral rehydration solutions tested, indicating close parallelism between the two models despite the species and methodological differences. Although the relationship between the findings of these studies to the handling of oral rehydration solution in diarrhoeal disease states remains uncertain, we believe they do support the view that animal models may have a part to play in the preliminary screening of oral rehydration solutions before clinical trial.

Adult

Efficacy of oral rehydration solutions in a rat model of secretory diarrhea.

Controversy continues regarding the ideal composition of glucose/electrolyte solutions used for oral rehydration of infants and children with acute diarrhea. We have used cholera toxin-treated rat small intestine as a model of secretory diarrhea to assess the efficacy of oral rehydration solutions by intestinal perfusion. All solutions tested reversed net water secretion but a hypotonic bicarbonate-free solution was more effective than other solutions, including the World Health Organization oral rehydration solution (p less than 0.003). Net sodium secretion persisted with all solutions tested but there was a significant linear relationship between sodium concentration of the solution perfused and net sodium transport (r = 0.75, p less than 0.05). Cholera toxin treatment alone and in combination with perfusion of oral rehydration solutions significantly reduced plasma sodium concentration and osmolality (p less than 0.05), the effects being most marked with low sodium solutions. Although direct parallelism between observations in this animal model of secretory diarrhea and human diarrheal disease has not been established as yet, the model may be useful in assessing clinical efficacy of new oral rehydration solutions and in systematic analysis of the relative benefits of their individual components.

Animals

Oral rehydration of neonates and young infants with dehydrating diarrhea: comparison of low and standard sodium content in oral rehydration solutions.

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.

Body Weight

Oral rehydration solution without bicarbonate.

The efficacy of oral rehydration solution without bicarbonate was compared with World Health Organisation oral rehydration solution in 98 young children in a double blind and randomised clinical trial. These children had varying degrees of dehydration and acidosis caused by acute watery diarrhoea. The mean serum bicarbonate concentration on admission was 13.3 mmol(mEq)/1 in the former and 13.1 mmol(mEq)/1 in the latter group of children. All but three children who received the rehydration solution without bicarbonate were successfully treated; three treatment failures were attributed to persistent vomiting and severe diarrhoea (greater than 10 ml/kg/hour). Correction of acidosis was slower in the non-bicarbonate treated than the control group during the first 24 hours' treatment (P less than 0.001). By 48 hours, however, acidosis was corrected and mean serum bicarbonate had risen to 17.1 mmol(mEq)/1 compared with 18.9 mmol(mEq)/1 in the control group (P greater than 0.05). Some failures due to sustained acidosis and persistent vomiting and diarrhoea should be expected. Oral rehydration solution without bicarbonate may be used where complete formula solution is not available.

Acidosis

Evaluation of the effects of varying solute content on the efficacy of oral rehydration solutions in a rat model of secretory diarrhoea.

A series of in vivo steady-state perfusion studies in cholera toxin-induced secreting rat intestine were carried out to investigate net water, sodium, and potassium absorption and water influx and efflux from a range of oral rehydration solutions (ORSs) in which the glucose content had been partially replaced by amino acids or food supplements and the sodium content had been reduced to 60 mM. The reference solution used was the World Health Organization formula. There was a significant correlation between the osmolality of the ORS and the net water absorption (r = -0.911; p < 0.02). The greatest net water absorption occurred using comminuted chicken- and tapioca-supplemented ORS.

Absorption

Assessment of water and solute absorption from experimental hypotonic and established oral rehydration solutions in secreting rat intestine.

Water and solute absorption from three experimental hypotonic oral rehydration solutions (HYPO-ORS; sodium 45, 60 and 75 mmol/L, glucose 90 mmol/L), the World Health Organization recommended ORS (WHO-ORS; sodium 90 mmol/L, glucose 111 mmol/L), and the British National Formulary recommended ORS (BNF-ORS; sodium 35 mmol/L, glucose 200 mmol/L), have been assessed by perfusion studies in cholera toxin-induced secreting rat intestine. Net water absorption was greatest from the most hypotonic solution (HYPO-45; P less than 0.05). UK-ORS prevented net water secretion and WHO-ORS promoted moderate net water absorption. Net sodium secretion was seen with all solutions but was least from WHO-ORS and greatest with BNF-ORS (P less than 0.01). Glucose absorption was similar from BNF-ORS, WHO-ORS and HYPO-45 and in each case was greater than glucose absorption from HYPO-60 and HYPO-75 (P less than 0.05). These results suggest that net water and sodium absorption from ORS may be enhanced if osmolality is reduced by decreasing the glucose content.

Animals

In search of a super solution: controlled trial of glycine-glucose oral rehydration solution in infantile diarrhoea.

In a double blind trial a glycine fortified oral glucose electrolyte solution was evaluated in a group of infants and small children (n=25) with moderate to severe dehydration due to acute diarrhoea, and was compared with a matched control group (n=26) receiving only glucose based oral rehydration solution. It is seen that the diarrhoea stool output, duration of diarrhoea, and volume of oral rehydration fluid required to achieve and maintain hydration are significantly lower in the group receiving glycine fortified glucose electrolyte solution. The possibility of developing an oral rehydration solution which could also act as an absorption promoting drug is discussed.

Administration, Oral

Improved water and sodium absorption from oral rehydration solutions based on rice syrup in a rat model of osmotic diarrhea.

Rice syrup solids, rice protein, and casein hydrolysate were added to experimental oral rehydration solutions in various combinations and tested in a rat intestinal perfusion system. Chronic osmotic diarrhea was induced in juvenile rats by supplying the cathartic agents, magnesium citrate and phenolphthalein, in their drinking water for 1 week. The experimental oral rehydration solutions were compared with standard oral rehydration solutions containing 20 gm/L or 30 gm/L of glucose and with each other to determine if there were significant differences in net water, sodium, or potassium absorption. An oral rehydration solution containing 30 gm/L of rice syrup solids had a net water absorption rate significantly higher than that of the standard 20 gm/L glucose-based oral rehydration solution (2.1 +/- 0.62 versus 1.5 +/- 0.48 microliters/[min x cm], p less than 0.05). Casein hydrolysate did not significantly affect net water absorption. However, combinations of 30 gm/L rice syrup solids and 5 gm/L casein hydrolysate significantly increased (p less than 0.05) net sodium and potassium absorption compared with the 20 gm/L glucose-based oral rehydration solution but not versus rice syrup solids alone. Oral rehydration solutions containing 30 gm/L rice syrup solids plus 5 gm/L rice protein, and 30 gm/L rice syrup solids plus 5 gm/L casein hydrolysate, had net water absorption rates significantly higher than the rate of a 30 gm/L glucose-based oral rehydration solution (2.5 +/- 0.36 and 2.4 +/- 0.38, respectively, versus 0.87 +/- 0.40 microliters/[min x cm], p less than 0.05). Rice protein and casein hydrolysate, however, did not significantly affect net water, sodium, or potassium absorption when added to rice protein glucose-based oral rehydration solutions. An inverse correlation between osmolality and net water absorption was observed (r = -0.653, p less than 0.02). The data suggest that substitution of rice syrup solids for glucose in oral rehydration solutions will improve water absorption and that rice syrup solids in combination with protein hydrolysates may, in addition, promote better sodium and potassium uptake.

Administration, Oral

Experimental models for the investigation of water and solute transport in man. Implications for oral rehydration solutions.

For patients suffering from mild to moderate dehydration, oral rehydration therapy has proved a simple and efficacious treatment. There remains, however, a need to develop improved oral rehydration solutions (ORS), and suitable experimental models are required to develop and assess new formulations. The ideal model for such investigations would take into account rates of gastric emptying, influx and efflux of water and solutes in the intestine, and the consequent changes in body composition. As no such definitive model is currently available, a variety of techniques are used to examine parts of the process of intestinal absorption. Clinical studies which assess the recovery of dehydrated patients during therapy using different ORS will ultimately evaluate the efficacy of treatment. However, ethical considerations, the relative insensitivity of this technique and the exacting nature of such studies make this approach unsuitable for the development of specific ORS. Gastric emptying of solutions can be determined by a variety of techniques, among which the radioactive tracer method offers the advantage of having no direct effect on the emptying rate, giving almost continuous measurement and allowing the use of relatively small volumes of fluids. Perfusion techniques allow measurement of the net flux of water and solute in predetermined sections of the intact human intestine. Measurement of the rate of accumulation in the circulation of orally ingested tracer molecules for water and solutes can estimate unidirectional flux. This method allows for the rates of gastric emptying and intestinal absorption of the test substance, but the rate of efflux of the tracer from the vascular space must be known to calculate net uptake. Each of these models has limitations, and care must be taken in interpreting the results in a clinical context. However, their use in the development of improved formulations is well established.

Fluid Therapy

Management of acute diarrhoea in diabetic patients using oral rehydration solutions containing glucose, rice, or glycine.

OBJECTIVE: To assess the risk of hyperglycaemia with two standard oral rehydration solutions that contain carbohydrate compared with a carbohydrate free solution during rehydration of diabetic patients with acute diarrhoea. DESIGN: Prospective randomised allocation to one of three oral rehydration solutions (World Health Organisation (glucose), rice, or glycine) groups after admission to hospital with acute diarrhoea. SETTING: Dhaka hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh. SUBJECTS: 45 diabetic patients aged between 15 and 60 who had had diarrhoea for fewer than three days on admission. MAIN OUTCOME MEASURES: Fluctuation of blood glucose concentrations measured three times a day, daily stool output, and time taken for recovery from diarrhoea. RESULTS: There were no significant differences in blood glucose concentrations, stool output, and duration of recovery from diarrhoea among the three groups. CONCLUSIONS: Oral rehydration solutions containing glucose, rice powder, or glycine can be safely administered to diabetic patients with acute diarrhoea and some dehydration.

Acute Disease

Quality of home use of oral rehydration solutions: results from seven HEALTHCOM sites.

This study examined the volume of oral rehydration solutions given to children during diarrhea and the length of time the solutions are administered. It also attempted to test the importance of individual and contextual factors--especially mothers' knowledge--in explaining the administration of oral rehydration solutions. Data about the treatment of an episode of child diarrhea within the last three months were collected from large samples of mothers in seven sites in Africa, Asia, and Latin America. The results showed that oral rehydration solutions were given in smaller volumes and for shorter periods of time than recommended. The majority of children received at least a glass (200-250 ml) of solution on the first day, but few received more than that. Daily administration of packet-based solutions or of sugar-salt solutions (promoted in two of the countries) during diarrhea was generally quite low, ranging from 16 to 60% of cases given an oral rehydration solution. However, in four out of six sites, at least half of the children with diarrhea for more than one day were given an oral rehydration solution for more than one day. The majority of children were given some form of other fluids (e.g. more water, special teas, or continued breastfeeding), but their value in preventing dehydration was not clear because the volume of other fluids given could not be assessed. Few of the hypothesized predictors of administration explained the variation in volume or duration of ORS/SSS administration within any specific country or across sites. The research points to the need for more information on the decision process used by mothers when treating their children's diarrhea and on outside factors influencing this process.

Adult

[Ultrasonic study of gastric emptying of various oral rehydration solutions].

Gastric emptying of 4 different oral rehydration solutions was investigated by ultrasound in 7 healthy volunteers in a randomized double-blind study. The final gastric emptying times were 32.9 +/- 4.72 minutes for the glycine solution, 55.1 +/- 9.85 minutes for the glucose (WHO) solution. 60.8 +/- 11.58 minutes for the polycose solution and 58.6 +/- 10.12 minutes for the rice-flour solution (p less than 0.05). Gastric emptying times showed considerable person-to-person variability. Based on identical gallbladder volumes before and 60 minutes after ingestion of the rehydration solutions, there was no indication of cholecystokinin stimulation by any of the solutions tested.

Adult

[Oral rice-based rehydration solution (SRO), alternative of SRO of WHO in acute diarrhea in malnourished patients].

BACKGROUND: Although malnutrition is frequently associated with diarrhea, most oral rehydration solutions have been tested in well-nourished children. The study tests efficacy of rice, a traditional treatment for diarrhea in Madagascar. PATIENTS AND METHODS: 150 severely malnourished children, aged 6 months to 3 years, took part in this randomized trial. All the children were given oral rehydration solution, (100 ml/kg) in the first 6 hours. The first group (68 children) was given a solution containing glucose, (20 g/l). The second group (82 children) was given a solution containing rice powder (50 g/l). Treatment was then continued according to WHO recommendations, including feeding after rehydration (mixture of milk, oil and sugar). RESULTS: The age, weight, height, duration of diarrhea before admission, degree of dehydration and pathogens in stools of the two groups were comparable on admission. Only 2 patients were withdrawn from the trial. The percentage of death was the same in both groups: 16% of those given glucose and 15% of those given rice-based rehydration solution. The weight gains were similar in both groups; the duration of diarrhea was 89 +/- 6 hours in the glucose-fed groups and 68 +/- 4 hours for those given the rice-based rehydration solution (p < 0.02). CONCLUSIONS: Both glucose and rice-based rehydration solutions are equally effective for rehydrating severely malnourished children with acute diarrhea. The rice-based rehydration solution also reduces the duration of diarrhea.

Acute Disease

Studies of water movement across the gut using oral rehydration solutions in a rat perfusion model.

AIM: To measure water influx and efflux, as well as net water, sodium and potassium absorption from a range of oral rehydration solutions (ORS) in which the glucose content had been partially replaced with the amino acid leucine or with food supplements. METHODS: A series of in vivo steady-state perfusion studies in normal rat intestine. The oral rehydration solutions contained 60 or 90 mmol/L of sodium. The reference solution used was the World Health Organization (WHO) formula. RESULTS: There was a significant negative correlation between the oral rehydration solution osmolality and net water absorption (r = -0.722, P < 0.05). The highest net water absorption occurred using comminuted chicken supplemented oral rehydration solution containing 60 mmol/L sodium (P < 0.001). This oral rehydration solution also showed a significant increase in the rate of influx of water (P < 0.05) in comparison with the WHO formula containing 60 mmol/L sodium. CONCLUSION: This work provides further evidence that food-based oral rehydration solutions, including non-vegetable sources, may have a useful role to play in the management of patients with acute diarrhoea.

Amino Acids