Acta Anaesthesiol Scand 2009; 53: 843–851
Printed in Singapore. All rights reserved
‘Liberal’ vs. ‘restrictive’ perioperative fluid therapy – a
critical assessment of the evidence
M. BUNDGAARD-NIELSEN1,2, N. H. SECHER2 and H. KEHLET1
1
Section of Surgical Pathophysiology, and 2Department of Anaesthesia, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Background: Several studies have assessed the effect of a
‘liberal’ vs. a ‘restrictive’ perioperative fluid regimen on
post-operative outcome. The literature was reviewed in
order to provide recommendations regarding periopera-
tive fluid regimens.
Methods: A PubMed search identified randomized clinical
trials and cited studies, comparing two different fixed fluid
volumes on post-operative clinical outcome in major surgery.
Studies were assessed for the type of surgery, primary and
secondary outcome endpoints, the type and volume of admi-
nistered fluid and the definition of the perioperative period.
Also, information regarding perioperative care and type of
anaesthesia was assessed.
Results: In the seven randomized studies identified, the
range of the liberal intraoperative fluid regimen was from
2750 to 5388 ml compared with 998 to 2740 ml for the
restrictive fluid regimen. The period for fluid therapy
and outcome endpoints were inconsistently defined and
only two studies reported perioperative care principles
and discharge criteria. Three studies found an improved
outcome (morbidity/hospital stay) with a restrictive fluid
F LUID administration is an integrated part of care
for almost any surgical procedure and conse-
quently an everyday issue for most anaesthesiolo-
gists. Perioperative fluid therapy has received
increased interest in recent years because several
studies have demonstrated that the strategy for
fluid therapy may influence the post-operative
outcome.1–6 Obviously, hypovolaemia is recog-
nized as a risk factor leading to adverse effects
ranging from minor organ dysfunction to multi-
organ failure and even death. Conversely, liberal
administration of fluid may impair pulmonary,
cardiac and gastro-intestinal functions, contribut-
ing to post-operative complications and prolonged
recovery.1,4,6 Yet, with no established definition of
normovolaemia, it has been difficult to monitor
how much volume is required to ensure an optimal
r 2009 The Authors
Journal compilation r 2009 The Acta Anaesthesiologica Scandinavica Foundation
ACTA ANAESTHESIOLOGICA SCANDINAVICA
doi: 10.1111/j.1399-6576.2009.02029.x
Review Article
regimen whereas two studies found no difference and two
studies found differences in the selected outcome para-
meters.
Conclusion: Liberal vs. restrictive fixed-volume regimens
are not well defined in the literature regarding the defini-
tion, methodology and results, and lack the use of or
information on evidence-based standardized periopera-
tive care-principles (fast-track surgery), thereby preclud-
ing evidence-based guidelines for procedure-specific
perioperative fixed-volume regimens. Optimization of
perioperative fluid management may include a combina-
tion of fixed crystalloid administration to replace extra-
vascular losses and avoiding fluid excess, together with
individualized goal-directed colloid administration to
maintain a maximal stroke volume.
Accepted for publication 24 April 2009
r 2009 The Authors
Journal compilation r 2009 The Acta Anaesthesiologica Scandinavica Foundation
outcome. Attention has been directed towards
different volume regimens referred to as ‘liberal’
or ‘high’ vs. ‘restricted’ or ‘low’. In minor ambula-
tory/semi ambulatory procedures, more than 18
randomized trials have investigated the effect of
administering more or o than  1 l of fluid and
conclude that more than 1 l of crystalloid results in
reduction of symptoms related to dehydration.2,4,7
However, the data comparing crystalloid regimens
in major procedures have not provided similar
clear recommendations.
Therefore, the purpose of this review was to
assess the randomized trials comparing a liberal
vs. a restricted fixed-volume crystalloid regimen
in major surgery in order to establish information
for clinical practice and guidelines for future
studies.
843
M. Bundgaard-Nielsen et al.
Methods
A PubMed search identified randomized clinical
trials comparing the effect of two different fixed
fluid volumes on one or more post-operative clin-
ical outcome parameters in adults undergoing
major surgery. Search terms ‘fluid therapy’ and
‘outcome’ were combined and limited to rando-
mized human studies published in English and
with patients 418 years in the period 1966–2008,
May 22. Additional studies were identified from
review articles and papers cited in original papers.
Analysis
Studies were assessed for information regarding
the type of surgery, number of patients and pri-
mary and secondary outcome endpoints. More-
over, the type and volume of administered and
lost fluid, weight before and after surgery and the
definition of the perioperative period were regis-
tered. Finally, information regarding perioperative
management, type of anaesthesia and the use of
epidural analgesia was assessed.
Results
From the 187 identified studies, only seven rando-
mized studies were selected according to the search
strategy (Table 1). Six studies included major ab-
dominal surgery8–13 and one study included knee
arthroplasty.14 Studies addressing abdominal sur-
gery included colorectal procedures8–12 or a variety
of abdominal procedures.13
‘Liberal’ vs. ‘restrictive’ fluid regimen
Two studies reported pre-operative fluid adminis-
tration and then only in the liberal groups (Table
2).9,12 The definition of a liberal vs. a restrictive
intraoperative fluid regimen differed between stu-
dies. The range of a liberal intraoperative fluid
regimen was from 2750 to 5388 ml compared with
998 to 2740 ml for the restrictive fluid regimen (Fig.
1). Consequently, a restrictive fluid regimen in one
study9 differed only 10 ml from what was defined
as liberal in another trial.10 Post-operatively, the
studies reported a volume that ranged from 1500 to
2900 ml in the liberal group and between 500 and
2170 ml in the restricted group. However, post-
operative volume administration was only re-
ported in four studies. Five studies provided data
on fluid intake/administration vs. fluid losses ex-
pressed as a change in body weight (Table 2).8–11,14
844
Only two of these studies reported a conventional
fluid balance of 3.7 l in the liberal group and 0.2 l in
the restricted group at day 48 and 2.3 l in the liberal
group and 1.2 l in the restricted group at day 0.14
Indications for additional fluid administration
Five studies provided additional fluid besides the
fixed-volume regimen. In the study by Brandstrup
et al.9, the restricted group was provided with a
synthetic colloid (HAES 6%) 1 : 1 according to
blood loss; the liberal group received 1000–
1500 ml of saline with a blood loss  500 ml, and
additional blood loss was replaced with additional
HAES. In the study by MacKay et al.10 blood
products were provided; however, no indication
of these or other colloid products was given. In the
two studies by Holte et al.11,14 a fixed volume of
colloid of 7 mg/kg was given.
In the study by Nisanevich et al.13 a
CVPo15 mmHg was an indication of colloid ad-
ministration or pharmacologic support, and blood
was transfused with a haematocrit o24% (o30% in
patients with cardiac morbidity). Kabon et al.12
provided additional fluid if diuresis waso1 ml/
kg/h or if MAPo70% of preinduction.
The intra- vs. the post-operative period
When assessing the fluid volume administered
intraoperatively, different periods were reported
ranging from ‘intraoperative’8 to ‘intraoperative
including PACU stay’11 to ‘day of operation’10,
which was not further specified. The post-opera-
tive period was defined from 1 h post-operatively12
‘to midnight’8or as the first post-operative day.9,10
One study primarily evaluated the post-operative
period.8 In the fast-track studies by Holte et al.,11,14
intravenous fluids were not provided post-opera-
tively and fluid needs were managed by oral
intake.
Outcome endpoints
Wound infection,12 gastric emptying time,8 pul-
monary function,11,14 post-operative complica-
tions9,13 and death13 were used in six studies as
the primary outcome parameters (Table 1). In one
study, no primary endpoint was defined but gas-
trointestinal function, complications and fitness for
discharge were evaluated.10 Five studies reported
length of hospital stay (LOS),8,10,11,13,14 but only
three studies reported well-defined discharge cri-
teria.10,11,14 Finally, gastrointestinal recovery was
 Table 1
Perioperative methodology and result of fixed volume randomized trials.
Study and year Procedure/ ASA I/II/ Fast- Blinding Epi Epi Anaesthesia Outcome Result
pt (n) III/IV (%) track intraop post-op
Lobo8 2002 Hemi – No No No No – Gastric Low: " GI recovery
colectomy/20 emptying time # LOS: High 9 days, low 6 days

Brandstrup9 Colorectal 47/51/2/0 No Assessor Yes Yes – Complications Low: # complications

2003 resection/141

Kabon12 2005 Colon 10/75/15/0 No – – – i.v.: thio/ Wound ! Wound infection

resection/253 fentanyl, vola: infection
iso/NO

Nisanevich13 Major abdominal 22/52/26/0 Yes Assessor No Yes i.v.: thio/ Death and Low:
2005 surgery/142 fentanyl, vola: complications " GI recovery
iso/NO # complications, LOS (High 9
days, low 8 days).
! death

Mackay10 2006 Colorectal 5/70/24/1 No Assessor – – – Recovery ! GI recovery, LOS (7.2

resection/69 days), complications

Holte14 2007 Arthroplasty/48 29/48/23/0 Yes Double Yes Yes Epi/spinal Perioperative High:
physiology and # vomiting
organ function " coagulation, pulmonary
function
! exercise capacity, pain,
nausea, appetite, well-being,
fatigue, ileus, post-op
hypoxaemia, LOS

Holte11 2007 Colonic 22/25/53/0 No Double Yes Yes i.v.: prop/ Physiological High:
surgery/32 remi recovery # pulmonary function,
vasoactive hormones, total
complications
! exercise capacity, ileus,
pain, well-being, thirst,
headache, dizzy/drowsiness,
fatigue, LOS

" , increased/improved; ! , no change;

# , decreased/reduced; vola, volatile anaesthetic; prop, propofol; remi, remifentanil; Low, low fluid regimen; High, high fluid regimen; GI, gastro-intestinal; i.v., intravenous.
‘Liberal’ vs. ‘restrictive’ perioperative fluid therapy

845
M. Bundgaard-Nielsen et al.

Intraoperative Postoperative
6000 6000
5000 5000

Volume (ml)
4000 4000
3000 3000
2000 2000
1000 1000
0 0

7 11
28

5 12
39

3
6 10

5 12
7 14

39

6 10
02 8
05 1

05 1
00

00

00
00
00

00

0
00

00
20
20

20
0
.2

.2

2
.2
.2

.2

2
.2

.2
l.
tru al.
al

Ka al.
vic al.
ta

a
al
al

al

al

al

al
et

Ka p et
et
e

et
et

et

et
et

et
et

et
bo

bo
lte
n

h
y

on
lte

y
tru

Ka
bo

vic
Lo

Lo
Ho
Ho

b
ds

ds
Ka

ac

ac
ne

ne
an

an
M

M
sa

sa
Br

Br
Ni

Ni
Fig. 1. Intraoperative and post-operative administered fluid volume in randomized trials comparing ‘high’ vs. ‘low’ fluid regimens. Black
bar, ‘high’ volume regimen; Grey bar, ‘low’ volume regimen. Post-operative period as defined in Table 2.

reported in one trial13 and a battery of physiologi-
cal recovery variables was utilized as secondary
outcome variables in two studies.11,14
Outcome result
Studies with improved outcome following a restricted fluid
regimen (Table 2). Three of seven studies found that
a restrictive fluid regimen improved outcome after
major abdominal surgery, with two studies show-
ing improved gastro-intestinal recovery and a re-
duced LOS from 9 to 6 days8 and from 9 to 8 days,
respectively.13 Two studies also showed an overall
reduced incidence of complications (Table 1).9,13
However, the two trials reporting LOS did not
define any criteria for discharge.8,13 All three stu-
dies reported use of crystalloid, of which one study
used a balanced solution (Ringers lactate)13 and two
studies used saline and dextrose/glucose8,9 (Table
2). Two studies reported additional use of colloid
(HAES 6%, HES 200/0.5).9,13 One study did not
provide ASA classes8 and one study included only
a small number of ASA III patients (2%).9 In the
remaining study, ASA ranged from I to III (18%).13
Patients with impaired renal function, congestive
cardiac failure, hepatic disease, diabetes mellitus,
ascites, peritoneal metastasis, impaired mobility,
anaemia or those taking drugs affecting gastroin-
testinal mobility were excluded in the study by
Lobo et al.,8 whereas pregnancy, lactation, mental
disorders, alcohol consumption 435 U/week, dia-
betes mellitus, renal insufficiency, disseminated
cancer, secondary cancer, inflammatory bowel dis-
ease or disease hindering epidural analgesia were
the exclusion criteria in the study by Brandstrup
et al.9 In the study by Nisanevich et al.13 hepatect-
omy, age o18 years, pregnancy, coagulopathy, renal
or hepatic dysfunction and congestive heart failure
were the exclusion criteria.
One study reported that epidural analgesia was
not used perioperatively8 and one study used
epidural analgesia both intra- and post-operatively9
and the last study only used epidural analgesia
post-operatively.13 However, no information was
provided with regard to the site (thoracic vs. lum-
bar) or the dose/composition of the epidural regi-
men. Two studies were assessor blinded,9,13 and
one study was not blinded.8 Updated perioperative
evidence-based care principles including pre-opera-
tive information, optimized opioid-reduced epi-
dural and systemic analgesia, avoidance of bowel
preparation, early post-operative mobilization and
oral nutrition,15–17 were not described in any of
the three studies recommending a restrictive fluid
regimen.8,9,13
Studies with no difference in outcome (Table 2). Two
studies in colonic surgery showed no difference
between the liberal and the restrictive fluid regi-
men with outcome expressed as wound infection12
or gastro-intestinal recovery and LOS (7.2 days).10
Patients with fever, infection, susceptibility to ma-
lignant hyperthermia, congestive heart failure, use
of diuretics, renal failure and a history of pulmon-
ary oedema were excluded in the study by Kabon
et al.12 For MacKay et al.10 renal impairment,
physical disability requiring long-term care, insu-
lin-dependent diabetes mellitus, total colectomy,

846
 Table 2
Perioperative fluid administration and losses in millilitres.
Study Pre Intra Post
H L Definition All Cryst vol, Colloid vol, Blood Blood Diuresis Definition All Cryst Diuresis Weight gain
type type loss kg/24 h
H L H L H L H L H L H L H L H L H L H L
Lobo8 – – Intra 2800 2500 2800 2500 0 0 0 0 238 275 1190 776 To midnight 2900 600 2900 600 1190 1741 2.6 0.6
S1D S1D

Brandstrup9 500 0 To 5388 2740 – – – – – – 500 400 – – First post- 1500 500 – – – – 2.8 0.6
midnight op day
S1G S1G HAES HAES
Kabon12 700 0 Intra – – 3900 2500 – – – – 322 333 490 310 1 h post-op – – 1100 600 – – – –
– –
Nisanevich13 – – Intra 3878 1408 – – – – – – 440 400 – – 24 h 2012 2170 – – – – – –
RL RL HAES HAES
Mackay10 – – Day 2750 2000 2750 2000 – – – – – – – – Day 1 2600 2000 2600 2000 – – 1.1  0.5
of OP post-op
S1D S1D
14
Holte – – Intra 4250 1740 3275 815 500 500 0 0 0 0 – – – – – – – – – 2.1 0.6
RL RL HES
Holte11 – – Intra1 5050 1640 3900 1140 500 500 0 0 305 200 1150 700 – – – – – – – 2.0 0.2
PACU
RL RL HES

Pre, pre-operative; Intra, intraoperative; Post, post-operative; All, all administered volume; Cryst, crystalloid; Definition, definition of period; H, high volume group; L, low volume
group; Post-op, post-operative; OP, operation; PACU, post-anaesthetic care unit; –, no information; S1D, saline and dextrose; S1G, saline and glucose; RL, ringeŕs lactate; HES,
hydroxyl ethyl starch 130/0.4; HAES, hydroxyl ethyl starch 200/0.5.
‘Liberal’ vs. ‘restrictive’ perioperative fluid therapy

847
M. Bundgaard-Nielsen et al.
abdominoperineal resection and low-anterior re-
section requiring a defunctioning stoma were the
exclusion criteria. Both studies reported the use of
crystalloid but the type was only stated in one
study (saline and dextrose).10 The use of colloid
was not reported. Details regarding anaesthesia
were only provided in one of the studies,12 and
information on epidural analgesia was not given.
Updated perioperative evidence-based care princi-
ples including pre-operative information, opti-
mized opioid-reduced analgesia, avoidance of
bowel preparation, early post-operative mobiliza-
tion and oral nutrition were not described in the
two studies without a difference in outcome.
Studies with differences in outcome (Table 2). The two
blinded studies regarding knee arthroplasty14 and
colonic surgery11 showed benefit from a restrictive
or a liberal fluid regimen in different functional
parameters. For both studies, age o50 years,
weight 4110 kg, BMI440, inability to perform
the pre-operative test programme, ASA IV, insu-
lin-dependent diabetes mellitus, NYHA class IV or
MIo3 month, FEV1o1 l, psychiatric disorder, al-
cohol consumption 45 U/day, glucocorticoid and
anticoagulant therapy or inability to provide in-
formed consent were the exclusion criteria. In the
colonic surgery study, additional exclusion criteria
were inflammatory bowel disease, and in the knee
arthroplasty study, a contraindication to tranexa-
mic acid/epidural catheter, chronic opioid treat-
ment and morphine intolerance were also the
exclusion criteria for participation. The study in
knee arthroplasty found reduced vomiting, im-
proved pulmonary function and enhanced coagu-
lation with the liberal regimen, but no difference
between groups in exercise capacity, pain, nausea,
appetite, well-being, fatigue, ileus, post-operative
hypoxaemia or LOS (4 days).14 The study in colonic
surgery found an improvement in pulmonary
function and post-operative hypoxaemia and a
reduced vasoactive hormonal response (aldoster-
one, renin and AT-II concentration) on administer-
ing a liberal fluid regimen. Although the total
number of complications was reduced (Po0.01),
the number of patients with complications was not
significantly reduced (P 5 0.08).11 In addition, ex-
ercise-capacity, pain, nausea, thirst, headache,
dizzy/drowsiness, fatigue, ileus and LOS (‘high’:
2.5 days; ‘low’: 3 days) were not different
(P 5 0.52). Both studies used a balanced crystalloid
(Ringer’s lactate) and a colloid (HES 140/0.4). Also,
both studies were double-blinded and with up-
848
dated perioperative evidence-based care principles
including pre-operative information, optimized
opioids-reduced analgesia, avoidance of bowel
preparation, early post-operative mobilization
and oral nutrition.15–17 In both studies, well-de-
scribed epidural anaesthesia was used intra- and
post-operatively and the type of general anaesthe-
sia was provided in the colonic surgery study.
Discussion
Inconsistent outcome results and study designs
have been reported with the use of a liberal vs. a
restrictive fluid regimen. These inconsistencies re-
late both to the amount of administered fluid
volume in the liberal vs. restrictive fluid regimens,
indications for additional fluid, and to the defined
intra- and post-operative period as well as infor-
mation on perioperative care principles hindering
direct comparison and interpretation. Accordingly,
it is recommended to abandon the terms liberal and
restrictive when referring to the size of a fixed-
volume fluid regimen. Although changes in body
weight were reported in most studies, a conven-
tionally calculated fluid balance was only provided
in two studies. Nevertheless, the studies suggest
that the perioperative crystalloid excess impairs the
post-operative outcome.
Study design
Exclusion criteria were extensive in most trials. In
order to apply the study findings to daily clinical
practice, we consider that the patients included
need to be representative for the procedure-specific
population. In this context, the study by Brandstrup
et al.9 only included a limited number of ASA III
patients (ASA I/II/III: 47/51/2%) and did not
represent the general population undergoing color-
ectal resection. Nevertheless, the worse outcome
demonstrated by this relatively ‘healthy’ popula-
tion by a liberal fluid regimen leading to a weight
gain suggests that fluid excess should be avoided.
Standardized evidence-based perioperative care
principles
The majority of identified studies, except for the two
double-blinded studies,11,14 did not describe perio-
perative care principles and discharge criteria in
detail. This is unfortunate because pre-operative
information, optimized non-opioid analgesia, avoid-
ance of bowel preparation, early post-operative mo-

bilization and oral nutrition improve post-operative
outcome per se.15–17 Thus, the study in abdominal
surgery applying the ‘fast-track’ methodology had a
median hospital stay of  3 days in both groups11 in
contrast to the studies reporting a reduction in LOS
from 9 to 6 days8 and 9 to 8 days13 with a ‘restricted’
regimen. Consequently, perioperative care needs to
be defined and evidence-based care principles
should be adopted in order to evaluate the effect of
fluid management per se.4 The same applies to semi-
ambulatory procedures where application of evi-
dence-based perioperative care and a liberal fluid
regimen ( 3 l) improved the post-operative out-
come in the context of exercise capacity, balance
function, thirst, dizzy/drowsiness and the hormonal
stress response compared with a restricted regimen
( 1 l), probably reflecting functional hypovolaemia
with the restricted regimen.7
Outcome parameters
In elective surgery, perioperative death is a rare
event and studies with death as an outcome vari-
able require large sample sizes. Only one study
used death as a primary outcome variable,13 while
LOS has been widely used as a secondary outcome
variable. The LOS depends on multiple factors and
when precise discharge criteria are not defined,
interpretation of LOS remains elusive. Thus, the
two studies using LOS as an outcome parameter
and advocating a restrictive fluid regimen did not
describe discharge criteria.8,13 A reduction in post-
operative surgical complications is a tempting
evaluation of the benefit of one fluid regimen
over another, provided that the registered compli-
cation is related to fluid therapy. Thus, the role of
fluid management in urinary tract infections may
be questioned, when exact criteria for use and
removal of a urinary bladder catheter are not
provided.9 Therefore, in studies addressing the
role of fluid therapy, it would be of interest to
evaluate functional outcome variables with a
known or at least theoretically assumed relation-
ship with the amount of fluid administration.4
Type of fluid
The relative role of the optimal administration of
crystalloid vs. colloid ratio has not been resolved.
However, there is evidence favouring balanced
solutions with an electrolyte concentration similar
to that found in plasma and large volumes of e.g.
‘Liberal’ vs. ‘restrictive’ perioperative fluid therapy
saline should be avoided because they induce
hyperchloraemic acidosis.18
Clinical and research strategies
Because differences in surgical trauma, pre-opera-
tive hydration, anaesthetic technique, co-morbidity,
gender and age are likely to influence the fluid
needs, a fixed-volume regimen is unlikely to both
prevent hypovolaemia and the risk of hypervolae-
mia for every patient (Fig. 2).19 Therefore, rather
than using a fixed volume of crystalloids as the
main strategy of perioperative volume handling, it
should be used as a background fluid regimen to
replace extra-vascular fluid losses and with a focus
on avoiding undesirable fluid excess and maintain-
ing bodyweight.9 A more rational strategy for
perioperative fluid therapy could also include a
tailored individualized treatment optimizing the
intravascular volume by providing maximization
of cardiac stroke volume with colloid boluses, the
so-called individualized ‘goal-directed therapy’
concept.20–22 This strategy has improved outcome
in 10 randomized trials20,23,24 and may, in contrast
to the fixed-volume regimens, offer a definition of
‘normovolaemia’.20,25 Thus, rather than choosing
between a fixed-volume regimen and a goal-direc-
ted concept, an approach is to combine the two
strategies because they replace losses from the
extra- and intravascular fluid compartments, re-
spectively.
Conclusion
It is of concern that the literature pertaining to a
liberal vs. a restrictive fixed-volume regimen is
inconsistent regarding the definitions, methodol-
ogy and defined outcome parameters, and most
studies are hampered by the lack of information on
evidence-based standardized perioperative care
principles (fast-track surgery). Therefore, evi-
dence-based guidelines for optimal procedure-spe-
cific perioperative fixed-volume regimens cannot
be formulated. Rational perioperative fluid man-
agement may include a combination of fixed crys-
talloid administration to replace extra-vascular
losses and individualized goal-directed colloid ad-
ministration to maintain a maximal cardiac stroke
volume. Yet, we consider that such an approach
needs to be examined in procedure-specific studies
combined with evidence-based principles for peri-
operative care (fast-track surgery) in order to de-
fine optimal perioperative fluid management.26
849
M. Bundgaard-Nielsen et al.

morbidity

procedure
comorbidities
preop hydration
bowel preparation
anaesthesia / neuroaxial blockade

↑ risk of:
↑ risk of:
oedema
organ hypoperfusion ileus
SIRS PONV
sepsis pulm complications
multi organ failure cardiac demands

hypovolaemia normovolaemia hypervolaemia

Fig. 2. Relationship between perioperative administered fluid volume and post-operative morbidity and factors influencing shift of the
curve (arrow). Boxes indicate the risk of complications associated with deviation from normovolaemia. Modified from Bellamy.19 SIRS,
systemic inflammatory response syndrome; PONV, post-operative nausea and vomiting.

Finally, we consider it important to evaluate the
role of fluid therapy in outcome in high-risk pa-
tients, rather than excluding such patients in future
studies.
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Address:
Morten Bundgaard-Nielsen
Department of anaesthesia 2041
Rigshospitalet
University of Copenhagen
DK-2100 Copenhagen
Denmark
e-mail: morten.bundgaard-nielsen@rh.regionh.dk
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