Pediatrics
VOLUME 16 JULY 1955 NUMBER 1
ORIGINAL
ARTICLES
HYPERNATREMIA
IN INFANTS
An
Evaluation
of
the
Clinical
and
Biochemical
Findings
Accompanying
this
State
By Laurence Finberg, M.D.,* and
Harold
E.
Harrison, M.D.I
T HAS become apparent in recent yearsthat there is a group of dehydrated
in-fants in whom management of the
physio-logical disturbance is especially difficult,
despite the administration of repair solu-tions ordinarily effective. Two phenomena
were found present in many of these
in-fants: manifestations suggesting nervous
system injury which were sometimes severe,
and an increased concentration of sodium
in the serum. If the hypematremia were in
any way causally related to the nervous
system injury, it would be highly important to establish criteria for the early recognition
of hypernatremic dehydration and to
de-vise treatment regimens for its
manage-ment.
The existence of hypematrema, or
“hy-From Division of Pediatrics of the Baltimore City Hospitals, and the Department of Pediatrics
of the Johns Hopkins University School of
Medi-cine, Baltimore, Maryland.
With the technical assistance of Evelyn Fleish-man.
This paper was presented ti part at the meeting
of the American Pedjatric Society on May 3,
1954.
(Submitted for pullieatlon October 27, 1954; accepted March 14, 1955.)
* ADDRESS: Baltimore City Hospitals, 4940 Eastern Avenue, Baltimore 24, Maryland.
perosmolarity,” as a significant
physiologi-cal disturbance in infants has been docu-mented in the literature since 1850.13 In
1947, Rapoport4 refocused attention on
some of the clinical features and cited cases
which indicated the complex derangements
of extracellular and intracellular
electro-lytes accompanying this state.
The purpose of the present study is to
correlate the clinical, biochemical, and
pathological findings in infants with hyper-natremia in order to facilitate the recogni-tion of this state, and to indicate optimal
management. To do this, an analysis was
made of the findings in 88 infants studied
over the past 7 years in whom concentra-tions of sodium in the serum over 150
mEq./1. were found.
MATERIAL
AND
METHODS
Eighty-one of the patients included in this
study constitute all of the diagnosed cases of
hypernatremia in infants under 2 years of age
at the Baltimore City Hospitals during the 7
years, 1947 to 1953 inclusive. In 69 of these,
the cause for admission was diarrheal disease.
The other patients include 4 infants who
de-veloped diarrhea in the hospital nursery, and
8 infants with hypernatremia accompanying
respiratory infections. Seven additional
TABLE I
ADMISSIONS OF 1)IAIuuIEAL I)ISEA5E, 1947-1953
Nun-bet
Deaths
Mor-tailty
(per cent)
Serum Na<15O mEq./l. Serum Na>150 uiEq./1.
Totals
O5 69
74
4 8
J
.O 11.6
4.4
x’9.35; p<.Ol
Home are included in the over-all evaluation
of the biochemical disturbances.
The analyses for electrolytes and urea
nitro-gen were performed on the serum obtained
from venous blood. Sodium and potassium
were determined by flame photometry; chloride
by the method of Van Slyke and Sendroy;5
CO2 content by the method of Van Slyke and
Neil;6 phosphorus by the method of Fiske
and Subbarow; and urea nitrogen by the
method of Van Slyke.8 Serum calcium prior
to 1953 was determined by the method of
Kramer and Tisdall.9 Since that time a micro
method using 0.2 ml. of serum has been
em-ployed.bo The results with this technique have
agreed within 5 per cent with those obtained
by the Kramer-Tisdall method when
simul-taneous determinations were done on the same
sample of serum.
In the balance study, the serum water was
determined by drying a weighed aliquot of
measured volume to constant weight in an
oven at 105#{176}C.The Donnan factor of 0.96
was used in calculating the concentration of
sodium and chloride in extracellular water.
RESULTS
It was apparent that a large majority of
the infants with hypernatremia were suf-fering from diarrheal disease. The predis-posing factors and manifestations of
hyper-natremic dehydration were studied by
con-trasting such infants to other infants with diarrheal disease and dehydration in whom the concentrations of sodium in the serum
were determined to be less than 150
mEq/1. Table I provides a summary of
the mortality data in 274 infants with severe diarrhea admitted to the Baltimore
City Hospitals over a 7-year period, divided according to the maximum attained con-centration of the serum sodium. Severity was determined by clinical criteria which included any or all of the following: shock,
marked weight loss, tissue changes of
extra-cellular fluid depletion, persistent vomiting,
and convulsions or disturbances of
con-sciousness. Two hundred five make up the
group with serum sodium concentrations
under 150 mEq./1. Four of these patients
died-a mortality rate of just under 2 per
cent. Sixty-nine patients were in the group
with hypernatremia. Sixty of them had high
serum sodium levels on admission, whereas
in the other 9 the serum sodium
con-centrations rose after treatment. The
cmi-cal and biochemical features of the
“iatro-genic” group differed in no way from the others. Of the 69 patients, 8 died-a mor-tality of 11.6 per cent. The mortality rate
difference between the 2 groups is
statisti-cally significant. (Yates correction of the Chi Square method.’)
The age distribution of the infants
ad-mitted with hypernatremia associated with
diarrhea was not significantly different from that of the infants with diarrhea and de-hydration without elevation of serum
so-dium. In the total group, 65 per cent of the
infants were less than 5 months of age. However, the incidence of prematurely born infants appears greater in the
hyper-natremic group than in the group with
normal or reduced serum sodium levels,
Serum Na <150 mEq./l. Serum Na>150 mEq./1.
22 of 205
S2of 69
11.0 46.4
9 of 22 30 of 32
41 94 TABLE II
EXAMINATIONS OF SPINAL FLUID BECAUSE OF CENTRAL NERVOUS SYSTEM SIGNS IN 274 PATIENTS WITH DIARRHEAL DISEASE
Patients HavIng Lumbar PuncturesProtein> 50 mg./100 ml.
Number Number
Per Cent Per Cent
Examined Examined
diarrhea had received very large amounts of salt orally. This occurred because of the
mother’s error in giving a solution con-taining a tablespoon or more of salt per quart of water rather than the hypotonic salt solution prescribed. The physiological disturbance in these patients with excessive
salt intake appeared to be the same as
that in the infants whose sodium intake was
not high but who had been deprived of
water.
In about two-thirds of the infants with hypernatremia there were manifestations referable to the nervous system. The most common symptoms were alterations of
con-sciousness which varied from moderate
lethargy to coma. Kerpel-Fronius has also
commented on the changes in states of
consciousness of infants with hypertonic
dehydration.2 In those who could be
aroused, marked irritability was present and
often associated with a high-pitched cry. Changes in muscle tone ranged from mild
increase in tone with exaggerated deep
tendon reflexes to marked rigidity, muscle
twitchings and frank convulsions. These symptoms and signs led the staff to perform a lumbar puncture in over half of the total number of patients with hypernatremia.
Table II shows that in the series of 274
infants with diarrheal disease lumbar
punc-tures were done because of meningismus
or other neurological manifestations in 32 of 69 patients with hypematremia and in only 11 per cent of the other patients. The characteristic finding in the spinal fluid was an increased concentration of protein with-out pleocytosis. This was found in SO of the
32 spinal fluids obtained from infants with
central nervous system manifestations
as-sociated with hypernatremia. It is
recog-nized that because systematic examinations of the spinal fluid were not done in all pa-tients with diarrheal disease, the results are not conclusive but do suggest that the
in-creased protein concentration in the
cere-brospinal fluid of the infants with
hyper-natremia is a significant finding. At autopsy,
2 infants with hypernatremia had extensive
subarachnoid hemorrhage. Severe perma-nent neurological residua developed in 4
patients who were apparently normal
be-fore the episode of hypernatremic dehydra-tion.
The severity of the neurological and spi-nal fluid findings have not been directly related to the magnitude of the increase
in sodium concentration. As mentioned
above 4 infants developed hypernatremia following excessive ingestion of salt. All 4 of these infants showed manifestations of
central nervous system injury, and in 1
of them the nervous system damage was
severe and irreversible. In these patients the sequence of events clearly indicates that the hypematremia anteceded the nervous system damage.
Despite the fact that the subsequent
weight curve indicated marked reduction of
body water at the time of admission, al-most half of the infants did not appear to
be significantly dehydrated when first
ex-amined. Because of the predominance of
the nervous system signs and lack of ob-vious evidence of dehydration the
Intale
Stool Total
Balance
Post-treatment body water
(assumed) = 3.528 1.
TABLE III
STUDY OF PATIENT AL. DURING PERIOD OF FIRST 24 HOURS OF REHYDRATION A. Balance Data
Output
Urine
11() 1170.Oml. 191.Oml. 410.Oml. 600.Oml. *
Na 17.6 mEq. 5.4mEq. 1.6mEq. 2LOmEq. - 3.4mEq.
K 7.2mEq. 9.8niEq. 5.lmEq. 14.9niEq. - 7.7mEq.
Cl 10.8 mEq. 5.8 niEq. 21.2 inEq. 27.0 mEq. - 16.2 mE.
* Because water losses due to insensible loss through skin, lungs and sweat were not measured, the net change in water is taken to be the change in body weight.
Initial Body Weight 4625 gm.
24-hour Body Weight 5040 gm.
Net Change +415 gm.
B. Serum Concentrations
Na CO2 Cl K Ca Urea N
mEq./l. mg./100 ml.
Initial
24-hour
161 10.8 141 5.2
143 20.1 115 3.7
4.4 38.4
8.2f 12.9
t ‘The patient received Igm of calcium gluconate intravenously during this period.
not given due consideration in several such
infants until laboratory results were
avail-able. A doughy or “scierema-like” texture
of the skin and subcutaneous tissues, though
striking in a few patients, was not constant
enough to be of consistent diagnostic help.
In an effort to elucidate the shifts of
water and ions in this disturbance, a
bal-ance study was carried out during the first
24 hours of treatment of a patient (A. L.) who developed hypernatremia during a
re-lapse of diarrhea which occurred while in
the hospital. During the balance period the
patient was treated with a large amount
of water and relatively little sodium, re-ceiving 225 ml./kg. of water with an aver age final concentration of sodium of 15 mEq./l. in the total fluids given. The intake of water and electrolytes were quantita-tively measured, and the stools and urine
were collected and analyzed. The net
changes in water and electrolyte balance and serum electrolyte concentrations are
given in Table III Calculations from the
balance data were then made, based on
the assumptions: That the chloride ion was
exclusively extracellular; that the body water content was 70 per cent of the re-hydrated (nonedematous) weight; that 25 per cent of this rehydrated weight repre-sented extracellular water, and that the increment in weight measured the increase of body water.
The assumption that the body water
content after 24 hours of treatment was
normal may not be accurate but
consider-able deviations from these assigned values
will not vitiate the conclusions drawn from this study with regard to the relative incre-ments of water added to the extracellular and intracellular compartments. The as-sumption of the extracellular position of the chloride is, however, a fundamental
one. No corrections were made for the
small fraction of chloride in red cells. The
3500
3000
2500
-,, , I-’
EC F,
1110 ml.
A ICF13.7701cF
I C F2
2268 ml. ICF,
2003 ml.
E
LU
I-1500
>%
0 1000
500
C
Fic. 1. The left side of the diagram shows the calculated compartments of the patient’s body water prior to hydration. The right side of the diagram depicts the assumed total body water and its distribu-tion subsequent to recovery (see text). Areas designated by the symbol indicate the calculated addi-tions to each compartment. The abbreviations EFC and ICF mean extracellular fluid and intracellular
= 2.268 1.
= 127.5* mEq./1.
= 160* mEq./1.
= 160.8 mEq.
= 177 mEq. = 1.11 1.
= 3.113 1.
= 2.003 1. fluid, respectively.
WATER DISTRIBUTION BEFORE AND AFTER HYDRATION PT.A.L, RECOVERY WI. 5040 GM.
DEHYDRATED
Post-treatment ECF (assumed) = 1.260 1.
Post-treatment ICF Post-treatment extracellular
chloride concentration Pre-treatment extracellular
chloride concentration Post-treatment body chloride
= 127.5
x
1.26 Pre-treatment body chloride= 160.8 + 16.2
Pre-treatment ECF = 177/160 Pre-treatment total body
water=3.528- .415
Pre-treatment ICF = 3.113 - 1.110
* Serum chloride concentration corrected for
serum water and Donnan effect.
RECOVERY
- -
-E CF2
1260 ml.
Figure 1 shows graphically one of the
re-suits of these calculations, which suggest
that water was added to the intracellular
and extracellular compartments in
incre-ments representing similar proportions of
their initial volumes. This means that
two-thirds of the total water retained was added
to the intracellular compartment. A second result of the calculations shows that the
re-TABLE IV
SERUM ELECTROLYTE DETERMINATIONS IN PATIENTS WITH HIGH SERUM Na AND Low SERUM K
CONCENTRA-TIONS AT THE TIME OF MAXIMAL NON-PROTEIN NITROGEN RETENTION
Na CO2 (‘I K
.
Urea NmEq./l. Jt. A.W. E.P. T.S. MA. V.T. S.W. TB. 170 155 165 164 151 180 182 30.8 9.3 18.3 30.9 7.6 22.5 13.2 115 131 121 121 125 155 152 mg./100 ml. 56.0 52.4 164.0 19.4 91.8 110.0 (NPN) 108.0 (NPN) 2.9 3.4 3.3 2.9 3.3 2.8 3.3
urea nitrogen retention. There are examples of both elevated and reduced serum bicar-bonate concentrations in this group.
Another relationship of special interest
involves the behavior of the serum calcium
in these patients. Serum calcium
determina-tions were made in 38 patients with
hyper-natremia and concentrations below 9 mg./
100 ml. were found in 28 of them. In 7
infants serum calcium levels of 7 mg./100 ml. or less were found. The serum calcium
was determined on admission in SO of these
patients and it was below 9 mg./100 ml.
18 times. Serum calcium was determined
on admission in 65 patients with diarrhea and dehydration with normal or low serum sodium levels and reduction of calcium concentration below 9 mg./100 ml. occurred
only S times. (Below 7 mg./100 ml. once.)
Figure 2 shows a scatter diagram of
admis-sion serum calcium concentrations plotted
against the sodium concentrations in the hypernatremic group. There appears to be a partial inverse correlation, and the calcu-lated correlation coefficient is - .34. There
was no correlation found in the patients
CORRELATION BETWEEN
ADMISSION SERUM NA AND CA CONCENTRATIONS
0 0
0 0 0
0 0
00 2
1) 0
8 0 o
000 00000
0
I80
sult was obtained by comparing the
prod-uct of the pre-treatment concentration of
extracellular sodium and the calculated extracellular fluid volume (ECE1), with the
post-treatment product of the sodium
con-centration and the assumed post-treatment
volume (ECF2).
Pre-treatment NaE = 165 mEq./1.
x
1.11 1. = 183mEq.
Post-treatment Na = 146 mEq./1. x 1.26
1. = 184 mEq.
The over-all body sodium change meas-ured by the balance was -3.4 mEq. of Na.
Even if allowances are made for possible
extrarenal losses of sodium no important
change in intracellular sodium is indicated. In the total group of 88 patients studied the bicarbonate concentration of the serum on admission was reduced below 15 mEq./l.
58 times, fell between 15 and 27 mEq.Il.
23 times, and exceeded 27 mEq./l. 7 times.
Interrelations among the extracellular cat-ions are of considerable interest. In a num-ber of the patients the serum potassium concentrations were reduced below normal despite impairment of kidney function as indicated by urea retention. This is illus-trated in Table IV, which shows the serum concentrations of sodium, bicarbonate, chloride, potassium and urea nitrogen in
7 of these patients at the time of maximal
50 70
SERUM NA MEQ,/L.
r -0.34
CORRELATION BETWEE N ADMISSION SERUM CA AND P CONCENTRATIONS
12
00
0 0 0 0 o
0 0
o a 00
0 g 00
0
0 0
0
6 os.)
0
0
Ui0 4
3 4 5 6 78 9 0
SERUM P
MG./I0O CC.
Fic. 3.
CORRELATION BETWEEN
ADMISSION SERUM CA AND UREA N CONCENTRATIONS
00
000,
0
(0 0 0 000 0 0
o
Ut-, 0 0 0
o000 0
0 0 0
11) o 0
6
0
10 20 30 40 50 60 70 80 90 100
UREA N MG./IO0 CC.
0
I
4
X
X
X X
X X
Q.t-) 0
X
X
x
X
x
x
X X
X
X X
X
10 20 30 40 50 60 70
UREA N
MC /1 00 CC
Fic. 5.
80 90 100 CORRELATION BETWEEN
ADMISSION SERUM P AND UREA N CONCENTRATION
with serum sodium concentrations below 150 mEq./l. It was thought that the hypo-calcemia might be accounted for on the basis of hyperphosphatemia, but no appar-ent correlation is seen in these same
pa-tients between the admission serum calcium
and phosphorus levels (Fig. 5). A further check on this point is shown in Figure 4, in which serum calcium is plotted against the blood urea nitrogen concentration. Here again, no correlation is seen. Figure
5 correlates the serum phosphorus and
blood urea nitrogen concentrations in the same patients and shows the expected
cor-relation between elevation of serum phos-phorus and of blood urea nitrogen levels.
The hypocalcemia was observed in the
relatively small group of patients whose
serum bicarbonate concentrations were
elevated (under 7 mg./100 ml. in 2 in-stances) as well as in the larger group with
reduced bicarbonate concentrations.
DISCUSSION
Before the physiologic disturbance of
hypematremic dehydration occurs it is
obvious that water loss disproportionate to sodium loss from extracellular fluid must occur. In the group of cases in which the
hypernatremia was associated with
respira-tory infections the major factor was lack of intake of water which was probably aggra-vated by increased water losses through the skin and lungs. The role of such
in-creased insensible water losses has been
stressed by Rapoport.4’12
The majority of our patients had diarrhea as a prominent underlying symptom so that concomitant electrolyte loss would be
ex-pected. Gamble and Wallace13 have
em-phasized the fact that with abrupt cessation of water intake the water loss in diarrhea
is disproportionately greater than the
inEq./i.
* Low sodium intake started.
All of the patients in the present series had
a history of acute curtailment of water
in-take; however, patients with normal serum sodium concentrations may have apparently
similar histories. Thus additional factors
must be sought. Mention has already been made of increased extrarenal water losses. The relative inadequacy of maximal renal
osmotic concentration in young infants13”4
might be significant in the pathogenesis of
this syndrome. The apparent increased
in-cidence of hypernatremia in infants who
were prematurely born supports this con-tention.
The stool’ water of infants with diarrheal disease has a lower concentration of sodium than does extracellular fluid so that loss of water in relative excess of sodium might be expected to occur with large stool
vol-umes.’5 Insufficient studies have been made
to determine whether the sodium concen-tration in stool water is lower for the hyper-natremic group than for those infants with normal sodium levels.
The present study demonstrates the cor-relation of hypernatremia with nervous sys-tem injury manifested by clinical signs, cerebrospinal fluid changes, and autopsy
findings of intracranial hemorrhage. Similar
cases have occurred in whom the hyper-natremia and the evidences of central nerv-ous system injury followed excessive salt ingestion. This suggests that hypernatremia
or its necessary concomitant, intracellular dehydration, is responsible, at least in part, for the nervous system damage observed. On the other hand a number of reports
have indicated that the serum sodium
con-centration may be elevated following brain
lesions due to trauma, brain surgery, and
a variety of encephalopathies.’#{176}9 The sug-gestion that renal regulation of osmotic concentration might be under central nerv-ous system control has been made but sim-ple deficiency of water intake in the stu-porous patient has also been proposed as an explanation of the hypernatremia.’7 This latter factor is illustrated by the fol-lowing case:
A 4-year-old girl, C. M., was admitted to
the neurosurgical service with multiple
in-juries, including a skull fracture, following an
automobile accident. Following an emergency
craniotomy and vigorous treatment for the ensuing shock the patient was comatose. After receiving parenteral fluid (1000 ml. glucose
in distilled water) over the next 24 hours, the
patient was started on a stomach tube regimen
of 1000 to 1200 ml. per day of cows’ milk.
During 5 days (3 to 7 inclusive) of this
manage-ment she remained comatose and she ran a
fever varying between 1010 and 102.5#{176}F. On
the eighth day, her condition seemed to be
deteriorating and pediatric consultation was
sought. At this point the feeding mixture was shifted to a low sodium milk (Lonalac#{174}) plus added carbohydrate and the total fluid intake
TABLE V
STUDIES ON C.M., AGE Foun YEARS, A PATIENT WITH HEAD INJURY Wito DEVELOPED ILYPERNATREMIA
Serum Concentration Urine
Days Na CO, Cl Urea N Vol. Na Cl
mEq./l. mg./100 ml. ml./3i hr.
2 189 22.1 101 60 500+
6 149 25.1 108 25 03
7 160 22.8 122 34 310
8* 155 21.3 119 36
10 151 24.7 113 39 1340 15.6 35.6
11 144 27.5 107 17
Days
Adm 2
4
5
12
Na CO2 (‘I
mEq./l.
163 15.5 142
- 18.5 140
158 16.2 136
148 27.8 110 187 25.4 108
(“a Urea N
mg./100 ml.
- 50.0
6.2
-- 14.2
6.6 12.2 9.6 10.4 increased to 2000 ml. per day. The serum
electrolyte studies are summarized in Table
V. Within 5 days there began a gradual im-provement in her state of consciousness a:id in a few weeks she appeared to have recovered
completely from any neurological damage.
In this patient hypernatremia appears to have resulted in a child with brain
in-jury from inadequate water intake. Young
infants and unconscious patients of all
ages have in common an inability to re-spond of their own volition to the physio-logic thirst mechanism, which theoretically
may predispose to hypernatremia. On the
other hand sick infants require proportion-ately large water intakes to compensate for
increased extrarenal water losses and the
inability to achieve the maximal urine os-motic concentration found in the older sub-ject.’3”4 Study is needed to determine whether the patients with primary damage to the brain also have increased water
re-quirements.
The hypocalcemia noted in these patients constitutes another corollary of hypernat-remia in the present study. The data shows that many of the patients studied were hypocalcemic prior to institution of therapy, so that dilution of extracellular calcium due to treatment cannot be the primary cause of the reduced calcium concentration al-though this may be a contributing factor in the later phase. The data also indicate that hyperphosphatemia secondary to di-minished renal function is not a necessary factor. It, therefore, appears likely that some
previously undescribed effect influences the
equilibrium between the skeletal calcium
and the extracellular fluid calcium. Whether this is a direct effect of the concentration of sodium ion remains to be seen. It is noteworthy that in the same year that he described the clinical features of hyper-osmolarity, Rapoport,’#{176} along with his co-workers, also described the “post acidotic state” in infants with diarrheal disease. These latter patients, who had been treated with large amounts of sodium salts includ-ing sodium bicarbonate were often
hypo-calcemic, and their description resembles
the hypernatremic infants in present series
very closely. Data on serum sodium and
chloride concentrations are not available in most of Rapoport’s patients, but it seems
quite probable that a common factor in
many of their hypocalcemic patients and
the patients reported in this study is a high serum sodium concentration.
Finally, some implications for optimal
therapy may be drawn from this study. The
group of patients whose clinical response
was most satisfactory received a total
quan-tity of 200 ml. of fluid per kg. of body weight in the first 24 hours. The concentra-tion of sodium in the total fluid given was less than 40 mEq./l. The possible harmful
effects of giving higher concentrations of
sodium to such patients, amounts which are
sometimes employed in the treatment of
severe dehydration, is illustrated by the
following case.
A 6-month-old infant, W. C., had been thought to be developing normally prior to an illness which began about a week before ad-mission to the hospital. The illness was
char-acterized initially by diarrhea, which became
severe during the 48 hours preceding
admis-sion. During this period he took no fluids. Just before coming to the hospital he had a gen-eralized convulsion. On admission he was coin-atose and febrile. He appeared desperately
ill, but it was noted that his skin turgor was
normal. He was treated during the first 24
hours with 200 ml./kg. of water, containing
an average concentration of 100 mEq./l. of
TABLE VI
SERUM ELECTROLYTE DETERMINATIONS ON W.C., AGE SIX MONTHS; TREATED WITH RELATIVELY
LARGE AMOUNTS OF SODIUM
ORIGINAL ARTICLES
sodium. Salmonella paratyphi A was cultured
from his stool. At the end of 36 hours, after seeming to improve, he had another severe
convulsive episode. He remained a spastic,
unresponsive child thereafter, although he
con-tinued to live for some years. Table VI shows
a summary of some determinations of serum
electrolytes. It was thought that he might have
had a dural sinus thrombosis. The
cerebro-spinal fluid on the fifth hospital day was
xanthochromic, pressure normal, and contained
148 mg. of protein per 100 ml.
This patient is representative of the pa-tients in this series who have had severe neurological residua. It is noteworthy that the initial treatment contained much more sodium than we would now believe advisa-ble for hypernatremic patients.
On the other hand, we have the impres-sion that rapid dilution of the extracellular fluid by intravenous administrations of glu-cose in distilled water may precipitate con-vulsions even though the serum sodium is not reduced below the normal range. The following illustrates this point:
The diagnosis of hypernatremia was
sus-pected at the time of admission in a
7-week-old infant, P. S., from the history plus
a “doughy” skin and muscle spasticity. She
was treated with 100 ml./kg. of glucose in
distilled water intravenously without any
so-dium salts over an 8-hour period. At the end
of this time she had a generalized convulsion.
The serum calcium at that time was
deter-TABLE VII
SERUM ELECTROLYTE DETERMINATIONS ON P.S., AGE SEVEN WEEKS; TREATED INITIALLY WITHOUT
SODIUM SALTS
Days
Serum Concentrations
Na CO3 Cl Urea N
mEq./l. mg./100
Adm. 8hr.
1
2
3
172 4.0 158
- 7.4 111
136 12.1 111
148 16.8 117
141 20.2 103
80.0
-65.6
41.4
30.8
mined to be 8.4 mg./100 ml. Her subsequent
course was uneventful after sodium salts were
given. A summary of the data is given in
Table VII. The changes in the sum of the
concentrations of the serum chloride and
bi-carbonate indicate the extent of the reduction of sodium concentration at the time of the
convulsion. Although the serum sodium
con-centration following treatment is within the
accepted range of normal, the clinical effect of
rapid reduction from an abnormally high level
appears similar to that seen in water intoxica-tion.
Infants with hypematremic dehydration
may also have deficits of total extracellular
sodium if extracellular volume is greatly
reduced even though the initial serum so-dium levels are high.
Some patients have had persistently low levels of serum potassium with high bicar-bonate concentration after initial treatment.
Restoration of a normal electrolyte pattern
in these patients was not accomplished until this potassium deficit was remedied by oral or parenteral intake of potassium. Hypo-calcemia, when present, was corrected by the intravenous injection of calcium glu-conate solutions.
SUMMARY AND CONCLUSIONS
It has been shown that hypernatremia may accompany dehydration in infants with diarrhea and with infections associated with interference with water intake. Suit-able modification of the treatment of
de-hydration for these patients has appeared
to improve the results of their care.
Hypernatremic dehydration may be sus-pected from the history and clinical features
and is readily diagnosed by laboratory
pro-cedures.
The occurrence of neurological manifesta-tions, some of which may be irreversible,
is a feature of outstanding importance.
Despite loss of body water the usual
changes in tissue turgor and the circulatory state associated with severe dehydration
may not be present.
ataque al sistema nervioso, a veces sumamente repair solution should be relatively dilute
with respect to sodium. The best results have been obtained by administering fluids which, if combined, would have a final
sodium concentration of from 15 to 40
mEq./l.
Hypocalcemia has been a frequent
corn-plication and more study is needed to
elucidate its pathogenesis. Awareness of its occurrence facilitates therapy.
As in other types of dehydration in
in-fants, the potassium deficit may be
impres-sive and should be corrected promptly after restoration of renal function.
The somewhat special treatment indi-cated for patients with hypernatremic de-hydration makes recognition important. Recognition or suspicion from clinical signs and rapid laboratory diagnosis are essential for optimal management.
REFERENCES
1. Schmidt, C.: Charakteristik der
epidem-ischen Cholera gegenuber Verwandten
Transsudationsanomalieen. Leipzig, G.
A. Rehyer, 1850.
2. Kerpel-Fronius, E.: Ueber die
Wechsel-beziehungen zwischen Kochsalz und Res-tickstoff. Ztschr. ges. exper. Med., 85: 235, 1932.
3. Tarail, B., Bass, L. W., and Runco, A.
S.: The frequency and nature of
hy-pertonicity of the body fluids in infantile
diarrhea. Abstract in program of the
Society for Pediatric Research. Am.
J.
Dis. Child., 86:658, 1953.4. Rapoport, S.: Hyperosmolarity and hyper-electrolytemia in pathologic conditions of childhood. Am.
J.
Dis. Child., 74:682, 1947.5. Van Slyke, D. D.: The determination of chlorides in blood and tissues.
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Biol. Chem., 58:523, 1923-24.6. Van Slyke, D. D., and Neill,
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M.: The determination of gases in blood and other solutions by vacuum extraction and manometrie measurements.J.
Biol.Chem., 61:523, 1924.
7. Fiske, C. H., and Subbarow, Y.: The col#{244}rimetric determination of phos-phorus.
J.
Biol. Chem., 66:375, 1925. 8. Van Slyke, D. D.: The manometricde-termination of urea in blood and urine by the hypobromite reaction.
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Biol. Chem., 83:449, 1929.9. Kramer, B., and Tisdall, F. F. : A simple technique for the determination of
cal-cium and magnesium in small amounts
of serum.
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Biol. Chem., 47:475, 1921. 10. Harrison, H. E. : Unpublished data.11. Mainland, D. : Elementary Medical
Sta-tistics. Philadelphia, Saunders, 1952. 12. Rapoport, S. : The role of overventilation
in diseases of infancy. Ann. paediat.,
176:137, 1951.
13. Gamble,
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L., and Wallace, W. M. :Ex-hibit at the Fifth International Congress
of Pediatrics, New York, 1947. Cf. also
Gamble,
J.
L. : Chemical AnatomyPhysi-ology and Pathology of Extracellular
Fluid, 6th Ed. Cambridge, Harvard, 1947.
14. Pratt, E. L., and Snyderman, Selma E.: Renal water requirement of infants fed evaporated milk with and without added carbohydrate. PEDIATRICS, 1 1:65, 1953.
15. Weil, W. B., and Wallace, W. M. The
pathogenesis and symptomatology of
hy-pertonic dehydration. Abstract in
pro-gram of the American Pediatric Society. Am.
J.
Dis. Child., 88:364, 1954.16. MacCarty, C. S., and Cooper, I. S.:
Neu-rologic and metabolic effects of bilateral ligation of the anterior cerebral arteries
in man. Proc. Staff Meet., Mayo Clin.,
26:185, 1951.
17. Welt, L. G., Orloff,
J.,
Kydd, D. M., and Oltman,J.
E.: An example of cellular hyperosmolarity.J.
Clin. Investigation, 29:935, 1950.18. Welt, L. C., Seldin, D. W., Nelson, W.
P., III, German, W. F., and Peters,
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P.: Role of the CNS in metabolism of
electrolytes and water. Arch.
mt.
Med.,90:355, 1952.
19. Higgins, C., Lewin W., O’Brien,
J.
R. P.,and Taylor, W. H.: Metabolic disorders
in head injuries. Lancet, 1:61, 1954.
20. Rapoport, W., Dodd, K., Clark, M. and Sylim, I.: Postacidotic state of infantile
diarrhea: symptoms and chemical data.
Am.
J.
Dis. Child., 73:391, 1947.SPANISH ABSTRACT
Hipernatremia en Lactantes Valoraci#{243}n de los Hallazgos ClinIcos y Bioqulmicos
de
este
cuadro
El manejo de los trastomos fisiol#{243}gicos de ciertos niflos deshidratados es particularmente dificil a pesar de la administraci#{243}n de
solu-ciones consideradas efectivas; 2 fen#{243}menos
sevro, y aumento de Ia concentraci#{243}n de sodio plasm#{225}tico. De existir una relaci#{243}n causal hiper-natremia y lesi#{243}nnerviosa, serla de gran im-portancia establecer criterios para el reconoci-miento temprano de Ia deshidrataci#{243}n hipema-tr#{233}mica a fin de instituir regImenes terap#{233}uticos apropiados. Este trabajo trata de correlacionar con tales objetivos, los hallazgos dlinicos, bio-quImicos y patol#{243}gicos en pacientes con hiper-natremia.
Se estudiaron 88 lactantes con concentraci#{243}n s#{243}dicaen plasma superior a 150 mEq/litro; en 69 de ellos la causa de admisi#{243}n fue diarrea y
otros 4 Ia tuvieron ya hospitalizados; en 8 la
hipernatremia se debi#{243} a infeceiones respira-torias; se agregan 7 casos de otra instituci#{243}n para la valoraci#{243}n total de los trastomos
bio-qulmicos. Se investigaron sodio, potasio,
do-ruros, contenido en CO2, f#{243}sforo, nitr#{243}geno
ureico y calcio de sangre venosa. Los factores
predisponentes y las manifestaciones clmnicas se
compararon con los de otros 205 ninos con
diarrea y deshidrataci#{243}n con concentraciones
de sodio inferiores a 150 mEq.; en #{233}stosIa
mortalidad fu#{233}menor a 2%; en los ni#{241}oshiper-natr#{233}micos fu#{233}de 11.6%, diferencia estadIsti-camente significativa.
En las dos terceras partes de los ni#{241}oscon
hipernatremia se observaron diversas
manifes-taciones nerviosas: alteraciones de la concien-cia, irritabilidad, excitaci#{243}n, cambios del tono
muscular (hiperreflexia tendinosa, rigidez
muscular, fibrilaciones musculares o
convul-siones), que obligaron a estudiar el lIquido
c#{233}falo-raquIdeo; se observ#{243} aumento de las protelnas sin pleocitosis en 30 de los 32 niflos puncionados. A la autopsia dos ni#{241}oscon hiper-natremia mostraron hemorragia subaracnoidea extensa. Cuatro pacientes normales previamente a su deshidrataci#{243}n hipernatr#{233}mica, presentaron despu#{233}s lesiones residuales neurol#{243}gicas severas
y permanentes. Estos hallazgos sugieren que la
hipernatremia o su concomitante necesario, la
deshidrataci#{243}n intracelular, es responsable, aunque sea en parte, de las lesiones nerviosas;
se han encontrado hallazgos similares en casos
de ingestion excesiva de sal, y viceversa,
con-centraciones elevadas de sodio consecutivas a
lesions cerebrales diversas. Debe secordarse que’
tanto lactantes como pacientes inconscientes de
cualquier edad tienen una incapacidad comiin
de responder a los mecanismos fisiolOgicos de
la sed, lo que teoricamente puede predisponer
a la hipernatremia; por otra parte los niflos
enfermos requieren mayores ingestiones de
agua para compensar sus exageradas p#{233}rdidas
hIdricas extrarenales e incapacidad de alcanzar las concentraciones osm#{243}ticas urinarias m#{225}ximas de los sujetos de m#{225}sedad.
A pesar de Ia p#{233}rdida de peso por reducciOn
de agua corporal la mitad de los niflos no se
vieron significativamente deshidratados al
ex-aminarse por primera vez. Se practicaron
estudios de balance en uno de los pacientes
hipematr#{233}micos con el objeto de esciarecer los fiujos de agua y iones atribuIbles a estos tras-tomos diarreicos (v#{233}asetabla III).
En 88 pacientes estudiados al hospitalizarse, la concentraciOn de bicarbonato plasm#{225}tico se encontrO abajo de 15 mEq. 58 veces, entre 15 y 27 mEq. 23 veces y sobre 27 mEq. en 7 ocasiones. El potasio plasm#{225}tico fue bajo en cierto rn’imero de pacientes. Las concentra-ciones plasm#{225}ticas de sodio, bicarbonato,
cloruro, potasio y nitrOgeno ureico se
pres-entan en la tabla IV.
El calcio presentO tambi#{233}n relaciones de
inter#{233}s especial; en 28 de los 38 pacientes sus
niveles fueron inferiores a 9 mg. % y en 7
niflos inferiores ann a 7 mg.; estudio similar
en 65 pacientes con diarrea y niveles normales
0 bajos de sodio mostrO concentraci#{243}n de
calcio abajo de 9 mg. sOlo en 3 ocasiones. No
se encontrO correlaciOn aparente entre
hipo-calcemia e hiperfosfatemia o cifras elevadas de
nitrOgeno ureico; asimismo se observ#{243} tanto en ni#{241}os con niveles altos como bajos de
bicar-bonato. La hipocalcemia en estos pacientes
existla previa al tratamiento, de tal manera que
Ia diluciOn de calcio extracelular no puede
achac#{225}rsele como causa primaria aun cuando
puede ser un factor contribuyente en una fase
posterior; tampoco puede serb la
hiperfos-fatemia secundaria al hipofuncionamiento renal;
por bo tanto, debe existir algimn factor aitn no
descrito que influya sobre el equilibrio del
calcio esquel#{233}tico y extracelular.
En Ia actualidad el tratamiento de Ia
deshi-drataciOn de estos enfermos hipernatr#{233}micos ha
mejorado sus condiciones; en vista de que
existe un gran deficit acuoso intracelular Ia
soluci#{243}n reparadora debe ser muy baja en
sodio. Al parecer los mejores resultados se han
obtenido al administrar 200ml. de lIquido por
kilo de peso en las 24 horas, de mezcla de
soluciones cuya concentraci#{243}n sOdica final sea
de 15 a 40 mEq. por litro. Debe recordarse Ia
hipocalcemia por su frecuencia, corregible por
inyecciOn intravenosa de soluciones de
corregirse empleando Ia via parenteral u oral, tan pronto como se recupere ba funciOn renal. Los signos clInicos se#{241}alados, los datos de
laboratorio y los antecedentes del caso son
esenciales para el diagnOstico preciso y la
terap#{233}utica Optima de los pacientes con
de-shidrataci#{243}n hipematr#{233}mica.
INTERLINGUA ABSTRACT
Hypernatremia in Infantes:
Un
Evaluta-tion
del
Constatationes
Clinic
e
Bio-chimic que Accompania Iste Condition
In recente annos il es devenite apparente
que il existe un gruppo de infantes dishydrate
in qui be tractamento con sobutiones de reparo
que es ordinarimente efficace non attinge le
expectate resultatos. In multes inter iste
in-fantes esseva observate (1) manifestationes
in-dicative de un lesion pIus o minus sever del
systema nervose e (2) un augmentate
concen-tration del natrium in be sero. Proque II non es
impossibibe que iste hypernatremia es
causal-mente connectite con be lesion del systema
nervose, il es evidentemente multo urgente
establir criterios pro le prompte recognition de
dishydration hypernatremic e elaborar ap-propriate regimes pro su tractamento.
Le objectivo del presente studio es (1)
cor-relationar be constatationes clinic, biochemic, e pathologic in infantes con hypernatremia a fin de facibitar be recognition de iste condition e (2) indicar le mebior procedimento therapeu-tic.
Le base del studio es be experientias con 88
infantes de minus que duo annos de etate,
ob-servate durante be passate septe annos, in qui
concentrationes del natrium seral de plus que 150 mEq/l esseva incontrate. Le resultatos obtenite es le sequente.
Ii esseva demonstrate que hypematremia
pote accompaniar dishydration in infantes con
diarrhea, e con infectiones, associate con dis-turbationes del ingestion de aqua. Appropriate modificationes del tractamento de dishydration
in iste casos pareva mebiorar le resultatos
obtenite.
Dishydration hypernatremic es conjecturabibe super be base del historia e del manifestationes
clinic del patiente. Su diagnose per medios
laboratorial non es difficile.
Le presentia de manifestationes neurologic, a vices de character irreversibile, es un possi
bilitate de major importantia. In despecto de
su perdita d’ aqua corporee, il es possibile que
be patiente non exhibi be cambiamentos de
histoturgr e be stato circubatori que es usual
in dishydration sever.
Proque in iste typo de dishydration ib existe
un grande deficit intracellular de aqua, be
solution de reparo debe esser distinguite per
un rebativemente basse concentration de
natrium. Le melior resubtatos esseva obtenite
per be administration de fluidos cuje
com-binate concentration de natrium haberea essite
inter 15 e 40 mEq/l.
Hypocalcemia esseva un frequente compli-cation. Le clarification de su pathogenese
re-(luire studios additional. Le recognition de su
