Reduced osmolarity oral rehydration solution for persistent diarrhea in infants: A randomized controlled clinical trial

doi:10.1067/mpd.2001.112161

The Journal of Pediatrics

Volume 138, Issue 4, April 2001, Pages 532-538

https://doi.org/10.1067/mpd.2001.112161 Get rights and content

Abstract

Objective: We evaluated and compared the efficacy of the World Health Organization (WHO) oral rehydration solution (ORS) and 2 different formulations of reduced osmolarity ORSs in infants with persistent diarrhea. Study design: Infants with persistent diarrhea (n = 95) were randomized to 1 of the 3 ORSs: WHO-ORS (control, n = 32), a glucose-based reduced osmolarity ORS (RORS-G, n = 30), or a rice-based reduced osmolarity ORS (RORS-R, n = 31) for replacement of ongoing stool losses for up to 7 days. Major outcome measures were stool volume and frequency, ORS intake, and resolution of diarrhea. Results: Although there were variations from one study day to another, the stool volume was approximately 40% less in the reduced osmolarity ORS groups; consequently, these children required less ORS (22% for RORS-G and 27% for RORS-R groups). A higher proportion of children in the RORS-R groups also had resolution of diarrhea during the study period. No children in any of the treatment groups had hyponatremia. Conclusion: Reduced osmolarity ORS is clinically more effective than WHO-ORS and may thus be advantageous for use in the treatment of children with persistent diarrhea. (J Pediatr 2001;138:532-8)

Section snippets

Patients and Methods

The study was conducted at the Clinical Research and Service Centre of the International Centre for Diarrhoeal Disease Research, Bangladesh, between July 1995 and June 1997. Male children (aged 4 to 24 months) who were not grossly malnourished (weight for age >60% of National Center for Health Statistics median) and who had a history of watery diarrhea for >14 days were admitted to the clinical study ward. The presence of and severity of diarrhea were confirmed by observing the children for 24

Results

In total, 118 children were screened for the study and observed for 24 hours; 95 children fulfilled the study criteria (stool output >60 mL/kg) and were assigned to treatment regimens: 32 to WHO-ORS, 30 to RORS-G, and 33 to RORS-R. Two patients in the RORS-R group were withdrawn from the study because of development of acute respiratory tract infection requiring special care on day 2 of the study (Fig 1).

. Treatment profile of study population (n).

The admission characteristics of the 3 treatment

Discussion

The most important observation in our study was the effect on purging, an indicator of absorption efficiency of ORS. The absorption efficiency of RORS was better than that of the WHO-ORS. Although there were variations from one study day to another, the stool volume was approximately 40% less in the RORS groups. Consequently, the children in the RORS groups also required less ORS, and their stool frequency was also less. A higher proportion of children in the RORS groups had resolution of

Acknowledgements

ICDDR, B acknowledges with gratitude the commitment of USAID to the Centre’s efforts. We thank Ms Afia Khatun and Azmira Begum, Dr Rasheduzzaman, and nursing staffs of the Clinical Study Ward of the Clinical Research and Service Centre of ICDDR, B, for their excellent service. We are grateful to Prof D. Sack and Drs ASG Faruque and T. Ahmed for helpful comments on the article.

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In the gastrointestinal tract, ionic balance, fluid absorption, and secretion are vital to maintain homeostasis allowing for the maintenance of a membrane potential, adequate nutrient intake, normal gut motility, protection against microbes, and epithelial cell viability. This homeostatic state relies on the normal physiological function of the small and large intestinal cells and a complex array of hormonal mechanisms that control gut motility as well as entry and exit of fluid into the gastrointestinal lumen. Approximately, 8–10 L of fluid pass through the small intestinal lumen daily. It is remarkable that in health, the small intestine absorbs all but 1.5 L and the colon absorbs the rest leaving approximately 100 mL of fluid to be lost in stool. Intestinal ion transport mechanisms play a significant role in determining overall fluid balance in the gut, namely chloride secretion, electroneutral sodium chloride absorption and electrogenic sodium absorption. Moreover, a variety of hormones and neurotransmitters are synthesized locally in the intestinal mucosa and modify intestinal ion transport either directly by binding to receptors on the basolateral membrane of enterocytes or indirectly via the release of other effectors. In certain pathophysiologic states, the finely tuned ionic-fluid exchange becomes dysfunctional as a result of the failure of compensatory pro-absorptive/antisecretory mechanisms. Different pathophysiological mechanisms causing diarrhea, mainly secretory, osmotic, inflammatory, altered intestinal transit and loss of functional absorptive area, have been elucidated.
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Citation Excerpt :
An attempt to reduce this complication led to the development of hypo-osmolar solutions. Hypo-osmolar ORT in children with persistent diarrhea reduced stool output by approximately 40% and provided a greater resolution of diarrhea compared with standard ORT.29 Concerns regarding an increased risk of hyponatremia proved to be unfounded.30
Management of children with infection-associated persistent diarrhea
2004, Seminars in Pediatric Infectious Diseases
Diarrhea is the leading cause of death in children younger than 5 years of age; persistent diarrhea accounts for 30 to 50 percent of those deaths in developing countries. Malnutrition, immunosuppression, young age, and an increase in the preceding diarrhea burdens are risk factors for the development of persistent diarrhea. Although many viruses, bacteria, and parasites can produce persistent diarrhea, enteropathogenic Escherichia coli, enteroaggregative E. coli, Giardia, Cryptosporidium, and Cyclospora are the most important of these agents. With currently available tests, identifying a specific cause usually is difficult. Newer sensitive molecular tests must be used for studying the epidemiology of persistent diarrhea in children. Management includes rehydration, adequate diet, micronutrient supplementation, and antimicrobials. Persistent diarrhea seriously affects nutritional status, growth, and intellectual function. Meeting these challenges is profoundly important, particularly in developing countries.
Efficacy and safety of a modified oral rehydration solution (ReSoMaL) in the treatment of severely malnourished children with watery diarrhea
2003, Journal of Pediatrics
Citation Excerpt :
An ORS with sodium concentration reduced to the level contained in ReSoMaL does not seem to be supported by the results of our study. In recent years, there has been growing interest about the use of hypotonic or reduced osmolarity ORS (lower sodium and lower glucose ORS) in the treatment of diarrhea, because some clinical studies have demonstrated better efficacy, especially in reduced need for unscheduled intravenous fluids.21–27 Based on these findings, a WHO/UNICEF expert committee meeting28 recommended a revised formulation of reduced-osmolarity ORS (Na 75, Cl 65, K 20, citrate 20, glucose 75 mosmol/L, osmolarity 245 mosmol/L) for use in children and adults for all causes of diarrhea, including cholera; however, the issue of the best ORS remains controversial, and criticism persists.29,30
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).
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.
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).
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.

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^☆: Supported by USAID, Washington, grant No. HRN-A-00-96-90005-00 (under Cooperative Agreement).

^☆☆: Reprint requests: Shafiqul A. Sarker, MBBS, MD, Clinical Sciences Division, ICDDR, B, Mohakhali, Dhaka 1212, Bangladesh.

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Original ArticlesReduced osmolarity oral rehydration solution for persistent diarrhea in infants: A randomized controlled clinical trial☆,☆☆

Abstract

Section snippets

Patients and Methods

Results

Discussion

Acknowledgements

Gastroenterology

J Pediatr

Lancet

Descriptive epidemiology of persistent diarrhoea among young children in rural northern India

Bull World Health Organ

Persistent diarrhoea in children in developing countries: memorandum from a WHO meeting

Bull World Health Organ

Persistent diarrhea as a cause of childhood mortality in rural Bangladesh

Acta Paediatr

Deaths due to dysentery, acute and persistent diarrhoea among Brazilian infants

Acta Paeditr

Persistent diarrhoea

J Trop Pediatr

Is a low-osmolarity ORS solution more efficacious than standard WHO ORS solution?

J Paediatr Gastroenterol Nutr

High sugar worse than high sodium in oral rehydration solutions

Acta Pediatr Scand

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

Acta Paediatr

Clinical experiences with a hypotonic oral rehydration solution in acute diarrhoea

Acta Paediatr

Original Articles
Reduced osmolarity oral rehydration solution for persistent diarrhea in infants: A randomized controlled clinical trial☆,☆☆