The neonatal response to massive fluid infusion

The Neonatal Response To Massive Fluid Infusion ByMARC I. ROWE AND

ABE-

ARANco

T

HE PURPOSE of this study was to determine the tokrance of as well as the metabolic and hemodynamic respon$es of the newboti dog to a rapid and massive intravenous infusion. Two commdnly used preparations, 5% dextrose in water and normal saline, were chosen as the test soltitions. Alth&~gh many investigators have found that the normal adult animaW and human334 can withstand large volumes of intravenous fluid, there is a common impression that the tolerance of the neonate to this challenge is much less. MATEXUALSAND METBODS Protocol:All puppies were healthy mongrels in the,&st 7 ddys of life. Admission to the experiment was determined by criteria developed over the past 4 years.5 The puppies were placed in one’ of two groups and received a cqntinuous intravenotis infusion of 58 dextrose in water (D & W group) or normal saline solution (NS group). Each group consisted of 10 animals balanced for age, litter, and weight. Data frdm 10 preliminary experiments demonstrated that intravenous fluid delivered at a r&e greater than 6 times the approximate blood volume (75 cc/kge) resulted in rapid death, while sm’vival was prolonged at slower rates. We chose a flow rate for both test solu~ons of approximately 6 blood volumes per hour (450 cc/kg/hr, 7.5 cc/kg/min). The infusion began as soon as baseline hemddynamic measurements and blood and urine samplizs were obtained. The fluid was delivered continuously by a syringe pump until the death of ti &ma]. Vuscu&zr Cant&z&n: All operative procedures were done under 0.5% local xylocaine anesthesia. Large incisions, considerable disskction, raising of skin flaps, and loose wound closure resulted in great losses of edema fluid from the wounds during the experiment necessitating a mod&a&n of our standard cannulation technique.5.7 The wounds were made smaller and directly over the vessels, no flaps were raised, and dissection was limited to the area of the vessels. Wound edges were tightly approximated with Michel clan+ after placement of the catheters. A 0.27 inch ID polyvinyl catheter was passed from the right femoral artery to the midabdominal aorta for arterial blood pressure measurements. A secqnd catheter ~(1s placed into the left common iliac artery via the left femoral artery for bItid sampling. Fluids were infused into the right .common iliac vein. Central venous pressure measurements were made through a cannula introduced into the left femoral vein and advanced to the inferior vena cava at the level of the diaphragm. Bladder Catheterization: Urine was collected from a 16-gauge flanged plastic catheter From the Vni~ersity of Miami School of Medicine; the Neonatal Newborn Reseurch Laboratory; Jackson Memoriul Hospital; and the Animal Research Laboratoy, Veterans Administration Hospital, Miami, Fla. Presented before the Surgicul Section of the American Acadamy of Pediatrics, San Francisco, Calif., October 17-19, 1970. Supported by National Institutes of Health Grant 7 ROl HD 04154-01, Veterans Administration Grant 01/7596, and the John A. Hartford Foundation, Inc. MARC I. ROWE,M.D.: Associate Professor of Surgery and PediaWics; Chief, Division vf Pediatric Surgeq, University of Miami School of Medicine; Neonatal Newborn Research Laboratory, Veterans Administration Hospital; Jackson Memorial Hospital, Miami, Flu. ABELARDO ARANCO, M.D.: Resident, Department of Surgery, Vniuersity of Miami School of Medicine, Miami, Fla. JOURNALOF PFDLUFUC SURGERY,VOL.~,No.3 (J~~~),1971

365

366

ROWE

AND ARANGO

Table 1. $y:amgee CIOUP

NS D&W

Age

(Days)

%Z11 (Minutes)

Total Infusion (ml/kg)

&id Adm;ni;)tered m

137 93

1024.5 700.15

389.6 271

4 3.4

ApITgahgte Average Befqre I%Y

WA;?;

O(“‘S’

m

l”%?on

380.4 387.3

-‘!p:

652.6 579.9

78.9 49.5

placed into the bladder through a suprapubic cystostomy. A short verticle midline incision just below the umbilicus allowed extraperitoneal exposure of the bladder. Meawrements:Arterial and venous pressure were measured with Statham transducers, pulse rate calculated from arterial pulse tracings and temperature monitured from rectal thermistor probes. Determinations were recorded every 15 min. The animals were weighed at the beginning of the experiment and at death. Serum sodium and o&molality, hematocrit, and blood sugar were determined every 15 min. Arterial blood pH, pCO,, and p0, were measured every 30 min. All blood withdrawn for sampling was replaced with an equal volume of mother’s blood. Urine was measured every 15 min. The specific gravity, concentrations of each sample were determined.

osmolality,

sugar,

and sodium

RESULTS

Ten puppies

of similar

weight

and age were studied

in each group.

Survival Time and Volume Znfused The water ( 1025 Table

normal saline group survived for a longer period than the dextrose and group (137 versus 93 min) and tolerated a greater volume of fluid ml/kg versus 700 ml/kg or 13.7 blood volumes versus 9.3 blood volumes; 1).

Clinical Findings The most striking clinical findings were the rapid development of generalized edema, ascites, hydrothorax, and frequent frothy sputum. The average animal almost doubled his body weight. Table 1 illustrates the average initial weight, final weight, average volume of fluid infused, and urine output. From these data an estimate of the volume of edema fluid lost through the wounds can be calculated. The normal saline solution group lost an average of 39 cc from their wounds, the dextrose in water group 29 cc.

Hemodynumic Measwements The responses of the puppies in both groups was similar (Fig. 1). Arterial blood pressure and pulse rate fell steadily. Central venous pressure rose .gradually. Blood and serum measurements are shown in Figs. 2 and 3. Hematocrit initially fell rapidly in both groups (Fig. 2). The decline continued in the normal saline group. In the dextrose in water group, hematocrit after the decline rose slightly, remained elevated for 45 min, and then fell again. At the time of the rise in hematocrit, gross hemolysis was noted in the serum of the dextrose in water group.

367

NEONATAL RESPONSE TO FLUID INFUSION

200 PULSE RATE I countr/min)

100 _ O60 -

ARTERIAL

-

BLOOD

40 -

PRESSURE (mm Hg)

20 -

20 CENTRAL VENOUS PRESSURE

10 -

(mmHg)

Fig. l.-Hemodynaxnic to infusion.

O-

responses

~ 0

15

I

I

;o

45

I 60

75

90

10

MINUTES

The changes in arterial blood gases and pH were similar in both groups. The pH fell, pOz rose slightly, and pC0, increased. The serum osmolality response differed in the two groups (Fig. 3). Osmolality immediately fell in the dextrose in water group and then rose after 30 min to the preinfusion level. The serum osmolality of the normal saline group steadily increased to a high of 310 mOsm. Serum sodium rose gradually in the normal saline group to a high of 160 meq/liter. There was a steady fall in sodium with the dextrose in water infusion (Fig. 3). Blood sugar increased rapidly in the dextrose in water group to a maximum of 2260 mg!Z. The normal saline puppies’ blood sugar remained relatively constant throughout the experiment (Fig. 3).

0

I

1

1

15

30

’ 45

’

1

1

t

60

75

90

105

MINUTES

Fig. 2.-Hematocrit changes with dextrose in water and normal saline infusions.

ROWE AND ARANGO

SERUM SODIUM (mEq/litsr

I

SERUM SUGAR (me %I

1/I

I

$-i

b 1;

/

I

I

I

I

30

45

I :

60

;5

do

10:

Fig. 3.-Serum

MINUTES

changes with

infusion.

Urine output quickly rose in both groups to a flow rate almost 12 times the preinfusion level (Fig. 4). The peak output was reached in 45 min for the dextrose in water group and 60 min for the normal saline group. Urine flow then decreased until the death of the animals. The pattern of change in the urine specific gravity during infusion differed in the two groups (Fig. 5). Specific gravity fell abruptly in the puppies receiving saline solution to 1.004 at 45 min. Specific gravity increased from 1.015 to 1.020 in the dextrose in water group in the first 15 min of the experiment and

1

500 -

URINE )SMOLALITY

400 -

(mOsm) 200 -

VOLUME

1.000

I

I

I

/

I

I

I

1

I

1

I

I

I

I

IS

30

45

60

75

90

,O!

0

MINUTES

Fig. 4.-Urine with infusion.

output per 15 min

I

I

0

I

I

I

,

1

,

I5

30

45

60

75

90

‘, 105

MINUTES

Fig. 5.-Urine osmolality and specific gravity responses during saline and dextrose in water infusions.

369

NEONATAL ReSPONSE TO FLUID INFUSION

then fell only to rise again late in the experiment. The urine specific gravity of the dextrose in water group always was higher than that of the normal saline group. The changes in urine osmolality in both groups were similar (Fig. 5). There was a rapid fall during the first 45 min and then a slight rise. The patterns and magnitude of changes in urine sodium excretion differed. There was an increase in the puppies receiving normal saline solution to 175 meq/liter, a value above the serum level. After an initial slight increase, urine sodium fell to a very low level in the dextrose in water puppies (Fig. 6). The urine sugar concentration decreased to 17 mg% in the saline group but rose to levels higher than the serum, 3518 mg!Z in the 5% dextrose in water puppies (Fig. 6). DISCUSSION The newborn puppy had an unexpectedly great tolerance to massive and rapid intravenous infusions of normal saline solution and to 5% dextrose in water. The average puppy tolerated 1025 ml/kg of normal saline solution over a 2 hr and 15 min period. If a 70 kg man were to tolerate an equal amount, he would have to receive 71,680 ml in slightly over 2 hours. The mechanism of death in both groups was apparently related to cardiac failure. The decreasing arterial blood pressure and pulse rate, the rising venous pressure, the metabolic acidosis, and the frequent finding of frothy sputum suggested circulatory overload. Cardiac output measurements to evaluate the degree of cardiac failure would have been helpful.1 It is our feeling that determinations of cardiac output by the dye indicator dilution technique during overinfusion experiments are unreliable. Because of the great dilution of the blood by the infusion, the hematocrit falls and the optical density of the blood changes. Calibrations performed before or after the infusion would not be valid for dye curves done during the greater part of the experiment because of the rapidly changing

URINE SUGAR Ime %I

Fig. f&-Changes sugar.

in urine sodium and

0

IS

30

.45

60

MINUTES

I I 75

I 1 90

, , 105

370

ROWE AND ARANGO

character of the blood. Only if calibrations are done before each dye curve measurement could this technique be employed. The more rapid death of the neonatal dogs infused with dextrose in water possibly was related to the low serum sodium and the hemolysis that developed midway through the experiment. The differences in response of the serum osmolality to the two test solutions were related to the changing sodium and sugar concentrations of the puppy’s serum. Sodium is the major determinant of serum osmolality. The sodium concentrations steadily increased during normal saline infusion and the osmolality rose. Sodium fell with dextrose in water infusion and the serum osmolality initially decreased. Blood sugar in the dextrose in water group rose to a very high level and this produced a late rise in serum osmolality. The neonatal puppy responded to overinfusion with a tremendous increase in urine output. The animals receiving normal saline solution had an average urine output of 79 ml in 137 min. A 70 kg man would have to excrete 14,520 ml of urine in the same time to equal this output. The urine volume accounted for 21% of the total fluid infused into the animal during the experiment. Approximately 10%of the infusion was lost through the wounds as edema fluid and the remainder was retained by the animal. Urine osmolality fell steadily in both groups of animals, but urine specific gravity increased in the puppies that received dextrose in water. Osmolality decreased in the normal saline group in spite of a rising urine sodium. Unlike serum osmolality, the osmolality of urine is not primarily related to sodium concentrationbut to other solutes such as urea, ammonium ion, and potassium. With increased water excretion, these solutes presumably are diluted resulting in a low total solute concentration and a low urine osmolality. Osmolality is a measure of the number of particles in solution rather than their size, weight, or shape. For this reason, even with the increase in sugar in the urine, the osmolality of the urine initially fell in the dextrose in water group. However, specific gravity is related to the weight of the particles in solution so that the animals that received dextrose in water had an increased specific gravity. The excretion of sodium to levels above the serum in the normal saline group suggested that in the neonatal dogs renal function is adequate to excrete a sodium load. SUMMARY

Twenty newborn puppies 0 to 7 days of age had continuous intravenous infusions of normal saline or 5%dextrose in water until death. The survival time and the volume of fluid tolerated was greater with normal saline than dextrose in water. Massive edema developed in both groups of animals. The hemodynamic responses were similar but changes in the blood and urine differed. When the animals received saline solution, urine sodium concentration exceeded serum levels. The newborn puppy has a great tolerance to intravenous infusion and is able to respond with an increase in urine flow.

371

NEONATAL. RESPONSE TO FLUID INFUSION REFERENCES

1. Johnson, G., Jr., and Lanbert, J.: Response to rapid intravenous administration of an overload of fluid and electrolytes in dogs. Ann. Surg. 167:561, 1968. 2. Yeomans, A., Porter, R. Il., and Swank, R. L.: Observations on certain manifestations of circulatory congestion induced in dogs by rapid infusion. J. Clin. Invest. 22: 33, 1943. 3. Warren, J. V., Brannon, E. S., Weens, H. S., and Stead, E. A., Jr.: Effect of increasing the blood volume and right atrial pressure on the circulation of normal subjects by intravenous infusions. Amer. J. Med. 4:193, 1948.

4. Altschule, M.D., and Gilligan, D. It.: The effects on the cardiovascular system of fluids administered intravenously in man. II. The dynamics of the circulation. J. Chn. Invest. 17:41, 1938. 5. Arango, A., and Rowe, M. I.: The neonatal puppy as an experimental subject. Biol. Neonat. (in press). 6. Rowe, M. I., and Arcilla, R.: Hemodynamic adaption of the newborn to hemorrhage. J. Pediat. Surg. 3:268, 1968. 7. Rowe, M. I., and Arcilla, R.: Thermoregulation and the neonatal response to hemorrhage. Ann. Surg. 172:76, 1970.