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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

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

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

[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

Cereal based oral rehydration solutions.

A total of 257 boys (age range 4-55 months), who had acute diarrhoea with moderate to severe dehydration, were randomly assigned to treatment with either the World Health Organisation/United Nations Childrens Fund (WHO/Unicef) recommended oral rehydration solution or cereal based oral rehydration solution made either of maize, millet, sorghum, or rice. After the initial rehydration was achieved patients were offered traditional weaning foods. Treatment with oral rehydration solution continued until diarrhoea stopped. Accurate intake and output was maintained throughout the study period. Efficacy of the treatment was compared between the different treatment groups in terms of intake of the solution, stool output, duration of diarrhoea after admission, and weight gain after 24, 48, and 72 hours, and after resolution of diarrhoea. Results suggest that all the cereal based solutions were as effective as glucose based standard oral rehydration solution in the treatment of diarrhoea.

Dehydration

Evaluation of the efficacy of oral rehydration solutions using human whole gut perfusion.

Whole gut perfusion in humans was used to compare the effect on intestinal water and electrolyte transport of the World Health Organisation oral rehydration solution (solution II, composition in mmol/l: glucose 111, sodium 90, bicarbonate 30, potassium 20; 308 mOsm/kg); a hypertonic commercial oral rehydration solution (solution III, glucose 188, sodium 50, bicarbonate 20, potassium 20 mmol/l; 335 mOsm/kg); and three experimental bicarbonate free, hypotonic oral rehydration solutions: solution IV (glucose 111, sodium 60, potassium 20 mmol/l; 260 mOsm/kg), solution V (glucose 80, sodium 60, potassium 20 mmol/l; 219 mOsm/kg), and solution VI (glucose 80, sodium 30, potassium 20 mmol/l; 177 mOsm/kg). Perfusion of the intestine with a standard cleansing solution (solution I, sodium 125, potassium 10, bicarbonate 20, sulphate 40, mannitol 80 mmol/l; 275 mOsm/kg) confirmed published data on minimal water and sodium absorption. Experimental solution VI produced maximum water absorption (mean (SE) +1660.0 (29.8) ml/h) significantly greater than solution II (+1195.3 (79.5) ml/h), III (+534.7 (140.3) ml/h), IV (+1498.0 (42.7) ml/h), and V (+1327.7 (24.4) ml/h; p less than 0.05). Sodium absorption was significantly greater with solution II (+97.4 (7.9) mmol/h) compared to VI (+43.3 (7.8) mmol/h; p less than 0.01) but not compared to IV (+67.2 (13.0) mmol/h). A hypotonic oral rehydration solution such as solution VI may provide optimal replacement treatment for patients with acute diarrhoea.

Adult

Evaluation of malto-dextrin/glycine oral rehydration solution.

The efficacy and safety of malto-dextrin/glycine-based oral rehydration solution (ORS) when compared with the glucose-based oral rehydration solution (WHO) was evaluated in a randomized double-blind clinical trial. Thirty-one subjects and 31 controls were studied. The mean values of the ORS intake, stool output, duration of diarrhoea, urine output, weight gain and serum electrolytes were comparable in both the study and the control groups (p > 0.05). It was found that the malto-dextrin/glycine ORS offered no therapeutic advantage over the standard glucose ORS (WHO). In view of the accidental preponderance of children of significantly lower nutritional status among the control group (p < 0.05), it is likely that the efficacy of malto-dextrin/glycine ORS might actually be less than that of the glucose ORS.

Diarrhea, Infantile

[Treatment of acute diarrhea in infants and young children with a new formulated oral rehydration solution].

49 infants and children with acute diarrhea with mild to moderate dehydration have been rehydrated orally with a newly composed oral rehydration solution. This solution differs from the traditional WHO recommended rehydration solution in a lower sodium content of 60 mval/l and replacement of bicarbonate 25 mval/l by an equimolar amount of citrate. The taste of the solution was improved by addition of flavour. All infants and children - including 8 infants less than 3 months of age - were successfully rehydrated. The solution was well accepted; no side effects have been observed. The sodium content remained normal in all patients.

Bicarbonates

Efficacy of a standard United Kingdom oral rehydration solution (ORS) and a hypotonic ORS assessed by human intestinal perfusion.

Human triple-lumen intestinal perfusion was used to compare water and solute absorption from the oral rehydration solution (ORS) most widely used in the United Kingdom and a new experimental hypotonic ORS (HYPO-ORS). HYPO-ORS (osmolality 210 mOsm/kg) promoted significantly greater water absorption than UK-ORS (7.03 +/- 1.1 vs 2.73 +/- 1.0 ml cm-1 h-1; P less than 0.01). HYPO-ORS produced net sodium and chloride absorption whereas the low sodium UK-ORS produced a net secretion of these ions. Bicarbonate absorption was also greater from HYPO-ORS although potassium and glucose absorption were similar from both solutions. This study suggests that UK-ORS may not promote optimal water and solute absorption and that clinical studies with HYPO-ORS are indicated.

Adult

Use and safety of home-made oral rehydration solutions: an epidemiological evaluation from Bangladesh.

Home-made oral rehydration solutions (ORS) have been promoted in developing countries for preventing dehydration due to diarrhoea. Evaluations of this method must take into account the effective usage rates achieved and the safety of the solutions used. A community programme organized by the Bangladesh Rural Advancement Committee (BRAC) has visited over a third of all the households in Bangladesh and taught the preparation and use of an oral rehydration solution made from lobon (common salt) and gur (unrefined sugar)--abbreviated to LGS. An evaluation study based on over 7000 households enabled different usage rates to be calculated for four different diarrhoea types. The overall usage of LGS for all diarrhoea episodes was around 5-10% but for what the people called 'Severe Diarrhoeas' or cholera it was found to be between 25% and 52%. The mother's ability to prepare a safe Lobon-gur solution appeared to deteriorate about six months after training and it was significantly poorer in the Second Phase than the First Phase of the BRAC programme.

Adolescent

The role of human perfusion techniques in the assessment of oral rehydration solutions.

Early human intestinal perfusion studies provided valuable information on gut transport procession in vivo. Subsequently, similar models have proved a useful means of assessing the efficacy of glucose-electrolyte oral rehydration solutions. In contrast to clinical trials they enable quantification of water and solute movement across the small intestine and, unlike animal studies, results are directly applicable to man. However, limitations exist, including the fact that a short, usually normal, segment of intestine is studied. Recent studies confirm the relationship between oral rehydration solution sodium concentration and sodium movement; the stimulatory effect of glucose on sodium and water movement; and the detrimental effect of high glucose content. Glycine, bicarbonate, citrate and acetate provide little additional benefit for water absorption when added to solutions containing glucose. Preliminary comparative studies of results obtained in the rat and in man show parallels between these models suggesting they may be complimentary methods of assessing new oral rehydration solutions.

Humans

A comparison of rice-based oral rehydration solution and "early feeding" for the treatment of acute diarrhea in infants.

To compare the use of rice-based oral rehydration solution (R-ORS), with the introduction of food immediately after rehydration ("early feeding"), using standard glucose-based oral rehydration solution (G-ORS) in the management of acute diarrhea, we conducted a four-cell randomized, controlled trial among 200 hospitalized Egyptian infants between 3 and 18 months of age. During the rehydration phase (first 4 hours), three groups were given G-ORS and a fourth group was given R-ORS. During the subsequent maintenance phase, the control group was given a soy-based, lactose-free formula (G-ORS + SF), a second group (G-ORS + RF) was given a rice-based formula, and a third group (G-ORS + rice) was given boiled rice. The fourth group (R-ORS + SF) continued to receive R-ORS for the first 24 hours of the maintenance period, followed by a soy-based lactose-free formula. During the first and second 24 hours of the maintenance period, infants in the three treatment groups had a lower mean stool output in comparison with the control group (p = 0.006 and 0.03, respectively). The mean total stool output in the R-ORS + SF group was significantly lower than in the control group (p = 0.02). There were no statistically significant differences among the four groups in the mean duration of diarrhea. We conclude that (1) infants who were given R-ORS had reduced total stool output (by 35%) compared with the control group and (2) feeding of boiled rice or a rice-based formula immediately after rehydration therapy was as efficacious as treatment with R-ORS alone for 24 hours, followed by feeding with a soy-based, lactose-free formula.

Acute Disease