Trainer Attachment 5D: Oral rehydration therapy: the scientific and technical basis
DR. NORBERT HIRSCHHORN
John Snow Public Health Group
National Control of
Diarrheal Diseases Program
When a child has diarrhea it loses body fluids - mainly essential
minerals and water - and becomes dehydrated. So mix up some salts and sugar in
water, and feed the solution to the child, as much as he/she will take until the
child is no longer dehydrated, and diarrhea has slowed down or stopped. Make
sure the child continues to take food or breast milk.
This is oral rehydration therapy, and it seems so simple
(compared, say, to manipulation of genes or artificial hearts) that one may
wonder what science has had to do with ORT, or why we need continue scientific
studies on ORT. Many older physicians, nurses, or mothers have protested, "This
is nothing new, we have been practicing ORT for years" Some of the great
clinicians wrote about ORT thirty to forty years ago - Darrow, Harrison,
Chatterjee. But this is precisely the point: they wrote about using ORT, but did
not know how ORT works (nor to be fair, could they have them and so there was no
further development or spread of their anecdotal experience until some decades
later. Even today, when we fail to understand and use the scientific approach,
we continue erroneous or wasteful methods of therapy; actually, this is the case
in all fields of medicine and public health. Not everyone who practices ORT must
be a scientist, but the spirit of inquiry and joy of discovery which suffuses
science may be shared by all. The spirit of inquiry is present in five stages:
1. Observation - using all one's senses to
capture events and think about them: it was noticed that children with
dehydration drank the oral rehydration solution vigorously and greedily and,
when nearly hydrated, slowed down and often went to sleep.
2. Measurement - taking one's observations and gauging some
values on scales of time, length, amount, and degree: children who drank oral
rehydration solution at will tended to drink close to what their initial deficit
was, as measured by intake, output, and change in body weight.
3. Creative hypotheses - thinking through the implications
of a measured observation and asking interesting questions: who can choose more
closely the correct amount of fluid for rehydration, the dehydrated child or the
4. Testing experimenting - within the ethical boundaries of
conduct, designing, with proper statistical force and safeguards against bias, a
test of the hypothesis: in certain situations, children freely drinking oral
rehydration solution became hydrated faster and reached better fluid and mineral
balance than those on intravenous solutions controlled by physicians.
5. Application - using the results of scientific testing
for the widest possible benefit. It is as Jon Rohde and Robert Northrup have
written, "taking science where the diarrhea is" Human information must be shared
across all political and other boundaries.
The data and information I will present in this paper have gone
through several of these five stages of scientific inquiry.
ORT developed from two streams of inquiry, if I may use a liquid
metaphor. The first established what dehydration actually meant, how it related
to the clinical picture of the dying child, and what was needed to reverse the
situation. Believe it or not, this line of inquiry has taken nearly eighty years
to come to satisfactory resolution. The second line, still ongoing, is the
discovery of how the intestinal tract handles the movement of salts, nutrients,
and water between the body and the outside world.
The picture of the dying child is hauntingly familiar. The baby
has lost about 10% of its weight in fluid. This amounts to one liter of fluid in
a ten-kilogram child, or about a quart in a twenty-two pound baby. Now the child
has hollow, sunken eyes; its pulse is feeble or absent; its breathing is deep
and rapid; the skin, when pinched, tends to remain dented and inelastic; the
abdomen many be distended; urine has ceased to flow; the mouth is parched; the
eyelids do not quite shut properly; there are no tears. Dry as the child may be,
vomiting and watery diarrhea persist nearly to the end, and this stage may be
reached in as little as ten to twenty hours after onset of illness.
Virtually all these signs are due to loss of salt, water,
potassium, and sodium bicarbonate, all essential ingredients for life. Most of
the loss is in the watery stool, and some, especially in the case of potassium,
is from the urine. Regardless of the cause of diarrhea (rotavirus, cholera, E.
coli, etc.) or whether in Baltimore or in Bengal, once the child reaches these
clinical signs the amount of loss of water and minerals is roughly the same
(Table 1) This is fortunate in a way, because the replacement therapy may be
uniform and does not require us to know which specific microbe is doing the
mischief. Incidentally, while the loss of potassium is of the same magnitude as
that of sodium, the body stores of potassium are several times larger. So
replacement of sodium is more urgent and also helps conserve potassium.
Although the extreme case I have portrayed is present in 1% to 2%
of all bouts of diarrhea, it is sobering realize that with very few visible
signs of dehydration beyond thirst, the child may have already lost 5% of body
weight, halfway to death, in as little as five to ten hours. By the time parents
become alarmed, there may be only a few hours left in which to find competent
help. The majority of children who die, however, do linger for two to three
days: they have received some fluid, probably of dubious value, by mouth or
intravenously; the diarrhea may have slowed a little if various medicines are
tried. But by this time the parents may have exhausted their money or the skills
and resources of the local practitioner, and the nearest hospital is miles away.
The child needs fluid therapy: effective, affordable, trustworthy, nearby.
But we learned about ORT only after we knew how to apply
intravenous therapy. Beginning in the mid-1940s, diarrhea research centers in
Dhaka, Calcutta, Manila, Cairo, Baltimore, and Taipei proved that intravenous
solutions containing sodium chloride, potassium chloride, sodium bicarbonate (or
lactate or acetate) in a well-determined combination could be given rapidly so
that severely dehydrated children could, Lazarus-like, be resuscitated within
two to four hours. Lives are saved by the use of a polyvalent solution,
administered quickly with the correct proportion of ingredients. ORT is
successful foremost because of this principle, first discovered for intravenous
therapy. And we must still rely on intravenous fluids if the child is so
severely dehydrated that it cannot drink at all. With this principal exception,
what then makes ORT preferable to the intravenous route?
- It can be given by persons with little formal
education, even in the home.
- It needs no sterile equipment.
- It is inexpensive (a boon, incidentally, even to well-equipped
- It is safer and, under most circumstances, more effective.
- In a pinch, a less-effective formula can be prepared at home
from table salt and table sugar (sucrose)
- It allows parents to participate in the care of their children.
- It is comforting to the child and to the parents.
Let us now consider the second stream of inquiry that led to the
development of ORT: how the intestine handles salts and water
"What a piece of work is man," given form by skeleton, powered by
muscles, coordinated and programmed by a chemical-electric skein of nerves and
brain, nourished and defended by a red liquid distantly related to the
The intestine is but a hollow tube connected to the outside world
at both ends, the core around which the rest of the body is wrapped. The
intestine does many things, but its prime job is to take food, break it into
basic molecules that are usable by the body's cells, and transport these
molecules across the one-cell-thick lining that separates inside from out. To
digest food, it seems necessary to increase the surface area of the tube by
multiple folds on the surface of the tube and by fingerlike projections from
these folds, called "villa," which carry multiple digestive enzymes at or near
their surface. If the surface area is much reduced, as occurs in the disease
called "spree," key nutrients and vitamins are not absorbed. It also seems
necessary to suspend the particles in liquid and let digestive enzymes do their
chemical work. The ultimate source of the digestive liquid is the blood stream,
from which the intestine abstracts and secretes salty water free of blood or
serum. Secretion of salts and water seems largely to be the function of the
youngest cells in the lining, called the "crypt cells" end is controlled by a
marvelously organized sequence of enzymes, minerals, and small chemical
messengers which ´'know" just when to turn the flow on and off. Infectious
agents which cause diarrhea are able to turn the cell mechanisms for secretion
to a fixed "on" state until new cells replace the infected ones, usually in two
to four days, or until the microbes and toxins are cleared out by the defense
mechanisms of the body.
It has been estimated that the intestine of a healthy adult
secretes one hundred liters - 264 U.S. gallons - or more of fluid each day;
amazing, of course, but, given the total surface area of two million square
centimeters (the size of a ballroom carpet seventy by thirty feet), one hundred
liters represents but one drop per square centimeter per day Since the well
nourished adult body contains only forty-five liters of fluid altogether and the
adult would die if just seven to ten liters were permanently lost, there must be
a rapid, certain mechanism to put the digestive fluid back into the bloodstream
nearly as quickly as it is secreted. In what is surely one of the neater bits of
engineering, the very molecules produced by the liquidy digestion are the ones
that help transport the salts and water back across the intestinal cell, from
there to return to the inner pools of body fluid. The molecules that work this
way are principally glucose, the simple sugar derived from starch or table
sugar; galactose, a component of milk-sugar; and amino acids and peptides, the
products of protein digestion. Each of these molecules combines with sodium,
probably in close to a one-to-one ratio, and these dyads cross the cell
membrane, per haps by linking in a menage-a-trots to carrier protein molecules
anchored in the membrane. Water is pulled along by osmosis, and other minerals
(potassium, bicarbonate, more sodium) follow along, caught up in the stream, as
it were. Most of this absorption appears to take place in the upper, more
exposed regions of the villi, so that if there is extensive damage to villi
from, say, viral diarrhea, oral rehydration may fail: failure occurs in about 5%
to 10% of seriously ill children.
What is rather elegant about this system is that glucose, amino
acids, and peptides seem to enter the cell linked to sodium, but each class of
molecules joins with different carrier molecules or finds separate entrances
specific to each. One predicts that if one adds an amino acid - glycine, say -
to glucose in an oral rehydration solution, more fluid will be absorbed than if
glucose or glycine are used alone. This is just what happens, and, as you shall
hear shortly, this phenomenon promises a major advance in oral rehydration
therapy. But for the moment, let us leave the alimentary canal and return to the
The formula for the oral rehydration solution was originally
devised to combat epidemic outbreaks of cholera in which both adults and
children are affected and where lifesaving intravenous fluids are scarce. The
salts are packed in flat aluminum foil packets, paid for and stockpiled by
UNICEF ready for shipment to any country on demand. The formula, often referred
to as the "WHO formula,' was originally devised as a compromise between what
adults needed and children could tolerate. The composition, however, is more
inspired than that suggests (Table 2). The amount of salt is sufficient to
replace sodium and water losses in severe de: hydration (Table 1), although
adults may need to drink extra amounts. Glucose at 2% is optimal, as many
studies suggest that water is best absorbed when glucose and sodium are in the
ratio of one-to-one, and glucose does not exceed a concentration of 2 1/2%.
Potassium deficit is only partially met by this formula because it is unsafe to
completely replace losses so fast, but initial replacement must be started
quickly (some suggest increasing the replacement rater Acidosis is corrected
much faster with bicarbonate than without This formula has proved surprisingly
versatile in the treatment of hundreds of thousands of children and adults, with
documented success in #5% to 95% of cases, under the following range of
- in persons who are able to drink;
- in malnourished children and the well nourished;
- in bacterial and viral causes of dehydrating diarrhea;
- with serum sodium levels as low as 110 milliequivalents per
liter to as high as 165 extremes immediately threatening to life;
- with severe derangement of the blood alkaline-acid balance to
the acid side (a condition called acidosis);
- in tropical climates and Baltimore winless;
- with no visible dehydration up to loss of body fluid equivalent
to 10% of body weight.
- with voluminous, continuing loss of diarrhea, up to 10
milliliters per kilogram body weight per hour.
Even vomiting does not bar success except in a few instances; in
fact, vomiting decreases in direct proportion to the degree of rehydration with
ORT what makes ORT so versatile, in addition to its balanced formula, is that
most children drink as much oral rehydration solution as is offered up to nearly
the amount of which they are deficient. When they are hydrated, or nearly so,
they seem to lose their taste for the fluid, then they either fall asleep, or
cry for food.
Crying for food: we must think of ORT as more than simply
rehydration with a solution of salts and sugar. ORT also means restoration,
quickly, of a normal diet. It is now well established that a principal cause of
malnutrition in children of the Third World is repeated episodes of diarrhea.
The reasons are several and interactive:
- children lose their appetite for food because of
salt and water loss and acidosis;
- children are often made to fast when they have diarrhea,
sometimes for several days, because it is feared that food makes diarrhea worse;
- potassium loss may make muscle tone too weak for eating and
- when a child is ill, anxiety and restlessness burn up calories
from the child's own stores of fat and protein (which may be already seriously
- diarrhea and fasting independently damage digestive enzymes in
the intestinal tract, leading to malabsorption and loss of food that is eaten.
- with each serious bout of diarrhea, a child loses weight and may
never catch up to its potential for growth and good nutrition.
In well-designed studies in the Philippines, Iran, Turkey, India
and Panama, ORT appeared to protect against acute weight loss with an episode of
diarrhea when the parent was also encouraged to continue to feed the child
despite the diarrhea. Breast milk, soft foods and porridges, even fish and fruit
and breads were advised. ORT restores a child's appetite u within a few hours,
so suddenly this advice made sense to parents. The protective effect was most
apparent in those already undernourished, and in those with repeated episodes of
diarrhea and protection seemed to last several months. But of course no food, no
We do not know, exactly how ORT works to protect nutrition, but we
observe regularly that rapid restoration of fluid and mineral balance restores
appetite. Potassium may play a key role here; there is also an intriguing
possibility, based on studies of adults who go without food, that the glucose in
ORT may help restore or protect intestinal digestive enzymes. The parent
certainly finds feeding the child more acceptable, and the child becomes more
Oral rehydration therapy is, thus, two therapies: rehydration and
continued feeding. ORT has already been proved to reduce mortality from
diarrhea. It would be an amazing achievement if ORT could also reduce the
prevalence of malnutrition.
This hope leads me to consider an impending development in ORT.
Often, parents" and physicians' prime concern is to stop the diarrhea, and until
they see otherwise, they do not believe that rehydration is the first order of
business. ORT does not stop diarrhea, which generally runs its own course of a
few days; we spend a lot of effort getting that point across. Perhaps we soon
will have the means to slow stool loss even while rehydrating the child.
You will recall, back in the alimentary canal, that the different
breakdown products, or metabolites, of digestion (sugars, peptides, amino acids)
linked up to sodium and promoted salt and water absorption through different
gates in the intestinal cell membrane. There is now sufficient evidence that if
we combine these metabolites in a single oral solution, we not only rehydrate
but can actually decrease the total loss of stool. Peptides and amino acids are
particularly necessary in the combination because they act on absorption all
along the small intestine, whereas the action of glucose is more confined to the
upper portion. Absorption of peptides and amino acids are also far less
susceptible than glucose to damage by diarrhea. So the next step is to develop
an enriched ORT, one that combines salt, potassium, bicarbonate, glucose or a
simple starch, and peptides or a simple protein. Here are some expected
advantages of such a formula.
- Diarrhea is lessened.
- With less diarrhea, there will be less waste of nutrients in
regular food, and possible more protection of intestinal enzymes.
- Common local foods, already familiar to parents, may be adapted
to form an enriched ORT.
Early studies with such a formula are encouraging. We look forward
now to a burst of research to define its optimal composition, the range of
severity of illness it can be used for, its advantages over the WHO solution and
food given separately, its cost and distribution. We will need to consider,
also, how we can enlist parents to prepare and use an enriched ORT at home.
Where does all this take us? From a global public health view, it
is possible that ORT is nothing more than a palliative until research produces
effective antidiarrheal vaccines. Now. sadly, for many children, ORT merely
postpones death. Optimists among us hope ORT programs will enable people to
trust other health services, such as family planning, to encourage better
nutrition and hygienic practices, to improve the health worker's morale, and to
help achieve "Health for All".
We hope these hopes prove true; they need testing. But little can
be advanced, I believe, as long as nations fail to make human welfare the first
This brings me full circle to the beginning of this paper.
The international agencies sponsoring this conference have done a
lot for our children. They support research; they supply services and
technicians; through a generous network of information they link scientists from
Boston to community health workers in Bangladesh; but most of all they
demonstrate that the global village exists: in helping our neighbor's child
survive we establish our common humanity.
AVERAGE WATER AND SALT LOSSES IN SEVERE DIARRHEA OF A
10-KILOGRAM CHILD BEFORE TREATMENT (milliequivalents)
COMPOSITION OF THE "WHO FORMULA" FOR ORAL
Grams per Liter Solution
Chemical Concentration in Millimoles per Liter Solution