Nurses encouraging a patient to drink an Oral Rehydration Solution
to combat dehydration caused by cholera.
Oral rehydration therapy (
ORT) is
a simple, cheap, and effective treatment for
dehydration associated with
diarrhea, particularly
gastroenteritis, such as that caused by
cholera or
rotavirus. ORT consists of a
solution of
salts and
sugars which is taken
by mouth. It is used around
the world, but is most important in the
developing world, where it saves millions
of children a year from death due to
diarrhea—the second leading cause of death in
children under five.
Definition
The definition of ORT has changed over time, broadening in scope
and encompassing a definition of a specific therapy appropriate for
rehydration. Initially, in the early 1980s, ORT was defined only as
the official solution prescribed by the
WHO/
UNICEF. It was later changed
in 1988 to also encompass recommended home fluids, as it was noted
that access to the official preparation was not always readily
available. It was amended once again in 1988 to include continued
feeding as appropriate management. In 1991, the definition was
changed to define ORT as any increase in administered fluids. The
final change came in 1993, and is the definition used today, which
states that ORT is an increase in administered fluids and continued
feeding.
Administration
According to current WHO/UNICEF guidelines, ORT should begin at
home with "home fluids" or a home-prepared "sugar and salt"
solution at the first sign of diarrhea to prevent dehydration.
Feeding should be continued at all times. However, once dehydrated,
the regimen should be switched to official preparations of
Oral Rehydration Solution (
ORS)
at the appropriate dosing times to ensure adequate hydration.
During the home-prepared stage, care should be taken to select the
proper type of fluid to administer. The fluids given must contain
both sugar and salt in the proper amounts. Liquids without both
these components must be avoided. Too little or not enough of
either can be ineffective and/or detrimental. Liquids without salt
can lead to low body salt (
hyponatremia) because the diarrheal stool
contains salt and must be replenished. Additionally, sugar must
also be present in the administered fluid because salt absorption
is coupled with sugar in the intestine via the
SGLT1 transporter.
Appropriate drinks to administer during the home-prepared stage
include official ORS solutions, salted rice water, salted
yogurt-based drinks, and vegetable or chicken soup with salt.
Clean water should always be used when
preparing a solution. Drinks to be avoided include soft drinks,
sweetened fruit drinks, sweetened tea, coffee, and medical tea
infusions with diuretic effects due to high sugar content and/or
caffeine. In addition, drinks with a high concentration (
osmolarity) of sugar can worsen diarrhea as they
draw water out of the body and into the intestine because of their
hypertonicity.
If dehydration ensues even when ORT is begun with a home-prepared
solution, if available, a qualified health professional should
manage further rehydration with ORS solution to ensure proper
electrolyte balance and to facilitate
rapid rehydration, and treatment of the underlying cause of
dehydration if appropriate.
Availability
By definition, ORT is available anywhere that adequate nutrition is
available. ORS, on the other hand, is typically packaged in
pre-measured sachets that are ready to be mixed in with water
(generally 1
L). These are available via
commercial manufacturers or supplied by local/regional governments
or relief agencies such as
UNICEF. In 1996
alone, UNICEF distributed 500 million sachets of ORS to over 60
developing nations. Among the commercial suppliers, many variations
in formulations abound and there is no restriction as to what
formulation can be marketed as ORS. As such, some vendors include
extra sugar or other flavoring to make the product more palatable,
popular examples in the US being the various flavors and
formulations of
Pedialyte.
Where ORS sachets are not available, home-prepared solutions are
typically used. Many recipes exist, but most are some
easy-to-remember combination of water, sugar, and salt. An example
of such is 1 level teaspoon of salt, 8 level teaspoons of sugar,
and (optionally) 4 ounces of orange juice; mixed into 1 liter of
clean water. If the water source is questionable, it should be
boiled for 10 minutes and allowed to cool before mixing the
solution.
WHO/UNICEF definition of ORS
The
WHO and
UNICEF jointly
maintain the official guidelines for the contents of reduced
osmolarity ORS packets. These guidelines
are used by manufacturers of commercial ORS packets that are
available for purchase and were last updated in 2006. The reduced
osmolarity ORS solution has a total osmolarity of 245 m
mol/
L.
Zinc supplementation
There is an additional recommendation of
zinc
supplementation for the management of diarrheal disease in addition
to ORS, particularly for pediatric patients. For children under
five, zinc supplementation significantly reduces the severity and
duration of diarrhea and is strongly recommended as a supplement
with ORS for dehydrated children. Preparations are available as a
zinc sulfate solution for adults, a
modified solution for children, and also a tablet form for
children.
Switch to reduced osmolarity ORS
In 2003, WHO/UNICEF changed the ORS formula to a reduced osmolarity
version from what it had been recommending for over two decades
prior. This change was in response to numerous studies that showed
that the standard ORS formula was ineffective in reducing diarrheal
stool output compared to other solutions, including rice water.
Additionally, further studies showed that a reduced osmolarity
solution not only decreased stool output, but also resulted in less
vomiting and fewer unscheduled intraveneous therapy. Although
UNICEF certifies reduced osmolarity ORS for all forms of
dehydration, at least one study cautions that for high stool output
cholera-based diarrhea, reduced osmolarity ORS may not sufficiently
replenish electrolyte levels, leading to
hyponatremia. Though the actual consequence of
this appeared negligible, further study was recommended.
The change reduced the osmolarity of the ORS solution from 311
m
mol/
L to
245 mmol/L. The ingredients reduced in concentration were
glucose and
sodium chloride.
Potassium and
citrate
concentrations remained the same. The benefits of the reduced
osmolarity ORS are reducing stool volume by about 25%, reducing
vomiting by nearly 30%, and reducing the need for unscheduled
intraveneous therapy by 33%.
Physiological basis
Fluid from the body is normally pumped into the
intestinal lumen
during digestion. Since this fluid is typically
isosmotic with
blood, it
contains a high concentration of
sodium
(approx. 142 m
Eq/L). A
healthy individual will secrete 20-30
grams of
sodium per day via intestinal secretions. Nearly all of this is
reabsorbed by the intestine, helping to maintain constant sodium
levels in the body (
homeostasis).
Because there is so much sodium secreted by the intestine, without
intervention, heavy continuous diarrhea can be a very dangerous and
potentially life-threatening condition within hours. This is
because liquid secreted into the intestinal lumen during diarrhea
passes through the gut so quickly that very little sodium is
reabsorbed, leading to very low sodium levels in the body (severe
hyponatremia). This is the motivation
for sodium and water replenishment via ORT.
Sodium absorption via the intestine occurs in two stages. The first
is at the outermost cells (intestinal
epithelial cells) at the surface of the
intestinal lumen. Sodium passes into these outermost cells by
co-transport facilitated diffusion (
symport diffusion) via the
SGLT1 protein. From there, sodium is pumped out of the
cells (
basal side) and into the
extracellular space by
active transport via the
sodium potassium pump.
The co-transport of sodium into the epithelial cells via the SGLT1
protein requires
glucose or
galactose. Two sodium ions and one molecule of
glucose/galactose are transported together across the
cell membrane through the SGLT1 protein.
Without glucose or galactose present, intestinal sodium will not be
absorbed. This is the reason glucose is included in ORS
solutions.
History
Prescriptions from the ancient physician
Sushruta date back over 2500 years with treatment
of acute diarrhea with
rice water,
coconut juice, and
carrot soup. However, this knowledge did not carry
over to the Western world, as dehydration was found to be the major
cause of death secondary to the 1829 cholera pandemic in Russia and
Western Europe. In 1831,
William Brooke O'Shaughnessy
noted the loss of water and salt in the stool of cholera patients
and prescribed
intravenous fluid
therapy (IV) to compensate. The results were remarkable, as
patients who were on the brink of death from dehydration recovered.
The mortality rate of cholera dropped from 70% to 40% with the use
of
hypertonic IV solutions.
IV fluid replacement became entrenched as the standard of care for
moderate/severe dehydration for over a hundred years. ORT replaced
it with the support of several independent key advocates that
ultimately convinced the medical community of the efficacy of
ORT.
In the late 1950s, ORT was prescribed by
Dr. Hemendra Nath Chatterjee in
India for cholera patients. Although his findings predate
physiological studies, his results failed to gain credibility and
recognition because they did not provide scientific controls and
detailed analysis. Credit for discovery that in the presence of
glucose, sodium and chloride became absorbable during diarrhea (in
cholera patients) is typically ascribed to Dr. Robert A. Phillips.
However, early attempts to translate this observation into an
effective oral rehydration solution failed, due toincorrect
solution formula and inadquate methodology.
In the early 1960s, biochemist
Robert
K. Crane discovered the
sodium-glucose
cotransport as the
mechanism for intestinal glucose absorption. Around the same time,
others showed that the intestinal mucosa was not disrupted in
cholera, as previously thought. These findings were confirmed in
human experiments, where it was
first shown that a glucose-saline oral therapy solution
administered in quantities matching measured diarrhea volumes was
effective in significantly decreasing the necessity for IV fluids
by 70-80%. These results helped establish the physiological basis
for the use of ORT in
clinical
medicine.
The events surrounding the
Bangladesh Liberation War in 1971
convinced the world of the effectiveness of ORT. As medical teams
ran out of intravenous fluids to treat the spreading cholera
epidemic, Dr.
Dilip Mahalanabis
instructed his staff to distribute Oral Rehydration Salts (ORS) to
the 350,000 people in refugee camps. Over 3,000 patients with
cholera were treated, and the
death
rate was only 3.6%, compared to the typical 30% seen in
intravenous fluid therapy. The fact that ORT was delivered
primarily by family members instead of trained staff across such a
large population in an emergency fashion was demonstrative proof of
the utility of ORT against cholera.
Between 1980 and 2006, ORT decreased the number of wordwide deaths
from 5 million a year to 3 million a year. Death from diarrhea was
the leading cause of infant mortality in the developing world until
ORT was introduced. It is now the second leading cause of mortality
for children under 5, accounting for 17% of all deaths, second only
to
pneumonia, at 19%. Its remarkable
success has led to naming the discovery of its underlying
physiological basis as "potentially the most important medical
advance this century." ORT is part of UNICEF's GOBI program, a low
cost program to increase child survival in developing countries,
including Growth monitoring, ORT, Breastfeeding, and Immunization.
Despite the success and effectiveness of ORT, its uptake has
recently slowed and even reversed in some developing countries.
This raises concerns for increased mortality from diarrhea and
highlights the need for effective community-level behavioral change
and global funding and policy.
The individuals and organizations involved in the development of
ORT have been recognized widely.
The 2001 Gates Award for Global Health was
awarded to the Centre for Health and Population
Research
for its role in the development of ORT. In
2002, the first
Pollin Prize for Pediatric
Research was awarded to Dr. Norbert Hirschhorn, Dr.
Dilip Mahalanabis, Dr.
David Nalin, and Dr. Nathaniel F. Pierce for
their contributions in the discovery and implementation of ORT. For
promoting the use of ORT, the 2006
Prince Mahidol Award was awarded to Dr.
Richard Alan Cash, Dr.
David Nalin, and
Dr.
Dilip Mahalanabis in the field
of public health; and to Dr. Stanley G Schultz in the field of
medicine.
References
- Robert K. Crane, D. Miller and I. Bihler. “The restrictions on
possible mechanisms of intestinal transport of sugars”. In:
Membrane Transport and Metabolism. Proceedings of a Symposium held
in Prague, August 22–27, 1960. Edited by A. Kleinzeller and A.
Kotyk. Czech Academy of
Sciences, Prague, 1961, pp. 439-449.