This document discusses how perioperative fluid balance influences postoperative outcomes. It begins by describing how fasting, anesthesia, and surgery affect the body's ability to regulate internal and external fluid balance. Abnormal fluid balance can negatively impact organ function and surgical recovery. The goal of fluid therapy for elective surgery patients is to maintain effective circulatory volume while minimizing interstitial fluid overload. Optimal fluid management should aim for a "zero fluid balance" and avoid overhydration, while ensuring patients are not fluid depleted prior to surgery.

1. 6
How perioperative fluid balance influences
postoperative outcomes
Dileep N. Lobo* DM, FRCS
Senior Lecturer in Gastrointestinal Surgery/Consultant Hepatopancreaticobiliary Surgeon
David A.L. Macafee DM, MRCS
Specialist Registrar in Surgery
Simon P. Allison MD, FRCP
Professor of Clinical Nutrition
Division of Gastrointestinal Surgery, Section of Surgery, E Floor, West Block, University Hospital,
Queen’s Medical Centre, Nottingham NG7 2UH, UK
Fasting, anaesthesia and surgery affect the body’s physiological capacity not only to control its
external fluid and electrolyte balance but also the internal balance between the various body
fluid compartments. Conversely, abnormalities of fluid and electrolyte balance may adversely af-
fect organ function and surgical outcome. Perioperative fluid therapy has a direct bearing on out-
come, and prescriptions should be tailored to the needs of the patient. The goal of fluid therapy
in the elective setting is to maintain the effective circulatory volume while avoiding interstitial
fluid overload whenever possible. Weight gain in elective surgical patients should be minimized
in an attempt to achieve a ‘zero fluid balance status’. On the other hand, these patients should
arrive in the anaesthetic room in a state of normal fluid and electrolyte balance so as to avoid the
need to resuscitate fluid-depleted patients in the anaesthetic room or after the induction of
anaesthesia. Optimal fluid delivery should be part of an overall care package that involves
minimization of the period of preoperative fasting, preoperative carbohydrate loading, thoracic
epidural analgesia, avoidance of nasogastric tubes, early mobilization, and early return to oral
feeding, as exemplified by the enhanced recovery after surgery programme.
Key words: fluid therapy; electrolytes; sodium; perioperative care; postoperative complications;
outcome.
* Corresponding author. Tel.: þ44 115 8231149; Fax: þ44 115 8231160.
E-mail address: dileep.lobo@nottingham.ac.uk (D.N. Lobo).
1521-6896/$ - see front matter ª 2006 Elsevier Ltd. All rights reserved.
Best Practice & Research Clinical Anaesthesiology
Vol. 20, No. 3, pp. 439–455, 2006
doi:10.1016/j.bpa.2006.03.004
available online at http://www.sciencedirect.com

2. Fasting, feeding, trauma and sepsis, emergency and elective surgery, and anaesthesia all
affect the body’s physiological capacity not only to control its external fluid and elec-
trolyte balance but also the internal balance between the various body fluid compart-
ments. Conversely, abnormalities of fluid and electrolyte balance may adversely affect
organ function and surgical outcome.
This review will briefly consider normal fluid and electrolyte physiology before
describing the pathophysiological consequences of trauma, sepsis, anaesthesia, surgery,
and the therapeutic implications of such changes, concentrating mainly on work
published during the past 10 years, but also referring to some key earlier studies. It
will focus on the effects of perioperative fluid balance on the outcome of elective
surgery.
NORMAL PHYSIOLOGY
On average, the human body is 60% water, divided between the extracellular space
(20% of body weight) and the intracellular space (40% of body weight) by the cell
membrane and its energy-dependent sodium pump, which ensures that the cation
Naþ
(135–145 mmol/L) and its salts are the main osmotic agents supporting the integ-
rity of the extracellular fluid volume.1–5
Because of the Gibbs–Donnan equilibrium
which maintains electrical neutrality across the cell membrane, Kþ
plays a similar
role within the intracellular fluid (ICF), balanced largely by the negative charges on in-
tracellular proteins.6
The extracellular fluid (ECF) is divided further into the intravas-
cular and extravascular interstitial spaces by the capillary membrane and the oncotic
pressure of the plasma proteins. Albumin, however, leaks slowly out of the circulation
through the fine capillary pores at a rate of 5%/hr, being returned via the lymphatic
system and the thoracic duct.7
Another important flux is between the ECF and the
gut, with a turnover of 8–9 L/day of water (and electrolytes) from oral intake and in-
testinal secretions. Fasting and feeding affect this flux since sugars and amino acids en-
hance jejunal salt and water absorption and short-chain fatty acids have similar effects
in the colon.8
Post-absorption, the metabolism and distribution of nutrients are also
linked to electrolyte physiology.
Throughout evolution, animals have developed physiological defences to cope with
water lack or excess and with shortage of salt. Not until modern times, too late for it
to mould our physiology, have we been faced with salt excess, which we therefore
handle most inefficiently.4,9,10
PATHOPHYSIOLOGY
The metabolic reaction to injury involves not only the well-known metabolic re-
sponses but also important changes in fluid and electrolyte physiology. Salt (NaCl)
and water are retained avidly in the first few days, called by Moore2
‘the sodium re-
tention phase of injury’. Convalescence and recovery are heralded by a return of the
capacity to excrete any salt and water overload acquired during the earlier phase.
Patients are, therefore, extremely susceptible to errors in fluid prescription early after
injury or surgery, and the urine may contain little salt despite a large overload. Fluid
retention after ether anaesthesia was first noted in 190511
, and the hazards of saline
overload were first reported in 1911.12
440 D. N. Lobo et al

3. The transcapillary escape rate of albumin from the circulation into the interstitial
space increases from 5 to 15%/hr after major surgery and may take up to 10 days
to return to normal.7,13
Sepsis and other complications may prolong this period.
This, and the vasodilatory effects of anaesthetic agents which increase the intravascular
volume requirement (i.e. decrease the effective circulatory volume), have important
therapeutic implications.
With the protein catabolic response to injury, Kþ
is released from the cell as the
number of negative charges is reduced. This may result in hyperkalaemia if severe
catabolism is associated with renal failure. Conversely, the anabolic or convalescent
phase of injury, during which glycogen and protein are resynthesized, causes rapid
uptake of Kþ
leading to hypokalaemia unless adequate amounts are supplemented.
In severe critical illness there may be a breakdown in cell membrane function,
allowing sodium to accumulate intracellularly in abnormally high concentrations, causing
extracellular hyponatraemia – the so-called sick cell syndrome.14
It should be recog-
nized, however, that more than 90% of cases of hyponatraemia in surgical patients
are caused by excessive administration of hypotonic fluids; the response to injury
diminishes free water clearance as well as Naþ
excretion. True salt deficiency is rarely
a contributory cause of hyponatraemia in surgical patients unless significant volumes of
gastrointestinal fluids have been lost or pooled within the gut during illness.
THE EFFECTS OF CRYSTALLOID INFUSIONS IN NORMAL
SUBJECTS AND THEIR IMPLICATIONS FOR PATIENTS
Studies using mathematical models to analyse volume kinetics of Ringer acetate solu-
tion in healthy volunteers demonstrated a more pronounced dilution of serum albu-
min when compared with that of haemoglobin and blood water, suggesting a larger
expandable volume for albumin15–17
and raising the possibility that rapid crystalloid in-
fusion may increase the albumin escape rate from the intravascular space. Large vol-
umes (50 mL/kg over 1 hr) of 0.9% saline infusion in volunteers can produce
abdominal discomfort and pain, nausea, drowsiness and decreased mental capacity
to perform complex tasks, changes not noted after infusion of identical volumes of lac-
tated Ringer’s solution.18
Saline infusions were also associated with a persistent acido-
sis and delayed micturition.
In an attempt to determine which of three intravenous solutions was most effective
in establishing urine flow in healthy volunteers, Heller et al19
rapidly infused 20 mL/kg
of 5% dextrose, 5% dextrose–0.45% saline, or 0.45% saline immediately after voiding.
They found that the mean total urine volume after 5% dextrose was 1181 mL, signif-
icantly greater than after the other two solutions (825 mL and 630 mL respectively),
which did not differ from each other, suggesting, as one might expect, that 5%
dextrose is more effective than sodium-containing solutions in promoting rapid
diuresis.
Drummer et al20
studied the urinary excretion of water and electrolytes and the
changes in hormones controlling salt and water homeostasis during the 48 hr after
an infusion of 2 L 0.9% saline over 25 min, and after a 48-hr control experiment. Urine
flow and urinary electrolyte excretion rates were significantly increased during the 2
days after the saline infusion. These long-term changes were paralleled by altered wa-
ter and sodium balances and also by elevated body weights that returned to baseline
with an approximate half-life of 7 hr. The authors suggested that vasopressin, atrial
natriuretic peptide, and catecholamines were unlikely to be of major importance for
Perioperative fluid balance and postoperative outcomes 441

4. the renal response to this hypervolaemic stimulus. The rennin–angiotensin–aldoste-
rone system (RAAS) was suppressed during 2 days post-infusion, which correlated
with the effects of saline load on sodium excretion. However, the closest relationship
with Na excretion was observed for the kidney-derived member of the atrial natri-
uretic peptide family, urodilatin, which was considerably increased during the long-
term period up to 22 hr post-infusion. Thus, these data show that the human body
in the supine position requires approximately 2 days to restore normal sodium and
water balance after an acute saline infusion, and that urodilatin and the RAAS might
participate in the long-term renal response to such an infusion and in the mediation
of circadian urinary excretion rhythms.
To investigate further the dilutional effects of crystalloids, in the absence of inflam-
mation, normal subjects were infused with either 2 L of 0.9% saline or 5% dextrose
over 1 hr in a randomized, double-blind crossover study.21
Following saline, the serum
albumin concentration dropped within 1 hr by 20% from baseline. This dilution was
sustained beyond 6 hr, and only one third of the administered sodium and water
was excreted by this time. In contrast, although 5% dextrose resulted in an immediate
fall in serum albumin concentration by 16%, this returned to normal 1 hr after infusion
as the water load was rapidly excreted. A further comparison of the effects of 2-L in-
fusions of 0.9% saline and lactated Ringer’s solution over 1 hr in healthy volunteers has
shown that while 0.9% saline had greater and more prolonged blood and plasma
volume-expanding effects than lactated Ringer’s solution, reflected by the greater dilution
of the haematocrit and serum albumin and the sluggish urinary response, these effects
were at the expense of the production of a significant and sustained hyperchlorae-
mia.22
The greater diuresis of water after lactated Ringer’s solution compared with
0.9% saline may be partly explained by its lower osmolality and the reduced antidiu-
retic hormone secretion that this may have engendered. The greater excretion of so-
dium after lactated Ringer’s solution, despite the fact that it contains less sodium than
0.9% saline, is more difficult to understand, unless an effect of the chloride ion and the
[Naþ
]:[Clÿ
] ratios of the two solutions is considered (1:1 for 0.9% saline and 1.18:1
for lactated Ringer’s solution). The low [Naþ
]:[Clÿ
] ratio may be a problem, causing
hyperchloraemic acidosis. Large amounts of infused saline produce an accumulation
of chloride which the kidney is unable to excrete rapidly.23
This may be because the
permeation of the chloride ion across cell membranes is voltage-dependent, and the
amount of chloride in the intracellular fluid is a direct function of the membrane
potential. The cellular content of all other anions, especially phosphate, must ac-
commodate to changes in chloride caused by administration of parenteral fluids.23
Hyperchloraemia also causes renal vasoconstriction and reduces the glomerular
filtration rate.
In a prospective, double-blinded, randomized crossover study by Holte et al24
, 12
healthy volunteers with a median age of 63 years received an infusion of lactated
Ringer’s solution at a rate of 40 mL/kg (median 2820 mL) or 5 mL/kg (median 353 mL)
on two separate occasions over a 3-hr period. The authors found that infusion of
40 mL/kg of lactated Ringer’s solution led to a significant decrease in pulmonary func-
tion and a significant weight gain for 24 hr but without effects on exercise capacity.
Oedema compromises both pulmonary gas exchange and tissue oxygenation, and pro-
duces an increase in tissue pressure in organs surrounded by a non-expandable capsule
(such as the kidney), thereby slowing microvascular perfusion, increasing arteriove-
nous shunting, and reducing lymphatic drainage, all of which facilitate further oedema
formation. Fluid accumulation in the lungs also increases the risk of pneumonia. Re-
moval of excess alveolar fluid is achieved by active sodium transport and the gradient
442 D. N. Lobo et al

5. between the hydrostatic and colloid osmotic pressures. Active sodium transport is af-
fected by fluid administration and by the release of proinflammatory cytokines, both of
which occur perioperatively.25
Apart from avoiding fluid overload, encouraging early
mobilization and deep breathing exercises and maintaining a mid-thoracic epidural
will additionally optimize oxygen delivery and minimize postoperative respiratory
complications. Acidosis impairs cardiac contractility, reduces responsiveness to ino-
tropes, decreases renal perfusion, and can be lethal in combination with hypothermia
and coagulopathy.26
Hyperchloraemic acidosis, as a result of saline infusions has been
shown to reduce gastric blood flow and decrease gastric intramucosal pH in elderly
surgical patients27
, and both respiratory and metabolic acidoses have been associated
with impaired gastric motility in pigs.28
Just as fluid overload causes peripheral oedema,
it may also cause splanchnic oedema resulting in increased abdominal pressure, asci-
tes29
, and even the abdominal compartment syndrome.30
This in turn may lead to a de-
crease in mesenteric blood flow and a further exacerbation of the process, leading to
ileus or functional obstruction of anastomoses, increased gut permeability, intestinal
failure, and even anastomotic dehiscence.4,8,31
Fluid excess may also result in an in-
creased incidence of deep vein thrombosis.31
PERIOPERATIVE FLUID THERAPY: THE PROBLEM AND
SOME SOLUTIONS
‘The objective of care is restoration to normal physiology and normal function of organs, with a
normal blood volume, functional body water and electrolytes. This can never be achieved by
inundation.’32
‘Efforts in the past to restrict fluids. have led to problems of oliguria, anuria and occasionally acute
renal shutdown. Many (if not most) instances of postsurgical shock were unquestionably related to
this same practice of forced hypovolaemia.’33
‘Errors in fluid management (usually fluid excess) were the most common cause of perioperative
morbidity and mortality.’34
The above quotations, and the pathophysiological changes described, emphasize the
difficulties facing the surgeon and anaesthetist in prescribing fluids in order to obtain
optimal physiological benefit and avoid adverse effects. This is easier to achieve with
elective compared with emergency surgery, when compromises may need to be made,
accepting some interstitial fluid overload in the interests of adequate resuscitation
and maintenance of the effective circulatory volume.
The administration of parenteral fluid and electrolytes in the perioperative period
has a bearing on outcome, and the past decade has seen a renewed interest in this
aspect of surgical care. Audits and surveys have shown that the task of prescribing fluid
and electrolytes is often left to the most junior member of the team, and that a rela-
tively weak knowledge of the subject leads to much variability in prescribing that can
result in adverse events and prolonged hospital stay.34–39
The 1999 report of the UK National Confidential Enquiry into Perioperative
Deaths34
has emphasized that fluid imbalance leads to serious postoperative morbidity
and mortality, and estimated that 20% of the patients studied had either poor docu-
mentation of fluid balance or unrecognized and untreated fluid imbalance. It was
recommended that there should be more training in fluid management for medical
and nursing staff to increase awareness and spread good practice, and that fluid man-
agement should be accorded the same status as drug prescription. A recent paper40
Perioperative fluid balance and postoperative outcomes 443

6. and the accompanying editorial41
provide reminders that errors in fluid prescription
are common in hospital practice and are dangerous, particularly at the extremes of
life. An audit from the UK examined postoperative fluid therapy in 71 patients and
found that 17% of these patients developed morbidity related to fluid therapy.39
The tonicity of the infused fluid must also be taken into account. It is particularly dan-
gerous to administer large volumes of hypotonic fluids to the elderly as this may result in
fatal hyponatraemia.42
Changes in plasma sodium are almost always a reflection of
changes in water not sodium balance. A change of 1 mmol/L in plasma sodium concen-
tration is associated with a gain or loss of 280 mL of water in a 70-kg young man, but
with half that amount in a 45-kg elderly woman, who is therefore more easily overloaded
by ill-informed therapy. Severe hyponatraemia (<120 mmol/L) can cause cerebral oe-
dema, particularly in the elderly, and the importance of slow correction at a rate less
than 8 mmol/L/day to avoid osmotic demyelination cannot be overstressed.40,41
At the
other end of the spectrum, the very young and the veryold are at risk of cerebral oedema
if hypernatraemia and hyperosmolar states are corrected too quickly, e.g. in non-ketotic
hyperglycaemia. A volume deficit should be corrected, but the osmolar concentration
should be reduced slowly to allow equilibration between ECF and brain.
Even modest deficits or excesses of salt and water can cause physiological derange-
ment and hence adverse clinical consequences in terms of complications, outcome,
and rate of recovery from disease. When prescribing fluid and electrolytes it is, there-
fore, important to understand the relationship between internal and external balance
and the effects of starvation and injury in order to prevent the adverse physiological
and clinical consequences of errors in treatment.
Attention to detail and better education are the keys to better prescribing of par-
enteral fluids, and the prescriber must ask two questions: (1) Does the patient need
parenteral fluid?, and (2) Why does the patient need fluid? If the answer to the first
question is yes, there are three possible responses to the second: (a) to correct an
intravascular or extracellular fluid volume deficit (i.e. the treatment of hypovolaemia),
(b) to replace ongoing losses (e.g. a patient with a gastrointestinal fistula), or (c) to
supply maintenance requirements (e.g. the uncomplicated postoperative patient).
In health, the average human requires 25–35 mL/kg/day of water, 0.9–1.5 mmol/kg/
day of sodium, and approximately 1 mmol/kg/day of potassium. This constitutes the
maintenance requirement and, in the average 70-kg person, amounts to 1.7–2.5 L
water, 60–105 mmol sodium and 70 mmol potassium/day. Patients also require 400
Calories (100 g dextrose)/day to prevent starvation ketosis. These requirements are
usually met by adding 60–80 mmol potassium to 2.0–2.5 L of 4% dextrose in 0.18%
sodium chloride. If this volume of dextrose saline is exceeded, patients are likely to
develop hyponatraemia which can sometimes be life-threatening.
When patients require more than 2.5 L/day, it usually means that they have ongoing
losses or that they may be hypovolaemic. Patients with ongoing losses must be pre-
scribed like-for-like replacement of the losses in addition to the maintenance require-
ments. It is therefore important to know the electrolyte content of the fluid being lost
in order to provide the appropriate replacement. With chronic or large-volume losses,
minerals and trace elements such as magnesium and selenium may also need to be
replaced.
Salt-containing crystalloids and colloids are used during resuscitation to restore the
effective circulatory volume. The ability of a solution to expand the plasma volume is
dependent on the volume of distribution of the solute, so that while colloids are
mainly distributed in the intravascular compartment, dextrose-containing solutions
are distributed through the total body water and hence have a limited and transient
444 D. N. Lobo et al

7. volume-expanding capacity. Isotonic sodium-containing crystalloids are distributed
throughout the extracellular space, and textbook teaching suggests that such infusions
expand the blood volume by one third of the volume of crystalloid infused. In practice,
however, the efficiency of these solutions to expand the plasma volume is only 20–
25%, the remainder being sequestered in the interstitial space.21,22
In the severely injured and the critically ill, with a major inflammatory response
there is leucocyte activation and increased microvascular permeability.7
Increased cap-
illary permeability leads to a leak of plasma proteins, electrolytes and water from the
intravascular compartment to the interstitial space. This may be protective, as it allows
immune mediators to cross the capillary barrier and reach the site of injury or infec-
tion. However, increased capillary permeability may also lead to intravascular hypovo-
laemia and expansion of the interstitial space. Such patients may require large amounts
of sodium-containing crystalloids to maintain intravascular volume and oxygen delivery
to the cells, although artificial colloids allow the use of lower volumes.
Salt and water overload may often be an inevitable consequence of resuscitation.
However, continuing to give large volumes of salt-containing fluids for ‘maintenance’
may cause unnecessary and increasingly positive cumulative salt and water balance.
The average ECF overload after the first 2 days of resuscitation of patients with sepsis
has been shown to be in excess of 12 L, which takes about 3 weeks to excrete.43
The
association of increased capillary permeability and profound positive fluid balance with
multi-organ failure is being recognized, and attempts to limit interstitial oedema have
been beneficial.
In the post-acute phase, patients transferred from the intensive care unit may be
grossly oedematous and have 10–20 L of excess extracellular fluid. Using low-volume
and zero- or low-sodium feeds, diuretics, and in a few cases 20% salt-poor albumin, the
oedema usually resolves over 7–14 days, and the serum albumin concentration rises by
1 g/L for every 1 kg loss of excess fluid.44
Loss of this excess fluid is usually accompa-
nied by an improvement in the general condition of the patient, increased mobility, and
the ability to increase oral food intake.
Nevertheless, it must be remembered that a good surgical outcome requires more
than just attention to fluid balance. The role of meticulous surgical technique, antibi-
otics, and modern anaesthetic practice and agents in smoothing the perioperative
course of patients cannot be overstated.45,46
PERIOPERATIVE FLUID THERAPY – EFFECTS ON ORGAN
FUNCTION AND OUTCOME: THE EVIDENCE
Retrospective and cohort studies
Lowell et al47
prospectively monitored 48 consecutive patients admitted to an ICU
postoperatively. They found that the 40% who gained >10% weight from preoperative
or premorbid records, indicative of fluid overload had significantly greater morbidity
and length of ICU stay. Mortality in the patients who gained >10% body weight was
31.6% (versus 10.3% in the group that gained <10% body weight) and increased
with greater weight gain, with patients who gained >20% body weight having a mortal-
ity rate of 100%. There were no differences in admission APACHE II scores in the
different groups.
Arieff48
retrospectively analysed the records of 13 patients, with a mean age of
38 years and no comorbidity, who had died from postoperative pulmonary oedema.
Perioperative fluid balance and postoperative outcomes 445

8. He found that pulmonary oedema was neither detected nor predicted by conventional
monitoring parameters such as heart rate, mean arterial pressure, central venous
pressure, and urine output. He also suggested that postoperative pulmonary oedema
is more likely within the initial 36 hr when net fluid retention exceeds 67 mL/kg/day.
He then reviewed the records of 8195 patients undergoing major surgery at two uni-
versity hospitals over 1 year and found that the overall incidence of postoperative pul-
monary oedema was 7.6%, being fatal in 11.9%; 2.6% of the patients who developed
pulmonary oedema had no comorbidities, and the net fluid retention in these patients
was 90 mL/kg/day, suggesting that excessive perioperative fluid infusion was the most
likely cause of the pulmonary oedema.
The records of 36 patients admitted to the intensive care unit with septic shock,
excluding those who needed dialysis, were reviewed, and it was found that while all
11 patients who achieved a negative fluid balance of >500 mL on one or more of
the first 3 days of admission survived, only five of 25 patients who failed to achieve
this state of negative fluid balance by the third day of treatment survived.49
The
authors concluded that at least 1 day of net negative fluid balance on the first 3
days of treatment strongly predicted survival.
In a study performed to identify risk factors for complications and mortality asso-
ciated with elective pneumonectomy in 107 patients, 31 patients (29%) suffered from
one or more postoperative complications, and the overall mortality rate was 10.3%.50
Logistic regression analysis indicated that positive fluid balance exceeding 4 L during
anaesthesia was associated with a higher risk of postoperative complications than
blood loss exceeding 1 L, and was the strongest risk factor for postoperative pulmo-
nary complications and mortality.
In a non-randomized pilot study of 56 consecutive patients undergoing near-total
oesophagectomy, Neal et al51
restricted intraoperative intravenous fluids to achieve
an intraoperative urine output of 0.3–0.5 mL/kg/hr in an attempt to reduce fluid shifts
into the interstitium of the lungs and gut. If the urine output fell below this range,
further fluids were administered and inotropes and fluid were used, when required,
to maintain systolic blood pressure within 20% of baseline. Postoperatively, patients
received 1–1.5 mL/kg/hr of lactated Ringer’s solution until enteral nutrition was
started on day 3 or 4, and a urine output of 20–30 mL/hr was accepted in patients
with a normal serum creatinine concentration. Patients also received frusemide as
required between days 2 and 6 to assist excretion of fluid overload. All patients
were extubated in the operating theatre, and no patient developed postoperative
renal insufficiency or respiratory failure. Complications occurred in 18% of patients,
and there were no deaths within 30 days. Although there was no control group in
this study with which to compare the effects of a ‘restrictive’ fluid regimen, the re-
sults suggest that excellent surgical results can be obtained by avoiding fluid overload
and resisting the temptation to achieve an unnecessarily high urine output in the set-
ting of multimodal care.
A retrospectivecohort studyof 100 patients undergoing colonic and rectal resections
found that by day 5 the mean cumulative total intravenous fluid input was between 10 and
13 L and that of sodium between 874 and 1168 mmol.38
Although this study has the
drawbacks of being retrospective, the authors were able to show that despite compara-
ble ASA grades, POSSUM scores, operative magnitude and blood loss, patients under-
going colonic resections receiving a mean of 149 mmol sodium/day were more likely
to develop postoperative complications than those receiving a mean of 115 mmol
sodium/day in the postoperative period. No differences in complication rates were
noted for patients undergoing rectal surgery.
446 D. N. Lobo et al

9. Randomized controlled trials and meta-analyses
Mitchell et al52
randomized 101 patients with pulmonary oedema to management based
on pulmonary artery wedge pressure (n ¼ 49) or extravascular lung water (n ¼ 52),
and found that the latter group showed less than half the cumulative fluid balance, had
reduced interstitial oedema, and spent significantly fewer days on the ventilator and in
the intensive care unit.
The belief that prolongation of gastric emptying time and persistent ileus postoper-
atively was related to hypoalbuminaemia53
led Woods and Kelly54
to test the hypoth-
esis that raising the serum albumin concentration to >35 g/L with albumin infusions
would result in shortening of the duration of postoperative ileus. They selected 83
patients undergoing elective major vascular surgery and randomized them either to
receive (n ¼ 37) or not to receive (n ¼ 32) postoperative albumin infusions. Albumin
was infused until the serum albumin concentration exceeded 35 g/L. Further infusions
were given if the serum albumin concentration fell below that level. Although serial
serum albumin concentrations were significantly higher in the albumin replacement
group, the authors were not able to demonstrate a significant difference in either
the duration of ileus (albumin 4.06 versus no albumin 4.16 days) or the time to resume
an oral intake (4.0 versus 3.75 days). Postoperative hospital stay and complication rates
were also similar in the two groups. These authors54
, however, did not record the fluid
balance status of these patients, and a similar degree of hydration (or overhydration) in
the two groups could explain the almost identical results when the endpoints were
compared. If patients in both groups were infused with similar volumes of crystalloids,
the albumin group ran the risk of a greater expansion of intravascular volume, a factor
that could explain the lack of difference. This lends credence to the theory that it is
salt and water balance, and not the serum albumin concentration per se, that is the
determinant of recovery from postoperative ileus.
We conducted an unblinded physiological experiment to study the clinical conse-
quences of modest fluid gains by randomizing 20 patients undergoing uncomplicated
colonic surgery to receive postoperative intravenous fluids according to hospital prac-
tice at the time i.e. 3 L water and 154 mmol sodium/day (standard group) or 2 L
water and 77 mmol sodium/day (restricted group).55
Although intraoperative fluid
therapy was not controlled, patients in the two groups received similar amounts of
water and sodium intraoperatively. The primary endpoint was solid- and liquid-phase
gastric emptying time, measured by dual-isotope radionuclide scintigraphy on the 4th
postoperative day. There was a 3-kg greater weight gain in the standard group, reflect-
ing positive salt and water balance, compared with zero balance in the restricted
group. There was no significant difference between the groups when urine output, uri-
nary sodium excretion, and blood urea concentration were compared. In the standard
group, solid- and liquid-phase gastric emptying times (T50) were significantly longer
(median: 175 versus 72.5 min, P ¼ 0.028 and 110 versus 73.5 min, P ¼ 0.017 respec-
tively); passage of flatus was 1 day later (median: 4 versus 3 days, P ¼ 0.001); passage
of stool 2.5 days later (median: 6.5 versus 4 days, P ¼ 0.001). Although the study was
not designed to look for a difference in complication rate, patients in the restricted
group had fewer side-effects and complications and were able to be discharged 3
days earlier. These results suggest that salt and water retention is not a harmless
and inevitable epiphenomenon, and should be avoided where possible by restricting
maintenance fluids to the amount necessary to achieve zero balance. This is not to
deny the need for adequate replacement of additional losses of intravascular or extra-
cellular fluid.
Perioperative fluid balance and postoperative outcomes 447

10. In a randomized, multicentre, observer-blinded study, Brandstrup et al56
have
also demonstrated that among patients undergoing colorectal resections, a group
receiving a fluid regimen restricted to that necessary to maintain a constant
body weight (i.e. zero balance) had fewer complications and better outcome
than a group given standard perioperative fluids causing a 3–7-kg increase in
body weight. This was especially apparent when cardiopulmonary complications
were looked at (24% in the standard group and 7% in the restricted group,
P ¼ 0.0007). A dose–response relationship was noted between postoperative com-
plications and increased volumes of intravenous fluid causing postoperative weight
gain. Patients in the standard group (n ¼ 72) received 500 mL 0.9% saline for the
period of preoperative fasting and 500 mL 6% hydroxyethyl starch (HES) in 0.9%
saline as preload before epidural analgesia. For third-space losses, these patients
received 7 mL/kg/hr of 0.9% saline for the first hour of surgery, 5 mL/kg/hr for
the next 2 hours, and 3 mL/kg/hr thereafter. The first 500 mL of blood loss was
replaced with 1.0–1.5 L of crystalloid, and 6% HES was given for further blood
loss. Postoperatively on the day of the operation, these patients received 1–2 L
crystalloid, and thereafter fluid requirements were guided by recommendations
from the treating surgical units. On the other hand, patients in the restricted group
(n ¼ 69) received 500 mL 5% dextrose in water for the fasting period, and no pre-
load was given for epidural analgesia. Blood loss was replaced with 6% HES on
a volume-for-volume basis. No fluid replacement was made for third-space losses.
Postoperatively, these patients received 1000 mL 5% dextrose in water, and losses
through drains were replaced with equal volumes of 6% HES. A weight gain in
excess of 1 kg was treated with frusemide. The authors felt that elimination of pre-
loading and replacement of third-space losses, as well as maintenance of body
weight (i.e. a zero fluid balance state), result in improved outcome in the restricted
group.
More recently, Nisanevich et al57
prospectively evaluated the impact of two in-
traoperative fluid regimens on postoperative outcome in 152 patients undergoing
elective abdominal surgery. Patients were randomly assigned to receive, intraoper-
atively, either liberal (liberal protocol group [LPG], n ¼ 75; bolus of 10 mL/kg
followed by 12 mL/kg/hr) or restrictive (restrictive protocol group [RPG], n ¼ 77;
4 mL/kg/hr) amounts of lactated Ringer’s solution. Although the total amount of
intravenous fluid infused intraoperatively was significantly greater in the LPG than
in the RPG (3.8 versus 1.4 L), there was no difference in the volume of fluid
infused on each of the first 3 postoperative days (2.2 L/day). Intraoperative and
postoperative blood pressure, pulse rate and oxygen saturation were similar in
the two groups. There were no deaths in either group, but significantly fewer
patients developed complications in the RPG than in the LPG (16.9% versus
30.6%, P ¼ 0.046). Patients in the LPG passed flatus and faeces significantly later
(1 and 2 days later, respectively), and had a significantly longer postoperative hos-
pital stay (9 versus 8 days) than those in the RPG. Significantly larger increases in
body weight were observed in the LPG compared with the RPG (P 0.01), provid-
ing further evidence that even modest fluid (and salt) overload in the perioperative
period can lead to a poorer outcome.
Arkilic et al58
tested the hypothesis that supplemental crystalloid administration
during and after elective colon resection increases tissue perfusion and tissue
oxygen pressure by randomizing 56 patients undergoing colon resection to receive
conservative (8 mL/kg/hr, n ¼ 26) or aggressive (16–18 mL/kg/hr, n ¼ 30) fluid manage-
ment. Patients received crystalloids, but the exact nature of the fluid infused is not
448 D. N. Lobo et al

11. mentioned. They found that although haemodynamic and renal responses were similar
between the groups, intraoperative tissue oxygen tension, postoperative subcutane-
ous oxygen tension and capillary blood flow were significantly greater in patients given
supplemental fluid. The authors, however, do not provide information about other
outcome measures such as postoperative complications and hospital stay, and it is dif-
ficult to form any firm conclusion from this study. A further randomized controlled
trial undertaken by the same group and using identical fluid infusion regimens has
shown that supplemental crystalloid administration did not reduce the risk of postop-
erative wound infection.59
Preoperative optimization of fluid and electrolyte balance is important, especially in
the elderly, if postoperative outcome is to be improved. Patients receiving preopera-
tive bowel preparation for colorectal procedures can be moderately dehydrated
(1–2 L) or have major electrolyte imbalance.60,61
Two recent randomized controlled
trials have shown that careful concurrent administration of either intravenous62
or
oral rehydration solutions63
may help to restore normal balance, with care being taken
to avoid excess, and improve outcome. Even though conclusions from a recent meta-
analysis call into question routine mechanical bowel preparation prior to colorectal
operations64
, these studies emphasize the importance of restoring the effective circu-
latory volume prior to the induction of anaesthesia.
Avoidance of prolonged preoperative fasting, allowing patients a normal diet on the
day prior to the operation, and provision of free fluids and a carbohydrate drink up to
2 hr before the induction of anaesthesia46
not only decreases postoperative insulin re-
sistance but also ensures that patients are more likely to reach the anaesthetic room in
a state of adequate hydration, and that the anaesthetist does not have to play ‘catch up’
and resuscitate a dehydrated patient. These issues are dealt with in more detail else-
where in this volume (Chapter 573
).
In a randomized trial of 138 patients, Wilson et al65
have shown that preoper-
ative optimization of oxygen delivery using fluid optimization strategies and ino-
tropes in patients with coexistent medical conditions undergoing major elective
surgery could result in a significant and cost-effective improvement of postopera-
tive outcome.
Mythen and Webb66
randomized 60 patients with a preoperative left ventricular
ejection fraction 50% undergoing elective cardiac surgery to test the hypothesis
that perioperative plasma volume expansion would preserve gut mucosal perfusion.
Patients in the control group were treated according to standard practices. The
protocol group received additional 200-mL boluses of 6% HES to obtain a maxi-
mum stroke volume (as measured by trans-oesophageal Doppler) after induction
of general anaesthesia. These boluses were repeated every 15 min until the end
of surgery, except for the period when the patient underwent cardiopulmonary
bypass. Fewer patients in the protocol group (7% versus 56%, P 0.001) showed
evidence of gut mucosal hypoperfusion (gastric intramucosal pH 7.32, measured
by gastric tonometry) at the end of surgery. The protocol group also fared signif-
icantly better than the control group when the number of patients in whom major
complications developed (0 versus 6), and the mean durations spent in the hospi-
tal (6.4 versus 10.1 days) and in the intensive care unit (1 versus 1.7 days) were
compared.
A meta-analysis of two studies, randomizing a total of 130 patients, to determine
the optimal method of fluid volume optimization for adult patients undergoing surgical
repair of hip fracture has been undertaken by the Cochrane group of reviewers.67
Both studies involved invasive advanced haemodynamic monitoring during the
Perioperative fluid balance and postoperative outcomes 449

12. intraoperative period only. One study randomized patients to ‘normal care’ or optimi-
zation using trans-oesophageal Doppler.68
The other randomized patients to ‘normal
care’, trans-oesophageal Doppler, or central venous pressure monitoring.69
In each
study, invasive monitoring led to a significant increase in the volume of fluid infused
and a reduction in length of hospital stay. The odds ratio for in-hospital fatality was
1.44 (95% confidence interval 0.45–4.62).
Gan et al70
, using a similar protocol to that used by Sinclair et al68
, prospectively
randomized 100 patients undergoing major elective surgery with an anticipated
blood loss 500 mL to a control group (n ¼ 50) that received standard intraopera-
tive care or to a protocol group (n ¼ 50) that, in addition to standard care, received
intraoperative plasma volume expansion guided by trans-oesophageal Doppler to
maintain maximal stroke volume. Although the volume of crystalloid and packed
red blood cells administered intraoperatively were similar in the two groups, pa-
tients in the protocol group received significantly greater amounts of 6% HES
than those in the control group (847 versus 282 mL). Patients in the protocol group
had a significantly higher stroke volume and cardiac output at the end of surgery
compared with those in the control group, and had a shorter postoperative hospital
stay (mean 2 days shorter, median 1 day shorter). They also tolerated oral intake of
solid food earlier than the control group, with a lower incidence of postoperative
nausea and vomiting.
Another study assessed the use of intraoperative oesophageal Doppler-guided
fluid management to minimize hypovolaemia on postoperative hospital stay and the
time before return of gut function after colorectal surgery in 128 patients who
were prospectively randomized to oesophageal Doppler-guided or central venous
pressure-(CVP)-based (conventional) intraoperative fluid management.71
The fluid
protocol in the intervention group was guided by oesophageal Doppler, whereas pa-
tients in the control group were managed using routine cardiovascular monitoring
aiming for a CVP between 12 and 15 mmHg. The median postoperative stay in the-
Doppler-guided fluid group was 10 versus 11.5 days in the control group (P 0.05).
The median time to resuming full diet in the Doppler-guided fluid group was 6 versus
7 days for controls (P 0.001). Patients in the Doppler-guided group achieved signif-
icantly higher cardiac output, stroke volume, and oxygen delivery. Twenty-nine
(45.3%) patients in the control group had gastrointestinal complications compared
with nine (14.1%) in the Doppler-guided group (P 0.001), and overall morbidity
was also significantly higher in the control group (P ¼ 0.013). The authors were
unable to demonstrate a statistically significant difference in intestinal permeability,
serum endotoxin concentration, inflammatory markers, or quality of life between
the two groups. Although the authors have been able to demonstrate a better out-
come in patients in the Doppler-guided group, the hospital stay was much greater
than that achieved in trials in which perioperative fluid therapy was restricted.55–57
It must also be pointed out that the authors of the trials using trans-oesophageal
Doppler do not specify the protocol used for postoperative fluid therapy, and
volumes of fluid infused postoperatively have not been mentioned. It is possible
that postoperative fluid regimens may have had some bearing on outcome, and
further trials in which both intraoperative and postoperative fluid regimens are
controlled are required.
The almost universal practice of preoperative fasting results in some patients ar-
riving in the anaesthetic room with a fluid deficit. Induction of anaesthesia in patients
with a fluid deficit further reduces the effective circulatory volume by decreasing
sympathetic tone. Inadequate fluid resuscitation and decreased tissue perfusion can
450 D. N. Lobo et al

13. lead to gastrointestinal mucosal acidosis and poorer outcome66
, but this must be bal-
anced against the deleterious effects of tissue oedema and hyperchloraemic acidosis
caused by excessive administration of saline solutions.26,31
The studies using trans-
oesophageal Doppler have shown that optimization of left ventricular stroke volume
by administration of colloid boluses can result in improved outcome, but it should be
remembered, taking into account the Frank–Starling curve, that after a point further
fluid challenges could result in overfilling and a decrease in left ventricular perfor-
mance. Infusion of fluid after this response will lead to fluid overload with no benefit,
and even possible detriment, to the patient. This emphasizes the importance of the
use of trans-oesophageal Doppler for monitoring of stroke volume when giving these
fluid challenges. In addition, appropriate boluses of colloid expand the effective circu-
latory volume to a greater extent and produce less interstitial oedema than equiva-
lent boluses of crystalloid.
Holte et al72
, in a double-blind study, randomized 48 patients undergoing laparo-
scopic cholecystectomy to receive either 15 mL/kg (group 1) or 40 mL/kg (group 2)
of lactated Ringer’s solution intraoperatively. Although there was no significant differ-
ence in intraoperative and postoperative haemodynamics between the two groups, the
authors found that infusion of larger volumes of lactated Ringer’s solution led to sig-
nificant improvements in postoperative pulmonary function and exercise capacity and
a reduced stress response. Nausea, general well-being, thirst, dizziness, drowsiness,
fatigue, and balance function were also significantly improved, and significantly more
patients fulfilled discharge criteria and were discharged on the day of surgery with
the high-volume fluid substitution. The findings of this study, especially the effects
on pulmonary function, contradict earlier work done by the same group on healthy
volunteers.24
Most of these studies support the concept of prescribing fluids to maintain optimal
physiological function while avoiding inadequate replacement or unnecessary overload,
both of which may adversely affect outcome.
SUMMARY AND CONCLUSIONS
Perioperative fluid therapy has a direct bearing on outcome, and prescriptions
should be tailored to the needs of the patient. The goal of fluid therapy in the
elective setting is to maintain the effective circulatory volume while avoiding inter-
stitial fluid overload whenever possible. Weight gain in elective surgical patients
should be minimized in an attempt to achieve a ‘zero fluid balance status’. On
the other hand, patients should arrive in the anaesthetic room in a state of normal
fluid and electrolyte balance so as to avoid the need to resuscitate fluid-depleted
patients in the anaesthetic room or after the induction of anaesthesia. Daily weigh-
ing, where possible, is the best measure of fluid gain or loss. Fluid balance charts,
while helpful, have inherent inaccuracies, and reliance upon them alone can lead to
inaccuracies in prescription.
Optimal fluid delivery should be part of an overall care package that involves
minimization of the period of preoperative fasting, preoperative carbohydrate
loading, thoracic epidural analgesia, avoidance of nasogastric tubes, early mobiliza-
tion, and early return to oral feeding, as exemplified by the enhanced recovery
after surgery programme.46
Too much or too little fluid can adversely affect
outcome.
Perioperative fluid balance and postoperative outcomes 451

14. REFERENCES
1. Edelman IS Leibman J. Anatomy of body water and electrolytes. The American Journal of Medicine 1959;
27: 256–277.
2. Moore FD. Metabolic Care of the Surgical Patient. Philadelphia: W.B. Saunders; 1959.
3. Rose BD Post TW. Clinical Physiology of Acid-base and Electrolyte Disorders. New York: McGraw-Hill;
2001.
*4. Lobo DN. Sir David Cuthbertson medal lecture. Fluid, electrolytes and nutrition: physiological and
clinical aspects. The Proceedings of the Nutrition Society 2004; 63: 453–466.
*5. Grocott MPW, Mythen MG Gan TJ. Perioperative fluid management and clinical outcomes in adults.
Anesthesia and Analgesia 2005; 100: 1093–1106.
6. Nguyen MK Kurtz I. Quantitative interrelationship between Gibbs–Donnan equilibrium, osmolality of
body fluid compartments, and plasma water sodium concentration. Journal of Applied Physiology 2006;
100: 1293–1300.
7. Fleck A, Raines G, Hawker F et al. Increased vascular permeability: a major cause of hypoalbuminaemia
in disease and injury. Lancet 1985; 1: 781–784.
8. Macafee DA, Allison SP Lobo DN. Some interactions between gastrointestinal function and fluid and
electrolyte homeostasis. Current Opinion in Clinical Nutrition and Metabolic Care 2005; 8: 197–203.
9. Allison S. Fluid, electrolytes and nutrition. Clinical Medicine 2004; 4: 573–578.
10. Macallum AB. The paleochemistry of body fluids and tissues. Physiological Reviews 1926; 6: 316–357.
11. Pringle H, Maunsell RCB Pringle S. Clinical effects of ether anaesthesia on renal activity. British Medical
Journal 1905; ii: 542–543.
Practice points
achieve oral intake as early as possible postoperatively
it is only too easy to give too much fluid, sodium and chloride intravenously
the aim of administration of parenteral fluid should always be clear (main-
tenance, replacement or resuscitation)
parenteral fluids must be administered to maintain the effective circulatory vol-
ume while attempting to minimize interstitial fluid overload
judicious fluid prescribing should ensure that the type, composition, rate of in-
fusion, and electrolyte concentrations of the fluid are appropriate for each in-
dividual patient
Research agenda
to find effective ways of improving fluid prescription through education
to conduct animal studies to further define the effects of salt and water excess
on organ function and wound healing
to conduct further clinical studies in different groups of surgical patients to
define optimal fluid prescriptions appropriate to various clinical situations
to study further the changes associated with surgery in the fluid distribution
between the body’s compartments (internal balance) and to find better ways
of maintaining effective circulatory volume without interstitial overload
to work with industry to develop more physiologically balanced carrier
solutions for colloids
452 D. N. Lobo et al

15. 12. Evans GH. The abuse of normal salt solution. Journal of the American Medical Association 1911; 57: 2126–
2127.
13. Anderson JA, Lobo DN, Lawes SC et al. Sequential changes in serum albumin, c-reactive protein and
transcapillary escape rate of albumin in patients undergoing major abdominal surgery (abstract). Clinical
Nutrition 2002; 21(supplement 1): 29.
14. Flear CT Singh CM. Hyponatraemia and sick cells. British Journal of Anaesthesia 1973; 45: 976–994.
15. Hahn RG Drobin D. Urinary excretion as an input variable in volume kinetic analysis of Ringer’s
solution. British Journal of Anaesthesia 1998; 80: 183–188.
16. Hahn RG Svensen C. Plasma dilution and the rate of infusion of Ringer’s solution. British Journal of
Anaesthesia 1997; 79: 64–67.
17. Svensen C Hahn RG. Volume kinetics of Ringer solution, dextran 70, and hypertonic saline in male
volunteers. Anesthesiology 1997; 87: 204–212.
18. Williams EL, Hildebrand KL, McCormick SA Bedel MJ. The effect of intravenous lactated Ringer’s
solution versus 0.9% sodium chloride solution on serum osmolality in human volunteers. Anesthesia
and Analgesia 1999; 88: 999–1003.
19. Heller MB, Crocco T, Prestosh JC Patterson JW. Effectiveness of different crystalloid i.v. solutions in
establishing urine flow. The Journal of Emergency Medicine 1996; 14: 1–3.
20. Drummer C, Gerzer R, Heer M et al. Effects of an acute saline infusion on fluid and electrolyte metab-
olism in humans. American Journal of Physiology 1992; 262: F744–F754.
21. Lobo DN, Stanga Z, Simpson JAD et al. Dilution and redistribution effects of rapid 2-litre infusions of
0.9% (w/v) saline and 5% (w/v) dextrose on haematological parameters and serum biochemistry in
normal subjects: a double-blind crossover study. Clinical Science 2001; 101: 173–179.
22. Reid F, Lobo DN, Williams RN et al. (Ab)normal saline and physiological Hartmann’s solution: a random-
ized double-blind crossover study. Clinical Science 2003; 104: 17–24.
*23. Veech RL. The toxic impact of parenteral solutions on the metabolism of cells: a hypothesis for
physiological parenteral therapy. The American Journal of Clinical Nutrition 1986; 44: 519–551.
24. Holte K, Jensen P Kehlet H. Physiologic effects of intravenous fluid administration in healthy
volunteers. Anesthesia and Analgesia 2003; 96: 1504–1509.
25. Matthay MA, Fukuda N, Frank J et al. Alveolar epithelial barrier. Role in lung fluid balance in clinical lung
injury. Clinics in Chest Medicine 2000; 21: 477–490.
26. Ho AM, Karmakar MK, Contardi LH et al. Excessive use of normal saline in managing traumatized
patients in shock: a preventable contributor to acidosis. The Journal of Trauma 2001; 51: 173–177.
27. Wilkes NJ, Woolf R, Mutch M et al. The effects of balanced versus saline-based hetastarch and crystal-
loid solutions on acid-base and electrolyte status and gastric mucosal perfusion in elderly surgical pa-
tients. Anesthesia and Analgesia 2001; 93: 811–816.
28. Tournadre JP, Allaouchiche B, Malbert CH Chassard D. Metabolic acidosis and respiratory acidosis
impair gastro-pyloric motility in anesthetized pigs. Anesthesia and Analgesia 2000; 90: 74–79.
29. Mayberry JC, Welker KJ, Goldman RK Mullins RJ. Mechanism of acute ascites formation after trauma
resuscitation. Archives of Surgery 2003; 138: 773–776.
30. Balogh Z, McKinley BA, Cocanour CS et al. Supranormal trauma resuscitation causes more cases of
abdominal compartment syndrome. Archives of Surgery 2003; 138: 637–642 [discussion 642–633].
*31. Holte K, Sharrock NE Kehlet H. Pathophysiology and clinical implications of perioperative fluid
excess. British Journal of Anaesthesia 2002; 89: 622–632.
32. Moore FD Shires G. Moderation. Annals of Surgery 1967; 166: 300–301.
33. Layon JA, Bernards WC Kirby RR. Fluids and electrolytes in the critically ill. In Civetta JM, Taylor RW
Kirby RR (eds.). Critical Care. Baltimore: Lippincott, 1992.
34. Callum KG, Gray AJG, Hoile RW et al. Extremes of Age: The 1999 Report of the National Confidential
Enquiry into Perioperative Deaths. London: National Confidential Enquiry into Perioperative Deaths;
1999.
35. Lobo DN, Dube MG, Neal KR et al. Peri-operative fluid and electrolyte management: a survey of
consultant surgeons in the UK. Annals of the Royal College of Surgeons of England 2002; 84: 156–160.
36. Lobo DN, Dube MG, Neal KR et al. Problems with solutions: drowning in the brine of an inadequate
knowledge base. Clinical Nutrition 2001; 20: 125–130.
37. Stoneham MD Hill EL. Variability in post-operative fluid and electrolyte prescription. British Journal of
Clinical Practice 1997; 51: 82–84.
Perioperative fluid balance and postoperative outcomes 453

16. 38. Tambyraja AL, Sengupta F, MacGregor AB et al. Patterns and clinical outcomes associated with routine
intravenous sodium and fluid administration after colorectal resection. World Journal of Surgery 2004;
28: 1046–1051 [discussion 1051–1042].
39. Walsh SR Walsh CJ. Intravenous fluid-associated morbidity in postoperative patients. Annals of the
Royal College of Surgeons of England 2005; 87: 126–130.
40. Shafiee MA, Bohn D, Hoorn EJ Halperin ML. How to select optimal maintenance intravenous fluid
therapy. QJM: monthly journal of the Association of Physicians 2003; 96: 601–610.
41. Sterns RH Silver SM. Salt and water: read the package insert. QJM: monthly journal of the Association of
Physicians 2003; 96: 549–552.
42. Lane N Allen K. Hyponatraemia after orthopaedic surgery [editorial]. British Medical Journal 1999;
318: 1363–1364.
43. Plank LD, Connolly AB Hill GL. Sequential changes in the metabolic response in severely septic
patients during the first 23 days after the onset of peritonitis. Annals of Surgery 1998; 228: 146–158.
44. Lobo DN, Bjarnason K, Field J et al. Changes in weight, fluid balance and serum albumin in patients
referred for nutritional support. Clinical Nutrition 1999; 18: 197–201.
45. Kehlet H Wilmore DW. Multimodal strategies to improve surgical outcome. American Journal of Sur-
gery 2002; 183: 630–641.
*46. Fearon KC, Ljungqvist O, Von Meyenfeldt M et al. Enhanced recovery after surgery: a consensus review
of clinical care for patients undergoing colonic resection. Clinical Nutrition 2005; 24: 466–477.
47. Lowell JA, Schifferdecker C, Driscoll DF et al. Postoperative fluid overload: not a benign problem.
Critical Care Medicine 1990; 18: 728–733.
48. Arieff AI. Fatal postoperative pulmonary edema: pathogenesis and literature review. Chest 1999; 115:
1371–1377.
49. Alsous F, Khamiees M, DeGirolamo A et al. Negative fluid balance predicts survival in patients with
septic shock: a retrospective pilot study. Chest 2000; 117: 1749–1754.
50. Moller AM, Pedersen T, Svendsen PE Engquist A. Perioperative risk factors in elective pneumonec-
tomy: the impact of excess fluid balance. European Journal of Anaesthesiology 2002; 19: 57–62.
51. Neal JM, Wilcox RT, Allen HW Low DE. Near-total esophagectomy: the influence of standardized
multimodal management and intraoperative fluid restriction. Regional Anesthesia and Pain Medicine
2003; 28: 328–334.
52. Mitchell JP, Schuller D, Calandrino FS Schuster DP. Improved outcome based on fluid management in
critically ill patients requiring pulmonary artery catheterisation. American Review of Respiratory Disease
1992; 145: 990–998.
53. Mecray PM, Barden RP Ravdin IS. Nutritional edema: its effect on the gastric emptying time before
and after gastric operations. Surgery 1937; 1: 53–64.
54. Woods MS Kelley H. Oncotic pressure, albumin and ileus: the effect of albumin replacement on
postoperative ileus. The American Surgeon 1993; 59: 758–763.
*55. Lobo DN, Bostock KA, Neal KR et al. Effect of salt and water balance on recovery of gastrointestinal
function after elective colonic resection: a randomised controlled trial. Lancet 2002; 359: 1812–1818.
*56. Brandstrup B, Tonnesen H, Beier-Holgersen R et al. Effects of intravenous fluid restriction on postop-
erative complications: comparison of two perioperative fluid regimens: a randomized assessor-blinded
multicenter trial. Annals of Surgery 2003; 238: 641–648.
*57. Nisanevich V, Felsenstein I, Almogy G et al. Effect of intraoperative fluid management on outcome after
intraabdominal surgery. Anesthesiology 2005; 103: 25–32.
58. Arkilic CF, Taguchi A, Sharma N et al. Supplemental perioperative fluid administration increases tissue
oxygen pressure. Surgery 2003; 133: 49–55.
59. Kabon B, Akca O, Taguchi A et al. Supplemental intravenous crystalloid administration does not reduce
the risk of surgical wound infection. Anesthesia and Analgesia 2005; 101: 1546–1553.
60. Beloosesky Y, Grinblat J, Weiss A et al. Electrolyte disorders following oral sodium phosphate admin-
istration for bowel cleansing in elderly patients. Archives of Internal Medicine 2003; 163: 803–808.
61. Seinela L, Pehkonen E, Laasanen T Ahvenainen J. Bowel preparation for colonoscopy in very old
patients: a randomized prospective trial comparing oral sodium phosphate and polyethylene glycol elec-
trolyte lavage solution. Scandinavian Journal of Gastroenterology 2003; 38: 216–220.
62. Sanders G, Mercer SJ, Saeb-Parsey K et al. Randomized clinical trial of intravenous fluid replacement
during bowel preparation for surgery. The British Journal of Surgery 2001; 88: 1363–1365.
454 D. N. Lobo et al

17. 63. Barclay RL, Depew WT Vanner SJ. Carbohydrate-electrolyte rehydration protects against intravascu-
lar volume contraction during colonic cleansing with orally administered sodium phosphate. Gastroin-
testinal Endoscopy 2002; 56: 633–638.
*64. Slim K, Vicaut E, Panis Y Chipponi J. Meta-analysis of randomized clinical trials of colorectal surgery
with or without mechanical bowel preparation. The British Journal of Surgery 2004; 91: 1125–1130.
65. Wilson J, Woods I, Fawcett J et al. Reducing the risk of major elective surgery: randomised controlled
trial of preoperative optimisation of oxygen delivery. British Medical Journal 1999; 318: 1099–1103.
66. Mythen MG Webb AR. Perioperative plasma volume expansion reduces the incidence of gut mucosal
hypoperfusion during cardiac surgery. Archives of Surgery 1995; 130: 423–429.
*67. Price JD, Sear JW Venn RM. Perioperative fluid volume optimization following proximal femoral
fracture. Cochrane Database of Systematic Reviews 2004 (1): CD003004.
68. Sinclair S, James S Singer M. Intraoperative intravascular volume optimisation and length of hospital
stay after repair of proximal femoral fracture: randomised controlled trial. British Medical Journal 1997;
315: 909–912.
69. Venn R, Steele A, Richardson P et al. Randomized controlled trial to investigate influence of the fluid
challenge on duration of hospital stay and perioperative morbidity in patients with hip fractures. British
Journal of Anaesthesia 2002; 88: 65–71.
*70. Gan TJ, Soppitt A, Maroof M et al. Goal-directed intraoperative fluid administration reduces length of
hospital stay after major surgery. Anesthesiology 2002; 97: 820–826.
*71. Wakeling HG, McFall MR, Jenkins CS et al. Intraoperative oesophageal Doppler guided fluid manage-
ment shortens postoperative hospital stay after major bowel surgery. British Journal of Anaesthesia
2005; 95: 634–642.
72. Holte K, Klarskov B, Christensen DS et al. Liberal versus restrictive fluid administration to improve
recovery after laparoscopic cholecystectomy: a randomized, double-blind study. Annals of Surgery
2004; 240: 892–899.
73. Nygren J. The metabolic effects of fasting and surgery. Best Practice Research Clinical Anaesthesiology
2006; 20: doi:10.1016/j.bpa.2006.02.004.
Perioperative fluid balance and postoperative outcomes 455