16 FLUID, ELECTROLYTE AND
METABOLIC MANAGEMENT
Peter D. Thomas
16.1 Introduction
The medical management of the severely head-injured
patient involves manipulations of the intracranial
pressure (ICP), cerebral perfusion pressure (CPP),
seizure control, fluid and electrolyte therapy and
nutritional support. The goal of fluid management is
homeostasis, i.e. to provide appropriate parenteral
and/or enteral fluid to maintain intravascular vol-
ume, left ventricular filling pressure, cardiac output,
blood pressure and ultimately oxygen delivery (ḊO2)
to tissues, when normal physiological functions are
often altered by surgical and traumatic stress and by
anesthetic agents. A specific aim is to prevent second-
ary neuronal damage due to inadequate ḊO2 to the
brain; this requires adequate ventilation and oxy-
genation as well as cardiac output. The most obvious
consequences of inappropriate fluid resuscitation are
shock from insufficient volume replacement, and
pulmonary edema from overhydration.
Glucose, lipids, protein, vitamins and essential trace
elements are provided in order to retard the ‘auto-
cannibalism’ of visceral protein for gluconeogenesis.
Fluid planning must be individualized and take into
account the patient’s cardiac, renal, pulmonary, nutri-
tional, functional and premorbid state.
Fluid and electrolyte abnormalities may result from
the brain injury itself, e.g. diabetes insipidus, from
therapy and from other injuries. The relationship
between systemic abnormalities of water, electrolytes
and acid–base metabolism and the brain can be
approached from two vantage points:
 the effects of CNS lesions on renal function, water
and electrolytes;
 the effects of metabolic abnormalities on the CNS.
16.2 Rationale of metabolic support
The outcome after a severe head injury is influenced
by age, pre-accident health, the severity of the primary
Head Injury. Edited by Peter Reilly and Ross Bullock. Published in 1997 by Chapman & Hall, London. ISBN 0 412 58540 5
injury and any of six potentially preventable second-
ary insults: intracranial hematoma, raised ICP, seiz-
ures, meningitis, hypoxia and hypotension (Price,
1992). About 20% of patients with head injuries also
suffer injury to other systems. The injured brain is
highly vulnerable to hypoxia and ischemia, which
may exacerbate neuronal damage by a number of
mechanisms, including the release of excitotoxic neu-
rotransmitters such as glutamate (Zwimpfer and
Moulton, 1993). Extracranial injury that does not result
in hypotension or hypoxia appears to have little
influence on outcome (Jennett, Teasdale and Braak-
man, 1979). Hence preventing and aggressively treat-
ing hypotension and hypoxia are essential parts of the
early management of all patients with head injury.
Approximately 50% of patients admitted to the
hospital in a coma following head injury will require
craniotomy (Butterworth and De Witt, 1989). Others
who do not require craniotomy may require anes-
thesia and surgery for other major injuries. The
anesthesia and surgery can both affect fluid and
electrolyte status.
Intravenous therapy is an integral part of both the
initial resuscitation phase and the later maintenance or
supportive phase of management. The primary aim of
resuscitation is to achieve satisfactory ventilation and
restore intravascular volume, cardiac output and tissue
perfusion, thereby preventing the sequelae of shock,
acute renal and multiple organ failure and secondary
neuronal damage. The secondary aim is correction of
any underlying disorder. In adults prolonged hypoten-
sion is rarely due to head injury alone, unless the injury
is massive and brain death is imminent, and concealed
hemorrhage must be sought. In infants and young
children, hypovolemic shock may result from blood
loss in a large extradural hematoma, especially if there
is additional bleeding under the scalp. Shoemaker has
demonstrated that O2 transport variables (ḊO2 and
oxygen consumption – V̇O2) can reliably predict
outcome in postoperative surgical patients. Conversely
when these variables are manipulated in a controlled
294 FLUID, ELECTROLYTE AND METABOLIC MANAGEMENT

prospective manner, outcome can be improved (Shoe-
maker et al. 1982, 1988). The determinants of oxygen
delivery are summarized in Figure 16.1. Fluid resusci-
tation augments preload, increases stroke output and
total systemic flow, thereby increasing oxygen delivery.
Care must be taken to avoid hemodilution, which may
simultaneously reduce arterial oxygen content and
prevent an increase in ḊO2 despite improvement in
cardiac index. Oxygen saturation should be maintained
at 90% or greater in accordance with the recommenda-
tion of the American College of Chest Physicians
Consensus Conference on Mechanical Ventilation
(Slutsky, 1993).
Following resuscitation, fluid therapy aims to main-
tain euvolemia, provide normal daily requirements
and replace any continuing losses. It is usually
combined with nutritional support.
Cerebral autoregulation determines the relationship
between cerebral blood flow (CBF) and metabolic
needs (metabolic coupling) and systemic hemody-
namics (pressure autoregulation). When metabolic
coupling is intact, cerebral oxygen delivery is deter-
mined by metabolic need and is unaffected by minor
changes in blood pressure or viscosity. Both aspects of
cerebral autoregulatory function may be impaired
following traumatic brain injury, so that cerebral
oxygen delivery is influenced by cerebral perfusion
pressure (CPP) and blood viscosity (Shoemaker et al.,
1988). Thus maintaining a normal CPP is a key aspect
of the management of the head-injured patient.
Most severely injured patients develop only small
changes in serum electrolyte concentrations, even
though there are large fluid and electrolyte shifts
between body compartments. Thus it is important to
understand the physiological basis of the common
electrolyte problems, the factors controlling electrolyte
distribution and extracellular fluid volume and the
distribution of administered fluids since the choice of
intravenous fluids will influence brain metabolism
and volume (Sutin, Ruskin and Kaufman, 1992). From
this knowledge appropriate therapeutic strategies can
be developed.
16.3 Basic principles
16.3.1 FLUID DISTRIBUTION
The total body water content of humans is approx-
imately 60% of body weight (Figure 16.2). Two-
thirds is located in the intracellular and one-third in
the extracellular compartment (Harrison, Darrow
and Yannet, 1936). The extracellular compartment
can be further subdivided into interstitial (protein-
poor) and intravascular (protein-rich) compartments.
Normally, 75% of the extracellular water is contained
within the interstitium and 25% in the vasculature.
There are marked differences in electrolyte content
between intracellular and extracellular fluids: potas-
sium is predominantly intracellular, and sodium and
chloride extracellular (Gamble, Ross and Tisdall,
1923). The energy-consuming Na+ –K+ pump is

Figure 16.1 Systemic oxygen delivery – ḊO2 (ml/min) – is

determined by the product of the oxygen content of the
blood and total systemic blood flow. The major determinants
of each component are pictured. Hb = hemoglobin; % SAT =
percentage saturation of Hb; PaO2 = partial pressure of
oxygen in arterial blood; 0.0031 = solubility coefficient for Figure 16.2 Distribution of body water in a 70 kg man (45.5
oxygen in plasma. liters).

required to maintain these concentration gradients,
which are sustained during sodium overload or
depletion states. Distribution of water between the
intracellular and extracellular compartments is
determined by osmosis.
Extracellular fluid includes water ‘attached’ to bone
and dense connective tissue, as well as free trans-
cellular or ‘third-space’ fluid formed by secretions
from epithelia and other membranes. Free trans-
cellular fluid includes cerebrospinal fluid (CSF), urine,
gastrointestinal and other secretory fluid, which may
have strikingly different osmolalities from the two
major body fluid compartments (Shoemaker, 1982).
Although this third space may be greatly expanded in
disease states such as ascites, pleural effusion, para-
lytic ileus or bowel obstruction, it is separated from
other body fluid compartments by epithelium and
therefore does not communicate freely with them. The
third space can be thought of as ‘parasitic’ – it is
generated at the expense of the other two compart-
ments but is not available to ‘come to their rescue’ in
states of hypovolemia. Since most forms of expansion
of the extracellular fluid do not involve the third space
fluids and the amount of water attached to bone and
dense connective tissue is relatively fixed, the normal
body water distribution can be simplified as shown in
Figure 16.3.
Figure 16.3 Simplified distribution of body water in a 70 kg
man. The forces that influence fluid distribution between the
compartments are shown in italics.
BASIC PRINCIPLES 295
Cell membranes are normally relatively impermea-
ble to ions but freely permeable to water. Water,
electrolytes and energy substrates continually move in
and out of cells to maintain a dynamic steady-state
relationship and major fluid and electrolyte shifts
occurring with disease are often associated with only
minimal serum concentration changes. For example, a
decrease in extracellular sodium concentration and
osmolarity following an infusion of 5% dextrose in
water is followed by diffusion of water into the cells
until the osmotic pressure between the two compart-
ments is equal. Conversely, an increase in extracellular
sodium concentration and osmolarity after infusion of
hypertonic saline is followed by movement of water
from the intracellular to the extracellular compart-
ment. Infusion of an isotonic electrolyte solution does
not alter the osmolarity of the extracellular compart-
ment and therefore does not lead to shifts of water into
or out from the intracellular compartment.
Water movement between the two components of
the extravascular space is determined primarily by
differences in protein concentration. Colloid osmotic
pressure (COP) is the net osmotic pressure across the
capillary membrane resulting from the impermeabil-
ity of the endothelium to plasma proteins. Because
physical confinement of protein molecules produces
an osmotic imbalance, water moves from interstitial
space into the blood stream. Crystalloid molecules
cannot establish a pressure gradient because they
move freely across the capillary membrane.
Protein molecules are negatively charged and
attract a small number of positive ions, preventing
them from diffusing across the endothelium. These
retained ions produce an additional osmotic pressure
(called the Donnan equilibrium effect). Some 60% of
normal COP is produced by protein molecules (75%
by albumin, the rest mainly by globulins and fibrino-
gen); 40% is produced by the electrostatically held
cations. However, if the plasma protein concentration
rises, the influence of the Donnan equilibrium effect
on COP increases disproportionately, producing a
curvilinear relationship between total protein concen-
tration and COP.
COP is measured by placing a protein solution on
one side of a semipermeable membrane and a protein-
free solution on the other side. Fluid moves through
the membrane until a pressure is generated that
prevents further osmosis. This pressure is defined as
the COP (Morissette, 1977). Plasma COP in normal
ambulatory patients is approximately 25 mmHg, in
supine patients 22 mmHg and in an Intensive Care
Unit patient 18–20 mmH (Weil et al., 1974, 1981;
Rackow, Fein and Leppo, 1977). Although protein is
the primary determinant of osmotic pressure in
peripheral tissues, it contributes very little to the total
number of particles dissolved in plasma. Total plasma
296 FLUID, ELECTROLYTE AND METABOLIC MANAGEMENT
osmolality is normally 285 mosmol/kg, of which
plasma protein accounts for less than 1 mosmol/kg.
Infusing an iso-oncotic solution such as 5% albumin
in isotonic saline expands the intravascular space
without producing a shift of water from other com-
partments. A hyperoncotic solution such as 25%
albumin expands blood volume to a extent greater
than the volume infused by drawing water and
electrolytes from the interstitium. However water
does not diffuse from the intracellular space if
extracellular osmolarity remains unchanged.
Starling defined the forces influencing the bulk
movement of water between the vascular and inter-
stitial compartments (Starling, 1896). Pappenheimer
and Soto-Rivera derived a mathematical expression
for these forces, referred to as the Starling equation of
transcapillary exchange: (Pappenheimer and Soto-
Rivera, 1948).
Qf = Kf [(Pc – Pi) –  (c – i)]
where Qf = total fluid flow across the capillary
membrane; Kf = fluid filtration coefficient; Pc =
capillary hydrostatic pressure; Pi = interstitial hydro-
static pressure;  = osmotic reflection coefficient; c =
capillary oncotic pressure; i = interstitial oncotic
pressure.
The four pressures in this equation are called the
Starling forces. The net driving pressure favoring
filtration is Pc – Pi. The hydrostatic pressure within the
capillary is the major force driving fluid into the
interstitium and is essentially unopposed by the
interstitial hydrostatic pressure. This is usually
slightly negative and approaches zero or becomes
slightly positive only when substantial amounts of
edema accumulate (Meyer, Meyer and Guyton, 1968;
Guyton, Granger and Taylor, 1971). The plasma COP
is thus the only force acting to retain fluid within the
intravascular space. The interstitial COP works in the
opposite direction; the net effect of these opposing
forces is described by c – i
Kf, the filtration coefficient, has two components: Lp,
the hydraulic conductivity, which describes how
rapidly fluid can pass through the microvascular
exchange barrier (capillary membrane, interstitial gel
and terminal lymphatics) and S, the capillary surface
area available for filtration (Granger, 1979; Harms et
al., 1981; Demling et al., 1982). If either component of
Kf increases, e.g. through damage to the endothelial
membrane or dilatation of precapillary vasculature in
response to increased cardiac output (CO), the rate
and amount of fluid filtered increase independently of
changes in the Starling forces (Peters and Hargens,
1981).
The reflection coefficient  defines the capacity of
the capillary membrane to prevent translocation of
proteins. If  = 1, the membrane is totally impermea-
ble and proteins are able to exert their full oncotic
force; if  = 0, the membrane permits protein to pass
without impedance (Peters and Hargens, 1981). 
varies in capillary membranes throughout the body,
being approximately 0.9 for systemic and 0.7 for lung
capillaries (Wittmers, Bartlett and Johnson, 1976). The
net effect of the Starling forces across capillaries is to
produce fluid movement from the intravascular to the
interstitial space. Accumulation of interstitial fluid in
the lung is much more life-threatening than peripheral
edema formation and there has been great interest in
evaluating factors that are likely to reduce the risk of
clinically significant pulmonary edema (Allen et al.
1987; Civetta, 1979; Crandall et al., 1983).
Modest increases in pulmonary capillary hydro-
static pressure or decreases in plasma oncotic pressure
do not result in pulmonary edema because the lung
has mechanisms for resisting accumulation of inter-
stitial fluid. In the first place, the pulmonary inter-
stitial hydrostatic pressure (Pi) is normally slightly
negative (Civetta, 1979; Levine et al., 1967; Taylor et al.,
1982). When fluid first begins to accumulate in the
interstitium, the pressure rapidly increases (i.e. com-
pliance is low). This increase in hydrostatic pressure
opposes any further fluid entry by decreasing the
hydrostatic pressure gradient, Pc – Pi (Allen et al.,
1987). However, as interstitial fluid pressure rises
above atmospheric, resistance to fluid transport
through the interstitium decreases markedly and
further increases in fluid volume cause only minimal
increases in interstitial hydrostatic pressure (Levine et
al., 1967; Goldberg, 1980). Pi appears to level off
between 1 and 5 mmHg in severe pulmonary edema
(Battacharya, Gropper and Staub, 1984).
A second mechanism which resists the accumula-
tion of pulmonary interstitial fluid is a decrease in the
interstitial oncotic pressure resulting from the accu-
mulation of protein-poor fluid (Granger,1979). Pulmo-
nary interstitial oncotic pressure is normally about
75% of the plasma level and the oncotic gradient
across the pulmonary capillary membrane (c – i) is
only 4–6 mmHg. If serum COP decreases, interstitial
oncotic pressure will decrease proportionately as fluid
enters the interstitial space, avoiding a change in the
oncotic gradient (Granger, 1979; Demling, 1980; Deml-
ing et al., 1979).
Thirdly, large protein molecules such as albumin are
normally excluded from a substantial part of the
interstitial fluid volume by the density of the interstitial
matrix. However, as the degree of hydration increases
the fibers in the interstitial matrix are stretched apart,
allowing protein molecules to enter previously
unavailable space (Granger, 1979). This lowers i,
widens the transcapillary oncotic gradient (c – i), and
thus opposes further pulmonary edema formation.

Lymphatic drainage is the fourth and probably
most important safety factor. Experimental studies
have shown that the lymph flow rate can increase
tenfold when interstitial fluid volume or pressure
increases.
The blood–brain barrier is formed by a closely
woven mesh of capillary cells joined by a continuous
array of tight junctions (zonula occludens) with an
effective pore size of 0.7–0.9 nm. Because the blood–
brain barrier is a lipid membrane with small pores, it
is easily permeated by water and very small or
lipophilic molecules. The blood–brain barrier is rela-
tively impermeable to electrolytes, water-soluble non-
electrolytes and plasma proteins. The endothelial cells
in peripheral tissues are joined by interspersed tight
junctions and the effective endothelial pore size is
about 4–5 nm. Because of the large pore size in
peripheral tissues, the endothelial membrane is freely
permeable to water and electrolytes, but only partially
permeable to plasma proteins. In the peripheral
tissues there is an active lymphatic system, which
helps reabsorb interstitial fluid. In the brain, however,
there are no lymphatics. When the blood–brain barrier
is injured, the barrier becomes permeable to electro-
lytes and large plasma proteins such as albumin
(Zornow et al., 1988). Hypertonic fluids will only
remove interstitial and intracellular fluid from regions
of the brain where the blood–brain barrier is intact,
and will have no effect on areas where the blood–
brain barrier is permeable to electrolytes.
The difference in membrane function between the
blood–brain barrier and the endothelium in periph-
eral tissues is of practical importance. For example, if
the intravascular concentration of sodium is increased
from 140 mmol/l to 150 mmol/l, there will only be a
small and short-lasting effect on the peripheral inter-
stitial tissues, owing to the free movement of both
sodium and water across the endothelium. However
such a change in sodium concentration will have a
pronounced effect on the brain. The osmotic pressure
gradient will increase drawing water from the brain
interstitium to the intravascular space.
16.3.2 OSMOLALITY AND TONICITY
Osmolality is the number of dissolved particles in a
kilogram of solvent (water) and determines the
osmotic force of the solution (Shoemaker, 1982). Cell
membranes are highly permeable to water, which will
diffuse across them rapidly to maintain osmotic
equilibrium between the extracellular and intracel-
lular fluid compartments (Brobeck,1973). Hence the
relative volumes of the compartments will be deter-
mined by their sodium and potassium content.
Plasma osmolality can be measured directly or
calculated approximately by means of the formula:
BASIC PRINCIPLES 297
POSM = 2PNa+ + glucose + urea
where the concentration of sodium, glucose and urea
are all expressed in mmol/l (Worthley, Guerin and
Pain, 1987).
The plasma sodium (PNa+) level is multiplied by
two to account for anions. This rule of thumb does not
take into account the low-concentration cations such
as potassium, calcium and magnesium or organic
molecules such as creatinine, amino acids and lactate.
This error of exclusion is balanced by the presence of
multivalent anions such as sulfate and phosphate
which contribute fewer particles per equivalent than
do univalent ions.
Although urea is included in the calculation of
osmolality, it diffuses readily across cell membranes
and does not influence relative compartment volumes
(Brobeck,1973). Exogenous solutes such as mannitol or
alcohol may create an ‘osmolar gap’ between the
measured and unmeasured osmolalities (Table 16.1).
This formula must be interpreted in conjunction
with the clinical assessment of fluid status as, for
example, an increased osmolality may result either
from excess sodium or a deficit of water.
Tonicity defines effective osmolality, i.e. the osmotic
force due to the particles which cannot permeate
between compartments. Because all body fluids must
be in osmotic equilibrium, changes in tonicity, regard-
less of their cause, will result in fluid shifts between
the ECF and the ICF in order to re-establish osmotic
equilibrium. The administration of hypertonic fluids
such as 50% dextrose or hypertonic saline will increase
the tonicity of the ECF and result in fluid shifts into
the extracellular compartment. Thus patients with
osmotic hypertonicity will have a contracted intra-
cellular compartment.
This effect had been applied to the treatment of
patients with cerebral edema in whom intracellular
and extracellular volumes can be decreased by achiev-
ing hypernatremia. Conversely in hyponatremic states
the tonicity of the ECF is decreased and water must
shift into and expand the intracellular fluid to main-
tain osmolality. As brain expansion is limited by the
confines of the cranial vault, severe hyponatremia
Table 16.1 Osmotically active particles
Extracellular fluid Intracellular fluid
Sodium Potassium
Glucose Magnesium
(Mannitol) Inorganic phosphate
Urea* Urea*
Ethanol* Ethanol*
*These particles are distributed freely in body water. Other
particles are unable to permeate compartments.
298 FLUID, ELECTROLYTE AND METABOLIC MANAGEMENT

may result in raised intracranial pressure (ICP). Urea
increases osmolality but not tonicity because it passes
freely through biological membranes, and will not
alter the intracellular volume,.
16.3.3 DISTRIBUTION OF ADMINISTERED FLUID IN
THE BODY
All infused fluids may be considered as being com-
posed of plasma equivalents (colloidal solutions),
saline equivalents (crystalloid solutions) or water
equivalents. Plasma equivalents remain essentially
confined to the circulation as a result of their oncotic
pressure. Saline equivalents are distributed between
the interstitium and plasma, but remain restricted to
the extracellular fluid compartment because of their
sodium content. Water equivalents are distributed
according to the distribution of water in the body
(Figure 16.2).
(a) Plasma equivalents
Plasma equivalents include blood, its components and
colloids. Blood may be administered either whole, or
in its component form; the latter is preferred, as
fractionation optimizes the availability of the various
blood components for special situations and improves
the survival of the stored blood elements. Its use is
limited by cost and availability, the risks of allergic
reactions and infection, the delays necessary for cross-
matching and a limited shelf life.
Patients who are bleeding acutely are best treated in
part with whole blood since this also replaces clotting
components and platelets. Otherwise hypovolemia
can be treated effectively by colloid or crystalloid
solutions, and oxygen transport function can be
restored by red-cell concentrates, although these take
several hours to be fully effective since storage impairs
oxygen dissociation.
The absolute minimum acceptable hematocrit in the
trauma patient is difficult to determine. The goal of
blood transfusion is to maintain an adequate level of
tissue oxygenation, but the focus in clinical medicine
has been on the level of serum hemoglobin or the
hematocrit. It has been estimated that tissue ḊO2 is
optimal when the hematocrit is 33% (Sutin, Ruskin
and Kaufman, 1992), but the effect on ḊO2 may not be
the same as the effect on oxygen utilization. A
consensus development conference on perioperative
red cell transfusion concluded that available evidence
did not support the recommended practice of main-
taining hemoglobin levels at 10 g/dl or hematocrits at
30% (Consensus Development Conference, 1988). In
the United States, the National Blood Resource Educa-
tion Program guidelines for red blood cell transfusion
state that adequate oxygen-carrying capacity can be
met by a hemoglobin of 7 g/dl (hematocrit of approx-
imately 21%) or even less when the intravascular
volume is adequate for perfusion. The guidelines add
the caveat that the decision to transfuse a given
patient should be based on consideration of the
patient’s age, etiology and degree of anemia, hemody-
namic stability and presence of coexisting cardiac,
pulmonary or vascular disease. While the normal
brain is very tolerant to anemia, the limits of iso-
volemic anemia are unknown. Because autoregulation
may be impaired after injury, it cannot be assumed
that the safe lower limit of the hematocrit is the same
as in the neurologically normal subject.
Colloidal solutions comprise preparations of plasma
or high-molecular-weight synthetic substances (Table
16.2). These fluids do not cross capillary membranes
readily and are initially confined mainly to the
intravascular space. If the colloidal solution has an
oncotic pressure that is higher than that of the plasma
interstitial fluid will move into the intravascular space
and expand the plasma volume by more than the
administered volume of colloidal solution, hence the
term ‘plasma expander’.
Plasma-protein derivatives
These include 5% normal serum albumin, which
contains human albumin 50 g/l and sodium

Table 16.2 Colloidal solutions

Volume Mean mol. Protein Sodium content Oncotic Half-life Side effects Cost/bottle
Type (ml) wt (kDa) content (mmol/bottle) pressure Other constituents (%)* (Aust$)

Normal serum 500 69 5% (25 g) 70 Iso-oncotic – 5–10 d 0.02 (0.004) 60.00

albumin
Concentrated 100 69 20% (20 g) 10 5 – 5–10 d 0.01 (0.003) 85.00
albumin
Dextran 70 500 70 6% 77 or 0  2.5 – 12 h 0.07 (0.017) 8.00
(Macrodex)
Polygeline 500 35 3.5% 72 Iso-oncotic Potassium, 5 mmol/l; 4h 0.15 (0.05) 12.50
(Haemaccel) calcium, 6 mmol/l

*Percentage incidence of all reactions. Percentage incidence of major (grade-3 and grade-4) reactions in parentheses.

140 mmol/l, concentrated (20%) albumin, which con-
tains 200 g/l of albumin and less sodium (100 mmol/l).
The latter is usually restricted to hypoproteinemic
patients with either hypernatremia or fluid overload. A
500 ml infusion of 5% albumin expands the intra-
vascular volume by 450–500 ml (Lamke and Liljedahl,
1976). After 2 hours, under conditions of normal
capillary permeability, 90% remains within the intra-
vascular space (Rainey and English, 1988). Eventually
the administered albumin is distributed throughout the
extra cellular space (Rainey and English, 1988). After
infusion of 100 ml of concentrated albumin (20%), the
plasma volume continues to increase over the next
30–60 minutes to achieve a final blood volume
expansion of 400–450 ml. Redistribution of 350 ml of
interstitial fluid to the intravascular space is necessary
for this to occur. In patients with extracellular or total
body water depletion, equilibration is slow and
incomplete (Beecher, 1945). Therefore, in acute hypovo-
lemia, 5% albumin should be given rather than the
hyperoncotic form. The 20% albumin solution is
usually used in patients with concomitant hypovole-
mia and elevated extracellular fluid volume.
The duration of vascular retention and the hemody-
namic effects of infused albumin solutions depend
greatly on the patient’s disease state. This variability
may result from ‘leakage’ into the interstitium, prefer-
ential binding of albumin in the skin and wound, or
increased catabolism.
Albumin has several unique effects that differentiate
it from other colloids as well as from crystalloids
(Emerson, 1989). Albumin can bind reversibly with
both anions and cations, which allows it to regulate
the extracellular concentration of various substances
such as iron, lipids and bilirubin (Emerson, 1989).
Albumin also has the ability to act as a free radical
scavenger and may limit lipid peroxidation (Holt,
Ryall and Campbell, 1984; Wasil et al., 1987; Stocker,
Glazer and Ames, 1987; Pirisino et al., 1988). These
properties may in the future become the major reason
for choosing albumin as a resuscitative fluid.
Albumin may also play a role in maintaining
normal microvascular permeability to protein mole-
cules. Endothelial cells contain pores through which
protein molecules may leave the vascular space.
Albumin may help regulate the permeability of these
pores. Hypoalbuminemia increases capillary permea-
bility and restoring the albumin level reduces permea-
bility to normal (Harms et al., 1981; Demling et al.,
1982). However, the intravascular albumin level neces-
sary to maintain normal microvascular permeability is
not known.
Plasma-protein solutions are heated to 60°C for 10
hours during processing and are free of transmissible
diseases (Rainey and English, 1988). Severe side-
effects, such as hypotension, which is probably due to
BASIC PRINCIPLES 299
kinin activation, are rare. Because of their long half-life
care must be taken to avoid circulatory overload in
patients who have been resuscitated with plasma-
protein solutions and appropriate hemodynamic mon-
itoring is required.
Synthetic colloidal solutions
Dextrans are polysaccharides composed of glucose
molecules polymerized into chains of various lengths.
They are classified according to molecular weight and
are available in isotonic saline or 5% dextrose. Because
of their shape dextran molecules are hyperoncotic –
i.e. they have the water-attracting equivalent of
several individual molecules; thus they produce a
plasma-volume expansion of about 120% of the
infused volume (Scheinkestel et al., 1989).
Potentially life-threatening toxic effects may compli-
cate dextran administration, including acute renal
failure, anaphylaxis and bleeding diathesis (Atik,
1969). Dextran 40 has been associated with acute renal
failure due to irreversible plugging of the renal
tubules; Dextran 70 is rarely associated with the
development of acute renal failure.
The incidence of anaphylactoid reactions after dex-
tran administration was reported to be 0.032%. Dextran
40 produced fewer reactions than Dextran 70 and severe
reactions were uncommon (Ring and Messmer, 1977).
Dextran 70 and, to a lesser extent, Dextran 40
produce a dose-related hemostatic defect. This has a
number of mechanisms but is due primarily to a
reduction in platelet adhesion and aggregation nor-
mally mediated by factor VIIIR:antigen activity (Alex-
ander et al., 1975). Dextran also lowers the levels of all
clotting factors by hemodilution, coats blood vessel
walls and cellular elements and impairs the elasticity
and tensile strength of fibrin clots (Atik, 1967; Weiss,
1967; Adelson, Crosby and Roeder, 1955; Karlson et al.,
1967; Muzaffar et al., 1973). Primary hemostasis is
affected and clinically the picture mimics von Will-
ebrand’s disease. Bleeding is more likely in patients
with pre-existing coagulation abnormalities. To mini-
mize this risk, the volume of dextran infused should
be limited to 20 ml/kg/d or 1.5 g/kg/d (Atik, 1967).
Some 50–70% of infused dextran is excreted by the
kidneys and the rest is slowly metabolized.
Because of their interference with coagulation,
dextrans are rarely used in the management of
severely injured patients.
Polygeline (Haemaccel, Hoechst) consists of urea-
bridged gelatin, molecular weight range 5000–50 000;
mean 35 000, derived from cattle-bone gelatin and
suspended in saline. It is an effective plasma volume
expander in critically ill patients (Edwards et al., 1989;
Mishler, 1984). The low-molecular-weight gelatin por-
tion distributes readily through the ECF and produces
300 FLUID, ELECTROLYTE AND METABOLIC MANAGEMENT

Table 16.3 Composition of commonly prescribed electrolyte solutions

Crystalloid solutions Water-equivalent solutions

Isotonic Hartmann‘s (Ringer’s 5% dextrose 4% dextrose
(0.9%) saline lactate) solution in water in 0.18% saline

Glucose (g) – – 50 40
Calories (kcal) – – 205 164
Na+ (mmol/l) 150 131 – 30
K+ (mmol/l) – 5 – –
Cl– (mmol/l) 150 111 – 30
Ca2+ (mmol/l) – 2 – –
Lactate (mmol/l) – 29 – –
Osmolarity (mosmol/l) 300 279 277 282
pH 6.0 5.1 3.5–6.5 3.5–6.5

a plasma volume expansion of only about 70% of the
infused volume. Renal excretion accounts for 85% of
elimination, fecal excretion for 10% and the remainder
is metabolized to non-essential amino acids. Polyge-
line contains potassium and calcium and this must be
remembered when large volumes are infused. Rapid
infusions cause histamine release, which usually takes
the form of urticaria, but anaphylaxis has been
reported (Scheinkestel et al., 1989). Gelatin products
are not associated with renal failure or coagulopathy.
(b) Crystalloid solutions
Crystalloids are isotonic mixtures of sodium chloride
and other physiologically active solutes (Table 16.3).
Sodium is the major component of crystalloid fluids
and the distribution of infused sodium will determine
the distribution of infused crystalloid fluids. Since
sodium is the major solute in the extracellular space
and 80% is extravascular (Edelman and Leibman,
1959), infused sodium will reside primarily in the
extravascular compartment.
Physiological saline and Hartmann’s solution are
the two most frequently used crystalloids and their
volume-expanding effects are identical (Cervera and
Moss, 1975). Figure 16.4 shows the effect of colloid
and crystalloid infusions on blood volume in criti-
cally ill adults. Physiological saline and Hartmann’s
solution are both freely permeable across the vas-
cular membrane and distribute evenly throughout

Figure 16.4 The influence of colloid and crystalloid infusion on blood volume in critically ill adults. (Source: redrawn from
Shippy, Appel and Shoemaker, 1984.)

the extracellular space. In normal individuals
approximately 25% of the infused volume remains
within the blood vessels when equilibrium is reached
(usually within 20–30 minutes). In other words, for
every liter of infused crystalloid approximately
750 ml will pass into the interstitium and 250 ml will
remain in the plasma. Thus interstitial edema is a
necessary consequence of volume resuscitation with
crystalloids and should not, unless excessive, be
interpreted as evidence of fluid overload. However,
the volume of crystalloid used in resuscitating
patients with head injury should be tempered by the
possibility of worsening brain edema.
Crystalloids are well suited for replacing extrac-
ellular fluid losses (dehydration); they are also used to
replace blood loss, based on the notion that acute
hemorrhage (or hypovolemia) causes an interstitial
fluid deficit that must also be replaced. Indeed,
crystalloids have proven effective in resuscitating
patients following acute hemorrhage and continue to
be widely used for this purpose (Moss and Gould,
1988; Dodge and Glass, 1982; Tranbaugh and Lewis,
1985; Shackford, 1987; Horton, Landreau and Tuggle,
1985; Lowe et al., 1979; Virgilio et al., 1979).
Crystalloids are non-toxic and do not produce
anaphylactoid reactions.
(c) Water-equivalent solutions
Solutions of 5% dextrose or 4% dextrose in 0.18%
isotonic saline are essentially water rendered isotonic
to prevent local red-cell lysis at the infusion site. At
most infusion rates insufficient dextrose is present to
alter blood glucose levels, so the fluid is distributed
evenly throughout total body water. Thus for every
liter of solution administered, two-thirds will enter the
intracellular space and one-third the extracellular
space. Three-quarters of the extracellular fluid will be
in the interstitium and one-quarter in the plasma.
Thus about 8% only of the infused volume remains in
the circulation. For this reason 5% dextrose solution is
the fluid of choice for patients with ischemic heart
disease or congestive cardiac failure, since it does not
expand the circulation and increase the cardiac work-
load.
Dextrose and cerebral ischemia
The observation that carbohydrates promote ischemic
damage in the central nervous system is not new but
seems forgotten (Voll and Auer, 1988). The central
nervous system relies on glucose for much of its
energy needs. When cerebral ischemia develops,
glucose infusion will promote anaerobic glycolysis
and produce large quantities of lactic acid, which,
BASIC PRINCIPLES 301
accumulating locally, can reduce flow even further.
Thus dextrose infusion during experimental cardio-
pulmonary resuscitation was associated with a much
higher mortality (Lundy et al., 1987). At this stage, the
routine infusion of glucose is not recommended in
patients at risk of cerebral insufficiency.
Other fluids such as 1 liter of half-isotonic 0.45%
saline can be regarded as comprising 500 ml of isotonic
saline and 500 ml of free water.
(d) Hypertonic saline
Hypertonic saline will increase the osmolality of the
ECF, causing a water shift from cells to re-establish
osmotic equilibrium. One liter of a 3% saline solution
contains 510 mmol each of sodium and chloride – a
total of 1020 osmotically-active particles. These will be
remain in the ECF, thus increasing its number of
osmotically active particles by 25% and its volume by
7%. ECF osmolality will rise to 339 mmol/kg. To re-
establish osmotic equilibrium, about 1.5 liters of water
will shift from the ICF into the ECF. Thus the 1 liter of
a 3% saline solution will increase the ECF volume by
about 2.5 liters in total. As in other states of ECF
expansion, three-quarters of this volume (1.9 l) is
distributed to the interstitium and one-quarter (0.6 l)
to the plasma, explaining the propensity of hypertonic
saline to cause pulmonary and peripheral edema
(Table 16.4).
Hypertonic saline is effective in restoring volume
after hemorrhage (Gala et al., 1991), endotoxic shock
(Horton and Walker, 1991), trauma (Mattox et al., 1991;
Vassar et al., 1991) and burn injury (Griswold et al.
1991; Monafo, Halverson and Schechtman, 1984).
Several clinical studies have suggested a better sur-
vival after resuscitation with hypertonic solutions
compared with isotonic fluids (Mattox et al., 1991;
Monafo, Halverson and Schechtman, 1984; Vassar et
al., 1991).
Hypertonic solutions have a greater volume-
expanding capacity than equal volumes of isotonic
crystalloid solutions. Approximately three times the
volume of 0.9% NaCl compared with 3.0% NaCl was
Table 16.4 Body compartment expansion according to
type of resuscitation fluid: compartment expansion (ml)
per 1000 ml of administered fluid
Fluid Plasma Interstitium Intracellular
Colloid 1000 0 0
Isotonic (0.9%) saline 250 750 0
5% dextrose 83 250 667
Half isotonic (0.45%) 167 500 133
saline
3% saline 600 1900 –1500
302 FLUID, ELECTROLYTE AND METABOLIC MANAGEMENT
required to restore MAP in a canine hemorrhage
model, although the overall amount of sodium admin-
istered did not differ between the two experimental
groups. Because small infusion volumes cause rela-
tively large increases in intravascular fluid volume,
blood volume restitution is rapid; however this effect
is short-lived (Gala et al., 1991).
Hypertonic solutions may reduce edema formation
in non-injured tissues (Battistella and Wisner, 1991;
Cross et al., 1988; Wisner, Schuster and Quinn, 1990).
This may be particularly useful in head-injured
patients. Several studies of resuscitation in experi-
mental brain injury have found that hypertonic
solutions are more effective at lowering intracranial
pressure and decreasing edema in the uninjured
cerebral hemisphere than isotonic fluids (Battistella
and Wisner, 1991; Wisner, Schuster and Quinn, 1990).
In a study of trauma victims with concomitant head
injuries, hypertonic saline resuscitation was associated
with increased survival compared with Hartmann’s
solution (Vassar et al., 1991).
At present hypertonic saline, with or without the
addition of colloid, is most commonly used for
volume resuscitation after trauma or burns. The
efficacy of small volumes and the rapidity of admin-
istration make its use convenient. Other reported
benefits of hypertonic compared to isotonic solutions
are improved pulmonary gas exchange (Boldt et al.,
1991), increased renal cortical and gut mucosal blood
flow (Behrman et al., 1991), decreased bacterial trans-
location (Reed et al., 1991a) and the induction of
natriuresis (Gala et al., 1991) and kaliuresis (Battistella
and Wisner, 1991).
Although these properties would be advantageous
in many clinical situations, the use of hypertonic
solutions is not without problems. In an experimental
model, increased bleeding, probably due to vasodila-
tation, was reported if hypertonic fluid was admin-
istered within 15 minutes of injury (Krausz et al.,
1992). If more than 10% of normal plasma volume is
replaced with hypertonic saline, increases in pro-
thrombin time and activated partial thromboplastin
time and a decrease in platelet aggregation are
observed (Reed et al., 1991b). If large volumes of
hypertonic saline are used, potential complications
include hypernatremia, hyperchloremia, hyperosmo-
larity, hypokalemia, metabolic acidosis, intracellular
dehydration, cerebral hemorrhage, inhibition of lipol-
ysis, hyperosmolar coma and central pontine myeli-
nolysis (Carvajal and Parks, 1988; Cross et al., 1988;
Griffel and Kaufman,1992). These complications are
related directly to the solute load infused and
inversely to the patient’s volume of distribution.
When using hypertonic saline serum sodium levels
(less than 160 mmol/l) and serum osmolarity (less
than 320 mosmol/l) require close monitoring.
16.4 Fluid resuscitation
16.4.1 SHOCK
When hypovolemia is severe, tissue oxygenation
becomes impaired and the clinical and metabolic
features of shock appear. The need for prompt
restoration of adequate plasma volume under such
circumstances is well recognized (Shoemaker, 1976;
Shires and Canizaro, 1973). Hypotension has a mark-
edly deleterious effect on the outcome from traumatic
head injury and indeed from other injuries (Price and
Murray, 1972; Siegel et al., 1991). Hence patients with
head injury should receive sufficient intravenous fluid
resuscitation to avoid hypovolemia and hypotension
(Buchman, Menker and Lipsett, 1991; Levison and
Trunkey, 1982). Few issues in critical care medicine
have prompted as much diversity of opinion as the
most appropriate asanguineous fluid to achieve this
goal (Virgilio, Smith and Zarins, 1979; Shoemaker and
Hauser, 1979; Velanovich, 1989).
The primary abnormality in hypovolemic shock is a
reduction of plasma volume. Absolute or relative
plasma volume deficits contribute to the disturbances
of tissue oxygenation in the other three types of
circulatory shock, cardiogenic, obstructive and septic,
and these also may occur in the head-injured patient.
Decreased plasma volume produces a decrease in left
ventricular end-diastolic volume and stroke volume.
Although sympathetic nervous system activation can
initially maintain cardiac output (CO) by inducing
tachycardia and arterial pressure by producing vaso-
constriction, at some point compensatory limits are
reached and CO and systemic blood pressure may
suddenly fall.
There is clear agreement that the major goal of
treatment of circulatory shock associated with hypo-
volemia is rapid restoration of blood volume and
tissue oxygenation (Rackow et al., 1983; Weil and
Henning, 1979). The use of asanguineous fluids for
initial resuscitation provides better restoration of
capillary blood flow than does immediate transfusion.
Moderate hemodilution, for example, to a hemoglobin
level of 10–12 g/dl, is well tolerated by most patients,
and does not lower ḊO2 if intravascular volume is
maintained (Messmer, 1975).
16.4.2 CHOICE OF FLUID
The hemodynamic response to fluid infusion is influ-
enced by the choice of fluid, vascular tone and cardiac
compliance. Several studies have directly compared
the plasma volume-expanding and hemodynamic
effects of colloids and crystalloids. In these studies, a
preselected volume of fluid was administered rather
than a volume adjusted on the basis of physiological

response. In stable postoperative patients plasma
volume responses were compared to 1 liter infusions
of 6% Dextran 70, 6% hetastarch, 5% albumin, 3.5%
urea-bridged gelatin (Haemaccel) and physiological
saline. Significant increases in plasma volume occur-
red with all colloids but not with physiological saline.
The greatest increases occurred with Dextran 70
(790 ml) and 6% hetastarch (710 ml; Figure 16.5; Lamke
and Liljedahl, 1976).
In acutely ill postoperative patients Lazrove and
associates evaluated responses to infusion of 500 ml of
5% albumin and 6% hetastarch over 1 hour, using a
prospective, randomized crossover design (Lazrove et
al., 1980). Both solutions significantly increased
plasma volume, CO, ḊO2 and V̇O2. Plasma volume
expansion lasted for 1–5 hours with albumin and for
at least 3 hours with hetastarch. Similar hemodynamic
effects of 5% albumin and 6% hetastarch were repor-
ted in a series of critically ill patients by Puri and
associates (1983).
The relative effectiveness in critically ill patients of 1
hour infusions of 500 ml of whole blood, 5% albumin,
6% Dextran 70, 10% Dextran 40 and 1 liter of Ringer’s
lactate were compared (Shoemaker, 1976). Blood and
colloid infusion produced significant increases in
blood volume, CO, stroke volume, left ventricular
stroke work index, central venous pressure (CVP) and
pulmonary arterial wedge pressure (PAWP), but
improvements after crystalloid infusion were insignif-
icant, even though twice the volume was infused
(Figure 16.6). In a later study by the same group
involving critically ill patients with ARDS, 100 ml of
25% albumin was compared with 1000 ml of Ringer’s
lactate (Hauser et al., 1980). Plasma volume increased
by an average of 465 ml with 25% albumin but by only
194 ml with Ringer’s lactate. Significant increases in
ḊO2 and V̇O2 occurred only in the albumin group.
Figure 16.5 Plasma volume expansion after infusion of 1
liter of (1) Dextran 70, (2) 6% hexastarch, (3) 5% albumin, (4)
modified fluid gelatin and (5) NS in postoperative patients.
(Source: reproduced from Lamke and Liljedahl, 1976, with
permission.)
FLUID RESUSCITATION 303
Figure 16.6 Maximal changes in blood volume (ml) versus
change in cardiac output (l/min) after infusion of 500 ml of
whole blood or colloids and 1000 ml of RL in critically ill
patients. (Source: reproduced from Shoemaker, 1976, with
permission.)
Thus the more potent volume expanding properties
of colloids compared to crystalloids may permit more
rapid restoration of hemodynamic stability in hypo-
tensive critically ill patients (Shoemaker et al., 1981;
Modig, 1986). Our current clinical practice is to use
both. In the resuscitative phase the emphasis is on
volume restoration and we use mainly colloid; in the
maintenance phase we use mainly crystalloid.
16.4.3 MONITORING
Changing vascular and cardiac compliances in the
shock patient make it difficult to rely on any single
hemodynamic measurement to define adequate resus-
citation. The adequacy of volume resuscitation is
measured by blood pressure, heart rate and urine
output, which reflect a summation of many different
processes and are only gross estimates of end-organ
perfusion (Lowell et al., 1990). Mean arterial pressure
(MAP), heart rate, central venous pressure (CVP) and
pulmonary arterial wedge pressure (PAWP) do not
reflect intravascular volumes in a linear fashion
(Dawidson et al., 1991; Shippy, Appel and Shoemaker,
1984). CVP may fall during fluid infusion if blood
volume expansion results in decreased autonomic-
nervous-system-induced arteriolar and venous vaso-
constriction (Baek et al., 1975). Changes in left ven-
tricular compliance during fluid resuscitation may
also limit the usefulness of PAWP as a measure of left
ventricular end-diastolic volume (preload; Calvin,
Driedger and Sibbald, 1981).
Even with sophisticated monitoring techniques,
such as Swan–Ganz catheterization and oxygen sat-
uration monitoring, the adequacy of resuscitation and
304 FLUID, ELECTROLYTE AND METABOLIC MANAGEMENT
Table 16.5 Guidelines for fluid challenge utilizing pulmonary arterial diastolic or pulmonary arterial wedge pressure
monitoring: 7/3 rule for fluid challenge. PAWP = pulmonary arterial wedge pressure (mmHg); PADP = pulmonary
arterial diastolic pressure (mmHg). (Source: adapted from Weil and Henning, 1979)
PAWP/PADP
For 10 min before challenge < 12
< 16
≥ 16
During 10 min infusion Change > 7
Change ≥ 3
Immediately after 10 min infusion Change > 3, ≤ 7
After 10 min wait Change > 3
Change ≤ 3
oxygen delivery to individual tissue beds in vital end
organs cannot be determined. Poole et al. demon-
strated this in an experimental canine shock model.
Despite restoration of MAP and cardiac output (CO),
cerebral blood flow did not return to preshock levels
(Poole et al., 1986).
Nevertheless for clinical purposes the hemody-
namic response to fluid resuscitation should be
assessed by using the fluid challenge technique
originally described by Weil and Henning (Table 16.5;
Weil and Henning, 1979). When this is combined with
sequential measurements of CO and measurements of
tissue oxygenation (lactate, ḊO2, V̇O2 and mixed
venous oxygen saturation) the risks of under- and
over-resuscitation are minimized (Shoemaker and
Czer, 1979).
16.4.4 CRYSTALLOIDS VERSUS COLLOIDS
The basic disagreement that initiated the colloid versus
crystalloid controversy was a conceptual one. Those
favoring crystalloids believe that an extracellular fluid
deficit plays a primary role in the pathophysiology of
hypovolemic shock and therefore repletion of this
deficit is essential. Colloid proponents believe that
decreased blood volume and reduced oxygen trans-
port are the critical pathophysiological factors in
hypovolemic shock; therefore, rapid and complete
repletion of the intravascular compartment is critical
for resuscitation.
In a series of experimental and clinical studies
initiated in the early 1960s, Shires and associates
showed that severe hemorrhagic shock was associated
with a large decrease in extracellular volume, caused
predominantly by intracellular shift of interstitial fluid
in addition to external losses or shift in the intra-
vascular space (transcapillary refill; Shires et al., 1964,
1972; Carrico, Canizaro and Shires, 1976). In a canine
hemorrhagic shock model, animals resuscitated with
shed whole blood alone or whole blood plus 10 ml/kg
plasma had a significantly higher mortality than
Fluid infusion rate
200 ml  10 min
100 ml  10 min
50 ml  10min
Stop
Continue infusion without interruption
Wait 10 min
Stop
Repeat fluid challenge
animals resuscitated with whole blood and 50 ml/kg
Ringer’s lactate (Figure 16.7; Shires et al., 1964). In a
baboon model of hemorrhagic shock, microelectrodes
were used to monitor transmembrane potential gra-
dients across individual skeletal muscle cells. Sus-
tained cell depolarization, a 49% decrease in extrac-
ellular water, and 6% increase in intracellular water
increased intracellular sodium and decreased intra-
cellular potassium were all recorded, suggesting a
failure of the ATPase-dependent Na+ –K+ pump
(Shires et al., 1972). Resuscitation with balanced salt
solution produced a return of the potential difference
to normal together with a decrease in intracellular and
an increase in extracellular volume. Similar alterations
in water distribution were described in patients with
circulatory shock and those undergoing major oper-
ative procedures (Shires, 1965; Shires, Williams and
Brown, 1960). These changes also resolved with
infusion of balanced salt solutions.
Figure 16.7 Survival after resuscitation of dogs from
hemorrhagic shock. Each group consisted of 10 dogs, bled
into shock by the Wiggers method. The RL group received
fluid equivalent to 5% of body weight followed by return of
shed blood. The plasma group received 10 ml/kg of donor
plasma plus shed blood. The blood group received shed
blood alone. (Source: reproduced from Shires et al., 1964, ©
1964, American Medical Association, with permission.)

There is however, considerable controversy regard-
ing the methods used by Shires and colleagues to
measure extracellular fluid volume (Shoemaker, 1976;
Roth, Lax and Malone, 1969). Using different tech-
niques and models of hemorrhagic shock, other groups
have found either a minimal decrease in extracellular
volume accountable by the plasma volume loss or else
an increase in extracellular volume (Roth, Lax and
Malone, 1969; Serkes and Lang, 1966; Moore et al.,
1966). There is similar debate about the changes in
extracellular volume after major surgery, where no
significant change was found in patients after chol-
ecystectomy and increases were found in patients after
cardiac surgery (Roth, Lax and Malone, 1969).
Despite this there is considerable evidence, from
experimental models of severe hemorrhagic shock and
from clinical studies of traumatic shock, that subjects
can be successfully resuscitated with balanced salt
solutions and blood (either whole blood or packed red
blood cells) without the need for colloidal solutions
(Lowe et al., 1979; Moss et al., 1981; Weaver et al., 1978).
In the study of Lowe et al. (1979), patients with
traumatic abdominal injuries requiring laparotomy
were resuscitated randomly with either Ringer’s
lactate or 4% albumin together with washed red blood
cells for the entire emergency room and intraoperative
period. Crystalloids alone were used postoperatively.
Clinical criteria (systemic blood pressure, pulse and
urine output) were used as the end points for
resuscitation. Both groups of patients were resuscitated
successfully and overall mortality was low (4.3%).
There was no difference between the two groups in the
need for postoperative ventilatory support. Since most
patients in this study were not in shock on admission,
the results might not be applicable to patients who are
in severe hemorrhagic shock. Moss et al. (1981) repeated
the study in a group of patients with traumatic shock,
defined as systolic arterial pressure of 80 mmHg or the
need for five or more red blood cell transfusions before
surgery, with similar results. Pulmonary edema did not
complicate the use of colloid or crystalloid in either of
these studies. In both studies similar volumes of colloid
and crystalloid were needed for resuscitation. This
surprising finding may be due to the use of clinical
rather than physiological end points for fluid resuscita-
tion. Whether the successful outcome with crystalloid
resuscitation in these studies is related to replacement
of an interstitial fluid deficit or to the limited amount of
the infused solution that remains in the circulation has
not been ascertained. Despite the numerous studies
comparing crystalloids to colloids, none has unequivo-
cally demonstrated a distinct survival advantage with
either therapy.
The current recommendations of the American
College of Surgeons for initial resuscitation of patients
with traumatic injury (hemorrhagic shock) include
EFFECTS OF INTRAVENOUS FLUIDS ON THE BRAIN 305
rapid infusion of up to 2 liters of Ringer’s lactate until
hemodynamic stability is restored. If the patient
remains unstable packed red blood cells are then
infused. The use of two to four large-bore intravenous
lines can compensate for the much more limited
volume expansion produced by crystalloids. Compli-
cations of this approach to fluid infusion are minimal
(Moss et al., 1981).
The choice of fluids in patients with massive
bleeding that is difficult to control, or those with pre-
existing medical problems, is more controversial. In
these situations fluid administration may result in
fluid overload and subsequent morbidity. The risk of
pulmonary edema has been central to the debate over
the relative merits of crystalloids versus colloids. As
mentioned earlier, capillary membrane permeability,
capillary hydrostatic pressure, colloid osmotic pres-
sure (COP) and pulmonary lymph flow are all
important factors in the development of pulmonary
edema. Despite claims to the contrary (Virgilio et al.,
1979), weight gain and systemic edema due to fluid
infusion are not benign problems (Falk, 1991; Lowell et
al., 1990). Decreased chest wall compliance due to
tissue edema may occur following hydration with
crystalloid (Brinkmeyer et al., 1981). Peripheral edema,
particularly in a debilitated patient, can cause
decreased mobility and subsequent skin breakdown.
Tissue oxygenation is decreased when edema is
present (Heughan, Niinikoski and Hunt, 1972) and
wound healing may be impaired (Falk, 1991; Man-
galore and Hunt, 1972; Niinikoski, Hengan and Hunt,
1972).
Edema of the gastrointestinal tract may result in
ileus and intolerance for enteric alimentation (Falk,
1991). The potential for bacterial translocation and the
development of systemic sepsis and multiple systems
organ failure may also be increased (Baker et al., 1988;
Wilmore et al., 1988).
In addition, systemic edema can increase time on
mechanical ventilation, require diuresis or dialysis
and lengthen the stay in the ICU
16.5 Effects of intravenous fluids on the
brain
Parenteral fluid therapy, particularly in patients with
head injury, may increase brain swelling, intracranial
pressure and neurological dysfunction and this may
be reflected in increased mortality and morbidity
(Vassar et al., 1991; Battistella and Wisner, 1991; Falk,
1991; Fein et al., 1982). However, there is little
information available on the relative effects of colloid
or crystalloid administration on cerebral edema for-
mation in normal subjects or in patients with brain
injury and decreased intracranial compliance (Zornow
et al., 1988).
306 FLUID, ELECTROLYTE AND METABOLIC MANAGEMENT
16.5.1 THE EFFECTS OF CRYSTALLOIDS AND
COLLOIDS ON THE NORMAL BRAIN
Early studies in animals demonstrated brain shrinkage
in response to infusion of hypertonic solutions and
expansion in response to hypotonic solutions (Weed
and McKibben, 1919a, b). In general, hypertonic fluids
decrease both brain interstitial and intracellular vol-
ume and thus decrease ICP, and hypotonic fluids have
the opposite effects. It was not possible to determine
from these studies whether the increase in ICP and
cerebral water content with hypotonic solutions was
due to a decrease in plasma osmolality or a decrease in
colloid oncotic pressure (COP). To clarify this issue,
Zornow, Todd and Moore (1987) examined the acute
effects of changes in plasma osmolality and plasma
COP in normal rabbits with an intact blood–brain
barrier. In one group COP was decreased without a
change in plasma osmolarity, whereas in a second
group a hypo-osmolar condition was produced with-
out change in the COP. Cerebral edema, estimated by
changes in brain specific gravity, developed only in the
hypo-osmolar group, suggesting that changes in COP
do not influence intracranial water distribution in the
absence of brain injury (Figure 16.8). These and other
studies demonstrate that when the blood–brain barrier
is intact, brain volume is strongly influenced by plasma
osmotic pressure and is unaffected by changes in
plasma oncotic pressure (Hindman et al., 1990). The
brain, like a red blood cell, swells in a hypotonic
solution and contracts in a hypertonic solution.
The effects of fluid resuscitation in experimental
hemorrhagic shock on ICP and cerebral edema in
animals with intact blood–brain barriers have been
evaluated in several studies (Poole et al., 1986; Prough et
al., 1985; Gunnar et al., 1986). In different models, fluid
Figure 16.8 Acute cerebral effects of changes in plasma
osmolality and oncotic pressure in normal rabbits. The
lower the specific gravity, the greater the brain water
content **p < 0.01 versus other groups. (Source: from Zor-
now, Todd and Moore, 1987, with permission.)
resuscitation with hypertonic crystalloid solutions was
consistently associated with a lower ICP than fluid
resuscitation with Ringer’s lactate, physiological saline
or 10% Dextran 40 (Prough et al., 1985; Gunnar et al.,
1986, 1988). Resuscitation with 6% hetastarch was
associated with significantly lower ICP than resuscita-
tion with Ringer’s lactate (Poole et al., 1986).
The unique structural characteristics of the cerebral
capillaries (the blood–brain barrier) limit the effects
of changes in COP on cerebral water distribution.
The intercellular pores of non-cerebral capillaries are
approximately 65 Å in diameter. Ionic solutes such as
sodium and chloride are able to migrate freely
between the interstitium and the intravascular space
and therefore have no influence on water distribu-
tion (Zornow, Todd and Moore, 1987). High-molec-
ular-weight compounds like albumin and urea-
bridged gelatin are retained in the intravascular
space and produce an oncotic gradient that tends to
retain water in the capillaries. Because of the small
pore size (8 Å) of cerebral capillaries, changes in
serum electrolyte content (osmolarity) have signifi-
cant effects on water movement. An osmotic gradient
of 1 mosmol/l produces a hydrostatic gradient of
19.3 mmHg. Because there are so few protein mole-
cules compared with the number of inorganic ions,
their effect is minimal (Albright, Latchaw and Robin-
son, 1984). A 10 mm decrease in COP during crys-
talloid resuscitation has the same effect on cerebral
water distribution as a decrease in osmolality of only
0.5 mosmol/l. Clearly the influence of changes in
osmolarity on cerebral water distribution dwarfs the
effects of alteration of COP.
16.5.2 THE EFFECTS OF CRYSTALLOIDS AND
COLLOIDS ON THE BRAIN AFTER INJURY
Patients with severe traumatic injuries often require
resuscitation with large volumes of intravenous fluid
to restore hemodynamic stability. When a head injury
is also present, the choice of fluid for resuscitation may
influence the development of brain edema. Animal
studies confirm that damage to the blood–brain
barrier (e.g. by cryogenic injury) increases the permea-
bility of capillaries to both proteins and electrolytes so
that osmotic and oncotic gradients cannot be estab-
lished (Zornow et al., 1988; Weed and McKibben,
1919a). In these circumstances capillary hydrostatic
pressure determines the rate at which edema forms.
When hemorrhagic shock was combined with cryo-
genic brain injury, brain water fell in uninjured brain
after resuscitation with hypertonic saline but not in
areas of brain injury where the blood–brain barrier
was damaged (Wisner, Schuster and Quinn, 1990).
Other animal studies evaluating the effects of fluid
resuscitation in hemorrhagic shock on neurological

function have shown that, although ICP in animals
resuscitated with hypertonic saline was significantly
lower, cerebral perfusion pressure was significantly
higher in those receiving 6% hetastarch compared
with those receiving hypertonic saline or physio-
logical saline. Neurological function was also best in
the hetastarch group, suggesting that restoration of
cerebral perfusion pressure is a more important goal
than change in ICP alone. The vasodilatory effect of
hypertonic saline may have resulted in a lower mean
arterial pressure compared with hetastarch.
These experimental results reaffirm that hypertonic
saline will shift water from the intracellular to the
extracellular space. Ringer’s lactate is a hypo-osmolar
solution and 6% hetastarch is iso-osmolar; hence the
differing effects of these solutions on ICP can be
explained by their osmolarities.
The lower ICP after resuscitation with hypertonic
crystalloid solutions may assist in restoring of cerebral
blood flow and ḊO2, but there is not universal
agreement on this issue (Prough et al., 1986).
The days of keeping the patient with a head injury
‘dry’ are over. There is no good evidence supporting
fluid restriction as a means of limiting cerebral edema
after brain injury (Morse et al., 1985). Dehydration
increases sympathetic stimulation, metabolism and O2
demand (Beckstead et al., 1978). Indeed, the ther-
apeutic aim is now to maintain euvolemia and normal
physiological indices, especially cerebral perfusion
pressure. Animal studies support this approach
(Smith et al., 1982; Ito et al., 1979).
16.6 Metabolic response to injury
16.6.1 OVERVIEW
Major injury, whether surgical or accidental, evokes
predictable metabolic, hormonal and hemodynamic
responses (Buckingham, 1985; Table 16.6). Changes in
carbohydrate metabolism include increased endoge-
nous hepatic glucose production (gluconeogenesis)
and reduced glucose clearance (insulin resistance),
which results in hyperglycemia. Fat becomes the
major body fuel; therefore lipolysis is increased and
lipogenesis is retarded. Changes in protein metabo-
lism are manifested by negative nitrogen balance
Table 16.6 Metabolic response to injury
 Altered protein homeostasis
 Hypermetabolism
 Altered carbohydrate metabolism
 Sodium and water retention
 Increased lipolysis
METABOLIC RESPONSE TO INJURY 307
reflecting accelerated net protein breakdown (catabol-
ism). The magnitude of these changes is proportional
to the extent of the injury (Weissman, 1990).
16.6.2 STARVATION
Starvation, i.e. lack of nutrient input, often accom-
panies injury, while nutrient utilization is normal at
the cellular level. During starvation, metabolic adapta-
tion occurs, with the aim of conserving essential
tissues. There is little or no activation of metabolic
mediators and the system is still able to respond to
normal physiological stimuli. Glycogen reserves are
only small, approximately 200–400 g; thus liver glyco-
genolysis is only useful for 24 hours. Decrease in
insulin and increase in glucagon secretion result in
protein and fat breakdown to provide energy. Amino
acids are converted to pyruvic acid, acetyl CoA and
tricarboxylic acid (Krebs) cycle intermediates. Glyc-
erol from fat is fed into the glycolytic pathway and
fatty acids form acetyl CoA, some of which enters the
Krebs cycle inside the mitochondria; some is con-
verted to ketones, which are used by skeletal muscle
and brain. Protein catabolism results in increased
urinary loss of urea, sodium, potassium, magnesium
and calcium. As the new energy pathways become
established, protein breakdown decreases and fat
becomes the chief energy source, supplying 75–90% of
the calories. The basal metabolic rate decreases as a
result of decreasing lean body mass, decreased phys-
ical activity, and decreased thyroxine production.
These changes are summarized in Figure 16.9.
In the absence of sepsis or injury, the starved patient
can usually be rapidly converted to the anabolic state
by administering moderate amounts of nutritional
substrate.
16.6.3 METABOLIC STRESS
When surgery, trauma or sepsis occur, a new process is
activated (Cerra, 1986). Injured or dead tissue, divid-
ing organisms, severe perfusion deficits and resolving
hematomas activate mediator systems that affect end-
organ function, producing the clinical, physiological
and metabolic manifestations of the response to stress.
This process is dynamic, and begins with a lag or ebb
phase during which there is little metabolic activity.
This is followed by a flow phase during which
metabolic activity increases and peaks, usually on day
3 or 4 after injury. The processes then abate over
another 3–4 days, unless a complication ensues. In the
event of a new stress, the process reactivates and
reaches a new peak.
The resting energy expenditure rises to an amount
that depends on the type and severity of the stress.
At high levels of stress, 30% or more of the increased
308 FLUID, ELECTROLYTE AND METABOLIC MANAGEMENT
Figure 16.9 Acute non-stressed fasting metabolism. The initial flow of substrate is designed to provide glucose for obligate
and non-obligate glucose users. With time, ketones and fats become the main energy substrates, resulting in daily urinary
nitrogen excretion.
energy expenditure appears to come from the oxida-
tion of amino acids, 30–40% from glucose and
30–40% from fat. With activation of metabolic media-
tors by trauma, gluconeogenesis becomes less
responsive to exogenous nutritional substances (sec-
tion 16.6.4(b)). Thus, administered glucose has pro-
gressively less inhibiting effect on lipolysis, proteol-
ysis and gluconeogenesis. Glucose calories, as well as
other calories, which are in excess of the existing
demands promote lipogenesis, with excess CO2 pro-
duction and hepatic dysfunction.
Proteolysis increases and amino-acid flux attempts
to meet the demands of energy production and
protein synthesis. Ureagenesis is increased and more
nitrogen is present in the urine. Gluconeogenesis is
increased; peripheral glucose uptake is normal, but
much of the glucose is recycled as lactate and
alanine. Thus, increased plasma glucose and lactate
levels are a normal part of the response. Ketosis is
relatively depressed. These changes are summarized
in Figure 16.10.
Malnutrition usually develops rapidly in post-
traumatic patients, taking days instead of the weeks
needed in simple starvation. It is difficult to exclude
the effects of bedrest (disuse) on some of the para-
meters. Indeed, in patients with isolated closed-head
injuries many reports have described persistent
excretion of large amounts of urinary nitrogen up to
weeks after severe head injury. However some stud-
ies indicate that the response abates in 5–7 days
unless a complication ensues. The early nitrogen
excretion appears to reflect the stress response,
whereas the persistent nitrogen excretion may be due
to bedrest and disuse in a largely young and mus-
cular group of patients.
In some instances under new stimuli the process
reactivates and the state of persistent hypermetabol-
ism with or without the development of multiple
system organ failure ensues (Cerra, 1986). Risk fac-
tors include severe perfusion shock, severe septic
shock, persistent septic sources, and recurrent septic
episodes.
16.6.4 MEDIATORS OF THE RESPONSE TO INJURY
(a) The neuroendocrine axis
The mechanisms initiating, regulating and sustaining
this response are not all identified. It is known that
injured patients have elevated levels of the anti-
insulin hormones: cortisol, glucagon, and the cate-
cholamines. Insulin levels are usually elevated, but
not sufficiently to prevent the commonly noted
hyperglycemia. Growth hormone, aldosterone and
ADH are also elevated. These elevations may in part
be neurally mediated via the hypothalamus (Hume
and Egdahl, 1959). Patients with severe head injury
may develop abnormalities of fluid and electrolyte
balance because of damage to the neuroendocrine
axis (e.g. diabetes insipidus following pituitary dam-
age; Figure 16.11).
 METABOLIC RESPONSE TO INJURY 309

Figure 16.10 Summary of moderate to severe stress metabolism. The neuroendocrine and intrinsic mediator systems
modulate the metabolic machinery to mobilize fat and amino acid stores, which provide a continuous supply of fuel to meet
increased energy demands and provide an increased supply of substrate for the production of stress proteins. Increased
urinary nitrogen excretion is one result of the process. BCAA = branched-chain amino acids.

(b) Cytokines lemia), nausea and emesis, and hypoglycemia. Of

these, osmotic stimulation is the most important for
Several non-endocrine factors play important roles in
fine control of ADH secretion and maintenance of
the response to stress. These include interleukin-1 (IL-
water balance. A number of drugs used in critically ill
1), tumor necrosis factor (TNF), IL-2 and gamma-
patients affect ADH secretion. Halothane and mor-
interferon (IFN). The reader is referred to the extensive
phine in high doses increase ADH release, while
review of this subject by Weissmann (1990).
phenytoin and chlorpromazine inhibit ADH release.
Positive pressure ventilation also increases secretion.
16.6.5 EFFECT OF STRESS ON FLUID AND The thirst mechanism assists by controlling fluid
ELECTROLYTE MOVEMENTS intake to some extent in the conscious patient.
The second objective is to keep the total sodium
The changes in electrolyte concentrations and fluid
content of the ECF within normal limits and thus
distribution after trauma and critical illness have been
maintain a normal ECF volume. Since sodium is the
extensively studied. In the normal subject neural,
major cation of the ECF and the body adjusts the water
hormonal, hemodynamic and renal mechanisms func-
around it to maintain a normal sodium concentration,
tion in a highly integrated manner to preserve sodium
the total number of sodium ions in the ECF will
and water homeostasis. There are two main objectives.
determine the ECF volume. Large deviations from
The first is to keep the concentration of sodium in the
normal in the ECF sodium content cause fluctuations
ECF within a very narrow range. Together with its
in the circulating blood volume. Both volume contrac-
associated anions, sodium constitutes more than 90%
tion and expansion can have serious effects on brain
of the total solute in the ECF and controls the
function, particularly in the presence of pre-existing
distribution of water between the cells and the
brain damage (Aubry and Nankin, 1965). Normally,
extracellular space. Large deviations from normal in
ECF sodium is regulated by several closely coordi-
ECF sodium concentration cause cells to shrink or
nated mechanisms that adjust the amount of sodium
swell, which may have serious consequences for brain
lost through the kidneys.
function. Sodium concentration is kept constant by
finely adjusting the water content of the ECF through  The relative fullness of the ECF is sensed by
the secretion of antidiuretic hormone (ADH, vasopres- receptors located in low- (intrathoracic) and high-
sin; Figure 16.12). At least four independent physio- pressure (intra-arterial) areas of the cardiovascular
logical stimuli release ADH into the blood stream: system. When changes in ECF volume occur, renal,
osmotic, hemodynamic (hypotension and/or hypovo- neural and hormonal mechanisms modulate renal
310 FLUID, ELECTROLYTE AND METABOLIC MANAGEMENT

(a)

(b)

Figure 16.11 Hypothalamic control of pituitary secretion. (a) Vasopressin and oxytocin are secreted in the paraventricular
and supraoptic nuclei of the hypothalamus and transported in the axons of the supraoptico-hypophyseal tract to the
posterior lobe of the pituitary gland; these hormones are then released into the circulation. (b) Hypothalamic releasing
hormones are formed in the hypothalamus and are transported to a capillary plexus formed by the superior hypophyseal
arteries around the median eminence and infundibular stem of the hypothalamus; these hormones there enter into the
vascular system and are taken by the portal veins to the adenohypophysis. (Source: reproduced from Brown, David and
Reilly, 1995, with permission.)
 METABOLIC RESPONSE TO INJURY 311

Figure 16.12 Control of body fluids. This shows the pituitary gland at the top of the diagram, the heart in the center and
the two kidneys. The factors affecting ACTH, ADH and catecholamine release are shown and the effects on the kidney of
these two hormones are simplified at the bottom of the diagram. The possible results of the kallikrein system, natriuretic
hormone and angiotensin are also included.

sodium excretion such that renal sodium and water
excretion fall when absolute or relative ECF volume
is low and increase when ECF volume is high. The
renal mechanisms influencing sodium excretion in
response to changes in ECF volume are listed in
Table 16.7.
 Physical factors in the peritubular capillary environ-
ment are one of the principal mechanisms influenc-
ing Na+ excretion in response to changes in ECF
volume. When renal perfusion pressure falls or
oncotic pressure in the peritubular capillary increa-
ses, the balance of Starling forces favors sodium and
water reabsorption in the proximal tubule. Con-
versely, if the hydrostatic pressure in the peri-
tubular capillary is increased, sodium excretion
occurs. Changes in the resistance of the glomerular
afferent or efferent arteriole affect renal sodium
reabsorption independent of changes in renal perfu-
sion pressure or oncotic pressure. Vasodilatation
(e.g. with low-dose dopamine) increases capillary
Table 16.7 Renal mechanisms influencing sodium
excretion in response to changes in ECF volume
 Physical factors in peritubular capillary environment
(i.e. hydrostatic and oncotic pressure)
 Changes in resistance of afferent or efferent arteriole
 Renal adrenergic nerve fibers
 Hormonal mechanisms–renin–angiotensin–aldosterone;
atrial natriuretic peptide (ANP)
312 FLUID, ELECTROLYTE AND METABOLIC MANAGEMENT

hydrostatic pressure and renal sodium excretion,  retention of Na+ and water; water is retained
while vasoconstriction (e.g. heart failure) reduces relatively more than Na+, leading to dilutional
hydrostatic pressure and renal sodium excretion. hyponatremia.
Adrenergic nerve fibers innervate the renal tubules
These changes are maximum on the first and second
and may influence renal sodium excretion inde-
day after injury and persist for 4–7 days. They are
pendent of changes in renal hemodynamics. Stim-
more pronounced after severe trauma (Verney, 1954).
ulation enhances sodium reabsorption, while dener-
vation reduces renal Na+ reabsorption.
 The major hormonal mechanism influencing renal 16.7 Fluid therapy in uncomplicated
sodium excretion is the renin–angiotensin–aldos- postoperative and post-traumatic states
terone system. The juxtaglomerular apparatus
senses a reduction in effective blood volume, renin 16.7.1 FLUID AND ELECTROLYTE REQUIREMENTS
is released from the kidney, ultimately increasing
angiotensin II and aldosterone levels. Aldosterone Abnormal fluid losses occur through:
increases distal tubular sodium reabsorption and
 external routes, such as hemorrhage, GI losses,
potassium excretion. Angiotensin II also increases
wounds and burns; CSF otorrhea in young children
systemic vascular resistance and proximal tubular
can sometime be clinically significant;
sodium reabsorption by increasing resistance in the
 internal shifts into the interstitial water or extra-
efferent arteriole.
cellular water;
ANP is produced both in atrial myocytes and within  local edema due to surgical wounds, crushing
the CNS is also important in body sodium regulation injuries, burns, venous thrombosis;
(Needleman and Greenwald, 1986; Samson, 1987). Its  fluid accumulation in the transcellular space, e.g.
actions tend to oppose those of ADH and angiotensin, pleural effusion, ascites and paralytic ileus.
and so it appears to play a role in regulating fluid and
Fluid replacement must take into account basal losses,
electrolyte balance. ANP may play a role in local
additional extrarenal losses and distributional chan-
control of brain volume as well as electrolyte and
ges, based on an understanding of the underlying
water content. ANP is released into the systemic
physiological and metabolic changes.
circulation from the atria, stimulated by increased
Once a stable circulation has been established, water
intravascular volume or by increased atrial pressure
replacement in adult patients with no oral intake
independent of intravascular volume, and under salt-
should equal urinary losses, usually 1000–1500 ml/d,
loading conditions as with infusion of hypertonic
plus insensible water losses, usually 600–800 ml/d,
saline. ANP decreases renal vascular resistance and
minus the volume of endogenous water released by
increases glomerular filtration rate. It induces natriur-
tissue breakdown during semistarvation. In uncom-
esis and diuresis and inhibits the renin–angiotensin–
plicated, afebrile postoperative patients, the latter is
aldosterone axis. ANP also reduces systemic vascular
usually only 100–200 ml but may be as much as
resistance and blood pressure.
1000 ml in a critically ill trauma patient with sepsis.
Fluid balance disturbances are common among
Thus, replacement volume is approximately
patients with head injury and are often multifactorial.
1500–3000 ml/d, depending on weight, age, sex and
Hyponatremia has often been attributed to a cerebral
overall status. Elderly patients with underlying car-
salt-wasting state or to inappropriate secretion of
diac or renal disease usually require less.
antidiuretic hormone (SIADH; as noted earlier, a
Water requirements increase by about 300 ml/d for
moderate degree of ADH secretion is part of the
each 1°C elevation in body temperature. Fluid require-
response to stress). However, hyponatremia may in
ments are greatly increased by shock, multiple
fact often be iatrogenic (Bouzarth et al., 1982; Nelson et
trauma, sepsis, postoperative complications and other
al., 1981). Hypernatremia and hyperosmolarity are
critical illnesses. Under these conditions, criteria for
present in many head-injured patients as a con-
fluid therapy are based primarily on hemodynamic
sequence of the fluid restriction and hyperosmolar
factors and adequate oxygen delivery.
agents used to manage the increases in intracranial
Basal sodium requirements are met by the daily
pressure. Hypothalamic dysfunction can cause diabe-
administration of 500 ml of physiological saline
tes insipidus with hypernatremia.
(75 mmol/d) plus the estimated volume of extrarenal
The major fluid/electrolyte changes immediately
fluid losses (e.g. nasogastric suction, diarrhea, CSF
after acute injury are:
and other fistulae, and pleural or peritoneal drains).
 release of K+ by the cells, leading to transient In an uncomplicated postoperative patient, 40 mmol
relative hyperkalemia, increased K+ excretion and potassium per day is usually sufficient, unless the
subsequent reduction of total body K+; patient is suffering from renal failure or upper GIT

bleeding. Such patients may develop hyperkalemia
and thus usually need less K+ replacement. Fluid
therapy of brief duration does not usually require
magnesium, but debilitated patients who do not have
renal failure may benefit from 10–15 mmol Mg2+
daily.
Nutritional support plays an integral role in the
management of metabolic stress. The time to initiate
nutritional support is not completely settled. It is
generally agreed that oxygen transport must be
restored, stabilized and maintained prior to beginning
nutritional therapy. In a previously well nourished
patient, our practice is to wait a few days, whereas in
a severely malnourished patient, therapy should begin
as soon as O2 transport is stabilized.
16 7.2 NUTRITIONAL REQUIREMENTS
Nutrition may be administered via the enteral or
parenteral route. The essential requirements are as
follows.
(a) Calories
Energy as carbohydrate or fat is given to meet the
metabolic needs of the patient (i.e. basal metabolic rate
plus additional demands). Sufficient energy of non-
protein origin must be given to prevent infused
protein being used as an energy source. Energy is
measured in kilocalories (kcal) or kilojoules (kJ) – one
kilocalorie = 4.184 kilojoules. A satisfactory ratio of
non-nitrogen kilocalories per gram of nitrogen is 150:1
(each 6.25 g protein yields 1 g nitrogen).
Although numerous equations and nomograms
have been used to estimate metabolic rate and
nitrogen requirements, none predict accurately which
caloric or nitrogen substrate will be utilized most
effectively. Furthermore, substrate utilization varies
during the course of an illness.
The increase in metabolism during the acute phase
of injury is short-lived, and nutritional requirements
fall rapidly within 2–5 days as shock, pain and sepsis
resolve and recovery begins. During convalescence
very few hospital patients expend more than
1500–2000 kcal (6300–8400 kJ) per day.
Glucose
Glucose and lipid solutions are the standard intra-
venous energy substrates. In a normal person a daily
infusion of 4 mg/kg/min of glucose suppresses gluco-
neogenesis maximally Approximately one-third of the
infused glucose is oxidized immediately and the
remainder is stored as glycogen or lipid. Increasing the
infusion rate increases the amount of glucose stored,
thus increasing O2 utilization and CO2 production. A
FLUID THERAPY IN UNCOMPLICATED STATES 313
greater caloric intake is unnecessary in most patients
and may be detrimental in those with severe respira-
tory failure, particularly if infusion rates of greater than
7 mg/kg/min (equivalent to 700 g of dextrose or
2800 kcal/d in a 70 kg subject) are used. Excessive
glucose administration may lead to hepatic steatosis,
hyperbilirubinemia and an elevated alkaline
phosphatase.
In patients requiring parenteral nutrition, glucose
should be used as the major caloric source and infused
at a rate no greater than 30 kcal/kg/d (equivalent to
500 g of dextrose or 2000 kcal/d in a 70 kg subject).
Each gram of glucose provides approximately 4 kcal.
Lipid
Intravenous lipids are available as emulsions similar
in particle size to chylomicrons, and are cleared as
such by the body. Chylomicrons are acted upon by
plasma lipoprotein lipase to form free fatty acids and
glycerol, which are either oxidized or stored as lipid.
Although there is an increasing trend toward the
routine use of lipid solutions as an energy source,
these expensive substances have no advantages over
dextrose. Lipid solutions are only necessary to provide
the essential fatty acids linolenic and linoleic. In the
absence of essential fatty acids, linoleic and hence
arachidonic acid levels fall and skin lesions (desqua-
matous dermatitis) may result. Approximately 9 kcal
is provided for each gram of fat used by the body.
(b) Protein
The normal adult only needs an oral intake of 20 g of
protein to meet daily protein requirements. Protein
ingested in excess of this amount is broken down to
provide energy and nitrogenous wastes. In the acutely
ill patient, the minimal quantity of protein required is
unknown, but it is unlikely to exceed 50 g/d in a
patient who is not losing protein externally. The
usually quoted requirement is 1–2 g/kg body weight
per day.
Normal adults require 20 L-amino acids for protein
synthesis, although only leucine, isoleucine, valine,
lysine, threonine, phenylalanine, methionine and tryp-
tophan cannot be synthesized and are therefore
essential. In patients requiring parenteral nutrition,
histidine, arginine and cysteine may also be
required.
For effective nitrogen utilization, a ratio of essential
to total amino acids of 2:5 is advisable, and should
reflect the amino acid profile of a normal diet. To
reduce the oxidation of amino acids as an energy
substrate, a source of alternate energy should be
administered simultaneously in a ratio of 150 kcal for
each 1 g of nitrogen.
314 FLUID, ELECTROLYTE AND METABOLIC MANAGEMENT

(c) Vitamins and trace elements Table 16.8 Recommended daily allowance (RDA) of
vitamins for adults (MVI-12 contents)
Vitamins are dietary compounds that act as cofactors Vitamin RDA (mg) MVI-12(mg)
for intermediary metabolism. Patients may develop a
deficiency of the water-soluble C and B group vitamins A 1 1
and vitamin K within 4 weeks of parenteral nutrition; D 0.005 0.005
E 10 10
hence they should be administered to all patients K 0.1 –
receiving intravenous nutrition at doses equivalent to B1 (thiamin) 1.5 3
normal daily requirement (Table 16.8). Vitamin defi- B2 (riboflavin) 1.6 3.6
ciency may rarely affect neurological assessment. B6 (pyridoxine) 2.2 4
The essential trace elements are those present in the Niacin 18 40
Folic acid 0.4 0.4
body in amounts of less than 50 g/g tissue, and are B12 0.003 0.005
required in the diet in milligram quantities or less per Biotin 0.05 0.06
day. They are usually defined by their deficiency states, Pantothenic acid 5 15
i.e. a reproducible functional and/or structural abnor- Ascorbic acid 60 100
mality associated with a specific biochemical change MVI-12 does not contain vitamin K
which is prevented or reversed by the element.
With the exception of zinc, the body stores of the
essential trace elements, copper, iodine, iron, man-
ganese, cobalt, selenium, chromium and molybdenum possible. In many patients the gut provides an
are usually adequate for patients requiring parenteral adequate portal of entry for nutritional support at a
nutrition for less than 3 months. A total of 2.5 mg of zinc much reduced risk. By keeping bacteria and toxins
per day will normally maintain the zinc balance, within its lumen, the gut has a role in host defense. In
although, in patients with diarrhea, up to five times this states of metabolic stress, especially coupled with gut
amount may be required. Table 16.9 summarizes starvation, mucosal permeability increases, allowing
parenteral nutrient intake for adults. Trace element movement of enteric bacteria to the regional lymph
deficiency can result in neurological manifestations, nodes and thence to the systemic circulation.
which may interfere with the neurological assessment Proven benefits of enteral feeding include main-
of the head-injured patient and wound healing, as is the tenance of an intestinal ‘barrier’ and better immune
case with some vitamin deficiency syndromes. There is function, improved liver blood flow following shock
little data regarding the optimal amounts of provision and better wound healing. Gut feeding can be started
of trace elements to critically ill patients. Guidelines early even in the presence of a mild ileus, although
will only be established when more accurate methods early feeding does not attenuate the metabolic
are developed for assessing and monitoring trace response to blunt trauma (Eyer et al., 1993). Exercise,
element status in patients in intensive care. even when done passively, is a potent anabolic
Gastric atony is usually present during states of stimulus and retards nitrogen mobilization in criti-
metabolic stress and responds poorly to motility cally ill and injured patients. While vigorous nutri-
enhancers. Gastric feeding is associated with a very tional support appears to affect mortality favorably
high incidence of aspiration and great care must be and speed recovery from head injury, nutrient admin-
taken to avoid this. These problems are alleviated by istration alone cannot override the metabolic response
using sites for feeding distal to the pylorus and in our to head injury (Clifton et al., 1984; Young et al., 1985).
view enteral nutrition should be used whenever Despite adequate caloric administration, severe head

Table 16.9 Usual daily dose range of parenteral nutrient intake for the adult

Nutrient Amount Comment

Water 2500–3500 ml 30–40 ml/kg/d

Calories 2500–3500 30–40 kcal/kg/d
Glucose 600–900 g
Protein equivalent (as amino acids) 60–130 g 1–2 g/kg/d
Na+ 100–120 mmol ↑ with GI losses; ↓ in elderly, CCF
K+ 80–120 mmol ↓ with renal failure
Ca2+ 4–10 mmol
Mg2+ 12–15 mmol ↑ with GI losses
PO4 10–15 mmol ↑ when glucose alone is given; ↓ with renal failure

injury is followed by negative nitrogen balance,
weight loss and depression of immune status and of
plasma protein levels.
(d) Nutrition and outcome
Since protein-calorie malnutrition can adversely affect
the structure and function of many organs, including
the lungs (Arora and Rochester, 1982), heart (Heyms-
field et al., 1978), gastrointestinal tract (James, 1971)
and musculoskeletal system (Jeejeebhoy, 1986) as well
as wound healing (Haydock and Hill, 1987) and
immune function, nutritional support might be expec-
ted to have a beneficial effect on mortality and
morbidity following head injury.
However, although there are studies that suggest
that nutritional support is beneficial in supporting
general metabolism following head injury (McMahon
et al., 1993), a significant relationship between nutrient
intake and outcome has not been proved.
16.8 Disorders of water and electrolyte
balance
Hypovolemia (from aggressive use of diuretics),
hyperosmolarity (from osmotic diuretics, hyperglyce-
mia resulting in glycosuria, and diabetes insipidus)
and disorders of sodium metabolism (especially the
syndrome of inappropriate ADH secretion – SIADH)
are common problems in head-injured patients. These
and other disorders may cause secondary brain injury
through their effects on cerebral perfusion, intra-
cranial pressure and neuronal function.
16.8.1 HYPONATREMIA
Hyponatremia (plasma Na+ < 135 mmol/l) is seen in
5–12% of patients with severe head injury (Steinbok
and Thompson, 1978). It is especially important,
since the osmotic buffering capacity of the brain may
be impaired following primary brain injuries. ECF
osmolality is reduced in all cases of hyponatremia in
the absence of abnormal solute accumulation, and
even small decreases in osmolality may cause brain
edema, impairing brain function and increasing ICP.
The pathogenesis of hyponatremia is summarized in
Table 16.10.
Hyponatremia may occur in association with dif-
ferent levels of body fluid tonicity (Table 16.11) and
so be classified as isotonic, hypertonic or hypotonic,
based on the measured plasma osmolality. Hypona-
tremia following head injury is hypotonic and is
usually thought to be due to SIADH. The risk of
hyponatremia seems greater in those with severe
head injuries, chronic subdural hematoma and basal
skull fracture (Steinbok and Thompson, 1978; Doczi
et al., 1982). There are numerous reports alleging that
DISORDERS OF WATER AND ELECTROLYTE BALANCE 315
Table 16.10 Pathogenesis of hyponatremia (ADH =
antidiuretic hormone; GI = gastrointestinal)
 Shift of water from the cell (e.g. hyperglycemia,
mannitol infusion)
 Shift of sodium into the cell (e.g. potassium loss)
 Retention of water (e.g. syndrome of inappropriate
ADH secretion, edematous states)
 Loss of sodium (e.g. through kidneys, GI tract, skin)
this type of hyponatremia is due to renal salt wasting
caused by an unknown humoral substance released
in response to cerebral injury (‘cerebral salt wasting’);
however, the evidence is not strong and the reported
cases most probably represent SIADH (Oh and Car-
roll, 1992). Deterioration in level of consciousness,
new focal deficits, myoclonus, seizures or increasing
ICP should alert the physician to the possibility of
hyponatremia and hypo-osmolality in the patient
with a severe brain injury.
(a) Isotonic hyponatremia
An apparent decrease in serum sodium concentration
(measured by flame photometry) occurs when the
mass of the non-aqueous components of serum is
increased by severe hyperlipidemia or hyperproteine-
mia. This is usually referred to as pseudo-hypona-
tremia and can be readily identified by finding a
normal serum osmolality (Weisberg, 1989).
(b) Hypertonic hyponatremia
In patients with an increased amount of an imper-
meant solute (i.e. one that is unable to cross the blood–
Table 16.11 Common causes of hyponatremia
Isotonic
 Pseudohyponatremia
– Hyperlipidemia
– Hyperproteinemia
Hypertonic
 Hyperglycemia
 Mannitol, glycerol or sorbitol excess
Hypotonic
 Water retention
– Syndrome of inappropriate antidiuretic hormone
secretion
– Syndrome of inappropriate antidiuresis
– Psychogenic polydipsia
– Transurethral resection of the prostate (TURP)
syndrome
 Salt depletion
– Adrenocortical failure
– Diuretic excess
 Potassium depletion
316 FLUID, ELECTROLYTE AND METABOLIC MANAGEMENT
brain barrier), such as glucose, mannitol, glycerol or
sorbitol, osmotic equilibration occurs by water shift-
ing from the ICF to the ECF, thus diluting the ECF
sodium. In such circumstances, hyponatremia is often
associated with an elevated measured osmolality. For
every 1 mmol/l rise in glucose above a plasma glucose
level of 5.6 mmol/l, the plasma sodium decreases by
0.288 mmol/l (Katz, 1973; Crandall, 1974; Jenkins and
Larmore, 1974; Robin et al., 1979). The corrected
sodium value is derived from the formula:
Corrected Na value = measured plasma Na+
(plasma glucose value –
5.6)  0.288.
(c) Hypotonic hyponatremia
Hyponatremia is almost always caused by an excess of
total body water. This may be due to excessive
infusion of hypotonic or water-generating intravenous
fluids such as 5% dextrose, 1.5% glycine or 0.45%
saline, particularly when administered rapidly or in
the presence of high circulating ADH levels. Hypona-
tremia may rarely be due to loss of exchangeable
sodium or potassium (Fuisz, 1963).
Since hyponatremia may be associated with an
alteration in both total body water and total body
solute the ECF volume may be increased (hyper-
volemia), decreased (hypovolemia) or unchanged
(isovolemia; Humes, 1986).
In health, a fluid intake of up to 15–20 liters may be
tolerated before water is retained. However, less water
is needed to produce hyponatremia in individuals in
whom there is also an increase in non-osmotic
stimulation of ADH by hypovolemia, hypotension,
pain, nausea or postoperative stress (Hayes, 1968;
Chung et al.,1986; Sinnatamby et al., 1974), or a
reduction in urinary osmotic excretion, as in patients
with a reduced urea production, or a reduction in
renal capacity to respond to ADH.
The proposal that disease may cause a ‘sick cell’
syndrome (Flear and Singh, 1973; Flear, Gill and Burn,
1981) in which ECF sodium leaks into cells and
produces hyponatremia is a misconception (Leaf,
1974; Bichet and Schrier, 1982).
Loss of potassium may cause hyponatremia as
sodium shifts into the cell in exchange for K+.
Syndrome of inappropriate ADH secretion (SIADH)
This syndrome is defined as hyponatremia due to an
elevated level of ADH inappropriate for the prevailing
osmotic or volume stimuli (Robinson, 1985; Bartter
and Schwartz, 1967). ADH secretion from the neu-
rohypophysis is no longer under normal regulatory
influences. The criteria for the diagnosis of SIADH are
listed in Table 16.12.
Table 16.12 Criteria for the diagnosis of the syndrome of
inappropriate secretion of antidiuretic hormome (SIADH)
 Hypotonic hyponatremia
 Urine osmolality greater than plasma osmolality
 Urine sodium excretion greater than 20 mmol/l
 Normal renal, hepatic, cardiac, pituitary, adrenal and
thyroid function
 Absence of hypotension, hypovolemia, edema and
drugs
 Correction by water restriction
SIADH is a form of dilutional hyponatremia; ECF
volume is usually increased by 3–4 liters and periph-
eral edema does not occur. Because of the expanded
ECF volume, glomerular filtration rate is increased
and the renin–angiotensin–aldosterone mechanism is
suppressed, resulting in a decrease in the renal
absorption of sodium.
Syndrome of inappropriate antidiuresis (SIAD)
This syndrome is defined as hyponatremia due either
to increased ADH secretion initiated by stimulation of
high- or low-pressure baroreceptors, or to a reduction
in non-ADH renal water excretion mechanisms
(Robertson, 1989). The causes of SIAD are listed in
Table 16.13.
(d) Clinical features of hyponatremia
Hypotonic hyponatremia is almost always caused by
excess total body water, and the symptoms are due
Table 16.13 Causes of syndrome of inappropriate
antidiuresis
Baroreceptor-mediated
 Hypovolemia
– Addison’s disease
– Hepatic failure
– Nephrotic syndrome
– Drugs: frusemide, thiazides
 Cardiac failure
Cortical influences
 Pain, anxiety and nausea
– Postoperative
– Trauma
Drugs
 Narcotics, barbiturates, chlorpropamide, phenothiazines,
carbamazepine, tricyclics, nicotine derivatives, clofibrate,
vincristine, vinblastine, cyclophosphamide
Reduction in renal response to antidiuretic hormone
 Renal failure
 Hypothyroidism
 Addison’s disease
 Drugs: indomethacin, frusemide, thiazides

to the cerebral water excess (cerebral edema; Waste-
rlain and Posner, 1968). Normally the brain partially
adapts to the hypo-osmolality within 24 hours,
reducing the cerebral water excess by losing or
inactivating intracellular osmotically active solutes
(Arieff, 1984, 1985; Arieff and Guisado, 1976; Arieff,
Liach and Massry, 1976).
If the patient develops hyponatremia of 125 mmol/l
(osmolality 260 mosmol/kg) acutely, that is within 3
days, then symptoms of cerebral edema usually occur.
These include headache, anorexia, nausea, weakness,
lethargy, confusion, disorientation, blurred vision,
muscle cramps, coma and seizures (Arieff, 1984;
Arieff, Liach and Massry, 1976; Plum and Posner,
1980).
Chronic hyponatremia, on the other hand, with
plasma sodium values well below 125 mmol/l, may be
well tolerated because of cerebral osmotic compensa-
tion (Arieff, 1984). Thus the mortality associated with
hyponatremia is usually related to its rate of develop-
ment rather than its severity. Chronic hyponatremia
has a mortality of less than 10% (Sterns, 1987),
whereas a mortality up to 50% has been reported with
acute hyponatremia (Robertson, 1989).
(e) Diagnosis of hyponatremia
The evaluation of hyponatremia with hypo-osmolality
begins with a clinical assessment of volume status and
measurement of urinary indices (Table 16.14). How-
ever, volume status can be difficult to assess clinically
in a critically ill patient. ECF volume may be affected
by blood loss, the amount and type of fluid admin-
istered and the use of diuretics. Urinary Na+ measure-
ments are affected by the use of osmotic and non-
osmotic diuretics. Figure 16.13 summarizes our
diagnostic approach to hyponatremia.
Acute hyponatremia is usually due to excess water,
as in dextrose solutions administered inappropriately
to patients in the postoperative period. Diagnosis is
based on measurement of plasma osmolality, osmolar
gap and urinary sodium. The osmolar gap is the
Table 16.14 Extracellular volume (ECV) and urinary
sodium (uNa+) in hyponatremia and hypo-osmolality
uNa+
Diagnosis ECV (mmol/l)
Dehydration Decreased < 10
Congestive heart failure, cirrhosis Increased < 10
Renal disease, adrenal insufficiency, Decreased > 25
diuretics
SIADH Normal or > 25
increased
DISORDERS OF WATER AND ELECTROLYTE BALANCE 317
difference between the measured osmolality and the
calculated osmolality (2  Na+ + glucose + urea, where
plasma sodium, glucose and urea are measured in
millimoles per liter; Worthley, Guerin and Pain, 1987).
When there is an excess of total body water, urinary
sodium is usually greater than 40 mmol/l and plasma
urea is low. In the rare case of hyponatremia due to
salt depletion, urinary sodium is usually less than
20 mmol/l and the plasma urea and uric acid are often
high (Humes, 1986). In patients with head injuries
hyponatremia will almost always be associated with a
urinary osmolality of greater than 100 mosmol/kg.
The presumptive diagnosis of SIADH can be con-
firmed if simply restricting fluids results in a reduc-
tion of urinary Na+ losses and correction of hypona-
tremia. The clinical picture most often confused with
SIADH is a patient with isotonic fluid loss, usually
due to diuretics, who is treated with hypotonic fluid
replacement. In this situation, the body preserves
volume at the expense of tonicity – a form of
hypotonic dehydration. It should be stressed that the
absence of an increase in ECF volume excludes a
diagnosis of SIADH.
Chronic hyponatremia accompanies other diseases
and it is important to differentiate SIADH from
sodium depletion due to prolonged vomiting, adrenal
insufficiency or hypopituitarism.
(f) Treatment of hyponatremia
Treatment aims to remove excess water and treat of
the underlying cause.
Chronic hyponatremia (> 3 days’ duration)
If the patient is asymptomatic and hyponatremia has
been present for more than 3 days, fluid restriction
and removal of any precipitating factor is often all that
is required (Cluitmans and Meinders, 1990). Fluid
should be restricted to less than 500 ml/d. The rate of
correction should be no greater than 12 mmol/l/d
(0.5 mmol/l/h) and is continued only until the plasma
sodium is 130 mmol/l (Laureno and Karp, 1988;
Sterns, Riggs and Schochet, 1986; Plum and Posner,
1980; Cluitmans and Meinders, 1990; Norenberg and
Papendick, 1984). If fluid deprivation is difficult to
sustain in patients with SIADH or SIAD then patients
with hyponatremia and chronic CCF may benefit from
an ACE inhibitor added to frusemide (furosamide).
This will inhibit the stimulation of thirst and ADH
release by angiotensin II (Dzau and Hollenberg, 1984;
Packer, Medina and Yushak, 1984). However, in these
patients a direct ADH inhibitor such as phenytoin may
be of greater value (Mulinari et al., 1990). This has been
used to reduce ADH release from the hypophysis in
318 FLUID, ELECTROLYTE AND METABOLIC MANAGEMENT

Figure 16.13 Diagnostic approach to hyponatremia. Arrows indicate the direction of change; single and double arrows
indicate the magnitude of change. Iso = isotonic; N = normal; V = variable. In hypertonic hyponatremia due to
hyperglycemia, the corrected plasma Na+ = plasma Na+ + (plasma glucose – 10)/3 mmol/l.

patients with SIADH due to CNS disorders including
head injury (Martinez-Maldonado, 1980).
Complications of treatment of chronic hyponatremia
In chronic hyponatremia the brain is less able to
tolerate rapid correction and may develop central
pontine and extrapontine myelinolysis if hypertonic
saline is used. The lesions of central pontine myelinol-
ysis (CPM) are caused by the destruction of myelin
sheaths in the center of the basilar portion of the pons
and may extend from the midbrain to the lower pons.
The clinical features range from coma, flaccid quad-
riplegia, facial weakness and pseudobulbar palsy to
minor behavioral changes without focal findings. The
onset may be from one to several days after the
hyponatremia has been corrected and may require
MRI to confirm the diagnosis (Brunner et al., 1990).
While an association with CPM and correction of
hyponatremia has been reported, the relationship
between CPM and the rapidity of correction of
hyponatremia has not been firmly established in
clinical practice. In 170 cases of CPM, hyponatremia
occurred in only 28% of patients, most of whom were
corrected slowly (Ayus, Krothapalli and Arieff, 1985),
an observation that has been confirmed by others
(Tormey, 1990). Nevertheless, there is persuasive
experimental evidence for the association between
rapidity of correction of chronic hyponatremia and
CPM (Norenberg and Papendick, 1984).

Acute hyponatremia (< 3 days duration)
In this condition, the rate of reduction of plasma
sodium is 0.5 mmol/l/h or greater and/or the hypo-
natremia is of less than 3 days duration (Cluitmans
and Meinders, 1990). It is often associated with
inappropriate intravenous fluid administration and
with the postoperative period (Arieff, 1986). The total
water excess in adults ranges from 5–10 liters.
The rate of correction of acute hyponatremia should
be no greater than 2 mmol/l/h of sodium until the
plasma level has increased to 120 mmol/l or by a
maximum of 20 mmol/l during the first 24 hours
(Arieff and Guisado, 1976; Ayus, Krothapalli and
Arieff, 1987, 1988).
This is achieved initially by intravenous administra-
tion of hypertonic saline given at 50–70 mmol/h. It is
important to note that the purpose of using hypertonic
saline is not to correct a saline deficit, since there is in
fact not a total Na+ deficiency, but rather the hyper-
tonic saline draws water into the intravascular com-
partment and reduces brain edema. A spontaneous or
frusemide-induced diuresis (e.g. by 20–40 mg intra-
venously) is then required to excrete the water excess.
When the plasma sodium has increased to 120 mmol/
l, precautions should be taken to prevent the plasma
sodium rising to greater than 130 mmol/l over the
next 24 hours. If the hyponatremia presents with
convulsions, then urgent correction of the cerebral
edema using 250 mmol of hypertonic sodium chloride
over 10 minutes (equivalent to 500 ml of 20% man-
nitol), has been used. This will immediately elevate
the plasma sodium in adults by about 7 mmol/l (Table
16 15; Worthley and Thomas, 1986).
Table 16.15 Treatment of severe hyponatremia (ACE =
angiotensin-converting enzyme; ADH = antidiuretic
hormone)
Acute hyponatremia
 Fluid restrict to 500 ml/d or less
 Hypertonic saline (50–70 mmol/h)
 Diuresis of 160 ml/h or greater
 Rate of correction
– First day: no greater than 20 mmol/l/d (2 mmol/l/h)
until plasma sodium 120 mmol/l
– Second day: attempt to keep plasma sodium between
130 and 135 mmol/l
 Seizures: 100–250 mmol hypertonic saline over 10 min
Chronic hyponatremia
 Fluid restrict to 500 ml/d or less
 Rate of correction:
– No greater than 12 mmol/l/d (0.5 mmol/l/h) until
the plasma sodium is 130 mmol/l
 Drugs
– Lithium, demeclocycline
– Phenytoin
– ACE inhibitor
– ADH inhibitor
DISORDERS OF WATER AND ELECTROLYTE BALANCE 319
Complications of treatment of acute hyponatremia
The complications reported with the use of hypertonic
saline include congestive cardiac failure, cerebral
hemorrhage – intracerebral and subdural, presumed
due to tearing of bridging veins – and CPM. To reduce
the incidence of congestive cardiac failure, CVP or
PAWP should be monitored throughout saline admin-
istration. Cerebral hemorrhage will only occur if there
is an inappropriate administration of hypertonic
saline in normonatremic states (Finberg, Luttrell and
Redd, 1959).
16.8.2 HYPERNATREMIA
Hypernatremia is defined as a plasma sodium greater
than 145 mmol/l. It is always associated with hyper-
osmolality and may be caused by water depletion,
excessive administration of sodium salts or both
(Table 16.16).
In water-depleted states, the thirst mechanism
normally stimulates a conscious individual to drink
water. Thus water loss only produces hypernatremia if
the patient is unconscious or otherwise physically
unable to drink. Excessive administration of sodium
salts is a rare cause of hypernatremia and usually only
occurs through therapeutic misadventure.
Hypernatremia is the usual cause of hyperosmolar
states in neurosurgical patients, although marked
Table 16.16 Causes of hypernatremia
Water depletion
Extrarenal loss
 Exposure
 GIT losses
Renal loss
 Osmotic diuresis
– Urea, mannitol, glycosuria
 Diabetes insipidus
– Central (neurogenic)
Post-traumatic, postoperative
Metastatic tumors, craniopharyngioma, pinealoma,
cysts
Meningitis, encephalitis
Fat embolism
Granulomas (TB sarcoid)
Idiopathic
– Nephrogenic
Congenital
Hypercalcemia
Hypokalemia
Drugs: lithium, amphotericin B
Renal diseases: chronic pyelonephritis; medullary
sponge kidney; polycystic kidney; analgesic
nephropathy; postobstructive uropathy; multiple
myeloma; amyloid; sarcoid
Salt gain
 Hypertonic saline or sodium bicarbonate
320 FLUID, ELECTROLYTE AND METABOLIC MANAGEMENT
hyperglycemia may contribute to hyperosmolality in
states of insulin resistance, such as in sepsis, or as a
result of inadequate insulin administration with par-
enteral nutrition.
(a) Clinical features
Hypernatremia is usually symptomatic if plasma
sodium is 155–160 mmol/l or greater (equivalent to an
osmolality of 330 mosmol/kg or greater). This equates
to a water depletion of 6 liters or greater in a 70 kg
man (Arieff, 1984). Clinical features include pyrexia,
restlessness, weakness, paralysis, irritability, drowsi-
ness, lethargy, confusion, tremor, hyper-reflexia, seiz-
ures and coma (Ross and Christie, 1969). The signs of
hypernatremia are due mainly to increased effective
osmolality, which reduces brain cell volume (Oh and
Carroll, 1992). As already noted, hypernatremia is
much better tolerated if it develops slowly. Increase of
the brain volume may be accomplished by intra-
cellular shift of sodium, potassium and chloride, and
the accumulation of organic solutes, mainly taurine
and other amino acids (Lohr, McReynolds and Gri-
maldi, 1988). Normalizing brain volume in chronic
hypernatremia therefore requires an increase in the
total solute content of the brain. A sudden lowering of
the osmolality of the ECF may cause a shift of water
into the brain cells with resultant cerebral edema.
(b) Diabetes insipidus
Diabetes insipidus (DI) is characterized by polyuria
(3–15 l/d) and polydipsia due to the complete or
partial failure of ADH secretion (central or neurogenic
DI), or decrease in the renal response to ADH
(nephrogenic DI; Table 16.16). Both situations result in
an inability to concentrate urine and to conserve
Figure 16.14 Differential diagnosis of hypernatremia. Posm = plasma osmolality; DI = diabetes insipidus.
solute-free water in the face of appropriate stimuli.
Head injury is a common cause of central DI. A very
early onset is characteristic of major hypothalamic
damage and is associated with a high mortality (Seckl,
Dunger and Lightman, 1987).
Head-injured patients with fractures involving the
base of the skull and sella turcica appear to be at
increased risk of DI (Crompton, 1971; Edwards and
Clark, 1986). Diabetes insipidus is common in
patients prior to brain death. Traumatic DI is thought
to be caused by a shearing injury to the pituitary
stalk. The time of onset is variable, but it usually
appears after 5–10 days (Kern and Meislin, 1984). In
most cases of post-traumatic DI the onset is charac-
terized by polyuria, hypernatremia and plasma
hyperosmolality, sometimes as early as 12–24 hours
after injury. If the damage is limited to the pituitary
or lower pituitary stalk, the DI may only be tran-
sient, and this is usually the case. High stalk lesions
or injury to the hypothalamus usually cause perma-
nent DI. Since most patients in ICU are unable to
control their own water intake, hemodynamic insta-
bility may occur with untreated DI.
Nephrogenic DI is often mild because the patient
can usually produce an isotonic urine; thus the
diuresis is limited to 3–5 l/d.
(c) Diagnosis
Every patient with hypernatremia may be considered
to have an inadequate water intake, either absolute or
relative. Excessive sodium administration as the cause
of hypernatremia is usually obvious from the history.
Whether hypernatremia is due to insufficient water
intake or to excessive water loss can be determined by
measurements of urine osmolality (Figure 16.14).
Normal concentration of urine (urine osmolality
 DISORDERS OF WATER AND ELECTROLYTE BALANCE 321
> 700 mosmol/l) suggests that the main problem is Table 16.17 Treatment of diabetes insipidus (DI) in the
insufficient water intake, with or without excessive critically ill ICU patient
extrarenal water loss. Urine osmolality between Remarks
700 mosmol/l and the osmolality of plasma suggests
partial central DI, osmotic diuresis, diuretic therapy, 1 Confirm diagnosis Altered consious state or inability
acquired (partial) nephrogenic DI or renal failure. A to detect thirst or take oral fluids.
Hypertonicity (> 295 mosmol/kg),
high (> 30 ml/kg/h) urine volume may be the first sign hypernatremia, inappropriately
of diabetes insipidus, but is also seen in osmotic dilute urine. DI may be transient
diuresis. A urine osmolality below that of plasma or permanent; permanent form
suggests either complete central DI or nephrogenic DI. seen in one-third of patients with
Laboratory investigations show hypernatremia, per- trauma or neurosurgery. Presence
of associated anterior pituitary
sistently hypotonic urine and low urine osmolality, hypofunction not uncommon in
usually less than 200 mosmol/l. In milder cases urine patients with severe head trauma.
osmolality may not be below that of plasma, and may 2 Replace free water Free H2O deficit (liters) =
be 300–600 mosmol/l. Patients with central DI are deficit 0.6  (body weight [kg])  ([Na+/
unable to increase urinary osmolality during fluid 140] – 1)
restriction, but remain sensitive to exogenous ADH. Parenteral replacement of half of
Patients with partial DI have urinary volumes much deficit immediately; rest over
24–36 hours. Use 5% dextrose, not
less than those with complete DI. Other causes of saline solutions
polyuria which should be considered in the head-
injured patient include osmotic diuretics (mannitol, 3 Give maintenance Labor-intensive; inaccurate fluid
fluids and replace balance may occur with high
iodinated contrast-medium), severe hyperglycemia urine output volumes of urine
and fluid overload. In contrast to DI, a solute diuresis hourly with
is usually accompanied by a higher urinary osmolality dextrose solutions
(between 250 and 320 mosmol/l; Shucart and Jackson, 4 Daily weight Not always available in adult ICU
1976).
5 Close monitoring
of electrolytes and
(d) Treatment of hypernatremia fluid balance
6 Aqueous If urine output remains excessive
Hypotension due to a reduction in intravascular fluid vasopressin (AVP) (> 200–250 ml/h) in the absence of
volume should be treated by isotonic saline infusions diuretics or, if maintenance of fluid
to replace the intravascular volume and improve balance is difficult or
tissue perfusion before hypotonic solutions are used. hyperosmolality is present give
5–10 U subcutaneously or i.m.
Pure water depletion is treated by water administra-
tion. (In a conscious patient with normal gastro- 7 Desmopressin More recent regimen. Synthetic
intestinal function, oral ingestion of water is encour- (DDAVP) for analog of AVP with longer half-life
patients with and fewer vasoconstrictive effects.
aged.) If intravenous fluid is required, 5% dextrose or severe DI Give 1–2 µg subcutaneously or i.v.
hypotonic saline solutions (e.g. 0.45% saline) are often every 12–24 h or by nasal
used, as sterile water through a peripheral vein causes insufflation of 5–20 µg every 12 h.
hemolysis (Krumbhaar, 1914). In rare cases, where Watch for water intoxication
saline and dextrose solutions are deemed inadvisable; (hyponatremia and elevated
urinary osmolality) during
for example, in a patient who is volume-depleted and therapy; withhold DDAVP
severely hypernatremic, central venous administra- periodically to document
tion of sterile water can be used without causing persistence of DI.
hemolysis (Worthley, 1986).
The rate of increase in osmolality should be no
greater than 2 mosmol/kg/h (Arieff, 1984; Arieff and
Guisado, 1976). Hypernatremia due to excess sodium lower ICP. The aim is not to induce hypovolemia,
is treated by water and diuretic administration which may be detrimental, but rather to maintain a
(Addleman, Pollard and Grossman, 1985). The man- normovolemic state while increasing serum sodium,
agement of DI depends on the cause (Table 16.17). osmolality and tonicity, thus decreasing the extrac-
ellular fluid volume within the brain. A serum
sodium level of 145–155 mmol/l and serum osmolal-
(e) Hyperosmolar therapy
ity of 300–320 mosmol/l are often generated, and
Intravenous 20% mannitol (1098 mosmol/l) a six- excessive dehydration may precipitate prerenal renal
carbon sugar similar to glucose, is often used to failure. Fluids are administered to maintain CVP
322 FLUID, ELECTROLYTE AND METABOLIC MANAGEMENT
between 5 and 10 mmHg. In young, otherwise fit
head-injured patients, pulmonary artery catheteriza-
tion is rarely indicated.
Mannitol is administered as an intermittent intra-
venous bolus (0.25–0.5 g/kg body weight) up to
4-hourly. Where the blood–brain barrier is intact,
mannitol remains within the intravascular and extrac-
ellular spaces (Sutin, Ruskin and Kaufman, 1992). It
has several effects, including an immediate increase in
circulating blood volume and arterial blood pressure
(Wise and Chater, 1962; Roberts et al., 1987). It also
reduces blood viscosity by hemodilution (Burke et al. ,
1981; Muizelaar et al., 1983) and by increasing red
blood cell deformability. It causes osmotic dehydra-
tion of the brain, which reduces the volume of
extracellular free water (Roberts et al., 1987), thus
decreasing brain volume and ICP as well as causing a
urinary osmotic diuresis. Repeated administration of
mannitol may result in a systemic hyperosmolar state
and dehydration, which should be avoided since
cerebral perfusion may decrease and renal failure may
occur. Repeated administration of mannitol may result
in its eventual movement through the blood–brain
barrier into the extracellular space, where the
increased oncotic pressure may retain free water and
worsen edema. Thus mannitol use should be restricted
to the minimum amount needed to control ICP and
CPP. Our practice is to measure serum osmolality
daily and cease mannitol if serum osmolality exceeds
320 mosmol/l.
Mannitol induces diuresis primarily by elevating
the osmotic pressure of the glomerular filtrate to such
an extent that the tubular reabsorption of water and
solutes is hindered. It promotes the excretion of
sodium; however, proportionately more water than
sodium is excreted. Excretion of potassium, chloride,
calcium, phosphorus, magnesium, urea and uric acid
are also increased. Mannitol is only very slightly
metabolized, if at all, to glycogen in the liver. It is
freely filtered by the glomeruli, with less than 10%
tubular reabsorption, and is not secreted by tubular
cells. The elimination half life in adults is about 100
minutes. Approximately 80% of a 100 g dose is
excreted unchanged in the urine within 3 hours. In the
presence of renal disease in which glomerular function
is impaired or in conditions that impair small vessel
circulation, such as congestive cardiac failure, cir-
rhosis with ascites, shock or dehydration, mannitol
clearance is lower than normal. Mannitol does not
cross the intact blood–brain barrier unless very high
concentrations are present in the plasma or the patient
has acidosis.
Hypertonic saline (7.5%) has also been used to
lower ICP in animal models of head injury (Freshman
et al., 1993). It was as effective as 20% mannitol in
treating elevated ICP caused by a space-occupying
lesion. Hypertonic saline has the additional benefit of
rapid small volume resuscitation of associated hemor-
rhagic shock (section 16.5.2).
16.8.3 HYPOKALEMIA
Hypokalemia is defined as a serum potassium of less
than 3.5 mmol/l or plasma potassium less than
3.0 mmol/l. It may be due to a reduction in total
body potassium, caused by a decreased oral intake,
increased renal or gastrointestinal loss, or to a com-
partmental shift of potassium from the ECF to the
ICF (Tannen, 1986). In contrast to Na+ and C1–,
which are predominantly in the ECF and regulated
by the kidneys, K+ is predominantly in the ICF; its
movements are primarily determined by nutritional
and metabolic factors (e.g. pH) and are mediated by
neural and hormonal influences (Schultze and Nis-
senson, 1980).
Hypokalemia may be caused by osmotic diuretics,
diabetes insipidus, steroids, catabolic losses in
trauma and secondary hyperaldosteronism (com-
monly caused by hypovolemia or cardiac failure).
Excessive renal K+ loss also occurs in the presence of
alkalemia and hypomagnesemia. Gastrointestinal K+
losses may be due to vomiting, nasogastric suction or
diarrhea. Intracellular shift of K+ occurs in metabolic
or respiratory alkalosis, exogenous insulin admin-
istration and endogenous or exogenous catechola-
mine administration.
(a) Clinical features
The clinical features of hypokalemia are listed in
Table 16.18. These include ventricular and supraven-
tricular arrhythmias, ileus, enhancement of digitalis
toxicity and hypokalemic nephropathy; nephropathy
occurs if hypokalemia is severe and prolonged and
results in impaired renal water conservation and
polyuria. If K+ depletion is severe neuromuscular
manifestations include weakness, hyporeflexia and
even paralysis. The muscular weakness can interfere
with attempts to wean patients from ventilatory
support in the ICU.
(b) Treatment
Treatment of hypokalemia is usually commenced
when plasma K+ is less than 3.0 mmol/l. While there is
normally a linear relationship between serum K+ and
total body K+ (Sterns et al., 1981), acid–base dis-
turbances and other causes of compartmental K+ shift
make estimates of total body K+ difficult in severely ill
patients. Thus K+ therapy must be monitored by
frequent estimations of serum K+. Serum magnesium
levels should be measured in patients with refractory

Table 16.18 Clinical features of hypokalemia
Cardiac
 Predisposition to digoxin toxicity
 Ventricular and atrial tachycardias
 Torsades de pointes
 ECG changes: PR prolongation, T-wave inversion,
prominent U waves
Skeletal muscle
 Weakness, hypotonicity
 Ascending paralysis, ventilatory failure
 Cramps, rhabdomyolysis
Gastointesinal
 Constipation, ileus
Central nervous system
 Depression, coma
Renal
 Nephrogenic diabetes insipidus (polyuria, polydipsia)
 Metabolic alkalosis
 Interstitial nephritis
 Predisposition to urinary tract infection
Endocrine
 Glucose intolerance
hypokalemia, since both electrolytes may be disturbed
together and hypokalemia may be difficult to correct
without concomitant correction of hypomagnesemia
(Tannen, 1986). Hypokalemia protects against hypo-
calcemic tetany; thus hypocalcemia should be cor-
rected before or together with the correction of
hypokalemia.
When hypokalemia is associated with metabolic
alkalosis the standard treatment is intravenous or oral
potassium chloride. If the patient has renal tubular
acidosis and hypokalemia, then potassium acetate is
given. If phosphate depletion is also present, potas-
sium phosphate may be administered. Phosphate can
only be infused slowly (at a maximum rate of
2–4 mmol/h/70 kg ) and is usually given to correct a
phosphate deficiency rather than potassium defi-
ciency; thus potassium chloride is often given
concomitantly.
Intravenous replacement of potassium should not
normally exceed 40 mmol/h. Plasma potassium levels
should be monitored at 2–6-hourly intervals (Tannen,
1986; Stockigt, 1977). Spironolactone, amiloride or
ACE inhibitors are more useful for preventing renal
potassium loss than for correcting an existing deficit
(Tannen, 1986).
16.8.4 HYPERKALEMIA
Hyperkalemia is defined as a serum potassium greater
than 5.0 mmol/l or plasma potassium greater than
4.5 mmol/l. It may be due to excessive intake, severe
tissue damage, decreased excretion or body fluid
DISORDERS OF WATER AND ELECTROLYTE BALANCE 323
compartment shift, or may be artifactual, due to
hemolysis after collection.
Hyperkalemia is uncommon in patients with an
isolated head injury unless overzealous use of osmotic
diuretics has caused renal failure. Apparent hyper-
kalemia may be seen with hemolysis or acidosis. In
patients with additional trauma, rhabdomyolysis and
massive transfusion of old blood may result in
hyperkalemia.
(a) Hypoaldosteronism (Barratt, 1981)
Hyporeninemic hypoaldosteronism
This usually occurs in patients who have non-insulin-
dependent diabetes mellitus and mild renal failure,
and may be provoked by cyclo-oxygenase inhibitors.
The patient is hyperkalemic with metabolic acidosis
(Type 4 renal tubular acidosis, RTA) and has an
elevated plasma creatinine and urea nitrogen. The
etiology is not known, although hyporeninemia, pros-
tacyclin deficiency and excess atrial natriuretic hor-
mone have all been implicated. Non-steroidal anti-
inflammatory drugs (NSAIDs), calcium-channel
blockers and beta-adrenergic blockers should not be
administered as they will contribute to the hypor-
eninemic state (Williams, 1986).
Primary hypoaldosteronism
This is characterized by normal or high renin levels
and is due to an enzymatic defect in the aldosterone
pathway.
Pseudo-hypoaldosteronism
This is characterized by normal or high levels of
aldosterone with a renal tubular resistance to the
action of the hormone. This disorder is commonly
caused by spironolactone and amiloride. The suppres-
sion of aldosterone production with hyperkalemia
(Edes and Sunderrajan, 1985) described with heparin
use is due to the antiseptic in commercial heparin
solutions and not to heparin (Jaques, 1985).
(b) Clinical features of hyperkalemia
The clinical features of hyperkalemia include tingling,
paresthesias, weakness, flaccid paralysis and hypoten-
sion. ECG changes include T-wave peaking, P-wave
flattening, PR prolongation (until sinus arrest with
nodal rhythm occurs), QRS widening, shortened QT
interval and deep S wave. Finally, a sine-wave ECG
pattern develops, which deteriorates to asystole,
occurring at plasma potassium levels of 7 mmol/l or
greater.
324 FLUID, ELECTROLYTE AND METABOLIC MANAGEMENT
(c) Treatment
+ Cook, 1985) but cannot be predicted by estimation of
For mild hyperkalemia (i.e. plasma K > 4.5 and
< 5.5 mmol/l) treatment usually involves reducing the
potassium intake, correcting renal failure, and treating
the cause (e.g. ceasing NSAIDs or spironolactone).
Treatment of severe hyperkalemia (i.e. plasma
K+ > 5.5 mmol/l) often involves the administration of
intravenous glucose and insulin, sodium bicarbonate
and calcium chloride (Table 16.19; Tannen, 1986),
although nebulized salbutamol (10–20 mg) may also
be useful as it can reduce the plasma potassium by
0.6–1.0 mmol/l after 30 minutes and will last for 2
hours (Williams, 1986). Resonium A has the capacity
to bind 3.1 mmol of potassium per gram by releasing
3.1 mmol of sodium. Calcium chloride (or gluconate)
does not reduce the plasma potassium and is used
only to counteract the toxic cardiac effects of hyper-
kalemia. Since all the methods of reducing the
potassium level are only temporary, treatment should
also be directed at the underlying cause, and may also
include dialysis.
16.8.5 HYPOCALCEMIA
Hypocalcemia occurs in up to 70% of patients in ICU
(Desai, Carlson and Geheb, 1988; Zaloga and Cher-
now, 1986). It is defined as a total plasma calcium less
than 2.2 mmol/l and may be caused by either a
reduced ionized or protein-bound calcium. In criti-
cally ill patients calcium loss due to increased tissue
sequestration of calcium may be associated with
pancreatitis, septicemia, burns or toxic shock (Cher-
now et al., 1982a; Zaloga, 1991). However, hypocalce-
mia is only important clinically when the physio-
logically active, ionized fraction (40% of total) is
reduced. Ionized calcium is lowered by alkalosis, by
high circulating free fatty acids, as in pancreatitis or
sepsis, and by agents that chelate calcium, such as
albumin infusions, bicarbonate administration and
high citrate loads administered with massive blood
transfusion (Zaloga and Chernow, 1986). Ionized
hypocalcemia (less than 1.15 mmol/l) occurs in
Table 16.19 Treatment of life-threatening hyperkalemia
Agent Dose
Intravenous
Dextrose and insulin 50 g dextrose
20 IU insulin
Sodium bicarbonate 50–100 mmol
Calcium chloride (10%) 5–10 ml (3.4–6.8 mmol)
Oral or rectal resonium A 50 g
Nebulized salbutamol 10–20 mg
15–20% of patients in the ICU (Zaloga, Chernow and
either total serum calcium or of ionized calcium
corrected for pH and serum albumin concentration
(Desai, Carlson and Geheb, 1987).
Common causes of hypocalcemia in head-injured
patients include respiratory alkalosis, sepsis, hypo-
magnesemia and rhabdomyolysis in the polytrauma
patient. Hypomagnesemia impairs both parathyroid
hormone (PTH) release and action. Critically ill
patients who are septic or who have unexplained
ionized hypocalcemia may be vitamin-D-deficient,
have an impairment of vitamin D metabolism or
action, or have impaired release of PTH (Desai,
Carlson and Geheb, 1987; Zaloga et al., 1984; Knochel,
1977). Hyperphosphatemia in severe rhabdomyolysis
causes hypocalcemia by calcium precipitation or
impaired vitamin D metabolism.
(a) Clinical features
Clinical manifestations of ionized hypocalcemia are
generally not evident until ionized calcium is less than
0.7 mmol/l. Signs include hypotension, impaired ven-
tricular function, bradycardia, bronchospasm and
laryngospasm. Weakness, tetany, hyper-reflexia, agi-
tation, confusion and seizures may occur, but are less
common than in patients with hypoparathyroidism.
The response to digoxin and catecholamines may also
be impaired by hypocalcemia.
(b) Treatment
Treatment is only undertaken if the patient is symp-
tomatic. Acute hypocalcemia may be corrected by
intravenous 10% calcium chloride (0.7 mmol calcium
per milliliter). Before initiating treatment, hypomag-
nesemia should be excluded, as hypomagnesemic
patients respond poorly to calcium. Calcium chloride
10%, 5 ml intravenously (i.e. 3.4 mmol) or 10 ml of
calcium gluconate 10% (i.e. 2.3 mmol) may be admin-
istered over 3–5 minutes. Rapid infusion of calcium
may result in unpleasant flushing, hypertension,
Onset (min) Duration (h)
10–15 3
60–240 1–2
1–5 1–2
120–240 3–12
30 2

bradycardia and atrioventricular nodal blockade, and
may precipitate digitalis toxicity. Persistent unex-
plained hypocalcemia requires further evaluation to
exclude hypoparathyroidism and vitamin D
deficiency.
16.8.6 HYPOPHOSPHATEMIA
Hypophosphatemia is defined as a fasting plasma
phosphate level of less than 0.8 mmol/l. Moderate
hypophosphatemia exists if the phosphate level is
between 0.32 and 0.8 mmol/l (Bohannon, 1989).
Severe hypophosphatemia exists when the plasma
level is less than 0.32 mmol/l (Hayek and Eisenberg,
1989). It may be caused by decreased intake, increased
excretion or intracellular redistribution.
Parenteral or enteral nutrition induces a transcellular
shift of phosphate from the ECF to the ICF via insulin-
mediated intracellular transport of phosphate with
glucose (‘refeeding syndrome’; Solomon and Kirby,
1990; Aubier et al., 1985). Respiratory alkalosis causes
intracellular shift of phosphate by stimulating glycol-
ysis and intracellular phosphate trapping. Hypophos-
phatemia induced by transcellular shift is associated
with hypophosphaturia and the normal body stores of
phosphate are maintained. Hypokalemia and hypo-
magnesemia may also promote hypophosphatemia by
impairing renal phosphate reabsorption.
(a) Clinical features
Clinical manifestations of hypophosphatemia are not
usually seen unless levels are markedly reduced, i.e. to
less than 0.3 mmol/l. Patients who are hyperventi-
lated or malnourished, alcoholic, septic or have
diabetic ketoacidosis are at increased risk of severe
hypophosphatemia, and diaphragmatic weakness and
respiratory failure may occur (Lau, 1986).
(b) Investigations
Patients with hypophosphatemia in the absence of
alkalosis and a urinary phosphate greater than
25 mmol/d,are suffering excessive renal loss. If the
urinary loss is less than 5 mmol/d, then renal loss is
excluded (Knochel, 1981). If hypophosphatemia is
associated with hypercalcemia, hyperparathyroidism
should be considered.
(c) Treatment
Hypophosphatemia is usually asymptomatic. If hypo-
phosphatemia is due to compartmental shift resulting
from respiratory alkalosis or to catecholamine infu-
sions, even though phosphate levels may decrease to
0.4 mmol/l, treatment with phosphate may not be
DISORDERS OF WATER AND ELECTROLYTE BALANCE 325
necessary. Generally, however, in the critically ill
patient, the phosphate level should be kept above
0.8 mmol/l, to ensure adequate respiratory, cardiac and
intracellular function. Phosphate at 40–80 mmol/24 h
may be administered orally or intravenously as sodium
or potassium phosphate (Chernow et al., 1989). If an
intravenous solution is administered as the dihydrogen
salt, an equimolar amount of Na+ or K+ and 80% of the
molar amount as H+ is administered with the phos-
phate. If it is administered as the monohydrogen salt,
then twice the molar amounts of sodium or potassium
are administered with the phosphate.
16.8.7 HYPOMAGNESEMIA
Hypomagnesemia is defined as a plasma level of less
than 0.7 mmol/l and is associated with a 24-hour urine
magnesium of less than 1 mmol/l in the absence of
abnormal renal magnesium losses. This is a common
electrolyte disturbance in ICU patients (Chernow et al.,
1982b; Kingston, Al-Siba and Skooge, 1986; Paymaster,
1976) and is caused by decreased intake or increased
loss. The causes are similar to those for hypophospha-
temia. Common causes in patients with head injury
include diuretics (osmotic and non-osmotic), diabetes
insipidus, respiratory alkalosis, sepsis and certain
drugs including aminoglycosides.
(a) Clinical features
Clinical features tend only to occur when the plasma
level is less than 0.5 mmol/l (Table 16.20; Paymaster,
1976; Fishman, 1965; Whang et al., 1984). The clinical
diagnosis of magnesium depletion is difficult because
only 1% of total body magnesium is contained in
plasma and because total plasma magnesium does not
accurately reflect the ionized fraction (55% of the
total), which is the physiologically active form. The
remaining plasma magnesium is bound to protein
(33%) or is chelated. Measurement of ionized magne-
sium is not available. Hypomagnesemia may be
associated with hypokalemia (due to renal loss),
Table 16.20 Clinical features of hypomagnesemia
Neurological
 Confusion, irritability, delirium, convulsions
 Ataxia, athetoid movements
 Weakness, tremors, cramps, tetany
Cardiovascular
 Tachyarrhythmias (torsades de pointes)
 Enhanced digoxin toxicity
Biochemical
 Resistant hypokalemia, hypocalcemia, renal tubular
acidosis
326 FLUID, ELECTROLYTE AND METABOLIC MANAGEMENT

hypocalemia (due to impaired release of PTH and

impaired peripheral action of PTH) and renal tubular
acidosis (RTA). In one study, more than 40% of
hypokalemic patients revealed an associated hypo-
magnesemia (Gums, 1987).

(b) Investigations
With magnesium deficiency, the renal loss is usually
minimal (0.05–0.10 mmol/d). An intravenous dose of
magnesium is normally excreted in the urine in 24
hours; thus 30 mmol administered over 8–12 hours
and a 24-hour collection of urine can be used as an
estimate of magnesium balance. Normally more than
60% of the dose is excreted; if less than 50% is excreted
the patient has a magnesium deficiency (Salem,
Munoz and Chernow, 1991).

(c) Treatment (a)

Symptomatic hypomagnesemia (e.g. causing refrac-

tory arrhythmias or seizures) is treated by intravenous
bolus injection of 5–10 ml of 49.3% MgSO4 solution
(2 mmol/ml magnesium; Cohen, Gambill and Eggers,
1977). Less severe degrees of hypomagnesemia are
treated by adding magnesium salts to the enteral or
parenteral solutions.

16.9 Special fluid and electrolyte

problems in the neurosurgical patient
16.9.1 NEUROGENIC PULMONARY EDEMA

Patients with a variety of central nervous system (b)

disorders, including head injury, may develop acute
pulmonary edema in the absence of cardiopulmonary
disease or other apparent causes. This neurogenic
pulmonary edema may follow head trauma (Ducker,
Simmons and Martin, 1969), intracranial tumors,
subarachnoid hemorrhage, stroke, seizures (Bonbrest,
1965), Guillain-Barré syndrome and meningitis.
Although the cause is unclear, it is thought that
neurogenic pulmonary edema may be due to massive
alpha-adrenergic discharge (Wray and Nicotra, 1978).
The sympathetic discharge increases systemic and
pulmonary vascular resistances. This transiently
increases left atrial pressure and pulmonary artery
wedge pressure (PAWP), and pulmonary capillary
disruption occurs. An animal model has also impli-
cated endothelial injury in its development (Minnear
et al., 1987). The altered pulmonary capillary permea-
bility results in the accumulation of pulmonary edema
fluid, which has a high protein content.
A previously healthy 24-year-old male was admit-
ted to ICU following a gunshot wound to the head
(Figure 16.15(a)). Frothy pulmonary edema fluid
Figure 16.15 A 24-year-old man suffered a gunshot wound
to the head. Shortly after admission to the ICU he developed
marked frothy sputum and oxygen desaturation. (a) The CT
scan shows the missile track and a ‘tight’ brain. (b) The chest
X-ray shows fluffy exudates bilaterally. There is a (Swan–
Ganz) catheter. Hemodynamic measurement confirmed a
non-cardiogenic basis for the pulmonary edema. Mechanical
ventilation and diuresis resulted in a successful outcome.
issued from the endotracheal tube and marked oxygen
desaturation was noted on pulse oximetry. He
required ventilation with 100% O2 and positive end-
expiratory pressure (PEEP); chest X-ray confirmed the
presence of pulmonary edema (Figure 16.15(b)). The
CVP was 10 mmHg. A Swan–Ganz catheter was
inserted to facilitate fluid management in this patient,
who subsequently made a satisfactory recovery.
The treatment of neurogenic pulmonary edema is
similar to the treatment of adult respiratory distress
syndrome (ARDS) from any cause. In addition to

ventilatory support with positive-pressure ventilation
and positive end-expiratory pressure (PEEP), fluid
management is of the utmost importance. Fluid intake
should be crystalloid solution, rather than protein-
containing solutions, and should be minimal. If PAWP
is monitored, it should be kept low (5–7 mmHg) to
minimize further extravasation of proteinacious fluid.
If mean arterial pressure or perfusion is inadequate,
inotropes should be used to maintain cerebral and
peripheral tissue perfusion. For a detailed account of
the respiratory management of neurogenic pulmonary
edema see Chapter 17.
16.9.2 NON-KETOTIC HYPERGLYCEMIC
HYPEROSMOLAR COMA
Non-ketotic hyperglycemic hyperosmolar coma
(NHHC) may occur following head injury, intra-
cerebral hemorrhage, brain tumor or cerebral infarc-
tion (Park, Meacham and Netsky, 1976). About two-
thirds of patients who develop NHHC have no history
of diabetes mellitus. Many have intercurrent infec-
tions, or are taking drugs that alter glucose tolerance,
such as steroids, phenytoin and thiazides, or are
dehydrated.
The diagnosis of NHHC is based on the findings of
hyperglycemia, glycosuria and a plasma osmolality
greater than 330 mosmol/l in the absence of ketosis.
Patients who have NHHC and are dehydrated
because of the osmotic diuresis are often potassium-
depleted. They may also have evidence of prerenal
renal failure which, if untreated, can progress to acute
renal failure.
Treatment is primarily correction of dehydration
and hypertonicity. Physiological saline is used for
volume replacement, together with careful monitoring
of serum and urine electrolytes and osmolality. After
sodium deficits have been corrected with physio-
logical saline, half physiological saline or dextrose/
saline (4% dextrose in N/5 saline) should be used to
replace water deficits. The hyperglycemia is usually
responsive to insulin.
16.9.3 SPINAL-CORD-INJURED PATIENTS
Cervical cord injury may cause spinal shock due to
anatomical or functional transection of the cord and
this may last for 1–3 weeks. The interruption to
sympathetic outflow results in vasodilatation, pooling
of blood in peripheral vascular beds and hypotension.
Reflex bradycardia also occurs, because the cardiac
accelerator nerves arise from segments T1–T4. The
hypotensive phase is usually preceded by a rise in
systemic pressure over 3–4 minutes as a result of
widespread initial sympathetic activation. This may
be particularly important in the presence of brain
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 Abnormalities of fluid, electrolyte and acid–base
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