CHAPTER 11 Hypotension and Shock Vineet Nayyar* *Intensive Care Unit, Westmead Hospital, New

South Wales, Australia. Introduction ‘Shock’ is a term used to denote a clinical syndrome of acute
haemodynamic compromise that results in a critical impairment of blood flow to vital organs to the
extent that normal cellular function cannot be sustained.1 Cellular injury caused by inadequate
delivery of oxygen and substrates to the tissues induces changes in the microvasculature that further
compromises tissue perfusion. This leads to a vicious cycle, which if not interrupted at the
appropriate time, leads to multiorgan failure and death. Shock is a medical emergency and an
important cause of morbidity and mortality worldwide. In spite of significant technological advances
in supportive care, shock, irrespective of its aetiology, remains a condition of high mortality. It is
therefore essential to have a clear conceptual approach to the problem.2 Classification
Hypoperfusion is the hallmark of shock. Shock has been traditionally classified according to the
haemodynamic profile and mechanism by which it occurs.3 It is useful to consider components of
the system that maintains tissue perfusion as comprising a pump (heart), conducting tubes
(vasculature) and the fluid that moves around (blood).2,3 Shock can then be considered to be due to
the following mechanisms: Loss of fluid or hypovolaemic shock: This type of shock occurs as a result
of either loss of whole blood (haemorrhage) or fluid (severe diarrhoea, polyuria) or due to shift of
fluid from one compartment of the body to another (burns, third spacing). Pump failure or
cardiogenic shock: This type of shock results from myocardial injury caused by ischaemia or
infarction (acute coronary syndrome), inflammation (myocarditis), toxins or trauma. Obstruction or
obstructive shock: This type of shock is due to a block in the free passage of blood through the
vascular system either due to a problem within the system (pulmonary embolus, ball valve
thrombus) or as a result of pressure from outside that occludes the system (three Ts: tension
pneumothorax, pericardial tamponade and tense abdomen). A high level of positive end expiratory
pressure (exogenous or endogenous) is an additional cause among patients on mechanical
ventilation. Vascular failure or vasogenic/distributive shock: This type of shock occurs due to
abnormal vasodilatation of existing vessels or opening up of previously closed vascular channels
(shunts) that result in a sudden increase in vascular space without sufficient volume of fluid available
to fill this space (relative hypovolaemia). This is seen as a result of a massive release of cytokines and
vasoactive substances (sepsis, anaphylaxis) or a sudden decrease in the sympathetic outflow (shock
due to spinal anaesthesia or spinal injury). These forms of ‘pure’ shock are seldom observed; in
clinical situations, the picture is often mixed.1 Sepsis with volume depletion and myocardial
dysfunction presents a picture of hypovolaemia with vasogenic and cardiogenic components. The
same is true of a patient with acute pancreatitis or one with severe burns. A patient with an acute
coronary syndrome and pulmonary embolism is likely to present with features of cardiogenic and
obstructive shocks. This kind of mixed picture is often superimposed on a wide variety of clinical
manifestations and metabolic abnormalities related to the primary disease, such that in an individual
patient, objective assessment is complex. Physiological monitoring at the bedside is therefore
required, not only for diagnosis but also for ongoing management.4 Clinical Assessment A high index
of suspicion is needed to make an early diagnosis.5 Unfortunately, there is no single sign, symptom
or laboratory test that is diagnostic of shock. A constellation of surrogate clinical features suggestive
of ineffective tissue perfusion are useful but these are neither consistently observed nor are very
specific. Inadequate perfusion, which lies at the core of the problem, can be due to a global decrease
in perfusion due to a poor cardiac output (CO) or as a result of misdistribution of cardiac output
leading to poor organ perfusion even when CO is normal or high. Clinicians have to rely on a
combination of systemic features and organ-specific ones to make the diagnosis. Systemic Features
Fall in the blood pressure or hypotension: Mean arterial pressure (MAP) <60 mm Hg or systolic blood
pressure (SBP) <90 mm Hg or a drop in SBP by >40 mm Hg (important to recognise shock in patients
with preexisting hypertension).2 Low blood pressure is a late manifestation of hypoperfusion in all
circumstances other than impending cardiogenic shock, where it is an early marker.5 Metabolic
acidosis: In patients with poor tissue perfusion, metabolic acidosis on arterial blood gas (ABG)
analysis is detected due to an increase in lactic acid production and reduced clearance of lactate by
the liver. Elevated levels of lactate are also seen in a variety of other conditions including those
associated with focal ischaemia. Although measurement of lactic acid is a useful tool to assess the
severity, changes in lactate levels do not occur soon enough for it to serve as an early marker of
shock.5 Organ-Specific Features Poor skin perfusion is evidenced clinically by cold, clammy
extremities or slow capillary refill time. Depending on the content of haemoglobin or the relative
proportion of deoxygenated haemoglobin in blood, skin may either be pale or cyanosed.1 Contrary
to the classical picture, the skin may feel warm to touch in patients with septic shock. Oliguria
defined as urine output less than 0.5 mL/kg/h for two consecutive hours. Dysfunction of heart, brain
and lungs can manifest clinically as the cycle of poor oxygen and substrate delivery to the tissues
perpetuates further injury to these metabolically active organs. Conceptually, a stage of
‘compensated’ shock precedes the onset of hypotension, wherein homeostatic mechanisms of the
body attempt to restore the arterial pressure.3 Clinical features of shock at this stage are very subtle
but as the shock state progresses from stages of lesser to greater severity, clinical signs become
more obvious and the derangement of metabolic processes in the body moves from reversible to
irreversible. Therapy should ideally be initiated as soon as its shock is recognised, as any delay in
restoration of perfusion results in damage to cerebral, myocardial, renal and splanchnic tissues
which further aggravates the problem. Pathophysiology Maintenance of vital organ perfusion is
critical to survival.3,4 Organ perfusion is dependent on an appropriate perfusion pressure, which, in
turn, is determined by two variables, the CO and vascular resistance. Cardiac output is the product
of the stroke volume and the heart rate. Stroke volume is a function of the preload, myocardial
contractility and afterload. Vascular resistance or impedance is a concept that takes into account not
only the cross sectional area of arteriolar vessel wall but also the length of vessels and viscosity of
blood as important determinants. Changes in vascular resistance also affect the afterload and also
the preload, resulting in a complex series of interactions between the heart and the vasculature.
Physiological mechanisms exist at the tissue and cellular level to regulate the rate of blood flow over
a wide range of perfusion pressures. These are well developed in the brain, heart and the kidneys. As
a result, a minor drop in systemic blood pressure does not immediately affect vital organ blood flow
or metabolism. Blood Volume and Arterial Pressure Intravascular volume and arterial blood pressure
are regulated very closely by means of several interrelated mechanisms, and it is not within the
scope of this chapter to discuss all the physiological and homeostatic mechanisms involved. In
situations such as acute bleeding, sepsis and anaphylaxis, the body withstands up to a point,
absolute or relative changes in blood volume. Initially, the body responds by activating
neurohumoral compensatory mechanisms designed to counteract a drop in arterial pressure.
Baroreceptor-mediated responses produce peripheral adrenergic vasoconstriction that compensates
for a fall in the cardiac output and keeps arterial pressure near normal. At the same time, heart rate
rises to compensate for a fall in stroke volume. Stimulation of the renin–angiotensin system
augments the sympathetic response, although adrenal catecholamines and vasopressin have very
little direct involvement at this stage. Sympathetic vasoconstriction is accompanied by a complex
vascular redistribution that initially favours cerebral, coronary and renal circulation and later only
the cerebral and coronary vascular beds. Vasoconstriction affects mainly the muscular, cutaneous
and splanchnic tissue beds. If a critical level of hypovolaemia is reached (loss of blood volume of
>20–30%) and remains untreated, a second phase of physiological responses is seen. There is a
significant drop in the blood pressure associated with relative bradycardia due to a central inhibition
of sympathetic activation seen in the first phase. During this hypotensive phase, medulloadrenal
secretion of adrenaline becomes significant and the renin–angiotensin–aldosterone system becomes
active along with a release of vasopressin from the neurohypophysis. Release of ACTH, elevated
levels of cortisol and thirst mechanisms of the body also play a role in this phase of hypovolaemia.
Major fluid shifts occur during hypovolaemic shock as the body attempts to restore plasma volume.
Once again, under the influence of the sympathetic system that constricts the precapillary resistance
vessels, the capillary hydrostatic pressure decreases and favours movement of interstitial fluid into
the vascular compartment. The sympathetic and renin–angiotensin–aldosterone system work
conjointly to reabsorb salt and water from the renal tubules in an attempt to restore blood volume.
Although initially beneficial, these adaptive measures eventually become harmful. Increased heart
rate and contractility increase myocardial oxygen demand, which in the context of overall decreased
perfusion causes or worsens ischaemia. The hypercatabolic state induced by sympathetic activation
makes tissues more vulnerable to changes brought about by a decrease in regional blood flow.
Uneven peripheral vasoconstriction can and does result in maldistributive flow and tissue
hypoxaemia. Compensatory mechanisms fail when losses amount to >20% of blood volume or
sometimes earlier in patients in whom the physiological reserve is poor (e.g. those with chronic
illnesses). Cardiac Output and Flow Pathogenetic mechanisms leading to cell death and apoptosis in
shock-like states are incompletely understood. One of the common denominators of the first three
types of shock (listed above) is a low cardiac output state. Patients with hypovolaemic, cardiogenic
or obstructive shock develop a severe decrease in cardiac output and a consequent decline in
perfusion of vital organs. Although compensatory mechanisms maintain the arterial pressure, this
may be, even in the early stages of shock, at the cost of cardiac output or regional blood flow.
Increased vascular resistance can maintain blood pressure for a while but it diminishes stroke
volume by affecting afterload. This reduces myocardial perfusion and in patients with cardiac
ischaemia exacerbates the injury and leads to a downward spiral into cardiogenic shock. If shock
continues, end-organ damage occurs precipitating acute respiratory distress syndrome, acute renal
failure, disseminated intravascular coagulation, multiorgan failure and death. Inflammation and
microvascular endothelial damage are now considered important components in the
pathophysiology of shock.3 Depending upon the type and magnitude of the primary insult, the
presence of accompanying comorbidities and timing of initial effective resuscitation, a number of
changes can be triggered in the microcirculation. Endothelial cells increase their production of
inducible nitric oxide in a number of vascular beds resulting in pathological shunting of blood.
Endothelial cells also express various adhesion molecules (selectin family), lose their anionic charge
and become leaky. Activated leucocytes release cytokines and reactive oxygen species, which further
disrupt microvascular structures and cellular components. Vascular-smooth muscle cells lose their
sensitivity to respond appropriately to adrenergic stimuli. There is thus stasis of blood in capillary
beds in the presence of an activation of tissue-factor-mediated procoagulant state, which results in
microvascular thrombosis and fibrin deposition. Individual capillary beds become functionally
occluded by either cellular aggregates, inadequate perfusion pressures or intense vasoconstriction.
Heterogeneous flow abnormalities in capillary beds cause vulnerable vascular beds to become
hypoxic such that local tissue oxygen tension falls below the capillary oxygen tension. This is
particularly pronounced at the venous end of capillaries where the diffusion distance for oxygen
between adjacent capillaries becomes excessive. Although these changes in vasculature are most
pronounced in patients with septic shock, they are also seen in patients with severe hypovolaemic or
cardiogenic shock. Although the precise origin of tissue dysoxia in sepsis is not clear, it may be a
combination of flow abnormalities at the venous end of capillaries and an instability of intracellular
pathways. Under normal conditions, ATP production by mitochondrial oxidative phosphorylation
accounts for >90% of total oxygen consumption by the body. Brearley et al.6 has shown nitric oxide
overproduction, glutathione depletion, mitochondrial dysfunction and decreased ATP
concentrations in muscle biopsies from septic patients suggesting a primary failure of biological fuel
production. Of note is the fact that even upon reversal of apparent signs of hypoperfusion, cellular
dysfunction may persist.5 This phenomenon is known as reperfusion injury and several mechanisms
have been proposed to explain its pathogenesis.7 Delays of up to 2 hours in appropriate
resuscitation of volume losses greater than 30% may not effectively correct cellular dysoxia. Despite
replacement of fluid losses, patients may develop a systemic inflammatory response syndrome and
then progress onto multiorgan failure. This reperfusion injury is thought to be mediated by toxic
metabolites and free oxygen radicals, although direct proof of their involvement in its pathogenesis
is still lacking. Oxygen Metabolism In health, oxygen is delivered in excess of tissue needs and
systemic O2 uptake is independent of delivery. When O2 delivery falls, tissue oxygenation is
maintained by increasing extraction. However, the ability to increase extraction is more efficient in
some organs (e.g. intestine, kidney) compared to some of the ‘vital’ organs (e.g. heart, brain). Thus
when O2 delivery falls because of decreased CO, blood pressure, flow or decreased oxygen-carrying
capacity, blood is redirected from non-vital to vital organs to maintain tissue oxygenation. However,
if O2 delivery continues to fall, the ability to compensate by redistributing blood flow in this way is
eventually exhausted. Tissue O2 uptake then becomes dependent on O2 supply, a point known as
the ‘critical’ O2 delivery point (Fig. 11.1). Following this dependency on adequacy of O2 supply, even
if it affects a select few organs, cellular ischaemia commonly occurs. If uncorrected, multiorgan
failure and death inevitably ensue. As a result of decreased tissue perfusion and inadequate tissue
oxygen delivery, cellular mechanisms of oxidative metabolism are deranged. Lactic acidosis (see
Chapter 8) is a marker of anaerobic metabolism. The extent of lactate elevation and associated
metabolic acidosis is closely correlated with both the degree of hypoperfusion and subsequent
mortality in patients with shock. Regional disturbances in perfusion are indicated by decreased
gastric intramucosal pH (pHi) (see later) or hepatic venous oxygen desaturation. Fig. 11.1
Relationship between oxygen consumption (VO2) and supply (DO2) under physiological (solid line)
and pathological conditions (dashed line). Principles of Management Shock is a clinical emergency.
Optimal management requires a balance between the need to institute therapy rapidly and the need
to complete a clinical assessment required to understand the cause.1,4 Often, both diagnostic and
therapeutic manoeuvres are performed simultaneously. A rapid assessment is quickly followed by
simple interventions aimed at supporting primarily the cardiovascular system. The immediate goal
involves interruption of ongoing insults, avoidance of further injury and identification of the shock
state.5 To achieve this effectively, the impact of each intervention is assessed and data obtained
thus, is used immediately to guide further therapy or revise strategy. This invariably requires
continuous and frequently, invasive monitoring, best provided in the intensive care unit (ICU) with
involvement of a multidisciplinary team led by an intensivist. Recognition of Shock The first step for
successful management of a shock state is early recognition.5 No single sign, symptom or laboratory
test is diagnostic of shock. Hypotension is, in fact, a late marker of hypoperfusion; in hypovolaemic
states, almost 20–30% of circulating volume is lost before hypotension sets in. Therefore, shock
should ideally be recognised before hypotension develops. For this reason, the clinician should be
alert to a group of non-specific signs, which when taken together in the appropriate clinical context
allows for an early diagnosis even in the absence of hypotension. Narrow pulse pressure, elevation
of diastolic pressure, tachycardia, cold clammy extremities and mottled skin are features of
catecholamine excess in response to a low blood volume or CO. Altered mentation, oliguria and
changes in respiratory function are suggestive of hypoperfusion of vital organs even in the presence
of seemingly normal blood pressure values. Metabolic acidosis and elevated lactate values are
surrogate markers of tissue hypoxia that have been used to identify patients with progressive
circulatory dysfunction and shock. Unfortunately, lactic acid changes do not occur soon enough to
serve as an early marker of shock. Prompt Resuscitation The first step in managing shock is to obtain
an intravenous access and start fluid administration unless the patient is already in pulmonary
oedema. Fluid resuscitation is best done through a large bore (16G) peripheral venous cannula.
Patients with polytrauma or those with suspected ongoing fluid or blood loss, at least two such
cannulas should be placed without any delay. Blood volume is a critical factor in maintaining
haemodynamic equilibrium and tissue perfusion and this consideration alone forms the basis of
‘Fluid First’ strategy for the management of almost all patients with hypotension and shock
irrespective of aetiology.1,2 Although fluid resuscitation should start without delay, patency of
airway and adequacy of oxygenation and ventilation are also an immediate concern. More often
than not, patients with shock require ventilatory support, either because of insufficient reserve to
compensate for severe metabolic acidosis or because hypoperfusion leads to obtundation and
inability to protect the airway. In shock, there is also an increase in oxygen consumption by
respiratory muscles working hard to keep up with increased demand. As a result, the percentage of
CO delivered to respiratory muscles increases from 2% during regular breathing to 20% in situations
of respiratory distress.5 With increased work of breathing, respiratory muscles also produce lactic
acid, which aggravates the existing metabolic acidosis and has the potential to create a vicious cycle.
If this cycle continues, a breakpoint is reached at which, lactic acid produced by respiratory muscles
either creates a demand upon itself to work even more vigorously or simply give up in muscular
fatigue. Positive pressure ventilation, if instituted under these circumstances, does impact adversely
on the stability of an already compromised circulation by further aggravating hypotension and
impairing ventricular filling. Therefore, starting fluids first makes sense for patients in shock rather
than following the well-established airway, breathing and circulation protocol for resuscitation.
Haemodynamic Monitoring Patients in shock require physiological monitoring in an ICU where
continuous assessment of the arterial pressure, urine output and respiratory rate is done routinely
and carefully. Once initial resuscitation has started, further enquiry into the underlying cause is
necessary to recognise the patterns of shock. At the simplest level, this involves an assessment of
volume status, traditionally provided by measurement of the central venous pressure (CVP). Studies
have shown that neither physical examination nor CVP monitoring is reliable in determining volume
status,5 and therefore, much of the traditional approach to shock built around this concept is faulty.
Occult fluid losses due to third spacing are frequently underestimated and peripheral oedema is
often mistaken as a sign of volume overload. Central venous pressure is a measure of ventricular
preload and that too of the right ventricle for which there is no optimum value but rather a range of
values that are appropriate for specific clinical situations. A well-placed, flow-directed pulmonary
artery (PA) catheter enables the acquisition of three types of data—pulmonary artery occlusion
pressure (PAOP), CO using thermodilution method and venous oxygen saturations (SvO2). These
three parameters allow for monitoring of preload, blood flow and tissue perfusion and thus place PA
catheter in a unique position to guide therapy in patients with shock.8 However, the utility of PA
catheter has been under scrutiny for sometime. A case–control study by Connors et al.9 first
demonstrated the use of PA catheter to be associated with increased resource utilisation and
mortality. A series of randomised trials performed ever since have reported on the role of PA
catheter in non-cardiac surgery, congestive heart failure, sepsis, ALI/ARDS and in a general ICU
patient.10–12 In the perioperative management, use of PA catheter did not influence mortality and
was associated with a greater incidence of pulmonary embolism. In critically ill patients with
congestive cardiac failure, management directed by the PA catheter did not affect mortality but
resulted in an increase in adverse events. A large trial evaluating the role of PA catheter in ALI/ARDS
secondary to sepsis also found no significant differences in mortality whether or not a PA catheter
was used. A well-designed randomised trial of general ICU patients13 similarly concluded by
demonstrating no evidence of benefit with the use of PA catheter. Despite these data, no studies
have specifically evaluated the role of PA catheters in patients with shock. Measures of Preload
Commonly used haemodynamic parameters, such as CVP or PAOP, are actually surrogate measures
of ventricular preload. In patients with lung disease, valvular pathology or ventricular dysfunction,
these values are often erroneous. In patients with shock, a change in CVP or PAOP bears little, if any,
correlation with stroke volume. Since the idea of measuring preload is to optimise CO, a dynamic
assessment of response to changes in preload is more useful than a static evaluation alone. Preload
is the wall tension in the ventricular wall at the end of diastole that represents the final stretch of
myocardium prior to the onset of ventricular systole. Myocardial fibre length at the end of diastole
determines the forcefulness of ventricular contraction—a non-linear relationship described in the
Frank–Starling curve. On the ascending limb of the Frank–Starling curve, increasing preload results in
an increase in CO. On the other hand, fluid loading on the plateau phase of the curve causes
pulmonary oedema or right ventricular dysfunction with no improvement in output. The concept of
fluid (or preload) responsiveness is built upon these fundamentals of physiology. There are static
and dynamic parameters that are valuable in predicting fluid responsiveness. Estimates of global end
diastolic volume (GEDV) obtained by transpulmonary thermodilution method (PiCCO® monitor) have
been shown to predict fluid responsiveness. Such static parameters are more useful when their
values are either high or low; they are less helpful when values are in the intermediate range.14
Dynamic parameters such as variations in arterial pulse pressure (pulse pressure variation [PPV]) or
left ventricular stroke volume (stroke volume variation [SVV]) induced by positive pressure
ventilation are more sensitive and specific markers of preload responsiveness. Greater the variation
in pressure or flow during a respiratory cycle, the more likely it is that the subject will respond
favourably to volume challenge. A PPV cut-off of >13% has been validated in septic patients as
indicative of fluid responsiveness.15 More recently, methods of predicting fluid responsiveness in
spontaneously breathing patients have been reported.16 Passive leg raising (PLR) has been shown to
predict response to a fluid challenge in critically ill patients by effecting an increase in venous return
to the heart. When both lower limbs are lifted in a straight line to an angle of 45o for 4 minutes,
stroke volume increases along with an increase in arterial pulse pressure.2 However, changes in
pulse pressure induced by leg raising show only a modest degree of specificity in predicting fluid
responsiveness.16 Demonstrating preload responsiveness means that giving fluids is an option, but
this information must always be interpreted in the context of other clinical features and disease
processes. False negatives occur in patients whose left ventricle is preload dependent but the right
ventricle (LV) is not. Although false positives are rare, it is worth remembering that normal
individuals with healthy hearts invariably demonstrate fluid responsiveness. Measures of Cardiac
Output Pulse contour analysis: This is based on the concept that the contour of arterial pressure
waveform is proportional to stroke volume. According to Wesseling’s formula, stroke volume is
directly proportional to the area of the aortic systolic pressure wave (As) and inversely proportional
to the vascular impedance (Z). Thus, Beat-to-beat stroke volume is calculated on the basis of an
algorithm in the PiCCO® and LiDCO® systems, each of which uses a different technique for
calibration of CO measurement. Calculations of stroke volume from the arterial pressure wave in the
Flotrac/Vigileo® system follow an algorithm, which evaluates the systolic and diastolic pressures
over time and estimates the standard deviation (SD) of the arterial pressure over a 20-seconds
window. Software then takes into account two additional factors: large vessel compliance and real
time change in peripheral resistance to compute a constant (K) which when multiplied by SD yields
an estimate of stroke volume.17 Oesophageal Doppler is a flexible ultrasound probe about the size
of a nasogastric tube that can obtain continuous CO by measuring blood flow velocity in the
descending thoracic aorta. Stroke volume is calculated as the product of mean velocity and cross-
sectional area of the thoracic aorta, which is estimated from a nomogram based on the patient’s
age, gender and height. An advantage of using Doppler is easy probe placement but a significant
disadvantage is maintaining its position over repeated measurements. Echocardiogram is
increasingly used to assess critically ill patients and is considered by many as the technique of choice
in haemodynamically unstable patients. By measuring the left ventricular outflow tract (LVOT)
diameter (d) and time velocity integral (TVI) from the Doppler signal, CO can be computed. Thus,
There is agreement over a wide range of values when CO estimates are referenced to measurement
by thermodilution. In the hands of an experienced operator, echocardiogram assumes an important
role in the non-invasive evaluation of a patient in shock. Transthoracic echocardiogram (TTE)
facilitates prompt definitive diagnosis of major cardiac disorders that are surgically correctable
(tamponade, mechanical complications of myocardial infarction, valvular lesions). Transthoracic
echocardiogram also provides information on the contractile state of the myocardium and allows for
certain pressures to be estimated (e.g. PA pressure). Transoesophageal echocardiogram (TEE) is used
to confirm endocarditis or aortic dissection in patients where this is suspected. Measures of Global
Perfusion Blood lactate concentrations: The association of raised lactate levels with circulatory
failure and anaerobic metabolism has led its utility as a marker of tissue perfusion in shock. Raised
serum lactate levels indicate poor tissue perfusion; thus, measurement of arterial blood lactate gives
a surrogate measure of the adequacy of tissue oxygenation and has been used to ascertain the
therapeutic response to steps taken in the management of shock. Serial measurement of lactic acid
level is a useful tool to assess severity and follow adequacy of therapy. Such trends are a better
prognostic indicator than a single value because early lactate clearance is associated with improved
survival in septic shock.18 Venous oxygen saturations (ScvO2, SvO2) assess the relationship between
oxygen delivery and oxygen consumption. The amount of oxygen delivered to tissues for use in
aerobic metabolism is determined by three variables; haemoglobin, oxygen saturation of
haemoglobin and CO. Thus, Oxygen consumption (VO2) is the percentage of delivered oxygen the
tissues use for cellular function. Oxygen consumption increases with fever, shivering, stress, pain,
agitation, increased work of breathing and seizures. After the tissues extract oxygen from blood, the
remaining oxygenation of venous blood can be measured from the PA (mixed venous oxygen
saturation, SvO2) or from the central venous circulation (central venous oxygen saturation, ScvO2).
Under normal circumstances, the SaO2–SvO2 difference is 20–25% yielding a SvO2 of 65–70%. The
ScvO2 values are 5–15% higher than SvO2 values in shock. Global tissue hypoxia develops when
systemic oxygen delivery is inadequate to meet tissue needs. This results in a low venous O2
saturation. Rarely, in patients with advanced shock, tissues are unable to extract oxygen due to a
metabolic block, a condition in which venous saturations are higher. When used to guide early
therapy of septic shock, ScvO2 has been shown to be a good indicator of tissue oxygenation
compared to vital signs.19 Measures of Regional Perfusion Gastric tonometry is a method to assess
regional perfusion in the gut. The splanchnic bed has a counter current circulation at the mucosal
level, rendering it especially susceptible to ischaemia. Global oxygen assessment may underestimate
gut perfusion, which, if affected, may lead to endotoxin or bacterial translocation across the gut
mucosal barrier. Intramucosal CO2 is used to derive intramucosal pHi. A low value is associated with
poor outcome, though the utility of this measure in clinical practice is still somewhat unclear.
Sublingual capnography (PsICO2) is a less invasive technique of essentially the same parameter as
PiCO2. In Marik’s study,20 sublingual pCO2 correlated with gastric pCO2. Elevated levels of pCO2 in
the sublingual mucosa indicate tissue hypoxia. This is, in fact, the indirect result of buffering of
excess hydrogen ions produced during anaerobic metabolism by bicarbonate. Orthogonal
polarisation spectral imaging (OPSI) investigations directed towards the assessment of the
microcirculation have used this technique to visualise the sublingual circulation. DeBaker et al.21
have observed a reduction of approximately half in the density of small vessels in patients with
severe shock. Sakr et al.22 found that microcirculatory disturbances improved rapidly in survivors
but not in those dying of multiorgan failure regardless of whether conventional parameters of shock
had resolved or not. Identification of Shock State Traditional Approach Types of shock are recognised
by the pattern of haemodynamic abnormalities seen in a patient (Table 11.1). In hypovolaemic
shock, the CVP is low due to a lack of volume to fill the vascular system. This reduces cardiac
preload, hence the CO. A reflex increase in sympathetic output due to a low arterial pressure results
in high systemic vascular resistance. In cardiogenic shock, on the other hand, the primary problem is
a reduction in CO. A reflex increase in sympathetic output once again results in a high systemic
vascular resistance. The clinical features of both these type of shock overlap; a simple intervention
like a central line that allows for a measurement of the CVP is helpful. Obstructive shock has a
pattern similar to cardiogenic shock. In distributive shock, there is relative hypovolaemia due to an
increase in the vascular compartment space. Cardiac output is typically high in this group of patients
as the afterload is low; hence these patients have warm, well-perfused extremities, but tissue
perfusion is not effective as it is maldistributed.1,2 Table 11.1 Fundamental Physiological
Abnormalities in Shock Table 11.2 Haemodynamic Parameters in Different Types of Shock Table 11.3
Causes of Cardiogenic Shock LV—left ventricle. Modern Approach An approach based on
measurement of CO and myocardial contractility is probably more useful in differentiating causes of
haemodynamic instability compared to one centred upon an assessment of the CVP. The
relationship between CO, myocardial contractility and SvO2 in shock is shown in Table 11.2. Changes
in cardiac output are generally mirrored by changes in SvO2 except in septic shock, where SvO2 is
decreased in the presence of normal or high CO. In severe sepsis, myocardial contractility as
assessed by echocardiogram is diminished even though the CO is high or normal. Irrespective of the
approach followed, a differential diagnosis of conditions potentially responsible for the shock state
needs to be entertained. If a patient is identified to have cardiogenic shock, then all possible causes
of cardiogenic shock need to be considered (Table 11.3). On the other hand, if sepsis seems likely,
then a search for a septic focus needs to be undertaken. Management of Shock—General Measures
Essentially, the aim of therapy is to restore tissue perfusion and oxygen delivery as rapidly as
possible. In order to achieve this, certain physiological endpoints are targeted in the belief that these
are necessary to achieve better outcomes (Table 11.4). Restoration of blood pressure and
optimisation of blood flow are both important but conflicting goals of therapy. Defence of Volume
The main goal of fluid therapy is to increase the plasma volume to a level where the body’s own
mechanisms can correct and compensate for hypovolaemia. A second goal is to raise the ventricular
preload to the extent that it impacts positively on the cardiac output. Restoration of volume deficit is
essential to survival of patients with hypovolaemia due to conditions such as major trauma,
haemorrhage and burns injury but is equally important in patients with sepsis, anaphylaxis and
spinal shock. Despite the importance of fluid therapy, controversy still exists over the choice of
crystalloids or colloids as the ideal resuscitation fluid.23 Arguments in favour of the use of
crystalloids include the observations that isotonic crystalloids expand the extracellular compartment
more effectively with less increase in extravascular pulmonary water due to rapid equilibration.
Postresuscitation and postoperative organ function appear to be better preserved with the use of
crystalloids especially with respect to cardiac, pulmonary and renal function. Crystalloid use
minimises the risk of anaphylactoid reactions and abnormalities in coagulation that are occasionally
seen with colloid infusions. Colloid infusions, on the other hand, require less volume and time and
have been shown to restore blood volume more effectively and for a longer duration compared to
isotonic crystalloids. Colloids have been variably shown to improve oxygen transport, myocardial
contractility and CO and at the same time decrease capillary permeability. Colloids are more costly
even though the resuscitation volume is smaller. Isotonic crystalloids often require more time and
larger volumes for resuscitation, and this contributes to the development of peripheral oedema. In
general, an isotonic solution (Normal saline, Ringer’s lactate) increases plasma volume by about 200
mL for every 1000 mL given intravenously. The volume of distribution is more limited and
elimination significantly slower when hypovolaemia is present. Table 11.4 Physiological Goals of
Therapy in Patients with Shock CNS— central nervous system; CVP—central venous pressure; MAP—
mean arterial pressure; PAOP—pulmonary artery occlusion pressure Controversy persists with some
authors recommending colloids and others crystalloids, using arguments essentially based on
measurement of haemodynamic parameters. A recent clinical trial undertaken with the aim of
assessing the impact of resuscitation fluids on outcome has shown no mortality benefit with use of
crystalloids compared to albumin. A subgroup analysis, however, has ruled in favour of crystalloids in
patients with head injury and pointed to an advantage with the use of colloids in septic, non-trauma
patients. Crystalloids therefore remain the volume replacement solutions of first choice, unless
severe haemodynamic instability in a patient (e.g. trauma) necessitates the use of blood products. In
the emergency resuscitation of warm septic patients with leaky capillaries, several experts
recommend a balanced combination of crystalloids and colloids. Irrespective of the fluid chosen, a
fluid bolus (3–6 mL/kg body weight) should always be followed by an evaluation of response to the
fluid challenge. Where cardiac factors are clinically suspected to be important in the pathogenesis of
shock, a fluid challenge should be undertaken with utmost caution and should involve only small
boluses of 100–250 mL of fluid. In contrast, fluid challenges for patients with ongoing blood or
volume loss are typically more aggressive and involve volumes up to 500–1000 mL at each step.
Restoration of intravascular volume can be judged clinically by an improvement in the blood
pressure, peripheral tissue perfusion and mentation. Likewise, an increase in the CVP (by >3 cm)2 or
PAOP signifies an improvement of the intravascular volume. Excessive or overenthusiastic fluid
resuscitation may result in leakage of fluid into the extravascular or interstitial space of the lung and
should therefore be avoided. Such a scenario is not infrequently encountered among patients with a
poor cardiac reserve and among those suffering from a systemic illness (e.g. sepsis) with leaky
capillaries. Patients with an established renal failure also tolerate large fluid boluses poorly. Patients
successfully resuscitated after a period of hypotension may require additional volume, as
redistribution of fluid causes depletion of intravascular volume. Capillary leak (e.g. in lungs) and
organ oedema (e.g. brain) are an unwanted consequence of aggressive fluid therapy that poses a
major problem in patients even after satisfactory restoration of systemic blood pressure. For this
reason, some practitioners recommend the use of hypertonic solutions in the resuscitation of
unstable patients with a head injury. Although a combination of hypertonic saline and small doses of
colloids restores blood volume much faster, a recent randomised, controlled trial in patients with
severe brain injury showed no difference in neurological outcome between those who had initial
resuscitation with hypertonic saline (7.5% saline) compared to patients who received conventional
therapy (isotonic fluids). Augmentation of Cardiac Output Cardiac output is the major determinant
of tissue perfusion and is the product of stroke volume and heart rate. An increase in the heart rate
usually increases the CO, but this is often at the cost of diastolic filling time and increased myocardial
energy consumption. An increase in heart rate is an immediate physiological response to a fall in
blood pressure or CO. Although desirable in the initial stages, sustained tachycardia can limit CO and
can, over time, create an unhealthy balance of supply versus demand resulting in an altered state of
inotropy of the heart. This, in turn, compromises the stroke volume, which is the amount of blood
ejected by the ventricle with each cardiac contraction. Stroke volume is determined by ventricular
preload, inotropic state of the heart and the afterload. Each of these factors is in turn affected by a
multitude of physiological and pharmacological influences, the details of which can be studied best
from a physiology textbook. The reason to pay attention to CO is based on our current
understanding for the need to rapidly restore tissue oxygen delivery as a goal in the management of
patients with shock. To enhance oxygen delivery to tissues, red cell mass, arterial oxygen saturation
and CO may be augmented singly or simultaneously. However, in most instances, CO is often the
only variable that is amenable to therapeutic intervention. Augmentation of CO is therefore a
therapeutic goal applicable to all forms of shock and has a purpose that runs parallel to the first
objective of restoring circulating volume in the management of shock. Although somewhat
controversial, most intensivists believe that accurate prediction of haemodynamic profile of patients
in shock is poor without serial or continuous measurement of CO. Cardiac output can be measured
by a number of techniques, among which thermodilution technique using a flow-directed pulmonary
artery catheter (PA catheter) is still the most popular. A well-designed clinical trial13 has recently
reported an increase in mortality among patients monitored in the ICU with a thermodilution CO
catheter. Patients in this trial included those admitted with shock and other medical/surgical
conditions commonly found in the ICU. It is difficult, in the absence of other data, to conclude
whether a subset of patients (especially those with shock) could benefit from the deployment of a
PA catheter. Nevertheless, this and other trials have brought into sharp focus the indications for use
of a PA catheter and more significantly, the nature of decisions taken on the basis of information
obtained from this device.17 Restoration of Tissue Perfusion Although shock has a haemodynamic
component that has been the focus of much discussion in the pathophysiology of the clinical state,
the most critical change takes place at the level of the microcirculation. In essence, all forms of shock
can be considered as a form of microcirculatory failure. Adequacy of cardiac performance or even
augmentation of cardiac output does not guarantee that all organs are perfused appropriate to the
regional demand. Regional perfusion (Q) is determined by inflow pressure (Pi), outflow pressure (Po)
and regional conductance (C) and the relationship between these parameters is defined by the
equation Po is just not equal to the venous pressure but depends on the tissue pressure also. Blood
flow through a capillary bed often ceases well above venous pressure (30–40 mm Hg) if the tissue
pressure is high (e.g. oedema). The pressure at which regional flow ceases is the closing pressure for
the region and depends on venous pressure, tissue pressure and tone of smooth muscle of terminal
arterioles and precapillary sphincters. In addition, cellular rheology of blood also plays a role. In
organs such as brain and kidney, autoregulation of flow occurs—a drop in perfusion pressure is
compensated for by an increase in conductance by changes in the vascular smooth muscle tone.
However, below the level of vasodilator reserve, flow falls linearly with pressure whereas above the
level of vasoconstrictor response, flow rises linearly with pressure. The lower threshold is 65 mm Hg
(50–100 mm Hg) for the brain and kidney. Thus, the current recommendation for the goal of MAP in
the treatment of shock is to maintain MAP above 65 mm Hg. However, the curve can be shifted to
the left (lower closing pressure) or right (higher closing pressure) depending on neurohumoral
influences. In other words, circulating or exogenously administered catecholamines can induce
variability in regional flow to different organ systems or in some cases, in different vascular beds of
the same organ. Such heterogeneity of flow uncouples regional and local flow from systemic
measures of flow and substrate delivery such that microcirculatory disturbances are poorly reflected
in global measures of oxygen delivery and consumption. Although volume expansion reverses these
changes, the density of perfused capillary in a vascular bed is also affected by rheological changes in
blood that invariably accompany fluid therapy for shock. The importance of the microcirculation
relates to its vital role in delivering oxygen and nutrients to the mitochondria.24 An improperly
functioning microcirculation leads to progressive organ dysfunction as a consequence of deficient
oxygen supply. Late stages of all forms of shock are played out in the microcirculatory arena.
Multiple physiological and immunological pathways are simultaneously activated resulting in an
excessive production of chemotactic cytokines, increased expression of cellular adhesion molecules
on endothelial cells as well as activation of the coagulation cascade. All these disturbances result in
microvascular damage, capillary leak and further accentuation of the tissue injury. Some or all of
these factors play a role in the onset of multiorgan failure. Management of Shock—Vasoactive Drugs
Vasoactive drugs should be used only after adequate fluid resuscitation. The choice of a drug is
based not only on the pattern of physiological effects (Table 11.5) but also on the evidence derived
from randomised clinical trials showing improvement in patient outcome (and not just improvement
in physiological variables). Unfortunately, trials of clinical efficacy are not available; a recent
Cochrane review25 served to highlight the lack of good quality evidence in a field supported by
superb basic research. Clinical practice therefore continues to be dominated by anecdote, personal
preferences and excessive reliance on physiological data. Drugs commonly used for haemodynamic
support in the ICU are dopamine, dobutamine, adrenaline (epinephrine), noradrenaline
(norepinephrine), isoprenaline and phenylephrine. Adrenaline, noradrenaline and dopamine are
catecholamines that occur naturally in the human body. Dopamine is the precursor of noradrenaline
and noradrenaline is the precursor of adrenaline. All of them have a short biological half-life largely
due to reuptake into tissues and degradation by catechol-O-methyl transferase in liver and lung. A
steady-state plasma concentration is achieved in 5–10 minutes after the drug reaches circulation.
Adrenaline, noradrenaline and isoprenaline all have hydroxyl groups on the b-carbon atom of the
side chain that confers a 100-fold greater potency (weight for weight) compared to dopamine or
dobutamine. Table11.5 Commonly Used Vasoactive Agents aDose-dependent effect especially for
dopamine. bMean arterial pressure. The recommended dosages are only a guide, as in clinical
practice the infused dose must be titrated to a desired effect. Use of vasoactive agents should be
tailored to the clinical situation along with careful monitoring of the response as marked
interindividual variability can exist. All drugs that cause vasoconstriction must be infused into a
central vein to avoid tissue necrosis, if extravasation inadvertently occurs. The only exception is
dobutamine or low-dose dopamine (<5 µg/kg/min) that may be started peripherally to treat shock
while a central line is being inserted. Dopamine Dopamine increases MAP chiefly by increasing
cardiac output and systemic vascular resistance at dosages of 5–10 µg/kg/min. The increase in CO is
mainly due to an increase in stroke volume and to a lesser extent to an increase in heart rate. At
dosages less than 5 µg/kg/min, it stimulates DA1 receptors in renal, mesenteric and coronary
circulation. Despite affording renal vasodilatation at low dose (2–5 µg/kg/min), dopamine does not
offer renal protection in critically ill patients.26 β-1 effects dominate at 5–10 µg/kg/min and α-1
effects are seen above 10 µg/kg/min. Doses greater than 20 µg/kg/min should not be used in the
absence of full haemodynamic monitoring. Although recommended by experts and used worldwide
as the drug of choice in the management of shock, there is evidence from a recent observational
study27 that its use is associated with worse outcome. Noradrenaline Noradrenaline is potent α- and
α-agonists. Clinical studies show that noradrenaline markedly increases MAP and improves
glomerular filtration by increasing glomerular perfusion pressure. Noradrenaline has a greater effect
on the efferent arteriolar resistance than the afferent one in the glomerulus. In hypovolaemic states,
on the other hand, use of noradrenaline has deleterious effects on renal function. Noradrenaline
increases MAP due to an increase in systemic vascular resistance (vasoconstrictive α-1 effect) with
variable changes in CO (normal or increased). In hyperdynamic septic shock, it is considered the
agent of choice in view of its powerful α effect. Although the recommended dose of noradrenaline is
0.01–0.1 µg/kg/min, higher doses have been used in septic shock (5 µg/kg/min). This may be due to
α-1 receptor downregulation seen in sepsis. Adrenaline Adrenaline increases MAP by increasing CO.
It has β-1-, β-2-agonist effects and a-agonist effect at higher doses. At doses of 0.01 µg/kg/min, it
has a predominant β effect whereas at dosages of 0.2 µg/kg/min it has a- and β-effects. Its combined
inotropic, chronotropic and vasoconstrictive effect makes it the ideal drug for use during cardiac
arrest. It has, in addition, bronchodilatory effect due to its β-2 action and hence, it is the drug of
choice for anaphylactic shock. Adrenaline has been shown to have a detrimental effect on
myocardial oxygen consumption, splanchnic blood flow and intermediary metabolism, all of which
have restricted its use as a vasoactive agent in septic shock. Isoprenaline Isoprenaline is a synthetic
catecholamine having β-1 and β-2 effects (β-1 > β-2). It is a chronotropic drug and produces an
increase in cardiac output and heart rate. As a result, there is increased myocardial oxygen
consumption. There is either no significant change or a fall in MAP due to β-2-receptor-induced
vasodilation. It is mainly useful in maintaining the heart rate in patients with heart block prior to
pacemaker insertion (in situations where it is not immediately possible to do so). It is also useful in
situations where the myocardium is poorly contractile, the heart rate is slow and the peripheral
resistance is high (cardiac surgery in patients on β-blockers, patients with β-blocker overdose). In
these situations, the dose is 0.5–10 µg/min. It is hardly ever used as an inotrope in shock as it does
not increase the MAP and can potentially cause tachyarrhythmias. Dobutamine Dobutamine is a
synthetic derivative of isoprenaline with predominant β-1- and β-2-agonist effects (β-2 > β-1) and a
weak action. It increases CO by increasing stroke volume with less direct effect on heart rate. Its
peripheral weak a action is offset by β-2- mediated vasodilation, and this may cause a drop in
diastolic blood pressure and induce a reflex tachycardia. It does not cause an increase in MAP and
hence is not the drug of choice where the MAP is low. Dobutamine is ideally used for a patient who
has severely depressed LV function with a low CO and elevated LV filling pressure but in whom
significant hypotension (MAP less than 70 mm Hg) is not present. Dobutamine reduces both, the
afterload and preload, and also reduces pulmonary vascular resistance. However, in severe cardiac
failure, β-receptors may be down regulated, so that it may not be as effective as expected.
Prolonged therapy with dobutamine for more than 72 hours may also cause receptor downgrading
and development of tolerance. Phenylephrine Phenylephrine is a selective α-1-agonist and is
potentially useful in situations where severe vasodilation is the cause of shock, for example
anaesthetic- induced hypotension. In comparison to noradrenaline, it reduces splanchnic blood flow
in patients and is rarely used in septic shock. Vasopressin Vasopressin constricts vascular smooth
muscle via the V1 receptors and causes water retention through its action on the V2 receptors on
renal tubules. Vasopressin is a more powerful vasoconstrictor than angiotensin II or noradrenaline,
but its effect in physiological doses is counterbalanced by a baroreceptor-mediated reduction in CO.
In recent years, vasopressin levels in septic shock have been shown to be significantly suppressed.28
Further data have suggested that intravenous infusion of vasopressin into patients with septic shock
results in a profound pressor response. Investigators have also documented efficacy in other
vasodilatory states including postcardiotomy shock, brain dead patients with haemodynamic
instability and drug-induced vasodilatory states (e.g. milrinone, levosimendan, ACE inhibitor). Supra-
physiological doses (>50 times) are needed in patients for their vasoconstrictor effects that are seen
predominantly in the skin, skeletal muscle and pancreas with relative sparing of the coronary and
cerebral vessels. Vasopressin in doses of 0.01–0.04 units/min raises MAP even in the presence of
acidosis and increases glomerular filtration by selective vasoconstriction of the efferent arteriole. For
all these reasons, it is favoured as a pressor agent in septic shock. Vasopressin and noradrenaline
were recently compared in a large randomised trial of septic ICU patients who were receiving
vasoactive agents to maintain blood pressure.29 There was no significant difference in the 28-day
mortality of patients or a change in long-term mortality at 90 days. Because of limited experience
and relatively long half-life, vasopressin should be used only after haemodynamic stabilisation with
other agents has been attempted. In patients with vascular disease, even small doses can precipitate
myocardial ischaemia. At the upper end of dosing, patients may develop digital ischaemia.
Notwithstanding these drawbacks, published data suggest that vasopressin can be used safely up to
4–6 days, if necessary. Digoxin The two main actions of digoxin are to reduce ventricular rate in
those with rapid ventricular response to a supraventricular arrhythmia and to improve myocardial
contractility in those with systolic heart failure. It is contraindicated in atrial fibrillation associated
with Wolff–Parkinson–White syndrome and in conditions where an inotropic agent is
contraindicated (diastolic dysfunction, hypertrophic cardiomyopathy). Despite a long history of use
and recent data supporting its beneficial haemodynamic effect, digoxin is infrequently used in
circulatory shock owing to its narrow therapeutic index and long half-life. Beside, there are many
other inotropes that have a better-quality effect. For therapy in patients who have not received
digoxin earlier, the initial dose is 10–20 µg/kg, followed 4–6 hours later by another 3.5–7 µg/kg.
Maintenance dose is equal to the daily excretion of digoxin and is 3.5–7 µg/kg/d in patients with
normal renal function. In renal failure, the dose is generally halved. Milrinone Milrinone is a
bipyridine phosphodiesterase III inhibitor with both inotropic and vasodilatory properties. It is 20
times more powerful than its precursor molecule, amrinone. When given to acutely ill patients, its
inotropic and vasodilatory effects occur with only a modest increase in heart rate and myocardial
oxygen consumption. It also reduces pulmonary vascular resistance. Milrinone is used in the
management of patients with post-cardiopulmonary bypass myocardial dysfunction and those with
congestive heart failure or cardiogenic shock at a dose of 0.25–0.75 µg/kg/min for periods up to 48
hours. Levosimendan Levosimendan belongs to a new class of inotropes that enhance the force of
contraction of the myocardium without enhancing the influx of calcium into the cytosol. As a calcium
sensitiser, it improves the CO of patients with cardiogenic shock and has the potential to increase
myofilament responsiveness in patients with sepsis. Levosimendan increases myocardial contractility
in a dose-dependent fashion in patients with LV dysfunction. Several studies have shown a beneficial
effect of levosimendan on clinical signs in patients with acute heart failure.30 The efficacy of
levosimendan for this indication has been compared to another inodilator, dobutamine, in three
large-scale trials.30 Apart from short-term haemodynamic improvement, changes in long term (>6
months) have not been seen except in patients chronically treated with β-blockers. Management of
Shock—Specific Measures Hypovolaemic Shock As a general rule, the fluid chosen to treat
hypovolaemia should most closely match the fluid lost. When gross hypovolaemia is present,
insertion of large bore peripheral cannulae is more appropriate than an urgent central line. Even if
inserted, a central venous catheter is probably not suitable for rapid infusion of fluids. While
managing patients with hypovolaemic shock, it is important to search for and control ongoing losses.
Nowhere is the situation more imperative than in the management of bleeding trauma patients.
Obvious external bleeding should be controlled with local pressure or with tourniquets. When the
response to resuscitation suggests ongoing overt losses, complex investigations should be kept to a
minimum and every effort should be made to organise urgent damage control surgery.4 Although
aggressive volume resuscitation prior to bleeding control is detrimental, delayed resuscitation, on
the other hand, is equally dangerous and is associated with onset of multiorgan failure.5 Coagulation
disturbances often complicate resuscitative attempts in trauma patients and require a well thought-
out strategy for correction of coagulation factors in the midst of replacement of blood losses.
Cardiogenic Shock Unless there are contraindications, patients with cardiogenic shock and surgically
correctable lesions of heart valves and intraventricular septum should undergo urgent surgery.
Systemic blood flow can be improved in patients with acute valvular regurgitation by afterload
reduction and intra-aortic balloon pump (IABP), but surgical correction improves the overall chance
of survival.4 The definitive management of atrial myxoma or valve dysfunction is also surgery.
Balloon valvuloplasty is increasingly being attempted for cardiogenic shock due to a stenotic valve
lesion. Hypoperfusion in patients with hypertrophic cardiomyopathy is exacerbated by measures
used to treat cardiogenic shock (inotropes, afterload reduction). Plasma expansion and β blockade
reduce outflow tract obstruction and improve cardiac output. Pathophysiological considerations
favour interventions to restore flow to occluded arteries in patients with myocardial infarction who
present with cardiogenic shock. A key to understanding is to realise that large areas of non-
functional but viable myocardium can cause or contribute to the development of cardiogenic shock.
Obstructive Shock In cardiac tamponade, inadequate heart filling leads to decreased CO and rapid
onset of shock. Treatment involves drainage of the pericardial fluid. Septic Shock In septic shock, in
addition to initial volume resuscitation, early appropriate antibiotic therapy with source control is
paramount. A recent observational study has convincingly shown an inverse relationship between
the time lag to start of therapy and survival among a group of septic patients.31 In other words,
longer the gap between onset of sepsis and start of antibiotic therapy, greater is the mortality.
Institution of appropriate antimicrobial therapy is also associated with improved survival. Evidence
derived from observational studies indicates that antibiotic therapy effective against the likely
causative micro-organism results in better patient outcomes.32