PREOPERATIVE ASSESSMENT

Combining fluid intake from food (1200 ml) and drink (1000 ml)
Fluid and electrolyte and adding water generated metabolically (300 ml) produces an
‘average’ intake of 2.5 l. This is balanced by insensible losses
balance, anaemia and blood from the skin and lungs (900 ml), faecal water content (100 ml)
and urine (1500 ml). This fluid ‘turnover’ represents a modest
transfusion fraction of the total fluid content of the body, which remains
relatively constant, and which is divided between the intracellular,
Iain Mackenzie interstitial, and circulating fluid volumes (Figure 1). The fluid in
each compartment has a specific composition (Figure 2). Losses
of water and electrolytes can be met by about 35 ml/kg/day of
water, together with 1–2 ml/kg day of sodium and 0.5–1 mmol/
kg/day of potassium.
This issue focuses on preoperative assessment, but this contribu-
tion addresses the management of fluid and electrolyte balance, Fluid movement
anaemia and blood transfusion in the perioperative period. Two f o rc e s d r i ve t h e m ove m e n t o f wa t e r b e t we e n
The UK National Confidential Enquiry into Patient Outcome compartments:
and Death (NCEPOD) report, ‘An acute problem?’, published in • osmotic gradients (created by differences in the concentration
2005, identified poor management of fluid as contributing to pre- of solutes either side of a membrane that is impermeable to the
ventable morbidity and mortality, and reflected the conclusions solutes, but permeable with respect to the solvent (water))
of earlier studies. Optimal management of fluid has the capacity • hydrostatic pressure gradients, determined within each com-
to significantly improve outcomes, although whether this is by partment by the relationship between compartment volume
augmenting or limiting fluid compared to ‘usual’ care depends (e.g. circulating volume) and the tension of the walls of the
on the patient populations studied. compartments (e.g. venous tone).
There is little or no hydrostatic pressure gradient between the intra-
cellular fluid (ICF) and extracellular fluid (ECF) compartments,
Volume regulation and electrolytes
so fluid movement between them is regulated by the osmotic
In health, euvolaemia is maintained by the regulation of: gradient. This is predominantly determined by the concentration
• fluid intake (thirst) in response to plasma osmolality via osmo- of electrolytes because of their overwhelmingly greater concentra-
receptors in the anterior hypothalamus which relay signals to tion compared to other osmotically active molecules (e.g. glucose,
the cerebral cortex proteins). Plasma osmolality can be measured in the laboratory
• excretion of urinary water in response to osmolality and volume or plasma osmolarity (see Denman, CROSS REFERENCE) can be
sensors in the major vessels of the thorax and the cardiac estimated:
chambers
• reabsorption of urinary sodium in response to the volume Estimated plasma osmolarity =
sensors. 2 × [Na+] plasma +2×[K+]plasma + [urea]plasma +[glucose]plasma

Iain Mackenzie is a Consultant in Intensive Care and Anaesthesia at Because of the difference between osmolality and osmolarity, the
Addenbrooke’s Hospital, Cambridge, UK. estimated plasma osmolarity would be expected to be less than

Distribution of fluid among body compartments

volume
ular
e asc
m trav volume Osmotic Notes
In
ma
lu

as RBC movement • The proportion of body weight accounted for by body water is
vo

Pl
inversely proportional to body fat, and ranges between 50% and 70%.
ui d

Hydrostatic In general, the proportion is greater in men (60%) than women (50%),
r fl

Colloids
movement
llula

and falls with age (increasing obesity and decreasing lean muscle mass).
me

This is not true for young children and neonates, where 70–80% of body
Extrace

titial fluid volu

Ions weight is body water. In general:

Total body water (TBW) in litres = 0.6 × body weight in kg (men)
Interstitial
0.5 × body weight in kg (women)
Intracellul

fluid Water
• Intracellular fluid (ICF) volume = 2/3 × TBW
• Extracellular fluid (ECF) volume = 1/3 × TBW
Inters

• Plasma volume = 1/4 × ECF

(Falls with age and physical inactivity from 1/4 to 1/5, except in trained
ar fl

Ions athletes.)
ui

• The circulating blood volume (Vb) is the sum of the red cell volume
d volu

and the plasma volume, and is estimated at 75 ml/kg for adults or

m

calculated from the plasma volume (Vplasma) and haematocrit (hct) as

e

follows:
1
Vb = × Vplasma
1–hct

SURGERY 23:12 453 © 2005 The Medicine Publishing Company Ltd

 PREOPERATIVE ASSESSMENT

Electrolyte composition, pH and osmolality of body compartments, secretions and commonly available fluids for
intravenous infusion
Plasma volume Clinical
Na+ K+ Ca2+ Mg2+ Cl– HCO3– pH Osmolality T½ (minutes) use
Body compartment
Plasma 142 4 2.5 1 100 25 7.4 280 – –
Interstitial fluid 145 4 2.4 0.9 118 27 7.4 280 – –
Intracellular fluid 12 155 ~0 15 8 10 7.2 280 – –

Secretions
Saliva 50–70 15–20 – – 10–15 30–50 6–7 – –
Gastric juice 150 5–10 – – 100–160 10–20 1–3.5 – –
Bile 180–220 6–8 – – 60–70 60–70 7–8 – –
Pancreatic juice 160 4 – – 30–60 80–120 8–8.3 – –
Small bowel 140 4 – – 100 25 7.8–8 – –

Crystalloids
Normal saline (0.9% NaCl) 154 – – – 154 – 5 300 80 R
Hartmann’s solution 131 5 2 – 111 a 6.5 275 68 R
Dextrose 4%, saline 0.19% 31 – – – 31 – 4.5 286 M
Dextrose 5% – – – – – – 4.2 278 19 M
Bicarbonate 8.4% 1000 – – – – 1000 8 2000 – A
PlasmaLyte 148™ 140 5 – – 98b – 5.5 294 R

Colloids
Haemaccel™ 145 5.1 6.25 – 145 – 7.25 293 240 R
Gelofusine™ 154 0.4 0.4 0.4 120–125 – 7.4 274 180 R
Hydroxyethyl starch (450/0.7) 154 – – – 154 – 5.5 300–310 75 R
Hydroxyethyl starch (130/0.4) 154 – – – 154 – 5.0 308 700 R
Dextran 40 154 – – – 154 – 3.5–7.0 280–324 180 T
Dextran 70 154 – – – 154 – 5.0 280–324 1500 R
HAS 4.5–5% 100–160 <2.25 – – 100–160 – 5.5 200–310 1000 R
HAS 20–25% 50–120 <10 – – 50–120 – 7.4 100–240 1000 R

a and A: Alkanization; M: Maintenance; R: Replacement; T: Thromboprophylaxis; b: Contains lactate as buffer.

the measured plasma osmolality by a quantity called the ‘osmolal
gap’, which is usually 9 ± 6 mosm/kg. An osmolal gap greater than
this suggests the presence of osmotically active (but unmeasured)
substances in plasma (e.g. ethanol, methanol, ethylene glycol,
acetone, mannitol, glycerol). At equilibrium, the osmolality of the
ECF and ICF are equal (Figure 2).
Fluid movement between the intravascular volume (IVV) and
interstitial fluid (ISF) compartments (where the semipermeable
membrane is formed by the vascular endothelium and its basement
membrane) is governed by hydrostatic and osmotic pressures. The
osmotic gradient is called the ‘colloid oncotic pressure’ because
this barrier is impermeable only to large molecules (colloids).
Albumin represents only 60% of plasma protein, but accounts
for 80% of the colloid oncotic pressure because its high negative
charge holds small cations in the plasma (Gibbs–Donnan effect).
Water flux between the IVV and ISF is determined by hydrostatic
and oncotic pressures according to the Starling equation:
Jv ∝ [(Pc – Pi) − σ(πc – πi)]
where Jv is the fluid flux, P is the hydrostatic pressure in the circula-
tion (Pc) and interstitium (Pi) respectively, π is the oncotic pressure
in the circulation (πc) and interstitium (πi) respectively, and σ is
the basement membrane reflectance coefficient (an index of how
‘porous’ the barrier is, which varies by tissue type).
The oncotic pressure gradient is largely a function of the plasma
protein (colloid) concentration because the interstitial fluid nor-
mally has little protein.
Sodium
Sodium is the principal extracellular cation and, with its associated
anions, accounts for most of the osmolality of the ECF. It is the

SURGERY 23:12 454 © 2005 The Medicine Publishing Company Ltd

 PREOPERATIVE ASSESSMENT
Disorders of sodium and water
Hypovolaemia Euvolaemia
Hyponatraemia
Sodium Sodium =
Water Water
Loss of fluid replaced by low-sodium or Stress (postoperative)
sodium-free solutions Dilutional hyponatraemia
Hypothyroidism
Glucocorticoid deficiency
Hypernatraemia
Sodium Sodium =
Water Water
Chronic or subacute loss of fluid (diuretics, Mild dehydration
burns, diarrhoea, fistula), post-obstruction,
polyuric renal failure, diabetes insipidus
key regulator of water flux. Unlike other electrolytes, disorders of
sodium homeostasis must be assessed in the context of hydration
(Figure 3). In surgical patients, the commonest cause of hyponat-
raemia is due to the replacement of fluid losses with low-sodium or
sodium-free solutions, particularly postoperatively, when increased
secretion of antidiuretic hormone is part of the stress response.
Acute hyponatraemia (developing in <48 hours) causes cerebral
oedema, with symptoms progressing from nausea, vomiting and
headache to somnolence, confusion, and finally seizures, brain-
stem herniation and death. In these patients, prompt correction to
increase the concentration of sodium in plasma by 2 mmol/l/hour
should continue until symptoms resolve. This may be achieved
using 3% sodium chloride infused at 1–2 ml/kg/hour together
with a loop diuretic. In contrast, symptomatic hyponatraemia
(confusion, somnolence, ataxia) that develops insidiously must be
treated with gradual correction because the brain compensates for
plasma hypo-osmolality by reducing intracellular osmolality. Under
these circumstances, correction of >15 mmol/l/24 hours may
precipitate central pontine myelinolysis. Chronic asymptomatic
hyponatraemia can be treated by fluid restriction or by identifying
and treating the underlying cause (e.g. dilutional hyponatraemia,
endocrine disorders, drugs).
Hypernatraemia is much less common because it is associated
with increased plasma osmolality, and usually accompanied by
thirst. Patients without access to water, unable to respond to thirst
(e.g. unconscious, cognitively impaired, psychiatric conditions,
bed-bound, very young) or with a depressed thirst response are
at risk. Symptoms of hypernatraemia include a depressed level
of consciousness, agitation, muscle twitching, hyperreflexia and,
particularly in children, seizures. The mortality in adults with a
sodium concentration in plasma of 160 mmol/l is about 75%,
which reflects the severity of the underlying conditions with
which hypernatraemia is usually associated. In those with a deficit
in circulating volume (Figures 4a and b), treatment consists of
returning circulating volume to normal with isotonic fluids, and
hypotonic fluids to restore total body water.
SURGERY 23:12 455
Oedema
Sodium
Water
Renal failure
Cardiac failure
Cirrhosis
Nephrotic syndrome
Sodium
Water
Primary hyperaldosteronism
Sodium administration
Potassium
The ECF contains only about 1% of total potassium in the body
because potassium is predominantly an intracellular cation. Potas-
sium homeostasis is achieved by matching urinary losses to intake
by secretion of potassium in the distal convoluted tubule. The ratio
of intracellular to extracellular potassium is maintained by the
action of Na+/K+-ATPase in the cell membrane, and determines the
resting membrane potential of excitable cells (see ‘Action potential
and nervous conduction’, page 425). Alterations in the potassium
concentration in the ECF may therefore reflect disturbance of total
potassium content in the body (intake, loss) or changes in the ratio
of extracellular to intracellular potassium (Figure 5).
Hyperkalaemia sufficient to cause ECG changes (prolonged PR,
widened QRS, peaked T waves) requires immediate treatment.
Calcium gluconate (10 ml of 10% i.v.) stabilizes the myocardium,
reducing the immediate risk of a dysrhythmia. It must be accom-
panied by treatment to reduce potassium concentrations in ECF,
such as dextrose and insulin (50 ml of 50% dextrose containing
15 IU soluble insulin infused over 30 minutes), nebulized salb-
utamol (5 mg) or, if central venous access is available, sodium
bicarbonate (1–2 ml/kg infused over 30 minutes). These treatments
reduce potassium in plasma by shifting potassium from the ECF
to the ICF and do not, therefore, reduce total potassium in the
body. Reduction of total potassium in the body requires enhanced
renal elimination (diuretics) or renal replacement therapy if renal
function is impaired.
Hypokalaemia can precipitate dysrhythmias, particularly in
patients on digoxin, and also requires prompt treatment when
symptomatic. Intravenous correction of severe hypokalaemia
requires cardiac monitoring, close observation and central venous
access if solutions of >40 mmol/l potassium are used. Accidental
over-rapid administration of solutions containing high concentra-
tions of potassium are likely to be fatal, and a pump (e.g. syringe
driver, volumetric or peristaltic pump) to control the infusion rate
is essential.
© 2005 The Medicine Publishing Company Ltd
 PREOPERATIVE ASSESSMENT

Fluid loss

a RBC b RBC 'Third-space' fluid losses.

Plasma Interstitial fluid losses. For simplicity, This term is applied if the
transcellular fluids (lymph, gastro- Plasma plasma volume is lost by
2° intestinal secretions, cerebrospinal sequestration to the
fluid, ocular fluid and urine) can be interstitium or body cavities
1° considered as a type of interstitial 1°
that usually contain little or
Interstitial fluid
fluid, although they are separated Interstitial fluid
no fluid, and therefore where
from the interstitial fluid by an the fluid loss is covert.
epithelial layer which secretes This usually occurs when
them and regulates their electrolyte 2°
Na+ the mechanisms that
2° composition. In this example, the 3° normally reabsorb fluid from
Water
losses are overt because the fluid these spaces fail or are
is lost from the body in the form of overwhelmed. Examples
urine, vomit, diarrhoea or insensible include tissue oedema,
losses (sweat, water vapour) or is ascites, pleural effusions, and
evacuated by drains (nasogastric the gastrointestinal tract.
c losses). d Blood loss
1°
1°

RBC RBC
Plasma Plasma

2°
2°

Interstitial fluid Interstitial fluid

Na+
3° Na+
Water 3° 3°
External (as opposed to internal, see Water
Figure 3) plasma volume losses occur
in subjects who have suffered burns. Loss of whole blood.

Volume loss
Fluid depletion may involve total body water, the ECF or the IVV
(Figure 4). The effect of fluid loss on electrolyte concentrations
in blood will depend on the composition of the lost fluid (Figure
2), as well as the volume and type of fluid the patient may have
received. Fluid losses are commonly hypotonic with respect to the
ECF (Figure 6), resulting in an increase in osmolality of the ECF,
and are partially compensated by the movement of water out of
the ICF (Figure 4a). A loss of up to 10% of body weight or 17%
of total water in the body (7 l in a 70 kg male) can be tolerated if
it occurs over hours rather minutes, and involves the ECF and the
ICF. Eventually, sufficient fluid is lost from the circulating volume
to cause circulatory failure (see below).
Loss of isotonic fluid from the ECF compartment has no effect
on the osmolality of ECF. This is the only factor involved in fluid
movement between the ECF and ICF, hence water does not re-
distribute out of the intracellular compartment until there is a
sufficient reduction in the circulating volume to trigger non-osmotic
mechanisms for the retention of salt and water:
• release of antidiuretic hormone
• suppression of release of atrial natriuretic peptide

Causes of hypokalaemia and hyperkalaemia

Hypokalaemia Hyperkalaemia
Increased renal loss Decreased renal clearance
• Drugs (e.g. diuretics, osmotic diuretics) • Renal failure
• Metabolic acidosis • Drugs (e.g. β-blockers, ACE inhibitors, amiloride)
• Magnesium depletion • Metabolic acidosis
Abnormal gastrointestinal losses • Adrenocortical failure
• Vomiting ICF ECF shift
• Diarrhoea • Tissue destruction (e.g. burns, crush injury, haemolysis, tumour
• Villous adenoma lysis)
ECF ICF shift • Metabolic acidosis
• Drugs (e.g. insulin, β-agonists)
• Metabolic alkalosis

SURGERY 23:12 456 © 2005 The Medicine Publishing Company Ltd

 PREOPERATIVE ASSESSMENT

Types of fluid loss

Hypotonic Isotonic
• Vomiting • Tissue oedema (decrease in endothelial basement membrane
• Diarrhoea reflectance co-efficient or loss of plasma protein)
• Burns • Losses from intracavitary drains (pleural, peritoneal)
• Ileus • Haemorrhage
• Inappropriate polyuria (diuretics, hyperglycaemia, mannitol,
diabetes insipidus, renal dysfunction)

• sympathetically-mediated redistribution of renal blood flow

• activation of the renin–angiotensin system.
Losses of isotonic fluid (Figure 6) are of two main types,
fluid shift from the circulating volume to the interstitial space
(tissue oedema) or body cavities (ascites, pleural effusions;
Figure 4b), or loss of plasma/whole blood (Figures 4c and d).
Compared to hypotonic fluid losses where the burden is shared
between the ECF and ICF, losses of isotonic fluid predominantly
affect the IVV and are less well tolerated. Clinical evidence of
circulatory failure becomes apparent after the loss of 15–20%
of the circulating volume (700 ml in a 70 kg male or 1.67% of
total body water) and decompensation occurs with the loss of
>30% of IVV.
Circulatory failure and intravascular volume resuscitation
Organ dysfunction, together with proximal (low blood pressure,
tachycardia) and distal (metabolic acidosis, low mixed venous
haemoglobin saturation) markers of circulatory failure may be
caused by pump failure or ‘functional’ intravascular hypovolaemia
(Figures 7 and 8). Functional IVV describes the IVV as perceived by
the body’s volume sensors, and can be considered as the product
of vascular tone and absolute IVV:
IVVfunctional = Tonevascular× IVVabsolute
Functional hypovolaemia can be caused by vasodilation or absolute
reduction of the IVV. The causes of circulatory failure are not mutu-
ally exclusive, and all three may coexist in some patients. Rapid
return of functional euvolaemia is the clinical priority, and therefore
hypotonic crystalloid solutions should be avoided because they
are distributed throughout total body water. In general, there is no
evidence to favour the use of isotonic crystalloids over colloids.
Exceptions include the resuscitation of trauma patients (evidence
is in favour of crystalloids) and sepsis (colloids may be preferable).
Initial resuscitation with either type of solution provides time to
assess blood biochemistry, haematology and coagulation, and to
crossmatch blood. If blood loss is immediately life-threatening,
group O Rhesus negative blood without specific crossmatching
may be needed, after consultation with the blood bank, if possible.
Maintenance of IVV and haematocrit must also be accompanied
by correction of coagulopathy with platelet concentrates, fresh
frozen plasma and cryoglobulin, if necessary.
Synthetic colloids
Synthetic colloids consist of isotonic crystalloid solutions containing

Features and differential diagnosis of circulatory failure

Pump failure Hypovolaemia Increased capacity

Features
Heart rate ↑ ↑
Blood pressure ↓ ↓
Confusion/agitation
Oliguria
Metabolic acidosis

Differential diagnosis
CVP High/normal Low Low
Cardiac output Low Low High/normal
SVR High High Low
Capillary refill Slow Slow Fast
Diastolic High High Low

CVP: Central venous pressure; SVR: Systemic vascular resistance.

SURGERY 23:12 457 © 2005 The Medicine Publishing Company Ltd

 PREOPERATIVE ASSESSMENT
Circulatory failure
Hypovolaemia
CVP
Heart
Venous Pump
capacitance failure
Increased
capacity
Renal
function
Third-space loss
a suspension of macromolecules of semi-synthetic polypeptides or
polysaccharides. The crystalloid solvent may be 0.9% sodium chlo-
ride, 5% dextrose or have an electrolyte profile similar to plasma
(Figure 2). The colloids may have specific effects with respect to
coagulation, crossmatching and the risk of adverse reactions.
Gelatins (semi-synthetic polypeptides): two forms of gelatin solu-
tion are available in the UK. Both are derived from cattle bone, but
by slightly different processes. Succinylated gelatin (e.g. Gelofusine
modified fluid gelatin, Physiogel™) is prepared by heating followed
by alkaline hydrolysis of the raw material and chemical linkage
of the resulting polymers with succinic anhydride as a coupling
agent. Urea-linked gelatin (Haemaccel™) is also extracted by heat-
ing, but the resulting molecules are crosslinked using methylene
di-isocyanate. Both solutions contain molecules with a range of
sizes (i.e. polydisperse rather than monodisperse) which can be
summarized as the weight-average molecular weight (Mw) or the
number-average molecular weight (Mn). Most of the administered
dose is excreted unchanged in the urine, with only 10–15% excreted
from the bowel and 3% metabolized. There is no long-term reten-
tion. The high calcium content of Haemaccel™ can precipitate clots
when mixed with citrated blood in the same giving set. This can be
prevented by flushing the giving set with a calcium-free crystalloid
or colloid. The raw material for the manufacture of these products
comes from the USA, where the incidence of bovine spongiform
encephalopathy is low, but the theoretical risk of transmitting new
variant Creutzfeld–Jacob disease remains.
Starches (semi-synthetic polysaccharides): hydroxyethyl
starches are derived from a waxy starch composed almost entirely
of amylopectin extracted from maize or sorghum. Resembling
glycogen, the polymerized D-glucose units are joined primarily
SURGERY 23:12 458
Circulatory failure is manifested by increased heart rate,
decreased blood pressure, and functional evidence of
organ hypoperfusion (e.g. confusion, agitation, oliguria).
Hypovolaemia, increased circulatory capacity, and pump
failure are the main causes and they are not mutually
exclusive. Hypovolaemia and increased capacity (sepsis)
are associated with a low central venous pressure, but
can be distinguished because hypovolaemia is
characterized by a low cardiac output and a high
systemic vascular resistance (cold peripheries, slow
capillary return, narrow pulse pressure), while increased
capacity is characterized by a normal or high cardiac
output and a low systemic vascular resistance (warm
peripheries, bounding pulses, wide pulse pressure).
by α-1,4 linkages with occasional α-1,6 branching linkages.
Hydroxyethyl groups are attached by ether linkage (to reduce
metabolic degradation) primarily at C2 of the glucose unit and to
a lesser extent at C3 and C6. The resultant material is hydrolysed
and fractionated to yield polydisperse colloids with the desired
ranges of molecular weight. The physicochemical properties of
hydroxyethyl starches are characterized by the size range of the
molecules and the proportion of hydroxyethyl groups to glucose
units (molar substitution), indicated in parentheses after the
product’s name (Mw/molar substitution, e.g. hydroxyethyl starch,
200/0.7). Higher-weight hydroxyethyl starches interfere with the
action of factor VIII and von Willebrand factor—an effect magni-
fied by higher degrees of substitution, higher C2:C6 ratios, and
infusion volumes of >1500 ml. Hydroxyethyl starches polymers
are thought to reduce capillary leak by ‘plugging’ holes in the
endothelial basement membrane, but their use in patients with
sepsis or septic shock is an independent risk factor for acute
renal failure. Molecules of hydroxyethyl starches 50 kDa in size
are rapidly eliminated by glomerular filtration. Larger molecules
are metabolized by naturally occurring amylases found in liver,
kidney, spleen and lung, with some of the polymers being taken
up by the reticuloendothelial system where they may persist for
prolonged periods. Administration of total doses of >3 g/kg are
associated with pruritus.
Dextrans (synthetic polysaccharides) are polymers of D-glucose
synthesized from sucrose by the bacterium Leuconostoc mesenter-
oides, in which 90% of the glucose molecules are linearly linked
by α bonds (1–6), with a very small degree of branching. Further
processing by partial hydrolysis and fractionation produces poly-
disperse solutions with different weight-average molecular weights,
commonly 40 kDa (dextran 40) and 70 kDa (dextran 70). As with
© 2005 The Medicine Publishing Company Ltd
 PREOPERATIVE ASSESSMENT
hydroxyethyl starches, the extent and speed of renal elimination
is a function of molecular weight, with 50% of a dextran 40 solu-
tion being renally excreted within a few hours of administration.
Many tissues also contain naturally occurring dextranases, and
metabolic degradation accounts for up to 10% of their elimina-
tion, with a further 10% being eliminated in the gut. Dextrans
improve microcirculatory flow by reducing erythrocyte aggregation
and leukocyte plugging, but interfere with platelet aggregation
(reducing circulating concentrations of von Willebrand factor),
and enhance fibrinolysis. The risk of a severe allergic reaction is
slightly greater for dextrans than for gelatins, but can be substan-
tially reduced by pre-administration of a small dose of dextran 1
(Mw 1 kDa), which acts as a hapten-binding agent. Dextran 1 is
not available in the UK.
Natural colloids
Human albumin solution is available as a dilute (4.5% or 5%)
or concentrated (20% or 25%) monodisperse solution containing
>90% albumin (Mn 66 kDa) that is free of clotting factors, blood
group antibodies or plasma cholinesterase. Although derived from
the plasma of multiple donors in very large quantities, the purifica-
tion steps (which include cold ethanol extraction, heat-inactivation
and, in some cases, chromatography) are very effective at removing
viruses. In the UK, human albumin solution is derived from human
plasma sourced from the USA to reduce the risk of transmitting
new variant Creutzfeld–Jacob disease. Albumin solutions do not
have a specific effect on blood coagulation, although there is some
evidence that human albumin solution may interfere with platelet
aggregation. Human albumin solution does not interfere with
blood crossmatching, and has a risk of adverse reaction similar
to gelatin solutions and hydroxyethyl starches, but is considerably
more expensive. Use of human albumin solution in critically ill
adults declined dramatically in the UK after the publication of a
meta-analysis in 1988 that concluded it was associated with excess
mortality. Criticized as methodologically flawed, this conclusion
has not been confirmed by a subsequent meta-analysis, and a
large randomized comparison of albumin versus saline to main-
tain intravascular volume in ICU patients detected no difference
in morbidity, mortality or length of stay. Hypoalbuminaemia and
low colloid oncotic pressure are associated with poorer outcomes
(although causality has not been established). In terms of main-
taining colloid oncotic pressure (rather than intravascular volume),
albumin has the advantage that resultant changes in albumin
concentration in serum can be measured. However, the association
between concentrations of albumin in plasma and colloid oncotic
pressure in serum is weakened in critically ill patients by changes
in the concentrations of other plasma proteins (e.g. acute-phase
proteins, immunoglobulins). Nevertheless, infusions of albumin
produce increases in albumin concentration in serum and colloid
oncotic pressure and, in some studies, improve outcome. In the
UK, dilute human albumin solution corrects a plasma–volume
deficit in patients with salt and water retention and oedema,
but not hypoalbuminaemia per se; concentrated human albumin
solution may be used to obtain a diuresis in hypoalbuminaemic
patients (e.g. in hepatic cirrhosis).
Blood
In the UK, blood is collected from unpaid volunteers, and put into
bags usually containing a mixture of citrate (to chelate calcium ions
SURGERY 23:12
and prevent clot formation) with adenine, phosphate and dextrose
(CAPD) as preservatives, giving the blood a shelf-life of 35 days.
Unprocessed, a donor unit contains 450–500 ml of whole blood,
which is screened for antibodies against syphilis, HIV-1, HIV-2,
hepatitis B and hepatitis C, and then typed for ABO blood group
and Rhesus D. Most donations are further processed by centrifuga-
tion to yield 250 ml of packed red blood cells, one unit of platelets
(about 70 ml) and 200 ml of plasma. The packed red blood cells
are diluted to a volume of about 350 ml with a mixture of saline,
adenine, glucose and mannitol to a haematocrit of 0.6–0.7, and
can then be frozen for long-term storage or refrigerated at 2–6°C
for use within the shelf-life. Since 1998 in the UK, blood has been
depleted of leukocytes by filtration, reducing the risk of sensitiza-
tion to leukocyte antigens.
Except in extreme circumstances (see above), blood for trans-
fusion is matched to the recipient’s blood group and Rhesus type;
in the UK, red cells from potentially suitable units of blood are
incubated with the serum of the intended recipient at 37°C to
check for compatibility. Subsequent transfusion requirements are
likely to require fresh serum for compatibility testing because of the
potentially rapid generation of red cell antibodies. Procedures for
crossmatching, labelling, collection, checking and administration
of blood must be extremely rigorous because of the potentially
fatal consequences of error.
Moderate degrees of chronic anaemia (haemoglobin of ≥8 g/dl)
may be correctable (≥10 g/dl) before surgery by giving supplements
(e.g. folic acid, iron, vitamin B12) rather than blood transfusion.
In the postoperative setting, the transfusion threshold is a hae-
moglobin concentration of 10 g/dl. In the absence of frailty or
cardiorespiratory disease, haemoglobin concentrations down to
8 g/dl are well tolerated, and transfusion in these patients may be
associated with increased mortality. There are additional consid-
erations with large-volume transfusion for major haemorrhage.
• Rapid infusion of blood at 4°C (which can be avoided by using
a blood warmer) quickly reduces body temperature, exacerbat-
ing any coagulopathy, impairing the delivery of oxygen and
increasing the risk of infection.
• The concentration of 2,3-diphosphoglycerate within the
erythrocytes of stored blood falls with time, shifting the oxyhae-
moglobin dissociation curve to the left and reducing the capacity
of blood to release oxygen to the tissues (see ‘Physiology of
breathing II’, page 430). Normal concentrations of 2,3-diphos-
phoglycerate are restored within 24 hours.
• Over time, intracellular potassium leeches out of the erythro-
cytes of stored blood, and the extracellular concentration of
potassium may rise to 30 mmol/l.
• Stored blood is deficient in factors V and VIII (corrected
with fresh frozen plasma) and fibrinogen (corrected with
cryoprecipitate).
• The risk of subsequent development of acute respiratory distress
syndrome or transfusion-related lung injury are related to the
volume of transfused blood.
Other risks associated with blood transfusion include:
• acute haemolytic transfusion reaction
• infusion of contaminated blood
• reactions due to non-ABO antibodies
• delayed haemolytic transfusion reactions
• anaphylaxis
• alloimmunization.
459 © 2005 The Medicine Publishing Company Ltd
 PREOPERATIVE ASSESSMENT
Some groups of patients will not (Jehovah’s Witnesses) or should
not (awaiting bone marrow transplantation, previous multiple
transfusions, multiple antibodies) receive blood; other techniques
to avoid blood transfusion should be considered (e.g. intraoperative
cell salvage, acute normovolaemic haemodilution).
Crystalloids
Simple electrolyte solutions that do not contain macromolecules are
termed crystalloids. They are iso-osmolar with respect to plasma
when used for volume replacement (Figure 2). Hyperosmolar solu-
tions are also available, but these are for specific purposes (e.g.
provision of glucose, alkalinization, rapid resuscitation). Depend-
ing on their tonicity, these solutions are distributed throughout the
ECF (isotonic) or total body water (hypotonic). Sodium chloride
0.9% (‘normal’ saline) is isotonic and iso-osmolar, but the abnor-
mally high concentration of chloride can cause a hyperchloraemic
acidosis which has been associated with impaired renal function,
poorer gastric perfusion and subjective discomfort. Haemodilution
with normal saline results in modest prolongation of the prothrom-
bin and activated partial thromboplastin times, an exaggerated
reduction of antithrombin III and enhanced platelet aggregation,
suggesting in vivo activation of the coagulation cascade.
Endpoints
Clinical estimation of absolute IVV is impractical and, given the
confounding effect of vascular tone (Figure 5), would be a dis-
appointing exercise. In health, homeostatic mechanisms maintain
the circulating volume (and total body water) within a narrow
range, and volume excursions below, or significantly above, this
normal range are poorly tolerated. As discussed above, ‘functional’
hypovolaemia may be caused by a decrease in volume or tone,
and culminates in the signs and symptoms of circulatory failure.
Conversely, modest loading of fluid is a normal physiological
response. Increased demand for substrate supply (e.g.stress, exer-
tion, pregnancy) is met by an increased cardiac output, generated
by an increase in end-diastolic ventricular volume, as well as
increases in heart rate and cardiac contractility. In the short term,
increased ventricular filling pressure (an important determinant of
end-diastolic volume), is achieved by the sympathetically-mediated
redistribution of intravascular volume from the abdomen, to the
heart and lungs. In the longer term, chronically increased demands
are met, in health and disease, by an increase in circulating volume.
Even in untrained individuals, fluid loading increases maximum
•
aerobic capacity (VO2 max), but not endurance.
Surgery and associated complications present a metabolic
challenge through the effects of pain, inflammation, substrate
mobilization and tissue repair. The magnitude of the metabolic
challenge is primarily determined by the procedure (e.g. hernia
repair versus radical cystectomy), surgical technique (skill, speed,
minimal damage to tissue) and any associated complications aris-
ing (e.g. sepsis, haemorrhage). Secondary demands may arise in
the process of trying to meet the primary metabolic burden of
surgery (myocardial infarction, heart failure, ischaemia-related
dysrhythmias). Failure to meet these demands results in morbidity
and mortality. Optimizing functional intravascular volume (fIVV)
•
allows each patient to reach his own VO2max, but this does not
•
guarantee that this VO2 (which depends on pre-existing cardiac
and pulmonary function) will be sufficient to meet the demands
of surgery. The goal of perioperative fluid therapy, therefore, is
SURGERY 23:12
to provide an appropriate intravascular volume for the ambient
vascular tone to maintain functional euvolaemia.
Intravascular volume (and functional euvolaemia) can be
maintained by daily weights in patients whose homeostatic
mechanisms are intact and who do not suffer changes in vascular
tone or vascular endothelial reflectance coefficient. This would
apply to patients undergoing day-case surgery or clean elective
surgery of short to moderate length. Most of these patients are
rendered mildly hypovolaemic before surgery because of prolonged
preoperative fasting and fluid restriction; restoration of euvolae-
mia with fluid loading (up to 40 ml/kg) pre- or intraoperatively
improves subjective outcome from day-case and minor surgery,
and is not controversial.
In more substantial elective surgery where third-space losses
are minimal and the principal source of morbidity is from fluid
overload (upper and lower gastrointestinal tract and thoracic sur-
gery), limiting perioperative or intraoperative fluids to compensate
for preoperative dehydration and intraoperative loss of fluid is
also beneficial. Equally, studies in vascular surgery have failed to
show benefit from fluid loading. This conservative approach to
fluid management in these patients contradicts current anaesthetic
practice, despite evidence that fluid overload is associated with
increased morbidity and mortality. However, there are two stud-
ies that paradoxically show benefit from fluid loading in patients
undergoing major elective surgery. These studies were conducted
in a heterogeneous groups of patients and did not specify pre-
operative bowel preparation or fluid management, and resulted
in smaller differences in fluid balance between the groups. It is
possible that in these studies patients were less well hydrated
before surgery and the intervention groups were ‘fluid loaded’ to
functional euvolaemia, leaving the ‘standard care’ groups relatively
hypovolaemic.
In the context of a significant preoperative fluid deficit or acti-
vation of a systemic inflammatory response with alterations in
vascular tone and capillary integrity (major blood loss, prolonged
surgery, sepsis), the principal source of morbidity is from hypo-
volaemia (absolute and relative). In these patients, attainment of
‘functional euvolaemia’ is difficult when titrating fluid therapy
against the traditional endpoints of heart rate, blood pressure or
urine output because they are compromised by the confounding
effects of pain (increase in antidiuretic hormone), vasodilation
(epidural analgesia, sepsis), cardiac dysfunction (ischaemic heart
disease, sepsis), intrinsic renal disease and absolute hypovolaemia
(bleeding, third-space losses). In these more complex cases, early
recourse to more sophisticated measures of intravascular volume
status (e.g. monitoring of central venous pressure, pulmonary
artery catheterization, oesophageal Doppler cardiac output moni-
toring, arterial pulse-contour analysis (PiCCO and LiDCO)), are
beneficial. u
CROSS REFERENCE
Denman E S. Osmolarity and partitioning of fluids. Surgery 2005; 23(6):
190–4.
460 © 2005 The Medicine Publishing Company Ltd