USE OF GLUCOSE, INVERT SUGAR AND FRUCTOSE FOR PARENTERAL FEEDING OF CHILDREN

(1)

USE OF

GLUCOSE,

INVERT

SUGAR

AND

FRUCTOSE

FOR

PARENTERAL

FEEDING

OF

CHILDREN

By Harold C. Lane, M.D., and Katharine Dodd, M.D.

Department of Pediatrics, University of Arkansas Medical Center

668

S

OLUTIONS of glucose have long been used

for parenteral fluid therapy to provide

calories and water and to reduce protein

catabolism, thus assisting in the

mainte-Ilance of positive nitrogen balance. They produce relatively few side effects when

compared with parenterably administered

fat emulsions or protein hydrobysate

solu-tions. Unfortunately, sufficient calories to

produce maximal sparing of protein and fat

and repletion of glycogen stores cannot be

supplied to some adults and almost all

in-fants and children by infusions of carbo-hydrates in water because of the large

vol-ume involved. This is especially true of

5% solutions; therefore, 10% solutions are

often used to increase the supply of calories

and reduce the volume of fluid

adminis-tered.

Fifty years ago glucose was considered

to be the only “physiologic” sugar and was

the chief carbohydrate used for intravenous

infusions. In 1915, in a paper entitled

“Pro-longed and Accurately Timed Intravenous

Injections of Sugar,” Woodyatt et al.1

con-eluded that glucose could be utilized for

an indefinite time without diuresis or

giy-cosuria by the normal rabbit, dog or man

at an intravenous rate of not more than 0.85

gm/kg/hr. In contrast, fructose was utilized

without glycosuria only at 0.15 gm/kg/hr

or less. Subsequently, other investigators

compared the utilization of invert sugar and

glucose and concluded that invert sugar was

better for rapid intravenous fluid therapy.

Almost all of these investigators

adminis-tered solutions of 10% invert sugar or glucose

intravenously to patients at rapid rates of

approximately 1.5 gm/kg/hr for periods of

1 hour or less. Weinstein2 found that the

(Submitted March 21, 1956, accepted April 30, 1957.) \Vith the technical assistance of Margaret Stitt.

ADDRESS: (K. D.) Little Rock, Arkansas.

tolerance rates for administration of glucose

were less than 0.75 gm/kg/hr, but near 1.50

gm/kg/hr for invert sugar. Reports that

in-vert sugar is utilized more quantitatively

during a short period of infusion than glu-cose have been confirmed by Bertino and co-workers, Lawton et al.,4 and Frost and

associates.5

The literature concerning comparative

utilization of glucose and fructose is con-fusing. Better utilization of infused

fruc-tose than glucose is reported by

Weichsel-baum et al.,6 N’loncrief and co-workers, and

Drucker et aU’ The excretion of infused

glu-cose and fructose in normal adults was

found to be approximately the same by

Miller and associates.9 All of these investi-gators administered tile s&utions of carbo-hydrate during a period of 1 or 2 hours.

Smith et al.,b0 using various long and short

periods of administration, did not confirm reports of better retention of invert sugar

than of glucose. Strub et al.,h1 likewise did

not find tllat invert sugar and fructose are

utilized better than glucose.

Although the metabolism of glucose,

in-vert sugar and fructose has been studied

extensively when solutions of these carbo-hydrates were administered intravenously to adults and to various species of animals, no study has been found in the literature, until recently, concerning their utilization in children.

This paper presents a comparison of the

utilization of 10 solutions of glucose,

(2)

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children incuded in the series were afebrile

and had no clinical evidence of diabetes or

hepatic or renal disease. Their ages ranged

between 2 months and 12 years. Each child

received some type of antibiotic during the

investigation, but no other medication was given.

METHODS

Intake of food and water was discontinued at midnight. Beginning at 8 AM., each patient was given a 6-hour infusion of 10% glucose

solution in water, 10% invert sugar, or 10%

fructose. At least one day of rest was ob-served before giving subsequent infusions.

So-butions were administered through a

pobyethy--lene tube inserted into the antecubital vein.

The patients were given 1.25 gm of sugar per

kilogram of body weight per hour for 6 hours at a rate as nearly uniform as possible. One third of the patients received the glucose

solu-tion the first day, one third the invert sugar,

and one third the fructose.

Before the infusion was begun a catheter was

inserted into the urinary bladder. A specimen

of urine was collected at 8 A.M., tested for the

presence of sugar and discarded. The urine was collected at the end of each hour from 9 AM. to 4 P.M. The infusion was discontinued at 2 P.M., but samples of urine were obtained

at 3 P.M. and 4 P.M. If reducing substance was

still present in the urine at the end of this time

an additional sample was collected 6 hours

later. The volume of urine collected each hour was measured and the amount of sugar deter-mined by Benedict’s quantitative method for

total reducing substance.12 Roe’s colorimetric

method for fructose’3 was used to determine the amount of reducing substance accounted for by fructose. All specimens were tested within 1 hour after collection.

Samples of capillary blood were obtained from a heel puncture at the beginning of the infusion and hourly thereafter from 9 AM. to

4 P.M. Protein-free filtrates were made

im-mediately and analyzed on the day of the

ex-periment. Total concentration of sugar in

the blood was measured by Nelson’s

photo-metric adaptation of Somogyi’s method.14 The

0 Baxter Laboratories Inc., Morton Grove,

Ilbi-nois, kindly furnished supplies of invert sugar and

of fructose. All sugars were dextro-rotary.

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(3)

GLUCOSE INFUSION

INVERT SUGAR INFUSION 300

250

200

150

100

50

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TOTAL BLOOD SUGAR

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FRUCTOSE INFUSION

GLYCOSURIA

0.38%.URINE LOSS

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670

PEDIATRICS

OCTOBER 1957

concentration of fructose in the blood was

measured by Roe’s modified Seliwanoff reac-tion.’3

After 4 P.M. the children were permitted to eat a regular diet unless gh’cosuria persisted.

RESU LTS

Table I lists the weight of each patient,

tile grams of reducing substance present in

the urine during each hour of the 8-hour

collection period, and the total for the 8

hours. Glucose produced the least amount

of reducing substance in the urine in 16 of

the 18 patients. In each of these 16, the

amount of reducing substance found in the

urine during infusions of invert sugar was

intermediate between the amounts present

during injections of glucose and of fructose.

In two patients the amount of reducing

sub-stance in the urine during infusions of

fruc-tose and of glucose was practically the same

while the amount during infusion of invert

sugar was only about half as much. It may

be noted that reducing substance was

usu-ally present in the urine bnby during the

first 2 or 3 hours of infusions of glucose, but

that it was present almost every hour

dur-ing administration of invert sugar and of

fructose. No glycosuria occurred in three

patients during the entire 6 hours of

infu-sions of glucose. Thirteen patients were

found to have no reducing substance in the

urine after the first 3 hours of the infusion

of glucose, and in eight of these glycosuria

was not present after the first 2 hours. In

contrast to total excretion of hexose, a

smaller quantity of reducing substance was

found in tile urine of 11 patients during the

first 2 hours of infusion of invert sugar than

during the same period of administration of

glucose. During the administration of invert

sugar and fructose, in all patients except

one (W.C.), the reducing substance in the

urine was practically all fructose. At the

end of the 8-hour collection period, the total

volume of urine obtained from each of the

18 patients was approximately the same

after infusions of each of the three different

carbohydrates.

Figures 1, 2, and 3 indicate the

concen-trations of sugar in the blood of J.B., A.A.,

and C.G., three patients who excreted sugar

in the manner typical of most patients. It

will be noted that the total concentration of sugar in tile blood ascended rapidly and then descended (luring tile first 2 to 3 hours

that glucose was given. The total

concen-tration of sugar in the blood did not rise as

high when invert sugar or fructose were

FRUCTOSURIA FRUCTOSURIA

2.55% URINE LOSS 6.3O% URINE LOSS

0 I 2345678 TIME IN HOURS

(4)

GLUCOSE INFUSION TOTAL BLOOD SUGAR

-- BLOOD FRUCTOSE

300

250

200

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I00

50

0

INVERT SUGAR INFUSION FRUCTOSE INFUSION

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GLYCOSUR.A

I.74% URINE LOSS

- FRUCTOSURIA FRUCTOSURIA

2.46% URINE LOSS 4.37% URINE LOSS

0 I 2 34567 8 I 2345678

TIME IN HOURS

FIG. 2. (Patient A.A.) Blood sugar bevels obtained during the 6-hour infusion period! and for 2 additional

hours. The rate of infusion was 1.25 gm/kg/hr.

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FIG. 3. (Patient C.G.) Blood sugar levels obtained during the 6-hour infusion period and for 2 additional hours. The rate of infusion was 1.25 gm/kg/hr.

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ARTICLES

671

given but tended to remain high for a

longer period. Although the concentration

of fructose in the blood accounted for only a small portion of the total sugar, fructose was constantly spilled in the urine. The

total amount of reducing substance in the

urine of the three patients was greatest

during iiijection of fructose and least during

administration of glucose.

Figure 4 depicts similar data on W.C.,

one of the two patients who excreted

gIn-cose in the urine throughout tile infusion

and for an hour thereafter, and who

ex-creted more sugar in tile urine during the

300 GLUCOSE INFUSION

250

200

FRUCTOSURIA

2.32% URINE LOSS

0 I 2 345678

TIME IN HOURS

TOTAL BLOOD SUGAR

- - - - - BLOOD FRUCTOSE

FRUCTOSURIA

4.07% URINE LOSS

(5)

INVERT SUGAR

INFUSION

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400 .

GLUCOSE

INFUSION

350

300

-250

200

150

100

50

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GLYCOSURIA

- - . - - BLOOD FRUCTOSE

FRUCTOSE INFUSION

9.69% URINE LOSS

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TIME IN HOURS

Fic. 4. (Patient \V.C.) Blood sugar levels obtained during the 6-hour infusion period and for 2 additional hours. The rate of infusion was 1.25 gm/kg/hr.

8.38#{176}LURINE LOSS

672 PEDIATRICS -

OCTOBER

1957

infusion of glucose than during that of

either invert sugar or fructose. It will be

noted that the concentration of sugar in the

blood during infusion of giucose rose far

higher than it did in the other patients and

remained high throughout the infusion.

When invert sugar was infused the total

concentration of sugar in the blood also

rose and both fructose and glucose were

ex-creted in the urine. Results recorded

dur-ing the infusion of fructose are similar to

those of the other children.

DISCUSSION

The results of the present study indicate

that the metabolism of glucose, invert

su-gar and fructose differs in several respects

when these carbohydrates are given rapidly

intravenously in a 10% solution to children

at a constant rate of 1.25 gm per kilogram

of body weight per hour for a period of 6

hours. Most of the chPdren retain glucose

best, invert sugar next best and fructose

least well. The data reveal that reducing

substance commonly appears in the urine

each hour during infusions of fructose and

invert sugar, but that in most children it is

present for only 2 or 3 hours during infu-sion of glucose. The observation is corre-bated with the finding that total concentra-tion of sugar in the blood tends to reach a high peak tile first hour or two during

in-fusion of glucose. The peak subsequently

declines even though the infusion is

con-tinned at the same rate. In general,

concen-trations of sugars in the blood after an

mi-tial rise are fairly uniform during infusions

of fructose and invert sugar, especially con-centrations of fructose.

The phenomenon of rapid rise followed

by rapid fall in concentration of sugar in

the blood during intravenous administration

of glucose has been observed by others.

Peters and Van Slyke15 cite Bang who

in-jected glucose intravenously at a constant

slow rate. Tile concentration of sugar rose

rapidly in the blood only to descend again

(6)

ARTICLES 673

Somogyi’6 and others have observed that larger amounts of glucose can be retained

after a “warming up period.” An initial slow

rate of infusion prevents undue loss of

glu-cose in the urine.

It may be postulated that during a 6-hour

infusion of glucose at a uniform rate of 1.25 gm per kilogram of body weight per hour the rising concentration of glucose in the

blood stimulates the production of insulin

which converts the glucose to glycogen.

This might result in a sharp decrease in concentration of glucose after the first 1 or 2 hours of infusion. Perhaps, on the other

hand, since fructose may be directly

ox-idized and converted to liver glycogen

with-out need for insulin the levels of fructose in the blood are relatively constant

through-out infusions of invert sugar and fructose.

The two children who did not follow the

usual pattern for some reason may not have had their insulin output stimulated as easily as the others by a high concentration of sugar in the blood. From this study it is ap-parent that one would have arrived at mis-leading conclusions as to the relative merits of long-term infusions of the various hexoses

if injections had been given for only 1 or 2

hours, as was done in most of the studies

on adults.

It is difficult to reconcile our findings

with those of Kaye and coworkers,17 who

administered 33 infusions to 21 infants most

of whom were less than 9 months of age.

The infusions were administered over a

pe-nod of 6 hours but the glucose was made up in a hypotonic solution of electrolytes rather than in water as was the glucose admin-istered in our study. When the rate was 1

gm/kg/hr fructose was utilized only slightly

less well than glucose. At a rate of infusion

of 2 gm/kg/hr there was a significant

differ-ence in favor of the utilization of fructose

but at this rate of infusion the subjects

re-ceiving fructose excreted a greater amount

of sodium than that infused, developed

aci-dosis and significant changes in pulse, res-piratory rate and size of the liver. Their data as well as ours therefore suggest that in

chil-dren who require intravenous fluid therapy

with maximum caloric intake for periods

longer than 2 hours glucose is to be

pre-ferred to fructose.

The data presented here apply only to

afebribe children. Although most of the sub-jects were recovering from some disease,

there was no sudden stress situation such as

an operation which might have altered the

production of insulin and other enzymes or

hormones. In order to obtain a more

corn-plete evaluation of the utilization of

glu-cose, invert sugar and fructose in sick

chil-dren, further studies should be carried out,

particu’arly since somewhat divergent effects were obtained at two pediatric cen-ters.

SUMMARY

Eighteen children were infused with 10

solutions of glucose, invert sugar and fruc-tose during a period of 6 hours at a rate of

infusion of 1.25 gm of sugar per kilogram

of body weight per hour. All but two of the

children had less glycosuria from

intra-venous administration of glucose than from

the administration of invert sugar or

fruc-tose. In 16 children glucose appeared in

the urine only during the first 2 or 3 hours

of infusion of glucose, but fructose was

gen-erally present in the urine during almost

all of the 6 hours of infusion of invert sugar

or of fructose. Eleven of the eighteen

pa-tients had more mebituria during the first 2

hours of infusion of glucose than during the

first 2 hours of infusion of invert sugar or

fructose. This contrasts with the total

amount excreted over an 8-hour period.

When glucose was administered, total

concentration of sugar in the blood

oh-tamed during the first 2 hours of infusions

were higher than concentrations obtained

during infusions of invert sugar and

fruc-tose; subsequently, there was often little

difference in total concentration of sugar ill

the blood during infusion of the three

hex-oses. Determinations of concentrations of sugars in the blood revealed that the renal

threshold for glucose was above 175 mg/

(7)

674

PEDIATRICS

OCTOBER

fructose was frequently as bow as 10 mg/

100 ml of blood.

There was no significant difference in

total volumes of urine obtained from each

patient at the end of 8-hour collection

pe-nods after infusions of the three

carbo-hydrates.

The present study suggests that in some

children who require intravenous fluid

ther-apy with maximum caloric intake for

pe-nods longer than 2 hours glucose is to be

preferred to invert sugar or fructose.

Whether glucose is the best choice for

chib-dren after operation or in situations of

severe stress remains to be demonstrated.

REFERENCES

1. Woodyatt, R. T., Sansum, W. D., and

Wilder, R. M. : Prolonged and accurately

timed intravenous injections of sugar.

J.A.M.A., 65:2067, 1915.

2. Weinstein,

J. J.,

and Roe,

J.

H.

: The util-ization of dextrose, levulose, and invert sugar by normal and surgical patients.

Part II. Am.

J.

Proct., 4:117, 1953.

3. Bertino,

J.,

Dawson, N., French, R.,

Mar-gen, S., and Kinsell, L. W. : Comparative

observations regarding utilization and excretion of infused glucose, fructose, and invert sugar, respectively.

J.

Clin. Endocrinol., 13:658, 1953.

4. Lawton, B. R., Curreri, A. R., and Gale,

J.

W. : Use of invert sugar solutions for parenteral feeding of surgical patients.

Arch. Surg., 63:561, 1951.

5. Frost, D. V., Miller,

J.

P., and Richards, R. K.: Some considerations regarding

invert sugar and dextrose.

J.

Appl. Physiol., 4:793, 1952.

6. Weichselbaum, T. E., Elman, R., and Lund, R. H. : Comparative utilization of fructose and glucose given intravenously.

Proc. Soc. Exper. Biol. & Med., 75:816,

1950.

7. Moncrief,

J.

A., Coldwater, K. B., and Elman, R. : Postoperative loss of sugar in urine following intravenous infusion of fructose (levubose). Arch. Surg., 67: 57, 1953.

8. Drucker, W. R., et al.: A comparison of the

effect of operation on glucose and

fruc-tose metabolism. Surg. Forum.

Phila-delphia, Saunders, 1952, pp. 548-555.

9. Miller, M., Drucker, W. R., Owens,

J.

E.,

Craig,

J.

W., and Woodward, H.:

Metabolism of intravenous fructose and

glucose ill normal and diabetic subjects.

J.

Clin. Invest., 31:115, 1952.

10. Smith,

J.

L., Beal,

J.

M., and Frost, P.: Comparative utilization of intravenous invert sugar and glucose. Surgery, 31:

720, 1952.

11. Strub, I. H., Best, W. R., Consolazio, C. F.,

and Grossman, M. I. : Utilization of in-travenously injected fructose and invert sugar in normal human subjects. Am.

J.

Clin. Nutrition, 2:32, 1954.

12. Hepler, 0. E. : Manual of Clinical

Lab-oratory Methods, 4th Ed. Springfield, Thomas, 1951, pp. 10-11.

13. Roe,

J.

H. : A coborimetric method for the determination of fructose in blood and

urine.

J.

Biol. Chem., 107:15, 1934. 14. Nelson, N. : A photometric adaptation of

the Somogyi method for the

determina-tion of glucose.

J.

Biol. Chem., 153: 375, 1944.

15. Peters,

J.

P., and Van Slyke, D. D.:

Quantitative Clinical Chemistry, Vol. 1,

2nd Ed. Baltimore, Williams & Wilkins,

1946, pp. 184-185.

16. Pareira, M. D., and Somogyi, M. :

Ra-tionale of parenteral glucose feeding

in the postoperative state. Ann. Surg.,

127:417, 1948.

17. Kave, R., Williams, M. L., and Barbero, G. : A comparative study of the metab-olism of glucose and fructose in infants (abstract). Am.

J.

Dis. Child., 93:85.

1957.

SUMMARIO IN INTERLINGUA

Glucosa,

Sucro

Invertite,

e Fructosa

in

le Alimentation

Parenteral

de

Patientes

Pediatric

Dece-octo patientes pediatric recipeva in-fusiones de solutiones de 10 pro cento de

glu-cosa, sucro invertite, e fructosa durante 6 horas

a proratas infusional de 1,25 g de sucro per

kg de peso corporee per hora. Omne be

pa-tientes con duo exceptiones habeva minus

glycosuria ab be administration de glucosa que ab sucro invertite o fructosa. In 16 casos gIn-cosa appareva in be urina solmente durante le prime duo o tres horas del infusion de glucosa, durante que fructosa esseva generalmente pre-sente in be urina quasi a transverso le integre periodo de 6 horas de infusion de sucro in-vertite 0 fructosa. Dece-un del 18 patientes habeva plus melituria durante be prime 2 horas

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ARTICLES

675

2 horas de infusion de sucro invertite o fructosa. Isto contrasta con be quantitate total del

ex-cretion durante un periodo de 8 horas.

Q

uando glucosa esseva administrate, be

nivel-los total de sucro sanguinee obtenite durante be prime 2 horas del infusion esseva plus alte que be nivelbos obtenite in infusiones de sucro in-vertite e fructosa. Subsequentemente, ib habeva

frequentemente pauc differentia inter le nivelbos total de sucro sanguinee pro be tres hexosas. Determinationes de sucro sanguinee revelava

que be limine renal pro glucosa esseva supra

175 mg pro 100 ml de sanguine, durante que

be limine pro fructosa esseva frequentemente

non plus que 10 mg pro 100 ml de sanguine.

Esseva notate nulle differentia significative

in be volumines total de urina obtenite ab le patientes individual ab fin de periodos de col-bection de 8 horas post infusiones del un o del altere del tres hydratos de carbon.

Le presente studio indica que glucosa es a

preferer a sucro invertite o fructosa in certe patientes pediatric qui require therapia a fluido

intravenose con nivebbos caloric maximal

du-rante periodos de plus que 2 horas. Si o non

glucosa es be infusion de election in patientes

postoperatori o in situationes de sever grados

de stress remane a demonstrar.

HAEMOLYTIC I)IsEA5E OF THE NEWBORN, W. Walker et al. (Lancet, 1 : 1309, June 29, 1957.)

Two well-known authorities on hemolytic disease undertake in this paper to

determine the causes for what they consider to be an excessive mortality from this disease in England and \Vales at the present time. They state that with correct use of exchange transfusion a mortality of not more than 5% of infants with hemolytic disease born alive should be expected. The authors express the opinion that the deaths at present are at least three times as numerous as should be expected with modern treatment. Analysis of the reported deaths seem to indicate two principal causes for this: (1) failure to anticipate the disease before birth or to recognize the disease early after birth, and (2) either failure to undertake an exchange transfusion

or to employ satisfactory technique in the exchange transfusion, particularly to give

an adequate exchange. They point out that the best results are to be expected in hospitals where a large number of cases are treated and considerable experience is acquired. In hospitals where the number of cases seen is small it is difficult for the staff to gain the necessary experience and familiarity with the technique of exchange transfusion and the general principles of diagnosis and management. A full discussion

(9)

1957;20;668

Pediatrics

Harold C. Lane and Katharine Dodd

FEEDING OF CHILDREN

USE OF GLUCOSE, INVERT SUGAR AND FRUCTOSE FOR PARENTERAL

Services

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