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Acta Anaesthesiol Scand 1993: 37: 170-1 75

Metabolic consequences of different perioperative


fluid therapies in the neonatal period
K. NILSSON,
K. SANDSTROM, S. ANDR~ASSON, and L. E. LARSSON
A. NIKLASSON’
Department of Paediatric Anaesthesia and Intensive Care and ‘Department of Paediatrics, &tra Hospital, Gothenburg, Sweden

Carbohydrate and fat metabolism during and after anaesthesia and surgery was studied in 14 neonates with
major congenital non-cardiac anomalies. They were either given a glucose solution until surgery or starved
for at least 4 h before surgery. Ringer-acetate alone or Ringer-acetate plus 10% glucose was used for the
intraoperative fluid therapy. After anaesthesia all neonates were given a 10% glucose solution. Concentrations
of glucose, free fatty acids, triglycerides, lactate, pyruvate, alanine, glycerol and 3-hydroxybutyrate were
measured at predetermined intervals pre-, intra- and postoperatively. Blood glucose concentrations rose
during surgery both in neonates given glucose before and during surgery ( n = 6 ) and in neonates not
given glucose before and during surgery ( n = 6 ) . Increased intraoperative levels of free fatty acids and 3-
hydroxybutyrate were found in neonates not given glucose before and during surgery. The triglyceride levels
were equal in both groups. In two neonates given glucose before surgery and Ringer-acetate during surgery
increased levels of 3-hydroxybutyrate were found, particularly in one patient who became hypoglycaemic.
In conclusion, starved neonates without intraoperative glucose supply mobilized fat and maintained blood
glucose concentrations.
Received 26 March 1991, accebted f o r publication in a revised version 4 July 1992
Key words: Anesthesia; fluid therapy; free fatty acids; 3-hydroxybutyrate; metabolism; neonates.

Glucose-containing solutions are usually recommended Fourteen neonates with major congenital non-cardiac defects were
studied in connection with operation within their first 144 h of life.
during anaesthesia in the neonatal period (1). The rea- The basic layout and the blood glucose values of 1 1 of the 14 patients
sons for this are the low stores of glycogen and the im- have been presented earlier (3). These 11 patients constitute a sub-
paired gluconeogenesisin the neonate (2). I n a previous group of this earlier randomized study (30 patients) on the influence
study blood glucose concentrations in neonates during of fluid regimens on perioperative blood glucose concentrations.
Three new patients (nos. 6, 11 and 12, Table 1) were recruited, as
and after surgery were found to be related to both the
only blood glucose and blood gases were available for a majority of
pre- and intraoperative glucose infusion (3). Blood glu- the original patients. The mean weight was 3.3 kg (range 2.4-4.0
cose concentrations were mostly stable when glucose kg), mean gestational age was 38 weeks (range 36-42 weeks) and
was given before and during surgery. Preoperative glu- mean age at operation was 39 h (range 6-144 h). The preoperative
nutrition was not manipulated for the study and followed the routines
cose followed by intraoperative Ringer-acetate resulted of the referring hospital or physician. Five neonates from the ran-
in an increased risk for hypoglycaemia. O n the other domized blood glucose study plus one added neonate had had a
hand, hypoglycaemia was not found when glucose was running infusion of 2 4 ml kg-’ h-’ 10% glucose (Glucos, ACO,
not given before and during surgery. Sweden) for at least 3 h when presented for anaesthesia (Group 1).
These neonates received an intraoperative fluid therapy of 3 ml kg-’
In normal healthy newborns an increasing pro- h-’ of 10% glucose (0.3 g kg-l h-I) in addition to Ringer-acetate
portion of the energy requirement is derived from glu- (Ringerdex, Pharmacia, Sweden). Four neonates from the blood
coneogenesis and fat mobilization (4).Our previous glucose study plus two recruited neonates had been starved for at
study on blood glucose concentrations during neonatal least 4 h (Group 2). Before that, one had been given breast milk and
two had had a glucose infusion. This “starved” group received only
surgery showed maintained blood glucose levels in Ringer-acetate intraoperatively. Group 3 consisted of two neonates
starved neonates without intraoperative glucose who also had a glucose infusion running preoperatively, but were
supply. The aim of this report is to describe the contri- randomized to receive a glucose-free intraoperative fluid supply. A
bu tion of fat mobilization and gluconeogenesis to the total infusion rate of 20 ml kg-’ was aimed at in all infants during
the first hour of surgery and after that the rate was reduced to 10 ml
energy homeostasis before, during and after surgery in ’
kg- h-’. Colloids were given in addition, if indicated. Postopera-
the neonatal period with and without peroperative tively, all infants had a 10% glucose solution with electrolytes at a
glucose infusions. rate of 5&1OO ml kg-’ 24 h-’ (5-10 g kg-l 24 h-I) according to the
age at time of operation.
Anaesthesia was induced with thiopentone 5 mg kg-’ and main-
PATIENTS AND METHODS tained with fentanyl (incremental doses of 2 pg kg-’, maximum 10
The study was approved by the Ethics Committee of the Medical pg kg-’) and nitrous oxide-oxygen as needed, judged by Sao, or
Faculty, University of Goteborg. Informed consent was obtained Spo,. Pancuronium or vecuronium 0.1 mg kg-’ was used for muscle
from the parents of all infants studied. relaxation. All children were ventilated using a Mapleson-D system.
PERIOPERATIVE FLUID THERAPY 171
After induction of anaesthesia, blood samples were taken from an preoperative fluid supply there were no statistically
indwelling arterial cannula. Samples were taken immediately before
the start of the operation and repeated every 30 min until the oper-
significant differences in total fluid infusion rates be-
ation was completed. Immediately upon arrival in the ICU, another tween Groups 1 and 2. The total intraoperative in-
sample was taken (End) followed by samples taken at 1, 4 and 8 h fusion rate (glucose+Ringer) was 17.7 k 3.5 ml kg-'
postoperatively. Samples were analysed for glucose and lactate in h-I in Group 1 and 15.3 f 5.8 m l . kg-]. h-' in Group
blood and triglycerides (TG), free fatty acids (FFA), glycerol, lactate, 2. In Group 1 the mean preoperative glucose infusion
pyruvate, alanine and 3-hydroxybutyrate (3-OHB) in plasma. Blood-
gases and acid-base status were determined at every sampling oc- rate was 3.4k0.9 ml kg-I h-' and the mean intra-
casion. operative glucose infusion rate was 2.9 _+ 0.2 ml kg-'
Blood glucose was measured using a glucose-6-phosphate dehydro- '.
h - The mean Ringer-acetate infusion rate during
genase method (5). Plasma for TG, FFA, 3-OHB, alanine and glycer- anaesthesia in Group 1 was 14.8 & 3.6 ml kg-' h-I.
ol was separated by centrifugation and plasma fractions were por-
tioned and frozen separately. Blood for lactate analysis was frozen
After surgery the mean glucose infusion rate was 3.6 f
after precipitation in 0.6 mol I-' perchloric acid. TG and FFA were 1.O ml kg-' h-' in all neonates (identical mean infusion
determined by gas-liquid chromatography (6). 3-OHB (7), pyruvate, rates in Groups 1 and 2 ) .
alanine (E), glycerol (9) and lactate (10) were analysed using enzy- Blood glucose levels did not differ between the neo-
matic tests. Blood gases and acid-base status were analysed with a nates given glucose (Group 1) and the starved neonates
Radiometer ABL 2 (Copenhagen, Denmark).
Two-way analysis of variance of the Wilcoxon signed rank test
(Group 2). In both groups, blood glucose concen-
was used for statistical differences in substrate concentrations before, trations rose during surgery (P<O.Ol, Table 2 and
during and after surgery within each group. Student's btest was used Table 3). Lactate and pyruvate tended to be higher,
for differences between intraoperative and postoperative levels within although not statistically significantly different in neo-
the two study groups where all intraoperative concentrations (includ- nates given glucose compared to starved neonates. Ala-
ing End-concentrations) were pooled and compared to all pooled
postoperative concentrations. Bonferroni correction was used to ad-
nine and glycerol tended to be lower, although not
just the P-value for multiple comparisons. A P-value<0.05% was statistically significantly different, in neonates given
considered significant. glucose compared to starved neonates. TG values
showed no difference between the neonates with differ-
ent fluid therapies during and after surgery. FFA did
RESULTS not change during and after operation among the neo-
The mean values presented in the text, tables and nates given glucose. In the starved neonates mean in-
figures originate from the two main study groups traoperative concentrations of FFA were significantly
(Group 1, glucose and Group 2, starved Ringer-ace- + higher (P<0.05, t-test) compared to neonates given
tate). Some data of interest from Group 3, the two glucose. Furthermore, FFA increased from the pre-
neonates with glucose preoperatively and only Ringer- operative concentrations to the last measured intra-
acetate intraoperatively, are commented on in the text operative concentrations in the starved group
but not used in the statistical comparisons of the study. ( P < 0.05, Wilcoxon's signed rank test). After surgery
Weight, gestational age and age at operation did not the starved neonates showed a falling mean FFA con-
differ between the groups (Table 1). Except for the centration compared to the mean concentration during

Table 1
Patient data and fluid therapy.
Gestational Age at Preop. Intraop. Intraop.
Weight age surgery glucose glucose Ringer
Group Patient Diagnosis (kg) (weeks) (h) (ml kg-' h-')
1 1 Oesophageal atresia 2.8 37 24 3.6 2.5 19
2 Oesophageal atresia 2.7 36 13 2.6 3.0 19
3 Duodenal atresia 2.4 36 19 2.9 2.9 14
4 Pulmonary cyst 3.7 38 7 2.8 2.8 15
5 Hydrocephalus 3.3 38 102 5.0 3.0 11
6 Myelomeningocele 4.0 39 14 3.3 3.0 11
2 7 Myelomeningocele 3.3 38 72 0 0 24
8 Abdominal tumour 4.0 42 114 0 0 21
9 Myelomeningocele 3.5 37 9 0 0 13
10 Myelomeningocele 3.8 36 6 0 0 12
11 Myelomeningocele 3.7 40 22 0 0 9
12 Duodenal atresia 2.4 36 71 0 0 13
3 13 Oesophageal atresia 3.3 42 11 2.4 0 23
14 Duodenal atresia 2.6 37 25 2.6 0 25
172 K. SANDSTROM ET AL.
Table 2
Metabolic measures (mmol.l-') preoperatively, after 30 and 60 min of surgery, at the end of anaesthesia and 4 and 8 h postoperatively in
Group 1, neonates given glucose preoperatively and during surgery (n=6). Mean values f 1 s.d. are given. Abbrevations: TG - triglycerides,
FFA - free fatty acids, 3-OHB-3-hydroxybutyrate.
Preop. 30' 60' End 4h 8h
Glucose 3.8f 1.5 4.3 f 1.5 4.4f 1.1 5.45 1.0 5.7 f 3.1 5.2 f 1.8
TG 0.56 f 0.21 0.58 f 0.20 0.47 f 0.09 0.67 f 0.25 0.69 f 0.38 0.60 f 0.26
FFA 0.57k0.19 0.6 1 f 0.20 0.63 f 0.21 0.47 f 0.23 0.50 f 0.26 0.36 f 0.19
Lactate 2.49 f 0.99 2.24 f 0.80 2.23 5 1.24 2.46 f 1.27 1.58 f 0.76 2.03 f 0.81
Pyruvate 0.1 1 f 0.06 0.1 1 f 0.06 0.1 I f 0.06 0.11 f 0.07 0.11 f0.04 0.10 f 0.04
Alanine 0.32 f 0.10 0.25 f 0.10 0.26 f 0.06 0.25f0.11 0.30 f 0.10 0.27 f 0.08
3-OHB 0.32 k 0.33 0.29 f 0.26 0.28 f 0.18 0.40 f 0.36 0.13f0.14 0.09 f 0.07
Glycerol 0.51 f 0.53 0.54 f 0.59 0.79 f 0.97 0.61 f 0.66 0.41 f 0.35 0.32 f 0.14

surgery (P<0.05, t-test). Mean postoperative concen- fant in Group 3 was 3.5 mmol 1-'. Compared to the
trations of FFA did not differ between the two study hypoglycaemic neonate, this neonate had less pro-
groups. Mean 3-OHB was elevated both before and nounced increases in FFA and 3-OHB concentrations.
during surgery among the starved neonates compared All neonates had blood gases and acid-base status
to the neonates given glucose ( P < O . O O l , t-test). After within the normal ranges during and after anaesthesia
surgery the starved neonates had the same concen- without any significant differences between the groups.
trations of 3-OHB as the neonates given glucose. Mean For all the patients, peroperative p H (mean s.d.) was
3-OHB was higher during surgery compared to mean 7.45 k 0.1 1 Po, was 12.0 5 6.7 kPa and Pco, was 4.0 f
postoperative concentration in the starved neonates 1.2 kPa. Standard bicarbonate concentrations in the
(P<O.OOl, t-test). The mean concentrations of blood neonates were in the normal ranges at all sampling
glucose, FFA and 3-OHB in the two groups at each occasions. The only exception was the hypoglycaemic
sampling occasion are plotted in Fig. 1 and 2. The neonate mentioned above, who coincidentally with
preoperative concentrations and the last concentrations the high 3-hydroxybutyrate concentration developed a
during surgery of FFA and 3-OHB are plotted in Fig. slight acidosis.
3.
In one of the two infants in Group 3, in which
the glucose infusion was stopped and replaced with DISCUSSION
Ringer-acetate, hypoglycaemia followed (Fig. 4). Blood glucose levels have previously been reported in
Blood glucose concentrations in this neonate were re- 11 of 14 of these infants (3). The neonates not given
peatedly below 2 mmol 1-' during the first hour of glucose before and during surgery maintained ade-
surgery. The lowest concentration was 1.2 mmol 1-I. quate blood glucose concentrations at the same level
This patient also had the highest levels of 3-OHB. as the neonates given glucose before and during
Standard bicarbonate in this patient decreased from surgery, as did the three additional patients recruited
21.6 to 19.6 mmol 1-'. Simultaneously FFA was the to this study. The increased blood glucose concen-
second highest noted in this study. The mean blood trations are probably caused by the surgical trauma,
glucose concentration during surgery in the other in- as is seen in adults ( 1 1) and older children ( 12). The

Table 3
Metabolic measures (mmol ' I - ' ) preoperatively, after 30 and 60 min of surgery, at the end of anaesthesia and 4 and 8 h postoperatively in
Group 2, starved neonates given no fluid before and Ringer during surgery (n =6). Means f 1 s.d. are given. Abbrevations: TG - triglycerides,
FFA - free fatty acids, 3-OHB-3-hydroxybutyrate.
Preop. 30' 60' End 4h 8h
Glucose 3.4f 1.1 4.4f 1.3 5.5 f 2.2 5.8 k 2.0 5.5 f 0.7 5.9 f 1.2
TG 0.57 f 0.24 0.60 f 0.25 0.62 f 0.25 0.61 f 0.25 0.65 k 0.23 0.60 f 0.26
FFA 0.76 f 0.27 0.76 f 0.35 1.13 f 0.57 0.75 f 0.26 0.40 f 0.23 0.35 f 0.25
Lactate 2.08 i 0.73 2.25f 1.14 2.25 f 0.71 1.61 f 0.67 1.58 f 0.76 1.89 _+ 0.80
Pyruvate 0.08 f 0.04 0.08 f 0.05 0.08 f 0.02 0.07 f 0.03 0.08 f 0.05 0.07 f 0.03
Alanine 0.34 f 0.10 0.31 f 0.09 0.35 f 0.08 0.35 k 0.09 0.38 f 0.07 0.37 f 0.08
3-OHB 0.74 f 0.35 0.95 f 0.46 1 .OO f 0.60 0.78 f 0.48 0.08 f 0.05 0.10 f 0.06
Glycerol 0.63 f 0.47 0.68 f 0.52 0.86 f 0.78 0.68 f 0.63 0.46 k 0.32 0.31 f0.16
PERIOPERATIVE FLUID THERAPY 173
Glucose FFA Mean &EM
mmol.L' 3-OHB rnrnol.l-'

1.5 1 FFA 3-OHB

1.0 4

0.5 - I

-
9
-
01
Preop End of Preop End of
surgery surgery
Fig. 3. Mean preoperative (Preop) and last mean intraoperative
Preop 30 rnin 60 min End 4h 8h concentrations (End of surgery) of FFA in the starved neonates 0
Fig. I . Mean concentrations of glucose, FFA and 3-OHB in neonates and in the neonates given glucose 0 and of 3-OHB in the starved
given glucose pre- and intraoperatively (n = 6 ) ;preop, at 30, 60 min, neonates A and in the neonates given glucose A . * denotes a statisti-
at the end of anaesthesia and 4 and 8 h postoperatively. Glucose cally significant difference in concentrations between Preop and End
(mmol.1-I) is plotted on the left axis, FFA 0 (rnmol.l-') and 3- of surgery (Wilcoxon's signed rank test).
OHB A (mmol . I - ' ) are plotted on the right axis.
operatively. These neonates showed only minor
changes in all measured parameters, except glucose.
ability of the neonate to respond to trauma and the Different fluid regimes may have contributed. In
endocrine and metabolic reactions to surgical trauma earlier reports only maintenance volumes of electro-
have recently been extensively studied (13, 14). Con- lyte-free glucose were used during surgery, with insuf-
siderably elevated levels of noradrenaline, adrenaline ficient peripheral circulation as a possible consequence.
and also of glucose, lactate, pyruvate, glycerol and Different anaesthesic practice in providing analgesia
ketone bodies have been documented immediately during operation may also be an important factor. All
after surgery in infants and neonates (13). All infants our patients were given up to 10 pg kg-' of fentanyl.
in these studies received a glucose infusion during I n the first of the cited studies the analgesic agents were
surgery. They could therefore be compared to the limited to nitrous oxide in oxygen and low inspired
group in our study receiving glucose pre- and intra- fractions of halothane (13). In the second study it was
shown that fentanyl almost eliminated the metabolic
reactions seen in the control group, which was only
Glucose FFA
given nitrous oxide as analgesia (14).
rnrno1.i' 3-OHB
6- mmot.C'
FFA
Glucose 3-OHB
5- 2.0
mrno1.i' mmol.I -'
4-

3-
1.6

1.2
1- 2.0
1.5

2- 0.8 - 1.0
1- 0.4
- 0.5
0
L 0
Preop 30 min 60 min End 4h 8h 0
Preop 30 rnin 60 min 90 min End 4 h
Fig. 2. Mean concentrations of glucose, FFA and 3-OHB in starved
neonates without fluid preoperatively and Ringer acetate intraopera- Fig. 4. One patient with glucose preoperatively and Ringer-acetate
tively ( n = 6 ) ; preop, at 30, 60 min, at the end of anaesthesia and 4 intraoperatively. Concentrations preop, at 30, 60, 90 min, at the end
and 8 h postoperatively. Glucose H (mmol . I-') is plotted on the left of anaesthesia and 4 h postoperatively. Glucose H (mrnol ' 1 - I ) is
axis, FFA 0 (mmol.l-') and 3-OHB A (mmol.1-I) are plotted on plotted on the left axis, FFA 0 (mmol.l-'), 3-OHB A (mmol.1-I)
the right axis. are plotted on the right axis.
174 K. SANDSTROM ET AL.

During surgery, slightly higher concentrations of lac- intraoperatively. As a consequence of this, the fat util-
tate and pyruvate were seen in the group given glucose ization and gluconeogenesis were both low. In starved
intraoperatively compared to the group given only neonates given only Ringer-acetate during surgery,
Ringer-acetate. The difference did not reach signifi- equally rising blood glucose concentrations were also
cant levels. Similarly alanine and glycerol concen- found. The most probable explanation is an adequate
trations tended to be higher in the surgical period gluconeogenesis. Simultaneously, these neonates
in the starved neonates compared to the non-starved showed a substantial release and utilization of fat. In
neonates. Glycogen mainly from the liver might pro- conclusion, it appears that the starved neonates
vide the maintained blood glucose concentrations dur- adapted to and could cope with a glucose-free peri-
ing surgery in the starved neonates. Gluconeogenesis operative fluid therapy and that the neonates given
from alanine and glycerol might also contribute to the peroperative glucose could handle the amount of glu-
maintained blood glucose concentrations. cose given in this study. Interruption of a running
High levels of 3-hydroxybutyrate before and during glucose infusion is unfavourable.
surgery were found in neonates without glucose supply.
Free fatty acids were also higher before surgery in the
starved neonates and during surgery concentrations ACKNOWLEDGEMENTS
rose. This indicates a higher fat utilization in these This study was supported by grants from The Goteborg Medical
neonates. A rapid transition of metabolism from glu- Society.
cose to fat as the main source of energy occurs in
normal neonates after birth (15). Rising concentrations
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