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Reduced osmolarity oral rehydration solution for treating dehydration caused by acute diarrhoea in children

  1. Seokyung Hahn1,*,
  2. Yaejean Kim2,
  3. Paul Garner3

Editorial Group: Cochrane Infectious Diseases Group

Published Online: 21 JAN 2002

Assessed as up-to-date: 27 NOV 2001

DOI: 10.1002/14651858.CD002847

How to Cite

Hahn S, Kim Y, Garner P. Reduced osmolarity oral rehydration solution for treating dehydration caused by acute diarrhoea in children. Cochrane Database of Systematic Reviews 2002, Issue 1. Art. No.: CD002847. DOI: 10.1002/14651858.CD002847.

Author Information

  1. 1

    Seoul National University Hospital, Medical Research Collaborating Center, Seoul, Korea, South

  2. 2

    Fred Hutchinson Cancer Research Centre, Department of Infectious Diseases, Seattle, USA

  3. 3

    Liverpool School of Tropical Medicine, International Health Group, Liverpool, Merseyside, UK

*Seokyung Hahn, Medical Research Collaborating Center, Seoul National University Hospital, 2nd Floor, 28 Yongon-dong Chongno-gu, Seoul, 110-744, Korea, South. hahns@snu.ac.kr.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 21 JAN 2002

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Background

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

Diarrhoea remains a leading cause of childhood death in middle and low income countries. The main complication is dehydration, which was treated with intravenous fluid infusion until the early 1960s. Oral rehydration solution (ORS) is now the mainstay of therapy and is particularly useful when intravenous fluids are in short supply, health services are basic, and there is a shortage of skilled personnel (Almroth 1995). The combination of salt and sugar enhances fluid absorption because sodium and glucose transport in the small intestine are coupled, and glucose promotes absorption of both sodium ions and water (Fordtran 1968). Diarrhoea is caused by derangement of fluid absorption and secretion from the gut, and coupling sodium and glucose allows absorption, even during active fluid secretion due to infection. Thus rehydration can take place even with large fluid losses, as seen in enterotoxic diarrhoea, such as that caused by cholera or infection with Escherichia coli (Guarino 2001).

ORS has proved both safe and effective worldwide in hospital settings, and is now widely used in the home to prevent dehydration (Mahalanabis 1973, Grant 1983).For more than two decades, the World Health Organization (WHO) has recommended the standard formulation of glucose-based ORS with 90 mmol/L of sodium and 111 mmol/L of glucose and a total osmolarity of 311 mmol/L. It remains unclear however, whether this is the optimum level of sodium. Laboratory work suggests that lower concentrations of sodium and glucose enhance solute induced water absorption (Farthing 1988, Hunt 1992). Papers report patients experiencing blood sodium levels above the normal of 150 mmol/L with standard solution (Finberg 1973).

The objective of this review is to critically appraise and evaluate all relevant randomized controlled trials addressing comparative effects of reduced osmolarity ORS with WHO standard ORS. One potential adverse effect of reduced osmolarity ORS is a deficiency of sodium is the blood (hyponatraemia), which can give rise to convulsions. We are also exploring the risk of this adverse outcome through trial and observational data.

We confined the review to children, as they are most vulnerable to dehydration and electrolyte imbalance from diarrhoea, and are the targets for large primary care child investments that include ORS sachet distribution. Severity, duration, and volume of diarrhoea are often primary outcomes in clinical ORS studies, but we sought a pragmatic outcome relevant to health providers. ORS aims to rehydrate children and avoid the need for intravenous fluid infusion. We therefore identified unscheduled intravenous fluid infusion as a primary outcome as this represents failed oral therapy.

 

Objectives

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

To compare reduced osmolarity oral rehydration solution with the World Health Organization recommended strength for treating diarrhoea in children.

 

Methods

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Criteria for considering studies for this review

 

Types of studies

Randomized controlled trials, defined as a trial in which the subjects followed were assigned prospectively to one of two or more interventions by random allocation. This excludes quasi-randomized designs.

 

Types of participants

Children with acute diarrhoea (history of less than 5 days).

 

Types of interventions

Experimental: Reduced osmolarity oral rehydration solution (total osmolarity 250 mmol/L or less with reduced sodium).

Control: World Health Organization standard oral rehydration solution (90 mmol/L sodium, 111mmol/L glucose, total osmolarity 311 mmol/L).

 

Types of outcome measures

 

Primary outcomes

Need for unscheduled intravenous fluid infusion during the course of treatment.

 

Secondary outcomes

  • Stool output.
  • Children vomiting during rehydration.
  • Asymptomatic hyponatraemia (defined as serum sodium less than 130mmol/L) during follow up.

 

Search methods for identification of studies

We used the following search terms to search all trial registers and electronic databases: child; diarrhoea; fluid therapy; oral rehydration; osmolar; and rehydration solutions.

We searched the following trial register: Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library (Issue 3, 2004).

We searched the following electronic databases: MEDLINE (1966 to July 2004); EMBASE (1988 to July 2004); and Current Contents (July 2004).

We also checked the citations of existing reviews and trial reports.

For unpublished data and ongoing trials, we contacted current researchers and key agencies, including the World Health Organization, the Centers for Disease Control and Prevention, Atlanta (USA), and the International Centre for Diarrhoeal Disease Research, Bangladesh.

 

Data collection and analysis

 

Selection of studies

SH and SK independently applied the inclusion criteria to all identified trials, and differences were resolved by discussion with the PG.

 

Data extraction and management

SH and SK extracted data on relevant outcome measures using a standardized data abstraction form.

 

Assessment of risk of bias in included studies

Each included trial was assessed in terms of adequacy of concealment of allocation, generation of allocation sequence, blinding, and follow up of patients, using the guidelines of the Cochrane Infectious Diseases Group. Studies excluded were detailed in the 'Characteristics of excluded studies'.

 

Data synthesis

We used the Mantel-Haenszel odds ratio (OR) for binary outcomes. The odds ratios were not estimated when neither intervention group found any event, which are indicated in the MetaView figures. We used the Standardized Mean Difference (SMD) for continuous outcomes. We combined studies using a fixed effect method. For all estimates, we calculated 95% confidence intervals. We tested statistical heterogeneity using Chi-square statistic with a P-value less than 0.1 indicating statistical significance. We had prespecified potential sources of heterogeneity for analysis. We examined publication bias using a funnel plot, and a regression approach (Egger 1997) to assess funnel plot asymmetry. We conducted a sensitivity analysis in relation to adequate allocation concealment.

After presentation of the results, an expert consultation group from the World Health Organization recommended a stratified analysis by mmol sodium (less than 75 mmol and 75 to 85 mmol), and this analysis is now included (WHO 2001).

 

Results

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Description of studies

See: Characteristics of included studies; Characteristics of excluded studies.

We identified 41 studies for inclusion, and 16 studies met the inclusion criteria. The progress through the stages of meta-analysis, using the process suggested in the QUOROM statement (QUOROM Group 1999), is shown below.

41 studies comparing oral rehydration solution (ORS) formulation for treating diarrhoea.

  • 6 excluded as not randomized controlled trials (RCTs);

35 remaining RCTs of ORS comparing formulation for treating diarrhoea patients.

  • 9 excluded as intervention was something other than reduced osmolarity ORS;

26 remaining RCTs reporting reduced osmolarity ORS in one treatment arm.

  • 6 excluded if control group did not use World Health Organization (WHO) standard ORS;

20 remaining RCTs reporting comparison of reduced osmolarity ORS with WHO standard ORS.

  • 2 excluded as not in children;

18 remaining RCTs reporting comparison of reduced osmolarity ORS with WHO standard ORS for treating children with diarrhoea.

  • 2 excluded as no relevant outcomes reported;

16 remaining RCTs reporting comparison of reduced osmolarity ORS with WHO standard ORS in children with diarrhoea in relation to need of unscheduled intravenous fluid infusion therapy and some measures of clinical illness.

  • 2 excluded (Mexico 1988, Mexico 1990b) as they appear to be duplicates of a third trial (Mexico 1990a). We have contacted the authors, but while awaiting clarification, we have included only the paper with the largest number of patients (Mexico 1990a).

13 remaining RCTs. As one paper reported on two trials, one in the USA and one in Panama, we present these as separate studies (Panama 1982, USA 1982).

This leaves a total of 14 included studies. These were from Egypt (2), Bangladesh (3), Mexico (1), Colombia (1), India (3), Panama (1), and the USA (1). Two other studies were multicentre trials; one was conducted in Brazil, India, Mexico, and Peru, and the other in Bangladesh, Brazil, India, Peru, and Vietnam.

Participants were children with acute non-cholera diarrhoea in all trials except three, which included cholera patients (Bangladesh 1995b, CHOICE 2001, India 2000b). In all but one which included children up to 5 years old (India 2000a), the participants' ages ranged between 1 and 36 months. All children had some degree of clinical dehydration. One trial treated all children on day 1 with intravenous fluid infusion, and those still producing 80 ml/kg/24h were then randomized (Bangladesh 1995a). In five trials (CHOICE 2001, India 2000b, Panama 1982, WHO 1995, USA 1982) severely dehydrated children were included. Five trials included malnourished children (Bangladesh 1995b, Colombia 2000, Bangladesh 1995b, India 2000a, India 2000b, Mexico 1990a). The number of breastfed children was reported in eight trials (Bangladesh 1995a, Bangladesh 1995b, Bangladesh 1996a, CHOICE 2001, Colombia 2000, Egypt 1996b, India 2000b, WHO 1995). Fully weaned children were included in one trial (Egypt 1994).

We deviated slightly from the osmolarity definitions in our peer refereed protocol published in The Cochrane Library. For reduced osmolarity, we had defined this to be lower than 250 mmol/L, but some studies defined this as higher, and we therefore extended our limit to a total osmolarity of 270 mmol/L. For the WHO standard ORS, defined as a total osmolarity of 311 mmol/L, we also included two studies that used a slightly different WHO standard ORS with a total osmolarity of 331 mmol/L but with the same sodium and glucose combination (Panama 1982, USA 1982). All but two trials used a glucose based reduced osmolarity ORS; one used sucrose (Bangladesh 1996a), and one used L-alanine with glucose (Bangladesh 1995a).

 

Risk of bias in included studies

 

Allocation

All of the studies were randomized controlled trials. Nine reported methods that assured adequate allocation concealment (WHO 1995, CHOICE 2001, Colombia 2000, Egypt 1996b, Bangladesh 1995a, Bangladesh 1995b, Bangladesh 1996a, India 2000a, India 2000b).

 

Blinding

Six studies (CHOICE 2001, Egypt 1996b, Bangladesh 1995b, Bangladesh 1996a, India 2000a, India 2000b) were double blinded. One of the Mexico studies was described as single blinded (Mexico 1990b), but this study is currently excluded from the analysis as it is thought to be a subset of patients reported in another paper which is included, where no details of blinding are given (Mexico 1990a). Eight studies did not mention blinding.

 

Inclusion of all randomized participants

Included trials had losses to follow up of less than 10% of randomized participants in all cases.

 

Effects of interventions

Meta-analyses of the four outcomes are illustrated in the MetaView summary analysis.

Information for the primary outcome of the need for unscheduled intravenous fluid infusion was found in 11 trials (n = 1996). In the meta-analysis of 8 trials, a statistically significant reduction for unscheduled intravenous infusion for participants receiving reduced osmolarity oral rehydration solution (ORS) when compared with World Health Organization (WHO) standard ORS was demonstrated (odds ratio 0.59, 95% confidence interval 0.45 to 0.79). 3 of the 11 trials reported that none of their patients needed intravenous fluid infusion in either group, and the odds ratios were not calculated for these trials.

11 trials reported stool output during rehydration. These trials measured stool output in various ways using different units. We therefore used the standardized mean difference to analyse these data. Since the stool output in diarrhoeal disease showed a positive skewed distribution with clinical improvement, we used a log-normal approximation. The pooled standardized mean difference in the log scale is -0.23 (95% confidence interval -0.33 to -0.14), which suggests that the reduced osmolarity ORS resulted in significantly less stool output when compared with the WHO standard ORS. Data from one trial (India 2000a) were not combined with the others in the meta-analysis because this trial measured stool output for a much longer period beyond rehydration phase. The individual results of all 12 trials are summarized in Appendix 1.

For children vomiting during rehydration, six trials reported these data. The tendency was for fewer patients to vomit in the reduced osmolarity ORS group (Odds ratio 0.71, 95% confidence interval 0.55 to 0.92).

For presence of hyponatraemia, six trials reported this outcome. Three of these six trials did not observe hyponatraemia in any participants, irrespective of their allocated group. The meta-analysis of three trials, during which participants developed hyponatraemia, showed no significant difference between the groups (odds ratio 1.45, 95% confidence interval 0.93 to 2.26).

We tested for statistical heterogeneity of treatment effect across trials using the Chi-square statistic for all meta-analyses, and the statistic is presented in each meta-analysis diagram. Results suggest no evidence of statistical heterogeneity (P-value > 0.1) for any outcome considered.

A funnel plot was prepared with the primary outcome. The regression method used to assess funnel plot asymmetry yielded an intercept of -0.104 with a P-value of 0.12, indicating no significant evidence of publication bias.

Sensitivity analysis carried out included studies where allocation concealment was clearly described as adequate and suggested little difference from the original meta-analysis. For example, the pooled odds ratios of the seven trials for the primary outcome with adequate allocation concealment was 0.61 (95% confidence interval 0.46 to 0.82).

A stratified analysis by sodium content of the ORS is presented. Hyponatraemia was not detected in the three studies examining the very low sodium ORS.

 

Discussion

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

We intended to examine treatment effects in cholera subgroup compared with non-cholera diarrhoea. A Cochrane Review of rice-based rehydration compared with glucose oral rehydration solution (ORS) showed that rice water was associated with lower stool volumes in cholera patients but not in diarrhoea from other causes (Fontaine 2000). The available data were insufficient however. Three studies (CHOICE 2001, Bangladesh 1995b, India 2000b) involved cholera patients, but a subgroup analysis for cholera patients was not available for meta-analysis. There were two studies (Farugue 1996, Alam 1999) in patients with cholera excluded from this review because they were in adults. Any recommendation for rehydration treatment for adults with cholera will need to take these and any other trials found through careful systematic searching into account.

This review examines trials of children admitted to hospital who were dehydrated because of diarrhoea. The trials do not provide any direct evidence for or against the use of ORS at home to prevent dehydration developing; nor do they provide any direct evidence that reduced osmolarity ORS is more effective in preventing dehydration in home-based care in this group.

We stand by our selection of unscheduled intravenous fluid infusion rather than volume of diarrhoea as the primary outcome, as specified in the original protocol. Some specialists consider that volume of diarrhoea is more appropriate, probably because it reflects the animal and human perfusion experiments that provide part of the rationale for a reduced osmolarity ORS. Unscheduled intravenous fluid infusion is pragmatic; it provides a measure of failed oral rehydration and has implications for the healthcare resources. For these reasons, we preserved this as the primary outcome.

When we reviewed the studies for inclusion, most trials reported unscheduled intravenous fluid infusion in the details of trial implementation, where exclusions and dropouts were described. As this was identified as our primary outcome at the protocol stage, we sought out these data and presented them as the primary analysis, and it is our opinion this shows a clear effect. This highlights the value for careful attention to the protocol for a systematic review before examining the trials, and provides an illustration of how non-specialist viewpoints can actually help in obtaining practical and useful answers from meta-analysis.

We found that reduced osmolarity ORS has beneficial effects over the WHO standard ORS in reducing needs for unscheduled intravenous fluid infusion, stool output during rehydration, and the number of patients with vomiting during oral rehydration treatment. Reduced osmolarity ORS has no further risk of developing hyponatraemia as compared to the WHO standard ORS. We are currently exploring the feasibility of obtaining data on convulsions (as evidence of symptomatic hyponatraemia) for the authors of the largest trial (CHOICE 2001).

The research evidence presented here relates to the ORS used for treating children with dehydration. ORS is used much more widely for preventing dehydration developing in children with diarrhoea. While this seems appropriate, the applicability to prevention is a judgement, and highlights the need for a systematic review to examine the policies of ORS provision and ORS formula in preventing dehydration in children with diarrhoea.

Findings from this review indicate reduced osmolarity ORS is more effective than WHO standard ORS in the first line treatment of dehydration in children with diarrhoea. It is not easy to be sure however, that this finding applies to a subgroup of patients with severe diarrhoea caused by cholera, where electrolyte loss is profound. This could increase the risk of hyponatraemia, result in adverse clinical events, and attenuate the advantages of reduced osmolarity ORS.

There is the possibility that policymakers and clinicians will judge that cholera reverses the balance of benefits and harms (that is, hyponatraemia will be more common, and outweigh the advantages of reduced osmolarity solution). If this is the case, then one option is to provide WHO standard ORS for people with suspected cholera, or in areas where cholera is prevalent. This is likely to be a logistical problem in areas where diarrhoea is common and coexists with cholera. The single formula sachet aids implementation of this lifesaving intervention. Providing different formulations complicates distribution. It means health workers have a more complicated task in providing the appropriate ORS. These factors may actually impair the effective delivery of any ORS to children.

Policymakers need to be careful if they decide against change a shift to reduced osmolarity solution in areas where cholera is common because of a putative risk around hyponatraemia. If they do this, then they are obliged to prove or disprove their belief in the superiority of WHO standard ORS through a randomized controlled trial in children with clinical cholera. The WHO has convened a expert working group to consider this review and related evidence. The group recommended that ORS for treating diarrhoea in children with non-cholera diarrhoea will be enhanced by shifting to a reduced osmolarity ORS, and propose a global shift to ORS with an osmolarity of 75 mEq/L of sodium (WHO 2001).

 

Authors' conclusions

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

 

Implications for practice

Oral rehydration solution (ORS) has saved many children's lives in low and middle income countries, and the sachets are widely used in primary care, based on standards set by the World Health Organization (WHO). This review summarized data from existing studies, and provide some evidence that dehydrated children given a solution with a lower osmolarity were less likely to need an intravenous infusion than those given WHO standard ORS. These results have important implications for policy, and WHO and UNICEF, based on this review, related data, and expert discussions, are recommending reduced osmolarity ORS be accepted as standard (WHO 2001).

 
Implications for research

We found insufficient data on cholera in children to make recommendations for this condition. Since cholera is a secretory diarrhoea and electrolyte loss is profound, if reduced osmolarity ORS is to be used in cholera, more trials to investigate this should be undertaken.

There is a need for a good systematic review examining the influence of policies of ORS provision in preventing dehydration and hospital admissions in children with diarrhoea.

 

Acknowledgements

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

To: Christopher Duggan; Olivier Fontaine; Sheila Bird for comments. We note that the data presented and the views expressed are entirely the responsibility of the authors.

 

Data and analyses

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
Download statistical data

 
Comparison 1. Reduced osmolarity ORS compared to WHO standard ORS

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Need for unscheduled intravenous fluid infusion111996Odds Ratio (M-H, Fixed, 95% CI)0.59 [0.45, 0.79]

 2 Stool output111776Std. Mean Difference (IV, Fixed, 95% CI)-0.23 [-0.33, -0.14]

 3 Episode of vomiting during rehydration61305Peto Odds Ratio (Peto, Fixed, 95% CI)0.71 [0.55, 0.92]

 4 Presence of hyponatremia after rehydration61120Peto Odds Ratio (Peto, Fixed, 95% CI)1.44 [0.93, 2.24]

 5 Need for unscheduled intravenous fluid infusion (sensitivity analysis)71688Odds Ratio (M-H, Fixed, 95% CI)0.61 [0.46, 0.82]

 6 Stool output (sensitivity analysis)61550Std. Mean Difference (IV, Fixed, 95% CI)-0.21 [-0.31, -0.11]

 
Comparison 2. Reduced osmolarity ORS (stratified by sodium concentration) compared to WHO standard ORS

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Need for unscheduled intravenous fluid infusion91925Odds Ratio (M-H, Fixed, 95% CI)0.59 [0.44, 0.78]

    1.1 60 to 74 mmol
4584Odds Ratio (M-H, Fixed, 95% CI)0.70 [0.43, 1.15]

    1.2 75 mmol to 84 mmol
51341Odds Ratio (M-H, Fixed, 95% CI)0.53 [0.37, 0.76]

 2 Stool output71591Std. Mean Difference (IV, Fixed, 95% CI)-0.20 [-0.30, -0.10]

    2.1 60 to 74 mmol
4586Std. Mean Difference (IV, Fixed, 95% CI)-0.31 [-0.47, -0.15]

    2.2 75 to 84 mmol
31005Std. Mean Difference (IV, Fixed, 95% CI)-0.13 [-0.26, -0.01]

 3 Episodes of vomiting61305Odds Ratio (M-H, Fixed, 95% CI)0.70 [0.54, 0.91]

    3.1 60 to 74 mmol
2104Odds Ratio (M-H, Fixed, 95% CI)0.59 [0.24, 1.47]

    3.2 75 to 84 mmol
41201Odds Ratio (M-H, Fixed, 95% CI)0.71 [0.54, 0.93]

 4 Presence of hyponatraemia61171Odds Ratio (M-H, Fixed, 95% CI)1.45 [0.93, 2.26]

    4.1 60 to 74 mmol
3190Odds Ratio (M-H, Fixed, 95% CI)Not estimable

    4.2 75 to 84 mmol
3981Odds Ratio (M-H, Fixed, 95% CI)1.45 [0.93, 2.26]

 

Appendices

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Appendix 1. Stool output


TrialsOutcomeValueORSDifferences

Low osmolarityWHO standard

WHO 1995Stool output at 24 h (g/kg)Geometric meann = 221; mean = 65; 95% confidence interval 58 to 73n = 218; mean = 86; 95% confidence interval 77 to 96Ratio standard/reduced = 1.32 95% confidence interval 1.12 to 1.54

India 2000aStool output during observation period (g/kg/d)Arithmetic meann = 33; mean = 61.0; standard deviation = 24.5n = 37; mean = 75.0; standard deviation = 29.4

Egypt 1996bStool output for rehydration phase (g/kg)Geometric meann = 94; mean = 11; 95% confidence interval 8 to 14n = 96; mean = 15; 95% confidence interval 12 to 20

Bangladesh 1995aStool output at 0 to 24 h (ml/kg)Arithmetic meann = 19; mean = 156; standard deviation = 113.4n = 19; mean = 193; standard deviation = 71.2

Colombia 2000Stool output for rehydration period (g/kg/h)Arithmetic meann = 71; mean = 5.6; standard deviation = 5.1n = 69; mean = 6.3; standard deviation = 5.0

Egypt 1994Stool output at 24 h (g/kg)Arithmetic meann = 20; mean = 165; standard deviation = 52n = 21; mean = 260; standard deviation 114

Bangladesh 1995bStool output at 0 to24 h (ml/kg)Arithmetic meann = 30; mean = 109; standard deviation = 73.8n = 30; mean = 110; standard deviation = 42.7

Bangladesh 1996aStool output at 0 to 24 h (g/kg)Arithmetic meann = 18; mean = 80.9; standard deviation = 45.3n = 28; mean = 117.8; standard deviation = 81.0

India 1984a; India 1984bStool output at 24 h (ml/kg)Arithmetic meann = 22; mean = 82.3; standard deviation = 60n = 22; mean = 88.1; standard deviation = 58.2

Panama 1982Stool output during first 8 h (ml/kg/h)Arithmetic meann = 33; mean = 4.3; standard deviation = 4.6n = 30; mean = 4.3; standard deviation = 3.3

USA 1982Stool output during the first 8 h (ml/kg/h)Arithmetic meann = 15; mean = 4.2; standard deviation = 3.9n = 20; mean = 4.6; standard deviation = 4.0

CHOICE 2001Stool output at 24 h (g/kg)Arithmetic meann = 341; mean = 114; standard deviation = 73.9n = 334; mean = 125; standard deviation = 91.4



 

What's new

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

Last assessed as up-to-date: 27 November 2001.


DateEventDescription

22 October 2008AmendedConverted to new review format with minor editing.



 

History

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

Protocol first published: Issue 4, 2000
Review first published: Issue 2, 2001


DateEventDescription

27 July 2004AmendedNew studies found but not yet included or excluded.

27 November 2001AmendedChanges made in response to feedback from specialists at the WHO/UNICEF oral rehydration salts formulation expert consultation. New York, 18 July 2001.

  1. Seizures outcomes to be sought (changes in progress)
  2. Egypt 1996a testing maltodextran excluded
  3. Secondary analysis stratifying by sodium levels (60 to 74, 75 to 85 mmol)



 

Contributions of authors

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

Seokyung Hahn and Yaejean Kim wrote the protocol, conducted the data extraction, data analysis and interpretation, and drafted the paper. Paul Garner advised on inclusion criteria and outcomes for the protocol, quality assessment and analysis, and helped write the review. Paul Garner is the guarantor.

 

Declarations of interest

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

We certify that we have no affiliations with or involvement in any organisation or entity with a direct financial interest in the subject matter of the review (eg employment, consultancy, stock ownership, honoraria, expert testimony).

The World Health Organization provided funds for us to conduct this review.

 

Sources of support

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Internal sources

  • Liverpool School of Tropical Medicine, UK.
  • Medical and Pharmaceutical Statistics Research Unit, University of Reading, UK.
  • Seoul National University Hospital, Korea, South.

 

External sources

  • World Health Organization, Switzerland.
  • Department for International Development, UK.

References

References to studies included in this review

  1. Top of page
  2. Abstract摘要
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Characteristics of studies
  18. References to studies included in this review
  19. References to studies excluded from this review
  20. Additional references
  21. References to other published versions of this review
Bangladesh 1995a {published data only}
Bangladesh 1995b {published data only}
Bangladesh 1996a {published data only}
CHOICE 2001 {published data only}
  • CHOICE study group. Multicenter randomized double blind clinical trial to evaluate the efficacy and safety of a reduced osmolarity oral rehydration solution in children with acute watery diarrhoea. Pediatrics 2001;107:613-8.
Colombia 2000 {published data only}
  • Bernal C, Velasquez C, Garcia G, Uribe G, Palacio C. Oral rehydration with a low-osmolarity solution in children dehydrated by diarrheric diseases. A controlled clinical study [Hidratacion oral con una solucion de baja osmolaridad en ninos deshidratados por enfermedades diarreicas: un estudio clinico controlado]. Saludarte 2000;1:6-23.
Egypt 1994 {published data only}
  • El-Mougi M, El-Akkad N, Hendawi A, Hassan M, Amer A, Fontaine O, Pierce N F. Is a low-osmolarity ORS solution more efficacious than standard WHO ORS solution?. Journal of Pediatric Gastroenterology and Nutrition 1994;19(1):83-6.
Egypt 1996b {published data only}
  • Santosham M, Fayad I, Zikiri MA, Hussein A, Amponsah A, Duggan C, et al. A double-blind clinical trial comparing World Health Organization oral rehydration solution with a reduced osmolarity solution containing equal amounts of sodium and glucose. Journal of Pediatrics 1996;128(1):45-51.
India 1984a {published data only}
  • Bhargava SK, Sachdev HP, Das Gupta B, Daral TS, Singh HP, Mohan M. Oral rehydration of neonates and young infants with dehydration diarrhea: compararison of low and standard sodium content in oral rehydration solutions. Journal of Pediatric Gastroenterology and Nutrition 1984;3(4):500-5. [MEDLINE: 85009156]
India 2000a {published data only}
  • Dutta P, Dutta S, Manna B, Chatterjee MK, De A, Bhattacharya SK. Hypo-osmolar oral rehydration salts solution in dehydrating persistent diarrhoea in children: double-blind, randomized, controlled clinical trial. Acta Paediatrica 2000;89:411-6.
India 2000b {published data only}
  • Alam S, Afzal K, Maheshwari M, Shukia I. Controlled trial of hypo-osmolar versus World Health Organization oral rehydration solution. Indian Pediatrics 2000;37:952-9.
Mexico 1990a {published data only}
  • Moreno-Sanchez H, Velasques-Jones L, Becerra FC, Faure A, Maulen I, Leon M de, et al. A comparative study on two oral rehydration solutions(ORS) containing 60 or 90 mmol/L of sodium and of different osmolalities [Estudio comparativo de dos soluciones de hidratacion oral conteniendo 60 o 90 mmol/L de sodio y con diferente osmolalidad]. Boletin Medico del Hospital Infantil de Mexico 1990;47(9):630-5.
Panama 1982 {published data only}
  • Santosham M, Daum L Dillman RS, Rodriguez JL, Luque S, Russel R, et al. Oral rehydration therapy of infantile diarrhea: a controlled study of well-nourished children hospitalized in the United States and Panama. New England Journal of Medicine 1982;306(18):1070-6.
USA 1982 {published data only}
  • Santosham M, Daum L, Dillman RS, Rodriguez JL, Luque S, Russel R, et alA, Benenson AS, Sack RB. Oral rehydration therapy of infantile diarrhea: a controlled study of well-nourished children hospitalized in the United States and Panama. New England Journal of Medicine 1982;306(18):1070-6.
WHO 1995 {published data only}
  • International Study Group on Reduced-osmolarity ORS solutions. Multicentre evaluation of reduced-osmolarity oral rehydration salts solution. Lancet 1995;345:282-5.

References to studies excluded from this review

  1. Top of page
  2. Abstract摘要
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Characteristics of studies
  18. References to studies included in this review
  19. References to studies excluded from this review
  20. Additional references
  21. References to other published versions of this review
Australia 1990 {published data only}
  • Cleghorn GJ, Shepherd RW, Patrick MK. Comparison of two oral rehydration solutions in children with gastroenteritis in Australia. Clinical Therapeutics 1990;12 Suppl A:81-5.
Australia 1993 {published data only}
  • Wall CR, Shepherd RW, Patric M, Chin S, Cleghorn G. Osmolality electrolyte and carbohydrate type and oral rehydration solutions: A controlled study to compare the efficacy of two commercially available solutions(osmolalities 240 mmol/L and 34 mmol/L). Journal of Diarrhoeal Diseases Research 1993;11(4):222-6.
Bangladesh 1978 {published data only}
  • Sack DA, Chowdhury AMAK, Eusof A, Ali MA, Merson MH, Islam S, et al. Oral hydration in rotavirus diarrhoea: a double blind comparison of sucrose with glucose electrolyte solution. Lancet 1978;2:280-3.
Bangladesh 1991 {published data only}
  • Akbar MS, Baker KM, Aziz MA, Khan WA, Salim AFM. A randomised, double-blind clinical trial of a maltodextrin containing oral rehydration solution in acute infantile diarrhoea. Journal of Diarrhoeal Diseases Research 1991;9(1):33-7.
Bangladesh 1996b {published data only}
Bangladesh 1999 {published data only}
  • Alam NH, Majumder RN, Fuchs GJ, CHOICE group. Efficacy and safety of oral rehydration solution with reduced osmolarity in adults with cholera: a randomised double-blind clinical trial. Lancet 1999;354:296-9.
Costa Rica 1987 {published data only}
  • Pizarro D, Castillo B, Posada G, Lizano C, Mata L. Efficacy comparison of oral rehydration solutions containing either 90 or 75 millimoles of sodium per liter. Pediatrics 1987;79(2):190-5.
Ecuador 1995 {published data only}
Egypt 1996a {published data only}
  • El-Mougi M, Hendawi A, Koura H, Hegazi E, Fontaine O, Pierce NF. Efficy of standard glucose-based and reduced osmolarity maltodextrin-based oral rehydration solution: effect of sugar malabsorption. Bulletin of the World Health Organization 1996;74(5):471-7.
Finland 1985 {published data only}
Finland 1986 {published data only}
Finland 1993 {published data only}
Finland 1997 {published data only}
Finland 1998 {published data only}
  • Rautanen T, Isolauri E, Salo E, Vesikari T. Management of acute diarrhoea with low osmolarity oral rehydration solutions and Lactobacillus strain GG. Archives of Disease in Childhood 1998;79:157-60.
France 1990 {published data only}
  • Mallet E, Guillot M, Le Luyer B, Morin C, Pollet F, De Meynard C. Comparison of two oral rehydration solutions in eutrophic infants with moderate acute diarrhea: results of an interim analysis. Clinical Therapeutics 1990;12 Suppl A:104-12.
Guinea-Bissau 1999 {published data only}
  • Valentiner-Branth P, Steinsland H, Gjessing HK, Santos G, Bhan MK, Dias F, et al. Community-based randomized controlled trial of reduced osmolarity oral rehydration solution in acute childhood diarrhea. Pediatric Infectious Diseases Journal 1999;18:789-95.
India 1978 {published data only}
India 1984b {published data only}
Iran 1983 {published data only}
Mexico 1988 {published data only}
  • Martinez-Pantaleon 0, Faure-Vilchis A, Gomez-Najera RI, Hernandez-Lopez M, Velasquez-Jones L. Comparative study of oral rehydration solutions containing either 90 or 60 millimoles of sodium per liter. [Estudio comparativo de dos soluciones de rehidratacion oral conteniendo 90 o 60 milimoles de sodio por litro]. Boletin Medico del Hospital Infantil de Mexico 1998;45(12):817-22. [MEDLINE: 89193920]
Mexico 1990b {published data only}
  • Velasquez-Jones L, Becerra F, Faure A, de Leon M, Moreno H, Maulen I, et al. Clinical experience in Mexico with a new oral rehydration solution with lower osmolality. Clinical Therapeutics 1990;12 Suppl A:95-103.
Myanmar 1991 {published data only}
  • Khin-Maunh-U, Myo-Khin, Nyunt-Nyunt-Wai, Mu-Mu-Khin, Mya-Thi, Thein-Thein-Myint. Comparison of glucose/elctrolyte and maltodextrin/glycine/glycyl-glycine/electrolye oral rehydration solution in acute diarrhea in children. Journal of Pediatric Gastroenterology and Nutrition 1992;13:397-401.
Russia 1997 {published data only}
Turkey 1985 {published data only}
  • Sokucu S, Marin L, Gunoz H, Aperia A, Neyzi O, Zetterstrom R. Oral rehydration therapy in infectious diarrhoea. Comparison of rehydration solutions with 60 and 90 mmol sodium per litre. Acta Paediatrica Scandinavica 1985;74:489-84.
Turkey 1986 {published data only}
USA 1972 {published data only}
  • Hirschhorn N, Cash RA, Woodward WE, Spivey GH. Oral fluid therapy of Apache children with acute infectious diarrhoea. Lancet 1972;7766:15-8.
USA 1986 {published data only}
  • Santosham M, Burns BA, Reid R, Letson W, Duncan B, Powlesland JA, et al. Glycine-based oral rehydration solutioin: reassessment of safety and efficacy. Jounal of Pediatrics 1986;109(5):795-801.

Additional references

  1. Top of page
  2. Abstract摘要
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Characteristics of studies
  18. References to studies included in this review
  19. References to studies excluded from this review
  20. Additional references
  21. References to other published versions of this review
Alam 1999
  • Alam NH, Majumder RN, Fuchs GJ, CHOICE study group. Efficacy and safety of oral rehydration solution with reduced osmolarity in adults with cholera: a randomised double-blinded clinical trial. Lancet 1999;354:296-9.
Almroth 1995
Egger 1997
Farthing 1988
Farugue 1996
Finberg 1973
Fontaine 2000
  • Fontaine O, Gore SM, Pierce NF. Rice-based oral rehydration solution for treating diarrhoea (Cochrane Review). Cochrane Database of Systematic Reviews 2000, Issue 3. [DOI: 10.1002/14651858]
Fordtran 1968
Grant 1983
  • Grant JP. The state of the world's children 1982-1983. UNICEF. New York: UNICEF, 1983.
Guarino 2001
Hunt 1992
Mahalanabis 1973
QUOROM Group 1999
  • Moher D, Cook DJ, Eastwood S, Okin I, Rennie D, Stroup DF, for the Quorum Group. Improving the quality of reports of meta-analyses of randomised controlled trials: the QUORUM statement. Lancet 1999;354:1896-1900.
WHO 2001
  • World Health Organization. Expert consultation on oral rehydration salts (ORS) formulation. Child and Adolescent Health and Development 2001; Vol. WHO/FCH/CAH/01.22:[18 July 2001].