Pediatric Anesthesia ISSN 1155-5645

SPECIAL INTEREST ARTICLE

Perioperative intravenous fluid therapy in children:

guidelines from the Association of the Scientific Medical
Societies in Germany
€ mpelmann1, Karin Becke2, Sebastian Brenner3, Christian Breschan4, Christoph Eich5,
Robert Su
€ hne6, Martin Jo
Claudia Ho € hr7, Franz-Josef Kretz8, Gernot Marx9, Lars Pape10, Markus Schreiber11,
Jochen Strauss & Markus Weiss13
12

1 Clinic for Anaesthesiology and Intensive Care Medicine, Hanover Medical School, Hanover, Germany
2 Department of Anaesthesiology and Intensive Care Medicine, Cnopf0 sche Kinderklinik/Klinik Hallerwiese, Nuremberg, Germany
3 Department of Pediatric and Adolescent Medicine, University Hospital Dresden, Dresden, Germany
4 Department of Anesthesia, Klinikum Klagenfurt, Klagenfurt, Austria
5 Department of Anaesthesia, Paediatric Intensive Care and Emergency Medicine, Auf der Bult Children0 s Hospital, Hanover, Germany
6 Department of Anesthesiology and Intensive Care Medicine, University Hospital of Leipzig, Leipzig, Germany
7 Section of Paediatric Anaesthesia, Department of Anaesthesia, Kantonsspital, Luzern, Switzerland
8 Department of Anaesthesiology and Intensive Care Medicine, Klinikum Stuttgart, Olgahospital, Stuttgart, Germany
9 Department of Intensive and Intermediate Care Medicine, University Hospital of RWTH Aachen, Aachen, Germany
10 Department of Pediatric Kidney, Liver and Metabolic Diseases, Hanover Medical School, Hanover, Germany
11 Department of Anesthesiology, Ulm University Medical Center, Ulm, Germany
12 Clinic for Anesthesiology, Perioperative Medicine and Pain Therapy, HELIOS Klinikum Berlin Buch, Berlin, Germany
13 Department of Anesthesia, University Children’s Hospital Zurich, Zurich, Switzerland

Keywords Summary
fluids, salt solutions; fluids, colloids; salt
solutions; fluids, child; age, infant; age, This consensus- based S1 Guideline for perioperative infusion therapy in chil-
neonate; age dren is focused on safety and efficacy. The objective is to maintain or re-
establish the child’s normal physiological state (normovolemia, normal tissue
Correspondence perfusion, normal metabolic function, normal acid- base- electrolyte status).
€mpelmann, Clinic for
Prof. Dr. Robert Su
Therefore, the perioperative fasting times should be as short as possible to
Anaesthesiology and Intensive Care
prevent patient discomfort, dehydration, and ketoacidosis. A physiologically
Medicine, Hanover Medical School, Carl-
Neuberg-Strasse 1, D-30625 Hanover, composed balanced isotonic electrolyte solution (BS) with 1–2.5% glucose is
Germany recommended for the intraoperative background infusion to maintain normal
Email: suempelmann.robert@mh-hannover. glucose concentrations and to avoid hyponatremia, hyperchloremia, and lipo-
de lysis. Additional BS without glucose can be used in patients with circulatory
instability until the desired effect is achieved. The additional use of colloids
Section Editor: Francis Veyckemans
(albumin, gelatin, hydroxyethyl starch) is recommended to recover normovo-
lemia and to avoid fluid overload when crystalloids alone are not sufficient
Accepted 14 August 2016
and blood products are not indicated. Monitoring should be extended in
doi:10.1111/pan.13007 cases with major surgery, and autotransfusion maneuvers should be per-
formed to assess fluid responsiveness.

Rationale for the selection of the subject matter of
the guideline
Pediatric anesthesia almost always includes periopera-
tive intravenous fluid therapy. Errors may result in com-
plications and negative outcomes. Therefore, in 2006,
the Scientific Working Group for Paediatric Anaesthesia
(WAKKA) of the German Society for Anaesthesiology
and Intensive Care Medicine (DGAI) published guide-
line recommendations for perioperative intravenous
fluid therapy in neonates, infants, and toddlers (1),
which have now been updated and revised in line with
the rules set forth by the Association of the Scientific
Medical Societies in Germany (AWMF).
Guideline objective
The purpose of the S1 Guideline is to contribute to ensur-
ing simple, effective, and safe perioperative intravenous
fluid therapy in children. The existing recommendations

10 © 2016 John Wiley & Sons Ltd

Pediatric Anesthesia 27 (2017) 10–18
 €mpelmann et al.
Su Perioperative intravenous fluid therapy in children

from 2006 were reviewed and updated, taking into
account recent developments. The formal outline as well
as content of the S1 Guideline were structured such that
it provides users with recommendations that are as clear
and simple as possible and furthermore acceptable from
the children’s perspective. The implementation of the S1
Guideline was intended to result in more favorable peri-
operative outcomes in children and a reduced risk of
infusion-related complications. This S1 Guideline should
be updated again at a later point in time, and reviewed as
to whether a S2 or S3 Guideline should be compiled.
Members of the panel compiling the guideline
The panel comprised 12 members with a background in
pediatric anesthesiology and pediatrics as well as clinical
and scientific expertise in the subject matter of the
planned S1 Guideline and the methodology of guidelines
and evidence-based medicine.
How a consensus was reached
A representative panel of experts compiled a guideline in
informal consensus development; the guideline was sub-
sequently reviewed and approved by the DGAI’s Execu-
tive Committee.
Handling of conflicts of interest
Possible conflicts of interest were declared in writing,
using a form sheet detailing tangible and intangible
interests. A complete list of updated conflicts of interest
statements from all participants is provided in the guide-
line report (http://www.awmf.org/leitlinien/detail/ll/001-
032.html). The guideline was compiled without any exter-
nal funding. There were no major disagreements in the
consensus process or the review by the DGAI.
controlled. Usually, an intraoperative background infu-
sion is given to meet perioperative maintenance require-
ments. If required, fluid therapy with crystalloids to
maintain normal ECFV and volume therapy with col-
loids to maintain normal BV can be given in addition.
To maintain normal metabolic function, the back-
ground infusion may also contain glucose.
Consensus-based fundamental statement
The objective of intraoperative infusion therapy is to
maintain or re-establish the child’s normal physiological
state (normovolemia, normal tissue perfusion, normal
metabolic function, normal electrolytes, and acid–base
status).
What has changed since the German guideline
recommendation from 2006?
Balanced isotonic electrolyte solutions with 1% glucose
were approved for general sale in 2009 in Germany and
need no longer be mixed on-site. A decentralized Euro-
pean authorization procedure was finalized in 2016 and
a similar solution will be available in many European
countries in near future. Balanced isotonic electrolyte
solutions, which mimic the composition of ECF more
closely, have replaced Ringer’s lactate and normal saline
solutions in most cases (Table 1). Clinical studies in crit-
ically ill adult patients have resulted in a great deal of
uncertainty regarding perioperative use of artificial col-
loids in children. There is more and more evidence sug-
gesting that liberal transfusion of blood products may
Table 1 Composition of extracellular fluid (ECF) and various elec-
trolyte solutions for perioperative intravenous fluid therapy in children
(in mmolL1)
ECF NaCla Ringer RLb BS-G1c

Cations
Introduction
Na+ 142 154 147 130 140
As compared to adults, small children have a larger K+ 4.5 – 4 5 4
extracellular fluid volume (ECFV), larger blood volume Ca2+ 2.5 – 2.3 1 2
Mg2+ 1.25 – – 1 2
(BV), higher metabolic rate, and higher fluid turnover
Anions
rate relative to their body weight. The objective of intra-
Cl 103 154 156 112 118
operative infusion therapy is to maintain the normal HCO3 24 – – – –
physiological state in children (normal ECFV, normal Acetate – – – – 30
BV, normal tissue perfusion, normal metabolic function, Lactate 1.5 – – 27 –
normal electrolytes, and acid–base status). Instances Glucose 2.78–5 – – – 55.5
where a loss of volume was underestimated are the most Theoretical osmolarityd 291 308 309 276 296
common cause of perioperative cardiac arrests in chil- a
Normal saline.
dren (2). Larger volume turnovers should therefore be b
Ringer’s lactate.
carefully anticipated and be managed by planning ahead c
Balanced electrolyte solution with 1% glucose.
so that the child’s condition remains stable and d
Σ (cations+anions).

© 2016 John Wiley & Sons Ltd 11

Pediatric Anesthesia 27 (2017) 10–18
Perioperative intravenous fluid therapy in children
increase morbidity in children (3,4). Use of blood pro-
ducts should therefore be reduced by preoperative opti-
mization, use of blood conservation techniques during
surgery and a restrictive approach to transfusion.
What is the role of preoperative fasting times?
Various studies (5–7) have shown that the currently re-
commended fasting rules for children (6 h for solid
foods, 4–6 h for infant formula, 4 h for breast milk, 2 h
for clear fluids (8,9)) are significantly exceeded in many
cases. In particular in small children, this may result in
patient discomfort, lack of cooperation, dehydration,
and a drop in blood pressure when anesthesia is
induced. If relevant glucose deficiency develops, break-
down of lipids and production of ketone bodies
increases, resulting in a decrease in bicarbonate concen-
tration and base excess (BE; ketoacidosis) (10–12). A
Cochrane meta-analysis found that children fasting for
more than 6 h did not benefit in terms of gastric fluid
volume or pH level, whereas the well-being of children
who were allowed to drink clear fluids up to 2 h before
induction of anesthesia was significantly better (13). The
volume of the clear fluid ingested did not affect gastric
fluid volume or pH level. Another clinical study showed
that postoperative well-being was also improved if the
children were allowed to eat and drink ad libitum,
whereas there was no difference in the incidence of post-
operative nausea and vomiting as compared to a fasting
group (14).
It is generally not beneficial to cause iatrogenic
dehydration, ketoacidosis, or reduced well-being by
excessively long-fasting times, only for those iatrogenic
conditions then to be resolved by differentiated periop-
erative intravenous fluid therapy. From the children’s
perspective, it is also more beneficial to keep preopera-
tive and postoperative fasting times as short as possible
in compliance with current guidelines, and to actively
encourage the children to drink clear fluids up to 2 h
before induction of anesthesia. In many children beyond
neonatal age who undergo very short procedures and
drink sufficient volumes, this might even render periop-
erative intravenous fluid therapy unnecessary. In various
pediatric departments and clinical studies, the clear fluid
used is (diluted) apple juice (10,11), which is usually
liked well by children and contains more carbohydrates
and electrolytes than water or tea. Fizzy drinks are gen-
erally not that great a choice as they contain too much
sugar and no electrolytes.
Consensus-based recommendations: Perioperative fast-
ing times for children should be as short as possible to
prevent patient discomfort, dehydration, and ketoacido-
sis. If preoperative and postoperative fasting times are
12
€mpelmann et al.
Su
short, perioperative intravenous fluid therapy should
not necessarily be performed in children beyond neona-
tal age who drink sufficient volumes and undergo short
procedures (<1 h) with a venous access in place.
Which solution for infusion should be used for the
intraoperative background infusion in children?
The purpose of the background infusion is to meet nor-
mal fluid and glucose requirements over the course of
the perioperative fasting time during which the children
are not allowed to drink. A ‘European consensus state-
ment for intraoperative fluid therapy in children’ from
2011 stated that solutions for the intraoperative back-
ground infusion in children should have an osmolarity
and sodium concentration as close to the physiologic
range as possible, should contain 1–2.5% glucose and
should also include metabolic anions (e.g., acetate, lac-
tate, or malate) (15).
As compared to the previously used hypotonic solu-
tions for infusion with 5% glucose (16), use of isotonic
solutions for infusion results in a lower risk of hypona-
tremia with possible encephalopathy, cerebral edema,
and respiratory insufficiency (17–26), and the lower glu-
cose concentration of 1–2.5% results in a lower risk of
intraoperative hyperglycemia (27–32). In particular, in
the perioperative setting, children are at risk of hypona-
tremia and cerebral edema, as they have a smaller
intracranial volume, and the increasing levels of the
antidiuretic hormone (ADH) when the body is subject
to stress inhibit the excretion of free water (21,23). Neo-
nates also have a higher risk of hyponatremia if hypo-
tonic solutions for infusion are used intraoperatively
(33). As compared to normal saline, hyperchloremic aci-
dosis occur more rarely if solutions for infusion with a
lower chloride concentration and acetate as bicarbonate
precursor are used (34,35). Two observational studies
demonstrated that intraoperative infusion of a balanced
isotonic electrolyte solution with 1% glucose with an
average infusion rate of 10 mlkg1h1 in neonates and
preschool children aged up to 4 years resulted in stable
circulatory conditions, sodium and glucose levels, and
acid–base status (36,37). An average intraoperative
background infusion rate of 10 mlkg1h1 is higher
than the maintenance rate calculated as per the 4-2-1
rule, which is justified given that fasting-related preoper-
ative and postoperative fluid deficits should be taken
into account from a pragmatic point of view. A clinical
study on children with tonsillectomy found that nausea
and vomiting occurred more rarely when
30 mlkg1h1 instead of 10 mlkg1h1 of fluid was
administered intraoperatively (38). In case of longer
surgeries and in particular in children with relevant fluid
© 2016 John Wiley & Sons Ltd
Pediatric Anesthesia 27 (2017) 10–18
 €mpelmann et al.
Su
deficit or excess, however, the background infusion rate
should be adjusted to the actual requirement if possible.
Perioperative glucose requirements may also vary
strongly. In case of children at risk (e.g., neonates and
premature infants, children with metabolic disorders)
and longer procedures, blood glucose levels should
therefore be measured regularly and glucose administra-
tion be adjusted to ensure normoglycemia. If blood glu-
cose concentrations intraoperatively increase within the
normal range or remain stable at the upper end of the
normal range, this can be regarded as a sign that suffi-
cient substrate is available. Perioperative glucose defi-
ciency in most cases results in a catabolic reaction with
glucose concentrations at the lower end of the normal
range, release of ketone bodies, and/or free fatty acids,
as well as decrease in BE (ketoacidosis) (10,29,31).
In children who are admitted to the operating theater
in a catabolic state (e.g., after long-fasting times) or who
have high metabolic rates or low glycogen reserves for
developmental reasons or due to disease (e.g., premature
infants, small neonates, parenteral nutrition, liver dis-
ease), a glucose concentration of 1% in the background
infusion may be too low (39). In these cases, the infusion
rate or glucose concentration of the background infu-
sion should be increased (6 ml glucose 40% in 250 ml
solution for infusion increase glucose concentration by
1%), or a glucose solution with a higher concentration
should be additionally given using an infusion or syringe
pump or, in case of hypoglycemia, as a bolus (e.g.,
200 mgkg1). Special care must be taken when adminis-
tering electrolyte-free glucose solutions with a higher
concentration; never may they flow freely as accidental
over-infusions may result in deleterious incidents (e.g.,
hyperosmolar hyperglycemic coma (40)). Many pedi-
atric anesthetists use a balanced isotonic electrolyte
solution with 1–2.5% glucose for the background infu-
sion in children up to school age. However, for shorter
surgeries (<1 h) without relevant tissue trauma (e.g.,
inguinal herniotomy, circumcision), a background infu-
sion containing glucose is not necessarily required in
children beyond neonatal age with short preoperative
fasting times if the children are allowed to drink and eat
again soon after the surgery (1,41).
Consensus-based recommendations: A balanced iso-
tonic electrolyte solution with 1–2.5% glucose should be
used for the background infusion. The background infu-
sion may be initiated with an initial infusion rate of
10 mlkg1h1 and be adjusted to the actual require-
ment during the further course (target: normal ECFV).
In case of children at risk and longer surgeries, blood
sugar levels should be measured regularly and glucose
administration should be adjusted (target: normo-
glycemia and stable acid–base status).
© 2016 John Wiley & Sons Ltd
Pediatric Anesthesia 27 (2017) 10–18
Perioperative intravenous fluid therapy in children
Which solutions for infusion should be used for
perioperative fluid therapy in children?
The purpose of perioperative fluid therapy is to replace
additional fluid deficits in order to maintain normal
ECFV. Small children have a larger ECFV than adults
(e.g., premature infants 60%, neonates 40%, infants
30%, adults 20% of body weight), but the composition
of the ECF is similar across all age groups. Therefore,
the same solutions for infusion as for adults can be used
for intraoperative fluid therapy in children. As com-
pared to ECF, conventional Ringer’s lactate solution is
somewhat hypotonic (276 instead of 308 mOsmolL1),
while isotonic sodium chloride solution contains too
much chloride (154 instead of 95–106 mmolL1,
Table 1). Therefore, infusion of large volumes may
reduce osmolarity or result in hyperchloremic acidosis.
In case of infusion of small volumes, these changes are,
however, usually compensated by the children. Balanced
isotonic electrolyte solutions mimic the composition of
ECF more closely. In a direct comparison, they are
therefore closer to the physiological range of children,
too, and also have fewer undesirable effects on osmolar-
ity and acid–base electrolytes balance (Table 1). In case
of preexisting imbalances, balanced isotonic electrolyte
solutions shift the status more toward the normal range.
These properties provide additional safety in case of
infusion of large volumes (32,41–43). In compliance with
the German S3 Guideline on Volume Therapy (44), bal-
anced isotonic electrolyte solutions can therefore also be
recommended for perioperative fluid therapy in chil-
dren. By way of exception, isotonic saline can be used
for chloride replacement in children experiencing vomit-
ing and severe hypochloremic alkalosis (e.g., pyloric
stenosis, gastroenteritis).
A perioperative fluid deficit may be caused by insuffi-
cient supply (e.g., long-fasting time: deficit equivalent to
fasting time multiplied by maintenance requirement as per
4-2-1 rule) or increased losses (e.g., gastroenteritis, ileus,
bleeding). A fluid deficit that developed slowly can best be
deduced from the disease-induced weight loss (weight
loss = fluid loss). If no precise weight from before the
onset of the disease is known, an estimate for the degree
of dehydration can also be based on clinical criteria (1%
dehydration equivalent to 10 mlkg1 fluid loss).
In patients with circulatory instability, the highest pri-
ority is to quickly restore the circulating BV. For that
purpose, balanced electrolyte solutions can be given as
repeat-dose infusions of 10–20 mlkg1 until the desired
effect is achieved (maximum volume, e.g., three times
10–20 mlkg1 to avoid interstitial fluid overload).
Whenever possible, preoperative deficits should be
replaced before anesthesia is induced.
13
Perioperative intravenous fluid therapy in children
Consensus-based recommendations: A balanced iso-
tonic electrolyte solution should be used for fluid ther-
apy (target normal ECFV). Preoperative deficits should
whenever possible already be replaced before anesthesia
is induced. In patients with circulatory instability,
balanced isotonic electrolyte solutions without added
glucose can be given as repeat-dose infusions of
10–20 mlkg1 until the desired effect is achieved.
Which solutions for infusion should be used for
perioperative volume therapy in children?
The purpose of perioperative volume therapy is to
quickly normalize BV, e.g., in case of circulatory insta-
bility or loss of blood. A normal BV is the most impor-
tant prerequisite for adequate venous return, which in
turn is an important prerequisite for adequate cardiac
output and sufficient tissue perfusion. A decrease in BV
initially shifts interstitial fluid toward the intravascular
space, stabilizing BV and reducing interstitial fluid
volume (45). Therefore, the first step to stabilize the cir-
culatory system should be liberal infusion of balanced
isotonic electrolyte solutions to maintain normal ECFV
and BV. In case of a large turnover of volume, however,
monotherapy with crystalloids necessarily results in an
interstitial fluid overload with hemodilution, which may
decrease oxygen supply and delay postoperative recov-
ery (46–48). In order to avoid this situation, colloids are
often used during major surgeries as the second step to
stabilize the BV more effectively and prevent interstitial
fluid overload, in particular when restrictive use of blood
products is desired (49,50). While artificial colloids are,
as compared to balanced isotonic electrolyte solutions,
more effective with view to volume, they are also associ-
ated with an increased risk of adverse reactions (e.g.,
allergy, impairment of hemostasis, and renal function).
Various clinical studies have shown that renal failure
in adult intensive care patients with sepsis occurred more
frequently after infusion of hydroxyethyl starch (HES)
(51–53). However, meta-analyses of studies on adult sur-
gical patients with HES found no adverse effects on
renal function (54,55). An observational study on
1130 surgical pediatric patients with HES also reported
no cases of HES-induced renal failure (56). According to
a recommendation by the European Medicines Agency
(EMA), HES can continue to be used to correct hypo-
volemia where treatment with crystalloids alone is not
considered to be sufficiently effective (57). On the other
hand, according to the German Medical Association’s
current guidelines for therapy with blood components
and plasma derivatives, alternative use of blood pro-
ducts only for volume therapy (e.g., not to correct ane-
mia or a coagulation problem) is not permissible (58). In
14
€mpelmann et al.
Su
compliance with the German S3 Guideline on Volume
Therapy (44) and the EMA recommendation (57), artifi-
cial colloids therefore can continue to be used for intra-
operative volume therapy in children with healthy
kidneys where treatment with crystalloids alone is not
sufficiently effective. A colloid overdose may cause
intravascular hypervolemia with a disturbance of the
vascular endothelial barrier function and dilutional
coagulopathy, and also has to be avoided (59,60).
Consensus-based statements: Colloids (albumin, gela-
tin [GEL], HES) are associated with more adverse drug
reactions than balanced electrolyte solutions. In children
with hypovolemia, colloids can be used intraoperatively
where crystalloids alone are not sufficiently effective and
blood products are not indicated. In order to avoid
hypervolemia, a restrictive approach to giving colloids
as infusions should be adopted (target normal BV).
For use in healthy children, there seem to be no signifi-
cant differences as regards clinical benefit–risk ratio
between the currently available artificial and natural col-
loids; at least, no clinical studies in children demonstra-
ting a preference with certainty are available to date. Use
of colloids in children also varies greatly from region to
region (49), which can be seen as a further sign suggesting
no great differences in clinical efficacy. As compared to
natural colloids (albumin or plasma protein solution),
artificial colloids (HES and GEL) are much more cost-
efficient and readily available without restrictions. Fur-
thermore, they are not subject to batch documentation
requirements. Assuming similar efficacy, the lower costs,
better availability, and less stringent documentation
requirements are arguments in favor of using artificial
colloids. As compared to HES, GEL triggers allergic
reactions more frequently in adults (61,62). At present, it
is, however, unclear whether this is also the case with
children as no large studies investigating use of GEL in
children beyond neonatal age are available yet. However,
a large multicentre study investigating use of GEL or fro-
zen plasma in neonates was conducted; this study showed
no difference in morbidity and mortality as compared to
a control group (63,64). GEL and HES may affect blood
coagulation, depending on the dose. With moderate doses
(total dose 10–20 mlkg1), adverse effects are likely to be
rather mild, and no bleeding diathesis is to be expected
(56,65–69). When it comes to HES, third-generation
products with a molecular weight of 130 000 Da
(HES 130), which are associated with fewer adverse reac-
tions, should also be the preferred choice in children (70).
In three clinical studies investigating use of HES 130 in
pediatric patients requiring cardiac surgery, no increase
in blood loss or renal failure was observed even after high
HES doses (total dose > 20 mlkg1) (71–73). In an
© 2016 John Wiley & Sons Ltd
Pediatric Anesthesia 27 (2017) 10–18
 €mpelmann et al.
Su Perioperative intravenous fluid therapy in children

observational study investigating use of HES 130 in 1130 clinical examinations (e.g., capillary refill time [sternum,
children, adverse events were found more rarely in cases forehead], skin turgor, fontanels). Intraoperative basic
where a moderate total dose (10–20 mlkg1) was given monitoring (pulse oximetry, capnography, blood pres-
than in cases where a high total dose (>20 mlkg1) was sure, ECG, body temperature) is sufficient for minor
given. No serious adverse drug reactions were observed procedures in children in normal hydration state. If
(56). In compliance with the German S3 Guideline on there is any doubt, (peripheral venous or capillary)
Volume Therapy (44), it is recommended to also use col- blood gas analyses (BGAs) may be performed to assess
loids in balanced solutions for children, as the acid–base the acid–base status (BE, lactate) and blood glucose
status is affected less by them (74). levels. Unfortunately, in children, cardiac output,
Consensus-based recommendations: In patients with ECFV, and BV cannot be measured directly using sim-
hypovolemia or circulatory instability, colloids (albu- ple means, and a blood pressure within (or near the
min, GEL, HES 130) can be given as repeat-dose infu- lower end of) the normal range does not guarantee suffi-
sions of 5–10 mlkg1 until the desired effect is cient cardiac output (75). In case of major procedures
achieved. GEL or HES 130 should be used in balanced with larger volume turnovers, it is therefore recom-
solutions. If HES is used, third-generation products mended to extend the monitoring (e.g., arterial and cen-
(HES 130), which are associated with fewer adverse tral venous catheters, serial BGAs) so that is easier to
reactions, should be the preferred choice. If possible, a assess the efficacy of the intraoperative infusion therapy.
moderate total dose (10–20 mlkg1) of HES 130 should In order to assess the fluid responsiveness, the position-
be given, and it should be used for an as short period of ing maneuver facilitating autotransfusion (Trendelen-
time as possible. The daily maximum dose (50 mlkg1) burg position, passive leg raising) proposed in the
should never be exceeded. German S3 Guideline on Volume Therapy (44) is unfor-
tunately not suitable for small children as the differences
in height produced by repositioning the body are insuffi-
How should perioperative intravenous fluid
cient. For a rough guide, fluid responsiveness may in
therapy in children be monitored?
these cases be evaluated by applying calculated external
The hydration state can be assessed rather well by pressure to the liver, causing BV to shift from the
enquiring about the actual fasting time and simple intraabdominal to the intrathoracic space. If there is
fluid responsiveness, the invasively measured blood pres-
Table 2 Perioperative intravenous fluid therapy in children (rule of 10s) sure and/or the endtidal CO2 in the capnography will
Solution for infusion Initial/repeated dose
increase (increase in pulmonary blood flow at constant
ventilation leads to a short-term increase in endtidal
Background infusion BS-Ga 10 mlkg1h1 CO2 (76,77)). Further parameters that can be used to
Fluid therapy BSb 910–20 mlkg1 assess fluid responsiveness are blood pressure curve vari-
Volume therapy Albumin, gelatin, HESc 95–10 mlkg1
ations over the breathing cycle (systolic blood pressure
Transfusion RBCd, FFPe, PTf 910 mlkg1
variation, pulse pressure variation), the perfusion index,
a
Balanced isotonic electrolyte solution with 1–2% glucose. or pleth variability index calculated based on pulse
b
Balanced isotonic electrolyte solution. oximetry and an echocardiographic measurement of
c
Hydroxyethyl starch. stroke volume or blood flow velocity (78–80). Due to
d
Red blood cells.
e catheter-related risks, pulmonary arterial or transpul-
Fresh frozen plasma.
f
Platelets.
monary thermodilution catheters are not routinely used

Table 3 Proposal for perioperative intravenous fluid therapy in children

Preoperative Keep fasting times short (clear fluids up to 2 h preoperatively)

Minor procedures Background infusion 10 mlkg1h1 BS-Ga
Intermediate procedures Adjust background infusion to actual requirements during the course of the procedure
Plus: BSb if additional fluid is required
Plus: colloidsc if additional BS is not sufficiently effective
Major procedures Same as intermediate procedures,
Plus: blood products in case of critical hemodilution
Postoperative Allow children to eat and drink soon after the procedure
a
Balanced isotonic electrolyte solution with 1–2% glucose.
b
Balanced isotonic electrolyte solution.
C
For example, albumin, gelatin, and hydroxyethyl starch.

© 2016 John Wiley & Sons Ltd 15

Pediatric Anesthesia 27 (2017) 10–18
Perioperative intravenous fluid therapy in children €mpelmann et al.
Su

in small infants. Pulse contour analysis has not been val-
idated in small children. Central venous pressure also
does not correlate with circulating BV or fluid respon-
siveness (79,81). In case of major surgeries, regular
BGAs should be performed at the start (baseline level)
and then in e.g., hourly intervals; central venous oxygen
saturation (ScvO2) over time can be used as fast and BE
and lactate concentration as slow indirect parameters
for tissue perfusion. When analyzing the BGAs, it is par-
ticularly important to note changes over time so that, in
case of a negative trend, countermeasures can be taken
before pathological levels are reached. Urinary excretion
usually decreases intraoperatively due to, for instance,
stress-related increase in ADH levels and/or a decrease
in renal perfusion (e.g., in case of procedures with pneu-
moperitoneum and increased intraabdominal pressure)
and is therefore not a valid parameter on which to base
intraoperative infusion therapy (82). In general, individ-
ual parameters on which the infusion therapy is based
should not be assessed in isolation, but rather under
consideration of the overall clinical constellation and
the other monitoring parameters.
Consensus-based recommendations: The hydration
state should be evaluated by way of a clinical examination
of the children (e.g., central capillary refill time, skin tur-
gor, fontanels). In order to assess fluid responsiveness, an
autotransfusion maneuver (e.g., pressure on liver, passive
leg raising) should be performed. In case of surgeries with
larger volume turnovers, monitoring should be extended
(e.g., arterial and central venous catheters). In case of
major surgeries, regular BGAs should be performed, and
in case of negative trends (ScvO2↓, BE↓, lactate↑), coun-
termeasures should be taken early.
Recommendations for clinical practice
In neonates and infants, a syringe pump or infusion
pump should be used for perioperative intravenous
fluid therapy in order to avoid accidental over-infu-
sions. The pumps should have a pressure limit. For
toddlers, gravity infusions with 250 ml containers are
also possible for short procedures. For premature
infants and neonates, it is generally recommended to
intraoperatively replace at least the deficit caused by
the preoperative fasting and the maintenance require-
ment with a balanced isotonic electrolyte solution with
1–2.5% added glucose. Additional solutions for infu-
sion for fluid and volume therapy can in neonates and
infants be given using perfusor syringes (20 ml or
50 ml) and, in case of older children, also as free-flow-
ing infusion. In order to avoid accidental over-infu-
sions, the superfluous amount can be removed from the
infusion container and be discarded. For pressure infu-
sions, compressible infusion containers (e.g., bags)
should always be used to prevent air embolisms. For
the initial dose, the ‘rule of 10s’, which is easy to imple-
ment, is a tried-and-true approach (Table 2). Over
time, infusion therapy should then be based on the chil-
dren’s actual requirements, determined by monitoring
that is adjusted as required (Table 3). The children
should be allowed to drink and eat again soon after the
surgery unless there are any other reasons against it (8).
Consensus-based recommendations: In neonates and
infants, a syringe pump or infusion pump should be
used for perioperative intravenous fluid therapy. In tod-
dlers, gravity infusions with 250 ml containers are also
possible. For pressure infusions, compressible infusion
containers (e.g., bags) should always be used.
Ethics approval
No ethics approval required.
Funding
The study received no external funding.
Conflict of interest
A complete list of updated conflicts of interest statements
from all participants is provided in the guideline report
(http://www.awmf.org/leitlinien/detail/ll/001-032.html).

References
1 S€umpelmann R, Hollnberger H, Schmidt J
et al. Recommendations for perioperative iv
fluid management in neonates, infants and tod-
dlers. An€
asth Intensivmed 2006; 47: 616–619.
2 Bhananker SM, Ramamoorthy C, Gei-
duschek JM et al. Anesthesia-related cardiac
arrest in children: update from the Pediatric
Perioperative Cardiac Arrest Registry.
Anesth Analg 2007; 105: 344–350.
3 Parker RI. Transfusion in critically ill chil-
dren: indications, risks, and challenges. Crit
Care Med 2014; 42: 675–690.
4 Crowley M, Kirpalani H. A rational
approach to red blood cell transfusion in the
neonatal ICU. Curr Opin Pediatr 2010; 22:
151–157.
5 Engelhardt T, Wilson G, Horne L et al. Are
you hungry? Are you thirsty? – fasting times
in elective outpatient pediatric patients. Pedi-
atr Anesth 2011; 21: 964–968.
6 Cantellow S, Lightfoot J, Bould H et al. Par-
ents’ understanding of and compliance with
fasting instruction for pediatric day case sur-
gery. Pediatr Anesth 2012; 22: 897–900.
7 Williams C, Johnson PA, Guzzetta CE et al.
Pediatric fasting times before surgical and
radiologic procedures: benchmarking

16 © 2016 John Wiley & Sons Ltd

Pediatric Anesthesia 27 (2017) 10–18
 €mpelmann et al.
Su
institutional practices against national stan-
dards. J Pediatr Nurs 2014; 29: 258–267.
8 Smith I, Kranke P, Murat I et al. Periopera-
tive fasting in adults and children: guidelines
from the European Society of Anaesthesiol-
ogy. Eur J Anaesthesiol 2011; 28: 556–569.
9 Becke K, Giest J, Strauß JM. [Recommenda-
tions for preoperative diagnostics, vaccina-
tions and fasting times in children]. An€asth
Intensivmed 2007; 48: S62–S66.
10 Maekawa N, Mikawa K, Yaku H et al.
Effects of 2-, 4- and 12-hour fasting intervals
on preoperative gastric fluid pH and volume,
and plasma glucose and lipid homeostasis in
children. Acta Anaesthesiol Scand 1993; 37:
783–787.
11 Castillo-Zamora C, Castillo-Peralta LA,
Nava-Ocampo AA. Randomized trial com-
paring overnight preoperative fasting period
vs oral administration of apple juice at 06:00-
06:30 am in pediatric orthopedic surgical
patients. Pediatr Anesth 2005; 15: 638–642.
12 Friesen RH, Wurl JL, Friesen RM. Duration
of preoperative fast correlates with arterial
blood pressure response to halothane in
infants. Anesth Analg 2002; 95: 1572–1576.
13 Brady M, Kinn S, Ness V et al. Preoperative
fasting for preventing perioperative compli-
cations in children. Cochrane Database Syst
Rev 2009; CD005285.
14 Radke OC, Biedler A, Kolodzie K et al. The
effect of postoperative fasting on vomiting in
children and their assessment of pain. Pediatr
Anesth 2009; 19: 494–499.
15 S€umpelmann R, Becke K, Crean P et al.
European consensus statement for intraoper-
ative fluid therapy in children. Eur J Anaes-
thesiol 2011; 28: 637–639.
16 Holliday MA, Segar WE. The maintenance
need for water in parenteral fluid therapy.
Pediatrics 1957; 19: 823–832.
17 Fraser CL, Arieff AI. Epidemiology, patho-
physiology, and management of hyponatremic
encephalopathy. Am J Med 1997; 102: 67–77.
18 Duke T, Molyneux EM. Intravenous fluids
for seriously ill children: time to reconsider.
Lancet 2003; 362: 1320–1323.
19 Choong K, Kho ME, Menon K et al. Hypo-
tonic versus isotonic saline in hospitalised
children: a systematic review. Arch Dis Child
2006; 91: 828–835.
20 Wang J, Xu E, Xiao Y. Isotonic versus hypo-
tonic maintenance IV fluids in hospitalized
children: a meta-analysis. Pediatrics 2014;
133: 105–113.
21 Arieff AI. Postoperative hyponatraemic
encephalopathy following elective surgery in
children. Paediatr Anaesth 1998; 8: 1–4.
22 Arieff AI, Ayus JC, Fraser CL. Hypona-
traemia and death or permanent brain dam-
age in healthy children. BMJ 1992; 304:
1218–1222.
© 2016 John Wiley & Sons Ltd
Pediatric Anesthesia 27 (2017) 10–18
Perioperative intravenous fluid therapy in children
23 Ayus JC, Achinger SG, Arieff A. Brain cell
volume regulation in hyponatremia: role of
sex, age, vasopressin, and hypoxia. Am J
Physiol Renal Physiol 2008; 295: F619–F624.
24 Carcillo JA. Intravenous fluid choices in criti-
cally ill children. Curr Opin Crit Care 2014;
20: 396–401.
25 Available at: http://www.apagbi.org.uk/sites/
default/files/Perioperative_Fluid_Manage-
ment_2007.pdf. Accessed 23 July, 2014.
26 Najafi N, Veyckemans F, Berghmans J et al.
Belgian recommendations on perioperative
maintenance fluid management of surgical
pediatric population. Acta Anaesthesiol Belg
2012; 63: 101–109.
27 Dubois MC, Gouyet I, Murat I et al. Lac-
tated Ringer with 1% dextrose: an appropri-
ate solution for peri-operative fluid therapy
in children. Paed Anaesth 1992; 2: 99–104.
28 Berleur MP, Dahan A, Murat I et al. Periop-
erative infusions in paediatric patients: ratio-
nale for using Ringer-lactate solution with
low dextrose concentration. J Clin Pharm
Ther 2003; 28: 31–40.
29 Mikawa K, Maekawa N, Goto R et al.
Effects of exogenous intravenous glucose on
plasma glucose and lipid homeostasis in
anesthetized children. Anesthesiology 1991;
74: 1017–1022.
30 Welborn LG, Hannallah RS, McGill WA
et al. Glucose concentrations for routine
intravenous infusion in pediatric outpatient
surgery. Anesthesiology 1987; 67: 427–430.
31 Nishina K, Mikawa K, Maekawa N et al.
Effects of exogenous intravenous glucose on
plasma glucose and lipid homeostasis in
anesthetized infants. Anesthesiology 1995; 83:
258–263.
32 S€umpelmann R. On water, salt and more . . .
infusion therapy for neonates, infants and
children. Anaesthesist 2011; 60: 8–9.
33 Edjo Nkilly G, Michelet D, Hilly J et al.
Postoperative decrease in plasma sodium
concentration after infusion of hypotonic
intravenous solutions in neonatal surgery. Br
J Anaesth 2014; 112: 540–545.
34 Witt L, Osthaus WA, Bunte C et al. A novel
isotonic-balanced electrolyte solution with
1% glucose for perioperative fluid manage-
ment in children – an animal experimental
preauthorization study. Pediatr Anesth 2010;
20: 734–740.
35 Disma N, Mameli L, Pistorio A et al. A
novel balanced isotonic sodium solution vs
normal saline during major surgery in chil-
dren up to 36 months: a multicenter RCT.
Pediatr Anesth 2014; 24: 980–986.
36 S€umpelmann R, Mader T, Dennhardt N
et al. A novel isotonic balanced electrolyte
solution with 1% glucose for intraoperative
fluid therapy in neonates: results of a
prospective multicentre observational
postauthorisation safety study (PASS). Pedi-
atr Anesth 2011; 21: 1114–1118.
37 S€umpelmann R, Mader T, Eich C et al. A
novel isotonic-balanced electrolyte solution
with 1% glucose for intraoperative fluid ther-
apy in children: results of a prospective mul-
ticentre observational post-authorization
safety study (PASS). Pediatr Anesth 2010; 20:
977–981.
38 Elgueta MF, Echevarria GC, De la Fuente N
et al. Effect of intravenous fluid therapy on
postoperative vomiting in children undergo-
ing tonsillectomy. Br J Anaesth 2013; 110:
607–614.
39 Hochhold C, Luckner G, Strohmenger U
et al. Intra-operative hypoglycemia and elec-
trolyte imbalance in a child with Apert syn-
drome during craniosynostosis surgery.
Pediatr Anesth 2014; 24: 352–354.
40 Witt L, Osthaus WA, Lucke T et al. Safety
of glucose-containing solutions during acci-
dental hyperinfusion in piglets. Br J Anaesth
2010; 105: 635–639.
41 Strauss JM, S€ umpelmann R. Perioperative
fluid management in infants and toddlers.
Anasthesiol Intensivmed Notfallmed Sch-
merzther 2013; 48: 264–271.
42 Steurer MA, Berger TM. Infusion therapy
for neonates, infants and children. Anaesthe-
sist 2011; 60: 10–22.
43 Zander R. Requirements to be met by opti-
mal volume substitution. An€ asth Intensivmed
2009; 50: 348–357.
44 Marx G, Schindler AW, Mosch C et al.
Intravascular volume therapy in adults:
guidelines from the Association of the Scien-
tific Medical Societies in Germany. Eur J
Anaesthesiol 2016; 33: 488–521.
45 Hall J. Guyton and Hall Textbook of Medi-
cal Physiology. Philadelphia, PA: Saunders
Elsevier, 2011.
46 S€umpelmann R, Schurholz T, Marx G et al.
Haemodynamic, acid-base and electrolyte
changes during plasma replacement with
hydroxyethyl starch or crystalloid solution in
young pigs. Paediatr Anaesth 2000; 10: 173–179.
47 Arikan AA, Zappitelli M, Goldstein SL et al.
Fluid overload is associated with impaired
oxygenation and morbidity in critically ill
children. Pediatr Crit Care Med 2011; 13:
253–258.
48 Hassinger AB, Wald EL, Goodman DM.
Early postoperative fluid overload precedes
acute kidney injury and is associated with
higher morbidity in pediatric cardiac surgery
patients. Pediatr Crit Care Med 2014; 15:
131–138.
49 Soderlind M, Salvignol G, Izard P et al. Use
of albumin, blood transfusion and intraoper-
ative glucose by APA and ADARPEF mem-
bers: a postal survey. Paediatr Anaesth 2001;
11: 685–689.
17
Perioperative intravenous fluid therapy in children
50 Lacroix J, Hebert PC, Hutchison JS et al.
Transfusion strategies for patients in pedi-
atric intensive care units. N Engl J Med 2007;
356: 1609–1619.
51 Brunkhorst FM, Engel C, Bloos F et al.
Intensive insulin therapy and pentastarch
resuscitation in severe sepsis. N Engl J Med
2008; 358: 125–139.
52 Myburgh JA, Finfer S, Bellomo R et al.
Hydroxyethyl starch or saline for fluid resus-
citation in intensive care. N Engl J Med 2012;
367: 1901–1911.
53 Perner A, Haase N, Guttormsen AB et al.
Hydroxyethyl starch 130/0.42 versus Ringer’s
acetate in severe sepsis. N Engl J Med 2012;
367: 124–134.
54 Van Der Linden P, James M, Mythen M
et al. Safety of modern starches used during
surgery. Anesth Analg 2013; 116: 35–48.
55 Martin C, Jacob M, Vicaut E et al. Effect of
waxy maize-derived hydroxyethyl starch 130/
0.4 on renal function in surgical patients.
Anesthesiology 2013; 118: 387–394.
56 S€umpelmann R, Kretz FJ, Luntzer R et al.
Hydroxyethyl starch 130/0.42/6:1 for periop-
erative plasma volume replacement in 1130
children: results of an European prospective
multicenter observational postauthorization
safety study (PASS). Pediatr Anesth 2012; 22:
371–378.
57 EMA. Available at: http://www.ema.eu-
ropa.eu/docs/en_GB/document_library/
Referrals_document/Solutions_for_infu-
sion_containing_hydroxyethyl_starch/Euro-
pean_Commission_final_decision/
WC500162361.pdf. Accessed 23 July, 2014.
58 Bundes€arztekammer. Available at:http://
www.bundesaerztekammer.de/downloads/
Querschnittsleitlinie_Gesamtdokument-
deutsch_07032011.pdf. Accessed 23 July,
2014.
59 Chappell D, Jacob M, Becker BF et al.
[Expedition glycocalyx. A newly discovered
“Great Barrier Reef”]. Anaesthesist 2008; 57:
959–969.
60 Chappell D, Jacob M, Paul O et al. Impaired
glycocalyx barrier properties and increased
capillary tube haematocrit. J Physiol 2008;
586: 4585–4586.
61 Laxenaire MC, Charpentier C, Feldman L.
[Anaphylactoid reactions to colloid plasma
substitutes: incidence, risk factors, mechanisms.
18
A French multicenter prospective study]. Ann
Fr Anesth Reanim 1994; 13: 301–310.
62 Ring J, Messmer K. Incidence and severity of
anaphylactoid reactions to colloid volume
substitutes. Lancet 1977; 1: 466–469.
63 Northern Neonatal Nursing Initiative Trial
Group. Randomised trial of prophylactic
early fresh-frozen plasma or gelatin or glu-
cose in preterm babies: outcome at 2 years.
Lancet 1996; 348: 229–232.
64 Northern Neonatal Nursing Initiative Trial
Group. A randomized trial comparing the
effect of prophylactic intravenous fresh fro-
zen plasma, gelatin or glucose on early mor-
tality and morbidity in preterm babies. Eur J
Pediatr 1996; 155: 580–588.
65 Haas T, Preinreich A, Oswald E et al. Effects
of albumin 5% and artificial colloids on clot
formation in small infants. Anaesthesia 2007;
62: 1000–1007.
66 Osthaus WA, Witt L, Johanning K et al.
Equal effects of gelatin and hydroxyethyl
starch (6% HES 130/0.42) on modified
thrombelastography in children. Acta Anaes-
thesiol Scand 2009; 53: 305–310.
67 Witt L, Osthaus WA, Jahn W et al. Iso-
volaemic hemodilution with gelatin and
hydroxyethylstarch 130/0.42: effects on
hemostasis in piglets. Paediatric Anaesth
2012;22:379–385.
68 Mauch J, Madjdpour C, Kutter AP et al.
Effect of rapid fluid resuscitation using crys-
talloids or colloids on hemostasis in piglets.
Pediatr Anesth 2013; 23: 258–264.
69 Chong Sung K, Kum Suk P, Mi Ja Y et al.
Effects of intravascular volume therapy using
hydroxyethyl starch (130/0.4) on post-opera-
tive bleeding and transfusion requirements in
children undergoing cardiac surgery: a ran-
domized clinical trial. Acta Anaesthesiol
Scand 2006; 50: 108–111.
70 Westphal M, James MF, Kozek-Langen-
ecker S et al. Hydroxyethyl starches: differ-
ent products–different effects. Anesthesiology
2009; 111: 187–202.
71 Akkucuk FG, Kanbak M, Ayhan B et al.
The effect of HES (130/0.4) usage as the
priming solution on renal function in chil-
dren undergoing cardiac surgery. Ren Fail
2013; 35: 210–215.
72 Van der Linden P, De Ville A, Hofer A et al.
Six percent hydroxyethyl starch 130/0.4
€mpelmann et al.
Su
(Voluven(R)) versus 5% human serum albu-
min for volume replacement therapy during
elective open-heart surgery in pediatric
patients. Anesthesiology 2013; 119:
1296–1309.
73 Miao N, Yang J, Du Z et al. Comparison of
low molecular weight hydroxyethyl starch
and human albumin as priming solutions in
children undergoing cardiac surgery. Perfu-
sion 2014; 29: 462–468.
74 S€umpelmann R, Witt L, Brutt M et al.
Changes in acid-base, electrolyte and hemo-
globin concentrations during infusion of
hydroxyethyl starch 130/0.42/6: 1 in normal
saline or in balanced electrolyte solution in
children. Pediatr Anesth 2010; 20: 100–104.
75 Osthaus WA, Huber D, Beck C et al. Corre-
lation of oxygen delivery with central venous
oxygen saturation, mean arterial pressure
and heart rate in piglets. Pediatr Anesth 2006;
16: 944–947.
76 Lumb A. Nunn’s Applied Respiratory Physi-
ology. Edinburgh: Churchill Livingstone,
2010.
77 Monnet X, Bataille A, Magalhaes E et al.
End-tidal carbon dioxide is better than arte-
rial pressure for predicting volume respon-
siveness by the passive leg raising test.
Intensive Care Med 2013; 39: 93–100.
78 Durand P, Chevret L, Essouri S et al.
Respiratory variations in aortic blood flow
predict fluid responsiveness in ventilated
children. Intensive Care Med 2008; 34: 888–
894.
79 Renner J, Broch O, Gruenewald M et al.
Non-invasive prediction of fluid responsive-
ness in infants using pleth variability index.
Anaesthesia 2011; 66: 582–589.
80 Pereira de Souza Neto E, Grousson S, Duflo
F et al. Predicting fluid responsiveness in
mechanically ventilated children under gen-
eral anaesthesia using dynamic parameters
and transthoracic echocardiography. Br J
Anaesth 2011; 106: 856–864.
81 Byon HJ, Lim CW, Lee JH et al. Prediction
of fluid responsiveness in mechanically venti-
lated children undergoing neurosurgery. Br J
Anaesth 2013; 110: 586–591.
82 Gomez Dammeier BH, Karanik E, Gluer S
et al. Anuria during pneumoperitoneum in
infants and children: a prospective study. J
Pediatr Surg 2005; 40: 1454–1458.
© 2016 John Wiley & Sons Ltd
Pediatric Anesthesia 27 (2017) 10–18