Intervention Review

You have free access to this content

Polymer-based oral rehydration solution for treating acute watery diarrhoea

  1. Germana V Gregorio1,*,
  2. Maria Liza M Gonzales1,
  3. Leonila F Dans2,
  4. Elizabeth G Martinez1

Editorial Group: Cochrane Infectious Diseases Group

Published Online: 14 APR 2009

Assessed as up-to-date: 10 NOV 2008

DOI: 10.1002/14651858.CD006519.pub2


How to Cite

Gregorio GV, Gonzales MLM, Dans LF, Martinez EG. Polymer-based oral rehydration solution for treating acute watery diarrhoea. Cochrane Database of Systematic Reviews 2009, Issue 2. Art. No.: CD006519. DOI: 10.1002/14651858.CD006519.pub2.

Author Information

  1. 1

    College of Medicine-Philippine General Hospital, University of the Philippines, Department of Pediatrics, Manila, National Capital Region, Philippines

  2. 2

    Philippine General Hospital, University of the Philippines, Departments of Pediatrics and Clinical Epidemiology, Manila, National Capital Region, Philippines

*Germana V Gregorio, Department of Pediatrics, College of Medicine-Philippine General Hospital, University of the Philippines, Taft Avenue, Manila, National Capital Region, 1000, Philippines. germana1@hotmail.com.

Publication History

  1. Publication Status: Unchanged
  2. Published Online: 14 APR 2009

SEARCH

 

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. Contributions of authors
  12. Declarations of interest
  13. Sources of support
  14. Differences between protocol and review
  15. Index terms

Acute diarrhoea, which is defined as three or more loose bowel movements in a 24-hour period (WHO/ICDDRB 1995), is one of the principal causes of morbidity and mortality among children in low-income countries. A 2003 review of 27 prospective studies from 20 countries published from 1990 to 2000 estimated the incidence of diarrhoea as 3.8 episodes per child per year for children less than 11 months of age and 2.1 episodes per child per year for children aged one to four years (Kosek 2003). It has a negative impact on quality of life and can result in considerable healthcare costs. Most of these diarrhoeal illnesses occur in low-income countries and are largely caused by infection. The cause is mainly viral in children aged less than five years, while both bacterial and viral pathogens are implicated in adults (Casburn-Jones 2004). Other causes of acute diarrhoea are disordered motility, such as irritable bowel syndrome, intake of certain drugs, or ileal bile acid malabsorption.

Since the 1980s, efforts to decrease the number of deaths from diarrhoea have been based on several interventions, including the improvement of water quality and sanitation, promotion of breastfeeding, and the introduction of treatment programmes that include oral rehydration therapy (Claeson 1990). Oral rehydration solution (ORS) was introduced in 1979 by the World Health Organization (WHO), and it rapidly became the cornerstone of programmes for the control of diarrhoeal diseases (Claeson 1990). The osmolarity of the original formulation is 310 mOsm/L (referred to as ORS ≥ 310) and consists of glucose (111 mmol/L), sodium (90 mmol/L), potassium (20 mmol/L), chloride (80 mmol/L), and citrate (10 mmol/L) or bicarbonate (30 mmol/L). The ORS was shown to improve signs of dehydration, including thirst, sunken eyeballs, sunken fontanelles, poor skin turgor, or a decreased or absence of urine output (WHO/ICDDRB 1995). It is considered as both safe and effective (Santosham 1991), and, since its introduction, it has been considered to be mainly responsible for the decrease in case-fatality rates from acute dehydrating diarrhoea (Victora 2000).

The physiological basis for the use of ORS ≥ 310 was the co-transport of glucose and sodium across the intestinal membrane (Santosham 1991). While this glucose-based ORS is effective in replacing the fluid from acute diarrhoea thus preventing further dehydration, it neither reduces stool loss nor shortens the duration of illness (Santosham 1991). Increasing the glucose concentration to greater than 111 mmol/L increases the osmotic load of the solution, which may further aggravate the fluid loss and induce hypernatraemia (Hunt 1992). In 2004, the WHO recommended a different formulation in which the glucose and sodium content were each reduced to 75 mmol/L to give a total osmolarity of 245 mOsm/L (referred to as ORS ≤ 270) (WHO 2004). ORS ≤ 270 reduces stool volume, shortens the duration of diarrhoea, and decreases the need for unscheduled intravenous therapy compared with ORS ≥ 310 (Hahn 2002).

New ORS formulations have been evaluated in attempts to improve the efficacy of ORS ≥ 310. Glucose polymer-based ORS (referred to as polymer-based ORS) may contain whole rice (amylopectins), as in rice-based ORS or rice syrups (maltodextrins). The difference is that the latter contains only a small amount of amino acids and protein. Other sources of polymers are wheat, sorghum, and maize (high amylase-resistant starch). In these polymer-based solutions, the glucose is slowly released after digestion and is absorbed in the small bowel, enhancing the reabsorption of water and electrolyte secreted into the bowel lumen during diarrhoea (Carpenter 1988; Pizarro 1991). Although ORS ≥ 310 is no longer recommended it remains unknown whether a polymer-based ORS is indeed more effective than a glucose-based ORS (ie ORS ≥ 310 or ORS ≤ 270).

A 1998 Cochrane Review of rice-based ORS for treating diarrhoea concluded that it significantly reduced the mean 24-hour stool output in adults and children with cholera or cholera-like diarrhoea, but results were inconclusive for infants and children with non-cholera diarrhoea (Fontaine 1998). Our Cochrane Review has updated the evidence on the use of polymer-based ORS (both rice and non-rice based) and expanded the primary outcome measures to include the number of participants who required unscheduled use of intravenous fluid therapy. Other primary outcome measures focus on the duration of diarrhoea and the stool output in the first 24 hours since these are considered crucial in the management of these patients and the first 24 hours is the period of greatest stool loss. Our Cochrane Review also aims to provide more insights into whether polymer-based ORS is more effective than glucose-based ORS, and to inform future research.

Patients are dehydrated during the first six to eight hours, but once rehydrated, feeding is initiated and stool losses are replaced volume per volume with the ORS. The effect of feeding a rice-based or starch-based food as soon as the participants are rehydrated could confound the effects of glucose polymer-based ORS (Alam 1992).

 

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. Contributions of authors
  12. Declarations of interest
  13. Sources of support
  14. Differences between protocol and review
  15. Index terms

To compare polymer-based oral rehydration solution (ORS) with glucose-based ORS for treating acute watery diarrhoea.

 

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. Contributions of authors
  12. Declarations of interest
  13. Sources of support
  14. Differences between protocol and review
  15. Index terms
 

Criteria for considering studies for this review

 

Types of studies

Randomized controlled trials.

 

Types of participants

Infants, children, and adults with acute watery diarrhoea (cholera and non-cholera associated) and mild, moderate, or severe dehydration, as defined by trial authors.

We excluded trials enrolling patients who were unable to drink or take in oral fluids, those in shock, and those with bloody diarrhoea or dysentery.

 

Types of interventions

 

Intervention: polymer-based ORS

ORS in which glucose was replaced by a commercial or a local preparation of a polymer (eg rice, wheat, maltodextrins, maize, sorghum, or corn), the electrolyte composition remaining unchanged between the two solutions.

 

Control: glucose-based ORS

ORS that contains glucose as a carbohydrate source with either 90 or 60 to 75 mmol/L of sodium.

 

Types of outcome measures

 

Primary

  • Total stool output (g/kg) during the first 24 hours after randomization.
  • Total stool output (g/kg) from randomization to cessation of diarrhoea.
  • Duration of diarrhoea (hours) from randomization until cessation of diarrhoea.

 

Secondary

  • Unscheduled intravenous fluid therapy.
  • Cases of vomiting.

 

Adverse events

  • All adverse events including hyponatraemia (serum sodium level ≤130 mmol/L) (low sodium), hypokalaemia (≤ 3 mol/L) (low potassium), and development of persistent diarrhoea.

 

Search methods for identification of studies

All relevant trials regardless of language or publication status (published, unpublished, in press, and ongoing).

 

Databases

We searched the following databases using the search terms and strategy described in Appendix 1: Cochrane Infectious Diseases Group Specialized Register (September 2008); Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library (2008, Issue 2); MEDLINE (1966 to September 2008); EMBASE (1974 to September 2008); and LILACS (1982 to September 2008). We also searched the metaRegister of Controlled Trials (mRCT) using 'diarrhoea' and 'oral rehydration solution' as search terms.

 

Researchers, organizations, and pharmaceutical companies

To help identify unpublished and ongoing trials, we conducted a communications or website search (May 2006 to September 2008) with individual researchers working in the field of general paediatrics and gastroenterology, and the following organizations who may be funding a similar study: WHO – Dr. Kevin Palmer, Regional Adviser, Waterborne and Parasitic Diseases, WHO Regional Office for the Western Pacific, Manila, Philippines; INCLEN (www.inclen.org); USAID (www.usaid.gov); Asian Development Bank (www.adb.org); and World Bank (www.worldbank.org). We also searched United Laboratories Philippines (www.unilab.com.ph) and Abbott International (www.abbott.com.ph) (pharmaceutical companies who manufacture oral rehydration solution) for any unpublished or ongoing trials.

 

Reference lists

We checked the reference lists of all studies identified by the above methods.

 

Data collection and analysis

 

Selection of studies

Two authors (GV Gregorio and LF Dans) independently assessed the results of the literature search to determine whether the title or abstract cited a randomized controlled trial. We retrieved the full reports of clinical trials considered by one or both authors to be potentially relevant as well as trials with unclear treatment allocation. We independently assessed the inclusion criteria of these trials using a standard eligibility form. We resolved any disagreements through discussion, or if this failed, by consulting another author (MLM Gonzales). We scrutinized trial reports to ensure multiple publication would be detected. We listed the excluded studies and the reasons for the exclusion.

 

Data extraction and management

Two authors (GV Gregorio and EG Martinez or MLM Gonzales) independently extracted the data from the trials using pre-tested data extraction forms. We extracted the number of participants who were randomized and the number analysed for all outcomes for each treatment arm in each trial to determine loss to follow up, whether loss was comparable across treatments, and to determine the type of analysis used. Since the primary outcome measures were continuous, we extracted arithmetic means and standard deviations for each treatment group and noted the number of participants in each group. In trials with multiple interventions (two or more different polymer-based ORS that were used as treatment groups) we pooled the means and standard deviations of the different polymer-based ORS across the treatment arms.

For dichotomous outcome measures, we recorded the number(s) experiencing the event and the numbers analysed in each treatment group. In the meta-analysis, for multiple treatment arms, we combined the numbers experiencing the outcome in two or more experimental interventions as appropriate and compared collectively with the control group.

We resolved any disagreements about data extracted by referring to the trial report and through discussion, or, if that failed, by consulting with another author. Where data were insufficient or missing, we attempted to contact the trial authors. GV Gregorio entered the data into Review Manager 5.

 

Assessment of risk of bias in included studies

Two authors (GV Gregorio and LF Dans or MLM Gonzales) independently assessed the risk of bias (methodological quality) of each trial using a prepared assessment form. We assessed the generation of allocation sequence and allocation concealment as adequate, inadequate, or unclear according to Jüni 2001. We also noted who was blinded, such as the trial participants, care providers, or outcome assessors, and classified the inclusion of randomized participants in the analysis as adequate if greater than 90% or inadequate if 90% or less. We used the results of the assessment to perform a sensitivity analysis. In the case of unclear or missing information, we made attempts to contact the authors. We resolved disagreements by discussion between review authors.

 

Assessment of reporting biases

We assessed the presence of publication bias by looking for asymmetry in the funnel plots. We also assessed asymmetry of the funnel plots using StatsDirect and considered a P value < 0.05 on Egger's bias test as significant.

 

Data synthesis

GV Gregorio analysed the data using Review Manager 5 and presented the results with 95% confidence intervals (CI). We determined and reported the percentage lost to follow up for all trials from the numbers randomized and the numbers analysed in each treatment group. Analyses were based on a complete-case approach. For the participants who did not adhere to the study protocol, their outcome was based on what was reported by the author (if an intention-to-treat analysis was done) or on data sought from the trial authors (if there was no intention-to-treat analysis).

We presented risk ratios (RR) for dichotomous outcomes. We determined continuous outcomes summarized as arithmetic means and standard deviations data using the mean difference (MD).

We checked the normality of the data by calculating the ratio of the mean over the standard deviation. If the ratio (mean/SD) was less than two, then it was likely that the data were skewed and therefore were not combined in the meta-analysis.

 

Subgroup analysis and investigation of heterogeneity

We evaluated the presence of statistical heterogeneity among the interventions by inspecting the forest plot and by performing a Chi2 test for heterogeneity using a P value of 0.10 to determine statistical significance. Also, we used a I2 value of 50% as an indication of moderate heterogeneity. If there was statistically significant heterogeneity, we used the random-effects model (DerSimonian and Laird method) to combine data, otherwise we applied a fixed-effect model.

We investigated heterogeneity using subgroup analyses. We subgrouped trials according to the osmolarity of glucose ORS (ORS ≥ 310 or ORS ≤ 270) and type of polymer (rice, wheat, maltodextrins, and sorghum). We also evaluated the effect of the participant age (< 19 years (paediatric) and ≥ 19 years (adult)) and of cholera as a pathogen. When there was substantial statistical heterogeneity (ie I2 = 100%), we did not combine the trials in the meta-analysis.

 

Sensitivity analysis

We performed sensitivity analyses to assess the robustness of the meta-analysis by excluding trials of a low methodological quality, that is, those that used an inadequate method of randomization, unconcealed treatment allocation, and inadequate inclusion of randomized participants in the analysis.

 

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. Contributions of authors
  12. Declarations of interest
  13. Sources of support
  14. Differences between protocol and review
  15. Index terms
 

Description of studies

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

 

Search results

Of the 212 clinical trials included in the primary search until 26 September 2008, 69 were assessed for inclusion in the review (none were multiple publications). Thirty-five trials met the inclusion criteria (see 'Characteristics of included studies'). We excluded the remaining 35 trials for the following reasons (see also 'Characteristics of excluded studies'): electrolyte composition of the intervention and the control group were not identical or not known (11); composition of treatment group was either unknown or not a polymer (eight); not a clinical trial on ORS but on the use of drugs in acute diarrhoea (four); control group used an oral saline solution (one) or an ORS that did not contain either a 90 or a 60 to 75 mmol/L of sodium (three); not a randomized controlled trial (one); no control group (one); not an efficacy but an effectiveness study (two); patients with persistent and not acute diarrhoea (two); and in two clinical trials, the primary or secondary outcome of interest of this review was not reported. Communication with researchers, an organization, and pharmaceutical companies yielded no further information with regards to unpublished or ongoing clinical trials on polymer-based ORS.

 

Setting

Most trials were conducted in India (10) and Bangladesh (nine). Other study centres were in Egypt (three) (El-Mougi 1988; Fayad 1993; El-Mougi 1996), Chile (two) (Guiraldes 1995a; Guiraldes 1995b), Mexico (two) (Maulen-Radovan 1994; Maulen-Radovan 2004), and one trial each was done in Australia (Wall 1997), Colombia (Bernal 2005), Madagascar (Razafindrakoto 1993), Malaysia (Iyngkaran 1998), Pakistan (Islam 1994), Philippines (Santos Ocampo 1993), Romania (Nanulescu 1999), and Sudan (Mustafa 1995). Only two trials were not done in a hospital setting. One was done in a paediatric clinic (Nanulescu 1999) and one in a rural treatment centre (Zaman 2007).

 

Participants

The 34 eligible trials included 4214 participants: 2269 used polymer-based ORS and 1945 used glucose-based ORS. In the individual trials, there was no statistically significant difference in the baseline characteristics between the two groups.

Age

Twenty-seven trials included children only (26 in children < five years old), five included adults only (Alam 1992; Bhattacharya 1998; Ramakrishna 2000; Hossain 2003), and two included both adults and children (Molla 1985; Dutta 1998). The two trials that included both adults and children randomized and reported the outcomes separately for each group.

Pathogen

In terms of the aetiology of diarrhoea, only eight trials randomized exclusively Vibrio cholerae positive patients (Molla 1989a; Alam 1992; Bhattacharya 1998; Dutta 1998; Dutta 2000; Ramakrishna 2000; Zaman 2001; Hossain 2003), while 21 included participants with mixed pathogens (both cholera and non-cholera), and five did not report the pathogen (El-Mougi 1988; Molla 1989b; Fayad 1993; Mustafa 1995; Sharma 1998).

 

Interventions

Twenty-eight trials compared two interventions (polymer versus glucose-based ORS), five trials compared three interventions (rice ORS versus non-rice ORS versus glucose-based ORS) (Alam 1987; Dutta 1988; Mustafa 1995; Ramakrishna 2000), and one trial≤ (Molla 1989b) compared six interventions (rice, millet, maize, potatoes, sorghum, and wheat ORS versus glucose-based ORS). Only five trials used an ORS ≤ 270 mOsm/L (Bhattacharya 1998; Iyngkaran 1998; Nanulescu 1999; Dutta 2000; Maulen-Radovan 2004), while 29 used ORS ≥ 310 mOsm/L.

Twenty-five trials used a variety of rice (uncooked, cooked, powdered, and pop rice) as a source of polymer, three utilized maltodextrins (Akbar 1991; Santos Ocampo 1993; El-Mougi 1996), two trials used amylase-resistant starch (Ramakrishna 2000; Ramakrishna 2008), and one trial each employed plain flour (Bernal 2005), mung beans (Bhan 1987) (with another arm of the trial using pop rice), and wheat (Alam 1987) (another arm using rice). One trial compared the efficacy of glucose ORS with several polymers in the form of wheat, millet, maize, rice, sorghum, and potatoes (Molla 1989b).

The polymer was prepared locally in 23 trials and obtained commercially in eight trials (Santos Ocampo 1993; Maulen-Radovan 1994; Guiraldes 1995a; Guiraldes 1995b; El-Mougi 1996; Faruque 1997; Zaman 2001; Maulen-Radovan 2004). The source was not reported in three trials (Akbar 1991; Nanulescu 1999; Hossain 2003).

Only one trial withheld feeding in the first 24 hours (Molla 1989b). In another trial (Alam 1992), the patients were randomized into the rice- and glucose-based ORS and further stratified as with and without food intake (Alam 1992). In this, only the data on participants with food intake were used in the review. Feeding was immediately started after hydration in 25 trials, while in seven the onset of refeeding was unclear (Patra 1982; Molla 1985; Bhattacharya 1998; Dutta 1998; Iyngkaran 1998; Dutta 2000; Ramakrishna 2000).

 

Outcomes reported

Most of the 34 trials reported the total stool output in the first 24 hours (25), total stool output from randomization to discharge (18), duration of diarrhoea (26), and unscheduled use of intravenous fluid (19). However, some of these outcomes were measured and reported in different units by the different studies and therefore not all the data could be used in the meta-analysis. Furthermore, we did not include the data in the meta-analyses if they were skewed: data for total stool output in 24 hours (Molla 1989a; Santos Ocampo 1993; Maulen-Radovan 2004; Bernal 2005); data on duration of diarrhoea (Santos Ocampo 1993; Mustafa 1995; Wall 1997); and data on total stool output from randomization to discharge (Santos Ocampo 1993).

There were a few trials that reported the number of participants with vomiting (nine) (Patra 1982; Bhan 1987; El-Mougi 1988; Mohan 1988; Alam 1992; Islam 1994; Mustafa 1995; Dutta 1998; Iyngkaran 1998), hyponatraemia (six) (Dutta 1988; Guiraldes 1995a; Bhattacharya 1998; Dutta 2000; Zaman 2001; Ramakrishna 2008), hypokalaemia (two) (Bhan 1987; Zaman 2007), and development of persistent diarrhoea (two) (Fayad 1993; Faruque 1997).

 

Risk of bias in included studies

See Appendix 2 for a summary of the assessment and the 'Characteristics of included studies' for details of each trial's methods.

Of the 34 trials, the methods used to generate the allocation sequence were adequate (computer-generated or random-numbers table) in 24 trials and unclear in the remaining 10 trials (Patra 1982; Bhan 1987; Mohan 1988; Molla 1989a; Razafindrakoto 1993; Mustafa 1995; Faruque 1997; Sharma 1998; Iyngkaran 1998; Nanulescu 1999).

Less than half of the trials (12) used an adequate method to conceal allocation. The method was unclear in the other 22 trials.

Blinding of the participants, providers, and assessors was only done in three trials (Akbar 1991; Santos Ocampo 1993; El-Mougi 1996). Blinding was difficult or impossible in most trials because of the difference in the appearance of the ORS formulation after reconstitution.

All but two trials included an adequate (> 90%) number of randomized participants in the analysis. The number was assessed as inadequate in two trials (Akbar 1991; Nanulescu 1999).

 

Effects of interventions

There were two trials that reported the effects on adults and children separately (Molla 1985; Dutta 1998). Thus, in the following results, there are some analyses that have more comparison groups than the number of trials reported.

 

Type of glucose ORS

Five trials compared polymer-based ORS with ORS ≤ 270, and 30 trials with ORS ≥ 310. Overall, the stool volume during the first 24 hours was lower in the polymer-based ORS group (1375 participants, 12 trials,  Analysis 1.1). There was substantial, significant heterogeneity (Chi2 test P < 0.00001, I2 = 100%). One trial with ORS ≤ 270 also showed lower stool volume (99 participants, Nanulescu 1999,  Analysis 1.1). The duration of diarrhoea varied from 30 to 81 and 34 to 91 hours in the polymer-based ORS and glucose-based ORS groups, respectively.

For ORS ≥ 310, overall duration was shorter in the polymer-based ORS group (977 participants, 12 trials,  Analysis 1.2) (Chi2 test P < 0.00001, I2 = 100%). For ORS ≤ 270, there was a similar difference (MD -5.98 g/kg, 95% CI -2.08 to -9.89; 194 participants, 3 trials,  Analysis 1.2), but we observed significant heterogeneity when we excluded Nanulescu 1999, the one trial with incomplete outcome data (Chi2 test P < 0.10, I2 = 63%).

There was a trend toward slightly fewer unscheduled intravenous infusions in the polymer-based ORS group compared with both the ORS ≥ 310 and ≤ 270 groups; neither was significant, but when both ORS groups were combined the difference was significant in favour of the polymer-based ORS (RR 0.75, 95% CI 0.59 to 0.95; 2235 participants, 19 trials,  Analysis 1.3, Figure 1). There was no statistically significant difference between the polymer-based and glucose-based ORS groups in the number of participants with vomiting ( Analysis 1.4), hyponatraemia ( Analysis 1.5), hypokalaemia ( Analysis 1.6), and development of persistent diarrhoea ( Analysis 1.7).

 FigureFigure 1. Any polymer-based ORS vs glucose-based ORS: unscheduled use of intravenous fluid.

 

Type of polymer

Stratification by types of polymer showed that participants in the rice-based ORS group had a lower stool output (1262 participants, 12 trials,  Analysis 2.1: subgroup 1) and duration of diarrhoea (1097 participants, 15 trials,  Analysis 2.2: subgroup 1) (Chi2 test P < 0.00001, I2 = 100%). Results with wheat-based ORS were consistent with this (MD -119.85 g/kg, 95% CI -114.73 to -124.97; 129 participants, 2 trials;  Analysis 2.1; subgroup 2). For sorghum (1 trial) and maltodextrin ORS (1 trial) the data were clearly skewed (mean/SD > 2) so the results are difficult to interpret. A sensitivity analysis showed similar results.

There was a decrease in the number of participants requiring intravenous fluid for those given rice-based ORS (RR 0.75, 95% CI 0.58 to 0.98; 1962 participants, 16 trials,  Analysis 2.3), but not for those given wheat-based ORS and maltodextrin-based ORS.

 

Effects of age and pathogen

The effects of age and type of pathogen were evaluated using trials that compared rice-based ORS with glucose-based ORS. In children, there was a significant decrease in the total stool output ( Analysis 3.1) and duration of diarrhoea ( Analysis 3.2) (Chi2 test, P < 0.00001, I2 = 100%). Among the adults, there was a significant decrease in the duration of diarrhoea (MD -7.11 hours, 95% CI -2.32 to -11.91; 228 participants, 4 trials,  Analysis 3.2: subgroup 2, Figure 2). All four trials were conducted with participants positive for V. cholerae.

 FigureFigure 2. Rice-based ORS vs glucose-based ORS: duration of diarrhoea, by age group.

Participants positive for V. cholerae had a lower stool output ( Analysis 3.3) when given a rice-based ORS. These effects were not seen among participants with non-cholera diarrhoea (Chi2 test P < 0.00001, I2 = 100%). The duration of diarrhoea was significantly shorter among those given rice-based ORS, regardless of the pathogen ( Analysis 3.4) (Chi2 test P < 0.00001, I2 = 100%). Sensitivity analysis of the above outcomes showed similar results.

 

Publication bias

We observed substantial, significant heterogeneity in the primary outcomes and therefore we decided to use a funnel plot for the secondary outcome, where the data were homogenous. We constructed a funnel plot of 19 trials comparing polymer-based ORS, and glucose-based ORS and measuring the outcome of unscheduled use of intravenous fluid (Figure 3). The funnel plot is asymmetric due to the absence of smaller trials at the base and to the right of the pooled estimate. This was confirmed by the test for funnel plot asymmetry, which indicated significant asymmetry (Egger: bias = -0.856208 (95% = -1.699023 to -0.013393, P = 0.0469)). Asymmetry in the funnel plot could result from possible selection bias where smaller studies reporting greater treatment benefit for the experimental group were published (publication bias). The gap in the bottom corner of the graph suggests that smaller studies without statistically significant effects remain unpublished. Differences in inclusion criteria (eg cholera positive versus any pathogen) and method of assessment of unscheduled use of intravenous fluid may also account for the asymmetry.

 FigureFigure 3. Funnel plot on the trials of polymer-based ORS vs glucose-based ORS, measuring the outcome of unscheduled use of intravenous fluid.

 

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. Contributions of authors
  12. Declarations of interest
  13. Sources of support
  14. Differences between protocol and review
  15. Index terms

The biochemical basis for the use of a polymer-based ORS is the presence of starch in rice, wheat, sorghum, and some fruits and vegetables (Carpenter 1988; Pizarro 1991). Even during diarrhoea, the digesting enzyme (amylase) is present in large amounts in the small intestine, so this starch is slowly broken down into glucose molecules. This glucose in turn provides the carrier molecules for co-transport of sodium and water across the intestinal epithelium, without the corresponding osmotic penalty that results if the quantity of glucose is further increased by the use of ORS ≥310.

There are three significant findings in this systematic review of 34 randomized controlled trials. First, there was a decrease in the need for unscheduled intravenous fluid among the participants given polymer-based ORS and in the subgroup of participants who were given rice-based ORS as compared with a glucose-based ORS. This indicates a decrease in the failure rate of oral rehydration when patients are given a polymer-based as compared to a glucose-based oral rehydration therapy. These results remained significant when a sensitivity analysis was carried out. However, the risk difference between the two ORS formulations is only 3%, with 34 patients needing treatment with a polymer-based ORS to prevent one episode of oral rehydration therapy failure. Is this result clinically important? While the use of polymers, such as rice, wheat, maize or potatoes, may be more acceptable as a treatment for diarrhoea, being foods that are familiar and readily available in the household, the preparation of the solution is more tedious. Polymers from local sources require cooking and have to be consumed within eight hours, especially in humid countries, to prevent bacterial growth and contamination. This is in contrast to the glucose-based ORS whose preparation only requires mixing the sachet of glucose and electrolytes in boiled water, and the solution may be consumed up to 12 hours in room temperature. It also has to be borne in mind that the clinical trials that were included in this meta-analysis do not allow one to conclude whether polymer-based ORS is indeed physiologically better than glucose-based ORS, as most of the trials immediately re-fed the patients after hydration. Patients with diarrhoea are dehydrated during the first six to eight hours, but once rehydrated, feeding is initiated. The effect of feeding a rice-based or starch-based food as soon as the participants are rehydrated could confound the effects of polymer-based ORS (Alam 1992) and may have led to an underestimate of the effect of glucose-based ORS (Molla 1989a). In a large multicentre trial, the use of a reduced osmolarity ORS (ORS ≤ 270) compared to a glucose-based ORS (ORS ≥ 310) was shown to decrease the need for unscheduled use of intravenous fluid by 33% (Choice 2001). In this review, most of the included clinical trials used ORS ≥ 310 compared to the newer ORS ≤ 270, which has a lower osmolarity. Whether polymer-based ORS is as effective as, or more effective than the reduced osmolarity ORS, which is presently recommended, remains a subject for investigation.

A second observation of this meta-analysis is the decrease in the duration of diarrhoea among V. cholerae positive adults who were given polymer-based ORS, which was not seen when the analysis was limited to participants with non-cholerae or mixed pathogens. This positive result was not demonstrated in children. The efficacy of rice-based ORS has previously been reported to decrease the stool output in the first 24 hours among V. cholerae positive patients, in both adults and children (Fontaine 1998). These findings, however, were not confirmed in the present review, possibly due to the marked heterogeneity of the pooled data. Moreover, in some of the trials, the data were skewed and could not be used in the meta-analysis. Nonetheless, the efficacy of polymer-based ORS in reducing the duration of diarrhoea among cholera-positive patients but not in patients with other types of pathogens maybe due to the difference in the diarrhoeal mechanisms between the two groups (Casburn-Jones 2004). In cholera, which is an enterotoxin-mediated diarrhoea, intestinal secretory processes are activated by the bacteria, leading to massive fluid and electrolyte losses, without any macro- or micro-damage to the intestinal mucosa. On the other hand, commonly encountered enteric pathogens in childhood diarrhoea, such as rotavirus, Salmonella spp, and Shigella spp cause injury to the intestinal mucosae leading to a decrease in intestinal absorption of fluid, electrolytes, and nutrients.

Lastly, an interesting finding of this meta-analysis is the decrease in the total stool output during the first 24 hours in patients given wheat-based ORS who were enrolled in two trials (Alam 1987, wheat; Molla 1989b, wheat). Apart from its carbohydrate content, the proteins present in wheat may also help in the transport of salt and water across the intestinal mucosa, further decreasing the stool output and duration of diarrhoea (Dagher 1996). The available data in this review, however, are only derived from two trials. The chemical quality and digestibility of wheat-based ORS, as well as its clinical efficacy and safety, warrants further research. The ultimate goal is to find an ORS that is cheap, readily available, acceptable, and effective in all types of diarrhoea.

A major limitation of this review is the substantial heterogeneity in the clinical trials, despite statistically significant results in the primary outcomes. Heterogeneity in the treatment effect may have been affected by the way the outcomes have been measured (methodological diversity). Ideally, measurement of stool output should be made by taking the difference in the weight of the diaper before and after use. In some studies in which both males and females were included (especially in the paediatric group) the urine output may have been inadvertently mixed with the stool, giving an erroneously higher stool output. In adults, three trials used a cholera cot to measure stool output (Bhattacharya 1998; Dutta 2000; Ramakrishna 2000), while one trial did not state the measurement method used (Alam 1992). The cholera cot has a bucket underneath to measure the stool output more accurately. It was also unclear in most of the trials whether the duration of diarrhoea was measured from the initial onset of the disease, before admission to the study, or only from admission up to the time of discharge. Different trials may also have used different criteria to define patients who warrant an unscheduled use of intravenous fluid. Despite these limitations, however, sensitivity analyses did not change the results when trials with unclear randomization, unclear allocation, and inadequate numbers of patients analysed were excluded, suggesting that the results of this review are robust.

 

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. Contributions of authors
  12. Declarations of interest
  13. Sources of support
  14. Differences between protocol and review
  15. Index terms

 

Implications for practice

Polymer-based ORS decreases the duration of diarrhoea among adults positive for V. cholerae and lowers the risk of unscheduled use of intravenous fluid, compared with a glucose-based ORS ≥ 310. Trial participants who were given a wheat-based ORS were also shown to have a decrease in total stool output in the first 24 hours; however, the data on wheat ORS were only derived from two trials. Glucose-based ORS, when accompanied by early feeding, may be just as effective.

 
Implications for research

The rationale for the use of polymer-based ORS is the slow release of glucose from starch, which provides the carrier molecules for sodium without the osmotic penalty that results if the quantity of glucose is increased by the use of ORS ≥ 310. Since the ORS presently recommended already has a reduced osmolarity (ORS ≤ 270), it will be of interest to compare the efficacy of ORS ≤ 270 with a polymer-based ORS in reducing the total stool output, the total volume of ORS intake, the duration of diarrhoea, and the risk of unscheduled intravenous fluid therapy. There is also a need for more trials on the efficacy of wheat-based ORS.

 

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. Contributions of authors
  12. Declarations of interest
  13. Sources of support
  14. Differences between protocol and review
  15. Index terms

This document is an output from a project funded by the UK Department for International Development (DFID) for the benefit of developing countries. The views expressed are not necessarily those of DFID.

 

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. Contributions of authors
  12. Declarations of interest
  13. Sources of support
  14. Differences between protocol and review
  15. Index terms
Download statistical data

 
Comparison 1. Type of glucose ORS: any polymer-based ORS vs glucose-based ORS

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

 1 Total stool output: during first 24 hours13Mean Difference (IV, Random, 95% CI)Totals not selected

    1.1 ORS ≥310
12Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    1.2 ORS ≤ 270
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 2 Duration of diarrhoea15Mean Difference (IV, Random, 95% CI)Totals not selected

    2.1 ORS ≥ 310
12Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    2.2 ORS ≤ 270
3Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 3 Unscheduled use of intravenous fluid212235Risk Ratio (M-H, Fixed, 95% CI)0.75 [0.59, 0.95]

    3.1 ORS ≥ 310
181909Risk Ratio (M-H, Fixed, 95% CI)0.78 [0.60, 1.01]

    3.2 ORS ≤ 270
3326Risk Ratio (M-H, Fixed, 95% CI)0.62 [0.36, 1.08]

 4 Vomiting (no. participants)10617Risk Ratio (M-H, Fixed, 95% CI)0.83 [0.65, 1.05]

    4.1 ORS ≥ 310
9554Risk Ratio (M-H, Fixed, 95% CI)0.87 [0.68, 1.11]

    4.2 ORS ≤ 270
163Risk Ratio (M-H, Fixed, 95% CI)0.56 [0.24, 1.34]

 5 Hyponatraemia (no. participants)6480Risk Ratio (M-H, Fixed, 95% CI)1.03 [0.52, 2.01]

    5.1 ORS ≥ 310
3335Risk Ratio (M-H, Fixed, 95% CI)2.25 [0.34, 14.92]

    5.2 ORS ≤ 270
3145Risk Ratio (M-H, Fixed, 95% CI)0.88 [0.43, 1.82]

 6 Hypokalaemia (no. participants)2Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    6.1 ORS ≥ 310
2260Risk Ratio (M-H, Fixed, 95% CI)1.29 [0.74, 2.25]

 7 Developed persistent diarrhoea (no. participants)2Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    7.1 ORS ≥ 310
2885Risk Ratio (M-H, Fixed, 95% CI)1.28 [0.68, 2.41]

 
Comparison 2. Type of polymer: polymer-based ORS vs glucose-based ORS

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

 1 Total stool output during the first 24 hours17Mean Difference (IV, Random, 95% CI)Totals not selected

    1.1 Rice-based ORS
13Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    1.2 Wheat-based ORS
2Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    1.3 Sorghum-based ORS
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    1.4 Maltodextrin-based ORS
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 2 Duration of diarrhoea18Mean Difference (IV, Random, 95% CI)Totals not selected

    2.1 Rice-based ORS
15Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    2.2 Wheat-based ORS
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    2.3 Sorghum-based ORS
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    2.4 Maltodextrin-based ORS
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 3 Unscheduled use of intravenous fluid212168Risk Ratio (M-H, Fixed, 95% CI)0.76 [0.59, 0.97]

    3.1 Rice-based ORS
181962Risk Ratio (M-H, Fixed, 95% CI)0.75 [0.58, 0.98]

    3.2 Wheat-based ORS
148Risk Ratio (M-H, Fixed, 95% CI)1.0 [0.15, 6.53]

    3.3 Maltodextrin-based ORS
2158Risk Ratio (M-H, Fixed, 95% CI)0.79 [0.31, 2.02]

 
Comparison 3. Effects of age and pathogen: rice-based ORS vs glucose-based ORS

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

 1 Total stool output during the first 24 hours, by age group13Mean Difference (IV, Random, 95% CI)Totals not selected

    1.1 Paediatric
11Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    1.2 Adults
2Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 2 Duration of diarrhoea, by age group15998Mean Difference (IV, Random, 95% CI)-7.19 [-11.80, -2.58]

    2.1 Paediatrics
11770Mean Difference (IV, Random, 95% CI)-6.81 [-12.10, -1.52]

    2.2 Adults
4228Mean Difference (IV, Random, 95% CI)-7.11 [-11.91, -2.32]

 3 Total stool output during the first 24 hours, by pathogen11Mean Difference (IV, Random, 95% CI)Totals not selected

    3.1 Cholera
3Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    3.2 Non-cholera
4Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    3.3 Mixed pathogens
5Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 4 Duration of diarrhoea, by type of pathogen12Mean Difference (IV, Random, 95% CI)Totals not selected

    4.1 Cholera
7Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    4.2 Non-cholera
3Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    4.3 Mixed pathogens
2Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 

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. Contributions of authors
  12. Declarations of interest
  13. Sources of support
  14. Differences between protocol and review
  15. Index terms
 

Appendix 1. Search methods: detailed search strategies


Search setMEDLINEbEMBASEbOTHERb

1REHYDRATION SOLUTIONSFLUID THERAPYoral rehydration

2FLUID THERAPYORAL REHYDRATION THERAPYfluid therapy

3oral rehydration solutionoral rehydration solutionORS

4ORSORS1 or 2 or 3

51 or 2 or 3 or 41 or 2 or 3 or 4glucose

6STARCHGLUCOSE-POLYMERrice

7glucoseSTARCHamylase

8riceglucoseamylopectin

9amylasericecorn

10amylopectinsamylasesorghum

11cornamylopectinsmaize

12sorghumcorn6-11/or

13maizesorghum4 and 12

146-13/ormaize

155 and 146-14

16Limit 15 to human5 and 15

17Limit 16 to human



aSearch terms used in combination with the search strategy for retrieving trials developed by The Cochrane Collaboration (Lefebvre 2008); upper case: MeSH or EMTREE heading; lower case: free text term.
bUsed for Cochrane Infectious Diseases Group Specialized Register, CENTRAL, and LILACS.

 

Appendix 2. Risk of bias assessment


TrialAllocation sequenceAllocation concealmentBlindingInclusion of randomized participants in analysis

Akbar 1991         AdequateAdequateParticipants, providers, outcome assessorsInadequate

Alam 1987  AdequateUnclearNoneAdequate

Alam 1992AdequateUnclearNoneAdequate

Bernal 2005AdequateAdequateUnclearAdequate

Bhan 1987UnclearUnclearNoneAdequate

Bhattacharya 1998  AdequateUnclearNoneAdequate

Dutta 1988AdequateUnclearUnclearAdequate

Dutta 1998AdequateUnclearNoneAdequate

Dutta 2000AdequateUnclearNoneAdequate

El-Mougi 1988AdequateUnclearNoneAdequate

El-Mougi 1996  AdequateAdequateParticipants, providers, outcome assessorsAdequate

Faruque 1997  UnclearUnclearNoneAdequate

Fayad 1993AdequateAdequateUnclearAdequate

Guiraldes 1995a  AdequateAdequateNoneAdequate

Guiraldes 1995b  AdequateAdequateNoneAdequate

Hossain 2003  AdequateAdequateNoneAdequate

Islam 1994  AdequateUnclearNoneAdequate

Iyngkaran 1998  UnclearUnclearNoneAdequate

Maulen-Radovan 1994  AdequateAdequateNoneAdequate

Maulen-Radovan 2004AdequateAdequateNoneAdequate

Mohan 1988UnclearUnclearNoneAdequate

Molla 1985  AdequateUnclearNoneAdequate

Molla 1989a  UnclearUnclearUnclearAdequate

Molla 1989bAdequateUnclearParticipants and providers not blinded; outcome assessors unclearAdequate

Mustafa 1995  UnclearUnclearUnclearAdequate

Nanulescu 1999  UnclearUnclearNoneInadequate

Patra 1982UnclearAdequateNoneAdequate

Ramakrishna 2000  AdequateUnclearParticipants and providers partially blinded; outcome assessors unclearAdequate

Ramakrishna 2008  AdequateAdequateAssessors but not the participants or providers were blinded because of the nature of the studyAdequate

Razafindrakoto 1993UnclearUnclearNoneAdequate

Santos Ocampo 1993AdequateAdequateParticipants, providers, outcome assessorsAdequate

Sharma 1998  UnclearUnclearNoneAdequate

Wall 1997  AdequateUnclearParticipants and providers not blinded; outcome assessors unclearAdequate

Zaman 2001AdequateUnclearNoneAdequate



 

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. Contributions of authors
  12. Declarations of interest
  13. Sources of support
  14. Differences between protocol and review
  15. Index terms

GV Gregorio was the principal investigator, wrote the protocol, carried out the risk of bias (methodological quality) assessment, data extraction and analysis, and wrote the final manuscript.

MLM Gonzales helped in writing the protocol, carried out the risk of bias (methodological quality) assessment and data extraction, and commented on the final manuscript.

LF Dans carried out the risk of bias (methodological quality) assessment.

EG Martinez carried out the data extraction and commented on the final manuscript.

 

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. Contributions of authors
  12. Declarations of interest
  13. Sources of support
  14. Differences between protocol and review
  15. Index terms

None known.

 

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. Contributions of authors
  12. Declarations of interest
  13. Sources of support
  14. Differences between protocol and review
  15. Index terms
 

Internal sources

  • Effective Health Care Research Programme Consortium, UK.

 

External sources

  • Department for International Development (DFID), UK.

 

Differences between protocol and review

  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. Contributions of authors
  12. Declarations of interest
  13. Sources of support
  14. Differences between protocol and review
  15. Index terms

  • Change in title: The title was changed to highlight the fact that this is a review of polymer-based ORS (not glucose-based ORS).
  • New author: EG Martinez joined the author team after the protocol was published.
  • Data extraction: We originally planned to extract count data by determining the total number of episodes in each group (if the episode is rare) or the number of person years in each group for each treatment arm (if the episode is common). However, during the assessment of the trials, the trials reported the number of participants with unscheduled use of intravenous fluid, and thus it was considered to be a dichotomous rather than a count outcome. Similarly, in the data extraction for number of episodes of vomiting, there were only four trials that reported this outcome, while nine clinical trials reported the number of participants with vomiting. It was decided that the latter would be reported. Other adverse effects that were reported in the trials, including number of participants with hypokalaemia (low potassium levels) and those with development of persistent diarrhoea (diarrhoea of more than 10 days' duration from onset), were also included in the review.
  • Data analysis: In multiple treatment arms with two or more polymer-based ORS as treatment groups, the outcomes were combined as appropriate and compared collectively with the control group. Most of the trials included both cholera and non-cholera cases, and this group was collectively termed as having mixed pathogens rather than non-cholera related diarrhoea.
  • Subgroup analyses: These were limited to the osmolarity of the glucose ORS, the type of polymer, and the effects of participant's age and pathogen. The source of the polymer and the effect of feeding were no longer evaluated as most of the polymers were locally prepared and all but two trials withheld feeding after hydration.
  • Publication bias: The presence of publication bias was confirmed with StatsDirect, a statistical software program.

* Indicates the major publication for the study

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. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Characteristics of studies
  17. References to studies included in this review
  18. References to studies excluded from this review
  19. Additional references
Akbar 1991 {published data only}
  • Akbar M, Baker K, Aziz M, Khan W, Salim A. A randomised double-blind clinical trial of a maltodextrin containing oral rehydration solution in acute infantile diarrhoea. Journal of Diarrheal Disease Research 1991;9(1):33-7.
Alam 1987 {published data only}
Alam 1987, rice {published data only}
  • Alam 1987 results for those given rice ORS.
Alam 1987, wheat {published data only}
  • Alam 1987 results for those given wheat ORS.
Alam 1992 {published data only}
Bernal 2005 {published data only}
  • Bernal C, Alcaraz G, Bolero J. Oral rehydration with a plaintain flour-based solution precooked with standardized electrolytes [Hidratacion oral con una solucion a based de harina de platano precocida con electrolitos estandrarizados]. Biomedica 2000;25(1):11-21.
Bhan 1987 {published data only}
  • Bhan MK, Ghai OP, Khoshoo V, Vasudev A, Bhatnagar S, Arora N, et al. Efficacy of mung bean (lentil) and pop rice based rehydration solutions in comparison with standard glucose electrolyte solution. Journal of Pediatric Gastroenterology and Nutrition 1987;6(3):392-9.
Bhan 1987, mung bean {published data only}
  • Bhan 1987 results for those given mung bean ORS.
Bhan 1987, rice {published data only}
  • Bhan 1987 results for those given rice ORS.
Bhattacharya 1998 {published data only}
  • Bhattacharya M, Bhattacharya S, Dutta D, Deb A, Deb M, Dutta A, et al. Efficacy of oral hypoosmolar glucose-based and rice-based oral rehydration salt solutions in the treatment of cholera in adults. Scandinavian Journal of Gastroenterology 1998;33(2):159-63.
Dutta 1988 {published data only}
  • Dutta P, Dutta S, Bhattacharya M, Bhattacharya S, Sinha A, Mondal B, et al. Comparative efficacy of three different oral rehydration solutions for treatment of dehydrating diarrhoea in children. Indian Journal of Medical Research 1988;87:229-33.
Dutta 1998 {published data only}
  • Dutta D, Bhattacharya A, Deb A, Chowdhury A, Nair G, Ramakrishna B, et al. Uncooked rice powder in oral rehydration solution: an alternative to glucose or cooked rice powder. Indian Journal of Medical Research 1998;107:257-62.
Dutta 1998, adults {published data only}
  • Dutta 1998 results for adults.
Dutta 1998, children {published data only}
  • Dutta 1998 results for children.
Dutta 2000 {published data only}
  • Dutta D, Bhattacharya MK, Deb A, Sarkar D, Chatterjee A, Biswas A, et al. Evaluation of oral hypo-osmolar glucose-based and rice-based oral rehydration solutions in the treatment of cholera in children. Acta Paediatrica 2000;89(7):787-90.
El-Mougi 1988 {published data only}
  • El-Mougi M, Hegazi E, Galal O, El Akkad N, El-Abhar A, Nour N, et al. Controlled clinical trial on the efficacy of rice powder-based oral rehydration solution on the outcome of acute diarrhea in infants. Journal of Pediatric Gastroenterology and Nutrition 1988;7(4):572-6.
El-Mougi 1996 {published data only}
  • El-Mougi M, Hendawi A, Koura H, Hegazi E, Fontaine O, Pierce N. Efficacy of standard glucose-based and reduced osmolarity maltodextrin-based oral rehydration solutions: effect of sugar malabsorption. Bulletin of the World Health Organization 1996;74(5):471-7.
Faruque 1997 {published data only}
  • Faruque ASG, Hoque SS, Fuchs GJ, Mahalanabis D. Randomized controlled clinical trial of rice versus glucose oral rehydration solutions in infants and young children with acute watery diarrhoea. Acta Paediatrica 1997;86(12):1308-11.
Fayad 1993 {published data only}
  • Fayad IM, Hasham M, Duggan C, Refat M, Bakir M, Fontaine O, et al. Comparative efficacy of rice-based and glucose-based oral rehydration salts plus early introduction of food. Lancet 1993;342(8874):772-5.
Guiraldes 1995a {published data only}
  • Guiraldes E, Trivino X, Figueroa G, Parker M, Gutierrez C, Vasquez A, et al. Comparison of an oral rice-based electrolyte solution and a glucose-based electrolyte solution in hospitalized infants with diarrheal dehydration. Journal of Pediatric Gastroenterology and Nutrition 1995;20(4):417-24.
Guiraldes 1995b {published data only}
  • Guiraldes E, Trivino X, Hodgson M, Quintana J, Quintana C. Treatment of acute infantile diarrhoea with a commercial rice-based oral rehydration solution. Journal of Diarrhoeal Disease Research 1995;13(4):207-11.
Hossain 2003 {published data only}
  • Hossain M, Salam M, Rabbani G, Kahir I, Biswas R, Mahalanabis D. Rice-ORS versus glucose-ORS in management of severe cholera due to Vibrio cholerae 0139 Bengal: a randomized, controlled clinical trial. Journal of Health Population and Nutrition 2003;21(4):325-31.
Islam 1994 {published data only}
Iyngkaran 1998 {published data only}
Maulen-Radovan 1994 {published data only}
  • Maulen-Radovan I, Fernandez-Varela H, Acosta-Bastidas M, Frenk S. Safety and efficacy of a rice-based oral rehydration salt solution in the treatment of diarrhea in infants less than 6 months of age. Journal of Pediatric Gastroenterology and Nutrition 1994;19(1):78-82.
Maulen-Radovan 2004 {published data only}
  • Maulen-Radovan I, Gutierrez-Castrellon P, Hashem M, Neylan M, Braggs G, Zaldo R, et al. Safety and efficacy of a premixed rice-based oral rehydration solution. Journal of Pediatric Gastroenterology and Nutrition 2004;38(2):159-63.
Mohan 1988 {published data only}
  • Mohan M, Antony T, Malik S, Mathur M. Rice powder oral rehydration solution as an alternative to glucose electrolyte solution. Indian Journal of Medical Research 1988;87:234-9.
Molla 1985 {published data only}
  • Molla A, Ahmed S, Greenough W. Rice-based oral rehydration solution decreases the stool volume in acute diarrhoea. Bulletin of the World Health Organization 1985;63(4):751-6.
Molla 1985, adults {published data only}
  • Molla 1985 results for adults.
Molla 1985, children {published data only}
  • Molla 1985 results for children.
Molla 1989a {published data only}
Molla 1989b {published data only}
Molla 1989b, rice {published data only}
  • Molla 1989b results for those given rice ORS.
Molla 1989b, sorghum {published data only}
  • Molla 1989b results for those given sorghum ORS.
Molla 1989b, wheat {published data only}
  • Molla 1989b results for those given wheat ORS.
Mustafa 1995 {published data only}
  • Mustafa S, Karrar Z, Suliman J. Cereal-based oral rehydration solutions in Sudanese children with diarrhoea: a comparative clinical trial of rice-based and sorghum-based oral rehydration solutions. Annals of Tropical Paediatrics 1995;15(4):313-9.
Mustafa 1995, rice {published data only}
  • Mustafa 1995 results for those given rice ORS.
Mustafa 1995, sorghum {published data only}
  • Mustafa 1995 results for those given sorghum ORS.
Nanulescu 1999 {published data only}
  • Nanulescu M, Popa M, Panta P, Butanariu A, Muresan M, Gocan S, et al. The efficacy of an oral-rice based electrolyte solution in infants with acute diarrhea as compared to a glucose-based electrolyte solution. Romanian Journal of Gastroenterology 1999;8(3):177-82.
Patra 1982 {published data only}
  • Patra FC, Mahalanabis D, Jalan K, Sen A, Banerjee P. Is oral rice electrolyte solution superior to glucose electrolyte solution in infantile diarrhoea?. Archives of Disease in Childhood 1982;57(12):910-2.
Ramakrishna 2000 {published data only}
  • Ramakrishna B, Venkataraman S, Srinivasan P, Dash P, Young G, Binder H. Amylase-resistant starch plus oral rehydration solution for cholera. New England Journal of Medicine 2000;342(5):308-13.
Ramakrishna 2000, amylase {published data only}
  • Ramakrishna 2000 results for those given amylase resistant starch.
Ramakrishna 2000, rice {published data only}
  • Ramakrishna 2000 results for those given rice ORS.
Ramakrishna 2008 {published data only}
  • Ramakrishna B, Subramanian V, Mohan V, Sebastian B, Young G, Farthing M, et al. A randomized controlled trial of glucose versus amylase resistant starch hypo-osmolar oral rehydration solution for adult acute dehydrating diarrhea. PLoS ONE 2008;3(2):e1587.
Razafindrakoto 1993 {published data only}
  • Razafindrakoto O, Ravelomanana N, Randriamiharisoa F, Rasoarivao V, Ramialimanana V, Rakotoarimanana D, et al. Rice-based rehydration solution: an alternative to glucose-based solutions in acute diarrhea in malnourished children [La solution de rehydration orale (SRO) a base de riz, alternative de la SRO de l'OMS dans la diarrhee aigue des malnutris]. Archives Francaises de Pediatrie 1993;50(2):101-5.
Santos Ocampo 1993 {published data only}
  • Santos Ocampo P, Bravo L, Rogacion J, Battad G. A randomized double-blind clinical trial of a maltodextrin-containing oral rehydration solution in acute infantile diarrhea. Journal of Pediatric Gastroenterology and Nutrition 1993;16(1):23-8.
Sharma 1998 {published data only}
  • Sharma A, Pradhan R. Comparative study of rice-based oral rehydration salt solution versus glucose-based oral rehydration salt solution (WHO) in children with acute dehydrating diarrhoea. Journal of Indian Medical Association 1998;96(12):367-8.
Wall 1997 {published data only}
  • Wall C, Swanson C, Cleghorn G. A controlled trial comparing the efficacy of rice-based and hypotonic glucose oral rehydration solutions in infants and young children with gastroenteritis. Journal of Gastroenterology and Hepatology 1997;12(1):24-8.
Zaman 2001 {published data only}
  • Zaman K, Yunus M, Rahman A, Chowdhury H, Sack D. Efficacy of a packaged rice oral rehydration solution among children with cholera and cholera-like illness. Acta Paediatrica 2001;90(5):505-10.

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. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Characteristics of studies
  17. References to studies included in this review
  18. References to studies excluded from this review
  19. Additional references
Agustina 2007 {published data only}
  • Agustina R, Lukito W, Suhardjo H, Murniati D, Bindels J. The effect of nutritional supplementation with a mixture of probiotic, prebiotic, fiber and micronutrients in infants with acute diarrhoea in Indonesia. Asia Pacific Journal of Clinical Nutrition 2007;16:435-42.
Alam 2008 {published data only}
  • Alam N, Ashraf H, Sarker S, Olesen M, Troup J, Salam M, et al. Efficacy of partially hydrolyzed guar gum added oral rehydration solution in the treatment of severe cholera in adults. Digestion 2008;4:24-9.
Ansaldi 1990 {published data only}
  • Ansaldi N, Dell'olio D, Poli E, Grandi G. Oral rehydration therapy in acute diarrhea in infancy. Comparison between two rehydration solutions [Importanza della reidratzaione orale nelle diarree acute infantili]. Minerva Pediatrica 1990;42(1-2):9-14.
Barclay 1995 {published data only}
Barragan-Guzman 1998 {published data only}
  • Barragan-Guzman B, Orozco-Alatorre L, Mariscal-Zuno S. Corn meal solution compared to oral saline solution in the treatment of children with acute diarrhea and high fecal output [Atole de maiz comparado con Vida Suero Oral en el tratamiento de ninos con diarrea aguda de gasto fecal alto]. Boletin Medico del Hospital Infantil de Mexico 1998;55(2):65-8.
Bhandari 2008 {published data only}
  • Bhandari N, Mazumder S, Taneja S, Dube B, Agarwal R, Mahalanabis D, et al. Effectiveness of zinc supplementation plus oral rehydration salts compared with oral rehydration salts alone as a treatment for acute diarrhoea in a primary care setting: a cluster randomised trial. Pediatrics 2008;121:e1279-85.
Cohen 1995 {published data only}
  • Cohen M, Mezoff A, Laney W, Bezerra J, Beane B, Drazner D, et al. Use of a single solution for oral rehydration and maintenance therapy of infants with diarrhea and mild to moderate dehydration. Pediatrics 1995;95(5):639-45.
Gutierrez 2007 {published data only}
  • Gutierrez C, Villa S, Mota F, Calva J. Does an L-glutamine containing glucose free oral rehydration solution reduce stool output and time to rehydrate in children with acute diarrhea? A double blind randomized clinical trial. Journal of Health Population and Nutrition 2008;25:278-84.
Hoekstra 2004 {published data only}
  • Hoekstra J, Szajewska H, Abu Zikri M, Micetic-Turk D, Weizman Z, Papadopoulou A, et al. Oral rehydration solution containing a mixture of non-digestible carbohydrates in the treatment of acute diarrhea: a multicenter randomized placebo controlled study on behalf of the ESPGHAN working group on intestinal infections. Journal of Pediatric Gastroenterology and Nutrition 2004;39(3):239-45.
Jirapinyo 1996 {published data only}
  • Jirapinyo P, Moran J. Comparison of oral rehydration solutions made with rice syrup solids or glucose in the treatment of acute diarrhea in infants. Journal of the Medical Association of Thailand 1996;79(3):154-60.
Kassaye 1994 {published data only}
Kenya 1989 {published data only}
  • Kenya P, Odongo H, Oundo G, Waswa K, Muttunga J, Molla A, et al. Cereal based oral rehydration solutions. Archives of Disease in Childhood 1989;47(4):226-9.
Lebenthal 1995 {published data only}
  • Lebenthal E, Khin-Maung-U, Khin-Myat-Tun, Tin-Nu-Swe, Thein-Thein-Myint, Jirapinyo P, et al. High-calorie, rice-derived, short-chain, glucose polymer-based oral rehydration solution in acute watery diarrhea. Acta Paediatrica 1995;84(2):165-72.
Molina 1995 {published data only}
  • Molina S, Vettorazzi C, Peerson J, Solomons N, Brown K. Clinical trial of glucose-oral rehydration solution, rice dextrin-ORS and rice flour-ORS for the management of children with acute diarrhea and mild or moderate dehydration. Pediatrics 1995;95(2):191-7.
Molla 1982 {published data only}
Molla 2000 {published data only}
Mota-Hernandez 1991 {published data only}
  • Mota-Hernandez F, Bross-Soriano D, Perez-Ricardez M, Velasquez-Jones L. Rice solution and World Health Organization solution by gastric infusion for high stool output diarrhea. American Journal of Diseases of Childhood 1991;145(8):937-40.
Murphy 1996 {published data only}
Patra 1984 {published data only}
Pelleboer 1990 {published data only}
  • Pelleboer R, Felius A, Goje B, Van Gelderen H. Sorghum-based oral rehydration solution in the treatment of acute diarrhoea. Tropical and Geographical Medicine 1990;42(1):63-8.
Pizarro 1991 {published data only}
  • Pizarro D, Posada G, Sandi L, Moran J. Rice-based oral electrolyte solutions for the management of infantile diarrhea. New England Journal of Medicine 1991;7(6):882-8.
Prasad 1993 {published data only}
Rabbani 2005 {published data only}
  • Rabbani G, Sack D, Ahmed S, Peterson J, Saha S, Marni F, et al. Antidiarrheal effects of L-histidine supplemented rice-based oral rehydration solution in the treatment of male adults with severe cholera in Bangladesh: a double-blind randomized trial. Journal of Infectious Diseases 2005;191(9):1507-14.
Raghupathy 2006 {published data only}
  • Raghupathy P, Ramakrishna B, Oommen S, Ahmed M, Priyas G, Dziura J, et al. Amylase-resistant starch as adjunct to oral rehydration therapy in children with diarrhea. Journal of Pediatric Gastroenterology and Nutrition 2006;42(4):362-8.
Roslund 2008 {published data only}
  • Roslund G, Hepps T, McQuillen K. The role of ondasentron in children with vomiting as a result of acute gastritis/gastroenteritis who have failed oral rehydration therapy: a randomized controlled trial. Annals of Emergency Medicine 2008;52:22-9.
Sabchareon 1992 {published data only}
  • Sabchareon A, Chongsuphajaisiddhi T, Kittikoon P, Chanthavanich P. Rice-powder salt solution in the treatment of acute diarrhea in young children. Southeast Asian Journal of Tropical Medicine and Public Health 1992;23(3):427-32.
Sarker 2001 {published data only}
  • Sarker S, Mahalanabis D, Alam N, Sharmin S, Khan A, Fuchs G. Reduced osmolarity oral rehydration solution for persistent diarrhea in infants: a randomized controlled clinical trial. Journal of Pediatrics 2001;138(4):532-8.
Sirivichayakul 2000 {published data only}
  • Sirivichayakul C, Chokejindachai W, Vithayasai N, Chanthavanich P, Pengsaa K, Wisetsing P, et al. Effects of rice powder salt solution and milk-rice mixture on acute watery diarrhoea in young children. Southeast Asian Journal of Tropical Medicine and Public Health 2000;31(2):354-9.
Teferedegn 1993 {published data only}
Yang 2007 {published data only}
  • Yang D, Guo W, Tian D, Luo X, He Y, Dai Y, et al. Efficacy and safety of reduced osmolality oral rehydration salts in treatment of dehydration in children with acute diarrhea - a multicenter, randomized, double blind clinical trial. Zhonghua Er Ke Za Zhi [Chinese Medical Journal] 2007;45:252-5.
Yartev 1995 {published data only}
  • Yartev J, Nkrumah F, Hori H, Harrison K, Armar D. Clinical trial of fermented maize-based oral rehydration solution in the management of acute diarrhoea in children. Annals of Tropical Paediatrics 1995;15(1):61-8.
Yurdakok 1995 {published data only}
  • Yurdakok K, Yalcin S. Comparative efficacy of rice-ORS and glucose-ORS in moderately dehydrated Turkish children with diarrhea. The Turkish Journal of Pediatrics 1995;37(4):315-21.
Zaman 2007 {published data only}
Zavaleta 2007 {published data only}
  • Zavaleta N, Figueroa D, Rivera J, Sanchez J, Alfaro S, Lonnerdal B. Efficacy of rice-based oral rehydration solution containing recombinant human lactoferrin and lysozyme in Peruvian children with acute diarrhea. Journal of Pediatric Gastroenterology and Nutrition 2007;44(2):258-64.

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. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Characteristics of studies
  17. References to studies included in this review
  18. References to studies excluded from this review
  19. Additional references
Alam 1992
  • Alam NH, Ahmed T, Khatun M, Molla AM. Effects of food with two oral rehydration therapies: a randomised controlled clinical trial [Effects of food with two oral rehydration therapies: a randomised controlled clinical tria]. Gut 1992;33(4):560-2.
Carpenter 1988
Casburn-Jones 2004
Choice 2001
  • Choice Study Group. Multicenter, randomized double blind clinical trial to evaluate the efficacy and safety of a reduced osmolality oral rehydration salts solution in children with acute watery diarrhea. Pediatrics 2001;107(4):613-8.
Claeson 1990
Dagher 1996
  • Dagher PC, Egnor RW, Taglietta-Kohlbrecher A, Charney AN. Short chain fatty acids inhibit cAMP-mediated chloride secretion in rat colon. American Journal of Physiology 1996;271(6 Pt 1):1853-60.
Fontaine 1998
  • Fontaine O, Gore SM, Pierce NF. Rice-based oral rehydration solution for treating diarrhoea. Cochrane Database of Systematic Reviews 1998, Issue 4. [DOI: 10.1002/14651858.CD001264.pub2]
Hahn 2002
  • 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. [DOI: 10.1002/14651858.CD002847]
Hunt 1992
Jüni 2001
Kosek 2003
  • Kosek M, Bern C, Guerrant RL. The global burden of diarrhoeal disease as estimated from studies published between 1992 and 2000. Bulletin of the World Health Organization 2003;81(3):197-204.
Lefebvre 2008
  • Lefebvre C, Manheimer E, Glanville J. Chapter 6: Searching for studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.0 (updated February 2008). The Cochrane Collaboration, 2008. Available from www.cochrane-handbook.org.
Pizarro 1991
Review Manager 5
  • The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). 5.0. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2008.
Santosham 1991
StatsDirect
  • StatsDirect Ltd. StatsDirect. 2.6. Altrincham: StatsDirect Ltd, 1 June 2008.
Victora 2000
  • Victora CG, Bryce J, Fontaine O, Monasch R. Reducing deaths from diarrhoea through oral rehydration therapy. Bulletin of the World Health Organization 2000;78(10):1246-55.
WHO 2004
  • World Health Organization. Dept. of Child and Adolescent Health and Development. Clinical management of acute diarrhoea: WHO/UNICEF joint statement [WHO/FCH/CAH/04.7]. Geneva: World Health Organization, 2004.
WHO/ICDDRB 1995
  • Joint WHO/ICDDR, B Consultative Meeting on ORS Formulation. 25 years of ORS: Joint WHO/ICDDR,B Consultative Meeting on ORS Formulation, Dhaka, Bangladesh, 10-12 December 1994 [CDR/CDD/95.2]. Geneva: World Health Organization, 1995.