Hypotonic Oral Rehydration Solution Research Articles

Water, mineral, and blood acid-base balance in calves with naturally occurring diarrhea receiving two alternative oral rehydration solutions or a placebo

Quantifying the water and mineral losses in feces is essential to determine the optimal composition of oral rehydration solutions (ORS) for diarrheic animals. In a randomized complete block design, this study evaluated water, mineral, and blood acid-base balance of calves with naturally occurring diarrhea receiving ORS or a placebo. On d 0, 45 calves (age: 18 ± 3.2 d; mean ± SD) were selected based on the presence of visual signs of diarrhea, such as dirty tail or wet feces, along with clinical symptoms evaluated by measuring the skin turgor and the degree of enophthalmos. On d 1, calves were divided into blocks of 3 animals based on blood base excess (BE) measured at 0900 h, and within each block, calves were randomly assigned to 1 of 3 treatments (15 calves per treatment) including (1) a hypertonic ORS (HYPER; Na+ = 110 mmol/L; 370 mOsm/kg; strong ion difference [SID] = 60 mEq/L), (2) a hypotonic ORS with low Na+ (HYPO; Na+ = 77 mmol/L; 278 mOsm/kg; SID = 71 mEq/L), and (3) a placebo consisting of lukewarm water with 5 g/L of whey powder (CON). Milk replacer (MR) was fed through teat buckets twice daily at 0630 h and 1700 h in 2 equally sized meals of 2.5 L from d 1 to 3 and of 3.0 L on d 4 and 5. Treatments consisting of 2.0 L lukewarm solutions were administered between milk meals from d 1 to 3 at 1200 h and 2030 h through teat buckets. Refusals of MR and treatments were recorded daily, and blood samples were collected from the jugular vein once daily at arrival in the afternoon of d 0 and at 0900 h from d 1 to 5 after arrival. Urine and feces were collected quantitatively over a 48-h period from 1200 h on d 1 to 1200 h on d 3, and a representative sample of each 24-h period was stored. In addition, the volume of extracellular fluid was evaluated on d 2 by postprandial sampling over a 4-h period relative to the injection of sodium thiosulfate at 1300 h. Total daily fluid intake (MR, treatment, and water) from d 1 to 3 was greater in HYPER (LSM ± SEM; 8.9 ± 0.36 L/d) and HYPO (7.8 ± 0.34 L/d) than in CON (6.6 ± 0.34 L/d). This resulted in a greater water balance (water intake - fluid output in urine and feces) in calves receiving ORS (59.6 ± 6.28 g/kg BW per 24 h vs. 39.6 ± 6.08 g/kg BW per 24 h). Fecal Na+ losses were greater in HYPER than in the other treatments (81 ± 12.0 mg/kg BW per 24 h vs. 24 ± 11.8 mg/kg BW per 24 h). Blood pH was higher in HYPO (7.41 ± 0.016) than CON (7.35 ± 0.016) over the 5 monitoring days, whereas HYPER (7.37 ± 0.017) did not differ with other treatments. In this experimental model, diarrheic calves were likely unable to absorb the high Na+ load from HYPER, resulting in greater Na+ losses in feces, which might have impaired the alkalinizing capacity of HYPER. In contrast, HYPO significantly sustained blood acid-base balance compared with CON, whereas HYPER did not. This suggests that low tonicity ORS with a high SID are more suitable for diarrheic calves.

Tonicity of oral rehydration solutions affects water, mineral and acid-base balance in calves with naturally occurring diarrhoea.

Recommendations for composition of oral rehydration solutions (ORS) for calves, particularly concerning Na+, glucose, and their combined effect on tonicity, are not in line with guidelines for humans. Thus, this study aimed to determine the effect of ORS tonicity on water, mineral and acid–base balance. Seventy‐two calves were selected based on the severity of dehydration and blood base excess (BE) on day 0. Five calves that did not develop diarrhoea were removed post‐inclusion from the study. Calves were allocated to blocks of four animals based on blood BE on day 1. Within each block, calves were randomly assigned to one of four treatments: (a) hypotonic ORS with low Na+ and lactose (HYPO); (b) isotonic ORS with low Na+and glucose (ISO); (c) hypertonic ORS with high Na+ and glucose (HYPER); and (d) control consisting of warm water including 5 g/L of whey powder (CON). Treatments were administered twice daily over a 3‐day period, in which calves were offered 2.0 L of treatment at 1300 and 2100 hr. Calves were fed 2.5 L of milk replacer at 0700 and 1630 hr from day 1 to 3 and 3.0 L from day 4 to 5, and had access to water. Calves were monitored for 5 days in which measurements included intakes, BW, blood sampling and collection of faeces on day 1 and urine from day 1 to 3. All ORS treatments maintained normal serum Na+, whereas CON did not. Calves in the HYPER group had lower blood pH and greater faecal Na+ losses than HYPO and ISO. Plasma expansion relative to baseline was higher in low tonicity ORS (+4.8%) when compared with CON (+1.0%). Urine osmolality was 30% higher in HYPER calves. In this experiment, low tonicity ORS were more effective at restoring water, mineral and acid–base balance than the hypertonic ORS.

Chinese clinical practice guidelines for acute infectious diarrhea in children.

The guidelines addressed the evidence-based indications for the management of children with acute infectious diarrhea in Chinese pediatric population. The experts group of evidence development put forward clinical problems, collects evidence, forms preliminary recommendations, and then uses open-ended discussions to form recommendations. The literature review was done for developing this guideline in databases including PubMed, Cochrane, EMBASE, China Biomedical Database, and Chinese Journal Full-text Database up to June 2013. Search the topic "acute diarrhea" or "enteritis" and "adolescent" or "child" or "Pediatric patient" or "Baby" or "Infant". For the treatment of mild, moderate dehydration, hypotonic oral rehydration solutions (ORS) are strongly recommended. Intravenous (IV) rehydration is recommended for severe dehydration, with a mixture of alkali-containing dextrose sodium solution. Nasogastric feeding tube rehydration is used for children with severe dehydration without IV infusion conditions with ORS solution. Regular feeding should resume as soon as possible after oral rehydration or IV rehydration. The lactose-free diet can shorten the diarrhea duration. Zinc supplements are recommended in children with acute infectious diarrhea. Saccharomyces boulardii and Lactobacillus Rhamnus are recommended to be used in acute watery diarrhea. Saccharomyces boulardii is recommended in children with antibiotic-associated diarrhea as well. Montmorillonite and Racecadotril (acetorphan) can improve the symptoms of diarrhea or shorten the course of acute watery diarrhea. Antibiotics are recommended with dysenteric-like diarrhea, suspected cholera with severe dehydration, immunodeficiency, and premature delivery children with chronic underlying disease; otherwise, antibiotics are not recommended. The principles of the most controversial treatments with of acute infectious disease are reaching to a consensus in China.

Acceptability and efficacy of a gel hypotonic oral rehydration solution in children with acute gastroenteritis.

Oral rehydration solution remains the mainstay of acute gastroenteritis therapy. The aim of this study was to investigate the acceptability of a new zinc-containing hypotonic super-oral rehydration solution (ORS) in a gel formulation and its efficacy in reducing the duration and severity of diarrhea in children. This was a randomized-controlled trial of children (5-36 months of age) observed for diarrhea lasting less than 24 h. Children were randomized to receive standard hypotonic ORS (group 1) or a gel hypotonic super-ORS containing zinc (group 2). The main study outcome was ORS intake in the first 24 h. ORS intake at 4 h, rate of diarrhea resolution at 72 h of treatment, total duration and severity of diarrhea, hospitalization, and adverse effects were also evaluated. Eighty-three children were enrolled (group 1: 40; group 2: 43). The amount of ORS consumed at 24 h was significantly higher in group 2 than in group 1. A similar result was observed at 4 h. The number of children who refused ORS (<10 ml/kg/day) was lower in group 2 versus group 1 (P=0.001). The number of children presenting diarrhea after 72 h of treatment was lower in group 2 versus group 1 (P=0.028). Also, the mean duration of diarrhea was shorter in group 2 than in group 1 (P=0.001). The hypotonic super-ORS containing zinc in a gel formulation had a positive effect on the severity of diarrhea. No patient required hospitalization. No adverse events were observed in either of the two study groups. The new zinc-containing hypotonic super-ORS in a gel formulation is effective in the management of childhood acute gastroenteritis.

Efficacy and safety of a new apple‐flavoured oral rehydration solution in children with acute gastroenteritis: a double‐blind randomized controlled trial

To assess the efficacy and safety of a new oral rehydration solution (ORS) with improved flavour in the management of children with acute gastroenteritis (AGE). Children 4 to 48 months of age with AGE (≥3 loose or watery stools per day for >1 but <5 days) with mild-to-moderate dehydration (3% to 9% loss of body weight) according to the World Health Organization criteria randomly received regular hypotonic ORS (Na 60 mmol/L, glucose 78 mmol/L) or the same hypotonic ORS with an apple taste. Of the 147 children randomized, 130 (88.4%) were available for intention-to-treat analysis. The proportion of children with the resolution of signs of dehydration in the experimental group compared with the control group was similar at 24 h (49/63 vs. 57/67, respectively, p = 0.28). There were also no significant differences in adequate weight gain (p = 0.48) and urine production at 24 h (p = 0.95) between groups. There were no differences between groups in any of the secondary outcome measures, including ORS intake. No adverse events were observed in the study groups. In an outpatient setting, there was no difference in efficacy between the study products. Both ORSs were equally effective and may be used interchangeably.

Efficacy of a New Hypotonic Oral Rehydration Solution Containing Zinc and Prebiotics in the Treatment of Childhood Acute Diarrhea: A Randomized Controlled Trial

To evaluate the efficacy of a hypotonic oral rehydration solution (ORS) containing zinc and prebiotics for treatment of acute diarrhea in children. We conducted a single-blind, prospective, controlled trial including children (age range, 3-36 months) with acute diarrhea randomly assigned to standard hypotonic ORS (group 1) or to new hypotonic ORS containing zinc and prebiotics (group 2). The main outcome was the rate of resolution of diarrhea at 72 hours. A total of 60 children in group 1 (34 male; mean age, 18.58 months; 95% CI, 15.5-21.6) and 59 in group 2 (36 male; mean age, 19.26 months; 95% CI, 15.9-22.6) completed the study protocol. The rate of diarrhea resolution at 72 hours was higher in group 2 (50% versus 72.9%, P = .010). Total ORS intake in the first 24 hours was higher in group 2 (50 mL/kg; 95% CI, 41-59 versus 22 mL/kg; 95% CI, 17-29; P < .001). The mean number of missed working days by the parents of children in group 2 was lower (0.39; 95% CI, 0.08-0.70 versus 1.45; 95% CI 1.02-1.88; P < .001). Fewer patients in group 2 needed adjunctive drugs for the treatment of diarrhea 6/59 versus 19/60, P = .004. No adverse events were observed in either of the two groups. The addition of zinc and prebiotics to ORS limits diarrhea duration in children.

Acute infectious diarrhea in children.

Acute infectious enteritis is one of the more common childhood diseases worldwide, especially in the first three years of life. Every year, in Germany, one in six children under age 5 is taken to a physician at least once because of infectious diarrheal disease. 10% of the children presenting with rotavirus infection are admitted to hospital. The existing national and international recommendations for the treatment of acute infectious diarrheal disease are inadequately followed, despite the high level of evidence on which they are based. Selective literature search based on national and international guidelines. The therapeutic goal is to replace the fluid and electrolyte losses resulting from diarrhea and vomiting. The administration of a hypotonic oral rehydration solution (ORS) is indicated to treat impending dehydration (infants aged up to 6 months with diarrhea and/or more than 8 watery stools in the last 24 hours and/or more than 4 episodes of vomiting in the last 24 hours), or when mild or moderate dehydration is already present. Oral rehydration with ORS given in frequent, small amounts over 3-4 hours is successful in more than 90% of cases. Regular feeding can be begun immediately afterward. Laboratory testing of blood or stool is usually unnecessary. Children who can be rehydrated orally or through a nasogastric tube should not be given intravenous fluids.

New hypotonic oral rehydration solution containing zinc and prebiotics for the management of children with acute gastroenteritis

New hypotonic oral rehydration solution containing zinc and prebiotics for the management of children with acute gastroenteritis

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

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. 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. 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. 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.

Intestinal transport of hypotonic oral rehydration solutions in the rat: regional difference of water and electrolyte absorption.

Intestinal transport of hypotonic oral rehydration solutions in the rat: regional difference of water and electrolyte absorption.

The management of acute diarrhoea

The successful management of acute diarrhoea depends upon correction of dehydration and electrolyte losses followed by maintenance of hydration and nutrition. Pillars of good practice have been defined by the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). They include fast oral rehydration over 3–4 h with hypotonic oral rehydration solution, rapid refeeding with a normal diet as soon as rehydration is complete, continuation of breastfeeding at all times and no unnecessary medications.

Management of acute diarrhoea with low osmolarity oral rehydration solutions and Lactobacillusstrain GG

Two hypotonic oral rehydration solutions with osmolarities of 224 mosmol/l (Na+ 60 mmol/l, glucose 84 mmol/l) and 204 mosmol/l (Na+ 60 mmol/l, glucose 64 mmol/l), respectively, and oral treatment withLactobacillus...

A trial in the Karelian Republic of oral rehydration and Lactobacillus GG for treatment of acute diarrhoea

In a controlled trial in Petrozavodsk, Karelia, the effects of oral rehydration and Lactobacillus strain GG (LGG) on recovery from acute diarrhoea (27% rotavirus, 21% bacterial aetiology) were studied in 123 children aged between 1 and 36 months of age. On admission to hospital, the patients were first randomized to receive either isotonic oral rehydration solution (ORS) with osmolarity 311 mosmol/l and sodium 90 mmol/l (WHO-ORS), or a hypotonic ORS with osmolarity 224 mosmol/l and sodium 60 mmol/l (Light-ORS), and thereafter randomized to receive either 5 x 10(9) colony forming units of LGG or a matching placebo. The two ORS performed equally for acute rehydration, and oral rehydration with either ORS was associated with a shorter duration of diarrhoea than intravenous rehydration (p = 0.036). Patients receiving LGG had a significantly shorter duration of watery diarrhoea [mean (SD) 2.7 (2.2) days] than those receiving the placebo [3.7 (2.8) days, p = 0.03]. LGG significantly shortened the duration of rotavirus diarrhoea but not diarrhoea with confirmed bacterial aetiology.

Randomised double blind study of hypotonic oral rehydration solution in diarrhoea

A hypotonic (osmolality 224 mmol/l, sodium 60 mmol/l) oral rehydration solution (ORS) was compared with an isotonic high glucose ORS (osmolality 304 mmol/l, sodium 60 mmol/l) in children with acute...

Water and electrolyte absorption and secretion

This review discusses the control of ion exchanges and paracellular channels, the influence of the enteric nervous system on salt and water transport, the role of an endogenous secretagogue, and the optimization of rehydration therapy in diarrheal states. A synergistic mechanism of action between Na+/H+ exchanges of the apical and basolateral membranes is postulated and glutamine is found to activate this exchange at a cellular level. Nitric oxide is implicated in the energy-dependent, stress-sensitive maintenance of paracellular channel integrity. Coordination of both absorptive and secretory states is mediated by the recruitment of a sophisticated local nervous system. Roles for the ligand that mimics a heat-stable enterotoxin are proposed and, in the wake of a sobering report on the recent cholera epidemic in Goma, an important study confirms the merits of hypotonic oral rehydration solution.

Absorption of a hypotonic oral rehydration solution in a human model of cholera.

The development of oral rehydration solutions (ORSs) has been one of the important therapeutic advances of this century. The optimal formulation, however, of ORSs for both cholera and other infective diarrhoeas is still debated. Part of the problem in developing ORSs has been the lack of adequate test systems for the assessment of new formulations before clinical trial. We have developed a jejunal perfusion, cholera toxin induced, secretory model in humans and have compared net water and solute absorption from a hypotonic ORS (HYPO-ORS: sodium 60 mmol/l, glucose 90 mmol/l, osmolality 240 mOsm/kg) and the British Pharmacopoeia recommended ORS (UK-ORS: sodium 35 mmol/l, glucose 200 mmol/l, osmolality 310 mOsm/kg) in six healthy volunteers. A plasma electrolyte solution (PES) was also perfused in all subjects to confirm a secretory state. Only HYPO-ORS reversed sodium secretion to absorption (p < 0.01). Both ORSs promoted net water absorption but this was greatest with HYPO-ORS (p < 0.01). Glucose and potassium absorption rates were similar for both ORSs whereas chloride absorption mirrored sodium absorption and was greatest from HYPO-ORS (p < 0.05). These results, in a biologically relevant model of secretory diarrhoea, suggest it may be possible to achieve improved rates of rehydration by the use of hypotonic ORS with mid range sodium concentrations.

Clinical experience with a hypotonic oral rehydration solution in acute diarrhoea

A hypotonic oral rehydration salts (ORS) solution with total osmolality of 224 mosmol/l was compared in an open clinical trial with an isotonic (osmolality 304 mosmol/l) ORS solution for the treatment of dehydration due to acute diarrhoea. Both ORS solutions had the same electrolyte composition with a Na+ concentration of 60 mmol/l. Children given the hypotonic ORS solution (n = 103) passed significantly fewer diarrhoeal stools, and their diarrhoea and hospital stay were shorter than those of children given the isotonic ORS solution (n = 135). We conclude that hypotonic ORS ("light" ORS) has clinical advantages over the standard ORS currently used in Finland.

Water and solute absorption from hypotonic glucose-electrolyte solutions in human jejunum.

While oral rehydration therapy with glucose-electrolyte solutions is highly effective, the optimal formulation has not yet been defined. Recent clinical studies suggest that stool volume, and thus water losses, may be reduced if glucose is replaced by a polymeric substrate which reduces osmolality. It is possible that the efficacy of glucose monomer based oral rehydration solutions (ORS) will also improve if osmolality is decreased. Using jejunal triple lumen perfusion in healthy adult volunteers net water and solute absorption were studied from three hypotonic solutions with different sodium concentrations (46, 60, 75 mmol/l) but identical glucose concentrations (90 mmol/l), thus allowing osmolality to rise (210, 240, and 270 mOsm/kg, respectively). Results from these solutions (ORS 45:210, ORS 60:240, and ORS 75:270) were compared with the World Health Organisation oral rehydration solution (WHO-ORS). Greatest water absorption was seen with ORS 60:240 (p less than 0.01). Sodium absorption from ORS 60:240 and WHO-ORS was similar and greater than sodium absorption from ORS 45:210 (p less than 0.05). Potassium and glucose absorption were greater from ORS 60:240 than from any of the other hypotonic solutions (p less than 0.05) and were equal to absorption from WHO-ORS). These results in a short segment of healthy human jejunum suggest that hypotonic ORS containing monomeric glucose may increase water 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.

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.