Double blind, randomised controlled clinical trial of hypo-osmolar oral rehydration salt solution in dehydrating acute diarrhoea in severely malnourished (marasmic) children

AIMS—To compare the clinical efficacy of hypo-osmolar oral rehydration salt (ORS) solution (224 mmol/l) and standard ORS solution (311 mmol/l) in severely malnourished (marasmic) children having less than 60% Harvard standard weight for age with dehydrating acute watery diarrhoea.
METHODS—In a double blind, randomised, controlled trial, 64 children aged 6-48 months were randomly assigned standard (n = 32) or hypo-osmolar ORS (n = 32).
RESULTS—Stool output (52.3 v 96.6 g/kg/day), duration of diarrhoea (41.5 v 66.4 hours), intake of ORS (111.5 v 168.9 ml/kg/day), and fluid intake (214.6 v 278.3 ml/kg/day) were significantly less in the hypo-osmolar group than in the standard ORS group. Percentage of weight gain on recovery in the hypo-osmolar group was also significantly less (4.3 v 5.4% of admission weight) than in the standard ORS group. A total of 29 (91%) children in the standard ORS group and 32 (100%) children in the hypo-osmolar group recovered within five days of initiation of therapy. Mean serum sodium and potassium concentrations on recovery were within the normal range in both groups.
CONCLUSION—Our findings suggest that hypo-osmolar ORS has beneficial effects on the clinical course of dehydrating acute watery diarrhoea in severely malnourished (marasmic) children. Furthermore, children did not become hyponatraemic after receiving hypo-osmolar ORS.

     

Hypo-osmolar oral rehydration salts solution in dehydrating persistent diarrhoea in children: double-blind, randomized, controlled clinical trial

A double-blind, randomized, controlled trial was conducted to compare the clinical efficacy of hypo-osmolar oral rehydration salts (ORS) solution (224 mmol/L) and standard ORS solution (311 mmol/L) in children with persistent diarrhoea who were prone to develop dehydration. Initially, 95 children aged between 3 and 24 mo were included in the study for overnight observation. Of these, 70 children who passed stool more than 2 g/kg/h were finally enrolled in the study and were randomly assigned either standard ORS or hypo-osmolar ORS. After decoding the identity of ORS, it was observed that 37 children were in the standard ORS group and 33 in the hypo-osmolar ORS group. Clinical parameters and microbiological findings of stool samples were comparable in the two groups at the time of enrolment. Total stool output (2.5 ± 1.1 vs 3.2 ± 1.6 kg; p = 0.04), duration of diarrhoea (114.8 ± 38.3 vs 145.4 ± 40.0 h; p = 0.002), total intake of ORS (5.4 ± 1.6 vs 7.8 ± 1.8 l; p = 0.002) and total fluid intake (7.9 ± 2.6 vs 10.0 ± 4.1 l, p = 0.01) were significantly less in the hypo-osmolar ORS group compared to the standard ORS group. However, the percentage of weight gain on recovery in the hypo-osmolar group was less compared to that of the standard ORS group, though the difference was statistically insignificant. Thirty-five (95%) children in the standard ORS and 33 (100%) children in the hypo-osmolar group recovered within 10 d of initiation of therapy and modified dietary management. Conclusion: Our findings suggest that hypo-osmolar ORS has beneficial effects on the clinical course of dehydrating persistent diarrhoea.     

Alanine- and glucose-based hypo-osmolar oral rehydration solution in infants with persistent diarrhoea: a controlled trial

To evaluate the efficacy of a hypo-osmolar and a standard (World Health Organization) oral rehydration salt (ORS) solution in persistent diarrhoea, a randomized controlled clinical trial was conducted in 55 children. After a 1-day observation period the children were assigned to one of three solutions: standard ORS (WHO-ORS) (osmolality 311 mosmol/1), hypo-osmolar ORS containing L-alanine and glucose (osmolality 255 mosmol/1) and iv polyelectrolyte solutions (osmolality 293 mosmol/1) for ongoing replacement of stool loss for the next 4 days. Excellent acceptability of ORS (101-160 ml/kg body weight/day) by the children was observed. There were no significant differences in the total intake of solutions and food, and frequency of stools among the groups Stool outputs were significantly less in infants receiving hypo-osmolar ORS than in those receiving WHO-ORS for 0-24h (p = 0.04), 0-48h (p = 0.01), 0-72h (p = 0.04) and 0-96h (p = 0.03). The results indicate a sufficient scope of ORS practice in persistent diarrhoea. Furthermore, we found that a hypo-osmolar ORS containing L-alanine and glucose is as efficacious as an iv solution and more effective than WHO-ORS for replacement of ongoing stool loss in persistent diarrhoea. Alanine-glucose ORS, hypo-osmolar solution, oral rehydration solution, persistent diarrhoea     

Evaluation of oral hypo-osmolar glucose-based and rice-based oral rehydration solutions in the treatment of cholera in children

In a randomized controlled clinical trial, the efficacy of a low-sodium low-glucose oral rehydration solution (ORS) and a low-sodium rice-based ORS was compared with standard WHO glucose ORS in the treatment of severe cholera in children aged 2-10y. In total, 120 children were evaluated for the study, of whom 58 patients were positive for Vibrio cholerae and were included in the study. Of these 58 cases, 19 received rice-based hypo-osmolar ORS, 20 received WHO-ORS and 19 received glucose-based hypo-osmolar ORS. The clinical characteristics (age, preadmission duration of diarrhoea, frequency of stool before admission, incidence of vomiting, body weight and volume of initial fluid requirement) were comparable in the three treatment groups. All patients received tetracycline in a dose of 50 mg/kg/d of body weight in 4 divided doses for 3 d. CONCLUSIONS: Patients who received rice-based hypo-osmolar ORS had subsequently reduced (p < 0.05) stool output, ORS consumption and diarrhoea duration than the patients who received either WHO-ORS or glucose-based hypo-osmolar ORS.     

Impact of zinc supplementation in malnourished children with acute watery diarrhoea

A double-blind, randomized, controlled clinical trial was conducted on 80 malnourished children with acute dehydrating diarrhoea to evaluate the efficacy of oral supplementation of zinc as an adjunct therapy to oral rehydration solution (ORS). After decoding it was observed that 44 children received zinc sulphate (177 mg/kg/day in three divided doses equivalent to 40 mg elemental zinc) in a syrup form and 36 children received only syrup placebo. Clinical parameters and microbiological findings of stool samples were comparable in the two groups at the time of enrollment. All the children (100 per cent) in the zinc supplemented group and 32 (89 per cent) children in the placebo group recovered within 5 days of hospitalization (p = 0.04). The zinc supplemented group had a significantly shorter duration of diarrhoea (70.4 +/- 10.0 vs. 103.4 +/- 17.1 h; p = 0.0001), passed less liquid stool (1.5 +/- 0.7 vs. 2.4 +/- 0.7kg; p=0.0001), consumed less oral rehydration solution (2.5 +/- 1.0 vs. 3.6 +/- 0.8 litre; p = 0.0001) and other liquids (867.0 +/- 466.1 vs. 1354.7 +/- 675.6 ml; p = 0.0001) as compared to the placebo group. Our findings suggest that zinc supplementation as an adjunct therapy to ORS has beneficial effects on the clinical course of dehydrating acute diarrhoea.     

Efficacy and safety of a modified oral rehydration solution (ReSoMaL) in the treatment of severely malnourished children with watery diarrhea

OBJECTIVES: Efficacy, development of overhydration, and correction of electrolyte disturbances of severely malnourished children with acute diarrhea using a modified oral rehydration solution for malnourished children (termed ReSoMaL and recommended by the World Health Organization [WHO]) were evaluated and compared with standard WHO-oral rehydration solution (ORS). STUDY DESIGN: Children age 6 to 36 months with severe malnutrition and acute watery diarrhea were randomized to ReSoMaL (n=65) or standard WHO-ORS (n=65). Major outcome measures included the number of children who developed overhydration and the number who corrected hypokalemia. RESULTS: The numbers of children who developed overhydration were not significantly different (ReSoMaL vs WHO-ORS, 5% vs 12%, P=.2). ReSoMaL corrected basal hypokalemia in a greater proportion of children by 24 hours (36% vs 5%, P=.0006) and 48 hours (46% vs 16%, P=.004) compared with WHO-ORS. More children on ReSoMaL than WHO-ORS remained hyponatremic at 48 hours (29% vs 10%, P=.017). Three children in the ReSoMaL group developed severe hyponatremia by 24 hours, with one experiencing hyponatremic convulsions (serum sodium, 108 mmol/L). CONCLUSIONS: ReSoMaL has a large beneficial effect on potassium status compared with standard ORS. However, ReSoMaL therapy may result in symptomatic hyponatremia and seizures in patients with severe diarrhea.     

Randomised controlled trial of zinc supplementation in malnourished Bangladeshi children with acute diarrhoea

OBJECTIVE: To evaluate the impact of zinc supplementation on the clinical course, stool weight, duration of diarrhoea, changes in serum zinc, and body weight gain of children with acute diarrhoea. DESIGN: Randomised double blind controlled trial. Children were assigned to receive zinc (20 mg elemental zinc per day) containing multivitamins or control group (zinc-free multivitamins) daily in three divided doses for two weeks. SETTING: A diarrhoeal disease hospital in Dhaka, Bangladesh. PATIENTS: 111 children, 3 to 24 months old, below 76% median weight for age of the National Center for Health Statistics standard with acute diarrhoea. Children with severe infection and/or oedema were excluded. MAIN OUTCOME MEASURES: Total diarrhoeal stool output, duration of diarrhoea, rate of weight gain, and changes in serum zinc levels after supplementation. RESULTS: Stool output was 28% less and duration 14% shorter in the zinc supplemented group than placebo (p = 0.06). There were reductions in median total diarrhoeal stool output among zinc supplemented subjects who were shorter (less than 95% height for age), 239 v 326 g/kg (p < 0.04), and who had a lower initial serum zinc (< 14 mmol/l), 279 v 329 g/kg (p < 0.05); a shortening of mean time to recovery occurred (4.7 v 6.2 days, p < 0.04) in those with lower serum zinc. There was an increase in mean serum zinc in the zinc supplemented group (+2.4 v -0.3 mumol/l, p < 0.001) during two weeks of supplementation, and better mean weight gain (120 v 30 g, p < 0.03) at the time of discharge from hospital. CONCLUSIONS: Zinc supplementation is a simple, acceptable, and affordable strategy which should be considered in the management of acute diarrhoea and in prevention of growth faltering in children specially those who are malnourished.     

Hypo-osmolar sucrose oral rehydration solutions in acute diarrhoea: a pilot study

Based on studies showing improved absorption of hypo-osmolar oral rehydration solutions (ORS) with reduced glucose and sodium concentration, a hypo-osmolar ORS with sucrose replacing glucose (sodium 60, potassium 15, chloride 60, citrate 5, sucrose 58mmoll^?1, calculated osmolality 198mOsmkg^?1) was compared with mildly hyperosmolar glucose ORS (WHO) in 46 children aged 6–30 months with acute diarrhoea and dehydration. In the hypo-osmolar sucrose ORS group (n = 18) faecal output was less by 30% during the initial 24 and 48 h compared with controls, suggesting better absorption. Sucrose may be a suitable alternative to glucose in an absorption-efficient hypo-osmolar ORS.     

Hypotonic oral rehydration solution in acute diarrhoea: a controlled clinical trial

In a controlled trial, a hypotonic oral rehydration solution (ORS) (Na⁺67, K⁺20, CP66, citrate 7, glucose 89mmol/1 osmolality 249 mosmol/kg) was compared with a standard WHO-ORS (Na⁺90, K⁺20, Cl^-80, citrate 10, glucose lllmmol/1, osmolality 311 mosmol/kg) in 60 children aged 5-24 months with acute watery diarrhoea. In the hypotonic ORS group, stool frequency, proportion of children who vomited, ORS requirements and purging rate over 24-48 h were reduced by 33% ( p = 0.01), 30% ( p = 0.02), 21% ( p = 0.067) and 21% ( p = 0.03), respectively. The proportion of children who vomited and the purging rate over 48 h were reduced by 23% ( p = 0.03) and 10% ( p = 0.097), respectively. Serum electrolytes after 48 h were comparable. The beneficial effect of hypotonic ORS was most marked in, and largely contributed by, the subgroup negative for rotavirus.     

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 diarrhoea in a randomised double blind study. The stool output and hence the mean consumption of ORS for maintenance hydration was less (p = 0.036) in patients receiving hypotonic (69 ml/kg) than isotonic (97 ml/kg) ORS. Hypotonic ORS was more effective in patients with rotavirus positive than with rotavirus negative diarrhoea.     

Insulin-like growth factor I response during nutritional rehabilitation of persistent diarrhoea.

OBJECTIVE: Evaluation of nutritional recovery, intestinal permeability, and insulin-like growth factor I (IGF-I) response in malnourished children with persistent diarrhoea and their relation to concomitant systemic infection(s). STUDY DESIGN: Open study of severely malnourished children (aged 6-36 months) with persistent diarrhoea (>/= 14 days) admitted for nutritional rehabilitation with a standardised rice-lentil and yogurt diet. Successful recovery was defined prospectively as overall weight gain (> 5 g/kg/day) with a reduction in stool output by day 7 of treatment. Data on coexisting infections and serum C reactive protein (CRP) were collected at admission. RESULTS: Of 63 children, 48 (group A) recovered within seven days of dietary treatment. These children had a significant increase in serum IGF-I (DeltaIGF-I%) and, in contrast to serum prealbumin and retinol binding protein, DeltaIGF-I% correlated with weight gain (r = 0.41). There was no correlation between the IGF-I response and intestinal permeability as assessed by urinary lactulose/rhamnose excretion. Treatment failures (group B) included more children with clinical (relative risk, 4.8; 95% confidence interval, 1.2 to 19.7) and culture proven sepsis at admission and higher concentrations of serum CRP (median (range), 36 (0-182) v 10 (0-240) mg/l) at admission. There was a negative correlation between admission CRP concentration and DeltaIGF-I% (r = -0.45). CONCLUSIONS: In comparison with serum albumin, prealbumin, and retinol binding protein, serum IGF-I increment is a better marker of nutritional recovery in malnourished children with persistent diarrhoea. The possible association of systemic infections, serum IGF-I response, and mucosal recovery needs evaluation in future studies.     

Randomised double blind study of hypotonic oral rehydration solution in diarrhoea

Accepted 19 November 1996
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 diarrhoea in a randomised double blind study. The stool output and hence the mean consumption of ORS for maintenance hydration was less (p = 0.036) in patients receiving hypotonic (69 ml/kg) than isotonic (97 ml/kg) ORS. Hypotonic ORS was more effective in patients with rotavirus positive than with rotavirus negative diarrhoea.

     

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

Aim: 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). Methods: 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. Results: 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. Conclusions: In an outpatient setting, there was no difference in efficacy between the study products. Both ORSs were equally effective and may be used interchangeably.     

Serum phosphorus in protein energy malnutrition

Phosphorus depletion in malnutrition has not generally received attention. Serum phosphorus was measured in healthy infants (1.8 mmol/L), in well-nourished infants with acute dehydrating gastroenteritis, and in infants suffering from malnutrition. Serum phosphorus levels were found to be low in well-nourished infants with acute dehydrating gastroenteritis (1.32 mmol/L) an exceptionally low in infants with kwashiorkor (1.10 mmol/L) especially when the latter condition was accompanied by severe diarrhoea (0.66 mmol/L). Hypophosphatemia, as well as hypokalemia, was associated with marked hypotonia. Low levels of serum phosphorus occurred in nine of the 10 malnourished children who died.     

Measles vaccination in severely malnourished Sudanese children

The clinical and serological responses to attenuated measles virus vaccine were compared in 35 severely malnourished and 35 well-nourished children. A third group of severely malnourished children, who received an injection of vitamin B12, served as controls. The children were observed for three weeks following vaccination. Paired sera were collected from each child before and after administration of the vaccine or vitamin B12 and measles antibody titres were estimated using HAI technique. The malnourished children who received measles vaccine developed higher fever of longer duration and had more lower respiratory tract disease than the other two groups but had fewer skin rashes than the well-nourished group. Sero-conversion rates were 96% had 92.6% in the malnourished and well-nourished vaccinated children, respectively. Antibody titres were lower in children who had marasmic/kwashiorkor than in the marasmic children.     

Is rice based oral rehydration therapy effective in young infants?

Rice based oral rehydration therapy (ORT) solutions have been shown to be superior to glucose oral rehydration salts (World Health Organisation (WHO) ORS) in reducing stool volume and duration of diarrhoea in children and adults. Rice based ORT has been used only sparingly in young infants, however, because of theoretical concerns about digestibility. A randomised controlled trial of rice based ORT (50 g rice and electrolytes identical to WHO ORS) and WHO ORS was carried out in 52 male infants less than 6 months old with moderately severe acute diarrhoea to evaluate efficacy and digestibility. Nineteen (70%) of 27 children who received rice based ORT and 18 (72%) of 25 children who received WHO ORS were treated successfully. The mean (SD) diarrhoeal stool output for the first 24 hours of treatment was significantly lower in the infants receiving the rice based ORT than in those receiving WHO ORS (101.0 (60.5) v 137.1 (74.6) g/kg). The stool output was also significantly less in the rice based ORT group in the second 24 hours. Infants in the rice based ORT group drank significantly less rehydration solution than infants in the WHO ORS group (mean (SD) 165.4 (77.4) v 217.9 (86.1) during the first 24 hours of treatment. There was no difference in the duration of diarrhoea between the groups. The volume of breast and formula feeding was similar in the two groups. No difference was seen in the frequency of finding reducing substances or acid pH in the stools of either group of children. The results suggest that rice based ORT is as effective as WHO ORS in infants with moderately severe diarrhoea and that rice based ORT is as well tolerated as WHO ORS in infants.     

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 osmolality 311mosmol/l and sodium 90mmol/l (WHO-ORS), or a hypotonic ORS with osmolality 224mosmol/l and sodium 60mmol/l (Light-ORS), and thereafter randomized to receive either 5 × 10⁹ 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.     

Evaluation of an oral rehydration solution with Na+ 60 mmol/l in infants hospitalized for acute diarrhoea or treated as outpatients

An oral rehydration solution (ORS) containing 60 mmol/l of Na+ (ORS60) was compared in a randomized trial with the ORS of WHO formula (Na+ 90 mmol/l = ORS90) for the treatment of diarrhoeal dehydration in 66 hospitalized infants aged 3 to 34 months. The infants had a 5 +/- 3% dehydration, and received within 6-10 hours 76 +/- 32 ml/kg of ORS60 or 74 +/- 41 ml/kg of ORS90 corresponding to a sodium input of 4.6 +/- 1.9 mmol/kg and 6.6 +/- 3.7 mmol/kg, respectively. Both treatments were found adequate and equally effective for the correction of dehydration and sodium deficit. The same ORS60 was also compared to a commercial low sodium glucose-electrolyte solution (sodium 35 mmol/l, glucose 3.5 milligrams) for ambulatory treatment of acute diarrhoea in infants. Satisfactory rehydration was achieved within 6 hours in 19 of 23 infants receiving ORS60 as opposed to 6 of 18 infants receiving the commercial solution (p less than 0.001); the poor result with the latter was in most cases attributed to a refusal by the infant to consume the sweetish solution. It is concluded that ORS60 is suitable for the treatment of isotonic diarrhoeal dehydration in hospitalized children as well as outpatients.     

Randomized, controlled, clinical trial of rice versus glucose oral rehydration solutions in infants and young children with acute watery diarrhoea

A randomized clinical trial was carried out to compare a packaged ready-to-mix rice oral rehydration solution (ORS) to the standard glucose ORS for the treatment of childhood diarrhoea. Children were of either gender, aged 3–35 months, presenting with a history of watery diarrhoea for 72 h or less. The main outcomes examined were stool output, ORS intake, duration of diarrhoea and nutritional recovery during follow-up at 16 d of illness. Stool output in the first 24 h (106 vs 107 g kg^-1), ORS intake in clinic (93 vs 102 ml per motion) and duration of diarrhoea (88 h vs 81 h) were similar in the two treatment groups. The few episodes that became persistent were similar (2%) in the two groups. The weight gain during follow-up was similar in the two ORS groups.     

Role of cereal-based oral rehydration therapy in persistent diarrhoea in children

A total of 2000 children aged under five and 12,500 diarrhoea episodes were studied prospectively for assessing the efficacies of R-ORS and G-ORS and for comparing them with that of a comparison area using drugs for treatment. Efficacy was evaluated in terms of ORS use rate, consumption of ORS per episode, duration of diarrhoea and rate of recovery. The data were analysed to compare the rate of persistent diarrhoea in the three areas. Mean ORS consumption was 946 ± 576 and 1236 ± 766 ml per episode of watery diarrhoea in the R–ORS and G–ORS areas respectively. The mean durations of watery diarrhoea were 3.3 ± 2.1, 5.4 ± 3.5 and 8.8 ± 5.5 days in the R-ORS, G-ORS and comparison area, respectively. The median durations for dysentery were 7, 9 and 12 days in the three areas respectively. The incidences of persistent diarrhoea following watery diarrhoea were 0.4, 3 and 12% in the R-ORS, G-ORS and comparison area respectively, and, following dysentric episodes, 8, 18 and 40%. The results of the study suggest that R-ORS can hasten recovery from both watery diarrhoea and dysenteries, thus reducing the incidence of persistent diarrhoea.