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Oral rehydration therapy a review

Alexander K.C. Leung, Pauline Darling and Claude Auclair
The Journal of the Royal Society for the Promotion of Health 1987 107: 64
DOI: 10.1177/146642408710700210

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64
Oral rehydration therapy
ALEXANDER K. C. LEUNG, MBBS, FRSH, FRCPC, FAAP, MRCP(UK), MRCPI, DCH(LON), DCH(1),
Clinical Assistant Professor of Paediatrics, University of Calgary, Alberta, Canada,
PAULINE DARLING, MSc, Clinical Research Associate, Abbott Laboratories Limited, Montreal,
Canada and CLAUDE AUCLAIR, PhD, Director of Clinical Research, Abbott
Laboratories Limited, Montreal, Canada
ABSTRACT
REHYDRATION AND maintenance of adequate fluid and
electrolyte balance is the key to the management of the child
with acute diarrheal disease. Oral rehydration treatment has
been shown to be simple, practical, inexpensive, highly
effective and safe for developing as well as for developed
countries. A better understanding of the physiological
mechanisms implicated in diarrheal illness as well as
extensive clinical testing of oral rehydration solutions have
lead to the improvement of the composition of electrolyte,
carbohydrate and base constituents. The widespread use of
oral rehydration therapy may result in a decreased need for
hospitalization and less discomfort and complications
which are associated with intravenous rehydration therapy.
INTRODUCTION
SEVERE DIARRHEAL disease remains one of the leading
causes of mortality and morbidity in children, especially in
children under the age of 3 in the less developed countries. In
those countries diarrheal attacks may occur as frequently as
once every month in young children2; cumulative mortalities
of 25-40% among children under the age of 5 are common.
Even in England and Wales, the number of children under
the age of 4 admitted to hospitals for the treatment of
gastroenteritis was 855 per 100,000 in the early seventies
with a mortality rate of 40 per 100,0003. Death due to acute
diarrheal illness can be prevented by adequate correction of
the fluid and electrolyte loss as the great majority of such
illnesses are self-limited. Thus rehydration and main-
tenance of proper fluid and electrolyte balance remains the
mainstay of treatment. Previously, intravenous therapy was
the only means available. Such treatment is not generally
possible in developing countries where most patients do not
have access to skilled medical personnel and hospitals. The
demonstration that orally administered glucose-electrolyte
solution can be life-saving in cholera has opened up an
important area for clinical research in the treatment of acute
diarrheal diseases regardless of etiologies. The implementa-
tion of oral rehydration therapy for treatment of
dehydration due to acute diarrhea ranks first among the
recent advances in paediatric medicine, and is the major goal
of the World Health Organization (WHO) to improve the
management of diarrheal diseases throughout the
developing world. Oral rehydration is simple, practical,
inexpensive, highly effective and technologically
appropriate for less developed areas as well as developed
countries.
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—
a review
HISTORICAL AND PHYSIOLOGICAL
HIGHLIGHTs.8
IN 1832, Thomas Latta treated 15 patients who had cholera
with intermittent intravenous saline and alkali4. Most
patients relapsed when the drip was discontinued. Ten of
these 15 patients died, yielding a mortality rate of 67%. He
was criticized at that time for this mode of treatment which
became quiescent for the rest of the century. Retro-
spectively, the remaining 5 patients might have died if they
were not offered fluid and electrolyte replacement. In 1916,
Howland and Marriot described acidosis in infantile
diarrhea and emphasized the need to give small amounts of
alkali5. In 1926, Powers treated infants with diarrhea with
citrated blood, glucose, sodium chloride and bicarbonate
infusions and oral water6. The mortality records, however,
did not show that these refinements improved the final
result. Hartmann et al. in 1938, reported their success with
sodium lactate for the treatment of acidosis associated with
diarrhea. Sixty cases of acidosis associated with nonspecific
diarrhea and eight associated with acute bacillary dysentery
were treated with sodium lactate and follow up data
indicated all but three of these were satisfactorily relieved . 7
In 1946, Govan and Darrow89advocated the use of
potassium supplements for the treatment of diarrhea in
infancts. They further suggested that the potassium
chloride-sodium chloride-lactate solution could be given
mouth after an intravenous infusion had been carried out
by4
for twenty four hours. Harrison demonstrated that an orally
administered carbohydrate electrolyte solution would be
efficient for the treatment of diarrhea and could be used
instead of parenteral therapy. None, however, appreciated
the specific role of glucose.
It was in the late 1950s that researchers started to
recognize that sodium transport and glucose transport are
coupled in the small intestine of animals 1112 and man&dquo; so
that glucose enhances absorption of sodium and water. In
1964, Phillips applied this observation to human studies. He
used oral glucose-electrolyte solutions with success in
treating patients with cholera during the E1 Tor cholera
epidemic in Taipei, thus demonstrating that glucose
mediated absorption of sodium and water remained intact
in cholera4. Hirschhorn et al extended this mode of therapy
to infants with enterogenic Escherichia coli enteritis and
other forms of infective diarrhea S. Oral rehydration
therapy with glucose-electrolyte solutions is therefore
rational and effective. In recent years, UNICEF/WHO has
recommended a solution containing, in mmol/liter: sodium,
90; potassium 20; chloride, 80; bicarbonate, 30; and glucose

111~. This can be prepared by adding sodium chloride (3.5
g), sodium bicarbonate (2.5 g), potassium chloride (1.5 g)
and glucose (20 g) to 1 liter of water. This universal
solution has been used successfully in a wide variety of
diarrheal disorders.
MECHANISMS OF DIARRHEA
EFFECTIVE REPLACEMENT of water and electrolyte in
patients with diarrhea would best be based on exact
knowledge of changes in composition of body fluid.
Diarrheal illnesses can be broadly classified into secretory or
malabsorptive types, and there may be overlapping of
the two. The former is due to noninvasive bacteria (e.g.
Vibrio cholerae, enterotoxigenic Escherichia coli) which
elaborate enterotoxins at the mucosal surface. These may in
turn activate the cyclic adenosine 3, 5 monophosphate
(cAMP) system with resultant enhancement of intestinal
secretion. The glucose-coupled sodium transport, however,
remains intact. The stools of secretory diarrhea are
characterized by their high sodium content (60-120
mmol/liter). Malabsorptive diarrhea is due to invasive
microorganisms (e.g. Rotavirus, Shigella, Campylobacter
jejunz) which
cause disruption and damage to the intestinal
mucosa. It should be noted that many invasive
icroorganisms also elaborate enterotoxins. While the
damaged areas are defective in active glucose absorption,
the absorptive capacity of unaffected villous cells may be
adequate to ensure sufficient absorption of glucose and
electrolytes. The sodium concentrations in malabsorptive
stools are usually less than 60 mmol/1. Stool potassium
concentrations do not show much variation in various types
of diarrhea 17. Also the purging rate is higher in cholera than
in noncholera diarrhea. In one study, the mean purging rate
was 60.1 ml/kg/8 hour for the former and 31.4 ml/kg/8
hour for rotavirus enteritis&dquo;.
SODIUM CONCENTRATIONS IN ORAL REHYDRA-
TION SOLUTIONS (ORS)
THE ORAL rehydration solution (ORS) having a sodium
concentration of 90 mmol/1 has been recommended by
UNICEF/WHO for rehydration in all age groups with
acute diarrhea of all causes, both in the developing and
developed countries. Since the stool sodium concentration
in noncholera diarrhea is less than 60 mmol/1, some
investigators have expressed concern that the high sodium
content in the WHO-ORS may induce hypernatremia in
well nourished ambulatory children with minimal
dehydration as well as in children under 2 years of age
because the latters relatively immature renal function and
large insensible water loss. Hypernatremia following the use
of such solutions in patients with noncholera diarrhea has
occasionally been reported 19 20 21 22.Chatterjee et al noted
that the incidence of periorbital oedema was higher in
children taking an ORS,O compared to a control group
taking an ORS60&dquo;. The safety and efficacy of ORS,, in
correcting dehydration without producing hypernatremia
have been proven by a number of investigators&dquo; 24 25 z6.It is
recommended that additional sodium-free water be
provided to children treated with such solutionS21 . Free
water can be given on demand or in a two-to-one regimen (2
parts of ORS followed by one part of plain water). Aperia et
al. noted slight transient hyponatremia in 4 of the 10 well
nourished Turkish infants who were rehydrated with a
solution containing only 40 mmol sodium per liter9.
Finberg suggests that three solutions of varying sodium
concentrations should be available for oral rehydration 18.
The choice of the solution would depend on the serum
sodium level and on whether rehydration or maintenance of
hydration (or prevention of dehydration) is intended.
However, it is impractical to use three different solutions,
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65
especially in developing countries. The development ot a
single solution is not only cheaper to produce but also easier
to distribute. Such a solution should be safe, free of
complications (hyponatremia or hypernatremia) and can be
given to children of all ages both for rehydration and
maintenance of hydration, regardless of the cause of the
diarrhea. Recent studies have shown that ORS containing
60 mmol of sodium per liter may serve this purpose28 29 30.
OTHER ELECTROLYTES IN ORS
POTASSIUM LOSSES in the stool in the range of 30 to 45
mmol/1 are common31. Insufficient replacement of
potassium losses may lead to muscle weakness,
constipation, ileus, cardiac arrhythmias, polyuria and
polydipsia. Nalin et al and Tamer et al. noted hypokalemia
during rehydration when 20 mmoul of potassium was given
21
31 . In contrast, none of the patients developed
hypokalemia or hyperkalemia when treated with a solution
containing 30 or 35 mmol/1 potassium 21 31. Based on these
observations, the optimal potassium concentration in ORS
would be in the range of 30 to 35 mmol/1.
Metabolic acidosis often complicates acute diarrhea, as a
result of fecal losses of bicarbonate and impaired renal
excretion of hydrogen ions. It is important to include
bicarbonate in an ORS to avoid acidosis; the ORS
recommended by the WHO has a bicarbonate concen-
tration of 30 mmol/l~6. The disadvantage of using
bicarbonate is that it reacts with glucose or sucrose,
especially with hot climate and high humidity, resulting in
brownish discolouration from the formation of furfural
compounds during storage 12 . This may in turn impair its
acceptability. Replacement of bicarbonate by acetate or
citrate may circumvent this problem. Recent studies have
shown that tripotassium citrate is as effective as sodium
bicarbonate; it can safely replace sodium bicarbonate and
potassium chloride for the treatment of diarrhea and
associated hypokalemia 32 . The concentration of citrate
should not be over 10 mmol/1 (30 meq/1) because of its
potential cathartic effect at higher concentrations.
OPTIMAL GLUCOSE CONCENTRATIONS IN ORS
ORAL REHYDRATION, based on knowledge of glucose-
enhanced sodium and water absorption, was first used in
1964 by Philips 14 when he treated patients with cholera
during the El Tor cholera epidemic in Taipei. In 1969,
Sladen33 showed that maximum absorption of glucose and
sodium were achieved when the concentration of glucose
was between 56 and 139 mmol/1 (1-2.5%). Hirschhorn et al
have found that 110 mmol/1 (2%) is the optimal
concentration 34. At glucose concentration higher than 139
mmol, the glucose-coupled transport system is saturated,
any excess of glucose may cause an osmotic diarrhea with
resultant loss of water from the intestine. The high glucose
content (5%-7.5%) of ORS might be the cause for the
increased incidence of hypernatremic dehydration seen in
the 1950s and 6Os35 36.
It is interesting to note that children with acute diarrhea
fed ORS have greater appetitie, recover slightly faster and
with better nutritional weight gain than those who are
fasted 32 . Also early carbohydrate refeeding with glucose
or sucrose has resulted in a significant increase in intestinal
sucrase and maltase activities3.
SUBSTITUTION FOR GLUCOSE WITH OTHER
CARBOHYDRATES
WITH THE exception of lactose, other common dietary
carbohydrates can be used. Sucrose is hydrolyzed by
intestinal sucrase into equimolar quantities of glucose
and fructose before it can be absorbed. Chatterjee et al. were
66
able to demonstrate that most of the children had normal or hyponatremic) of dehydration&dquo;. The amount of main-
nearly normal levels of sucrase in the jejunal mucosa even in tenance fluid has to be reduced by 25% because
the acute phase of diarrhea 38. The use of sucrose has been hypernatremic patients have high antidiuretic hormone
associated with higher rates of vomiting39, diarrhea25 40 and levels. Giving the normal amount of fluid may result in fluid
occasional sucrose malabsorption4. Although glucose is overload and cerebral edema49. With this approach, the risk
more desirable than sucrose, where glucose is too costly or of convulsions during oral rehydration of hypernatremic
unavailable, sucrose is the appropriate substitute. infants can be diminished. Also complications resulting
Maltose has been suggested as a possible alternative. from correction of hypernatremic dehydration are less likely
However, the scarcity and cost of the maltose precludes its than with intravenous fluid therapy50._
use. Caloreen, a glucose polymer, 125 g/1 has been tried with t~ .. .
;.:-. , .
,,

the view of providing more energy and nutrition to patients SUMMARY

at no extra osmotic cost. The molar concentration of
Caloreen is 110 mmol/1 which is the same as the glucose
concentration in WHO formula. However, on complete
hydrolysis, it yields 730 mmol/1. Hypernatremia and
convulsions have been reported which precludes further use
of this compound 42 43.
Rice is cheaper and more readily available than glucose
and sucrose. Rice on hydrolysis yields glucose, amino acids
(such as glycine and lysine) and oligopeptides. Its lower
osmolarity reduces the risk of increasing intestinal secretion.
There is some evidence, at least in infantile gastroenteritis,
that starch is better absorbed than glucose 44. Also, glycine
promotes absorption of sodium. Clinical studies have
shown that rice-powder electrolyte solutions are as effective
and safe as glucose or sucrose electrolyte solutions in oral
rehydration therapy4a as.
LIMITATIONS OF ORAL REHYDRATION THERAPY
THE EFFICACY of oral rehydration therapy in the treatment
of diarrhea is well established. Its failure rate is only about 5
per cent. Intractable vomiting may preclude adequate fluid
intake with resulting dehydration. Intravenous therapy is
superior to oral rehydration to resuscitate those in shock as
these patients need to have rapid fluid and electrolyte
replacement. Other limitations include patients who are
comatose or are too sick to take oral feedings, patients with
paralytic ileus and abdominal distension, patients with
severe stomatitis and extremely premature infants who are
unable to take oral feedings and children who refuse oral
rehydration solutions.
Monosaccharide malabsorption may be primary or, more
commonly, secondary. The former is inherited as an
autosomal recessive disorder. The latter is caused by
bacterial contamination of the duodenum and upper
jejunum; this often responds to administration of broad-
spectrum antimicrobials. In these groups of children, the
diarrhea will get worse when glucose containing solution is
given.
Children whose ongoing stool losses exceed 10 ml per
kilogram of body weight per hour may require intravenous
hydration as oral intake of a huge volume of fluid to
replace the deficit and for maintenance over an extended
period of time is rarely possible. Certain strains of
enteropathogenic E coli (such as 0115; Bls) have bacilli-
adherent qualities that may cause damage to microvilli and
affect the absorptive and secreting functions of intestinal
mucosa. Intravenous therapy may be necessary in a limited
number of patients who have diarrhea caused by these
particular strains of E coli as they may not respond to oral
rehydration therapy46.
Periorbital edema, a well known complication of oral
rehydration therapy, is easily reversible by decreasing the
intake of ORS47.
SPECIAL CONSIDERATION IN HYPERNATREMIC
DIARRHEAL DEHYDRATION
THE PRINCIPLE in the management of hypernatremic
dehydration is to replenish fluid slowly over 12 hours, rather
than 6 hours as with other kinds (isonatremic or
INTRODUCTION OF oral carbohydrate electrolyte solutions
for the treatment of dehydration due to acute diarrhea has
been one of the major therapeutic advances of this century.
The efficacy and safety of oral rehydration therapy is well
established. A decline in the diarrhea mortality rate has been
a consistent finding when it has been accessible to the
community and properly used. The extensive use of oral
rehydration therapy may result in a decrease in the need of
hospitalization and the discomfort and complications
associated with intravenous therapy. Although minor
refinements in its composition may still be possible, its role
in the treatment of diarrheal dehydration is unquestionable.
ACKNOWLEDGMENT ,
THE PUBLICATION of this manuscript was supported by .
grant from the Ross/Abbot Laboratories, Limited,
Montreal, Canada.
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