Br. J. Anaesth.

(1986), 58, 169-189

HYPOVOLAEMIC SHOCK

I. McA. LEDINGHAM AND G. RAMSAY

Most patients demonstrating the conventionally
accepted clinical features of shock, whatever its
cause, will respond favourably to the administration
of i.v. fluids. Thus, patients suffering from shock
attributable to sepsis, drug overdose and, on
occasion, myocardial infarction, manifest increased
cardiac output and improved tissue perfusion in
be expected to alter this pattern of response,
increasing the risk of a critical reduction in tissue
oxygen availability and subsequent complications.
In patients with acute upper gastrointestinal
haemorrhage, for example, the presence of
hypovolaemic shock, age over 60 years, and
haemoglobin concentration, at admission to hos-

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response to fluids, much as do patients with overt pital, of less than 10 g dl"1 were associated with
blood volume losses, for example following increased mortality (Macleod and Mills, 1982).
haemorrhage, burns and gastrointestinal obstruc- Not surprisingly, the additional insult of trauma
tion. Hypovolaemia, either relative or absolute, is augments the endocrine and metabolic effects of
therefore a universal accompaniment of all forms hypovolaemia (Benedict and Grahame-Smith,
of shock and its identification and elimination is 1978).
fundamental to the success of treatment. The reduction in blood volume following
This chapter will address the problem of hypo- thermal injury results from loss of plasma at the
volaemia as a contributing factor in impending site of burn and the rate and volume of plasma
shock. The pathophysiology and treatment of deficit are roughly proportional to the extent of the
established hypovolaemic shock will be outlined. area burned (Goodwin, 1984). The increase in
The value of prognostic indices in the shocked capillary permeability and subsequent sequestra-
patient will also be reviewed. tion of intravascular fluid in the extravascular space
lead to the formation of tissue oedema and an
increase in haematocrit, packed cell volume often
HYPOVOLAEMIA reaching 70-80% in the absence of rapid,
Aetiology adequate fluid replacement. The composition of
The effects of haemorrhage, a common cause of the oedema fluid closely resembles that of plasma
hypovolaemia, vary with the nature, duration and with respect to sodium and potassium concentra-
severity of blood loss, the patient's age and general tions (Baxter, 1974).
health, and with the speed, adequacy and nature Hypovolaemia may be a consequence of dehyd-
of resuscitation. In previously healthy young ration from either a primary deficit of water or a
adults, the acute loss of 10% of the total blood primary deficit of salt. A primary deficit of water
volume has been shown to reduce arterial pressure generally results from reduced intake rather than
by 7% and cardiac output by 2 1 % ; the loss of from increased loss. The commonest cause in
20% of the blood volume reduced arterial clinical practice is inability of the patient to
pressure by 15% and cardiac output by 41% acquire an adequate volume of fluid either because
(Hinshaw et al., 1961). Individual response is of exhaustion or disturbance of consciousness (as
remarkably variable and reduction in plasma in the case of intrinsic brain pathology or the
volume of as much as 25 % may occur without effects of drugs, e.g. sedatives) or because drinking
arterial hypotension (Hardaway, 1979). The is forbidden (as in the case of upper gastrointestinal
presence of cardiovascular disease or anaemia can operations). Causes of increased loss include
pituitary and nephrogenic diabetes insipidus
(Cohen, 1984). A primary deficit of salt arises not
IAIN M C A . LEDINGHAM, M.D., F.R.CS. (ED.)- F.R.C.P. (GLAS.),
F.R.S.E.; GRAHAM RAMSAY, M.B., CH.B., F.R.CS. (GLAS.);
from reduced intake, but from increased loss. The
Intensive Therapy Unit and University Department of deficiency may be of salt alone if the patient loses
Surgery; Western Infirmary, Glasgow G i l 6NT. both salt and water and replaces the water by
170 BRITISH JOURNAL OF ANAESTHESIA
TABLE I. The contrasting features of water depletion and salt depletion

Water depletion Salt depletion

Cause Deficient intake Excessive loss

(especially loss of
intestinal secretions)
Dehydration Cellular Extracellular
Thirst +++ Absent
Urine volume Scanty Normal (even increased
until late)
Lassitude + +++
Weakness Late Early
Vomiting Absent May be + + +
Plasma volume Normal until late Reduced+ + +
Haemoconcentration Late and slight Early and severe
Arterial pressure Normal until late Decreased+ + +
Blood urea Increased + Increased + + +
Blood sodium Slight increase Reduced + +

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Blood chloride Slight increase Reduced+ + +
Urine sodium Reduced + + + Reduced+ + +
Urine chloride Reduced Absent
Cause of death Uncertain. ? Increase in Peripheral circulatory
intracellular osmotic failure
pressure

drinking, as may happen in diarrhoea, copious because of multifactorial aetiology or prior

sweating or Addison's disease. A deficiency of
both salt and water occurs most commonly when
fluid is lost from the gastrointestinal tract as, for
instance, in intestinal obstruction, severe diarrhoea
and biliary and pancreatic fistula. Sodium loss in
excess of water also arises in a proportion of
patients with chronic renal failure and in uncon-
trolled diabetes mellitus.
The principal features of water and -\\t
depletion are contrasted in table I. A prim, y
deficit of water leads to cellular dehydration as a
result of the increase in tonicity of the extracellular
fluid and the metabolic response to stress; thus
circulatory failure from a shrinking blood volume
is a late manifestation of this syndrome. By
contrast, a primary deficit of salt leads to a
reduction in the volume of extracellular fluid
(including a reduction in blood volume), but not
to cellular dehydration. As blood volume contracts
there is increasing difficulty in maintaining an
adequate circulation.
Assessment and Measurement
Detection of the presence of hypovolaemia would
seem a relatively simple task and, in many
instances, the combination of overt fluid loss with
inadequate replacement makes for an easy diag-
nosis. In a proportion of patients, however, the
clinical presentation may be less clearcut, perhaps
(possibly inadequately documented) resuscitation.
Even when the existence of hypovolaemia is not in
doubt, accurate quantification of volume deficit is
often difficult. Subjective visual estimation of fluid
loss is fraught with problems and may be grossly
inaccurate. Blood loss may be assessed on the basis
that a hand represents 500 ml (Grant and Reeve,
1951) but the method takes no account of loss from
major vessels. In thermal injury, the figure of 4 ml
of plasma loss per kg body weight for each per cent
of body surface burned is widely accepted, but in
some cases may be a significant underestimate
(Goodwin et al., 1983). Clinical features of
dehydration are important for diagnostic purposes,
but cannot be used to quantify extracellular losses.
Thirst is an insensitive measure of water depriva-
tion and becomes obvious only after a deficit of
1.5 litre has occurred. Moderate to severe water
deprivation is associated with deficits of 4-10 litre.
Slight to moderate salt depletion, associated with
lassitude and orthostatic fainting, implies a deficit
of up to 4 litre of isotonic saline. Moderate to
severe salt depletion is associated with deficits of
6-10 litre (Marriott, 1947).
Although a number of methods are available for
measuring blood volume, they have not become
widely popular or practised outside a few
committed centres (Shoemaker and Monson,
1973) and the reasons are not hard to find. While
accurate in the presence of an intact and adequate
HYPOVOLAEMIC SHOCK
circulation, measurement of blood volume, nor-
mally using tracer substances, becomes less
reliable when microcirculatory abnormalities are
present, for example hypoperfusion (incomplete
mixing) and increased capillary permeability
(extravascular losses). The techniques themselves
are time-consuming, require technical expertise,
usually involve radioisotopes and cannot be
repeated frequently. The patient's normal blood
volume is not available for comparison (and
derived values, based on height and weight, are at
best approximations). Finally, volume loss from
extravascular sources, which may be substantial if
the injury or insult is of long duration, is not
measured.
For these various reasons, assessment of
hypovolaemia is usually made by a combination of
a careful history, clinical examination, estimation
of apparent or observed losses, and indirect
haematological and haemodynamic measurements
including haematocrit, heart rate and pulse
volume, arterial and venous pressures, and some
index of tissue perfusion, for example peripheral
skin temperature and urine output. Haemodyna-
mic measurement should always be considered as
complementing clinical appraisal and any discrep-
ancy between the two approaches viewed with
concern. Emphasis is placed on serial measure-
ments, particularly in response to resuscitation.
A clinical history must always be part of the
initial assessment, but may be difficult or
impossible to obtain in patients with disturbed
conscious level, or may need to be delayed in the
presence of life-threatening cardiovascular or
respiratory conditions. Some or all of this
information may have to be obtained indirectly.
Physical examination is best done in a logical
sequence, for example in systems or anatomical
regions, in order to avoid serious oversights. A
check-list or prepared form is of great value for
inexperienced or experienced clinicians alike, and
reduces time spent on paper work. The aim of the
initial examination is to identify the magnitude
and source of the hypovolaemia and to determine
which systems need to be monitored during
resuscitation.
Monitoring
Monitoring of the patient suffering from impending
or established hypovolaemic shock must be simple
but adequate. The following procedures are
recommended as a basis for initial management:
(1) insert large bore i.v. cannulae;
171
(2) insert central venous catheter for pressure
monitoring and blood sampling;
(3) insert arterial catheter;
(4) monitor ECG;
(5) insert bladder catheter (in the absence of
urethral injury);
(6) measure core and peripheral temperatures.
Cardiovascular parameters may be displayed
conveniently and continuously using simple
monitoring apparatus. The ECG is useful for
detecting arrhythmias and myocardial ischaemia,
but is not a reliable indicator of myocardial
function (Brock and Bowes, 1975). Intravascular
measurement of arterial and central venous
pressure has greatly facilitated management: the
catheter systems are easy to set up, reliable and
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accurate. The incidence of complications is low
when the techniques are in regular use by
experienced personnel (Swan and Ganz, 1983).
When these manoeuvres have been completed,
a series of measurements may be obtained which
include:
(1) conscious level;
(2) heart rate and rhythm, arterial and venous
pressures;
(3) respiratory rate and rhythm, blood-gas
analysis;
(4) core-peripheral temperature difference;
(5) urine output;
(6) haemoglobin/haematocrit;
(7) electrolytes/acidbase balance (serum and
urine);
(8) chest radiograph.
The coreperipheral (or peripheralenviron-
mental) temperature gradient is a useful non-
invasive indicator of the adequacy of peripheral
perfusion and, under certain circumstances,
closely reflects changes in cardiac output (Joly and
Weil, 1969). The blood-gas tensions may signal
early development of respiratory complications,
particularly when used in conjunction with the
inspired oxygen concentration, from which an
estimation may be made of the alveolar-arterial
oxygen tension gradient (or similar derived value).
Urine output is a simple and sensitive indicator of
total renal blood flow and its distribution within
the kidney.
Tests of haemoconcentration include measure-
ment of haematocrit or the haemoglobin concen-
tration, although neither can be relied upon to
indicate the magnitude of blood loss (in the case
of haemorrhage) during the acute stage. The same,
to a large extent, is true of plasma protein
172 BRITISH JOURNAL OF ANAESTHESIA
concentration although, assuming normal hepatic a value exceeding 15 mm Hg suggests left ventri-
function, restoration of plasma proteins is much cular failure. Interpretation of PCWP measure-
more rapid than that of red cell mass (which may ments may be especially difficult if hypovolaemia
take weeks). The haematocrit is more appropriately (with or without the use of mechanical ventilation
used to judge the effectiveness of blood transfusion and positive end-expiratory pressure) leads to
during resuscitation. Serum concentrations of intravascular pressure (in the measured segment of
sodium and chloride are often measured, but the lung) decreasing to less than alveolar pressure.
results can be difficult to interpret. A deficit of Again, the use of a fluid challenge may help to
sodium leads not to any striking reduction in resolve uncertainty about the validity of absolute
sodium concentration, but to water excretion and measurementslarge pressure increases with no
eventually to dehydration; a great deficit of improvement in left ventricular stroke volume
sodium may decrease the concentration from suggesting exhaustion of preload reserve (Wood
140 mmol litre"1 to 120 mmol litre"1 or a little less. and Hall, 1985).
An excess of sodium leads not to any striking The measurement of plasma oncotic (or osmotic)
increase of sodium concentration, but to water pressure (COP) was reported to be of additional
retention and eventually to oedema. Within recent value as a guide in fluid management and in

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years it has become customary to measure urine helping to differentiate between the various causes
electrolyte concentrations and osmolality in con- of pulmonary oedema. Assuming normal Starling
junction with serum concentrations. This has forces, pulmonary oedema is likely to occur if the
helped to rationalize therapy and, along with difference between COP and PCWP decreases to
haemodynamic measurements, makes it possible less than 5 mm Hg. Direct measurement of COP
to distinguish not only between pre-renal and has not become routine in clinical practice and,
intrinsic renal failure but also, in the case of the although controversial, recent evidence suggests
former, the principal deficit (salt or water). that a reasonable approximation may be obtained
The composite information obtained from this by calculation from serum total protein concen-
series of measurements is an adequate guide tration (Torrijos et al., 1985). More important,
during the early phase of resuscitation, but however, is the increasing disenchantment with
continuous monitoring is essential for longer-term the measurement itself. Many authorities now take
care. One of the most useful early procedures in the view that, since interstitial pressures do not
difficult cases is the "fluid challenge": changes in remain static in shock and are not measured, the
central venous and arterial pressures in response only valid parameter in this context is PCWP.
to i.v. administration of, for example, colloid
200 ml over 10 min, may indicate hypovolaemia or
cardiac failure, or both (Weil and Shubin, 1969). Cardiac output (litre min'1)
The rate and volume of subsequent fluid admin- 5.8 1tO
istration may thus be determined more accurately. PA catheter I . . \
It is wise to remember that normal initial meas- placed ^J^T *
urements may be misleading. f^ chest drain

On occasion, catheterization of the pulmonary

artery by means of a pulmonary flotation catheter
is indicated. Once in position, the catheter can be
used to measure right atrial pressure, pulmonary
artery pressure, pulmonary capillary wedge pres-
sure (PCWP) and cardiac output; pulmonary
angiography may also be performed. In the
sometimes complex haemodynamic circumstances
associated with hypovolaemic shock, the pulmon-
ary flotation catheter may aid fluid management, 10 20 30 40 | 50 60 70 80
evaluation of both right and left ventricular
function, management of acute interstitial pul- Time (min)
monary oedema and diagnosis of pulmonary em- FIG. 1. Continuous measurement of mixed venous oxygen
bolism. In the majority of cases, PCWP accurately saturation (SvoJ after placement of pulmonary artery flotation
reflects left ventricular end-diastolic pressure and catheter (at time 0).
HYPOVOLAEMIC SHOCK 173

Y* L^

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E~==] ~

FIG. 2. "Branch chain decision tree." (After Shoemaker (1984).)

Mixed venous oxygen tension or saturation is a fluid replacement after operation. In the first
reliable measure of the overall adequacy of tissue example, the diagnosis is not in doubt, the
perfusion and oxygenation (Kasnitz et al., 1976). complete package of physiological compensatory
Apparatus has been developed which allows mechanisms is immediately called into play and,
continuous measurement and display of mixed assuming rapid and adequate volume repletion,
venous oxygen saturation and which has proved to outcome depends on securing haemostasis. In the
be of practical value in the intensive care setting second example, the diagnosis may be less
(Weston and Ledingham, 1984). Acute changes in obvious, the clinical presentation obscured by
tissue oxygenation are rapidly detected (fig. 1) additional, time-dependent factors such as com-
(Woodcock, Murray and Ledingham, 1984). partmental fluid shifts, and the outcome influ-
Delays in resuscitation may be prevented by the enced to an extent by shock-related complications
use of one of the several management procedures such as intravascular coagulation. Clearly, indi-
or algorithms now available (fig. 2); reduction in vidual patients may feature anywhere in the
mortality and morbidity may result (Shoemaker, spectrum between those two extremeswith age,
Appel and Bland, 1983). general health and concomitant illness further
contributing to the ultimate clinical presentation.
Hypovolaemia is the most common cause of
HYPOVOLAEMIC SHOCK shock in a general hospital population (Ledingham
Pathophysiology et al., 1974). It is diagnosed when the clinical
The onset of hypovolaemic shock may be sudden, features of hypotension, tachycardia, pallor,
for example after major vessel injury, or more sweating, peripheral cyanosis, hyperventilation,
gradual, for example in association with inadequate clouding of consciousness and oliguria are pre-
174
Extracellular space
Active
transport
Na.Ca
FIG. 3. Diagram showing some important factors in cell volume and ion regulation in mnmmnlian cells.
(After Trump, McDowell and Arstila (1980).)
dominantly attributable to diminished venous
return. The latter may be the result of overt fluid
loss (directly or indirectly) from the circulation or
of sequestration of fluid within body spaces;
examples of such " third space " collections include
ascites, massive oedema, haemothorax, intestinal
obstruction and haemoperitoneum. Myocardial
failure and sepsis are, by definition, not of major
clinical significance in the early stages of hypo-
volaemic shock, although both factors will in-
evitably become important if the shock process is
not rapidly reversed. A critical reduction in oxygen
availability to the cell is thefinalcommon pathway
leading to death from shock of all varieties;
reduced substrate supply and accumulation of the
products of cell metabolism are contributing
factors (Ledingham, 1977; Nair, 1985).
Cellular dysfunction
At the cellular level, three important features of
cell injury may be considered: altered cell volume
regulation; altered energy metabolism; and the
suicide-bag concept of Lysosomes (Trump* Mc-
Dowell and Arstila, 1980). One of the earliest
consequences of reduced oxygen availability is a
decrease in cellular adenosine triphosphate (ATP)
BRITISH JOURNAL OF ANAESTHESIA
O2
Exog. substrate
Ischaemia
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Passive leaks
content (fig. 3). This essential energy source for
the ionic pump of the plasma membrane is
normally broken down to adenosine diphosphate
(ADP) and phosphate in the presence of ATP-ase.
The absence of the high energy phosphate bonds
leads to depression of pump function and cell
swelling, the cells tending to approach Gibbs-
Donnan equilibrium with an increase in intracell-
ular sodium, calcium and water content and a loss
of potassium and magnesium. In spite of these
observations, evidence of membrane dysfunction
in the face or normal tissue ATP concentrations
suggests that energy depletion is only one of a
number of factors involved (Shires and Shires,
1984). When oxygen tension decreases to a critical
value within the mitochondrion (thought to be of
the order of 0.1 kPa ( < 1 mm Hg) (Nunn, 1977)),
the electron transfer mechanism, which accounts
for 90% of the body's oxygen consumption,
becomes defective. Oxidative phosphorylation is
uncoupled and ATP production gradually ceases.
, Associated structural changes, visible on light and
electron microscopic examination, include mito-
chondrial swelling and disruption of the lining
membrane, initially involving only the outer layer.
Eventually the inner membrane also deterior-
HYPOVOLAEMIC SHOCK
ates as a result of continued low ATP concentra-
tions. ATP deficiency also contributes to two
other metabolic consequences of importance in
hypovolaemic shockabnormalities of calcium
flux within the cell (Sperelakis and Schneider,
1976) and lactic acidosis. Persistence of high
intracellular calcium concentrations leads to
myocardial cell fatigue failure and asystolic
cardiac arrest. Lactic acidosis, stimulated by
increased phosphofructokinase activity, augments
calcium slow channel inhibition at pH less than
6.8, as well as having adverse effects on other
enzyme systems. The hypothesis that lysosomes
contribute to the downward spiral of refractory
shock by dissemination of destructive enzymes is
undoubtedly attractive and, indeed, there is good
evidence that lysosomal disruption does occur, but
this would appear to follow, rather than cause, cell
death (Trump et al., 1976). Likewise, significant
structural changes in other cellular organelles tend
to occur late in the ischaemic process.
The aforementioned pattern of pathophysio-
logical disturbance occurs in all cells, but the
susceptibility of different cells to hypoxia and
ischaemia is very variable. Astrocytes, for example,
cease to function after seconds, whilst skeletal
muscle will function anaerobically for 30 min and
hepatic cells for several hours; increased supplies
of glucose are required to provide adequate
substrate for anaerobic glycolysis, which may be
a problem in low flow states. Clearly, in the
presence of complete ischaemia the progress of
cellular disintegration will be more rapid, but
(depending on a variety of factors) the kidney and
liver, for example, have survival times, at 37 C,
of 1-2 h. The plasma membrane and early
mitochondrial changes are readily reversible if the
cause of shock is promptly eliminated, and several
pharmacological agents are known to attenuate or
even reverse some of the adverse metabolic effects,
for example ATP-MgCl, (Peitzman et al., 1981;
Chaudry et al., 1983), glucose-insulin-potassium
(Bronsveld et al., 1984), calcium channel blockers
(Hackel et al., 1981) and steroids (Goldfarb and
Glenn, 1983). None of these agents is of proven
clinical value.
Neurohumoral mechanisms
The sequence of physiological events leading to
the fully established clinical presentation of
hypovolaemic shock is probably one of the best
known in emergency medicine and needs only a
brief summary here. Since the central disturbance
175
in shock is a critical reduction in oxygen
availability, the main vehicle for its propagation is
the cardiovascular system, although ultimately no
organ escapes involvement.
The central nervous system initiates the body's
homeostatic responses to acute injury (including
fluid loss) by mechanisms which are complex and
ill-understood. Multiple afferent stimuli (arterial
and venous pressures and volume, osmolality, pH,
hypoxia, pain and anxiety, tissue damage and
sepsis) reach the hypothalamus where they are
integrated and relayed to the sympathetic nervous
system and adrenal medulla. Simultaneously, the
anterior pituitary initiates the hormonal response
characteristic of the metabolic response to injury.
Preservation of the integrative function of the
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central nervous system may be critical in deter-
mining the fate of the shocked patient (Golden
and Jane, 1973).
Vasopressin (AVP) and adrenocorticotrophic
hormone (ACTH) are commonly regarded as the
principal "stress hormones". Increased produc-
tion of these hormones follows a variety of different
stimuli, principally increased osmolality (detected
by osmoreceptors in the hypothalamus), decreased
arterial pressure and volume (detected by vascular
mechanoreceptors and relayed via the tractus
solitarius) and psychological stress (relayed via the
limbic system). ACTH is released into the blood
stream in response to corticotrophin releasing
factor (CRF), the composition of which is still
uncertain, but would appear to comprise several
components including a 41-residue peptide
(CRF-41), vasopressin and adrenaline (Bucking-
ham, 1985). ACTH stimulates the production of
cortisol, which plays a major role in protecting the
organism from the effects of hypovolaemia.
Another anterior pituitary peptide, (3-endorphin
(derived from the same precursor as ACTH), is
also released during stress and is thought to
mediate longer-term neuronal and endocrine
changes. It was thought to have been implicated
in producing cardiovascular depression in shock
(Holaday et al., 1983), but a recent study (Watson
et al., 1984) has suggested that another endogenous
opiate, met-enkephalin, may be more important in
this connection (see below).
The basic endocrine activation in shock in-
volves release of the catecholamines and angio-
tensin, with related later increases in the plasma
concentrations of such hormones as cortisol,
growth hormone, glucagon, antidiuretic hormone
and aldosterone; the main metabolic action of
176
several of these hormones is mediated by the "cell
messenger" or intermediate cyclic adenosine
monophosphate. The combined effect is to
mobilize energy reserves and conserve salt and
water. In the short term these mechanisms may be
regarded as protective, but ultimately they lead to
the breakdown of cellular integrity.
There is a massive outpouring of catecholamines
in all forms of shock; plasma adrenaline concen-
trations exceed noradrenaline concentrations in
hypovolaemic shock (Benedict and Grahame-
Smith, 1978) while the reverse is true in septic
shock (Griffiths, 1972). In a recent study in
patients with traumatic shock, plasma catechola-
mine concentrations were found to correlate posi-
tively with Injury Severity Score; plasma
noradrenaline concentrations were significantly
higher on admission in non-survivors than in the
casualties who survived serious injury (Davies
et al., 1984). Angiotensin II, the most potent
vasoconstrictor known, is also released into the
blood following shock and has been incriminated
as a cause of heart failure after prolonged severe
haemorrhage (Morton et al., 1977); another
extracardiac cause of heart failure is the presence
in the blood of myocardial depressant factor
(MDF), a circulating peptide released from
hypoxic pancreatic acinar cells (Lefer, 1978).
Catecholamines and angiotensin II stimulate
secretion of one another and blockade of both
would appear to be necessary if complete abolition
of vasoconstriction is desired. A possible further
inter-reaction is with enkephalins, which are
stored with catecholamines in adrenal chromaffin
cells and which may suppress cholinergic-depen-
dent catecholamine release from the adrenal
glands (Kumakura, Karoum and Guidotti, 1980).
Opiate antagonists, for example naloxone, might
act either by blocking this suppression locally or
by antagonizing central enkephalinergic inhibi-
tion.
Other substances released into the blood during
shock include histamine, plasma kinins, comple-
ment components and arachidonic acid metabo-
lites. Histamine has long been thought to have a
role in the aetiology of shock. This vasodilator
substance is derived partly from the mast cell
granule, but there is also evidence that endotoxin
stimulates the rate of production of histamine by
activating histidine decarboxylase. The weight of
present evidence would suggest that histamine
does not play an important part in initiating
hypovolaemic shock.
BRITISH JOURNAL OF ANAESTHESIA
Plasma kinins are vasodilator polypeptides
which increase capillary permeability. They are
released by both hypoxia and endotoxaemia from
inactive precursors (kininogens) present in the
alphas-globulin fraction of the plasma protein.
The initial step appears to be activation of the
Hageman factor (Factor XII) which leads to
conversion of kininogen to kinin by proteolytic
enzymes (kallikreins) released from leucocytes
and injured tissues. Activation of the Hageman
factor also promotes complement activation, with
the subsequent release of a number of pharmaco-
logically active substances which appear to be
responsible for leucocyte aggregation and endo-
thelial cell damage. Putative local mediators of the
microvascular injury include the arachidonic acid
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metabolites, plasma or phagocyte-derived pro-
teases, fibrinogen degradation products (particu-
larly the fibrin D monomer) and toxic oxygen
radicles released by activated leucocytes. Sero-
tonin and histamine may play a secondary role
in the pulmonary vascular response to shock.
These various effects are unusual following un-
complicated hypovolaemia, but readily occur in
the presence of shock compounded by trauma or
sepsis (Whaley et al., 1979).
Prostaglandins and leukotrienes are synthesized
by cellular microsomes from arachidonic acid via
the cyclo-oxygenase and lipo-oxygenase pathways
respectively (fig. 4). Macrophages, neutrophils,
platelets and mast cells are all involved in the
generation of these substances, which have a wide
range of pharmacological effects on the cardiovas-
cular system. Prostaglandins of the E and F groups
exert directly opposing physiological actions in the
microcirculation; the ratio of the concentrations of
these metabolites in response to injury thus
appears to be of considerably greater importance
than their absolute values. The same is true for the
thromboxane:prostacyclin ratio in organs such as
the heart and lung (see below). These observations
may help to explain the indifferent results
obtained from early pharmacological attempts
(using, for example indomethacin and aspirin) to
block the adverse effects of the prostaglandins in
shock. The recent emergence of more selective
blocking agents may well improve this situation.
Leukotrienes are potent chemotactic factors and,
in addition, cause bronchoconstriction, vasocon-
striction and microvascular exudation of protein
(Piper, 1983). There are no clinically applicable
selective inhibitors of the lipo-oxygenase pathway;
glucocorticoids induce inhibition of the common
HYPOVOLAEMIC SHOCK
Cell membrane phospholipids
Stimulus (phospholipase)
5-HETE
Chemotaxis
LTB4 LTA4
Chemotaxis
T
Vasoconstriction
Bronchoconstriction LTD4
t Vascular permeability LTE4
FIG. 4. Arachidonic acid metabolites in inflammation.
arachidonate precursor, phospholipase A2, thus
blocking the production of both metabolic
pathways.
The presence of tissue injury or sepsis compli-
cating hypovolaemia is likely to promote the
production of interleukin 1 from macrophages.
This recently identified lymphokine appears to
depend on arachidonate metabolism for its
capacity to induce fever and regulate immune
function. Its importance in injury metabolism is
only beginning to be explored (Fleck, Colley and
Myers, 1985).
Regional and microcirculatory disturbances
The early catecholamine-induced vasocon-
strictor response in hypovolaemic shock is not
uniformly intense throughout the body and
redistribution of blood flow occurs in favour of
certain "vital" organs, notably the brain and the
heart. As a result, the main brunt of the initial
microcirculatory changes affects the skin, muscle
and gastrointestinal tract; the kidney response
varies with the rapidity of onset of hypovolaemia:
177
(Inhibited by steroids)
Chemotactic
lipids
Cyclo-oxygenase (inhibited by
\ ^ aspirin, indomethacln)
PGG2
Endoperoxides Peroxidase
PGH2
Prostacyclin Thromboxane
synthetase synthetase
PGI 2 TxA ?
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Anti-platelet aggregator Vasoconstriction
Vasodilatation Platelet aggregation
Potentiates oedema
6-keto-PGF 1 a TxB,
the slower the onset, the greater the opportunity
for "autoregulation" and diversion of flow to
juxtamedullary glomeruli. The magnitude of
reduction of bloodflowin some of the "non-vital"
areas is not reflected in any of the routine clinical
haemodynamic measurements and this is often not
appreciated. In a recent experimental study, for
example, a 10% reduction in blood volume
produced negligible changes in arterial pressure
and heart rate, but an almost 30% reduction in
colon bloodflowand oxygen availability (Gilmour
et al., 1980). The profound decrease in splanchnic
blood flow has important implications for liver
function, since approximately 70% of hepatic
blood flow normally traverses the portal vein.
Thus, although the liver cells themselves may be
relatively resistant to hypoxia, disturbances in
hepatocellular and reticuloendothelial function
are demonstrable (Saba and Scovill, 1975; Gottlieb
et al., 1984). Interaction between these two func-
tions is increasingly recognized to be important
in a variety of conditions associated with hepatic
ischaemia (Canalese et al., 1982).
178
Normal
Tissue homeoatasis
Interstitium
Capillary
FIG. 5. Effects of hypovolaemic shock on the interstitial fluid phase. The capillary surface area available
for blood-tissue exchange processes is decreased. Fluid is mobilized from the interstitial phase (resetting
of pre- to postcapillary resistance ratio) and from cells (glucose-osmotic factors). The result is an
increased interstitial colloid density and reduction of the free-fluid phase. (After Haljamae (1984).)
A number of additional factors can complicate
the microcirculatory response to shock. Autoregu-
lation may be adversely affected by pathological
changes in the blood vessels. In hypertension the
pressure/flow relationship is maintained but
shifted to the right, and in atherosclerotic disease
the relationship becomes linear; the net effect in
both conditions is to produce a greater decrease in
bloodflowfor a lesser decrease in arterial pressure.
It should be remembered also that the normal
vasoconstrictor responses to hypovolaemia may be
obtunded during the administration of general
anaesthetic, sedative or related agents, causing the
already reduced circulating blood volume to be
more widely spread. Maldistribution of tissue
perfusion is one of the more recently explored
aspects of shock and much has yet to be learned,
but it is known that, even when overall flow to an
organ or region seems adequate, the flow may be
traversing "preferred" route capillaries rather
than nutrient vessels, and shunting through
arteriovenous anastomoses may also occur (Silver,
1977).
An increase in blood viscosity further impairs
flow in the microcirculation, giving grounds for
the current belief that, in lowflowstates, a degree
of haemodilution (to a haematocrit of around
30%) produces improved oxygen delivery
assuming that arterial oxygen tension and cardiac
output are adequate. If the increased blood
BRITISH JOURNAL OF ANAESTHESIA
Hypovolaemic shock
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viscosity is unrelieved, rouleau formation occurs,
with aggregation of red cells and platelets,
particularly in vessels with a flow of less than
0.1-0.2 mm s"1. Platelet aggregation is enhanced
by many factors, including adenosine diphosphate,
thrombin, collagen fragments, hydrogen ions,
noradrenaline and endotoxin. Endotoxaemia may
readily occur in response to trauma, pancreatitis or
splanchnic ischaemia. The severity of the periph-
eral circulatory failure associated with these latter
conditions is, in part, attributable to the effects of
endotoxaemia on the complement, coagulation
and fibrinolysis cascades (Foulis et al., 1982).
No description of the microcirculatory response
to shock would be complete without mention of
the interstitial fluid compartment. The fluid
volume within this phase is substantial (almost
four times the plasma volume) and the bulk is
found in the skin, viscera and skeletal muscle. A
decrease in the "functional" extracellular fluid
volume follows sustained haemorrhage (Shires,
Carrico and Canizaro, 1973). In the early stage of
hypovolaemic shock, much of this volume loss is
accounted for by transfer to the vascular compart-
ment, with involvement of both the gel and
free-fluid phases of the interstitium (fig. 5)
(Haljamae, 1984). Later, as microvascular pressure
relationships alter, transport of fluid from the
vascular compartment into the interstitium
occurs; a proportion of this fluid enters the
HYPOVOLAEMIC SHOCK
hypoxic cells, to a degree which is dependent on
the severity and duration of the shock. The
gastrointestinal tract may be more vulnerable to
these effects than the muscle mass and, ultimately,
disintegration of the organism may be largely
influenced by absorption of toxic factors from the
gut (Haglund and Lundgren, 1978).
Hypovolaemic shock may prove fatal during the
acute phase if treatment is delayed or the
underlying cause cannot be controlled (Ledingham
et al., 1974). Recovery from the acute phase is
usually consistent with long-term survival, but
incomplete recovery, often associated with surgical
or septic complications, may lead to single or
multiple organ failurenotably involving the lung
and the kidney (Dove, Stahl and Delguercio,
1980). Microvascular and subcellular disturbances
of a widespread and refractory nature are present
and mortality is high (National Heart, Lung and
Blood Institute, 1979).
Treatment
The importance of prompt and adequate resusci-
tation in the early stages of hypovolaemia is clear,
often before the diagnosis can be confirmed. In
practice, acute resuscitation of a patient suffering
from any form of shock is influenced more by the
nature of the associated physiological disturbances
than by specific aetiological factors. Success of
subsequent treatment, on the other hand, is largely
dependent on detection and elimination of the
underlying cause. In many patients, considerable
overlap will exist between the two processes.
Initial resuscitation
The objective of treatment is to restore adequate
oxygen availability for the metabolic requirements
of the tissues. The immediate aims are to augment
intravascular volume, optimize cardiac output and
its distribution, and ensure adequate pulmonary
gas exchange. These aims are achieved by
minimizing further fluid loss and replacing
estimated loss with either colloid or crystalloid
solutions and transfusion with concentrated red
cells to a haematocrit of 30-35 %; by the judicious
use of pharmacological agents; and by the
administration of oxygen together with mechanical
ventilation when indicated.
The wise counsel, found in all first aid manuals,
of reducing the risk of further fluid loss in the
hypovolaemic patient appears to carry less weight
once the patient has crossed the hospital threshold
(Waddell, 1975). It should be realized that
179
avoidance of unnecessary movement, immobiliza-
tion of broken limbs, gentle handling of damaged
tissues and maintenance of pressure dressings
are as important in the accident and emergency
department, the operating theatre or the intensive
therapy unit as during pre-hospital transport. The
role of the G-suit or antishock trousers is
uncertain. Used at low pressure, the device may be
a useful splint and reduce venous pooling; at
higher pressure, compression of the inferior vena
cava and increase in afterload may result, together
with respiratory embarrassment. At best, it may
serve as a temporary expedient in the field
(Holcroft, 1982) or in gaining time in selected
patients with severe abdominal or pelvic haemor-
rhage. Whatever its role, there is no doubt that
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sudden deflation of this support before adequate
fluid replacement, can lead to dangerous hypoten-
sion. The practice of tilting the hypovolaemic
patient head-down in an attempt to augment
venous return is less frequently utilized than
formerly. There is certainly no evidence that this
manoeuvre achieves any consistent haemodynamic
improvement (Sibbald et al., 1979) and adverse
pulmonary and cerebral effects have been reported.
Raising the legs is an adequate and safe first aid
procedure.
Fluid administration
Strange to relate, perhaps, the type of fluid loss
in shocked patients does not influence the choice
of initial fluid replacement as much as the
perceived nature of the underlying physiological
disturbance. Thus, whether the loss be caused by
haemorrhage, burns or gastrointestinal pathology,
both colloid and crystalloid solutions are used in
the first instance; later adjustment of the fluid
regimen includes respectively whole blood (or red
cell concentrates), plasma substitutes or electrolyte
solutions. Successful resuscitation is dependent
more on the rapidity and adequacy of fluid
repletion than on the composition of the regimen.
Dispute as to the selection offluidfor resuscitation
(the "colloid v. crystalloid" controversy) centres
mainly on issues relating to philosophy, side-
effects and economics.
The arguments on both sides have been
outlined in a number of major reviews (Shoemaker
and Hauser, 1979; Virgilio, Smith and Zarins,
1979; Poole et al., 1982) and need not be reiterated
in detail. The terms "colloid" and "crystalloid"
were coined by Thomas Graham in 1861 and refer
respectively to solute particles that are larger or
180
smaller than an arbitrarily determined particle
weight, usually taken as 30 000 in the case of body
fluid components. In effect, this means that colloid
particles (e.g. albumin) will not pass through
semipermeable membranes.
The proponents of colloid solutions cite the
following arguments:
(i) Since the key problem in shock is considered
to be loss of circulating volume (mainly blood
plasma), replacement with colloid is more appro-
priate and, because of the smaller volumes
involved, is more rapidly effective (Shoemaker
et al., 1981).
(ii) Crystalloids, because of their prompt equilib-
ration with extracellular fluid (ECF), require to be
infused in amounts exceeding estimated losses by
three to four times. (In critically ill patients,
1000 ml of crystalloid solution was shown to
increase plasma volume by a mean of 194 ml,
whereas 500 ml of 5 % albumin produced a mean
increase of 700 ml (Shoemaker, 1976; Hauser et
al., 1980).)
(iii) Crystalloids reduce the colloid osmotic pres-
sure, thus favouring the occurrence of pulmonary
oedema (Rackow et al., 1983).
The proponents of crystalloid solutions, on the
other hand, would argue that:
(i) Since the key problem in shock is considered
to be shrinkage of the extracellular fluid compart-
ment, replacement with crystalloid is more
appropriate (Shires et al., 1960; Virgilio et al.,
1979).
(ii) Excess increase in pulmonary artery wedge
pressure is less likely to occur with crystalloids
because of their rapid equilibration with ECF
(Virgilio et al., 1979).
(iii) Crystalloids are free from the risk of the
occasional anaphylactoid reactions which can
occur with any colloid solution, but are mostly
associated with synthetic colloids (Messmer,
1984).
(iv) Crystalloids are much cheaper than natural or
synthetic colloid solutions (Moss et al., 1981).
As previously stated, it is clear that either
approach is likely to lead to successful resuscitation
in the majority of patients. Whichever approach is
chosen, the importance of rigorous, frequent and
comprehensive monitoring cannot be overstated
for reasons involving both the volume and
composition of the infused fluid. At all times,
careful judgment is required in striking the
optimum balance between the volume of fluid per
unit time needed for adequate tissue perfusion and
BRITISH JOURNAL OF ANAESTHESIA
that which will induce overload; the value of the
" fluid challenge " in this regard has been indicated
above. Concern about the adverse effects of
crystalloids in shock is centred mainly on the risk
that lactated Ringer's solution may aggravate
existing lactic acidosis, but extensive clinical
experience has failed to uncover a significant
problem (Shires and Shires, 1984). The adverse
effects of colloids include dilution of clotting
factors, disturbance of renal function and ana-
phylactoid reactions (Messmer, 1984). However,
even here the low incidence of reactions and the
possibility of prevention or treatment are such that
these agents may be used with safety provided
overdose is avoided (1.5 g/kg body weight per day
in the case of dextran).
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Many clinicians believe that the best results in
shock resuscitation are achieved using a combina-
tion of colloid and crystalloid solutions and there
is some evidence that oxygen consumption is
higher with the combination than with either
regimen alone (Smith and Norman, 1982).
Nevertheless, exploration of alternative fluid
programmes continues and recent enthusiasm has
been expressed for the use of hypertonic saline
solutions in the treatment of refractory hypovolae-
mic shock (de Felippe et al., 1980) and in severely
burned patients (Bowser-Wallace, Cone and
Caldwell, 1985).
Whole blood (or, optimally, red cell concentrates
with added colloid or crystalloid) will be required
in the treatment of major blood loss or burns. If
large quantities are transfused, dilution of clotting
factors (fibrinogen, factors V and VII, and
platelets) results, and replacement with fresh
frozen plasma and platelet transfusions may be
required (as indicated by the coagulation assays).
In the case of massive transfusion, blood warming
and filtration procedures are normally used, al-
though the evidence that microfilters prevent the
occurrence of respiratory complications is not
convincing (Derrington, 1985). As in the case of
"clear" fluids, development of artificial haemo-
globin solutions continues. These may be con-
sidered in two groupsstroma free haemoglobin
(SFH) solutions and fluorocarbons. The main
problem with SFH has been its very high oxygen
affinity, but recently developed products, inclu-
ding polymerized pyridoxalated haemoglobin
((SFH-PLP)n) with a P 80 of 20 mm Hg, appear
to have overcome this obstacle (De Venuto, 1982).
Of the fluorocarbons, Fluosol-DA is the most
promising and its use in the management of blood
HYPOVOLAEMIC SHOCK
loss in certain religious minorities has been
reported.
If hypovolaemic shock proves refractory to fluid
repletion (as outlined above) and oxygen adminis-
tration (see below), the following factors may be
responsible: initial underestimate of the degree of
hypovolaemia; failure to arrest haemorrhage;
cardiac tamponade or tension pneumothorax;
underlying sepsis; or delayed treatment, leading to
secondary cardiovascular effects (e.g. the release of
MDF).
Pharmacological agents
If elimination of surgical factors together with
restoration of blood volume and red cell mass fails
to restore cardiac output, then pharmacological
181
the adequacy of resuscitation. Occasionally, bicar-
bonate is required when pre-existing hyperkal-
aemia is exacerbated by a decreasing extracellular
pH as a result of non-respiratory acidosis.
Respiratory acidosis demands correction of vent-
ilation. Electrolyte balance is calculated from
knowledge of input, serial serum estimations and
analysis of 24 h urinary output and other measur-
able external losses. Diuretics may be required in
the later stages of resuscitation, usually to
minimize the risk of pulmonary overload; in this
context both frusemide and dopamine may be
administered by i.v. infusion.
Two further drugs are worthy of mention.
Corticosteroids have been given to shocked
patients after severe trauma (Rokkanen et al.,

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assistance may be required. Unquestionably, the 1974; Svennevig et al., 1984). A variety of
drugs most commonly used in these circumstances beneficial effects was noted, but mortality was
are the inotropic agents (to increase myocardial unaffected. In the recovery phase, particularly
contractility) with or without the use of vasodilators after shock of traumatic origin, persistent sym-
(to decrease afterload) (Foex, 1983). Dopamine pathetic overactivity is sometimes observed. Such
has proved attractive for its effects on both cardiac patients are at risk of increased intracranial
output and urine output. If administered by i.v. pressure and recurrent haemorrhage. The use of
infusion at a rate (2-20 ug kg"1 min"1) such that a drug such as labetalol, which combines a and
systolic arterial pressure does not increase above P-adrenergic blocking actions, has proved to be of
80-100 mm Hg, dopamine will normally induce a value in this situation (Morel, Forster and Suter,
gratifying diuresis. If the rate is increased, the 1984).
ot-adrenergic agonist action of the drug emerges
and arrhythmias occur. The risk of intrapulmon- Oxygenation/'ventilation
ary shunting should be noted, and that toxic side- Many patients with hypovolaemic shock suffer
effects increase with the passage of time, although
from hypoxaemia of varying degree and multifac-
withdrawal of this agent has been successfully torial aetiology. Once the airway is secured,
achieved after many days of administration. amongst the most important priorities are correc-
Dobutamine, acting directly on (Jj-adrenergic tion of this disturbance of pulmonary gas
receptors, may have a more pronounced inotropic exchange and elimination, as far as possible, of
action on the heart than dopamine, with less factors leading to increased oxygen consumption
marked effects on heart rate and excitability. A (e.g. pain and sepsis) (Halmagyi and Kinney,
manoeuvre which is gaining popularity is to use 1975; Arturson, 1977). In the presence of low
dopamine by low-dose infusion during the early blood flow (and possibly anaemia) a high inspired
stages of resuscitation to maintain renal perfusion
oxygen concentration will be required to improve
andif cardiac output requires to be augmented tissue oxygen availability. The judicious use of
either to increase the dose of dopamine or to addanalgesic drugs is not only humane, but will
dobutamine (with the aim of achieving the best significantly reduce oxygen consumption.
combination of pharmacological actions). Com- Ventilatory assistance is required when there is
monly used vasodilators are chlorpromazine, excessive respiratory work or ventilatory inade-
nitroprusside and nitroglycerin; selection should
be based on the predominant cardiovascular quacy with hypercapnia. Failure of adequate
disturbance. oxygenation (POQ, less than 8.7 kPa) when breath-
ing oxygen 15 litre min"1 through a high-flow
Acid-base imbalance rarely requires pharma- mask (Flo, approximately 0.7) represents a shunt
cological correction. Non-respiratory acidosis of 20-25 % of the cardiac output and calls for the
associated with perfusion failure is rapidly use of positive pressure ventilation. Techniques
self-correcting once cardiac output is improved which increase mean intrathoracic pressure, such
and its disappearance may be used as a marker of as positive end-expiratory pressure (PEEP) and
 182
constant positive airway pressure, should be used
with caution in hypovolaemic patients and the
optimum increased pressure should be selected to
provide maximum oxygen delivery (Suter, Fairley
and Isenberg, 1975); continuous measurement of
mixed venous oxygen saturation during the
application of PEEP will indicate changes in
oxygen delivery. PEEP improves gas exchange in
patients with pulmonary oedema, not by reducing
pulmonary oedema, but by increasing alveolar
volume (Hopewell and Murray, 1976); adverse
effects include renal dysfunction and pulmonary
barotrauma (Ginsberg, 1977; Tyler, 1983). In the
traumatized patient, coincidental head injury
would prompt the early use of mechanical
ventilation to reduce the risk of secondary
BRITISH JOURNAL OF ANAESTHESIA
the recovery phase, particularly with the ventilated
patient, one of the benzodiazepine agents, for
example, may be used to relieve anxiety or
agitation. Except in previously unconscious pat-
ients, non-depolarizing neuromuscular blocking
agents are never used without simultaneous
cortical sedatives.
Further treatment
In general, patients should be adequately
resuscitated from shock before surgery, but in
some instances this is not possible. In ruptured
ectopic pregnancy, for instance, it is often
impossible to maintain a normal arterial pressure
until bleeding is controlled and blood cleared from
the peritoneal cavity; in leaking aortic aneurysm

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deterioration of cerebral function (Jennett and it is often best to commence surgery as soon after
Carlin, 1978). initiation of resuscitation as reasonable, lest major
bleeding occurs; and in the presence of sepsis,
Analgesia normal cardiovascular function may be difficult to
Effective safe analgesia should not be withheld restore until the source is eliminated.
from hypovolaemic, especially injured, patients. Once haemodynamic stability has been achieved,
A variety of agents are available including pent- it is important to take immediate stock of further
azocine, buprenorphine, phenoperidine and fen- fluid needs, since even small amounts in excess of
tanyl, but morphine probably remains the most requirement will tend to provoke pulmonary
frequently used. There is no place for subcutan- oedema, whilst mild dehydration may be associated
eous or i.m. injection of these agents in hypovol- with an increased risk of renal failure. These
aemic shock. Because of impaired blood flow, complications are especially likely to occur in
absorption is unreliable, unpredictable and dan- association with major sepsis (Woodcock and
gerous. Increments of the chosen drug (e.g. Ledingham, 1985) and the persistence of tissue
morphine 2 mg) should be administered i.v. every and pulmonary oedema may have a bearing on
25 min until a satisfactory level of sedation is outcome. At this stage, methods designed to
achieved. It is rarely necessary to exceed decrease fluid retention may prove valuable,
10 mg per 70 kg body weight. Duration of action including the simultaneous administration of
i by this route is short, however, and the dose may salt-poor albumin and diuretics. If haemodialysis
' have to be repeated at 30-60 min intervals. All is in use, ultrafiltration is of particular value. In
narcotic analgesic drugs are peripheral vasodilatorsrecent years, the advent of continuous arterio-
acting on capacitance vessels. Hypotension venous haemofiltration has greatly facilitated
developing after administration generally indi- emergency fluid removal (Kaplan, Longnecker
cates unrecognized hypovolaemia. and Folkert, 1984).
Analgesic effects equal to those of morphine can Earlier comments about the importance of
be produced by 25-50 % nitrous oxide in oxygen. avoiding unnecessary movement in the shocked
For short term, occasional use (avoiding patients patient should not be misconstrued. Once adequate
with air collections in body cavities (e.g. pneumo- resuscitation has been achieved, such patients may
thorax) or head injury) nitrous oxide is of value. be moved within hospital or transported between
Infiltration of local analgesic drugs or nerve blockhospitals without difficulty, provided intensive
also deserve consideration in selected patients. care is maintained in the hands of experienced
Extradural and intrathecal blockade are not personnel (Bion et al., 1985).
recommended during resuscitation from shock
although once the initial resuscitation phase is
over, these techniques have their place. ASSESSMENT OF PROGNOSIS

The addition of a sedative drug is seldom From earliest times until the present day it has
necessary during the period of shock itself but, in been an intuitively attractive, although remarkably
 HYPOVOLAEMIC SHOCK
TABLE 11. Number and percent of patients with two or more values
in the normal range (Shoemaker, 1984)
Non-survivors Survivors
0/
No. No.
/o
MAP 29 78 68
HR 30 81 66
CVP 35 95 72
WP 11 30 21
Cardiac index 35 95 64
Mean of these variables 76
elusive, objective of those involved in the
management of shock to predict outcome in an
individual patient. As in other forms of prognosti-
cation the possible advantages of accurate predic-
tion are: more efficient use of existing resources;
facilitation of audit and comparison; improved
evaluation of new forms of treatment. Amongst the
problems in trying to determine the fate of
shocked patients are some which are related to
shock itself, such as its severity and duration and
the stage and effects of resuscitation, and others
which are common to any prognostic index, such
as aetiology, associated disease and age. One
further point concerns the seemingly simple
matter of definition of outcome. Whereas, in
earlier times when resuscitation techniques were
relatively basic, it was reasonable to consider
outcome from shock as being synonymous with
ultimate survival (and many publications made no
distinction), nowadays with increasingly sophisti-
cated procedures for initial management such
assumptions cannot be made. In centres properly
equipped and staffed for major emergencies,
successful resuscitation from most forms of shock
is now common, although subsequent mortality
remains substantial (Ledingham and McArdle,
1978).
Haemodynamic Variables
Prognosis in severe shock may be considered with
reference to the usually measured variables in
critically ill patients, amongst which those reflect-
ing cardiovascular function still take precedence.
The standard haemodynamic variables at the
onset of shock appear to be of little prognostic
value in hypovolaemic or traumatic shock. The
most commonly monitored variables in shock
(table II) are neither sensitive nor accurate in early
warning of death, the values being almost identical
in non-survivors and survivors (Shoemaker,
183
1984). However, reversal of shock is more
promptly achieved in survivors and serial meas-
urements during early resuscitation allow predic-
tion of outcome at 24 h, or even earlier, with a high
degree of accuracy (Chang et al., 1977; Cowan et
0/
al., 1984).
/o
89 More sophisticated haemodynamic measure-
87 ments may improve the accuracy of prediction in
95 certain circumstances. Perhaps the best known
28 example is that of cardiogenic shock secondary to
84
75
myocardial infarction, in which patients may be
classified into groups on the basis of cardiac output
and pulmonary capillary wedge pressure measure-
ments, with mortality varying from 1 % in the least
affected to over 60 % in the most severely affected
group (Forrester et al., 1976). In hypovolaemic
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shock, low cardiac output, persistently increased
pulmonary vascular resistance and low skin
temperature have some association with outcome,
but the reported degree of correlation varies
widely between centres. The ability to increase
standardized left ventricular stroke work in
response to intravascular fluid may also forecast a
successful result in hypovolaemic shock (Czer and
Shoemaker, 1980); a more generally applicable
test, based on the changes produced by dopamine
infusion on toe temperature seems to allow early
separation of survivors and non-survivors (Ruiz,
Weil and Carlson, 1979).
Vasoactive Mediators
Since both the systemic and pulmonary vascular
changes described above may be caused by the
release into the circulation of vasoactive substances
including the catecholamines, histamine, brady-
kinin, serotonin and arachidonic acid metabolites,
it is not surprising that blood concentrations of
these agents during the acute phase of shock may
relate to outcome. Increasingly selective pharma-
cological agents are being used to manipulate
these mediators in an effort to improve prognosis.
Grahame-Smith and his colleagues (Benedict
and Grahame-Smith, 1978; Davies et al., 1984)
demonstrated that the pattern of catecholamine
response can distinguish between shock of different
aetiology and, in respect of traumatic shock, a
positive correlation existed between adrenaline
concentrations at admission and Injury Severity
Scores exceeding 10; a similar relationship existed
with noradrenaline. Significantly higher concen-
trations of noradrenaline, although not adrenaline,
were seen in those with a fatal outcome. It is
probable that measurement of catecholamine
 184 BRITISH JOURNAL OF ANAESTHESIA
<* 500 3000 0
m
2500 if
o_ 400
2000 . '-z
J l 300 1500 g
1-3 200 1000
500
" 100

PEEP on
66.7
Start trial drug |
DIC ARDS dialysis 53.3 1>

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40-0
's'
26.7 2;

13.3

11

FIG. 6. Clinical course of a typical postsurgical septicaemia progressing to ARDS. An open prostatectomy
was complicated by rectal perforation and haemorrhage; intermittent positive pressure ventilation was
continued after operation, and septic shock (streptococcal) was diagnosed a few hours later. Antibiotics
were started immediately. A trial drug, dazoxiben, was used to inhibit thromboxane synthesis, but this
did not prevent development of disseminated intravascular coagulation, ARDS and renal failure. Death
occurred on the 11th day. The upper panel shows arterial concentrations of thromboxane B t , which
decreased to immeasurable values soon after dazoxiben was given, and 6-keto-PGF m (metabolite of
prostacyclin) which decreased over the next few days. The lower panel shows volume of lung water
(columns) (measured by the thermal-green dye double indicator dilution technique), which increased
abruptly from normal on the 3rd day after operation with the onset of ARDS. The degree of hypoxaemia
is measured by the alveolar-arterial oxygen tension gradient ( P P J

turnover will prove to be of greater value than
plasma values, but such techniques are not yet
clinically applicable. Histamine and bradykinin
changes have also been shown to relate to clinical
course and outcome, but predominantly in septic
shock (Griffiths, 1972; O'Donnell et al., 1976).
Of major current interest is the probability that
arachidonic acid products may be aetiologically
involved in one of the major complications of
shock, namely, the adult respiratory distress
syndrome. One study (Reines et al., 1982) showed
a highly significant increase in thromboxane B, in
non-survivors following septic shock, by compar-
ison with either survivors or controlschanges
which were reflected in the associated degree of
pulmonary dysfunction, as measured by the
alveolar-arterial oxygen tension gradient. Obser-
vations from this centre would confirm this
relationship, although attempts to modify these
effects by pharmacological means have so far
proved disappointing (fig. 6) (Woodcock and
Ledingham, 1985).
Metabolic changes
Metabolic determinants of outcome in severe
shock have attracted increasing attention. Adren-
ergic mechanisms produce metabolic effects either
indirectly via hormones or by direct action on
biochemical pathways. Insulin is inhibited, while
glucagon and cortisol are stimulated. The initiation
 HYPOVOLAEMIC SHOCK 185

8 10 12 14 16 18

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S 5 0 points Lactate (mmol litre"1)

0 2 4 6 8
Lactate (mmol litre"1)
FIG. 7. A comparison of the curves of survival probability and the values of S M computed for various
groups of shock: o = Septic; x = septic combinations; + haemorrhagic + trauma + combinations;
= cardiogeaic + combinations. (After Vitek and Cowley (1971).)

of these changes results in stimulation of glycogen-
olysis, lipolysis, gluconeogenesis and ketogenesis.
Glucose, lactate, pyruvate and alanine all show a
positive correlation with severity of injury (and, by
inference, with outcome) while ketone bodies are
inversely correlated; plasma cortisol correlates
positively with moderate injury and negatively
with more severe injury (Stoner et al., 1979;
Oppenheim, Williamson and Smith, 1980). After
initial resuscitation, continued stress (e.g. sepsis)
is associated with sustained plasma cortisol
concentrationsin the absence of inhibiting
mechanisms (Watt and Ledingham, 1984).
The relationship between poor perfusion and
lactic acidosis has been recognized for many years
and has led a number of authors to describe
"probability of survival" curves (Weil and Afifi,
1970; Vitek and Cowley, 1971). One of the
difficulties with such a relationship is that the
mean " S M " (50% probability of survival) may
vary from around 2 mmol litre"1 in the case of
cardiogenic shock to nearly 8 mmol litre"1 in
traumatic shock (fig. 7). Furthermore, while the
. association between lactate and outcome appears
close in traumatic and uncomplicated hypovol-
aemic shock, experience from this centre (Cowan
et al., 1984) in a group of patients suffering
predominantly septic shock, showed a more
complex relationship. Whole blood lactate concen-
trations at the onset of resuscitation were similar
in both the survivor and non-survivor groups.
Serial lactate measurements were better at predict-
ing outcome than single measurements. How-
ever, lactate measurements were less valuable than
serial measurements of simple haemodynamic
variables (table III).
Oxygen consumption less than 120 ml min"1
s
m in the early phase of shock and mixed venous
oxygen saturation less than 50% are commonly
associated with non-survival; in the case of septic
shock, prognosis is also poor when oxygen
consumption exceeds twice normal (Shoemaker et
TABLE III. The magnitude of the coefficient reflects the relative
strength of the contribution of that variable to the prediction of
outcome. ^Did not make a significant contribution to prediction;
the absence of these variables would not influence prediction
Variable Coefficient
Urine output at 3 h
Change in temperature gradient 0-3 h
0.52
-0.51
Change in mean arterial pressure 0-3 h 0.45
Mean arterial pressure at 3 h 0.44
Temperature gradient at 3 h -0.39
Change in urine output 0-3 h 0.19f
Whole blood lactate at 3 h 0.14f
Change in whole blood lactate 0-3 h 0.09f
186
al., 1973; Kasnitz et al., 1976). On the basis of
these and related observations (Haupt, Gilbert and
Carlson, 1985) it is clear that the relationship
between oxygen availability, oxygen consumption
and lactic acidosis may not be as simple as at first
thought. The initial metabolic changes in shock,
including gluconeogenesis, lead to a complex
series of adaptive changes in other organs (some
of the responses of which may be deficient) and it
is perhaps not surprising that examination of any
single event within the whole may be unrewarding
in terms of predicting outcome. Awareness of this
problem has led various groups of investigators to
construct biochemical "profiles" in which simul-
taneous account is taken of several haemodynamic
and metabolic disturbances and the pattern of
change observed in relation to clinical course. This
more rewarding, if complicated, approach is
clearly unsuitable in the routine management of
shock outside research centres. The optimal
system has yet to be devised, but there is general
recognition that metabolic and hormonal abnor-
malities contribute substantially to the haemo-
dynamic and substrate disturbances of shock and
must be considered in the development of scoring
systems.
As a consequence of the progressive metabolic
derangements of untreated or refractory shock,
serum enzymes ultimately become increased and
may be of prognostic value (Hardaway, 1981), but
interpretation of these changes is often difficult
after accidental or surgical injury.
In summary, it is clear that prognostic indices
are least reliable in the early stages of shock when Cowan,
their value would be greatest; that relatively
simple sequential haemodynamic measurements
can be a reasonable guide in the acute phase; and Czer, L. S. C , and Shoemaker, W. C. (1980). Myocardial
that prediction of outcome becomes increasingly
more accurate in the later stages of resuscitation. Davies.C. L., Newman, R. J.,Molyneux,S. G.,and Grahame-
For these reasons, it is the authors' belief that no
shocked patient should be denied the chance of
immediate and comprehensive resuscitation, that
the ultimate prognosis is markedly influenced by
the rapidity and effectiveness of early resuscitation, De Venuto, F. (1982). Haemoglobin solutions as oxygen-
and that the efficient use of intensive care facilities
depends on regular reassessment of progress Dove, D. B., Stahl, W. M., and Delguercio, L. R. M. (1980).
during the later phase of management.
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