CLINICALLY SIGNIFICANT PHYSIOLOGIC CHANGES FROM RAPIDLY ADMINISTERED HYPERTONIC SOLUTIONS: ACUTE OSMOL POISONING

(1)

(Received October 30, 1969; revision accepted for publication February 12, 1970.)

Presented in part to The American Pediatric Society in Atlantic City, New Jersey, on May 3, 1969. This investigation was supported in part by PHS Research Grant No. NB 04700.

ADDRESS: (R.E.K. ) Department of Pediatrics, Montefiore Hospital and Medical Center, 1 1 1 East 210th Street, Bronx, New York 10467.

Panrmics, Vol. 46, No. 2, August 1970

267

CLINICALLY

SIGNIFICANT

PHYSIOLOGIC

CHANGES

FROM

RAPIDLY

ADMINISTERED

HYPERTONIC

SOLUTIONS:

ACUTE

OSMOL

POISONING

Richard E. Kravath, M.D., Albert S. Aharon, M.D., G#{252}nerAbal, M.D.,

and Laurence Finberg, M.D.

Department of Pediatrics, Monte/lore Hospital and Medical Center, and Albert Einstein College of Medicine, Bronx, New York

ABSTRACT. The rapid injection of hypertonic

so-lutions, e.g., 0.9M sodium bicarbonate, creates a potential hazard from intracranial hemorrhage sec-ondary to the shift of water from the CNS and the accompanying fall in cerebrospinal fluid (CSF) pressure. CSF pressure and other relevant variables

were followed as 2.5M sodium chloride in a dosage of 10 mEq/kg given intravenously to cats

over periods of 3 and 60 minutes. The fast infusion

produced a sharp rise in CSF pressure followed by a precipitous fall. The rise parallelled the rise in

venous pressure and fall in hemoglobin secondary

to a transient increase in plasma volume. The

slower infusion produced neither the sudden rise in

CSF pressure nor the marked expansion of plasma

volume, but did produce the same fall in CSF

pressure. The rise in plasma volume and fall in hemoglobin concentration following a rapid hyper-tonic infusion may transiently improve the appear-ance of a cyanotic patient without necessarily im-proving his oxygenation. Since the osmolal load of these experiments is in the range of current clinical usage, when such osmolal loading is necessary,

slow administration is suggested to avoid

hemor-rhage. Pediatrics, 46:267, 1970, HYPRSOSMOLALITY, CF.REBROSPINAL FLUID PRESSURE, HYPERTONIC

5OLU-liONS, SODIUM CHLORIDE, MEAN CORPUSCULAR

HE-MOCLOBIN CONCENTRATION.

C

ORRECFION of acidosis in the respiratory

distress syndrome with rapid

intrave-nous injections of sodium bicarbonate has

been reported.14 Despite the lack of well

controlled clinical studies attesting to the

safety and effectiveness of this treatment, it

has come into widespread use. The

solu-lions of sodium bicarbonate in common use

are markedly hypertonic and contain 0.8 to

1.0 mEq/ml, giving them an osmolality

roughly six times that of blood. Pending

well controlled clinical trials of this

ther-apy, certain physiological and probably

pathophysiological consequences of the

rapid intravenous infusion of hypertonic

so-lutions should be considered. It has been

known since 1919 that rapid intravenous

infusions of large dosages of hyperosmolal

solutions produced marked reductions in

CSF pressure, which more recent studies6

have implicated in the production of

intra-cranial hemorrhages. While the dangers to

infants of changes in osmolal concentration

have been discussed before, the

impor-tance of the rate of infusion of hypertonic

solutions has not been elucidated.

There-fore, this study was designed to evaluate

the influence of the rate of infusion of

hy-pertonic solutions on CSF pressure and

other relevant variables using osmolal loads

of the same order of magnitude as those

now used in the therapy of acidosis.

Hyper-tonic saline infusions were used in these

studies to avoid the major pH change that

sodium bicarbonate would have produced.

The faster infusions produced much more

marked physiological disturbances that

have important clinical implications.

MATERIALS AND METHODS

Eight cats weighing 2 to 4 kg were

(2)

in-A

3

MINUTE INFUSION

H

CNANGE IN

mm

M,O

B

60 MINUTE INFUSION

I 4

----CHANGE IN

mm

Hg

o o 60 90

TIME, MINUTES

FIG. 1. Changes in cerebrospinal fluid pressure, venous pressure, and arterial pressure produced by the intravenous infusion of hypertonic saline in

mdi-vidual cats. Infusions are of 3 minutes duration (A) and 60 minutes dura-tion (B).

268 OSMOL POISONING

traperitoneally. Catheters were placed in

both femoral veins and one femoral artery.

The cats were then placed in the left lateral decubitus position and the head fixed in

flexion. The cisterna magna was

pene-trated with a scalp vein needle (usually 21

gauge) attached to a plastic three-way stop

cock and tuberculin syringe with a known

volume of isotonic saline filling the system.

In this way, the patency of the connection

could be assured with no loss of CSF and

without loss of sterility. The third opening

of the stop cock was connected to a U tube

water manometer of 1 mm bore for pressure

measurements. The use of a small bore

wa-ter manometer causes minimal damping of

the pressure changes.8 The catheter in the

femoral artery was used for blood sampling

and was connected to a mercury

manome-ter for pressure measurements. One femoral

vein catheter was connected to a water

ma-nometer for pressure recording and the

other was used for the infusions. Pressures

reported are those at low point of the

car-diac or respiratory cycles. Zero point for the

manometers was at the midpoint of the cat’s

body. Rectal temperatures were taken and

thermoneutrality maintained by use of an

electric heater. Stability of CSF pressure

was obtained before the experimental

pro-cedure was started.

Arterial blood samples were used for

anal-yses and were collected anaerobically in

plastic disposable 2% ml syringes with

hep-Cs,. PRESSURE

60 VENOUS PRESSURE

CHAE IN 20

mmM.O

o--I--20F

(3)

TABLE I

AVERAGE PRERSURER BEFORE AND

As-rim HYPERTONIC INFusIons

8-minute Infusions 60-minute Infusions

Initial High Low Initial High Low 269

arm solution (1,000 units/mi) filling the dead

space. Corrections were not made since the

volume of heparin was less than 1% that of

blood. Blood pH, Pco2, and Po2 were

de-termined immediately on an

Instrumenta-tion Laboratory Ultra-Micro pH/pCO2

analyzer, Model 113, #{176}by standard technique

on 0.5 ml of blood. Simultaneously the

hema-tocnt determinations were made in

hepari-nized micro-hematocrit tubes (length 75mm

I.D. 0.5 to 0.6 mm O.D. 1.4 to 1.75 mm)

sealed with clay at one end and spun for

5 minutes in an Adams Readacnt

Micro-Hematocrit Centrifuge.f Immediately after

spinning, the hematocrit tubes were viewed

under the scanning objective of an ordinary

laboratory microscope and readings in

mu-limeters were made using the vernier scale

mounted on the mechanical stage. A hair in

the eyepiece was first centered on the

clay-red cell interface and the reading on the

vernier scale taken. The mechanical stage

was then moved in a direction parallel to

the hematocrit tube and a reading taken at

the buffy coat-red blood cell interface and

again at the plasma-air interface. The length

of red blood cell column divided by length

of the total column gave the hematocrit. No

corrections were made for trapped plasma.

This technique gave a standard deviation of

± 0.25 units on 30 hematocrit

determina-tions on the same sample of cat blood.

Hemoglobin determinations were made

on 20 microliter samples of the arterial

blood drawn up in Adams disposable Sahli

Pipettes with accuracy ± 1%. The blood

was added to 5 ml of a solution made from

Drabkin’s dry mixture and after being

placed in matched cuvettes

(

12 X 75 mm),

was read in a Coleman Junior Spectropho-tometer, Model 6D standardized with

Hy-eel Cyanmethemoglobin Certified Standard.

0 Manufactured by Instrumentation Laboratory,

Incorporated, 1 13 Hartwell Avenue, Lexington,

Massachusetts 02173.

f Manufactured by Clay Adams, Incorporated, 299 Webro Road, Parsippany, New Jersey 07054.

*Manufactured by Clay Adams Incorporated. §Manufactured by Coleman Instruments

Cor-poration, 42 Madison Street, Maywood, Illinois

60153.

CSFmm/H2O 9 148 30 116 116 58

VP mm/H2O 84 138 59 66 76 64

AP mm/Hg 15 153 79 119 186 109

Mean corpuscular hemoglobin

concen-tration was calculated by dividing the

hemo-globin by the hematocrit and is expressed

as percent. The standard deviation of 15

calculations on the same sample of cat blood

was ±0.26. After centrifugation, osmolality

was determined on the supernatant plasma

in a

Fiske Osmometer Model Gil on 0.2 ml of

plasma. The remaining plasma was frozen.

Subsequently, determinations of sodium and

potassium were made on a NIL-FLAME

Photometer Model A-7000f on 0.1 ml of

plasma and chloride determinations were

made on a Luckler-Cotlove Chloridometer#

on 0.1 ml of plasma. Except for hematocrit,

duplicate determinations were not done.

Sodium chloride in a concentration of 2.5

mEq/ml (5 milliosmoles/mi or 14.6%) at

a dosage of 10 mEq/kg (4 cc/kg) was

in-fused over periods of either 3 minutes or 60

minutes by a Harvard Infusion Pump.**

EFFECT ON CSF, VENOUS, AND ARTERIAL PRESSURES

The effects on cerebrospinal, venous, and

arterial pressures of the fast infusion (10

mEq/kg in 3 minutes) are shown in part A

of Figure 1, and for the slow infusion (10

IIManufactured by Fiske Associates, Incorporat-ed, Quaker Highway, Uxbridge, Massachusetts 01569.

#{182}rManufactured by National Instrument Labora-tories, Incorporated, 12300 Parklawn Drive, Rock-vile, Maryland 20852.

# Manufactured by Buehler Instruments, Incor-porated, 1327 16th Street, Fort Lee, New Jersey 07024.

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HEA GL 08/N

NEMATOCRIT

---1---MCHC

:r---r

oIo

30 60 90

TIME,

MINUTES

270 OSMOL POISONING

A

B

3 MINUTE

INFUSION

60 MiNUTE

INFUSION

H 1- -I

OSMOLALITY

Fic. 2. Percentage change in osmolality, hemoglobin, hematocrit, and

MCHC produced by the intravenous infusion of hypertonic saline in

mdi-vidual cats. Infusions are of 3 minutes duration (A) and 60 minutes

duration (B).

mEq/Kg in 60 minutes

)

are shown in part

B of Figure 1 for the individual cats. The

average values are given in Table I. The

curves show the change in pressure from the

pressure before the start of the infusion as

zero, with time on the abscissa. With the

3-minute infusion, the CSF pressure rose

sharply and peaked an average of 56 mm

H2O above the initial pressure as the

infu-sion ended, followed by a precipitous fall

be-low the initial pressure averaging 62 mm

H2O. With the 1-hour infusion, there was no

initial rise but a gradual fall in CSF

pres-sure throughout the infusion, averaging 58

mm H2O.

The rise in CSF pressure with the

3-mm-ute infusions was paralleled by a rise in

venous pressure averaging 54 mm H2O,

fol-lowed by a fall in venous pressure. With

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* Specimens of blood were taken shortly after the point of maximum rise in venous pressure. t Plateau refers to the time after the CSF pressure had reached its minimum.

changes in venous pressure. With the rapid

infusions there was a sudden drop in

arte-rial pressure during the infusion averaging

45 mm Hg followed by a rise above the

ini-tial pressure. These changes were opposite

in

direction to the changes in CSF and

ye-nous pressure. A variable rise in arterial

pressure usually occurred during the slow

infusions.

EFFECT ON OSMOLALITY, HEMOGLOBIN,

HEMATOCRIT, AND MCHC

Part A of Figure 2 gives the percentage

change from preinfusion values for

osmolal-it)’, hemoglobin, hematocrit, and MCHC

against time for the 3-minute infusions, and

part B of Figure 2 gives the percentage for

the 60-minute infusions. Average values are

given in Table II. With the 3-minute

infu-sion, the osmolality rose abruptly an

aver-age of 13% and then fell to an average of

7% above preinfusion osmolality. With the

1-hour infusion, the osmolality did not rise

as precipitously, but at the end of 1 hour

both infusions produced similar changes in

osmolality. With the 3-minute infusion, the

hemoglobin dropped an average of 32%

and the hematocrit dropped an average of

38% with a subsequent rise. The 60-minute

infusion had much less effect on the

hemo-globin and hematocrit.

With both infusions, the percentage fall

in hematocrit was larger at every point than

the percentage fall of hemoglobin

concen-tration. This is reflected in the rise in

MCHC which follows the same general

curve as the osmolality. Average MCHC

rose 11% initially with the fast infusion and

then dropped to 5%. At the end of the

1-hour infusion, the MCHC had risen an

average of 7%. Figure 3 gives an example

of the good correlation between MCHC

and osmolality in one of the cats.

Changes in sodium and chloride

concen-tration parallelled the changes in osmolality

and MCHC, while potassium concentration

changes were variable. At the end of the

3-minute infusion, average pH had fallen

from 7.319 to 7.250 and with the 60-minute

infusion, the pH went from 7.324 to 7.269.

There was no significant effect of the

infu-sion on Pao2 or Paco2.

SIMULTANEOUS EFFECTS ON

BLOOD AND CSF

A full understanding of the dynamics of

the reported changes may be appreciated

best by viewing them simultaneously.

Fig-ure 4 shows these changes against time

from the start of the 3-minute infusion. The

ordinate on the left gives change in mm H2O

for the VP and CSF pressure from

prein-fusion pressure as zero. The ordinate on the

right gives changes in concentration for

os-molality, MCHC, hemoglobin, and

hemato-crit as percentage of preinfusion values. The

3-minute infusion caused a rise in CSF and

VP which peaked at the end of the infusion

followed by a sharp drop in CSF pressure

while the VP was still elevated. This rise in

TABLE II

AVERAGE BLOOD VALUF.S WITH HYPERTONIC INFUSIONS

3-minute Infusions 60-minute

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MCHC

%

-40

-39

-38

-37

-36

-35

-300

Yc ‘ 11.2575 0725 X

Sy.x ‘ 05305

r’+.949

. . . .

z1.1

I

380 400

272 OSMOL POISONING

320 340 360

OSMOLALITY mosm/L

FIG. 3. Correlation of MCHC with osmolality for one cat.

CSF and VP occurred at the same time that

the hemoglobin and hematocrit dropped

maximally and near the peak of the

osmo-lality and MCHC. As the venous pressure

returned toward the initial value, there was

an increase in hemoglobin and hematocrit

levels.

EFFECT OF INFUSION OF ISOTONIC SALINE AND OTHER SOLUTES

Following the injection of an equal

vol-ume (4 ml/kg) of isotonic saline, no

signffi-cant changes occurred. Intravenous

infu-sions of hypertonic solutions of sodium

bi-carbonate, sodium lactate, and mannitol

produced pressure changes grossly similar

to hypertonic sodium chloride.

DISCUSSION

Rapid Infusion

The rapid intravenous injection of

hyper-tonic saline caused a sudden rise in

osmo-lality of the plasma followed by an inrush of

extravascular water down an osmolal

gra-dient into the plasma, giving the observed

rise in venous pressure and fall in

hemoglo-bin concentration and hematocrit. At the

same time, but at a slower rate, the salt

dif-fused from the plasma down a

concentra-tion gradient. After several minutes, the

osmolal effect of the salt was distributed

throughout body water ending the osmotic

gradient across the capillary membrane.

Extracellular water was then redistributed across the capillary with the fall in venous pressure and rise in hemoglobin and

hemat-ocrit that was observed. These changes

in venous pressure probably produced the

parallel initial changes in CSF pressure.

In response to the rise in osmolality,

wa-ter shifted as well from both the CSF and

the brain cells into the blood. Since sodium

ions diffuse slowly into the central nervous

system while water moves rapidly, the

in-tracranial volume is only slowly restored.

This produces the lowering of CSF pressure

since the brain is rigidly encased. Almost

identical pressure changes were reported

by Weed and Hughson in 1921.

Slow Infusion

The slower infusions of the same dosage

of sodium chloride did not produce the

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pres-t mm H2 0

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 5 16 17 18 19 20

TIME IN MINUTES

sure and plasma volume seen with the

rapid infusions since the slower rate

per-mitted the gradual passage of salt and water

through the capillary. Therefore, no

mas-sive influx of water into the plasma

oc-curred. Instead there was a gradual

expan-sion of the entire extracellular fluid as one

pool, giving a smaller increase in plasma

vol-ume with the slower infusion since the

in-crease in plasma volume would then only be

proportional to its share of the extracellular

fluid. Since there was no sharp rise in

plasma volume and venous pressure, there

was no initial rise in CSF pressure but just

a gradual fall.

The observation that the intravenous

in-fusion of large doses of hypertonic

solu-tions may cause a drop in CSF pressure

and brain shrinkage has been well

docu-mented,101 and such solutions have been

used for that purpose.

Changes in Hemoglobin, Hematocrit,

and MCHC

The positive correlation between

osmo-lality and MCHC is of interest, as are the

changes in hemoglobin and hematocrit. The

intravascular infusion of the hyperosmolal

solutions drew water into the plasma from

extravascular sites giving the reduction in

hemoglobin and hematocrit. It also caused

a shift of water from the red blood cells,

dropping the hematocrit further without

further lowering the hemoglobin

concen-I

FIG. 4. Changes in osmolality, MCHC, venous pressure, hemoglobin, hematocrit, and cerebrospinal fluid pressure produced by the rapid intravenous infusion of hypertonic saline solution. Pressure changes

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274 OSMOL POISONING

tration, thus causing a rise in MCHC.

Sub-sequent changes in plasma volume might

alter the hemoglobin and hematocrit but

not the MCHC. Conversely, a fall in MCHC

should occur with a reduction in osmolality.

This phenomenon is well known and has

been intensively studied in v-itro16’17 but has

not had clinical application. Further studies

and more refined techniques may permit

the use of the red cell as an in vivo

osmom-eter. A study in humans in which hypertonic

solutions were infused and hemoglobin and

hematocrit levels were reported, showed

the expected rise in MCHC when

calcu-lated.18 The drop in pH observed is in the

expected range of a dilutional acidosis1#{176}but is too small to affect significantly the

MCHC.2#{176}

IMPLICATIONS

Rapid infusions of hypertonic saline with

osmolal loads in the therapeutic range

pro-duced a sudden rise in cerebrospinal fluid

and venous pressure followed by a

precipi-tous fall in cerebrospinal fluid pressure.

This may be particularly conducive to

in-tracranial hemorrhage since the rapid

infu-sion produced an increase in plasma

vol-ume and venous pressure at the same time

that the cerebrospinal fluid pressure was

falling. Dilatation during the passage of

hy-pertonic solutions through cerebral vessels has been demonstrated angiographically in

man.21 It has been shown that marked

drops in cerebrospinal fluid pressure

follow-ing intraperitoneal injections of hypertonic

solutions may produce intracranial

hemor-rhage in kittens, and this has been

postu-lated as the cause of the central nervous

system hemorrhage in infants with hyper-natremia.1#{176} This result could conceivably

be produced inadvertently as a side effect

of sodium bicarbonate therapy of acidosis.

It would most likely be safer to give

con-centrated solutions slowly enough to

mini-mize abrupt changes in plasma volume. We

can confirm that repeated infusions of

hy-pertonic solutions have a cumulative effect

in reducing CSF pressure,22 so that the

haz-ard may be increased with repeated

injec-tions. Since the adult cat excretes a sodium

load more rapidly than the human

prema-ture infant, these effects may be

exagger-ated in the infant. On the other hand the

open fontanel of the newborn infant may

modify these cerebrospinal fluid pressure

changes to an unknown extent, and the

larger pool of body water in the neonate

could also be considered. Even though

un-critical extrapolation from adult cats to

pre-mature infants is not wholly justifiable, the

basic physiological considerations are

prob-ably the same in both cases.

In addition, the transient improvement in

the color of a cyanotic patient on infusion

of hypertonic sodium bicarbonate2 may be

partially a reflection of hemodilution and a

reduction in the concentration of reduced

hemoglobin following expansion of the

plasma volume, rather than an indication of

improvement in oxygenation. The rapid

ex-pansion in plasma volume with rapid infu-sions of hypertonic solutions may in itself

have adverse effects on the

cardiorespira-tory system and might induce heart failure

and pulmonary edema.

Finally, serial determinations of

hemo-globin, hematocrit, and MCHC may be

use-ful in following therapy with hypertonic so-lutions.

SUMMARY

Rapid intravenous infusions of

hyper-tonic solutions have come into wide clinical

use. To study the importance of rate of

in-fusion of hypertonic solutions, 10 mEq/kg

of sodium chloride (2.5 mEq/ml) was

given intravenously at varying rates to anesthetized cats. The initial effect of a

rapid

(

3 minute

)

infusion was a sharp rise

in cerebrospinal fluid pressure averaging 56

mm H2O followed by a fall below the initial

pressure averaging 62 mm H2O. The venous

pressure paralleled the sharp rise in CSF

pressure and then fell gradually toward

preinfusion pressure. During the CSF

pressure rise, there was on average a 32%

drop in hemoglobin and 38% drop in hema-tocrit, reflecting a marked increase in blood

volume. In all animals, the hematocrit fell

(9)

calculated MCHC. As the VP and CSF

pressure fell, the hemoglobin, hematocrit,

and MCHC returned toward initial values.

Animals given the same infusion at a slower

rate

(

1 hour) demonstrated neither the

marked CSF and VP rise nor the

precipi-tous drop in hemoglobin, hematocrit, and

CSF pressure. The dose of hypertonic

so-dium bicarbonate in current usage is in the

osmolal range of these experiments, thus

compelling caution, lest intracranial

bleed-ing occur. A reduction in reduced

hemoglo-bin concentration in a cyanotic patient

might decrease cyanosis without improving

oxygenation. Serial hemoglobin, hematocrit,

and MCHC levels may be useful in

assess-ing hyperosmolal therapy.

REFERENCES

1. Usher, R. : Comparison of rapid versus gradual

correction of acidosis in RDS of

prematu-rity: A sequential study. (Abst. 83) Pediat. Res., 1:221, 1967.

2. Russell, G., and Cotton, E. K.: Effects of

so-dium bicarbonate by rapid injection and of oxygen in high concentration in respiratory

distress syndrome of the newborn. PEDIAT-ilIcs, 41 : 1063, 1968.

3. Oppe, T. E., Priestly, B. L., and Redstone, D.: Metabolic changes in the infant with respi-ratory failure. Pediat. Clin. N. Amer., 12: 723, 1965.

4. Hutchison, J. H., Kerr, M. M., Douglas, T. A.,

mall, J. A., and Crosbie,

J.

C. : A therapeutic

approach in 100 cases of the respiratory dis-tress syndrome of the newborn infant. PEDI-ATRICS, 33:956, 1964.

5. Weed, L. H., and McKibben, P. S.: Pressure changes in the cerebro-spinal fluid following

intravenous injection of solutions of various concentrations. Amer. J. Physiol., 48:512, 1919.

6. Luttrell, C. N., Finberg, L., and Drawdy, L. P. : Hemorrhagic encephalopathy induced

by hypernatremia. II. Experimental observa-tions on hyperosmolarity in cats. Arch.

Neurol., 1:153, 1959.

7. Finberg, L.: Dangers to infants caused by

changes in osmolal concentration.

PEDIAT-IICS, 40:1031, 1967.

8. Weed, L. H., Flexner, L. B., and Clark,

J.

H.:

The effect of dislocation of cerebrospmnal

fluid upon its pressure. Amer. J. Physiol.,

100:246, 1932.

9. Weed, L. H., and Hughson, W. : Systemic

effects of the intravenous injection of solu-tions of various concentrations with especial

reference to the cerebrospinal fluid. Amer.

J.

Physiol., 58:53, 1921.

10. Finberg, L., Luttrell, C., and Redd, H. : Patho-genesis of lesions in the nervous system in hypernatremic states. II. Experimental

stud-ies of gross anatomic changes and alterations of chemical composition of the tissues. PEDI-ATRICS, 23:46, 1959.

11. Rosomoff, H. L.: Effect of hypothermia and hypertonic urea on distribution of

intracra-nm! contents.

J.

Neurosurg., 18:753, 1961.

12. Holiday, M. A., Kalayci, M. N., and Harrah,

J.:

Factors that limit brain volume changes in

response to acute and sustained hyper

and hyponatremia.

J.

Clin. Invest, 47:1916,

1968.

13. Weed, L. H., and McKibben, P. S.:

Experi-mental alteration of brain bulk. Amer.

J.

Physiol., 48:531, 1919.

14. Foley, F. E. B.: Alterations in the currents and absorption of cerebrospinal fluid follow-in salt administration. Arch. Surg., 6:587, 1923.

15. Wise, B. L., and Chater, N. : The value of

hypertonic mannitol solution in decreas-ing brain mass and lowering cerebrospinal fluid pressure. J. Neurosurg., 19:1038, 1962.

16. Ponder, E. : Hemolysis and Related

Phenorne-non. New York: Grune and Stratton, 1948. 17. Gary-Bobo, C. M., and Solomon, A. K.:

Prop-erties of hemoglobin solutions in red cells.

J.

Gen. Physiol., 52:825, 1968.

18. Buckell, M. : Blood changes on intravenous

ad-ministration of mannitol or urea for

reduc-tion of intracranial pressure in neurosurgical patients. Clin. Sci., 27:223, 1964.

19. Winters, R. W., Scaglione, P. R., Nahas, C. C., and Verosky, M.: The mechanism of acidosis produced by hyperosmotic infusions. J. Chin.

Invest., 43:647, 1964.

20. Funder, J., and Wieth,

J.

0.: Determination of

sodium potassium and water in human red blood cells. J. Clin. Lab. Invest. ( Scand.),

18:151, 1966.

21. Huber, P., and Handa, J.: Effect of contrast material, hypercapnia, hyperventilation, hy-pertonic glucose and papaverine on the

di-ameter of the cerebral arteries. Angiographic determinations in man. Invest. Radiol., 2:17, 1967.

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1970;46;267

Pediatrics

Richard E. Kravath, Albert S. Aharon, Güner Abal and Laurence Finberg

ADMINISTERED HYPERTONIC SOLUTIONS: ACUTE OSMOL POISONING