Plasma amino acid changes in the postsurgical newborn during intravenous nutrition with a synthetic amino acid solution

Plasma Amino Acid Changes in the Postsurgical Newborn During Intravenous Nutrition With a Synthetic Amino Acid Solution By Gordon

Dale, Malcolm

Panter-Brick,

John Wagget,

and Gwendoline

Young

I

NTRAVENOUS NUTRITION has lessened the mortality and morbidity associated with the surgical management of major newborn problems of the gastrointestinal tract. The regimen used in Newcastle is based upon the use of a crystalline amino acid solution (Vamin-Glucose) with the additional calories provided by a soybean emulsion (Intralipid 20%) and 10% glucose. Vitamins and electrolytes are provided as detailed in Table 1. The solutions are pumped continuously throughout the 24 hr, using a delivery system with separate infusion pumps for the clear fluids and the fat emulsion.’ We have been particularly careful to avoid the dangerous effects of hyperaminoacidemia, and have monitored the plasma amino acid levels. MATERIALS

AND

METHODS

Fourteen newborn babies were treated with the regimen as stated (Table 2). All but two had intravenous nutrition commencing less than 48 hr after surgery to the gastrointestinal tract. The exceptions were a baby who had an ileus related to prematurity and pneumonia, and one with a postoperative malabsorption syndrome. The majority of babies were of low birth weight (mean preoperative weight: 2.36 kg). In each case the infusion rate was increased in increments over 3 days, achieving a final infusion rate of 350 mg of nitrogen/kg/day (I I5 Cal/kg/day: fat40 cal; glucose-75 Cal). Samples of venous blood were taken at the pre-infusion level and at the following rates of amino acid nitrogen infusion: 100, 150, 250 and 350 mg. nitrogen/kg/24 hr. Blood was drawn for these estimations between 9:00 AM and 9:30 AM each day, the time when our necessary biochemical investigations were being carried out. The heparinized samples were centrifuged immediately and deproteinized with solid sulphosalycilic acid (25 mg/ml of plasma). The amino acid estimations were carried out on a 60-cm column of Aminex A6 resin in a LKB Bio Cal BC IOOLamino acid analyzer, using the manufacturer’s recommended three-buffer system.

RESULTS

All the children studied on the regimen made weight gain is plotted on a percentile chart for The plasma amino acid concentrations for each in Fig. 2. Figures 3 and 4 show graphically the at different rates of infusion.

satisfactory progress and their Newcastle live births,? (Fig. 1). individual amino acid are given mean plasma amino acid levels

From the Departments of Child Health, Surgery, and Clinical Biochemistry, University of Newcastle upon Tyne. Newcastle upon Tyne, England. Supported by the Scientific and Research Committee of Newcastle Area Health Authority (Teaching). Presented before the XXII International Congress of the British Association of Paediatric Surgeons, Newcastle upon Tyne, England, July 30-August 1.1975. Address for reprints: G. Dale, Department of Clinical Biochemistry, Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP. England. o 1976 by Gnme & Stratton, Inc. lournol of PediatricSurgery, Vol.

11, No. 1 (February), 1976

17

DALE

18

Table

1.

Constitution

30 ml/kg/day

lntralipid

20 ml/kg/day

Glucose

150

10%

4-5

mmole/kg/doy

Potassium

3-4

mmole/kg/day

Calcium

0.5

mmole/kg/day*

Phosphorus

0.5

mmole/kg/doy*

Magnesium

0.15

Total

fluid

mmole/kg/day*

2 ml/liter

(Multibionto)

200

intoke

Vitamin

K

1 mg/wk

812

50 pg/l4 1 mg/14

Iron-dextron addition

to that

0.5

(Imferon) contained

in Vamin-Glucose

of fluid

ml/kg/day

Vitamin

Folic acid

‘In

ml/kg/day

Sodium

Vitamins

AL.

of Infurate

Vamin-Glucose 20%

ET

days doys

ml intramuscularly

every

14 doys

and Introlipid.

DISCUSSION

There are, perhaps, two approaches to the development of a satisfactory scheme of parenteral nutrition. On the one hand, the nutrients can be given by some generally accepted standard. In the case of intravenous nutrition this would require adequate amounts of a spectrum of L-amino acids containing a proper balance of the essential and nonessential components while also ensuring that there is neither an excess nor a deficit of a particular individual component. The composition of such a mixture may be based upon the amino acid content of a particular protein, such as casein, fibrin, or egg-white protein (and necessarily so if the product used is indeed a protein hydrolysate). However, delivery by the parenteral route, by-passing the liver, places vital tissues, particularly the brain, in the hazardous position of receiving high and frequently unmeasured concentrations of potentially toxic substances. The approach which we have tried to adopt is the alternative one. We use a synthetic amino acid mixture, avoiding the problems associated with protein hydrolysates, such as variability of composition, low-molecular-weight peptides, high salt content, etc. This particular mixture (Vamin-Glucose) contains not only amino acids essential to the adult, but also cystine, tyrosine, and histidine, which may be essential in the low-birth-weight infant. Our aim was to

Table Trocheo-esophageal Duodenal Meconium

Diogneses

of Patients

3 2

peritonitis

1

disease

1

and pneumonia

1

Gastroxhisis

1

Exomphalos Obstructed Totol

Treated 4

atresia

Hirschsprung’s Prematurity

2.

fistulo

hernia

with

postoperative

1

malabsorption 14

4.: 9 4.0

males

-

females

-

cases

-

-

8 3.5

lb kg

7 3.0 6 2.5 5

32

34

35

36

37

36

39

40

41

42

43

44

weeks

Gestational age Fig. 1. Weight gain in intravenously fed postsurgical newborn infants compared with Newcastle live Birth contiles.*

Present

data

Fig. 2. Plasma amino acid concentrations during infusion of 350 mg nitrogen/kg/day compared with the values for normal pmterm infants. The mean f standard deviation for normal pmterm infants’ are indicated.

20

DALE ET AL.

c

c

B

150

mg Nlkg124hr

I

c 100

I

I

150

250

mg N/kg/24

1 150

ii,. 250

mg N/kg/24

I

350 hr

/ c 100

350 hr

Fig. 3. (A) Changes in mean concentmtions of proline, alanine, and glycine am connected by heavy lines. The flne lines indicate significant changes according to the paired Student t-test (p < 0.05). (Note the linear rise in pro line with increasing mtes of infusion.) (B) Changes in mean concentmtions of glutamate, serine, and aspartate. (C) Changes in mean concentmtions of bmnched-chain amino acids.

PLASMA

AMINO

ACID CHANGES

Fig. 4. (A) Changes in mean concentrations of methionine, cystine, phenylalanine, tyrosine. (B) Changes in mean concentrations of lysine, histidine, and arginine.

21

and

infuse the solution at a rate which resulted in plasma amino acid levels not grossly different from reference values for healthy newborn infants of low birth weight.’ By using this approach, we avoid the problems of hyperaminoacidemia, in which, presumably, supply outstrips the ability of metabolic processes to handle one or more of the amino acid components. In addition, it is possible to identify those low plasma amino acid levels (suggesting a continuing tissue requirement) persisting despite the increase in the infusion rate. Considerable metabolic changes occur in the postoperative period, making interpretation of the data difficult; but it is possible to identify consistent and metabolically relevant changes in plasma amino acid levels during the period of increasing infusion rate. On the regimen employed, the plasma levels of some of the amino acidsnotably proline (Fig. 3A), glutamate (Fig. 3B), and the branched-chain amino acids (isoleucine, leucine, and valine, Fig. 3C)-increase progressively and significantly with increasing infusion rate. Others-such as cystine, tyrosine (Fig. 4A), histidine, lysine, and arginine (Fig. 4B)-do not increase appreciably above the pre-infusion level for any infusion rate up to 350 mg nitrogen/kg/ day. The mean levels of alanine, glycine, phenylalanine, and methionine increase significantly only at the higher rates of administration. Our aim has been to keep the mean plasma level of each amino acid within acceptable limits, defined arbitrarily as within two standard deviations of the mean values of Dickinson et ah3 The infusion of 350 mg nitrogen/kg/day using Vamin-Glucose nearly satisfies this requirement, although the levels of aspartate, glutamate, proline, valine, and isoleucine are in excess of this limit. On the other hand, no amino acid level is as much as one standard deviation below the mean reference value at this rate of infusion, the lowest in this respect being lysine.

22

DALE ET Al.

Accepting these constraints, an infusion rate of 350 mg nitrogen/kg/day is the maximum we can use since an additional increment would produce a significant and undesirable increase in those five amino acids-especially proline, isoleucine, leucine, and glutamate-implying inability to handle the increasing load. The nitrogen provision is lower than that used by many other workers, although close to the WHO recommended oral intake of 384 mg nitrogen/kg/ day,4 which includes 30% to allow for individual variability. It can be seen in Fig. 1 that the infants treated in this manner gain weight during the period of intravenous nutrition, although the weight gain is perhaps less than optimal. Certainly we would favor a higher rate of infusion if the infusate were to contain rather lower amounts of proline, isoleucine, leucine, and glutamate. The resultant deficiency in total nitrogen composition could be made up, at least in part, by those glucogenic amino acids which in our regimen have relatively low plasma levels-glycine (which is at a lower concentration in Vamin-Glucose than in most other commercial amino acid preparations) and alanine. It may be relevant that metabolic acidosis, a well-recognized complication of intravenous nutrition, particularly of crystalline amino acid preparations,5 is a phenomenon which we have seen infrequently, and is rarely attributable to this form of therapy. Indeed, metabolic alkalosis has been encountered on four occasions in three infants. We suspect that the high concentration in VaminGlucose of the bases glutamate and aspartate and the relatively low levels of arginine and lysine, which are effectively acidic, may have played a part in bringing about this rather worrying condition. We suggest, therefore, that a reduction of the glutamate and aspartate content and an increase in arginine and lysine might be beneficial, not only from the point of view of improving the amino acid balance, but also of hydrogen ion homeostasis. SUMMARY

Plasma amino acid concentrations during the therapeutic use of a crystalline amino acid solution are presented and discussed. In an attempt to avoid potentially dangerous hyperaminoacidemia, a maximum infusion rate of 350 mg nitrogen/kg/day was chosen. This resulted in the majority of the amino acids remaining within two standard deviations of normal mean3 although levels of aspartate, glutamate, proline, valine, and isoleucine are in excess of this limit. No amino acid level is as much as one standard deviation below the mean, the lowest in this respect being lysine. A moderate increase in nitrogen provision is probably desirable to improve weight gain, but this solution would result in undesirable increases in these amino acid concentrations. REFERENCES I. Coran AG: Long term total intravenous feeding of infants using peripheral veins. J Pediatr Surg 8:801, 1973 2. Neligan GA, Prudham D, Steiner H: The Formative Years-Birth, Family and Development in Newcastle-upon-Tyne. Oxford, Oxford University Press, 1974, p 68 3. Dickinson

JC,

Rosenblum

H,

Hamilton

PB: Ion exchange chromatography of the free amino acids in the plasma of infants under 2,500 gm. Pediatrics, 45606, 1970 4. WHO Technical Report Series No. 522, 1973, p 70 5. Heird WC, Dell RB, Driscoll JM, et al: Metabolic acidosis resulting from intravenous alimentation mixtures containing synthetic amino acids. N Engl J Med 28:943, 1972