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HYPOVOLAEMIC SHOCK
Most patients demonstrating the conventionally be expected to alter this pattern of response,
accepted clinical features of shock, whatever its increasing the risk of a critical reduction in tissue
cause, will respond favourably to the administration oxygen availability and subsequent complications.
of i.v. fluids. Thus, patients suffering from shock In patients with acute upper gastrointestinal
attributable to sepsis, drug overdose and, on haemorrhage, for example, the presence of
occasion, myocardial infarction, manifest increased hypovolaemic shock, age over 60 years, and
cardiac output and improved tissue perfusion in haemoglobin concentration, at admission to hos-
Y* L^
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 BRITISH JOURNAL OF ANAESTHESIA
O2
Exog. substrate
Extracellular space Ischaemia
Active
transport
Passive leaks
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 content (fig. 3). This essential energy source for
return. The latter may be the result of overt fluid the ionic pump of the plasma membrane is
loss (directly or indirectly) from the circulation or normally broken down to adenosine diphosphate
of sequestration of fluid within body spaces; (ADP) and phosphate in the presence of ATP-ase.
examples of such " third space " collections include The absence of the high energy phosphate bonds
ascites, massive oedema, haemothorax, intestinal leads to depression of pump function and cell
obstruction and haemoperitoneum. Myocardial swelling, the cells tending to approach Gibbs-
failure and sepsis are, by definition, not of major Donnan equilibrium with an increase in intracell-
clinical significance in the early stages of hypo- ular sodium, calcium and water content and a loss
volaemic shock, although both factors will in- of potassium and magnesium. In spite of these
evitably become important if the shock process is observations, evidence of membrane dysfunction
not rapidly reversed. A critical reduction in oxygen in the face or normal tissue ATP concentrations
availability to the cell is thefinalcommon pathway suggests that energy depletion is only one of a
leading to death from shock of all varieties; number of factors involved (Shires and Shires,
reduced substrate supply and accumulation of the 1984). When oxygen tension decreases to a critical
products of cell metabolism are contributing value within the mitochondrion (thought to be of
factors (Ledingham, 1977; Nair, 1985). the order of 0.1 kPa ( < 1 mm Hg) (Nunn, 1977)),
the electron transfer mechanism, which accounts
Cellular dysfunction for 90% of the body's oxygen consumption,
At the cellular level, three important features of becomes defective. Oxidative phosphorylation is
cell injury may be considered: altered cell volume uncoupled and ATP production gradually ceases.
regulation; altered energy metabolism; and the , Associated structural changes, visible on light and
suicide-bag concept of Lysosomes (Trump* Mc- electron microscopic examination, include mito-
Dowell and Arstila, 1980). One of the earliest chondrial swelling and disruption of the lining
consequences of reduced oxygen availability is a membrane, initially involving only the outer layer.
decrease in cellular adenosine triphosphate (ATP) Eventually the inner membrane also deterior-
HYPOVOLAEMIC SHOCK 175
ates as a result of continued low ATP concentra- in shock is a critical reduction in oxygen
tions. ATP deficiency also contributes to two availability, the main vehicle for its propagation is
other metabolic consequences of importance in the cardiovascular system, although ultimately no
hypovolaemic shockabnormalities of calcium organ escapes involvement.
flux within the cell (Sperelakis and Schneider, The central nervous system initiates the body's
1976) and lactic acidosis. Persistence of high homeostatic responses to acute injury (including
intracellular calcium concentrations leads to fluid loss) by mechanisms which are complex and
myocardial cell fatigue failure and asystolic ill-understood. Multiple afferent stimuli (arterial
cardiac arrest. Lactic acidosis, stimulated by and venous pressures and volume, osmolality, pH,
increased phosphofructokinase activity, augments hypoxia, pain and anxiety, tissue damage and
calcium slow channel inhibition at pH less than sepsis) reach the hypothalamus where they are
6.8, as well as having adverse effects on other integrated and relayed to the sympathetic nervous
enzyme systems. The hypothesis that lysosomes system and adrenal medulla. Simultaneously, the
contribute to the downward spiral of refractory anterior pituitary initiates the hormonal response
shock by dissemination of destructive enzymes is characteristic of the metabolic response to injury.
undoubtedly attractive and, indeed, there is good Preservation of the integrative function of the
Chemotactic
lipids
Cyclo-oxygenase (inhibited by
\ ^ aspirin, indomethacln)
5-HETE PGG2
Chemotaxis
Endoperoxides Peroxidase
T
Vasoconstriction PGI 2 TxA ?
arachidonate precursor, phospholipase A2, thus the slower the onset, the greater the opportunity
blocking the production of both metabolic for "autoregulation" and diversion of flow to
pathways. juxtamedullary glomeruli. The magnitude of
The presence of tissue injury or sepsis compli- reduction of bloodflowin some of the "non-vital"
cating hypovolaemia is likely to promote the areas is not reflected in any of the routine clinical
production of interleukin 1 from macrophages. haemodynamic measurements and this is often not
This recently identified lymphokine appears to appreciated. In a recent experimental study, for
depend on arachidonate metabolism for its example, a 10% reduction in blood volume
capacity to induce fever and regulate immune produced negligible changes in arterial pressure
function. Its importance in injury metabolism is and heart rate, but an almost 30% reduction in
only beginning to be explored (Fleck, Colley and colon bloodflowand oxygen availability (Gilmour
Myers, 1985). et al., 1980). The profound decrease in splanchnic
blood flow has important implications for liver
Regional and microcirculatory disturbances function, since approximately 70% of hepatic
The early catecholamine-induced vasocon- blood flow normally traverses the portal vein.
strictor response in hypovolaemic shock is not Thus, although the liver cells themselves may be
uniformly intense throughout the body and relatively resistant to hypoxia, disturbances in
redistribution of blood flow occurs in favour of hepatocellular and reticuloendothelial function
certain "vital" organs, notably the brain and the are demonstrable (Saba and Scovill, 1975; Gottlieb
heart. As a result, the main brunt of the initial et al., 1984). Interaction between these two func-
microcirculatory changes affects the skin, muscle tions is increasingly recognized to be important
and gastrointestinal tract; the kidney response in a variety of conditions associated with hepatic
varies with the rapidity of onset of hypovolaemia: ischaemia (Canalese et al., 1982).
178 BRITISH JOURNAL OF ANAESTHESIA
Normal Hypovolaemic shock
Tissue homeoatasis
Interstitium
Capillary
A number of additional factors can complicate viscosity is unrelieved, rouleau formation occurs,
the microcirculatory response to shock. Autoregu- with aggregation of red cells and platelets,
lation may be adversely affected by pathological particularly in vessels with a flow of less than
changes in the blood vessels. In hypertension the 0.1-0.2 mm s"1. Platelet aggregation is enhanced
pressure/flow relationship is maintained but by many factors, including adenosine diphosphate,
shifted to the right, and in atherosclerotic disease thrombin, collagen fragments, hydrogen ions,
the relationship becomes linear; the net effect in noradrenaline and endotoxin. Endotoxaemia may
both conditions is to produce a greater decrease in readily occur in response to trauma, pancreatitis or
bloodflowfor a lesser decrease in arterial pressure. splanchnic ischaemia. The severity of the periph-
It should be remembered also that the normal eral circulatory failure associated with these latter
vasoconstrictor responses to hypovolaemia may be conditions is, in part, attributable to the effects of
obtunded during the administration of general endotoxaemia on the complement, coagulation
anaesthetic, sedative or related agents, causing the and fibrinolysis cascades (Foulis et al., 1982).
already reduced circulating blood volume to be No description of the microcirculatory response
more widely spread. Maldistribution of tissue to shock would be complete without mention of
perfusion is one of the more recently explored the interstitial fluid compartment. The fluid
aspects of shock and much has yet to be learned, volume within this phase is substantial (almost
but it is known that, even when overall flow to an four times the plasma volume) and the bulk is
organ or region seems adequate, the flow may be found in the skin, viscera and skeletal muscle. A
traversing "preferred" route capillaries rather decrease in the "functional" extracellular fluid
than nutrient vessels, and shunting through volume follows sustained haemorrhage (Shires,
arteriovenous anastomoses may also occur (Silver, Carrico and Canizaro, 1973). In the early stage of
1977). hypovolaemic shock, much of this volume loss is
An increase in blood viscosity further impairs accounted for by transfer to the vascular compart-
flow in the microcirculation, giving grounds for ment, with involvement of both the gel and
the current belief that, in lowflowstates, a degree free-fluid phases of the interstitium (fig. 5)
of haemodilution (to a haematocrit of around (Haljamae, 1984). Later, as microvascular pressure
30%) produces improved oxygen delivery relationships alter, transport of fluid from the
assuming that arterial oxygen tension and cardiac vascular compartment into the interstitium
output are adequate. If the increased blood occurs; a proportion of this fluid enters the
HYPOVOLAEMIC SHOCK 179
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 183
1984). However, reversal of shock is more
TABLE 11. Number and percent of patients with two or more values promptly achieved in survivors and serial meas-
in the normal range (Shoemaker, 1984)
urements during early resuscitation allow predic-
Non-survivors Survivors tion of outcome at 24 h, or even earlier, with a high
degree of accuracy (Chang et al., 1977; Cowan et
0/
No. No. 0/
al., 1984).
/o /o
MAP 29 78 68 89 More sophisticated haemodynamic measure-
HR 30 81 66 87 ments may improve the accuracy of prediction in
CVP 35 95 72 95 certain circumstances. Perhaps the best known
WP 11 30 21 28 example is that of cardiogenic shock secondary to
Cardiac index 35 95 64 84
Mean of these variables 76 75
myocardial infarction, in which patients may be
classified into groups on the basis of cardiac output
and pulmonary capillary wedge pressure measure-
elusive, objective of those involved in the ments, with mortality varying from 1 % in the least
management of shock to predict outcome in an affected to over 60 % in the most severely affected
individual patient. As in other forms of prognosti- group (Forrester et al., 1976). In hypovolaemic
PEEP on
66.7
Start trial drug |
DIC ARDS dialysis 53.3 1>
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 pulmonary dysfunction, as measured by the
plasma values, but such techniques are not yet alveolar-arterial oxygen tension gradient. Obser-
clinically applicable. Histamine and bradykinin vations from this centre would confirm this
changes have also been shown to relate to clinical relationship, although attempts to modify these
course and outcome, but predominantly in septic effects by pharmacological means have so far
shock (Griffiths, 1972; O'Donnell et al., 1976). proved disappointing (fig. 6) (Woodcock and
Of major current interest is the probability that Ledingham, 1985).
arachidonic acid products may be aetiologically
involved in one of the major complications of Metabolic changes
shock, namely, the adult respiratory distress Metabolic determinants of outcome in severe
syndrome. One study (Reines et al., 1982) showed shock have attracted increasing attention. Adren-
a highly significant increase in thromboxane B, in ergic mechanisms produce metabolic effects either
non-survivors following septic shock, by compar- indirectly via hormones or by direct action on
ison with either survivors or controlschanges biochemical pathways. Insulin is inhibited, while
which were reflected in the associated degree of glucagon and cortisol are stimulated. The initiation
HYPOVOLAEMIC SHOCK 185
8 10 12 14 16 18
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- complex relationship. Whole blood lactate concen-
olysis, lipolysis, gluconeogenesis and ketogenesis. trations at the onset of resuscitation were similar
Glucose, lactate, pyruvate and alanine all show a in both the survivor and non-survivor groups.
positive correlation with severity of injury (and, by Serial lactate measurements were better at predict-
inference, with outcome) while ketone bodies are ing outcome than single measurements. How-
inversely correlated; plasma cortisol correlates ever, lactate measurements were less valuable than
positively with moderate injury and negatively serial measurements of simple haemodynamic
with more severe injury (Stoner et al., 1979; variables (table III).
Oppenheim, Williamson and Smith, 1980). After Oxygen consumption less than 120 ml min"1
s
initial resuscitation, continued stress (e.g. sepsis) m in the early phase of shock and mixed venous
is associated with sustained plasma cortisol oxygen saturation less than 50% are commonly
concentrationsin the absence of inhibiting associated with non-survival; in the case of septic
mechanisms (Watt and Ledingham, 1984). shock, prognosis is also poor when oxygen
The relationship between poor perfusion and consumption exceeds twice normal (Shoemaker et
lactic acidosis has been recognized for many years
and has led a number of authors to describe TABLE III. The magnitude of the coefficient reflects the relative
"probability of survival" curves (Weil and Afifi, strength of the contribution of that variable to the prediction of
1970; Vitek and Cowley, 1971). One of the outcome. ^Did not make a significant contribution to prediction;
the absence of these variables would not influence prediction
difficulties with such a relationship is that the
mean " S M " (50% probability of survival) may Variable Coefficient
vary from around 2 mmol litre"1 in the case of
cardiogenic shock to nearly 8 mmol litre"1 in Urine output at 3 h
Change in temperature gradient 0-3 h
0.52
-0.51
traumatic shock (fig. 7). Furthermore, while the Change in mean arterial pressure 0-3 h 0.45
. association between lactate and outcome appears Mean arterial pressure at 3 h 0.44
close in traumatic and uncomplicated hypovol- Temperature gradient at 3 h -0.39
aemic shock, experience from this centre (Cowan Change in urine output 0-3 h 0.19f
Whole blood lactate at 3 h 0.14f
et al., 1984) in a group of patients suffering Change in whole blood lactate 0-3 h 0.09f
predominantly septic shock, showed a more
186 BRITISH JOURNAL OF ANAESTHESIA
al., 1973; Kasnitz et al., 1976). On the basis of Baxter, C. R. (1974). Fluid volume and electrolyte changes of
these and related observations (Haupt, Gilbert and the early postburn period. CHn. Plait. Surg., 1, 693.
Carlson, 1985) it is clear that the relationship Benedict, C. R., and Grahame-Smith, D. G. (1978). Plasma
noradrenaline and adrenaline concentrations and dopamine-
between oxygen availability, oxygen consumption B-hydroxylase activity in patients with shock due to
and lactic acidosis may not be as simple as at first septicaemia, trauma and haemorrhage. QJ. Med., 47, 1.
thought. The initial metabolic changes in shock, Bion, J. F., Edlin, S. A., Ramsay, G., McCabe, S., and
including gluconeogenesis, lead to a complex Ledingham, I. McA. (1985). Validation of a prognostic score
series of adaptive changes in other organs (some in critically ill patients undergoing transport. Br. Med. J.,
291, 432.
of the responses of which may be deficient) and it Bowser-Wallace, B. H., Cone, J. B., and Caldwell, F. T.
is perhaps not surprising that examination of any (1985). Hypettonic lactated saline resuscitation of severely
single event within the whole may be unrewarding burned patients over 60 years of age. J. Trauma, 25, 22.
in terms of predicting outcome. Awareness of this Brock, P., and Bowes, J. (1975). Limitations of electrocardio-
problem has led various groups of investigators to scopyfailure of the electrocardiograph to warn of low
cardiac output. Anaesthesia, 30, 90.
construct biochemical "profiles" in which simul- Bronsveld, W., van Lambalgen, A. A., van den Bos, G. C ,
taneous account is taken of several haemodynamic Thijs, L. G., and Koopmans, P. A. R. (1984). Effects of
and metabolic disturbances and the pattern of glucose-insulin-potassium (GIK) on myocardial blood flow