Low-osmolarity oral rehydration solution (ORS)
New formulation of Oral Rehydration Salts (ORS) with reduced osmolarity
||Background: Two decades ago diarrhoea was responsible for around 5 million deaths
annually. Through major public health efforts primarily aimed at
preventing and treating dehydration this figure has decreased to around 2
million deaths. Prevention of dehydration is primarily achieved by
ensuring that children with diarrhoea are provided with more fluids than
usual, and/or increased frequency of breastfeeding, during the acute
episode. The combination of increased home fluids and the use of Oral
Rehydration Salts (ORS) for the treatment of dehydration have proven to be
a very powerful intervention for the prevention of childhood deaths from
For more than 25 years UNICEF and WHO have recommended a single
formulation of glucose-based ORS to prevent or treat dehydration from
diarrhoea irrespective of the cause or age group affected. This product,
which provides a solution containing 90 mEq/l of sodium with a total
osmolarity of 311 mOsm/l, has proven effective and without apparent
adverse effects in worldwide use. It has been well established, however,
that ORS solution does not reduce stool output or duration of diarrhoea.
For this reason the current ORS might have had less than optimal
acceptance by mothers and health workers, preferring a treatment that
causes diarrhoea to stop. During the past 20 years numerous studies have
been undertaken to develop an 'improved' ORS. The goal was a product that
would be at least as safe and effective as standard ORS for preventing or
treating dehydration from all types of diarrhoea but which, in addition,
would reduce stool output or have other important clinical benefits. One
successful approach is based on reducing the osmolarity of ORS solution to
avoid possible adverse effects of hypertonicity on net fluid absorption.
This was done by reducing the solution's glucose and salt (NaCl)
Studies to evaluate this approach were reviewed at
in July 2001*, and technical recommendations were made to WHO and
UNICEF on the efficacy and safety of reduced osmolarity ORS in children
with acute non-cholera diarrhoea, and in adults and children with
Launch of new formulation:
At UNICEF Supply Division, a bid for Reduced Osmolarity ORS was
launched in September 2003 and two manufacturers were approved for
the supply of new ORS formulation. The new ORS is in stock at UNICEF
Supply Division. Phase out of the old ORS and phase in of the new
ORS is taking place and the old ORS will for a short period of time
remain part of the New Emergency Health Kit, as a certain stock of
these kits was packed before the introduction of the new ORS. For
the moment, the price of new ORS is approximately 15 per cent lower
than the old ORS formulation.
|Reduced osmolarity ORS
|Reduced osmolarity ORS
Trisodium citrate, dihydrate
Composition of standard and reduced osmolarity ORS solutions
||Standard ORS solution
||Reduced Osmolarity ORS solutions|
(mEq or mmol/l)
(mEq or mmol/l)
(mEq or mmol/l)
(6, 14, 22-27)
(mEq or mmol/l)
(13, 15-18, 28-29)
Questions and Answers:
Why has a “New” Oral Rehydration Salts (ORS) formula been developed?
Why “reduced osmolarity”?
Is diarrhoea really that much of a problem for children?
When will the new ORS be available?
What do I do with the old ORS solution? Should I discard it and only use the new low osmolarity ORS solution?
What about local production of the new ORS?
How should the new ORS solution be given?
Is there any risk associated with the use of this new ORS?
What is the cost of the new ORS?
Frequently Asked Technical Questions:
- What should we advise mothers to give at home to a child with diarrhoea,
but who has no signs of dehydration?
- Should I continue to breastfeed my child with diarrhoea?
- Should we advise mothers to continue to feed a child who has diarrhoea?
- When should I take my child with diarrhoea to a health centre?
- What should I do in case of vomiting?
- What should I do in case of electrolyte disturbances in a child with
- What should I do if intravenous therapy is not available for a severely
- When should I suspect cholera in a child with diarrhoea?
- How can I assess for dehydration in a severely malnourished child?
- What should I do in case of fever in a child with diarrhoea?
- What should I do in case of convulsions in a child with diarrhoea?
- Should we give vitamin A to a child with diarrhoea?
- Should we give zinc supplementation to a child with diarrhoea?
- Can I give anti-diarrhoeal drugs to a child with diarrhoea?
- What antimicrobials can be used with ORS in the clinical management of
- How can we protect our water?
- How important is handwashing?
New item numbers:
The item numbers will change as follows, as the new formulation replaces the existing ORS:
1561110 - ORS, 1L sachet/Box-100
1561120 - ORS, 1L sachet/Box-100
1561111 - ORS, 1 L sachet/CAR-1000
1561121 - ORS, 1 L sachet/CAR-1000
1561120 Oral reh.salts,new formula,1L s/BOX-100
1561121 Oral reh.salts,new formula,1L s/CAR-1000
1561111 Oral rehydration salts 1L sach./CAR-1000
26 Water & electrolytes
General Description: NEW REDUCED OSMOLARITY ORS
Oral Rehydration Salts (ORS), a new reduced osmolarity formulation, sachet for 1
litre, box of 100 sachets.
Mixture of glucose and electrolytes, dry, powdered homogenous, packed in
hermetically sealed, laminated sachets each to contain:
Anhydrous glucose: 13.5 grams / litre.
Sodium chloride: 2.6 grams / litre.
Trisodium citrate dihydrate: 2.9 grams / litre.
Potassium chloride: 1.5 grams / litre.
Suitable flow agent may be used as an excipient.
Minimum requirements for raw materials:
Glucose: food grade
Other ingredients: BP, USP, Int. Ph. or Eur.ph.
Moisture of the finished product at the time of delivery less than 2%.
The contents of one sachet to be readily soluble in one litre of cold water to
give a clear colourless solution containing:
Glucose: 75 mEq ± 10%
NA+: 75 mEq or mmol / litre ± 10%
CL-: 65 mEq or mmol / litre ± 10%
Citrate: 10 mmol / litre ± 10%
K+: 20 mEq or mmol / litre ± 10%
Osmolarity: 245 mmol / litre
Specification for packing foil:
Polyethylene 50 microns,
Aluminium minimum 9 microns
Polyester 12 microns.
Size of sachet: Approximately 60 x 90 mm.
Sachet should have a cut or v-shaped nick for easy opening without spillage.
The oral powder must comply with the requirements stated under Oral Powder BP
and Oral Rehydration Salts BP.
Packaging and labelling:
Box of 100 sachets.
Required label text:
Blue on white background in English/French/Spanish languages on each sachet.
The UNICEF name/logo must be included.
Dehydration from acute diarrhoea.
In case of cholera a higher concentration of sodium may be required.
Fluid and electrolyte loss in acute diarrhoea, by mouth,
ADULT: 200 to 400 ml solution after every loose motion.
INFANT and CHILD: according to plans A, B or C.
(Please refer to WHO Formulary 2004 for details).
Vomiting. May indicate too rapid administration; hypernatraemia and
hyperkalaemia may result from overdose in renal impairment or
administration of too concentrated a solution.
Component of a kit:
9906604 - New emergency health kit - basic unit.
* Reduced osmolarity oral rehydration salts (ORS) formulation
Report from a meeting of experts jointly organized by UNICEF
and WHO. WHO/CAH/01.22; (back to
Programme Division and Supply Division have prepared detailed questions and
answers (Q&A) on the new ORS and common technical issues, provided below.
For more details, please contact the Pharmaceutical &
Micronutrients Team, UNICEF Supply Division, at email@example.com.
the United Nations Children’s Fund (UNICEF), Supply Division, April
11 December 2002
Application to change the composition of
Oral Rehydration Salts (ORS) in the next revision of the
WHO Model List of Essential Medicine
1. Summary Statement
For more than 25 years WHO and UNICEF have recommended a single
formulation of glucose-based Oral Rehydration Salts (ORS) to prevent or
treat dehydration from diarrhoea irrespective of the cause or age group
affected. This product, which provides a solution containing 90 mEq/l of
sodium with a total osmolarity of 311 mOsm/l, has proven effective and
without apparent adverse effects in worldwide use. It has contributed
substantially to the dramatic global reduction in mortality from
diarrhoeal disease during the period.
For the past 20 years, numerous studies have been undertaken to develop an
“improved” ORS. The goal was a product that would be at least as safe and
effective as standard ORS for preventing or treating dehydration from all
types of diarrhoea but which, in addition, would reduce stool output or
have other important clinical benefits. One approach has consisted in
reducing the osmolarity of ORS solution to avoid possible adverse effects
of hypertonicity on net fluid absorption. This was done by reducing the
solution’s glucose and salt (NaCl) concentrations .
Studies to evaluate this approach were reviewed at a consultative
technical meeting held in New York (USA) in July 2001 1, and technical
recommendations were made to WHO and UNICEF on the efficacy and safety of
reduced osmolarity ORS in children with acute non-cholera diarrhoea, and
in adults and children with cholera.
These studies showed that the efficacy of ORS solution for treatment of
children with acute non-cholera diarrhoea is improved by reducing its
sodium concentration to 75 mEq/l, its glucose concentration to 75 mmol/l,
and its total osmolarity to 245 mOsm/l. The need for unscheduled
supplemental IV therapy in children given this solution was reduced by
33%. In a combined analysis of this study and studies with other reduced
osmolarity ORS solutions (osmolarity 210-268 mOsm/l, sodium 50-75 mEq/l)
stool output was also reduced by about 20% and the incidence of vomiting
by about 30% . The 245 mOsm/l solution also appeared to be as safe and at
least as effective as standard ORS for use in children with cholera.
The reduced osmolarity ORS containing 75 mEq/l sodium, 75 mmol/l glucose
(total osmolarity of 245 mOsm/l) is as effective as standard ORS in adults
with cholera. However, it is associated with an increased incidence of
transient, asymptomatic hyponatraemia. This reduced osmolarity ORS may be
used in place of standard ORS for treating adults with cholera, but
careful monitoring is advised to better assess the risk, if any, of
Because of the improved effectiveness of reduced osmolarity ORS solution,
especially for children with acute, non-cholera diarrhoea, WHO and UNICEF
now recommend that countries use and manufacture the following formulation
in place of the previously recommended ORS solution with a total
osmolarity of 311 mOsm/l.
|Reduced osmolarity ORS
|Reduced osmolarity ORS
Trisodium citrate, dihydrate
2. Name of the Focal Point
This application is presented by the Department of Child and Adolescent
Health and Development (CAH) of the WHO. The focal point in this
Dr O. Fontaine Medical Officer, CAH
3. Organizations consulted or supporting the application
The new ORS formulation was officially released by WHO and partners during
the United Nations General Assembly Special Session on Children in New
York, 8 May. Dr Brundtland, Director General of WHO, Ms Bellamy, Executive
Director of UNICEF, Dr Peterson, Assistant Administrator of USAID, and the
Minister of Human Resources from India launched the new formula in a press
and photo event.
UNICEF, USAID and MSF are supporting this application.
4. International Non-proprietary name of the medicine
Oral Rehydration Salts
5. Individual medicine
Although ORS is an individualised medicine, with a very precise
composition, the EDL could also include the fact that WHO/UNICEF have
published criteria for acceptable ORS formulations. These criteria are
listed below; they specify the desired characteristics of the solution
after it has been prepared according to the instructions on the packet:
|The total substance concentration:
||(including that contributed by glucose) should be within the range
of 200-310 mmol/l
|The individual substance concentration:
|should at least equal that of sodium but
should not exceed 111 mmol/l
|should be within the range of 60-90 mEq/l
|should be within the range of 15-25 mEq/l
|should be within the range of 8-12 mmol/l
|should be within the range of 50-80 mEq/l
6. Public Health Relevance
We estimate that the dramatic improvement in home management of diarrhoea
that has taken place between 1990 and 1995 has saved about 1 million
children annually. In 1990, oral rehydration salts (ORS) were used in
approximately a third of diarrhoea cases, and by mid-decade the average
was 85% among 33 countries that accounts for almost half of the world’s
7. Treatment details
These have not changed at all and the information contained on page 397 of
the WHO Model Formulary is still perfectly adequate.
For children with acute non-cholera diarrhoea, reduced osmolarity
ORS solutions (215-245 mOsm/l) with 75 mEq/l or less of sodium and 75-90
mmol/l of glucose are safe. When compared with standard ORS solution,
these solutions were associated with reduced stool output, reduced
vomiting and, especially, reduced need for unscheduled IV therapy. With
regard to reduced stool output and reduced vomiting, this benefit may be
somewhat greater for solutions with <75 mEq/l sodium (210-260 mOsm/l) than
for a solution with 75 mEq/l sodium (245 mOsm/l). However, in terms of
reduced need for unscheduled IV therapy, the benefit was similar for
solutions with 75 mEq/l sodium (245 mOsm/l) and for those with <75 mEq/l
sodium (210-260 mOsm/l).
For children with cholera, reduced osmolarity ORS solutions
(245-268mOsm/l) containing 70-75 mEq/l of sodium and 75-90 mmol/l glucose
were at least as effective as standard ORS and, although further data
should be obtained during routine use, appeared to be safe.
For adults with cholera, a reduced osmolarity ORS solution with 75
mEq/l of sodium and 75 mmol/l of glucose is as effective as standard
WHO/UNICEF ORS solution.
All this information is available in tow recently published document:
(a) Reduced osmolarity oral rehydration salts (ORS) formulation – A report
from a meeting of experts jointly organised by UNICEF and WHO – Unicef
House, New York, USA, 18 July 2001 (WHO/FCH/CAH/01.22)
(b) S.K. Hahn, Y.J. Kim, P. Garner. Reduced osmolarity oral rehydration
solution for treating dehydration due to diarrhoea in children: systematic
review. Brit Med J 2001, 323:81-5.
In adults with cholera, some concern remained about the possible risk of
symptomatic hyponatraemia with this solution. This concern was not
considered sufficient to prevent the use of this solution to treat adults
with cholera. It was agreed, however, that, to gain additional clinical
data on the safety of reduced osmolarity ORS, the incidence of biochemical
and symptomatic hyponatraemia should be monitored when this solution is
first introduced for routine use. Because seizures are rare in adults with
cholera, an increase in the incidence of this symptom should be easily
10. Summary of data on comparative cost and cost effectiveness
A decision analysis model to evaluate possible economic benefits of using
reduced osmolarity ORS in place of standard ORS was considered.
Assumptions used in the analysis were based on consensus and results of
randomized clinical trials (where available) concerning (i) the incidence
of unscheduled intravenous fluid therapy in patients given standard or
reduced osmolarity ORS (15% for standard ORS, 9% for reduced osmolarity
ORS; range tested, 0%-100%), (ii) the probability of seizures in patients
who develop hyponatraemia (1%; range tested, 0%-20%) and, (iii) the
probability of death when intravenous fluid therapy is not available for
patients in whom dehydration is not corrected by oral therapy, or recurs
during therapy (50%; range tested, 1%-100%). A revised model was developed
that also included costs to the health care system for standard and
reduced osmolarity ORS, intravenous fluid therapy, evaluation and
treatment of seizures, and death.
The model was constructed as a decision tree with standard ORS and reduced
osmolarity ORS as the two options, with a time horizon of two days. The
constructed model, where possible, was biased against reduced osmolarity
ORS. The probability of needing IV under standard ORS therapy was taken as
0.15, based on the recently published meta-analysis (19). The reduction of
30 % in the need of IV if given reduced osmolarity ORS was based on the
same source. The probability of IV access was taken as 0.50, based on
opinion of the assembled experts. The probability of death, given the need
for IV therapy, but none available, was taken as 0.50, also based on the
opinion of the assembled experts. The probability of seizures, when given
reduced osmolarity ORS therapy, was taken as 0.01, the upper limit of
rates observed in all clinical trials of reduced osmolarity ORS indexed in
Medline. Standard ORS therapy was deemed not to lead to any
electrolyte-based morbidities. The following costs were included, all
based on expert opinion:
|cost of reduced osmolarity ORS per patient
cost of standard ORS per patient
cost of IV therapy per patient
cost of seizure diagnostic and treatment
cost of death, to health system
All results were checked by one-way and two-way sensitivity analyses on
Comparing the reduction in need for intravenous fluids, the incidence of
seizures, as well as costs (excluding the start-up cost of implementing
the program), the decision analysis model favoured the reduced osmolarity
ORS in all comparisons. Specifically, a total of 14,000 deaths per million
episodes of diarrhoea with some dehydration (moderate dehydration) would
be avoided with the reduced osmolarity ORS, by reducing the number of
treatment failures. This would be associated with a possible addition of
10,000 seizures per million episodes of diarrhoea with some dehydration,
almost all in young children. In other words, the estimated number of
seizures per death averted would be 0.7. This could result in a cost
savings of $500 per death averted, or $7.1 million per million episodes.
Using sensitivity analysis, reduced osmolarity ORS was always preferred,
regardless of changes in the rate of deaths with this model.
11. Summary of regulatory status of the medicine
12. Pharmacopoieal standards
The old formulation is included in the British Pharnacopoeia and the
We are going to contact the British Pharmacopoeia to explore the
possibility to have the new formulation of ORS included in their next
revision in 2004.
13. Proposed revised text for the WHO Model Formulary
The only change would concern the table on page 398, in section 26.1.1
entitled “Oral rehydration”, which should be changed with the following
|Oral rehydration salts
Glucose salt solution
||2.6 g/litre of clean water
||13.5 g/litre of clean water
||1.5 g/l of clean water
||2.9 g/l of clean water
When glucose and trisodium citrate are not available, they may be replaced
Sucrose (common sugar) 27 g/litre of clean water
Sodium bicarbonate 2.5 g/litre
of clean water
Eventually, an additional paragraph could be included to indicate what is
considered by WHO/UNICEF as an acceptable ORS formulation.
 Reduced osmolarity oral rehydration salts (ORS) formulation – Report from a meeting of experts jointly
organised by UNICEF and WHO. WHO/CAH/01.22
Low-osmolarity ORS On-line Resources
A complete and up-to-date list of the following and related resources can be found at
Enhanced Diarrheal Disease Control
Clinical management of acute diarrhoea (2004)
This official joint statement updates previous WHO/UNICEF
recommendations on the management of acute diarrhea, taking into
consideration new research findings that indicate the success of
interventions incorporating reduced-osmolarity ORS and zinc
World Health Organization (WHO), UNICEF
pdf English 241
pdf Español 409
pdf Français 418
Diarrhoea treatment guidelines including new
recommendations for the use of ORS and zinc supplementation for
clinic-based healthcare workers (2005)
These guidelines were developed to advise clinic-based health
workers on implementing the latest WHO/UNICEF recommendations for
ORS and zinc supplementation in the clinical management of
US Agency for International Development (USAID) Micronutrient
pdf English 401
Guidelines for new diarrhea treatment protocols for
community-based healthcare workers (2005)
These guidelines were developed to advise community health care
workers who assist parents with home treatment of children with
diarrhea with regard to the latest WHO/UNICEF recommendations.
USAID Micronutrient Program
pdf English 128
The treatment of diarrhoea: A manual for physicians and
other senior health workers (2005)
Developed for physicians treating infectious diarrhea in young
children, this manual has been updated to include guidelines for
the use of reduced-osmolarity ORS and zinc supplements.
pdf English 1
The evolution of diarrhoeal and acute respiratory
disease control at WHO: Achievements 1980–95 in research,
development and implementation (1999)
This document summarizes the evolution of WHO’s strategy toward
researching and implementing interventions for diarrheal disease
and acute respiratory disease control in the developing world,
including a focus on current integrated strategies for child
pdf English 504
Expert consultation on oral rehydration salts (ORS)
This meeting report provides background information essential to
an expert committee’s consensus toward reducing the osmolarity of
previous ORS standards.
WHO, UNICEF (WHO/FCH/CAH/01.22)
Improved formula for oral rehydration salts to save
children’s lives (2006)
This press release announces WHO and UNICEF adoption of the new,
reduced-osmolarity formulation of ORS and provides links to
informative resources from both organizations.
Monograph for oral rehydration salts (2005)
This updated monograph on the new, low-osmolarity formula of ORS
was revised to provide the quality specifications as adopted by
the WHO Expert Committee on Specifications for Pharmaceutical
Preparations in October 2005. The monograph was prepared for
inclusion in the fourth edition of The International
Pharmacopoeia, currently in press.
WHO, The International Pharmacopoeia
Oral rehydration salts: Production of the new ORS
Updated in 2006, this manual provides comprehensive information on
manufacturing the new formula of low-osmolarity ORS.
WHO, UNICEF (WHO/FCH/CAH/06.1)
pdf English 2.3
Implementing the new recommendations on the clinical
management of diarrhoea: Guidelines for policy makers and
programme managers (2006)
pdf English 336
This manual provides information to guide to introduction and/or
scale up of the new ORS formulation and zinc for clinical
management of diarrhoeal diseases.
pdf English 385
Managing acute gastroenteritis among children: Oral
rehydration, maintenance, and nutritional therapy (2003)
This publication provides guidelines for the use of ORS for
clinical management of diarrhea, discusses various formulations of
ORS, addresses challenges related to the administration of ORS,
and encourages the use of ORS in the home to potentially avoid
clinic visits and hospitalizations.
US Centers for Disease Control and Prevention. Morbidity and
Mortality Weekly Report. 52(RR-16):1-16.
pdf English 450
Reducing deaths from diarrhea through oral rehydration
This report evaluates global use of ORS and its impact on reducing
diarrheal disease mortality. The authors call for continued and
improved data collection regarding the use of ORS and note the
benefits such data offer toward informing public health policies
Victora CG, Bryce J, Fontaine O, Monasch R. Bulletin of the
World Health Organization. 78(10):1246-1255.
Treatment of diarrhoeal diseases: Information for
pharmacists and other drug sellers (2001)
This guide aims to improve the practices of pharmacists and drug
sellers by providing details on avoiding inappropriate
interventions for diarrhea, including underuse of ORS and overuse
WHO Department of Child and Adolescent Health and Development
Clinical trials of improved oral rehydration salt
formulations: A review (1994)
pdf English 882
The authors of this review assess the efficacy and use of
different formulations of ORS, as determined in previously
Bhan M, Mahalanabis D, Fontaine O, Pierce N. Bulletin of the
World Health Organization. 72(6):945–955.
Falling diarrhoea mortality in Northeastern Brazil: Did
ORT play a role? (1996)
This study provides data that supports the impact of ORS on
dramatic reductions in diarrhea deaths recorded after its
introduction in Brazil in the 1980s.
Victora C, Olinto M, Barros F, Nobre L. Health Policy and
pdf English 707
pdf English/Español 430
Impact of oral rehydration and selected public health
interventions on reduction of mortality from childhood diarrhoeal
diseases in Mexico (1996)
This study evaluates the impact of education, ORS introduction,
and sanitation improvements on the incidence of diarrheal disease
mortality in Mexico between 1978 and 1993.
Gutierrez G, et al. Bulletin of the World Health Organization.74(2):189–197.
Multicentre evaluation of reduced-osmolarity oral
rehydration salts solution (abstract only; 1995)
The investigators in this study compared the efficacy of reduced-osmolarity
and standard ORS in children with acute diarrhea in four
developing countries and determined that reduced-osmolarity ORS is
the more appropriate intervention for children with non-cholera
International Study Group on Reduced-osmolarity ORS Solutions.
Reduced osmolarity oral rehydration solution for
treating dehydration due to diarrhoea in children: Systematic
Hahn S, Kim Y, Garner P. British Medical Journal;
Another evaluation of standard versus reduced-osmolarity ORS, this
analysis involved data from 15 trials and determined that
treatment with reduced-osmolarity solution resulted in decreased
stool output and vomiting and reduced the need for intravenous
pdf English 122
updated: 23 April, 2014