The Treatment of Acute Diarrhea in Children. An Historical and Physiological Perspective

perspectives in nutrition
The treatment of acute diarrhea in children
An historical and physiological perspective13

Norbert Hirschhorn, M.D.
ABSTRACT This review examines the historical, physiological, clinical, and epidemiohogical
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evidence to support a method of therapy for children’s diarrhea that may be recommended for
general acceptance. The of fluid and nutritional
understanding and therapy
use of acute diarrhea
in childhood have progressed over the years to a point where acute mortality can be reduced to
nearly zero. At the same time, the ill effects on electrolyte balance and nutrition may be reduced
to a minimum. Through use of an oral glucose electrolyte solution with a carefully designed
composition, physiologically correct treatment may now be so simplified and inexpensive as to be
readily available to the remote, under-served areas of the world where most of the morbidity exists;
and be useful as well to more sophisticated settings. The method of therapy recommended in this
paper has several important departures from traditional teaching. It advocates rapid restoration of
extracehlular fluid with a polyelectrohyte solution containing sodium, base and potassium; use of an
oral glucose electrolyte solution for repletion of those not in shock and for maintenance; use of a
single oral glucose electrolyte solution for all age groups, regardless of diagnosis; and quite early
feeding with tolerated foods. Sodium loads given are generally higher than advocated by standard
pediatric teaching. The origins of that teaching and support for the newer approach come from a
detailed analysis ofcurrent knowledge in the epidemiological, clinical, and physiological aspects of
diarrheal illness. Am. J. Clin. Nutr. 33: 637-663, 1980.
“Copying from one book, it is said, is plagiarism, while Over the past three decades the study of
copying from two books is research.” (1) acute diarrhea in children (and adults) has
Acute diarrhea affects nearly 500 miffion led to important knowledge ofthe physiology
children annually worldwide (2), is the lead- of body fluids and the intestine, and of ther-
ing cause of death in children under 4 years apy. Table 1 suggests how this knowledge
old (3), and is a substantial cause of under- relates to the falling mortality rate. The es-
nutrition (4). This is the grim situation now sential elements, known sinceDarrow’s work
in the poor under-served parts of the world, (18-20) are adequate replacement of sodium
but it was the same in the West 70 years ago chloride, base, potassium and volume losses,
(5). Since then, sanitation, protected water and maintenance of nutrition. Workers at
supplies, and better medical therapy have clinical centers in Asia, Africa, and Latin
dramatically reduced the incidence of acute America recognized the need to translate
diarrhea, with a nearly hundred fold drop in these elements into a rational treatment that
mortality (6). was simultaneously simple, cheap, and appli-
Nonetheless, in the West, diarrhea still
ranks second to respiratory diseases as the ‘ From The John Snow Public Health Group, Boston,
cause ofnonsurgical pediatric admissions (6); Massachusetts 021 1 1.
2 Supported by Management Sciences for Health, a
approximately one-half the children receive
nonprofit foundation, Boston, Massachusetts.
intravenous therapy (7). Diarrhea causes one-
a Address reprint requests to: Norbert Hirschhorn,
fourth of the avoidable deaths in hospitalized M.D., John Snow Public Health Group, Inc., 141 Tre-
children (8). mont Street, Boston, Massachusetts 02 1 1 1.
The American JournalofClinical Nutrition 33: MARCH 1980, pp. 637-663. Printed in U.S.A. 637
638 HIRSCHHORN
TABLE 1
Changes in hospital mortality of children’s diarrhea
Year Event Hospital

mortality
1832 Latta (9) uses intermittent intravenous saline and alkali in Over 75%
cholera. Most relapse when drip ceased.
1912 Sellards (10) describes acidosis in cholera and uses alkali.

Howhand and Marriot (1 l)describe acidosis in infantile diarrhea 86%
and give small doses of alkali, with brief improvement.
1926 Powers (12) uses intermittent blood, glucose, saline and bicar- 33%
bonate infusions, and prescribes prolonged fasting.
1928-1938 Hartmann (13) uses sodium lactate to relieve acidosis; recurrent 51%
dehydration, however, causes high mortality.
1931-1933 Kareitz and Schick (14-16) use continuous saline dextrose 12-33%
infusions and recommend a 3-day fast.

1945 Mortality at Harriet Lane Home (Johns Hopkins) still quite 32%
high on regimen without potassium (17).
1946-1949 Darrow, at Hopkins, (17-20) does balance studies to measure 6%

salt-H2O deficits in diarrhea; emphasizes use of potassium in
addition to saline, base and water. Prescribes 1-5 day fast.
1948 Chung (21) urges continued feeding in spite of diarrhea; mor- 10%
tality unaffected, disease not prolonged, nutrition enhanced,
but fluid balance more difficult to achieve.
12-24% for
1947-1958 Rapoport (22), Finberg and Harrison (23) and others (24)
describe hypernatremic dehydration. hypernatremia
1958 Darrow’s solution (in mEq/L:Na61,Kl8, base 27) as sole 10%

intravenous fluid in tropics (25, 26).
1959 Watten et al. (27) measure water and electrolyte loss in cholera.
1950’s-1960’s In the West, better understanding of hypernatremia (28, 29), 0-5%

careful tailoring of intake, and laboratory monitoring (30)
put treatment of diarrhea on a scientific footing.
l960’s-1970’s In Asia, simplified methods of treatment of cholera and non- 2-3%

cholera diarrheas developed at cholera research laboratories,
based on physiologic studies (31, 32) emphasize speed and
large fluid volume for rehydration; simultaneous use of salt,
potassium, base; and early feeding.
1966-1979 Increasing use of oral glucose-electrolyte solutions in cholera 0-2%

and noncholera enteritis (33, 34).
cable under the adverse conditions and short- use of a single polyelectrolyte intravenous
ages of the developing world. fluid and a single oral glucose electrolyte
The key elements ofthe method developed
are: rapid restoration of salt and water deple- 4 “Volume repletion” and “volume depletion” are
tion with simultaneous correction of acidosis, more precise than “rehydration” and “dehydration.”
Still, the respective words will be used interchangeably
and administration of potassium; use of an
to mean electrolyte and water restoration or loss. The
oral glucose electrolyte solution for repletion4 word “fluid” also indicates solute and water rather than
of those not in shock, and for maintenance; water alone.
ACUTE DIARRHEA IN CHILDREN 639
solution, for all age groups; and early feeding Regimens and patients’ characteristics
with tolerated foods. This approach has been
successful both in well supplied hospitals (31- The death rate in hospitals from acute
33), and, spectacularly, in Bangladesh refugee diarrhea can and should be 2% or less,
camps under the worst of conditions (35). whether in a sophisticated urban hospital or
But the approach deviates considerably in a makeshift tent ward in a rural area. Most
from conventional pediatric teaching. Table ofthe excessive mortality that occurred in the
2 contrasts the differences in methods. Much past (Table I) came soon after admission and
ofcurrent pediatric teaching emphasizes slow was due mostly to uncorrected volume deple-
repletion of fluid losses; great concern over tion or electrolyte imbalance (3 1 , 37-40).
the sodium load, especially for infants; tailor- Given the importance of the first day in
ing of fluid therapy to each individual; and the fluid treatment ofsevere dehydration, the
the need to “rest the bowel” for several days. ranges of a first 24-hr fluid regimen associ-
A classic presentation of this approach was ated with improved survival should be de-
written in 1974 by Blair and Fitzgerald (36). fmed. It is unlikely that such data will ever
Given these differences, this paper has been be generated prospectively, but a retrospec-

prepared with several aims in mind: to review tive analysis of reported experience may pro-
the historical development of current pediat- vide clues. A literature search followed these
ric teaching about treatment of acute diar- rules for inclusion in the analysis: a study had
rheal disease; to collect and synthesize in one to specify clearly the first 24-hr volume and
review the epidemiological, clinical, and electrolyte regimen (intravenous and oral)
physiological data that explain both success- planned or actually received; the children had
ful and unsuccessful treatment regimens; and to have been visibly dehydrated, requiring at
on the strength of the synthesis, to reevaluate least some intravenous fluid; given the known
the hypotheses upon which these different adverse effects of omitting potassium (Table
treatment regimens are based. 1) and acidosis (41), regimens analyzed had
TABLE 2
Comparison of two approaches to treatment of dehydrating diarrhea
Traditional teaching Recently dcveIo
1. The physiological model Varying degrees of dehydration Within broad limits a simple and urn-
and tonicity require careful tal- fled therapeutic approach may be
bring of fluid therapy. taken.
2. Speed of rehydration 24-48 hr 4-6 hr
3. Choice of initial rehydratmg so- Hypotonic with sodium content Polyclectrolyte solution with sodium
lution 30-60 mEq/liter, especially for content 80-130 mEq/liter for all
infants. ages.
4. Use of potassium Only after urination commences. In polyelectrolyte solution.
5. Use of base Only for severe acidosis. In polyelectrolyte solution (bicarbon-

ate, lactate or acetate).
6. Use of oral fluids Small, infrequent sips of H20 in Ad libitum intake of glucosc-elcctro-
first 24 hr. lyte solutions for those able to drink
(in mM/hiter:Na 90, K20,
HC0330, glucose 1 1 1). Need for
intravenous fluid can often be dim-
mated.
7. Feeding Fasting for 24-48 1w, careful rein- Tolerated feeds as soon as appetite
troduction of food. restored (usually within 6-24 hr) in
small frequent amounts.
8. Principal concerns Overhydration, hypernatremia, Under hydration, hyponatremia, un-

persisting loose stools. der-nutrition.
640 HIRSCHHORN
to specify inclusion of potassium and base at mEq/liter; the effective sodium concentration
levels of at least 1 mEq per kilogram body of regimens associated with 3% mortality or
weight, respectively; and mortality reported less averaged 77 mEq/liter; the difference,
had to be related to the diarrheal illness. however, is statistically insignificant. At a
Fifteen studies reporting 20 regimens met minimum it can be said that, along with
these criteria (20, 25, 3 1, 32, 37, 38, 40, 42- potassium and base, the higher levels of so-
49). All were published after 1945. When dium-containing fluid administered were
ordered in terms of mortality, both higher compatible with improved survival, and may
and lower rates were described from Western have contributed to it.
and tropical countries, in urban and rural Although the successful regimens, higher
settings, among infants and toddlers, and in in volume and sodium than generally advo-
children well or poorly nourished. cated, have been used both in the West and
Five independent variables were analyzed the tropics, it is often said that children from
against mortality: sodium load, total volume, the tropics, or disadvantaged groups such as
“free water” volume, sodium load x total American Indian children, represent a “dif-
volume, and sodium concentration. All vari- ferent type of infant” than the Western child

ables were expressed as milliliters or miii- (5 1-53); and that regimens developed for the
equivalents per kilogram of body weight as former are inappropriate for children gener-
appropriate. Total volume and sodium load ally seen in American hospitals. Specifically,
included all intravenous and oral fluid and it is supposed that certain attributes render
sodium intake in the first 24 hr of hospitali- Western children less tolerant of fluid and
zation. Free water was calculated as that salt overload, or these other children more
component of fluid not bound to salt in terms tolerant.
of extracellular fluid sodium concentration In an attempt to test this hypothesis, the
(at a sodium concentration of 140 mEq/liter, clinical and biochemical attributes reported
a liter of solution has no free water, while one for Western and tropical children hospital-
at 70 mEq/liter has 500 ml free water); cal- ized were examined. Table 3 reviews 7 1 re-
culations for free water were further corrected ports written in the past three decades; from
for the potassium given. A composite index, the West (generally from urban teaching hos-
sodium load x total volume, was derived to pitals); from tropical areas (urban and rural);
examine any augmenting effect of one on the and, for comparison, studies of children pre-
other. Finally, the effective sodium concen- senting exclusively with hypernatremia (in-
tration (in milliequivalents per liter) was cluding four from the tropics). For each of
calculated by sodium load/total volume x the attributes listed-dealing with clinical,
1000. biochemical and bacteriologic measure-
The first four variables were plotted against ments-the mean values reported by each
mortality. Since mortality cannot be less than study were ranked. Where five or more re-
0%, computer-calculated hyperbolic curves ports characterized an average attribute in
rather than linear regressions were fitted to the group under study, a median value and
the data (Fig. 1). This analysis is susceptible the interquartile range (IQR) were calcu-
to the hazards of a retrospective review of lated.5 Although differences in reporting exist
multiply disparate studies, and randomness between series, this method of comparing
cannot be guaranteed since most outcomes means should reveal different tendencies be-
are not published. Statistically significant tween the three groups.
negative correlations with mortality were Several fmdings are of interest. First, con-
present for sodium load and the composite trary to accepted teaching, children with hy-
index, sodium load X total volume. A nega- pernatremia are, on the whole, neither
tive correlation of borderline significance was younger nor better nourished than the pop-
found for total volume. A weakly positive ulation with diarrhea from which they were
correlation between free water volume and
5 The IQR is a measure of dispersion about the me-
mortality was also found. The effective so- dian and is defined as the third quartile minus the first
dium concentration of regimens associated quartile. On Table 3, along with the medians, are pre-
with 6% mortality or greater averaged 60 sented the first and third quartile values.
I”.
Sc%Vt4Y LOAD (mEq/kg) TOTAL VOLUMEx SXIUM (m/aq/kq)

36
32
. D .
28
r’-0.40 r’ +026
24 p< 0.08 p<0.2
20
16
.
12
.
8
1
168 192W 216 240 264 288 60 80 100 140 160
TOTAL VOLUME (rn//kg) “FREE WATER” (rn//kg)
FIG. 1. An analysis was made of 15 studies depicting 20 fluid regimens used in the 1st day treatment of
dehydrating diarrhea in children. Sodium load (A), total volume x sodium load (B), total volume (C), and “free
water” volume (D) are displayed against mortality. Hyperbolic curves were fitted to the data by computer, with the
general equation Y = ho + b,x’ where Y - mortality, bo intercept, b, - regression coefficient and x - the
independent variable. Triangles represent two overlapping points.
drawn. Second, hypertonic dehydration does once severe volume depletion occurs, as in-
occur in tropical children, though not as com- dicated by clinical shock, the mean weight
monly as in the West. The incidence of hy- loss in all the groups is approximately 10%;
potonicity is several times greater in tropical and accumulated sodium losses on admission,
children with diarrhea. The differences, how- as measured by net retention studies, were
ever, are unlikely to be explained by differ- approximately the same in the few Western,
ences in evaporative water loss, the incidence tropical, and hypernatremia studies recording
of parenteral infection, carbohydrate intoler- these data. Traditional bacterial pathogens
ance, or sodium loss in the stool. Third, the (shigella, salmonella, enteropathogenic Esch-
severe consequences of diarrhea-marked erichia coli) were more often isolated from
volume depletion, acidosis, and hypokale- children hospitalized in the tropics, but reo-
mia-are seen with nearly equal prevalence virus-like agents seem to be equally distrib-
in the tropical and hypernatremic series, and uted worldwide. The diagnosis of enterotox-
more often than in the Western series. But, igenic E. coil has been confused by a variety
TABLE 3
Clinical and biochemical attributes of children with diarrhea
from different parts of the worldb
weatem Tropical Hypernatremic
No. ofstudies 18 21 16
No. of children 2764 5607 323
(median/series) 79 100 20
Attribute
I . Mean age (mo)
Median ?_ ! 2
1QR ±:JP EL4
2. Malnutrition, % with weight 5, 30, 38 26, 37
< 75% normal
Median
IQR
3. Volume depletion, % with 5-15%
loss body weight
Median ..2 .4
IQR 45-100 72-100 66-100

4. Mean % weight loss when clini-
cally “severe” 4, 8, 10, 13 7, 9, 9, l0
Median
IQR ELQ
5. Mean sodium loss, mEq/kg. in

severe dehydration 10, 10, 13 11 l3c, 8_l4c
6. Acidosis, % with pH < 7.3, or CO2
< 15
Median Th
IQR a?.:?
7. Hypokalemia, % with K < 3.5
(corrected for acidosis)
Median ..!
IQR L!4 .
8. ECF sodium on admission: % hy-

pertonic (Na > 150)
Median j_4 I
IQR 2z
% Hypotonic (Na < 130)
Median 12 4!
IQR zai
9. Mean evaporative loss, ml/kg/

day 64C 70 44, 44, 5 lc, 70C 50
10. % Children with parenteral infec-
tion 19, 19, 40
Median ii
IQR :2 11:42
1 1. Mean stool sodium, mEq/L (non-
cholera, acute) 60, 71 46, 56, 91 20
12. % Children with carbohydrate in-
tolerance 6, 25, SOC 24, 25, 77
13. % Children with enteric bacterial
pathogen 0, 0, 18
Median 1.4
IQR 1:11
14. % Children with rotavirus
Median 4
IQR
a Median values and IQR underlined. Single values, not underlined, are means from individual studies and
insufficient for calculation of median. b Reference numbers of studies included in Table 2: Western: 7, 18-20, 24,
37, 41, 45, 47, 50, 54-61; tropical: 32, 40, 44, 48, 62-78; hypernatremic: 22, 24, 45, 62, 66, 7 1, 79-87; C 88-
103. C Values indicate data from studies not otherwise included in total analysis.
642
of assay techniques; they are unlikely to be safety to about 40 mEq/liter each). Yet chil-
common pathogens in Western children (104, dren regularly respond well, perhaps better,
105), but cause 10 to 20% of episodes in to solutions closer in composition to the ECF
tropical and American Indian children (102, (Fig. 1).
106). In two studies ofApache children where A fourth seeming paradox is that children
the newer approach to treatment outlined in from the tropics with diarrhea are predomi-
Table 2 was used exclusively (33, 107), their nantly hyponatremic; yet their attributes
clinical and biochemical attributes resembled closely resemble those of hypernatremic chil-
both Western and tropical children: nutri- dren in severity of volume depletion, acidosis
tional status and severity of illness like the and hypokalemia.
Western children, hypotonicity like the trop- To resolve the paradoxes requires an over-
ical children; evaporative loss, stool sodium view of the pathophysiology of diarrheal de-
concentration and carbohydrate intolerance hydration.
like both.
None of the attributes examined, therefore, The pathophysiology of diarrheal
compel one to believe that tropical (or dehydration

Apache) children should be more tolerant of
sodium loads than Western children. Tradi- Figure 2 represents a synthesis of a wide
tional teaching has often dwelt on the differ- variety of data on the effects of and the body
ences in these attributes, especially tonicity, responses to diarrheal dehydration. Some ca-
as the basis for regimens tailored to each yeats are in order. The events depicted do not
category. This review will advance the hy- represent all the possible effects; neither is
pothesis that, within broad limits, a simpler, any weight assigned to predominant effects,
unified approach is not only possible, but or to the likelihood of interactions; and not
physiologically correct. The support for such all of the events have been investigated spe-
an hypothesis must be built on the resolution cifically in children’s diarrhea. But the for-
of four apparent paradoxes in the pathophys- mulation is a reasonable synthesis of the
iology of diarrheal dehydration. known and the likely responses to diarrheal
The first seeming paradox is that despite fluid loss.
the fact that fluid losses in stool, sweat, and In the overall formulation (the top portion),
expired air contain considerably more water diarrhea first induces a major effect on the
and less sodium than does the extracellular body through salt and water depletion, with
fluid (ECF), most children with diarrhea compensatory responses by the vascular,
present with a serum sodium concentration renal, and hormonal systems. The second
equal to or less than normal. major effect is on the intestine, inducing mal-
The second paradox has to do with the absorption and (iatrogenically) fasting or im-
source of fluid loss. Darrow in the United proper intake; various metabolic, evaporative
States (19) and Mahalanabis in India (70) and intestinal events follow. The first effect
measured the retention ofelectrolyte and wa- leads generally to hypotonic or isotonic de-
ter during the recovery phase. Both showed hydration. This response may be considered
that the estimated deficits of sodium and “normal” or compensatory in a more helpful,
potassium on admission were roughly equiv- homeostatic fashion. The second effect tends
alent (total ion loss 3 18 to 353 mEq/liter generally toward hypertonicity. This response
water loss), which indicated that intracellular may be considered “pathological” or a more
(ICF) and ECF fluid compartments are harmful compensation.
equally depleted in diarrhea. Yet measure- Throughout the discussions that follow, the
ments of the ECF compartment by the chlo- reader will be assisted by referring back to
ride-space (18, 19, 70) or with inulin (54) Figure 2.
show mostly ECF depletion.
The third paradox relates to the second: Hyponatremic dehydration
fluid regimens were designed to correct both Let us first consider the normal compen-
ICF and ECF ion and water loss with ap- satory events that follow quickly upon the
proximately equal concentrations of sodium loss of water, sodium, potassium and bicar-
and potassium (limited by considerations of bonate in the stool (midportion of Fig. 2).
644 HIRSCHHORN
DIARRHEA
A
Rer,o -Vascuor Ion and Water Sugor Intolerance, IntestinoIEvoporotive-
Responses Generolly - Depletion, Imbalance 4 Fosting,Inappropruote - Metabolic Responses
Produce HypOtOniC and Compensation Intake Generally Produce
or ISO?OflC Hypertonic or
Dehydration Isotonic Dehydration
DIARRHEA
B
No’, H on and Water Losses HCO3
‘:= r::::dRr;rIdo.AD;i////as
oseKCeII No’ to ECF
/ r- Decieosed Acdfcohon f [ireosed Respootion
I ECF I
F q c- NtC
No’
H
Inceosed
T -4----
hen Decreased Lose SaltWater
IGtKdney L ng
___________________________
I yper5Iycemio [imonoty ESemo
Increosed _, iii
Blood Volume Liet LosS
LoseK ‘V

No”’ess 120 Only HYPOTONICITY OR ISOTONICITY
ARRHEA
C DI
Cotoboisin. TheeDoys0’ 5’#{176};

tolerance ......Cows Milk
___
E.ces$ Sugar
Rena -
Concentro’on Jo sad Urea
K’ Increased
Ac,deme: Gijt HO and K’Loss,,,,,,,,,/’ Hsgh Protein Feed ;;creosed Neat Stress
Increosed E’OS’. ‘COSd H Reop P4O Loss i Eacess Salt ;‘[;aseo easai H20 Heidi
5odum etefltj Decreesid H20 intdie Le,ieo iCeil Sodium
HyemgieesO. Aodos irs incased

ri;;ereosed Heist
Sass’ L
HYPERTONICITY LSolute Load ]

FIG . 2. The events that follow onset of acute diarrhea are depicted to show how they may lead to volume
depletion that is hypo-, iso-, or hypernatremic. A, gives the general model; B, shows the predominant events generally
leading to hypo- or isonatremia; and C, shows the predominant events generally leading to iso- or hypernatremia.
See text for particulars.
(References 18, 19, 78, 107a-l21 contain data With even minimal ECF volume contrac-
providing the basis for the following ideas.) tion (loss of 2% of body weight or less), renin,
With the loss of potassium from the ECF angiotensin, aldosterone and antidiuretic hor-
to the stool, a chemical gradient is created mone (ADH) secretions are increased, and
that facilitates potassium (and water) move- the glomerular filtration rate (GFR) is de-
ment from the ICF to the ECF. Facilitated creased or redistributed. As GFR falls, acid-
by aldosterone, sodium (and water) tend to ification of the urine is also blunted and
move into the ECF. Protons (which accu- accumulating protons tend to be retained,
mulate in the ECF following bicarbonate loss which in turn may further promote tubular
in the stool, during tissue hypoperfusion, and secretion of potassium.
with ketosis of catabolism) also tend to dis- These actions lead to a compensatory re-
place ICF potassium. Since an effect of al- tention of salt and water, but proportionately
dosterone is to promote sodium retention and more ofthe latter. The first palpable response
potassium excretion via the kidney, a sub- to ECF contraction is thirst. If water is taken,
stantial proportion of the potassium deficit in it will be mostly retained as ADH increases
diarrheal disease may be accounted for in this distal tubule and collecting duct permeability
way. The effect of aldosterone may account to free water, facilitating its reabsorption.
for the observations of Darrow (19), and Even without much intake, water may be
Mann et al. (78), that potassium retention is generated internally, and retained, in the re-
inversely related to the volume of stool loss, sponse to stress by steroids and catechol
even though potassium loss in the stool can- amines which promote catabolism of body
not account for the total deficit. tissue; the latter aggravated by fasting.
We may now suggest resolutions for three sition have been used in rehydration therapy
of the four apparent paradoxes. First, the for years. Their apparent success, however,
tendency to hypernatremia, due to loss of derives in part from the avid retention of
more water than sodium, is counteracted by “maintenance” fluids over several days, and
avid retention of water (ingested or internally from the unproved view that severely dehy-
generated). drated children have lost, and therefore
The second paradox is also explained: fluid should be given, 15% or more of their weight
deficits in acute diarrhea, as measured by net in fluid (compare Reference 30, Table 3). The
retention studies, combine both ECF and use of hypotonic solutions more nearly ap-
ICF losses in roughly equal proportions; but proximating the ICF, however, explains the
the predominant contraction measured by necessity of the traditional practice to allow
chloride and inulin space takes place in the rehydration to proceed slowly over 24 to 48
ECF because sodium and hydrogen ions (and hr; a rehydrating fluid more nearly approxi-
water) replace ICF potassium (and water). In mating the ECF can be given more rapidly.
other words, ECF space contracts in two di- A hypothetical profile of a child most sus-
rections: out in the stool, and into the cell; so ceptible to hyponatremia may now be drawn.

that the net measured loss of volume appears It is a child with repeated bouts of diarrhea;
to come mostly from the ECF. with chronic potassium depletion; with per-
A resolution to the third paradox follows: haps slight, continued ECF volume contrac-
since it is continued ECF contraction that is tion; who is fasted; and who gets only salt-
at the root of these physiological changes, poor fluids once diarrhea starts. Many chil-
reversion to normal is more readily accom- dren in the tropics are found to suffer from
plished by solutions more nearly approxi- chronic or relapsing diarrhea at any time
mating the composition of ECF than ICF. surveyed (125, 126), and are predictably p0-
The more hypotonic a fluid is with respect to tassium depleted (76). Malnourished chil-
sodium, the less well it can quickly correct dren, with diarrhea much of the time, have
ECF contraction, unless proportionately chronically elevated levels ofrenin (127). And
more of that fluid is given (see Fig. 1B). It fmally, the usual fluids given children in the
should be noted that hypotonic dehydration, tropics (as well as to Apache children) are
once initiated, tends to be self-perpetuating, hypocaloric and virtually salt-free: tea, bar-
since vascular collapse and all the physiologic icy-water, rice-water, jello-water, or soft
responses thereto occur with less fluid loss drinks. Clearly, not all of these features need
than seen in isotonic or hypertonic dehydra- be present simultaneously to cause hypona-
tion (122). Preexisting, or uncorrected potas- tremia in any one child.
sium deficit may also perpetuate hypotonicity A solution to the fourth paradox posed-
by several possible mechanisms. There is cv- how hyponatremic children in the tropics and
idence that potassium depletion causes an hypernatremic children come to share several
increased secretion of renin (123), and pro- critical biochemical attributes-is yet to be
motes catabolism by impairment of insulin supplied. This will require a more intensive
secretion (124). Also, with potassium deple- analysis of how hypernatremia originates.
tion but normal hydration, sodium (and wa-
ter) may replace potassium (and water) in the Hypernatremic dehydration
cell causing ECF contraction and then ADH The dessication of the ICF in hypernatre-
secretion (1 17). The rational treatment then mia ( 128) can lead to serious neurological
should reverse these events by restoring vol- consequences; therefore, hypernatremia is a
ume quickly, correcting acidosis and reducing matter of great concern. Since the regimen
the potassium deficit with solutions approxi- this review has recommended contains more
mating the composition of the ECF. Under- sodium than traditionally used, it is also nec-
replacement of ECF fluid can perpetuate all essary to examine the pathogenesis of hyper-
the events listed above. This has been shown natremia to determine if the newer regimen
empirically by studies comparing regimens is as safe, from a theoretical point of view, as
higher and lower in sodium (41, 44, 93). it seems to be in practice. We may analyze
It must be acknowledged that solutions the predisposing events by means of three
more closely approximating ICF in compo- categories: The epidemiology of hypernatre-
646 HIRSCHHORN
mia, augmenting mechanisms, and abnormal 142); but ifGFR per unit oftotal body water,
water loss. or per unit extracellular fluid volume, or per
Epidemiology. Hypernatremia complicat- unit kidney weight are calculated, values
ing diarrhea is a condition of infants and equivalent to those in adults are reached by
toddlers of either sex. The median age in 16 one to two months of age (143, 144). Mc-
reported series is 7 months. But the median Cance et al. (143), who first called attention
age of the general group of children hospital- to the maturation question in 1941, decided
ized with diarrhea in the West is also 7 by 1957 that the latter method of comparison
months (Table 3). Hypernatremia has been was more rational. Finally, maximal concen-
reported both to have winter (28, 103, 129, trating ability reaches at least 85% of adult
130) as well as summer peaks ( 13 1 , 132), levels by the second month of life (143, 145-
suggesting that it reflects only the dominant 147) in the majority ofchildren, and certainly
diarrheal seasonal pattern in a particular lo- by 10 to 12 months in all. Any remaining
cale. Hypernatremia occurs both in the trop- difference between adults and children would
ics and in temperate zones, but is more com- permit conservation of only trivial amounts
mon in the latter (50, 66, 71, 73, 83, 84, 133, of water. So it would not seem that immature

134). It is said that better-nourished children renal function plays an important role in the
are more susceptible to hypernatremia (53). incidence of hypernatremia, where the me-
Data presented in two large series of hyper- dian age ofoccurrence is seven months (Table
natremia from the United States, however, 3).
found these children to suffer mild to severe A number of distinctly pathological renal
malnutrition, not different from the larger and metabolic events do occur that, once
group at risk (22, 28). In the tropics, hyper- hypernatremia is initiated, serve to perpetuate
natremia is more common in large, bottle-fed it. Renal concentrating ability (i.e., the ability
infants (73, 75, 83). The most important epi- to conserve water and excrete solute) does
demiological clue, however, is that while hy- not keep pace with the hypertonicity, espe-
pernatremia has been recognized for decades cially as persisting volume depletion causes
(23), there appears to have been a two-decade decreased delivery of sodium to the distal
epidemic, starting in the 1950’s and only now tubule, and free water is thus not generated
abating (129, 133, 135, 137). Ifthe documen- for retention. Potassium depletion (148) and
tation is valid, it must mean that certain hypertonicity itself (149) also affect the kid-
physiological mechanisms reputed to cause ney’s ability to excrete salt.
hypernatremia can only be predisposing, aug- Potassium depletion is generally not appre-
menting, or perpetuating, but not initiating. ciated as a perpetuating factor in hypernatre-
Augmenting mechanisms. Commonly cited mia. Yet the tendency to retain sodium and
predisposing events include the large ratio of develop edema in the face of body potassium
surface area to weight in children (138), and deficiency has been described for nearly three
the normally increased metabolic rate in cliii- decades by Darrow and others (20, 41, 54,
dren 6 to 15 kg (139), both of which dictate 150). The effects are multiple: on the renal,
a more rapid turnover of water. Small chil- ( 148, 15 1), hormonal ( 123), and cellular levels
dren are especially susceptible to metabolic (152, 1 13). Ramirez et al. (153) have demon-
water loss, especially under heat stress and strated in children that a potassium-free diet
fever (72, 84). But these phenomena only is associated with cumulative weight gain and
serve to confirm that hypernatremia more sodium retention beginning on the first day.
commonly affects infants and toddlers. Severe acidosis is commonly found with
It has been suggested by several authors hypernatremia (Table 3) and is a likely per-
that immature renal function in infants is an petuating factor. Acidemia stimulates the
important contributing factor to hypernatre- release of nonextracellular sodium (154).
mia (53, 140). If body surface area is used as With continued water loss, hypernatremia
the basis for comparison of renal functions, may ensue. Hyperosmolarity, in turn, induces
particularly for GFR and urinary excretion further hydrogen ion secretion from cells
of sodium, infants reach levels seen in young ( 155). With dehydration, the kidneys are less
adults by anywhere from 4 to 13 months (141, able to excrete acid (156). The burden of
compensation on the lungs is then increased; tration (10%) (169, 129).6 interesting con-
but with increased respiration, unfortunately, comitant clue to the pathogenesis of hyper-
water loss also increases. Moreover, as aci- natremia is the tendency of hypernatremic
dosis becomes severe, (pH less than 7.1), children to produce voluminous, watery stool
blood is shunted from the peripheral vessels low in sodium (28, 169). Normally, as stool
to the lungs causing puLmonary congestion rate rises, so does the stool sodium concentra-
(157). If carbohydrates are poorly absorbed, tion, approaching plasma levels; this occurs
additional protons are generated during bac- in adults with cholera (170) as well as in
terial fermentation of the sugars in the gut infants with noncholera enteritis (calculation
and are either transferred to the body fluids of data presented by Darrow et al. (18, 19).
or remove bicarbonate already secreted into Since stool fluid is rarely hypoosmotic to
the lumen (158, 159). Both acidosis and hy- plasma, voluminous stool low in sodium must
perosmolarity cause hyperglycemia (86, 160- contain other solutes such as organic metabo-
163) which, by an osmotic diuresis, can fur- lites. Such metabolites are generated in the
ther force renal water loss. gut during malabsorption of carbohydrates
We come back to our fourth, as yet unre- (17 1). Intestinal bacteria degrade undigested

solved, paradox. Since many children in the carbohydrates into many osmotically active
tropics with diarrhea are seriously potassium fragments that draw water into the lumen in
depleted and acidotic, why is hypernatremia the upper intestine. This may cause the pro-
not more common?.Or, how can hypokalemia duction of gas, distension and ileus and im-
predispose both to hypo- and hypernatremia? pair colonic absorption of salt and water
In fact, the known intolerance of malnour-
ished children to sodium (164), as evidenced 6 Several writers suggested that the sodium concentra-
by the development of edema or congestive tion of such formulas was to blame (24, 82). This is
failure, may have its roots in potassium defi- difficult to accept. Taitz and Byers (133) found children
ciency (165). But the latter develops over with hypernatremia had been fed improperly diluted
cow’s milk formula; the formulas, however, averaged a
some time, allowing for compensatory water
sodium content of only 33 mEq/liter with a range of 22
retention. Hypernatremia, on the other hand, to 66; Chambers’ and Steel’s figures (134) were 37 mEq/
happens quickly (66, 84). Some event causing liter, range 26 to 59. The original commercial sugar-
rapid and excessive water and potassium loss, electrolyte formula contained 50 mEq Na/liter. One
in addition to sodium retention, is necessary. report, however, showed that boiling skimmed milk
could elevate the sodium content to as high as 165 mEq/
The next section examines this point.
liter (85). Except for the latter, the sodium concentrations
Abnormal water loss. A search for a likely of suspect formulas reported are really not exceptional,
initiating cause of hypernatremia must start especially when one considers the therapeutic range of
with some of the early clinical observations. sodium used for rehydration (Fig. I).
That drinking milk during diarrhea often Several other authors believe hypernatremia may be
related to inappropriate caloric and protein loads (133,
causes clinical deterioration is quite an old
134). An excessive caloric load increases evaporative
observation. Howland (166), in 1921, noted water loss, a situation dramatically worsened under heat
that “ . . it is now generally
. appreciated that stress (132). Decreased intake of a high-solute fluid due
sugars initiate and perpetuate diarrhea . ..“
to calorie satiation may make matters worse, as ingestion
oflarge volumes ofeven a high-solute fluid such as cow’s
Infantile diarrhea, with profuse stools, dehy-
milk allows the kidney to generate free water (173).
dration and shock, was often called “alimen- Davies (174) has demonstrated, however, that a child
tary intoxication” and it was recognized that with mild diarrhea (30 ml/kg per day), receiving a
cow’s milk initiated or worsened the condi- normal amount of twice
concentrated cow’s milk, need
tion (12, 14, 164). When hypernatremia oc- only to concentrate urine to 706 mOsm/liter to maintain
water balance. The recent decrease in the incidence of
curs in the tropics it is related to cow’s milk
hypernatremia may reflect better feeding with low solute
feeding (7 1). Hypernatremia has been de- milk (136, 137); nonetheless, hypernatremia still occurs,
scribed in association with high-solute or hy- even in children on low-solute milk (137). It is rare in
perosmolar feeds such as boiled skim milk breast-fed children. The simplest reason why breast-fed
(82), hypertonic (10 to 20%) glucose solution children are less susceptible to hypernatremia (75), in
spite of the high lactose concentration (7 g/100 ml), in
(168), tinned milk formulas (133, 134, 137), addition to its low protein content, is that breast milk,
or commercial glucose-electrolyte solutions unlike cow’s milk, is taken only in small quantities at
containing dextrose polymers in high concen- each feeding.
648 HIRSCHHORN
(172). Voluminous, low sodium stools are the the contrary, with early prevention or correc-
result, in which potassium is also lost. Intes- tion of volume depletion, acidosis and potas-
tinal fermentation produces acidemia, while sium loss, both hyponatremia and hyperna-
distension and ileus increase fluid loss and tremia should be avoidable or easily cor-
the accompanying nausea reduces total in- rected. Perhaps we are relearning Darrow’s
take. If the incidence of hypernatremia has wisdom: “These patients with hypernatremia
followed an epidemic curve between the received.the usual fluid therapy used in other
1950’s and 1970’s, perhaps it may be related cases of diarrhea” (45).
to the common medical practice in that time It is now necessary to examine more closely
which promoted boiled skim milk plus sugar, some of the origins ofcurrent pediatric teach-
or dextrose polymer-salt solutions, as suitable ing which emphasize that an absolute ceiling
therapy for diarrhea. The hypothesis that for safe sodium intake exists, one regularly
carbohydrate intolerance is a principal initi- exceeded by the regimen recommended in
ating cause of hypernatremia awaits formal this review.
testing.
An hypothetical profile of a child most Sodium: striking the balance

susceptible to hypernatremia from diarrhea
may now be drawn. It is a child under 1 year In the mid-l950’s, Talbot, Butler and their
ofage, with a briefhistory ofdiarrhea, getting colleagues (88, 176-182) presented an encom-
complex carbohydrates at high concentration, passing framework for fluid therapy of adults
and with reduced intake or considerable in- and children which established “floors and
sensible loss of water. Once initiated hyper- ceilings” for the amounts of water and dcc-
natremia tends to be perpetuated by hypo- trolytes that could be safely administered.
volemia, hypokalemia, and acidemia. Ra- Their work came at the time when awareness
tional treatment then should reverse these of hypernatremia was most acute and formed
events be restoring volume, correcting aci- much of the intellectual underpinning for
dosis, reducing the potassium deficit, and traditional pediatric fluid therapy. Their
eliminating complex sugars from the diet (es- basic concepts may be summarized as follows:
pecially lactose). Some caution must be used There is a minimum and a maximum rate of
in the speed with which serum sodium con- administration of water and salt that can be
centration is reduced, but this caution should given without disturbance of body fluid com-
not permit perpetuation ofthe hypernatremic position. The body’s adjustment to fluid ad-
biochemical complex. A recent paper (175) ministered between the limits is by the usual
reported the use of a 0. 18% sodium solution neuroendocrine and renal homeostatic mech-
over 48 hr, with base given only for “severe anisms, but the fluid administered should be
clinical acidosis.” The patients suffered a 13% balanced as much as possible between mini-
death rate, slow rate of return to normal mal need and maximal tolerance (hence the
plasma osmolarity, and a high incidence of original use and meaning of the term “bal-
edema and thromboses. However, Finberg, anced solutions”). “Stress” due to injury, sur-
Rosenfield, et al. (87), who have studied hy- gery, or illness lowers the ceiling for maximal
pernatremia for three decades, now recom- tolerance. In treatment of dehydration, ICF
mend a regimen for the severely dehydrated and ECF losses are to be replaced simulta-
(over 10% weight loss or greater) that pro- neously with equal amounts of sodium and
vides up to 50 nil/kg in the first 4 to 5 hr with potassium; it is unnecessary or undesirable to
a solution containing 80 mEq/liter sodium replace all deficits within a few hours, once
and 25 mEq/liter base. In his most recent shock is corrected.
series, only 2/67 (3%) died. The fluid and Talbot and Butler suggested that the ceiling
sodium load he recommends for hypernatre- for daily sodium administration to acutely ill
mia is not remarkably different from what children would be 225 mEq/m2 surface area,
this review has suggested for all diarrhea in with 150 mEq the “balanced” amount given,
children. along with an equivalent amount of potas-
The regimen suggested in this review sium, in no more than 3500 ml/m2 fluid
(Table 2) does not, in fact, fit into any of the volume. In an 8-kg child, this works out to a
contributing factors for hypernatremia. On sodium load of 7.5 to 1 1.3 mEq/kg in 175
ml/kg volume (sodium concentration 43 to So far this review has dealt principally with
64 mEq/liter). Such a child, if severely vol- only the first 24 hr of therapy. It is possible
ume depleted, will have lost approximately that adverse effects of excess sodium loading
640 to 960 ml (80 to 120 mi/kg) of fluid and might be avoided if it occurs for only 1 day.
approximately 90 mEq of sodium, or 11 In fact, the mainstay of the regimen this
mEq/kg (see Table 3). The volume of fluid review recommends is the use of a single
and sodium thus recommended for rehydra- intravenous or oral polyelectrolyte solution,
tion is likely to be insufficient and only the both for initial deficit and continuing losses,
ceiling approaches adequacy (see Fig. 1). On with the addition of food and low-solute liq-
the basis of his balance studies, Darrow had uids. In practice, and on the average, this has
arrived at a much higher value, supplying an meant providing sodium to (for example):
average of 17 mEq/kg sodium in the first day Apache infants 14 mEq/kg per day for 2 to
of rehydration (20) at an overall concentra- 3 days (33, 107); Bengali children (average
tion of 86 mEq sodium per liter fluid volume. weight 8 to 9 kg) with cholera, and given
How, then, did Talbot and Butler derive their tetracycline, 1 1 mEq/kg per day for 2 days
ceiling for sodium administration for infants? (32); Bengali children (average weight 1 1 kg)

Two references are cited in Talbot’s syllabus with cholera, on no antibiotic, 20 mEq/kg
(88): Gamble et al. (1 83) and McCance and per day for 4 days (185); urban American
Widdowson (184). Gamble added salt to the infants, 13 mEq/kg per day for 3 days (19).
milk and water diet of a normal 7-kg child, In all these studies, however, enough water
providing sodium at 12 to 13 mEq/kg per was supplied to reduce the fmal sodium con-
day for 8 days in a concentration probably centration (total sodium per total water) to
no greater than 90 mEq/liter. While the child approximately 50 to 90 mEq/liter; and while
retained an excess of 1. 1 mEq Na/kg per transient puffmess (usually periorbital) was
day and gained water over eight days equiv- not uncommon, it was of no clinical conse-
alent to 4% of body weight, it apparently quence.
remained well. McCance, however, gave But pediatricians in general are more wor-
three premature neonates salted milk for 1 to ried about sodium retention and edema than
2 days, providing sodium at 22 mEq/kg per moderate under-replacement of saline defi-
day in a concentration range of 120 to 154 cits. In the 1940’s, a syndrome of “postaci-
mEq/liter. The neonates retained 10 to 14 dotic state of infantile diarrhea” (186) was
mEq/kg per day, gained water equivalent to described which followed vigorous saline and
10% of body weight, became puffy, oliguric, bicarbonate therapy without potassium. The
sick, and hypertonic. A key difference be- syndrome included nonpitting edema, tetany,
tween the two studies, in addition to the hypocalcemia, hypernatremia, hypokalemia,
undoubted susceptibility of the prematures, convulsions, and cerebral hemorrhage. These
may have been the fmal concentration of regimens included “normal” saline, or nor-
sodium-hence the availability of water for mal saline plus 1/6 molar lactate, or the
excretion-rather than the absolute amounts curious “3: 1 regimen” (three parts normal
given. An important difference between the saline to one part 2% sodium bicarbonate)
studies of Gamble and McCance and those (22, 187, 188). None had potassium. The 3:1
of diarrheal disease is, of course, the consid- regimen (Na at 177 mEq/liter) in one study
erable existing deficit ofsodium on admission was associated with a 17% mortality and a
in children with diarrhea. high incidence of hypernatremia (187); with
Regimens that rehydrate slowly with fluids a changeover to lactated Ringer’s (Na at 128
more like ICF in composition have several mEq/liter) the mortality fell to 3% and hy-
consequences, understandable from the gen- pernatremia was no longer documented (44,
eral model described in Figure 2: rehydration 91). In the regimen recommended by this
is not accomplished in the first day; hypona- review, the “postacidotic” syndrome has not
tremia is likely to be produced or persist; and been reported. Marked edema, or puLmonary
acidosis is prolonged, especially where diar- congestion, may be associated with severe
rhea continues during and beyond the first acidosis (157) or with potassium depletion
day. All these consequences have been deter- (20); then it reflects a serious problem. Slight
mined empirically (41, 44, 54, 92). puffmess about the eyes in a child otherwise
650 HIRSCHHORN
clinically well is commonplace, is not related lent. Data obtained from six independent
to electrolyte imbalance ( 13, 33, 54), and is lines of physiological and clinical research,
not a problem. Its presence indicates an cx- however, have given oral therapy a broader
cess fluid volume isotonic to ECF amounting significance with regard to both medical sci-
to I to 3% of body weight (33). Transient ence and health care delivery.
isotonic overexpansion after large doses of
NaC1 is seen both in adults (189-191) and A ctive cotransport of sodium and organic
children (183). The cause of delayed sodium substrates in the intestine
excretion is complex but several explanations The details of this line of research have
may fit: “Postloading antinatriuresis” de- been well summarized (194-196). Briefly,
scribes a brief period of renal tubular reab- several actively transported substances like
sorption of sodium in response to a sodium glucose, galactose, certain amino acids, some
load (192); after chronic salt depletion, salt disaccharides, and some dipeptides show an
and water are retained even when a hypo- absolute or partial dependence on sodium for
tonic salt solution is given (1 1 1); and fmally, their absorption, and the rate of sodium ab-
the very handling of children during sam- sorption is considerably increased in the pres-

pling procedures causes oliguria lasting up to ence of these substrates. While the kinetics of
an hour (193). the sodium-substrate interactions vary by
Talbot and Butler were also concerned that substrate class, a common effect, seen espe-
the stress ofiliness, through various hormonal cially in the intact intestine, is the simulta-
mechanisms, would increase sodium reten- neous enhancement of absorption of water
tion. This is quite true even to the extent that and of other salts, following electrochemical
low sodium loads, given slowly, can induce gradients (197-200). How much of the in-
edema and hypernatremia (41, 48, 82). The duced transport is transcellular, or active, and
same may be said of hypernatremia: children how much paracellular, or passive, is Un-
with this condition show intense retention of known.
sodium (54, 89). The relief of stress induced This effect on salt and water absorption
by volume depletion, however, is achieved by was applied successfully to cholera patients
rapid restoration of extracellular volume and when it was shown that the salt-substrate
electrolyte deficits, which means using rather cotransport was substantially intact, and that
more sodium than less. In fact, therapy that oral therapy with sodium, potassium, bicar-
just removes clinical shock does little to stop bonate, chloride, and glucose in a single so-
the responses to volume depletion (157). lution could maintain normal blood volume
The concepts developed by Darrow, Ta!- and electrolyte concentrations (201-203). The
bot, and Butler and their colleagues, while suggested ideal composition of an oral ther-
not proved correct in all respects, had a pro- apy solution was derived in large part from
found effect on pediatric fluid therapy be- research done on isolated membranes, animal
cause they were based on meticulous atten- models and human subjects. First, there is
tion to both physiologic and clinical infor- considerable evidence that glucose and so-
mation. A new concept in the treatment of dium are absorbed at close to a 1: 1 molecular
diarrhea-oral therapy-is similarly based, ratio (204-206). Second, maximal water and
and is the subject of the final section of this sodium absorption take place at administered
review. glucose concentrations between 56 to 140
mM/liter (197, 207, 208). At glucose concen-
Oral therapy with sugar-electrolyte solutions trations higher than 160 to 200 mM/liter,
water and salt absorption are reduced, an
Glucose-electrolyte solutions, taken by effect independent offluid tonicity (208-2 10).
mouth for rehydration and maintenance ac- Third, when sodium concentration is consid-
cording to carefully designed regimens (“oral erably below that of the normal jejunal con-
therapy” in shorthand), were developed to tents, secretion occurs even in the presence of
replace diarrheal fluid loss in cholera and glucose (21 1). Fourth, bicarbonate, in addi-
reduce the need for intravenous fluids in tion to correcting acidosis, also serves to en-
developing countries where cholera is preva- hance sodium absorption (213), but the pres-
ence of chloride is necessary for the full so- two studies indicate that oral therapy may be
dium-glucose effect ( 199). Fifth, glucose is safer than intravenous with respect to sodium
much better absorbed in the jejunum than in loading in children, and that any oral fluid
the ileum in man (213). Sixth, rapid flow without glucose (or some other appropriate
rates of lumenal contents (over 10 mi/mm) substrate) will considerably worsen diarrhea
reduce absorption substantially (209). 5ev- if even a slight depletion of blood volume
enth, the loss of sodium on admission in exists. Diarrhea itself affects intestinal ab-
acute, severe diarrheal disease averages from sorption, as the next section discusses.
76 to 109 mEq/liter of fluid loss in infantile
The effect of diarrhea on intestinal absorption
diarrhea (19, 70); and up to 120 mEq/liter of
stool (17, 70). Potassium losses may be simi- Morphological abnormalities in the intes-
larly extensive. tine accompany acute bacterial and viral diar-
Taking these eight points together, a ra- rheas, the severity of which correlate with
tional solution for oral therapy should, there- indices of malabsorption (217). Reversible
fore, be sufficiently concentrated in sodium changes in concentrations of enzymes asso-
to replace losses on a volume for volume basis ciated with absorption (Na-K ATPase, di-

so that patients do not need to drink exces- saccharidases) have also been documented
sively, thereby increasing flow rate and dcliv- (218-221). Persistent disaccharidase defi-
cry of a large load of glucose to the ileum. ciency (222, 223) and malabsorption of glu-
The glucose concentration should closely cose (224) have been documented in selected
match sodium on a molar basis. Potassium hospital cases. Malabsorption in children hos-
and base should be added (empirically this pitalized with acute diarrhea spans a spec-
has worked out to be 4 to 6 mEq/kg per day trum from clinical intolerance to lactose in
each). Such a fluid would then contain, per about half (72), to sucrose in a third, and to
liter, 75 to 100 mEq ofsodium, 20 to 30 mEq glucose in about 5% (222). Intolerance to
ofpotassium, 20 to 30 mEq bicarbonate (with glucose can be made manifest by increasing
chloride as the other anion) and 75 to 100 the concentration (225) and rate of adminis-
mM of glucose; the osmolarity would be 265 tration (226) of the sugar. Sugar malabsorp-
to 360 mOsm/liter. The formula promoted tion can lead to an increase in stool loss,
by the World Health Organization contains, continued morphological damage, bacterial
in millimoles per liter, Na90, K20, HCO3 overgrowth, gut ischemia, intolerance to all
30, C180, glucose 1 1 1; and 33 1 mOsm/liter.7 substrates and a downhill course in a minority
The renal solute load is 220 mOsm/liter. of children (159). From such clinical experi-
Lytren (per liter: 30 mEq Na, 556 mt glu- ences came the general injunction to rest the
cose, no bicarbonate, milliosmolarity 656), bowel absolutely during the acute phase, with
and Pedialyte (per liter: 30 mEq Na’, 278 restoration of full diet taking as long as a
mM glucose, no bicarbonate, milliosmolarity month (36).
387), both in common use, are examples of But there were always dissenters from this
unphysiological solutions. They have too lit- approach. Chung and Viscorova (227)
tIe sodium, too much glucose and are too showed in 1948 that children with acute diar-
concentrated. rhea fed milk and corn syrup (glucose poly-
Two other phenomena may be relevant to mers) recovered slightly faster and with better
the discussion. One, described in rabbits, is nutritional weight gain than those who fasted,
that sodium given by mouth stimulates natri- even though the latter group had less total
uresis five to 10 times greater than an equiv- stool output (227). A commercial formula
alent amount given intravenously (215). The containing casein hydrolysates plus glucose
effect is seen in normal and in sodium-dc- (Pregestimil) can replace stool salt and water
pleted animals. The second observation, in loss, and provide nutrition (33, 107). Even
humans, is that a physiological dose of ADH, children with “intractable” diarrhea, or with
a level attained naturally in volume depletion, malnutrition, gain weight and have less diar-
abolishes net salt and water absorption in the rhea on diets that are predigested but not
jejunum; but this effect is reversed when glu- 7 In grams per liter: NaC1 3.5, NaHCO3 2.5, KC1 1.5,
cose is added to the oral mixture (216). These glucose 20.
652 HIRSCHHORN
hypertonic (casein hydrolysates or commi- monia and other infections following bouts
nuted protein, amino acids, glucose or glucose of diarrhea and reduction of intake.
polymers, etc.) even to the point of not re- It may still be argued that, although pro-
quiring total parenteral nutrition (223, 228- longed fasting or reduced intake can be harm-
233). It is possible that these organic sub- ful, one should prove the positive effects of
strates facilitate salt and water absorption by feeding during diarrhea. The fourth line of
the intestine. Since each class of substrate research points the way.
(sugar, dipeptide, amino acid, etc.) appears to
interact with separate sodium-carriers in the The induction effect offeeding
intestinal membrane, there may be an addi- It is clear from numerous animal and hu-
tive effect when two or more substrate types man studies that intraluminal foodstuffs, car-
are used together. Such has been shown in bohydrate, and protein, increase intestinal
cholera when glucose and glycine are used digestive enzymes and cell proliferation in a
(234). It also seems possible that one sub- dose-related way, even without prior fasting
strate, glucose for example, could reverse the (237, 245-249). The inductions are somewhat
net secretion and attendant clinical symptoms specific: sucrose is a better inducer of sucrase

induced by malabsorption of another sub- than is glucose, for example. Diarrhea ap-
strate, like lactose. Bedine and Bayless (235) pears to sensitize this effect. In rats, after a
have shown this experimentally in men with week of mannitol-induced diarrhea, levels of
lactose intolerance. specific disaccharidases showed increased de-
Even so, feeding may increase stool output pendence on corresponding dietary substrates
(34). If fasting caused no harm, feeding might compared to controls without diarrhea. A
not be worth the extra difficulties in calculat- mixed carbohydrate diet was most protective
ing fluid balance. Darrow et al. (18) were against disaccharidase depletion during diar-
particularly concerned that this not happen. rhea. The effects were independent of
But, in fact, a third line of inquiry has shown changes in histology, or number of epitheial
the rapidly deleterious effects of fasting or cells (242).
even semistarvation. The evidence so far presented suggests that
both diarrhea and fasting affect intestinal
Fasting and intestinal function absorption that, when impaired, can lead to
With as brief a fast as 3 to 5 days, glucose, more prolonged diarrhea, more severe mal-
salt, water and amino acid absorption are absorption, and possible malnutrition. A fifth
substantially reduced, as are disaccharidases, line of investigation has recently related diar-
with or without changes in histology of the rhea and malnutrition in whole populations.
intestine (236-239). The effect is independent
of nitrogen or caloric balance, as total intra- The relationship ofdiarrhea to malnutrition
venous feeding alone causes depletion of in- From Mexico, The Gambia, Uganda, Gua-
testinal digestive enzymes and gut mass in as temala, Papua New Guinea, and India (4,
little as 3 days (240, 241). Since not all chil- 126, 250-254) have come longitudinal studies
dren with diarrhea are fasted for 3 days, it is on cohorts of children which now prove that
important to know what fasting and diarrhea diarrhea directly causes malnutrition. First,
appear to be additive in their effects on di- diarrhea is the overriding correlate with se-
saccharidases (242). quential weight loss in children, with malaria
Apart from the intestinal effects, brief fast- a distant second; episodes of respiratory ill-
ing has deleterious metabolic effects. For cx- ness and fever do not correlate with perma-
ample, 3 days of no food causes an aldoster- nent growth retardation (4, 126). Second, the
one-resistant natriuresis (243) which could cumulative difference in weight among six-
lead to hyponatremia. A 10-day hypocaloric month age-cohorts up to 84 months of age
diet in man causes a 42% decrease in venti- amounted to 1 1% between children with low,
latory response to hypoxia, and a 25% de- and children with high frequency rates of
crease in basal metabolic rate (244). This has diarrhea (4, 250); or the equivalent of about
meaning for marginally nourished children 100 g body weight per month (25 1). These
who are particularly susceptible to pneu- values account for a substantial proportion of
the weight deficits fmally incurred by chil- practice. In fact, it simply extended years of
dren in the tropics, which are only partially experience with a single intravenous solution
reversed by generous supplementation with that yielded the remarkably low mortality
a high protein and calorie diet (4). Third, rate of under 2% in children under 4 years of
faltering of growth is acutely related to each age (31).
episode of diarrheal illness (252), in part due Oral therapy had a solid impact on mor-
to catabolism and malabsorption, but also to tality in situations where standard intrave-
anorexia and decreased food intake as well nous therapy was scarce. In Bangladesh ref-
(253). Finally, nutritional deterioration alone ugee camps in 197 1, the death rate from
increases the likelihood of a subsequent epi- diarrheal diseases soared to 30%. Oral ther-
sode of diarrhea (254). Can appropriate therapy, vigorously administered by family mem-
apy reverse these events? The sixth line of bers (“give them as much as they will drink”)
research has begun to defme the range of helped reduce the mortality rate to about 1%
effectiveness of oral therapy, including its (35). Due to the severe shortage of materials
effect on nutrition. and staff, intravenous fluids were reserved to
resuscitate those in shock.

Current status of oral therapy In a home treatment program for Asian
Oral therapy with glucose and electrolytes Indian children 0 to 3 years old, case fatality
has been used in the past. Darrow in the rates fell from 3.2 to 1.4 per thousand after
1940’s ( 19), Harrison in the 1950’s (255), and oral therapy was introduced (258). The au-
Meneghello in the 1960’s (65) recommended thors used a salt-sucrose solution, about 1 to
the use of oral therapy as a supplement to 2 liters/day, with a sodium concentration of
intravenous fluids, or as a first step to feeding, about 100 mEq/liter.
or for use in the outpatient department. None, Administration of oral therapy by lesser
however, appreciated the specific role of glu- trained persons-whether in hospital, clinic,
cose, or described objective evidence of the or home-became feasible when it was shown
usefulness of oral therapy, or developed an that the majority of dehydrated infants and
optimal formula and method of administra- children would take oral therapy ad libitum
tion. up to the level of need as long as they were
Such evidence followed the discovery of strong enough to drink or suck, and the fluids
the biophysical principles involved. In 1967, were offered freely (33). Children in shock
under the tutelage of Robert A. Phillips, a were rehydrated intravenously within a few
group from the Cholera Research Laboratory hours with a lactated Ringer-like solution
in Dacca, Bangladesh reported that actively (plus potassium), then put on oral therapy.
transported sugars such as glucose and galac- The capacity of children to absorb the
tose (but not passively transported fructose) fluid, taken either by mouth or delivered by
in a polyelectrolyte solution could consider- nasogastric tube, is prodigious: reported rates
ably reduce the net volume of stool fluid in have ranged from 10 to 17 mi/kg per hour in
cholera (201). Nalin et al. (202) then showed the first 1 to 2 days of hospitalization (33,
that patients with cholera who received oral 256-262).
therapy required 80% less intravenous fluids In Costa Rica, of 1 l 3 children (3 to 15
for cure; that children over 2 years old and months, mean age 5.5 months) averaging vol-
adults, both with cholera, responded similarly ume depletion equivalent to 5% of body
to an oral solution of the same composition weight (one-third of them were 7 to 12%
(256); and that the amino acid glycine, when dehydrated), only six needed intravenous
added to the glucose in the oral therapy mix- fluids (261, 262). The rest were totally treated
ture could reduce total stool output further by oral therapy plus additional water. In two
(234). The Calcutta group, in the meantime, reports from India (259, 260), 57 of 59 chil-
helped defme effective concentrations of so- dren (ages 3 months to 4 years, median age
dium and glucose (208, 257) for both adults 1 year) were managed solely by glucose-elec-
and children. The use of a single solution for trolyte fluids given intragastrically despite an
any dehydrating diarrhea in all age groups acute fluid loss averaging 6 to 8% of body
seemed to be a startling departure from usual weight. Half the children had 24-hr stool
654 HIRSCHHORN
volumes over 80 g/kg. Of99 Apache children weights on discharge of Apache children on
(mean age 1 1 months; 28 were under 3 oral therapy and fed early, compared to those
months of age), one-half were moderately to of the previous year treated with intravenous
severely dehydrated, with stool losses aver- fluids, fasting, and slow return to diet (265).
aging 6 ml/kg per hour for the first 6 hr (33, The former group went home at 90 to 99% of
107). Only 10 required partial or total intra- the Harvard median (the average for Apache
venous rehydration; only one needed a na- infants and children generally), the latter at
sogastric drip because of failure to keep up 70 to 79%. Associated with this was the din-
orally with stool loss. The oral solutions used ical perception that children rapidly rehy-
contained 80 to 90 mEq of sodium per liter drated with oral therapy were vigorous and
(plus potassium, bicarbonate, and glucose) hungry soon after. It was hypothesized that
and corrected instances of both hypo and oral therapy would help improve or maintain
hypernatremia. In Bangladesh 57 children (5 nutrition by restoring appetite quickly and
to 30 months old, mean age 12 months) with helping mothers (and doctors) see the value
rotavirus diarrhea were treated completely of not fasting their children. Given the rela-
with oral therapy (World Health Organiza- tionship between diarrhea and malnutrition,

tion formula) and compared to 44 treated such a fmding would be ofsignal importance.
with intravenous fluids. All did well (263). The hypothesis was borne out in a study
Twenty-five to 88% of the children in the six done in collaboration with the Government
clinical studies cited above were febrile on of the Philippines and the World Health Or-
admission. Theoretically this should increase ganization (266). An oral-glucose-electrolyte
the risk of hypernatremia; but of the 328 solution (the World Health Organization for-
children, only three developed elevations of mula) administered at home to 464 Philippine
serum sodium, 150 to 155 mEq/liter, none children with diarrhea was associated with a
clinically obvious. Mortality in the six reports greater average weight gain, both during an
was nil. attack ofdiarrhea and over a 7-month period,
Nichols and Soriano (264) have criticized when compared to a control group. The
the concept of a single solution for diarrhea longer-term effect on weight, relative to a
regardless of etiology, indicating that differ- standard, was more pronounced in children
ent types of diarrhea produce stools with who had more than one attack of diarrhea in
different levels of sodium. Nonetheless, oral the period of observation than in those who
therapy has proved equally effective in any had only one attack. The magnitude of the
dehydrating diarrhea of children (the limita- longer-term weight gain was 3 to 5 percentage
tions to be described below), whether due to points towards the standard weight.
cholera (46), where the stool sodium is high The limitations oforal therapy are partially
(80 to 120 mEq/liter) (214); to reovirus (261, known. Vomiting has clearly not been limit-
263) where stool sodium is low (20 to 25 ing in the several hospital or field trials cited
mEq/liter); to shigella and other diarrheas above, except when those in shock have not
(33, 107) where stool sodium is intermediate been completely rehydrated intravenously
(40 to 50 mEq/liter). (267), or in the earliest stages of severe chol-
An important principle followed in these era (268). Nor have fever or high environ-
studies was early feeding with tolerated foods mental temperatures affected good outcomes.
and fluid. In Apache infants, a casein hy- Periorbital edema has been described ranging
drolysate-glucose-medium chain triglyceride from 6 to 25% of hospitalized children (33,
formula was started at full strength inter- 260), but was neither associated with hyper-
spersed with oral therapy, within the first 24 natremia or any untoward consequences
hr (107). Costa Rican children (261, 262) (therefore, not strictly a “limitation”). About
were given half-strength milk within 6 to 12 5% of children in a hospital, and fewer than
hr of admission. Indian children (259, 260)
8 A caveat is in order here. Feeding cow’s milk to a
were given dilute cow’s milk or breast milk
population of children with intestinal damage and po-
within 12 to 24 hours. The criteria for when
tassium depletion is likely to cause hypernatremia, and
to begin feeding appear to be complete re- has (260); oral therapy when combined with breast milk
hydration, and appetite.8 appears not to cause hypernatremia, even in reovirus
A remarkable difference was noted in the diarrhea (263).
1% in a clinic setting have glucose intolerance children more comfortable (33). It would be
(27, 33); they are made worse by oral therapy. useful to know how staff time is affected.
The condition is easily suspected on clinical It has recently been demonstrated by this
grounds (voluminous, watery stools; failure author and colleagues that lightly trained and
to rehydrate) and confirmed by simple bed- supervised Philippine village women can
side measurements of stool-reducing sub- teach mothers how to prepare and use oral
stances (33). Stool spillage of carbohydrate fluids, and to feed their children at home
can be quite high, even with an adequate during diarrhea. The clinical outcomes com-
clinical response, however. In reovirus diar- pared well to those in doctor-based clinics. A
rhea up to 30% of the administered glucose gratifying and significant increase in the
load appears in the stool (261). Oral therapy number of mothers who kept on feeding their
also fails in patients with very high rates of children during the illness was seen in the
stool loss, over 10 mi/kg per hour, perhaps course of a year (272).
due to fatigue in drinking so much (269). A The studies on oral therapy continue the
final possible limitation is the use of oral development of knowledge of diarrheal dis-
therapy in neonates with diarrhea. There is ease; their authors are conscious inheritors of

insufficient experience with this group to sup- the scientific and clinical fmdings of numer-
port a recommendation at this time. ous workers, past and living. The advances in
The study of oral therapy is now at the oral therapy also illustrate the felicitous
stage of finding the better strategies of dcliv- phrase of Rohde and Northrup (2), “taking
cry. For instance, sucrose is somewhat less science where the diarrhea is.”
effective than glucose in the oral solutions
(262, 263, 271) in the sense that stool volume
The author thanks Howard S. Frazier, M.D., David
tends to be larger and duration longer, failure R. Nalin, M.D., and Richard A. Cash, M.D. for their
rates slightly higher, and correction of dehy- careful reading ofthe manuscript, and Timothy N. War-
dration and biochemical abnormalities ncr, Ph.D., for his help on statistical analyses.
slightly slower. But where glucose is too costly
or unavailable, sucrose is the appropriate sub-
References
stitute. The addition of magnesium for mal-
nourished children is worthy of study. An- 1. HOWARD-JONES, N. Choleranomalies: The unhis-
other area, just now being explored, is tory of medicine as exemplified by cholera. Per-
whether the chemicals should be provided spective. Biol. Med. 15: 422, 1972.
2. ROHDE, J. E., AND R.S. NORTHRUP. Taking science
prepackaged or in the form of store-bought where the diarrhea is. In: Acute Diarrhoea in Child-
salt and sugar that the mother measures out hood. Ciba Fndn. Symp. 42: 339, 1976.
herself for domiciliary treatment. Issues of 3. PUFFER, R. R., AND C. V. SERRANO. Patterns of
access, safety, cost, and effectiveness in pre- mortality in childhood. Report of the Inter-Ameri-
can Investigation of Mortality in Childhood. Pan
venting volume depletion and electrolyte im-
American Health Organization Scientific Publica-
balance are all important here. Even fmding tion no. 262,
1973.
a suitable container for mixing will be a 4. MARTORELL, F., i-P. HABICHT, C. YARBROUGH, A.
problem in much of the world. More direct LECHTIG, R. E. KLEIN AND K. A. WESTERN. Acute
comparisons of oral fluids higher or lower in morbidity and physical growth in rural Guatemalan
children. Am. J. Diseases Children 129: 1296, 1975.
sodium content (e.g., 90 versus 50 mEq/liter) 5. AYKROYD, W. R. Nutrition and mortality in infancy
are needed. One study (260) attempted this, and early childhood: past and present relationships.
but gave virtually the same amount of total Am. J. Clin Nutr. 24: 480, 1971.
sodium to both groups. More recently, Nalin 6. VAUGHAN, V. C., AND R. J. MCKAY. The field of
pediatrics. In: Textbook of Pediatrics (10th ed),
has shown in Jamaican children that the so-
edited by W. E. Nelson. Philadelphia: W. B. Saun-
lution lower in sodium resulted in persistent ders 1975, p. 4.
(days) hyponatremia in five of 24 children, 7. MOFFET, H. L., H. K. SHULENBERGER AND E. R.
while the one higher in sodium resulted in
transient (6 hr), asymptomatic elevations of
serum sodium in three of 84 (D. Nalin, per-
9 Pizarro of Costa Rica has just completed a study of
sonal communication). 40 neonates, mean dehydration 6.6% of body weight.
In Western hospitals, the use of oral ther- treated with oral therapy and extra water; 39 required
apy instead of intravenous fluids can make no intravenous fluids (270).
656 HIRSCHHORN
BURKHOLDER. Epidemiology and etiology of severe B. VANIKIATI AND R. A. PHILLIPS. Water and dcc-
infantile diarrhea. J. Pediat. 72: 1, 1968. trolyte studies in cholera. J. Clin. Invest. 38: 1879,
8. OAKLEY, J. R., P. M. MCWEENY, M. HAYES-ALLEN 1959.
AND J. L. EMERY. Possibly avoidable deaths in 28. BRUCK, E., G. ABAL AND T. ACirro. Pathogenesis
hospital in the age group one week to two years. and pathophysiology of hypertonic dehydration
Lancet 1: 770, 1976. with diarrhea. Am. J. Diseases Children 115: 122,
9. LATFA, T. A. Malignant cholera. Documents com- 1968.
municated by the Central Board of Health, London, 29. BRUCK, E. G., ABAL AND T. ACETO. Therapy of
relative to the treatment of cholera by the copious infants with hypertonic dehydration due to diar-
injection ofaqueous and saline fluids into the veins. rhea. A controlled study of clinical, chemical and
Lancet 2: 274, 1832. pathophysiological response to two types of thera-
10. SELLARDS, A. W. Tolerance for alkalies in Asiatic peutic fluid regimen, with evaluation of late se-
cholera. Philippine J. Sci. 5: 363, 1910. quellae. Am. J. Diseases Children 1 15: 281, 1968.
1 1 . HOWLAND, J., AND W. M. MARRIOT. Acidosis oc- 30. WElL, W. B. A unified guide to parenteral fluid
curing with diarrhea. Am. J. Diseases Children 11: therapy. I. Maintenance requirements and repair of
309, 1916. dehydration. J. Pediat. 75: 1, 1969.
12. Powers, G. F. A comprehensive plan of treatment 31. NALIN, D. R. Mortality from cholera
and other
for the so-called intestinal intoxication of children. diarrheal diseases at a cholera hospital. Trop. Geog.
Am. J. Diseases Children 32: 232, 1926. Med. 24: 101, 1972.
13. HARTMANN, A. F., A. M. PERLEY, J. BASHMAN, M. 32. MAHALANABIS, D., J. B. BRAYTON, A. MONDAL

V. NELSON AND C. ASHER. Further observations on AND N. F. PIERCE. The use of Ringer’s lactate in
the metabolism and clinical uses of sodium lactate. the treatment of children with cholera and acute
J. Pediat. 10: 692, 1938. non cholera diarrhoea. Bull. World Health Organ
14. KARELITZ, S., AND B. SCHICK. Treatment of toxi- 46: 311, 1972.
cosis with the aid of a continuous intravenous drip 33. HIRSCHHORN, N., B. J. MCCARTHY, B. RANNEY, M.
of dextrose solution. Am. J. Diseases Children 42: A. HIRSCHHORN, S. T. WOODWARD, A. LACAPA,
781, 1931. R. A. CASH AND W. E. WOODWARD: Ad-libitum
15. KARELITZ, S. AND B. SCHICK. Treatment of alimen- oral glucose-electrolyte therapy for acute diarrhea
tary toxicosis. J. Am. Med. Assoc. 99: 366, 1932. in Apache children. J. Pediat. 83: 562, 1973.
16. KARELITZ, S. Continuous intravenous therapy in 34. Oral glucose/electrolyte therapy for acute diar-
pediatricswith special emphasis on its use in ali- rhoea. Lancet 1: 79, 1975.
mentarytoxicosis. Acta. Paedat. 16: 546, 1933. 35. MAHALANABIS, D., A. B. CHOUDHURI, N. G.
17. GOVAN, C. D., JR., AND D. C. DARROW. The use of BAGCHI, A. K. BHATrACHARYA AND T. W. SIMP-
potassium chloride in the treatment of the dehydra- SON. Oral fluid therapy of cholera among Bangla-
tion of diarrhea in infants. J. Pediat. 28: 541, 1946. desh refugees. Johns Hopkins Med. J. 132: 197,
18. DARROW, D. C. The retention of electrolyte during 1973.
recovery from severe dehydration due to diarrhea. 36. BLAIR, J., AND J. T. FITZGERALD. Treatment of
J. Pediat. 28: 515, 1946. non-specific diarrhea in infants. Clin Pediat. 13:
19. DARROW, D. C., E. L. PRATF, J. FLE1-F, JR., A. H. 333, 1974.
GAMBLE AND H. F. WIESE. Disturbances of water 37. ALEXANDER, M. B. Infantile diarrhea and vomiting.
and electrolytes in infantile diarrhea. Pediatrics 3: A review of 456 infants treated in a hospital unit
129, 1949. for enteritis. Brit. Med. J. 2: 973, 1948.
20. FLETF, J., E. L. PRATT AND D. C. DARROW. Meth- 38. ORTIZ, A. Diarrheal diseases. Acute diarrhea in
ods used in treatment of diarrhea with potassium young children. In: Diseases of children in the
and sodium salts. Pediatrics 4: 604, 1949. subtropics and tropics. Edited by: H. C. Trowell
2 1 . CHUNG, A. W. The effect oforal feeding at different and D. B. Jelliffe. London: Arnold, 1958, Chapter
levels on the absorption of foodstuffs in infantile 17.
diarrhea. J. Pediat. 33: 1, 1948. 39. KINGSTON, M. Electrolyte disturbances in Liberian
22. RAPOPORT, S. Hyperosmolarity and hyperelectro- children with kwashiorkor. J. Pediat. 83: 859, 1973.
lyternia in pathologic conditions ofchildhood. Am. 40. AHMED, I., AND J. K. G. WEBB. Childhood diar-
J. Diseases Children 74: 682, 1947. rhoea in S. India with particular reference to fluid
23. FINBERG, L., AND H. E. HARRISON. Hypernatremia and electrolyte disturbance. Ind. J. Child. Health
in infants. An evaluation of the clinical and bio- 12: 85, 1963.
chemical findings accompanying this state. Pediat- 41. CHEEK, D. B. Changes in total chloride and acid-
rics 16: 1, 1955. base balance in gastroenteritis following treatment
24. COLLE, E., E. AYOUB AND R. RAILE. Hypertonic with large and small loads of sodium chloride.
dehydration (hypernatremia): the role of feedings Pediatrics 17: 839, 1956.
high in solutes. Pediatrics 22: 5, 1958. 42. Puyrr, H. The Maghazi Rehydration Center. Au-
25. BowlE, M. D. The management of gastroenteritis gust-December 1961 Assessment Report. Courier
with dehydration in outpatients. S. African Med. J. 13: 73, 1961.
34: 344, 1960. 43. LAWSON, D. Management of gastroenteritis at the
26. JELLIFFE, D. Diarrhoea in childhood. In: Medical Hospital for Sick Children, Great Ormond Street,
Care in the Developing World, edited by M. King. 1948-49. Great Ormond Street J. 2: 1 10, 1951.
London: Oxford University Press, chapt. 15, 1966. 44. GUTMAN, R. A., D. J. DRUTZ AND G. E. WHALEN.
27. WATFEN, R. H., F. M. MORGAN, V. N. SONGKHLA, Double-blind fluid therapy evaluation in pediatric
cholera. Pediatrics 44: 922, 1969. Clin. 8: 30, 1954.

45. DARROW, D. C., AND J. S. WELSH. Recent experi- 63. MENEGHELLO, J., J. RossnLoT, F. MONCKEBERG
ence in the treatment of diarrhea in infants. J. AND C. AGUILO. Algunos aspectos en el tratamiento
Pediat. 56: 204, 1960. do la toxicosis del lactante. Boletin Medico Hosp.
46. SACK, D. A., S. Isui.i, K. H. BROWN, A. IsLi, A. InS. 13: 139, 1956.
K. M. I. KABIR, A. M. A. K. CHOWDHURY AND M. 64. MENEGHELLO, J., J. ROSSELOT, F. MONCKEBERG, S.
A. ALl. Oral therapy of children with cholera: A RuBlo, E. SILVA AND J. GONZALEZ. Terapeutica de
double blind comparison of sucrose with glucose- Ia toxicosis. Influenca de algunas pautas terapeuti-
electrolyte oral solution. J. Pediat. In press. cas en la evolucion de la toxicosis del lactante con
47. SMITH, H. L., AND J. N. EITELDORF. Parenteral especial referencia al empleo de la solucion Darrow.
fluid regimens in the treatment of severe diarrhea Rev. Chilena Pediat. 28: 20, 1957.
in infants. J. Pediat. 58: 1, 1961. 65. MENEGHELLO, J., J. Rossai.oT, C. AGUILO, F. MON-
48. BEATrY, D. W., M. D. MANN, H. DE V. HEESE AND CREBERG, 0. UNDURRAGA AND M. FERREIRO. In-
G. M. B. BERGER. Acute dehydrating gastroenteritis fantile diarrhea and dehydration: Ambulatory
in undernourished children. S. African Med. J. 48: treatment in a hydration center. Advan. Pediat. 11:
1563, 1974. 183, 1960.
49. RANIER-POPE, C. R. Fluid therapy in gastroenteritis 66. BowlE, M. D., D. MCKENZIE AND J. D. L. HANSEN.
with severe dehydration. A biochemically con- Hyperosmolarity in infantile gastroenteritis. S. Af-
trolled trial of regime in 40 patients. S. African rican Med. J. 32: 322, 1958.
Med. J. 36: 1087, 1962. 67. TRUSWELL, A. S. Results of out-patient treatment

50. IRONSIDE, A. G., A. F. TUXPORD AND B. HEY- of infantile gastroenteritis. S. African Med. J. 31:
WORTH. A survey of infantile gastroenteritis. Brit. 446, 1957.
Med. J. 3: 20, 1970. 68. TRUSWELL, A. S., J. D. L. HANSEN, C. FREESMAN
51. ABALLI, A. G. Single solution not ideal for oral AND T. F. SMIDT. Serum proteins in infants with
therapy of diarrhea. Lancet 2: 5 13, 1975. severe gastroenteritis. S. African Med. J. 37: 527,
52. WElL, W. B., JR. Editorial comment. J. Pediat. 83: 1963.
571, 1973. 69. RANS0ME-KUTI, 0., 0. ELEBUTE AND T. B.
53. BART, K. J., AND L. FINBERG. Single solution for AGUSTO-ODUTOLA. Interperitoneal fluid adminis-
oral therapy of diarrhoea. Lancet 2: 633, 1976. tration in children with gastroenteritis. Brit. Med.
54. KATCHER, A. L., M. F. LEVITr, A. Y. SWEET AND J. 3: 500, 1969.
H. L. HODES. Alterations of fluid and electrolyte 70. MAHALANABIS, D., C. K. WALLACE, R. J. KALLEN,
distribution and renal function in diarrhea of in- A. MONDAL AND N. F. PIERCE. Water and electro-
fancy. J. Clin Invest. 32: 1013, 1953. lyte losses due to cholera in infants and small
55. KERPEL-FRONIUS, E., AND J. VONOCZKY. Signifi- children. A recovery balance study. Pediatrics 45:
cance of changes in the tomcity of body fluids in 374, 1970.
infantile diarrheal dehydration. Ann Paediat. Fenn. 71. AHMED, I. AND T. B. AGUSTO-ODUTOLA. Hyper-
3: 403, 1957. natremia in diarrhoeal infants in Lagos. Arch. Dis-
56 HALTALIN, K. C., J. D. NELSON, R. RING III, M. ease Childhood 45: 97, 1970.
SLADOSE AND L. V. HINTON. Double-blind treat- 72. LIFSHITZ, F., P. COELLO-RAMIREZ AND G. Gt.rrIER-
ment study ofshigellosis comparing ampicillin, sul- aEz-ToPEm. Carbohydrate intolerance in infants
fadiazine and placebo. J. Pediat. 70: 970, 1967. with diarrhea. J. Pediat. 79: 760, 1971.
57. Sui-roN, R. E., AND J. R. HAMILTON. Tolerance of 73. PRINSLOO, J. G., AND KRUGER, H. Electrolyte and
young children with severe gastroenteritis to dietary nutrition status of Bantu children with gastroenter-
lactose: A controlled study. Can. Med. Assoc. J. 99: itis. S. African Med. J. 44: 491, 1970.
980, 1968. 74. WALKER, A. C., AND J. G. HARRY. A survey of
58. HALTALIN, K. C., H. T. KUMEISZ, L. V. HIrrroN diarheal disease in malnourished Aboriginal chil-
AND J. D. NELSON. Treatment of acute diarrhea in dren. Med.J. Australia 1: 904, 1972.
outpatients. Double-blind study comparing ampi- 75. KINGSTON, M. E. Biochemical disturbances in
dillin and placebo. Am. J. Diseases Children 124: breast-fed infants with gastroententis and dehydra-
554, 1972. tion. J. Pediat. 82: 1073, 1973.
59. SHEPHERD, R. W., S. TRUSLOW, J. A. WALKER- 76. GARCIA DE OLARTE, D, S. TRUJILLO H, 0. AGU-
SMITH, R. BIRD, W. CurriNG, R. DARNELL AND C. DELO N, J. D. NELSON AND K. C. HALTALIN. Treat-
M. BARKER. Infantile gastroenteritis: a clinical ment of diarrhea in malnourished infants and chil-
study of reovirus-like agent infection. Lancet 2: dren. Am.
J. Diseases Children 127: 379, 1974.
1082, 1975. 77. NICHOLS, B. L., J. ALVARADO M, J. RODRIQUEZ S,
60. ECHEVERRIA, P., N. R. BLACKLOW AND D. H. C. F. HAZELWOOD AND F. VrraRI E. Therapeutic
SMITH. Role of heat labile toxigenic Escherichia implications of electrolyte, water and nitrogen
coli and reovirus-like agent in diarrhoea in Boston losses during recovery from protein-calorie malnu-
children. Lancet 2: 1 1 13, 1975. trition. J. Pediat. 84: 759, 1974.
61. TRIPP, J. H., M. J. WILMERS AND B. A. WHARTON. 78. MANN, M. D., M. D. BowIE AND J. K. L. HANSEN.
Gastroenteritis: A continuing problem of child Total body potassium acid-base status and serum
health in Britain. Lancet 2: 233, 1977. electrolytes in acute diarrheal disease. S. African
62. CARDELLE, G., R. M. JIMENEZ AND M. G. VAZQUEZ. Med. J. 49: 709, 1975.
Alteraciones del metabolismo hidrosalino en el 79. TARAIL, R., L. W. BASS AND A. S. RUNCO. The
curso de las diarreas infantiles. Rev. Cubana. Lab. frequency and nature of hypertonicity of the body
658 HIRSCHHORN
fluids in infantile diarrhea. Am. J. Diseases Chil- 99. SCHOUB, B. D., H. J. KOORNHOF, G. LECTASAS, D.
dren 86: 658, 1953. W. PROZESKY, I. FREIMAN, E. HARTMAN AND H.
80. WElL, W. B., AND W. M. WALLACE. Hypertonic KASSEL. Viruses in acute summer gastroenteritis in
dehydration in infancy. Pediatrics 17: 171, 1956. black infants.
Lancet 1: 1093, 1975.
8 1. SKINNER, A. L., AND K. C. MOLL. Hypernatremia 100. DAVIDSON, G. P., R. F. BISHOP, R. R. W. TOWNLEY,
accompanying infant diarrhea. Am. J. Diseases I. H. HOLMES AND B. J. RUCK. Importance ofa new
Children 92: 562, 1956. virus in acute sporadic enteritis in children. Lancet
82. DEYour.G, V. R., AND E. F. DIAMOND. Possibility 1:242, 1975.
of iatrogenic factors responsible for hypernatremia 101. CRUICKSHANK, J. G., B. ZILBERG AND J. H. M.
in dehydrated infants. J. Am. Med. Assoc. 173: 104, AXTON. Virus particles and gastroenteritis in black
1960. and white children in Rhodesia. S. African Med. J.
83. SLONE, D., AND S. E. LEVIN. Hypertonic dehydra- 49: 859, 1975.
tion and summer diarrhea. S. African Med. J. 34: 102. RYDER, R. W., D. A. SACK, A. Z. KAPIKIAN, J. C.
209, 1960. MCLAUGHLIN, J. CHAKRABORTY, A. S. M. M. RAH-
84. MACAULEY, D., AND M. I. BLACKHALL. Hyperna- MAN, M. M. MERSON AND J. G. WELLS. Enteroxi-
tremic dehydration in infantile gastroenteritis. genic Escherichia cohi and reovirus-like agent in
Arch. Disease Childhood 36: 543, 1961. rural Bangladesh. Lancet 1: 659, 1976.
85. BERENBERG, W., F. MANDELL AND F. X. FELLERS. 103. KAPIKIAN, A. Z., H. W. KIM,R. G. WYATr, W. L.
Hazards of skimmed milk, unboiled and boiled. CLINE, J. 0. ARROBIO, C. D. BRANDT, W. H. RoD-
Pediatrics 44: 734, 1969. RIGUEZ, D. A. SACK, R. A. CHANOCK AND R. H.

86. MANDELL, F., AND F. X. FELLERS. Hyperglycemia PARROTF. Human reovirus-hike agent as the major
in hypernatremic dehydration. Clin. Pediat. 13: 367, pathogen associated with “winter” gastroenteritis
1974. in hospitalized infants and young children. New
87. ROSENFIELD, W., G. L. DEROMANO, R. KLEINMAN Engl. J. Med. 294: 965, 1976.
AND L. FINBERG. Improving the clinical manage- 104. GUERRANT, R. L., R. A. MOORE, P. M. KIRSCHEN-
ment of hypernatremic dehydration. Observations FELD AND M. A. SANDE. Role of toxigenic and
from a study of 67 infants with this disorder. Chin. invasive bacteria in acute diarrhea in childhood.
Pediat. 16:411, 1977. New Engi. J. Med. 293: 567, 1975.
88. TALBOT, N. B., R. H. RICHIE, J. D. CRAWFORD 105. GROSS, R. J., S. M. SCOTLAND AND B. ROWE.
AND E. S. TAGRIN. Metabolic homeostasis. A Syl- Enterotoxin testing of Escherichia cohi causing ep-
labus for those Concerned with the Care of Patients. idemic infantile enteritis in the U.K. Lancet 1: 629,
Cambridge: Harvard University Press, 1959. 1976.
89. KERRIGAN, G. A. Disturbances ofsodium and wa- 106. SACK, R. B., N. HIRSCHHORN, I. BROWNLEE, R. A.
ter homeostasis in hypernatremic infants. Am. J. CASH, W. E. WOODWARD AND D. A. SACK. Enter-
Diseases Children 98: 608, 1959. otoxigenic Escherichia coil-associated diarheal dis-
90. HEELEY, A. M., AND N. B. TALBOT. Insensible water ease in Apache children. New Engl. J. Med. 292:
losses per day by hospitalized infants and children. 1041, 1975.
Am. J. Diseases Children 90: 251, 1955. 107. HIRSCHHORN, N., R. A. CASH, W. E. WOODWARD
91. GRIFFITH, L. S. C., J. W. FRESH, R. H. WArrEN AND G. H. SPIVEY. Oral fluid therapy of Apache
AND M.
P. WILLAROMAN. Electrolyte replacement children with acute infectious diarrhoea. Lancet 2:
in paediatric cholera. Lancet 1: 1197, 1967. 15, 1972.
92. SPEROTFO, G., F. R. CARRAZZA AND E. MAR- 107a. DARROW, D. C., AND S. HELLERSTEIN. Interpre-
CONDES. Treatment of diarrheal dehydration. Am. tation of certain changes in body water and electro-
J. Chin. Nutr. 30: 1447, 1977. lytes. Physiol. Rev. 38: 1 14, 1958.
93. FLEWETr, T. H., H. DAVIES, A. S. BRYDEN AND M. 108. LEAF, A. The clinical and physiologic significance
J. ROBERTSON. Diagnostic electron microscopy of of the serum sodium concentration. New Engl. J.
faeces. II. Acute gastroenteritis associated with reo- Med. 267: 24, 77, 1962.
virus-like particles. J. Chin Pathol. 27: 608, 1975. 109. OPARIL, S., AND E. HABER. The renin-angiotensin
94. HOLMES, I. H., M. MATHAN, P. BHAT, M. J. ALBERT, system. New Engi. J. Med 291: 389, 446, 1974.
S. P. SWAMINATHAN, P. P. MAIYA, S. M. PEREIRA 1 10. C0NN, J. W., D. R. ROVNER AND E. L. COHEN.
AND S. J. BAKER. Orbiviruses and gastroenteritis. Normal and altered function of the renin-angioten-
Lancet 2: 658, 1974. sion-aldosterone system in man. Applications in
95. SEXTON, M., G. P. DAVIDSON, R. F. BISHOP, R. R. clinical research and medicine. Ann. Internal Med.
R. W. TOWNLEY, I. H. HOLMES AND B. J. RUCK. 63: 266, 1965.
Viruses in gastroenteritis. Lancet 2: 355, 1974. 111. CH0U, S-Y., L. F. FERDER, D. L. LEVIN AND J. G.
96. CONKLIN, R. H., H. L. DUPONT AND J. T. R0DRI- PORUSH. Evidence for enhanced distal tubule so-
QUEZ. Viral agents in acute infantile diarrhea from dium reabsorption in chronic salt-depleted dogs. J.
Houston and Guatemala. Chin. Res. 23: 26A, 1975. Chin. Invest. 57: 1 142, 1976.
97. BRYDEN, A. S., H. A. DAVIES, R. F. HADLEY, T. H. 112. GUR, A.,P. Y. ADEFUIN, N. J. SIEGEL AND J. P.
FLEWETF, C. A. MORRIS AND P. OLIVER. Rotavirus HAYSLETF. A study of renal handling of water in
enteritis in the West Midlands during 1974. Lancet lipoid nephrosis. Pediat. Res. 10: 197, 1976.
2: 241, 1975. 113. DARROW, D. C., AND E. L. PRATF. Fluid Therapy.
98. CAMERON, D. J. S., R. F. BISHOP AND G. P. DAV- Relation to tissue composition and the expenditure
IDSON. Rotavirus infections in obstetric hospitals. of water and electrolyte. J. Am. Med. Assoc. 143:
Lancet 2: 124, 1975. 365, 1950.
1 14. EKLUND, J., P-O. GRANBERG AND D. HALLBERG. hydration in infants. Arch. Disease Childhood 50:
Clinical aspects of body fluid osomolahity. Nutr. 610, 1975.
Metabol. 14: 74, 1972. 135. HOGAN, G. R. Hypernatremia-problems in man-
I 15. HARRINGTON, A. R. Hyponatremia due to sodium agement. Pediat. Chin. N. Am. 23: 569, 1976.
depletion in the absence of vasopressin. Am. J. 136. DAVIES, D. P., B. M. ANSAIR AND B. K. MANDAL.
Physiol. 222:
1972. 768, Hypernatremia and gastroenteritis. Lancet 1: 252,
116. MACKNIGHT, A.
D. C. Epithehial transport of po- 1977.
tassium. Kidney hnternat. I I: 391, 1977. 137. WHALEY, P., AND J. A. WALKER-SMITH. Hyperna-
117. HARRINGTON, J. T., AND J. J. COLTEN. Clinical tremi and gastroenteritis. Lancet 1: 51, 1977.
disorders ofurine concentration and dilution. Arch. 138. FINBERG, L. Hypernatremic dehydration. Advan.
Internal Med. 131: 810, 1973. Ped. 16: 325, 1969.
1 18. EARLEY, L. E., AND T. E. DAUGHARTY. Sodium 139. HOLLIDAY, M. A., AND W. E. SEGAR. The mainte-
metabolism. New Engl. J. Med. 281: 72, 1969. nance need for water in parenteral fluid therapy.
119. LEAF, A. Hyponatremia. Lancet 1: 1 1 19, 1974. Pediatrics.19: 823, 1957.
120. LE,F, A. Regulation of intracellular fluid volume 140. APERIA, A., 0. BROBERGER, K. THODENIUS AND R.
and disease. Am. J. Med. 49: 291, 1970. ZETFERSTROM. Development of renal control of salt
121. METCOFF, J., S. FRENK, T. YOSHIDA, R. T. PINEDO, and fluid homeostasis during the first year of life.
E. KAISER AND J. D. L. HANSEN. Cell composition Acta Paediat. Scand. 64: 393, 1975.
and metabolism in kwashiorkor (severe protein- 141. MCCANCE, R. A., AND W. F. YOUNG. The secretion
calorie malnutrition in children). Medicine 45: 365, of urine by newborn infants. J. Physiol. 99: 265,

1966. 1941.
122. HIRSCHHORN, N. The management of acute diar- 142. RUBIN, M. E., E. BRUCK AND M. RAPOPORT. Mat-
rhea in children: an overview. In: Progress in Drug uration of renal function in childhood: clearance
Research. Tropical Diseases II, Vol 19, edited by studies. J. Chin. Invest. 28: 1 144, 1949.
E. Jucker. Basel: Birkhauser Verlag, 1975, p. 527. 143. MCCANCE, R. A., N. J. B. NAYLOR AND E. M.
123. FLEMING, B. J., S. M. GENUTH AND A. B. GOULD. WIDDOWSON. The response of infants to a large
Laxative-induced hypokalemia, sodium depletion dose of water. Arch. Disease Childhood 29: 104,
and hyperreninemia. Effects of potassium and so- 1954.
dium replacement on the renin-angiotension-aldos- 144. WILKINSON, A. W. Some aspects of renal function
terone system. Ann. Internal Med. 83: 60, 1975. in the newly born. J. Pediat. Surg. 9: 103, 1973.
124. KNOCHEL, J. P. Role of glucoregulatory hormones 145. EDELMANN, C. M., H. L. BARNE-I-r AND V. TROUP-
in potassium homeostasis. Kidney Internat. 1 1: 443, KOU. Renal concentrating mechanisms in newborn
1977. infants. Effect of dietary protein and water content:
125. JOSE, 0. G., AND J. S. WELCH. Growth retardation, role of urea, and responsiveness to anti-diuretic
anaemia and infection with mahabsorption and in- hormone. J. Chin. Invest. 39: 1062, 1960.
festation of the bowel. The syndrome of protein- 146. POLACEK, E., J. VOCEL, L. NEUGEBAUEROVA, M.
calorie malnutrition in Australian Aboriginal chil- SEBKOVA AND E. VECHETOVA. The osmotic concen-
dren. Med. J. Australia 1: 349, 1970. trating ability in healthy infants and children. Arch.
126. ROWLAND, M. G. M., T. J. COLE AND R. G. WHITE- Disease Childhood 40: 291, 1965.
HEAD. A quantitative study into the role of infection 147. PRAI-r, E. L., B. BIENVENU AND M. R. WHYTE.
in determining nutritional status in Gambian vil- Concentration of urine solutes by young infants.
lage children. Brit. J. Nutr. 37: 437, 1977. Pediatrics 1: 181, 1948.
127. VAN DER WESTHUYSEN, J. M., E. KANENGONI, J. J. 148. SCHWARTZ, W. B., AND A. S. RELMAN. Metabolic
JONES AND C. H. VAN NIEKERK. Plasma renin and renal studies in chronic potassium depletion
activity in oedematous and marasmic children with resulting from overuse of laxatives. J. Chin. Invest.
protein energy malnutrition. S. African Med. J. 49: 32: 258, 1953.
1729, 1975. 149. FINBERG, L., B. F. RUSH, JR. AND C-S. CHEUNG.
128. FEIG, P. U., AND The hypertonic
K. K. MCCURDY. Renal excretion of sodium during hypernatremia.
state. New Engl. J. Med. 297: 1444, 1977. Am J. Diseases Children 107: 483, 1964.
129. FRANZ, M. N., AND W. E. SEGAR. The association 150. SCHLESINGER, B., W. PAYNE AND J. BLACK. Potas-
of various factors and hypernatremic diarrheal de- sium metabolism in gastroenteritis. Quart. J. Med.
hydration. Am. J. Diseases Children 97: 60, 1959. 24: 33, 1955.
130. FINBERG, L. Hypernatremic (hypertonic) dehydra- 151. COOKE, R. E. Certain aspects ofthe renal regulation
tion in infants. New Engl. J. Med. 289: 196, 1973. of body composition. Pediatrics 14: 567, 1954.
13 1. GAMSU, H. R. Medical evaluation of osmolar fac- 152. SPATER, H., A. HUNT, R. TODD, P. MEARA, M.
tors. Postgrad. Med. J. 51: 31, 1975. TERRY, J. D. CRAWFORD AND N. B. TALBOT. Dc-
132. DARROW, D. C., R. E. CooKE AND W. E. SEGAR. velopment and therapy of cellular sodium intoxi-
Water and electrolyte metabolism in infants fed cation in potassium deficiency. Metabolism 8: 28,
cow’s milk mixtures during heat stress. Pediatrics 1959.
14: 602, 1954. 153. RAMIREZ, M. A., J. M. BAETRL, Y. A. DE MARTINEZ
133. TAITZ, L. S., AND H. D. High caloric/os-
BYERS. AND G. G. The effect of potassium
GRAHAM. and
molar feeling and hypertonic dehydration. Arch. protein intakes on sodium homeostasis of infants
Disease Childhood 47: 257, 1972. and children. J. Trop. Pediat. Environ. Child
134. CHAMBERS, T. L., AND A. E. STEEL. Concentrated Health 19: 275, 1973.
milk feeds and their relation to hypernatremic de- 154. BERGSTROM, W. H., AND W. M. WALLACE. Bone as
660 HIRSCHHORN
a sodium and potassium reservoir. J. Chin. Invest. stasis and renal function in infancy. Postgrad. Med.
33: 867, 1954. J. 51: 25, 1975.
155. SoTos, J. F., P. R. DODGE AND N. B. TALBOT. 175. BANISTER, A., S. A. MATIN-SIDDIQI AND G. W.
Studies in experimental hypertonicity. II. Hyper- HATCHER. Treatment of hypernatremic dehydra-
tonicity of body fluids as a cause of acidosis. Pedi- tion in infancy. Arch. Disease Childhood 50: 179,
atrics28: 180, 1962. 1975.
156. KILDEBERG, P. Metabolic acidosis in infantile gas- 176. TALBOT, N. D., D. CRAWFORD AND A. M. B.rriR.
troenteritis. Acta Paediat. Scand. 54: 155, 1965. Homeostatic limits to safe parenteral fluid therapy.
157. HARVEY, R. M., Y. ENSON, M. L. LEWIS, W. B. New Engh. J. Med. 248: 1 100, 1953.
GREENOUGH, K. M. ALLY AND R. A. PANNO. He- 177. TALBOT, N. B., G. A. KERRIGAN, J. D. CRAWFORD,
modynamic studies on cholera. Effects of hypovo- W. COCHRAN AND M. TERRY. Application of ho-
lemia and acidosis. Circulation 37: 709, 1968. meostatic principles to the practice of parenteral
158. TORRES-PINEDO, R., E. CONDE, G. ROBILLARD AND fluid therapy. New Engl. J Med. 252: 856, 892,
M. MACDONALD. Studies on infant diarrhea. III. 1955.
Changes in composition ofsaline and glucose-saline 178. TALBOT, N. B., J. D. CRAWFORD, G. A. KERRIGAN,
solutions instilled into the colon. Pediatrics 42: 303, D. HILLMAN, M. BERTUCIO AND M. TERRY. Apphi-
1968. cation ofhomeostatic principles to the management
159. LIFSHITZ, F. Clinical studies in diarrheal disease of nephritic patients. New Engl. J. Med. 255: 655,
and malnutrition associated with carbohydrate in- 1956.
tolerance. In: Proceedings 9th International Con- 179. TALBOT, N. B., J. D. CRAWFORD AND C. D. CooK.

gress of Nutrition. Basel: Karger, 1975, vol. 1, p. Application of homeostatic principles to the man-
173. agement of nephrotic patients. New Engl. J. Med.
160. ROBERTS, W. Alimentary hyperglycemia simulating 256: 1080, 1957.
diabetic ketosis. Lancet 2: 754, 1964. 180. TALBOT, N. B., AND R. H. RICHIE. The advantage
161. NITZAN, M., AND S. ZELMANOVSKY. Glucose intol- of surface area of the body as a basis for calculating
erance in hypernatremic rats. Diabetes 17: 597, pediatric dosages. Pediatrics 23: 495, 1959.
1968. 181. BUTLER, A. M., AND R. H. RICHIE. Simplification
162. STEVENSON, R. E., AND F. P. BOWYER. Hypergly- and improvement in estimating drug dosage and
cemia with hyperosmolal dehydration in non-dia- fluid and dietary allowances for patients of varying
betic infants. J. Pediat. 77: 818, 1970. sizes. New Engl. J. Med. 262: 903, 1960.
163. SPIRER, Z., AND H. BOGAIR. Blood sugar in infants 182. BUTLER, A. M. The use of glucose, electrolyte,
with diarrhea. Lancet 2: 131 1, 1970. albumin, and amino acid solutions and whole blood
164. GARROW, J. S., R. SMITH AND E. E. WARD. Elec- in parenteral fluid therapy. Quart. Rev. Pediat. 15:
trolyte metabolism in severe infantile malnutrition. 34, 1960.
Oxford: Pergamon Press, 1968. 183. GAMBLE, J. L., W. M. WALLACE, L. ELIEL, M. A.
165. HANSEN, J. D. L., AND J. F. BROCK. Potassium HOLLIDAY, M. CUSHMAN, J. APPLETON, A. SHEN-
deficiency in the pathogenesis of nutritional oe- BERG AND J. PIorri. Effects of large loads of dcc-
dema in infants. Lancet 2: 477, 1954. trolytes. Pediatrics 7: 305, 1951.
166. HOWLAND, J. Prolonged intolerance to carbohy- 184. MCCANCE, R. A., AND E. M. WIDDOWSON. Hyper-
drates. Trans. Am. Pediat. Soc. 33: 1 1, 1921. tonic expansion of the extra-cellular fluids. Acta
167. FINKELSTEIN, H. Saughingskrankheiten. Amster- Pediat. 46: 337, 1957.
dam: Elsevier, 1938, cited by D. C. Darrow: Ther- 185. LINDENBAUM, J., W.
B. GREENOUGH, III AND M.
apeutic measures promoting recovery from the R. ISLAM. Antibiotic therapy ofcholera in children.
physiologic disturbances of infantile diarrhea. Pc- Bull. World Health Organ. 37: 529, 1967.
diatrics 9: 519, 1952. 186. RAPOPORT, S., K. DODD, M. CLARK AND I. SYLEM.
168. WARE, S. Hypernatremia and “glucose water”. Postacidotic state of infantile diarrhea: symptoms
Lancet 1: 494, 1976. and chemical data. Postacidotic hypocalcemia and
169. FINBERG, L. The possible role of the physician in associated decreases in levels of potassium, phos-
causing hypernatremia in infants dehydrated from phorus and phosphatase in the plasma. Am. J.
diarrhea. Pediatrics 22: 2, 1958. Diseases Children 73: 391, 1947.
170. PHILLIPS, R. A. Water and electrolyte losses in 187. UYLANGCO, C. V., R. N. CHAUDHURI AND J. A.
cholera. Federation Proc. 23: 705, 1964. VASCO. Lactated Ringer solution in the treatment
171. TORRES-PINEDO, R., M. LAVASTIDA, C. L. RIVERA, of pediatric cholera. J. Philippine Med. Assoc. 42:
H. RODRIGUEZ AND A. ORTIZ. Studies on infant 861, 1966.
diarrhea. I. A comparison of the effects of milk 188. FRANT, S., AND H. ABRAMSON. Epidemic diarrhea
feeding and intravenous therapy upon the compo- of the newborn. In: Therapeutics of Infancy and
sition and volume ofstcol and urine. J. Chin. Invest. Childhood, edited by H. R. Litchfield and L. H.
45: 469, 1966. Dembo. Philadelphia; F. A. Davis & Co., 1947.
172. CHRISTOPHER, N. L., AND T. M. BAYLESS. Role of 189. GRANT, H., AND F. REICHSMAN. The effects of the
the small bowel and colon in lactose-induced diar- ingestion of large amounts of sodium chloride on
rhea. Gastroenterology 60: 845, 1971. the arterial and venous pressures of normal sub-
173. ZIEGLER, E. E., AND S. J. FOMON. Fluid intake jects. Am. Heart J. 32: 704, 1946.
renal solute load and water balance in infancy. J. 190. CRAWFORD, B., AND H. LUDEMANN. The renal
Pediat. 78: 561, 1971. response to intravenous injection of sodium chlo-
174. DAVIES, D. P. Protein intake, osmohality, homeo- ride solutions in man. J. Chin. Invest. 30: 1456,
1951. M. MANJI. Effect of intragastric glucose-electrolyte

191. STEWART, J. D., AND G.
M. RoutKE. The effects of infusion upon water and electrolyte balance in
large intravenous infusions on body fluid. J. Chin. Asiatic cholera. Gastroenterohogy 55: 333, 1968.
Invest. 21: 147, 1942. 209. MODIGLIANI, R., AND J. I. BERNIER. Absorption of
192. ADKINS, T. G., AND V. M. BUCKALEW, JR. On the glucose, sodium, and water by the human jejunum
mechanism of anti-natiuresis following acute saline studies by intestinal perfusion with a proximal oc-
loading. Cliii. Res. 24: 34a, 1976. cluding balloon and at variable flow rates. Gut 12:
193. AMES, R. G. Urinary water excretion and neuro- 184, 1971.
hypophyseal term and premature
function in full 210. SAITO, Y., AND T. H0SHI. Effects of mucosal hy-
infants shortly after birth. Pediatrics 12: 272, 1953. perosmoharity on active sugar-invoked potential in
194. Ga,Y, G. M. Carbohydrate digestion and absorp- isolated small intestine of the toad. Japan. J. Phys-
tion. Role ofthe small intestine. New Engl. J. Med. iol. 23: 419, 1973.
292: 1225, 1975. 21 1. SANDLE, G. I., R. W. LOBLEY AND R. HOLMES. Oral
195. FIELD, M. New strategies for treating watery diar- therapy in cholera. New Engl. J. Med. 298: 797,
rhea. New Engl. J. Med. 297: 1121, 1977. 1978.
196. DESJEUX, J-F., C. TANNENBAUM, Y-H TAI AND P. 212. TURNBERG, L. A., J. S. FORDTRAN, N. W. CARTER
F. CURRAN. Effects of sugars and amino acids on AND F. C. RECTOR, JR. Mechanism of bicarbonate
sodium movement across small intestine. Am. J. absorption and its relationship to sodium transport
Diseases Children 133: 331, 1977. in the human jejunum. J. Clin. Invest. 49: 548,
197. SLADEN, G. E., AND A. M. DAWSON. Interrelation- 1970.

ships between the absorptions of glucose, sodium 213. OLSEN, W. E., AND F. J. INGELFINGER. The role of
and water by the normal humanjejunum. Chin. Sci. sodium in intestinal
glucose absorption in man. J.
36: 119, 1969. Chin. Invest. 47: 1 133, 1968.
198. MODIGLIANI, R., AND J. J. BERNIER. Effects of 214. NALIN, D. R., AND R. A. CASH. Sodium content in
glucose on net and unidirectional movements of oral therapy for diarrhea. Lancet 2: 957, 1976.
water and electrolytes in the human small intestine. 215. CAREY, R. M., J. R. SMITH AND E. M. ORrr.
Biol. Gastrol-Enterol. 5: 165, 1972. Gastrointestinal control of sodium excretion in so-
199. FORDTRAN, J. S. Simulation of active and passive dium-depleted conscious rabbits. Am. J. Physiol.
sodium absorption
by sugars in the human jejunum. 230: 1504, 1976.
J. Clin. 55: 728, 1975.
Invest. 216. SOERGEL, K. H., G. E. WHALEN, J. A. HARRIS AND
200. HELLIER, M. D., C. THIRUMAI AND C. D. J. E. GEENEN. Effect of antidiuretic hormone on
HOLDSWORTH. The effect of amino acids and di- human small intestinal water and solute transport.
peptides on sodium and water absorption in man. J. Chin. Invest. 47: 1071, 1968.
Gut 14: 41, 1973. 217. KENT, T. H., AND J. LINDENBAUM. Correlation of
201. HIRSCHHORN, N., J. L. KINZIE, D. B. SACHAR, R. jejunal function and morphology in patients with
S. NORTHRUP, J. D. TAYLOR, S. Z. AHMAD AND R. acute and chronic diarrhea in East Pakistan. Gas-
A. PHILLIPS. Decrease in net stool output in cholera troenterology 52: 972, 1967.
during intestinal perfusion with glucose-containing 218. HIRSCHHORN, N., AND I. H. ROSENBERG. Sodium-
solutions. New Engl. J. Med. 279: 176, 1968. potassium stimulated adenosine triphosphatase of
202. NALIN, D. R., R. A. CASH, R. ISLAM, M. MOLLA the small intestine of man: studies in cholera and
AND R. A. PHILLIPS. Oral maintenance therapy for other diarrheal diseases. J. Lab. Chin. Med. 72: 28,
cholera in adults. Lancet 2: 370, 1968 1968.
203. PIERCE, N. F., R. B. SACK, R. C. MITRA, J. G. 219. HIRSCHHORN, N., AND A. MOLLA. Reversible je-
BANWELL, K. L. BRIGHAM, D. S. FEDSON AND A. junaldisaccharidase deficiency in cholera and other
MONDAL. Replacement of water and electrolyte acute diarrheal diseases. Johns Hopkins Med. J.
losses in cholera by an oral-glucose electrolyte so- 125: 291, 1969.
lution. Ann. Internal Med. 70: 1173, 1969. 220. BISHOP, R. F., G. P. DAVIDSON, I. H. HOLMES AND
204. MALAWAR, S. J., M. EWTON, J. S. FORDTRAN AND B. J. RUCK. Virus particles in epithehial cells of
F. J. INGELFINGER. Interrelation between jejunal duodenal mucosa from children with acute non-
absorption ofsodium, glucose and water in man. J. bacterial gastroenteritis. Lancet 2: 1281, 1973.
Chin. Invest. 44: 1072, 1965. 221. AGUS, S. G., R. DOLIN, R. G. WYATt. A. J. T0U-
205. GOLDNER, A. M., S. G. SCHULTZ AND P. F. CUR- SIMIS AND R. S. NORTHRUP. Acute infectious non-
RAN. Sodium and sugar fluxes across the mucosal bacterial gastroenteritis: Intestinal histopathology,
border ofthe rabbit ileum. J. Gen. Physiol. 53: 362, histologic and enzymatic alterations during illness
1969. produced by the Norwalk Agent in man. Ann.
206. SCHEDL, H. P., AND J. A. CLIFTON. Solute and Internal Med. 79: 18, 1973.
water absorption by the human small intestine. 222. LIFSHITZ, F., P. COELLO-RAMIREZ AND M. L. CON-
Nature 199: 1264, 1963. TRERAS-GUITERREZ. The response of infants to car-
207. BIEBERDORF, H. P., 5. MORAWSKI AND J. S. FORD- bohydrate oral loads after recovery from diarrhea.
TRAN. Effect of sodium, mannitol, and magnesium J. Pediat. 79: 612, 1971.
on glucose, galactose, 3-0 methylglucose and fruc- 223. GREEN, H. L., D. R. MCCABE AND G. B. MEREN-
tose absorption in the human ileum. Gastroenter- STEIN. Protracted diarrhea and malnutrition in in-
ology 68: 58, 1975. fancy: Changes in intestinal morphology and disac-
208. PIERCE, N. F., J. G. BANWELL, R. C. MITRA, G. J. charidase activities during treatment with total in-
CARANASOS, R. I. KEIMOWITZ, A. MONDAL AND P. travenous nutrition or oral elemental diets. J. Pc-
662 HIRSCHHORN
diat. 87: 695, 1975. man. Gastroenterology 59: 404, 1970.

224. TORRES-PINEDO, R., C. L. RIVERA AND S. FERNAN- 240. LEVINE, G. M., J. J. DEREN, E. STEIGER AND R.
DEZ. Studies on infant diarrhea: II. Absorption of ZINNO. Role of oral intake in maintenance of gut
glucose and net fluxes ofwater and sodium chloride mass and disaccharidase activity. Gastroenterology
in a segment of the jejunum. J. Clin. Invest. 45: 67: 975, 1974.
1916, 1966. 241. GREEN, H. L., F. B. STIFEL, L. HAGLER AND R. H.
225. JAMES, W. P. T., B. S. DRASAR AND C. MILLER. HERMAN. Comparison of the adaptive changes in
Physiologic mechanism and pathogenesis of wean- disaccharidase, glycolytic and fructose diphospha-
ling diarrhea. Am. J. Chin. Nutr. 25: 564, 1972. tase activities after intravenous and oral glucose in
226. LUGO-DE-RIVERA, C., H. RODRIQUEZ AND R. normal man. Am. J. Chin. Nutr. 28: 1 122, 1975.
TORRES-PINEDO. Studies on the mechanism of 242. PERGOLIZZI, R., F. LIFSCHITZ, S. TEICHBERG AND
sugar malabsorption in infantile infectious diar- R. WAPNIR. Interaction between dietary carbohy-
rhea. Am. J. Chin. Nutr. 25: 1248, 1972. drates and intestinal disaccharidases in experimen-
227. CHUNG, A. W., AND B. VISCOROVA. The effect of tal diarrhea. Am. J. Chin. Nutr. 30: 482, 1977.
early oral feedings versus early oral starvation on 243. SPARK, R. F., R. A. ARKY AND P. R. BOULTER.
the course of infantile diarrhea. J. Pediat. 33: 14, Renin, aldosterone and glucagon in the natriuresis
1948. of fasting. New Engl. J. Med. 292: 1335, 1975.
228. LARCHER, V. F., R. SHEPHERD, D. E. M. FRANCIS 244. DOEKEL, R. C., JR.,
C. W. ZWILLICH, C. H. SCoo-
AND J. T. HARRIES. Protracted diarrhoea in infancy. GIN, M. KRYGER AND J. V. WElL. Clinical semi-
Analysis of 82 cases with particular reference to starvation. Depression of hypoxic ventilatory re-

diagnosis and management. Arch. Disease Child- sponse. New Engl. J. Med. 295: 358, 1976.
hood 52: 597, 1977. 245. ITZKOWITZ, S., S. B. CLARK AND N. S. ROSEN-
229. HYMAN, C. J., J. REITER, J. RODNAN AND A. L. SWEIG. Ileal glucose perfusion increases net proxi-
DRASH. Parenteral and oral alimentation in the mal intestinal disaccharidases. Chin. Res. 25: 660A,
treatment of nonspecific protracted diarrheal syn- 1977.
drome ofinfancy. J. Pediat. 78: 17, 1971. 246. NICHOLSON, J. A., D. M. MCCARTHY AND Y. S.
230. LEAKE, R. D., K. C. SCHROEDER, D. A. BENTON KIM. The responses of rat intestinal brush border
AND W. OH. Soy-based formula in in the treatment and cytosol peptide hydrohase activities to variation
of infantile diarrhea. Am. J. Diseases Children 127: in dietary protein content. J. Chin. hnvest. 54: 890,
374, 1974. 1974.
231. SHERMAN, J. 0., C. A. HAMLY AND A. K. KHACH- 247. ROSENWEIG, N. S., AND R. H. HERMAN. Control of
ADURIAN. Use of an oral elemental diet in infants jejunal sucrase and maltase activity by dietary su-
with severe intractable diarrhea. J. Pediat. 86: 518, crose or fructose in man. J. Chin. Invest. 47: 2253,
1975. 1968.
232. GRACEY, M., AND R. HENDERSON. The use of a 248. ROSENSWEIG, N. S., AND R. H. HERMAN. Dose
carbohydrate-free feeding formula in Australian response ofjejunal sucrase and maltase to isocaloric
Aboriginal children with chronic diarrhea. Austra- high and low carbohydrate diets in man. Am. J.
han Pediat. J. 10: 164, 1974. Chin. Nutr. 23: 1373, 1970.
233. MITCHELL, J. D., J. BRAND AND J. HALBISCH. 249. ASSAD, R. T., AND G. L. EAsiwooD. Epithelial
Weight-gain inhibition by lactose in Australian Ab- kinetics in small intestine of orally versus intrave-
original children. A controlled trial of normal and nously alimented rats. Chin. Res. 24: 627A, 1977.
lactose hydrolysed milk. Lancet 1: 500, 1977. 250. CONDON-PAOLONI, D., J. CRAVIOTO, F. E. JOHN-
234. NALIN, D. R., R. A. CASH, M. RAHMAN AND M. STON, E. R. DE LICARDIF AND T. 0. SCHOLL. Mor-
YUNUS. Effect of glycine and glucose on sodium bidity and growth of infants and young children in
and water absorption in patients with cholera. Gut a rural Mexican village. Am. J. Public Health 67:
11:768, 1970. 651, 1977.
235. BEDINE, M. S., AND T. M. BAYLESS. Modification 251. COLE, T. J., AND J. M. PARKIN. Infection and its
of lactose tolerance by glucose or a meal. Chin. Res. effect on the growth of young children: A compar-
20: 448, 1972. ison of the Gambia
and Uganda. Trans. Roy. Soc.
236. BILLICH, C., G. A. BRAY, T. F. GALLAGHER, JR., A. Trop. Med. Hyg. 71: 196, 1977.
V. HOFFBRAND AND R. LEVITAN. Absorptive ca- 252. BINNS, C. W. Food, sickness and death in children
pacity of the jejunum of obese and lean subjects. of the Highlands of Papua New Guinea. J. Trop.
Effect of fasting. Arch. Internal Med. 130: 377, Med. Environ. Child Health 22: 9, 1976.
1972. 253. MATA, L. J., R. A. KROMAL, J. J. URRUTIA AND B.
237. KNUDSEN, K. B., H.
M. BELLAMY, F. R. LECOCQ, GARCIA. Effect food intake
of infection
and on the
E. M. BRADLEY AND J. D. WELsH. Effect of fasting nutritional state: perspectives as viewed from the
and refeeding on the histology and disaccharidase village. Am. J. Chin. Nutr. 30: 1215, 1977.
activity of the human intestine. Gastroenterohogy 254. GuiI, 0. P., AND V. N. JAISWAL. Relationship of
55: 46, 1968. undernutrition to diarrhoea in infants and children.
238. STEINER, M., G. C. M. FARRISH AND S. J. GRAY. hnd. J. Med. Res. 58: 789, 1970.
Intestinal uptake of valine in calorie and protein 255. HARRISON, H. E. The treatment of diarrhea in
deprivation. Am. J. Chin. Nutr. 22: 871, 1969. infancy. Pediat. Chin. N. Am. 1: 335, 1954.
239. ADIBI, S. A., AND E. R. AuiN. Impaired jejunal 256. NALIN, D. R., R. A. CASH AND M. RAHMAN. Oral
absorption rates of essential amino acids induced (or nasogastric) maintenance therapy for cholera
by either dietary caloric or protein deprivation in patients in all age groups. Bull. World Health Or-
gan. 43: 361, 1970. dromes. Am. J. Chin. Nutr. 30: 1457, 1977.
257. SACK, R. G., J. CASSELLS, R. MITRA, C. MERRITF, 265. HIRSCHHORN, N., AND K. M. DENNY.Oral glucose-
T. BUTLER, J. THOMAS, B. JACOBS, A. CHAUDHURI electrolyte therapy for diarrhea: A means to main-
AND A. MONDAL. The use of oral replacement tain or improve nutrition? Am. J. Chin. Nutr. 28:
solutions in the treatment of cholera and other 189, 1975.
severe diarrhoeal disorders. Bull. World Health 266. International Study Group. A positive effect on the
Organ. 43: 351, 1970. nutrition of Philippine children of an oral-glucose-
258. KIELMANN, A. A., AND C. MCCORD. Home treat- electrolyte solution given at home for the treatment
ment of childhood diarrhea in Punjab villages. J. of diarrhoea. Bull. World Health Organ. 55: 87,
Trop. Pediat. Environ. Child Health 23: 197, 1977. 1977.
259. CHATrERJEE, A., D. MAHALANABIS, K. N. JALAN, 267. MAHALANABIS, D., R. B. SACK, B. JACOBS, A. M0N-
T. K. MAITRA, S. K. AGARWAL, D. K. BAGCHI AND DAL AND J. THOMAS. Use ofan oral glucose electro-
S. INDRA. Evaluation of a sucrose/electrolyte solu- lyte solution in the treatment of pediatric cholera-
tion for oral rehydration in acute infantile char- a controlled study. J. Trop. Pediat. Environ. Child
rhoea. Lancet 1: 1333, 1977. Health 20: 82, 1974.
260. CHATrERJEE, A., D. MAHALANABIS, K. N. JALAN, 268. NALIN, D., M. M. LEVINE, R. HORNICK, E.
T. K. MAITRA, S. K. AGARWAL, B. DUTrA, S. P. BERGQUIST, D. Hoovea, H. P. Houiy, D. WAiea-
KHATUA AND D. K. BAGCHI. Oral rehydration in MAN, J. VAN Bwtx, S. MATHENY, S. SOTMAN AND
infantile diarrhoea. Controlled trial ofa low sodium M. RENNELS. The problem of emesis during oral
glucose electrolyte solution. Arch. Disease Child- glucose-electrolytes therapy given from the onset of

hood 53: 284, 1978. severe cholera. Trans. Roy. Soc. Trop. Med. Hyg.
261. NALIN, D.
R., M. M. LEVINE, L. MATA, C. DE 73: 10, 1979.
CESPEDES, W. VARGAS, C. LIZANO, A. R. CORIA, 269. PALMER, D. L., F. T. Kosmi, A. F. M. R. Iswi,
A. SIMHON AND E. MOHS. Oral rehydration and A. S. M. M. RAHMAN AND R. B. SACK. Comparison
maintenance of children with rotavirus and bacte- of sucrose and glucose in the oral electrolyte ther-
rial diarrhoeas. Bull. World Health Organ. 57: 453, apy of cholera and other severe diarrheas. New
1979. EngI. J. Med. 297: 1 107, 1977.
262. NALIN, D. R., M. M. LEVINE, L. MATA, C. DE 270. PIZARRO, D., G. PUSADA, L. MATA, D. NALIN AND
CESPEDES, W. VARGAS, C. LIZANO, A. R. LORIA, A. E. MOHS. Oral dehydration of neonates with de-
SIMHON AND E. MOHS. Comparison ofsucrosc with hydrating diarrhocas. Lancet 2: 1209, 1979.
glucose in oral therapy of infant diarrhea. Lancet 271. MOENGINAH, P. A., Supaiwro, J. SonitTo, M.
2: 277, 1978. BACHTIN, Ds. SirralsNo, SUTARYO AND J. E.
263. SACK, D. A., A. M. A. K. CHOWDHURY, A. EUSOF, ROHDE. Oral sucrose therapy for diarrhea. Lancet
M. A. ALl, M. M. MERSON, S. IsLAM, R. E. BLACK 2: 323, 1975.
AND R. E. BROWN. Oral hydration in rota-virus 272. INTERNATIONAL Sniu GROUP. Beneficial effects
diarrhea: A double blind comparison of sucrose of oral electrolyte-sugar solutions in the treatment
with glucose electrolyte solution. Lancet 2: 280, of children’s diarrhea. 2. Studies in seven rural
1978. villages. J. Trop. Pediat. Environ. Child Health. In
264. NICHOLS, B. L., AND H. A. SORIANO. A critique of press.
oral therapy of dehydration due to diarrheal syn-

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perspectives in nutrition

The treatment of acute diarrhea in children

An historical and physiological perspective13

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Year Event Hospital

1912 Sellards (10) describes acidosis in cholera and uses alkali.

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1946-1949 Darrow, at Hopkins, (17-20) does balance studies to measure 6%

1958 Darrow’s solution (in mEq/L:Na61,Kl8, base 27) as sole 10%

1950’s-1960’s In the West, better understanding of hypernatremia (28, 29), 0-5%

l960’s-1970’s In Asia, simplified methods of treatment of cholera and non- 2-3%

1966-1979 Increasing use of oral glucose-electrolyte solutions in cholera 0-2%

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Traditional teaching Recently dcveIo

2. Speed of rehydration 24-48 hr 4-6 hr

4. Use of potassium Only after urination commences. In polyelectrolyte solution.

5. Use of base Only for severe acidosis. In polyelectrolyte solution (bicarbon-

8. Principal concerns Overhydration, hypernatremia, Under hydration, hyponatremia, un-

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Sc%Vt4Y LOAD (mEq/kg) TOTAL VOLUMEx SXIUM (m/aq/kq)

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weatem Tropical Hypernatremic

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5. Mean sodium loss, mEq/kg. in

8. ECF sodium on admission: % hy-

9. Mean evaporative loss, ml/kg/

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Cotoboisin. TheeDoys0’ 5’#{176};

HyemgieesO. Aodos irs incased

HYPERTONICITY LSolute Load ]

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cholera. Pediatrics 44: 922, 1969. Clin. 8: 30, 1954.

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1951. M. MANJI. Effect of intragastric glucose-electrolyte

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diat. 87: 695, 1975. man. Gastroenterology 59: 404, 1970.

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