REVIEW

CURRENT
OPINION Which intravenous fluid for the surgical patient?
Sweyn S. Garrioch and Michael A. Gillies

Purpose of review
This review appraises recent evidence and provides clinical guidance on optimal perioperative fluid
therapy.
Recent findings
Choice of perioperative intravenous fluid continues to be the source of much debate. Not all crystalloids
are equivalent, and there is growing evidence that balanced solutions are superior to 0.9% saline in many
situations. Recent evidence from the critical care population has highlighted risks associated with synthetic
colloids; this and the absence of demonstrable benefit in the surgical population make it difficult to
recommend their use in the perioperative period. Giving the correct amount of fluid may be as important
as the choice of the fluid used. There is increasing evidence that excessive positive fluid balance is harmful
to patients but there have been no randomized trials comparing maintenance fluid strategy. A knowledge
of the physiology and accurate estimation of fluid balance is important for water and electrolyte
homeostasis until the patient is able to resume adequate enteral nutrition.
Summary
Balanced crystalloids are the fluid of choice for perioperative resuscitation and optimization in patients not
requiring blood products. Avoidance of a grossly positive sodium and water balance during the
maintenance phase is likely to be important, but has not been assessed in randomized trials.
Keywords
balanced crystalloids, colloids, intravenous fluid, perioperative medicine

INTRODUCTION high proportion of perioperative morbidity and

Fluid therapy is a central, if highly controversial,
aspect of perioperative management, essential for
fluid and electrolyte homeostasis, adequate cardiac
output and tissue perfusion. Inappropriate fluid
therapy is associated with increased complications,
tissue oedema, delayed wound healing, fluid over-
load, kidney and other organ dysfunction, coagu-
lation abnormality and excessive transfusion
[1–13]. Despite over 175 years of experience with
intravenous fluids [14], many of the traditional
beliefs held around this therapy are not based on
robust scientific evidence, and many controversies
remain: type and composition of fluid; indication
for fluid therapy; resuscitation goals and endpoints.
A recent report into perioperative care suggested
that 20% of hospitalized adults receive inappropri-
ate fluid therapy [15].
Approximately 230 million patients undergo
surgery worldwide each year [16] and overall rates
of mortality are low, quoted at between 1 and 4%.
Epidemiological evidence, however, suggests that
this large number of surgical patients conceals
a smaller high-risk subgroup, accounting for a
mortality. In many patients having minor to mod-
erate elective surgery, choice of fluid may have a
limited bearing on outcome. There are few large
prospective trials examining the effect of particular
types of fluid or modes of fluid administration in the
wider surgical population. Moreover, low overall
rates of death and complication in patients under-
going routine surgery mean that any such trial
would need to be very large indeed. Hence, much
of the available data are extrapolated from studies in
other smaller patient groups (e.g. critically ill adults,
patients undergoing high-risk surgery) or studies
examining physiological endpoints. The high-risk
subgroup typically includes older, sicker patients
undergoing major or non-elective surgery [17]. In
these patients, certain aspects of perioperative care,
including fluid therapy, may have a more important
Department of Anesthesia, Critical Care and Pain Medicine, Royal
Infirmary of Edinburgh, Edinburgh, EH16 4SA, UK
Correspondence to Dr Michael Gillies, E-mail: Michael.Gillies@ed.ac.uk
Curr Opin Crit Care 2015, 21:358–363
DOI:10.1097/MCC.0000000000000222

www.co-criticalcare.com Volume 21
Number 4
August 2015

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 Perioperative fluid therapy Garrioch and Gillies

expansion. This has been attributed to more

KEY POINTS

Balanced crystalloid solutions are superior to 0.9%
saline in the majority of situations.

Lack of demonstrable outcome benefit for synthetic
colloids in surgical patients and harm in the critical
care population suggest synthetic colloids should not be
used in the perioperative period.

Avoidance of salt and water overload is an important
goal in the perioperative period.

Due to a lack of trial evidence, accurate charting and
good physiological knowledge are vital to good
maintenance fluid practice.

Further trials are required to determine optimal
perioperative fluid strategies.
bearing on the development of complications and
ultimate outcome.
The scope of this article is to appraise recent
evidence and provide clinical guidance with specific
regard to perioperative fluid therapy.
PHYSIOLOGICAL CONSIDERATIONS
Intravenous fluids fall into two broad categories:
crystalloid and colloid. Crystalloids are aqueous
solutions of electrolytes, small organic anions or
sugars, and are available in varying compositions
(Table 1). These small-solute molecules are able to
diffuse freely between fluid compartments. Crystal-
loids represent the original and the oldest form of
intravenous fluid therapy [14].
Colloids are suspensions of larger, insoluble
molecules, and offer the theoretical advantage of
longer plasma half-life and sustained volume
restricted diffusion properties and increased plasma
oncotic pressure. Colloids are traditionally classified
as naturally occurring (e.g. albumin) and synthetic
(e.g. HES, dextrans and gelatins). Studies in healthy
human volunteers suggest that much of a colloid
solution remains in the intravascular space at 1 h,
compared to only 20% of crystalloid solution [18].
In recent years, the traditional theories of fluid
mechanics, proposed by Starling, have been revised,
and a new model involving the glycocalyx layer
(GCL) has been proposed [19,20]. The GCL is a dense
layer of glycosaminoglycans, which lines and is
connected to the vascular endothelium. The GCL,
vascular endothelium and basement membrane
form a barrier between the intravascular and inter-
stitial spaces. The GCL is semi-permeable to anionic
macromolecules (such as albumin), impermeable to
red bloods cells, and maintains a relatively protein-
free space below. This results in a low colloid oncotic
pressure in the intracellular clefts. It is this oncotic
pressure which more accurately determines the
microcirculatory fluid filtration and thus the fluid
distribution in healthy and disease conditions.
Colloids are thought to adsorb to the GCL, restrict-
ing ultra-filtration and increasing plasma oncotic
pressure. In healthy condition, they increase plasma
volume expansion compared with crystalloids,
which diffuse freely into the interstitial space
(ISF). The GCL, however, can be damaged by rapid
infusion of fluids, hyperglycaemia, ischaemia,
surgery, sepsis and inflammation. This could
account for the observed interstitial expansion
associated with colloid infusion in surgical and crit-
ically ill patients. It may also explain the findings of
studies such as FEAST where bolus fluid therapy was
compared with maintenance infusion for resuscita-
tion of seriously unwell children in Africa. Despite

Table 1. Contents of commonly available crystalloid solutions

0.18% Sodium 0.45% Sodium

0.9% Sodium chloride with chloride with 5% Plasma-Lyte
Content Plasma chloride 4% glucose 4% glucose Glucose Hartmann’s 148

Sodium (mmol/l) 135–145 154 31 77 0 131 140

Chloride (mmol/l) 95–105 154 31 77 0 111 98
Potassium (mmol/l) 3.5–5.3 0 0 0 0 5 5
Bicarbonate 24–32 0 0 0 0 29 (lactate) 50 (27 acetate;
23 gluconate)
Calcium (mmol/l) 2.2–2.6 0 0 0 0 2 0
Magnesium (mmol/l) 0.8–1.2 0 0 0 0 0 1.5
Glucose (mmol/l) 3.5–5.5 0 222 (40 g) 222 (40 g) 278 (40 g) 0 0
pH 7.35–7.45 4.5–7.0 4.5 4.5 3.5–5.5 5.0–7.0 4.0–6.5
Osmolarity (mOsm/l) 275–295 308 284 376 278 278 295

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Postoperative problems
more rapid restoration of haemodynamic variables
in the bolus therapy group, mortality was increased
[21].
Crystalloid solutions
The most commonly used crystalloid in clinical prac-
tice is 0.9% saline [22], and it contains 154 mmol/l
of sodium and chloride ions. This is a higher con-
centration of chloride than that found in plasma
(approximately 100 mmol/l). Infusions of large
volumes of chloride-rich solutions, such as 0.9%
saline, can result in metabolic acidosis by altering
the strong ion difference [23]. This phenomenon has
been demonstrated both in healthy volunteers [24]
and surgical patients [25,26]. Hyperchloraemia may
also be associated with decreased renal blood flow
and glomerular filtration rate [24,27,28].
‘Balanced crystalloid solutions’ may offer a bet-
ter alternative to 0.9% saline. Balanced solutions
resemble plasma more closely and have lower
chloride ion concentrations than saline, chloride
ions being typically replaced with bicarbonate or
organic anions (e.g. acetate or lactate). Use of these
solutions may mitigate the undesirable effects of
normal saline on acid–base balance and renal blood
flow. Commonly used balanced solutions in clinical
practice include lactated Ringer’s solution, Plasma-
Lyte 148 or Stereofundin.
A recent large observational study of over 30 000
adult patients undergoing major abdominal surgery
compared morbidity and mortality between those
receiving 0.9% saline to 926 patients who only
received Plasma-Lyte 148 on the day of surgery
[29]. This showed a reduction in postoperative infec-
tion, renal failure requiring dialysis, blood trans-
fusion, electrolyte disturbance and acidosis in the
patients receiving the balanced crystalloid solution.
It also reported a reduction in unadjusted in-hospi-
tal mortality [5.6% in the 0.9% saline group to 2.9%
in the Plasma-Lyte 148 group (P < 0.001)]. Another
large cohort study of over 9000 patients showed an
increased 30-day mortality [odds ratio (OR) 2.05,
95% confidence interval (CI) 1.62–2.59] in non-
cardiac surgical patients who were hyperchloraemic
[30].
Some clinicians have traditionally avoided bal-
anced solutions in certain situations due to concerns
regarding hyperkalaemia, for example, renal failure,
during renal transplantation surgery and treatment
of diabetic ketoacidosis (DKA). However, there is
evidence to support the use of balanced crystalloids
in these situations. A randomized controlled trial
comparing 0.9% saline compared to Ringer’s lactate
solution in 51 patients undergoing renal transplant
surgery demonstrated higher rate of clinically
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significant hyperkalaemia (29 vs. 0%; P ¼ 0.05)
and metabolic acidosis (31 vs. 0%; P ¼ 0.04) in
patients receiving 0.9% saline, although there was
no significant difference in renal function [31]. In
liver transplantation, a high chloride-based fluid
regime has been associated with acute kidney injury
[32]. There is also evidence to support the use of
balance solutions in DKA [33,34].
A prospective, non-randomized study of 760
intensive care patients, comparing use of chloride-
rich solutions compared with balanced crystalloids,
demonstrated reduced acidosis with no change in
sodium or potassium concentrations [35]. In a sep-
arate analysis of these patients, the low chloride
group was found to have a significantly lower inci-
dence of RIFLE-defined acute kidney injury (8.4 vs.
14%; P < 0.001) and a lower need for renal replace-
ment therapy (6.3 vs. 10%; P ¼ 0.004) [36]. A large
cohort study in ICU patients with sepsis has also
shown an association with balanced crystalloid use
and reduced hospital mortality [relative risk (RR)
0.86, 95% CI 0.78–0.94] [37]. These findings suggest
that balanced crystalloids are the fluids of choice for
fluid resuscitation in the perioperative setting, and
the use of 0.9% saline should be reserved for specific
conditions such as replacement of gastric fluid
losses.
Colloids
Colloids are suspensions of large molecules, typi-
cally in 0.9% saline, but more recently in balanced
solutions. As described above, colloids have longer
plasma half-lives than their crystalloid counterparts,
increased plasma oncotic pressure and reduced
ultra-filtration. Hence they have been attractive
resuscitation fluids. However, in critical illness,
endothelial permeability is increased and these
larger molecules may diffuse into the interstitial
space, possibly resulting in reduced efficacy,
increased tissue oedema and end-organ damage.
Albumin 4 or 5% is considered to be the refer-
ence colloid solution. It is manufactured from blood
donation and is relatively expensive to produce. It
enjoyed widespread use as a resuscitation fluid until
1998 when a Cochrane review concluded that its use
was associated with an increased risk of death (RR
1.68, 95% CI 1.26–2.23, P < 0.01) [38]. This review
was heavily criticized for including an extremely
diverse group of small trials including burns,
trauma, septic, surgical and neonatal patients. How-
ever, it led to a rise in use of synthetic colloids, for
example, the starch and gelatine-based solutions
described below. The Saline versus Albumin Fluid
Evaluation (SAFE) study examined 6997 adults in
ICU in Australia and New Zealand [39]. The study
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compared resuscitation with 4% albumin to 0.9%
saline, and found no difference in 28-day mortality
or incidence of new organ failure between the two
fluids. Two predefined subgroups showed how the
same fluid might cause a different outcome in two
different situations. A harmful effect in patients
with traumatic brain injury in the albumin group
was observed (RR 1.63, 95% CI 1.17–2.26, P ¼ 0.003),
whilst there was a reduced risk of mortality in patients
with severe sepsis (RR 0.87, 95% CI 0.74–1.02,
P ¼ 0.09), which did not reach statistical significance.
Further randomized control trials have since been
completed, which have not confirmed albumin’s
beneficial effect in sepsis [40]. There is little evidence
to support the widespread use of albumin in the
perioperative period at present.
Over the past two decades, hydroxyethyl
starches (HES) and gelatins have been the most
widely used synthetic colloids. However, concerns
have existed about the potentially harmful effects
associated with their use for several years. HES
solutions have been shown to impair haemostasis
and increased postoperative blood loss [1]. Gelatin
solutions are used less widely and so have been less
well investigated; however, observational data have
shown them to be nephrotoxic to a similar extent as
HES [41]. Gelatins also have a significant rate of
anaphylaxis [42,43].
PERIOPERATIVE FLUID MANAGEMENT
A recent special article by the Acute Dialysis Quality
Initiative (ADQI) proposed four phases of fluid
therapy: resuscitation, optimization, maintenance
and de-escalation. This classification lends itself to
perioperative period, and we will consider the opti-
mum approach to fluid management under these
headings.
Resuscitation
Surgical patients may need resuscitation for hypovo-
laemia due to dehydration, haemorrhage or sepsis.
The management of major haemorrhage and blood
component therapy is not considered in this review;
however, colloidal solutions have been recom-
mended for the treatment of hypovolaemia. The
postulated advantages of rapid resuscitation, a sus-
tained increase in cardiac output and end-organ per-
fusion associated with colloids offer an attractive
theory of physiological benefit; however, clinical
evidence has not substantiated this. The SAFE study
described above not only demonstrated no overall
clinical benefit associated with the choice of fluid but
also that compared to animal and human volunteer
studies where crystalloid-to-colloid ratios of up to
4 : 1 had been required to reach the same endpoints,
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Perioperative fluid therapy Garrioch and Gillies
the ratio of administered saline to albumin was only
1 : 1.4. This finding has been replicated in other large
clinical trials using synthetic colloids; both the CRIS-
TAL and the VISEP studies found a similar ratio of
1 : 1.5 [2,44]. HES, in particular, is associated with
nephrotoxicity [2–4] and higher mortality when
used for resuscitation in the critically ill [3,45]. The
applicability of these studies to the wider surgical
population is not known; however, high-risk surgical
patients requiring resuscitation with colloidal
solution may become those who ultimately require
critical care. The CRISTAL study – an open-label,
randomized trial of 2857 patients – was published
in 2013 and assessed the outcome of crystalloid vs.
colloid for resuscitation of hypovolaemic ICU
patients, the majority of whom had severe sepsis.
This study found no difference in 30-day mortality,
but a reduction in 90-day mortality associated with
the use of colloid (RR 0.92, 95% CI 0.86–0.99,
P ¼ 0.03). However, the validity of this trial has been
questioned; several different colloid and crystalloid
solutions were used and it was conducted over a 9-
year period during which fluid practices evolved [44].
Current guidance recommends that semi-synthetic
colloids are avoided in the intensive care population;
due to these safety concerns and lack of demonstrable
superiority, they cannot be recommended in the
perioperative setting [46].
Optimization
In 1973, Shoemaker [47,48] observed that patients
suffering from surgical shock were more likely to
survive if they were able to achieve higher levels of
cardiac output (CO) and tissue oxygen delivery
(DO2). Since then, many trials of goal-directed hae-
modynamic therapy have been conducted, typically
involving administration of colloidal solutions to a
predetermined endpoint, with or without the
addition of low-dose inotropes. A recent authorita-
tive systematic review conducted on the subject
included 31 trials [49]. The OPTIMISE trial compared
a haemodynamic therapy algorithm with usual care
in 734 high-risk patients undergoing gastrointestinal
surgery [50]. Although this study reported a trend
towards a reduced incidence of a primary outcome of
death or complication within 30 days, it did not reach
statistical significance. An updated systematic review
and meta-analysis suggested haemodynamic therapy
was associated with reduced complication rate and
length of hospital stay. Few studies examine the type
of fluid used in haemodynamic therapy. A study by
Yates et al. [51] compared balanced crystalloid with
6% HES for haemodynamic therapy in 206 patients
undergoing major gastrointestinal surgery and found
no difference in outcome and similar volumes of fluid
administered to each group.
www.co-criticalcare.com 361
Postoperative problems
Table 2. Electrolyte content of various bodily fluids and average volumes in an adult
Bodily fluid Sodium (mmol/l) Potassium (mmol/l)
Gastric 50
Bile 145
Small bowel 140
Ileostomy 50
Colostomy 60
Diarrhoea 30–140
Maintenance and de-escalation
There have been no randomized trials comparing
different maintenance intravenous fluids, so prac-
tice in this area is based on clinical experience and
consensus opinion. The National Institute for
Health and Care Excellence (NICE) issued the fol-
lowing advice [52]: the maintenance requirements
of water in adults is 25–30 ml/kg/day; ideal body
weight is used in obese patients; 1 mmol/kg/day
of potassium, sodium and chloride is required;
50–100 g/day of glucose to limit starvation ketosis
is also recommended (this will not meet the
patients’ nutritional needs). The composition of
commonly available fluids is outlined in Table 1.
When calculating fluid requirement, additional
losses need to be taken into consideration, for
example, pre-existing deficits and extra losses from
drains or gastrointestinal tract. These additional
losses should be replaced with a fluid with similar
electrolyte composition, for example, 0.9% saline
for gastric fluid losses to prevent hypochloraemic
alkalosis. A summary of the electrolyte contents of
clinically important body fluids is provided in Table
2. The electrolyte content of intravenous medi-
cation (e.g. antibiotics) should also be considered;
these may also have high sodium content. It is
recommended that in addition to standard obser-
vations, fluid balance and body weights should be
recorded, and full blood counts, electrolytes and
renal function should be measured.
Liberal administration of fluids in the perioper-
ative period may result in a postoperative body-
weight increase of 3–6 kg. This may be due to
fluid given to fill the imaginary ‘third space’
[53–55], over-estimation of insensible losses,
replacement of a deficit which does not exist after
fasting [56] and targeting values of central venous
pressure which may be harmful. Evaporation from
open abdominal surgery is only in the region of
0.5–1 ml/kg/h [54], and this has been over-esti-
mated for many years. There is evidence that
we should strive to avoid a grossly positive fluid
balance as this is associated with poor patient out-
come [57–61]. Excessive maintenance fluid can
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Chloride (mmol/l) Volume/day (l)
15 140 2–3
5 100 0.5–1
11 70–130 Varies
4 25 0.5
15 40 0.1–0.2
30–70 Varies
contribute to this. De-escalation from intravenous
fluid to enteral nutrition should be made as soon
as possible.
CONCLUSION
Intravenous fluid therapy is an important aspect of
perioperative care. Evidence suggests that we may be
able to modify outcome by our choice of intrave-
nous resuscitation fluid particularly in high-risk
patients. Current clinical evidence favours the use
of balanced crystalloids for perioperative fluid
therapy and resuscitation. There is no evidence to
suggest that synthetic colloids are superior to crys-
talloids, and because of the possibility of harm, they
cannot be recommended in this setting. There are
no randomized trials comparing maintenance fluid
strategies, but avoidance of salt and water overload
appears to be important, as well as knowledge of the
electrolyte composition of any additional fluid
losses. Further research is required to address
optimal fluid balance aims and resuscitation end-
points in the perioperative setting.
Acknowledgements
None.
Financial support and sponsorship
Michael Gillies holds a Chief Scientist’s Office Scotland
NHS Research Scheme Fellowship.
Conflicts of interest
There are no conflicts of interest.
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