Circulation Flashcards
issues with applied cardiac physiology at bedside
The preload-dependent nature of LV performance is central to the understanding of applied cardiac physiology. In fact, documenting that LVEDV is above some minimal value, despite cardiac output and stroke work both being depressed, is essential for the diagnosis of cardiac pump dysfunction. Similarly, demonstrating that LVEDV is reduced in the setting of haemodynamic instability presumes the diagnosis of inadequate circulating blood volume as the most likely cause of the haemodynamic instability, even though other aetiologies, such as tamponade, cor pulmonale, and restrictive cardiomyopathies can coexist and require different treatments.
However, knowing LVEDV does not predict if LV stroke volume will increase in response to volume loading. Since a fundamental aspect of haemodynamic monitoring is to predict which patients will be preload-responsive, meaning that their cardiac output will increase in response to a fluid challenge, this lack of concordance between right atrial pressure, pulmonary artery occlusion pressure (‘wedge’ pressure), and even ventricular volumes, and subsequent changes in cardiac output in response to volume challenge can be disquieting. Still, it is a reality.
there are three techniques of proven utility in defining preload responsiveness:
the classic volume challenge, noting the magnitude of (1) the arterial pulse pressure or (2) left ventricular stroke volume variation during fixed tidal volume positive pressure ventilation, and (3) noting the change in mean cardiac output in response to a passive leg raising manoeuvre. For either pulse pressure variation (PPV, the ratio of maximal minus minimal pulse pressure to mean pulse pressure over five or more breaths) or stroke volume variation (SVV, the ratio of maximal minus minimal stroke volume to mean stroke volume over five or more breaths) to reflect preload responsiveness, the tidal volume must be fixed during unassisted positive pressure breathing and the sequential R-R intervals must be constant (i.e. no arrhythmias). In patients who are breathing spontaneously, and those with arrhythmias, the mean increase in flow 20 s after a passive leg raising to 30° gives a similar predictive value. In all cases, having a PPV greater than 13% or a SVV or mean increase in flow of more than 10% accurately predicts preload responsiveness as validated by many independent studies. PPV can be measured from the arterial pressure waveform and SVV calculated using numerous devices that assess beat-to-beat stroke volume using the arterial pressure waveform.
effects of systemic vasopressors in hoptension
Vasopressor therapy can reverse systemic hypotension, but at a price: the only way that it can increase MAP is by reducing blood flow through vasoconstriction.
Importantly, cerebral and coronary vascular circuits have minimal α-adrenergic receptors so their beds will not constrict.
Regrettably, in hypovolaemic states vasopressor support may improve transiently both global blood flow and MAP, but at the expense of worsening local nonvital blood flow and hastening tissue ischaemia.
preload and MAP as measures of adquacy of cardiovascular function?
, neither LV preload nor MAP are sensitive or specific measures of adequacy of cardiovascular function. Although the best measure of circulatory sufficiency is the maintenance of normal bodily functions, this analysis is often difficult to assess accurately at the bedside during states of stress. Furthermore, since metabolic demand can vary widely, there is no value of cardiac output orDo2that ensures circulatory sufficiency.
rdinal sign of increased circulatory stress is ??
One cardinal sign of increased circulatory stress is an increased O2extraction ratio, which manifests itself as a decreasing mixed venous O2saturation (Svo2). However, even this concept is useful only in limited conditions. Muscular activity effectively extracts O2from the blood because of the set-up of the microcirculatory flow patterns and the large concentration of mitochondria in these tissues. Thus, normal vigorous muscular activity can be associated with a marked decrease inSvo2despite a normal circulatory system. Muscular activities, such as moving in bed or being turned, ‘fighting the ventilator’, and breathing spontaneously increase O2consumption. In the patient with an intact and functioning cardiopulmonary apparatus, this will translate into an increase in bothDo2and O2consumption and a decrease inSvo2. However, in the sedated and ventilated patient,Svo2is a very sensitive marker of circulatory stress. There is no level of cardiac output which is ‘normal’, but there areDo2thresholds below which normal metabolism can no longer occur. UsingSvo2as a sensitive but nonspecific marker of circulatory stress, values less than 70% connote circulatory stress, less than 60% identify significant metabolic limitation, and values less than 50% frank tissue ischaemia.
pathophysiology of shock
The heart, vascular integrity, vasomotor tone, and autonomiccontrol all interact to sustain circulatory sufficiency. Circulatory shock reflects a failure of this system and results in an inadequate perfusion of the tissues to meet their metabolic demand, which can lead to cellular dysfunction and death.
Four basic functional aetiologies of circulatory shock can be defined:
(1) hypovolaemic, due to inadequate venous return (haemorrhage, dehydration),
(2) cardiogenic, due to inadequate ventricular pump function (myocardial infarction),
(3) obstructive, due to vascular obliteration (pulmonary embolism or tamponade), and
(4) distributive, due to loss of vasoregulatory control (sepsis).
tissue hypoperfusion in shock?
Tissue hypoperfusion is common in all forms of shock, with the possible exception of hyperdynamic septic shock.
This results in tissue hypoxia and a switch from aerobic to anaerobic metabolism, inducing hyperlactacidaemia and metabolic acidosis. However, hyperlactacidaemia, per se, is not a marker of ongoing tissue hypoperfusion because lactate clearance is often delayed or impaired in shock states, and processes such as exercise (seizure activity) can induce hyperlactacidaemia without cardiovascular insufficiency. Sustained circulatory shock results in cellular damage, not from anaerobic metabolism alone, but also from an inability to sustain intermediary metabolism and enzyme production necessary to drive normal mitochondrial performance. Metabolic failure due to sustained tissue hypoxia may explain why preoptimization and early goal-directed therapy improve outcome, whereas aggressive resuscitation after injury is not effective at reducing mortality from a variety of insults.
Hypovolemic shock
Hypovolaemia is the cardiovascular state in which the effective circulating blood volume is inadequate to sustain a level of cardiac output necessary for normal function without supplemental sympathetic tone or postural changes to ensure adequate amounts of venous return. It is a relative process and can occur through absolute blood loss, as with haemorrhage and trauma, or fluid and electrolyte loss, as with massive diuresis, diarrhoea, vomiting, or evaporation from large burn surfaces. The normal reflex response to hypovolaemia is increased sympathetic tone, vasoconstriction, and tachycardia. Cardiac output is often sustained by these mechanisms such that heart rate is increased and stroke volume decreased, whereas blood flow distribution is diverted away from the skin, resting muscles, and gut. With tissue hypoperfusion, lactic acidosis develops as a marker of tissue anaerobic metabolism. Thus, hypovolaemia initiates as tachycardia, reduced arterial pulse pressure, and (often) hypertension with a near normal resting cardiac output, followed by signs of organ hypoperfusion (oliguria, confusion) as cardiac output decreases. Systemic hypotension is the final presentation of hypovolaemic shock and—if the clinician waits for this before acting—ischaemic tissue injury is almost always present.
cardiogenic shock
Cardiac pump dysfunction can be due to either LV or RV failure, or both. LV failure, as described above, is usually manifest by an increased LV end-diastolic pressure, left atrial pressure, and (by extension) pulmonary artery occlusion (‘wedge’) pressure, which must exist to sustain an adequate LV stroke volume. Tachycardia is universal in the patient who is not β-blocked.
The most common cause of isolated LV failure in the critically ill patient is acute myocardial infarction. Usually, LV stroke work is reduced and heart rate increased. In chronic heart failure both cardiac output and systemic vasomotor tone may be normal, whereas in acute LV failure states both may be reduced. These combined haemodynamic interactions lead Forrester and colleagues to use a pulmonary artery occlusion (‘wedge’) pressure of 18 mmHgand a cardiac index of 2.2 as the cut-off to define heart failure states following acute myocardial infarction. However, neither cardiac output nor systemic vascular resistance is a sensitive marker of LV failure until cardiogenic shock develops. Since pulmonary artery occlusion (‘wedge’) pressure is the back pressure to pulmonary blood flow, increases associated with LV failure may lead to pulmonary oedema and hypoxaemia, and secondary pulmonary hypertension may subsequently impair RV ejection, inducing biventricular failure, peripheral venous hypertension, and peripheral oedema formation, the so-called ‘backward failure’.
The normal adaptive response of the host to impaired LV contractile function is to increase sympathetic tone, induce tachycardia, activate the renin-angiotensin system, retain sodium by the kidneys, and thus increase the circulating blood volume. Fluid retention takes time, whereas acute impairments of LV contractility can occur over seconds in response to myocardial ischaemia. Thus, the haemodynamic profile of acute and chronic LV failure can be different. Acute LV failure is manifest by increased sympathetic tone (tachycardia, hypertension), impaired LV function (increased filling pressure and reduced stroke volume), with minimal RV effects (normal central venous pressure), and increased O2extraction manifest by a lowSvo2.
obstructive shock
Obstruction in this context means mechanical obstruction of blood flow or ventricular filling. The most common cause of obstructive shock is pulmonary embolism leading to acute RV failure, but isolated RV dysfunction can occur in the setting of an acute inferior wall myocardial infarction, also as a consequence of pulmonary vascular disease (chronic obstructive pulmonary disease, primary pulmonary hypertension). When RV dysfunction predominates and is induced by pulmonary parenchymal disease, it is referred to as cor pulmonale, which is associated with signs of backward failure, elevated RV volume and pressures, systemic venous hypertension, low cardiac output, as well as reduced renal and hepatic blood flow.
Neither pulmonary vascular resistance nor mean pulmonary artery pressure need be grossly elevated for RV failure to be present. Indeed, and importantly, if pulmonary arterial pressures are greater than 30 to 35 mmHg, then pulmonary hypertension is probably chronic in nature because acute elevations of pulmonary arterial pressures above this level are not consistent with life. Elevations in central venous pressure of more than 12 mmHg also reflect fluid retention, suggesting further that there is a state of compensated RV failure.
Cardiac tamponade can occur from either (1) ventricular dilation limiting biventricular filling due to pericardial volume limitation, (2) acute pericardial effusion due to either fluid (inflammation) or blood (haemorrhage), which needs not be great in quantity, and (3) hyperinflation, which can act like pericardial tamponade to limit biventricular filling. The first two aetiologies are rarely seen, whereas the third commonly occurs. The cardinal sign of tamponade is diastolic equalization of all pressures, central venous pressure, pulmonary arterial diastolic pressure, and pulmonary artery occlusion (‘wedge’) pressure. Since RV compliance is greater than LV compliance, early on in tamponade there may be selective reduction in RV filling.
Distributive shock
Loss of blood flow regulation occurs as the endstage of all forms of circulatory shock, but as the initial presenting process it is common in sepsis, neurogenic shock, and adrenal insufficiency. Sepsis is a systemic process characterized by activation of the intravascular inflammatory mediators and generalized endothelial injury, but it is not clear that tissue ischaemia is an early aspect of this process.
Acute septicaemia is associated with increased sympathetic activity (tachycardia, diaphoresis) and increased capillary leak with loss of intravascular volume. Before fluid resuscitation this combination of processes resembles simple hypovolaemia, with decreased cardiac output, normal to increased peripheral vasomotor tone, and very lowSvo2, reflecting systemic hypoperfusion.
LV function is often depressed, but only in parallel with depression of other organs, and this effect of sepsis is usually masked by the associated hypotension that maintains low LV afterload. However, most patients with such a clinical presentation receive initial volume expansion therapy such that the clinical picture of sepsis reflects a hyperdynamic state rather than hypovolaemia, which has been referred to as ‘warm shock’ in contrast to all other forms of shock. The haemodynamic profile of sepsis is one of increased cardiac index, normal pulmonary artery occlusion (‘wedge’) pressure, elevatedSvo2, and a low to normal arterial pressure, consistent with loss of peripheral vasomotor tone.
Acute spinal injury, spinal anaesthesia, general anaesthesia, and central nervous system catastrophe all induce a loss of sympathetic tone. The resulting hypotension is often not associated with compensatory tachycardia, hence systemic hypotension can be profound and precipitate cerebral vascular insufficiency and myocardial ischaemia. Since neurogenic shock reduces sympathetic tone, biventricular filling pressures, arterial pressure, and cardiac output all decrease. Treatment consists of reversing the primary process and supporting the circulation with infusion of an α-adrenergic agonist, such as phenylephrine, dopamine, or noradrenaline
Acute adrenal insufficiency can present with hyperpyrexia and circulatory collapse. This is more common than might be guessed, based on the epidemiology of adrenal cortical disease, because many patients are receiving chronic corticocosteroid therapy for the management of systemic and localized inflammatory states, such as asthma or rheumatoid arthritis, and in such cases the added stress of trauma, surgery, or infection can precipitate secondary adrenal insufficiency, as can the (unwise) discontinuation of long-termsteroid treatment. Presentation is with nausea and vomiting, diarrhoea, confusion, hypotension, and tachycardia. Cardiovascular collapse is similar to that seen in neurogenic shock, except that the vasculature is not as responsive to sympathomimetic support
noradrenaline
actions
Noradrenaline has significant activity at α and β1-adrenoreceptors, resulting in a positive vasoconstrictor and inotropic effect. Its β1activity makes it the α1-agonist of choice in the patient with hypotension and known LV dysfunction.
Its positive vasopressor effect may enhance renal perfusion and indices of renal function in haemodynamically stable patients, and this effect may also be seen at higher doses when noradrenaline is used as a vasopressor in those with sepsis.
Both observations are likely related to elevation of MAP, the input pressure for organ perfusion. Prior concerns regarding renovascular vasoconstriction have not been validated in clinical trials in which fluid resuscitation has also been performed, and adding low-dose dopamine infusion with the hope of preventing renal ischemia has not proven effective and should be avoided.
Indeed, adding dopamine to norepinephrine infusions only increases the rate of arrhythmias without additional vasopressor effect.
- Direct α1, α2, and β1 agonist. Limited β2 agonist.
- Redistributed, neuronal uptake and enzyme metabolism.
* Efficacy (maximal effect) greater than phenylephrine (α1 only).
* HR variable, reflex decrease
* Contractility increased
* Cardiac output variable
* Blood pressure increased
* SVR increased
* PVR increased
* Risk of reduced organ perfusion (e.g. renal, hepatic, splanchnic). - Clinical use:
- Low SVR conditions (sepsis, ‘vasoplegia’ following CPB).
- Increase in SVR desired as well as positive inotropy.
- Phenylephrine ineffective.
- Dose: 0.01–0.3 μg/kg/min.
adrenaline actions
Adrenaline is a very potent catecholamine sympathomimetic that has markedly increased β2-adrenoreceptor activity compared with its molecular substrate, noradrenaline.
Adrenaline has potent chronotropic, inotropic, β2-vasodilatory, and α1-vasoconstrictor properties.
Its net vasopressor effect is the end result of the balance between adrenaline-mediated β2and α1adrenoreceptor stimulation. At low doses this balance may result in no net pressor effect, with a fall in the diastolic blood pressure.
Adrenaline, like noradrenaline, is known to have potent renovascular and splanchnic vasoconstrictor properties. Clearance rates are variable and mediated by both the COMT and monoamine oxidase systems.
Adrenaline also potentially stimulates both a pro-inflammatory response and increased glycolysis resulting in increased pro-inflammatory cytokine and lactate levels which may confuse bedside management if such parameters are being used to guide resuscitation.
Epinephrine (adrenaline)
•Direct α1, α2, β1, and β2-agonist.
•Rapid metabolism and neuronal uptake:
•Heart rate increase
•Contractility increase
•SVR decrease low dose, increase high dose
•PVR decrease low dose, increase high dose
•Cardiac output usually increase, can decrease at high doses
•Blood pressure increase
•Efficacy (maximal effect) greater than dopamine and dobutamine, with less tachycardia.
•Clinical usage:
•Increases myocardial work and oxygen consumption. Can precipitate ischaemia.
•Causes tachycardia and arrhythmias.
•Acidosis and elevation of plasma glucose and lactate occur. Most frequently in patients with hypertrophied left ventricles.
•Agent of choice in anaphylaxis.
•Low dose infusion can be very effective in post-CPB bronchospasm.
•Dose: 0.01–0.2 μg/kg/min. Cardiac arrest: 0.5–1.0 mg (high dose no longer recommended).
•Combination of low dose with low dose enoximone/milrinone is very effective, with minimal adverse effects due to low doses of each agent.
dobutamine
inotrope
Dobutamine
Dobutamine is a synthetic analogue of dopamine. It is utilized by continuous infusion as a positive inotrope, with the improvement in cardiac output noted to potentially increase renal blood flow, creatinine clearance, and urine output.
As a β1-agonist it will increase myocardial oxygen consumption, although autoregulatory increases in coronary blood flow usually fully compensate in the absence of flow-limiting coronary artery disease. A noted problem with dobutamine is the development of tachyphylaxis with prolonged (as little as 72 h) infusions, suggested to be due to the down-regulation of β1-adrenoreceptors.
- Direct β1-agonist, limited β2 and α1 agonism.
- Positive inotropy, vasodilator, can increase heart rate.
- Plasma half-life 2 minutes. Partly redistributed, partly hepatic metabolism and conjugation.
* Contractility increase
* Heart rate increase
* Cardiac output increase
* Blood pressure variable, can increase
* SVR decrease
* PVR decrease - Clinical usage:
- ‘Inodilator’ properties increase cardiac output, while increase in myocardial oxygen requirement is offset by vasodilator properties. Myocardial oxygen consumption increases less than with other catecholamines.
- Tachycardia less at low doses than with dopamine.
- Tachycardia and arrhythmias can limit use, particularly at high doses.
- Tachycardia more than Epinephrine (adrenaline) to achieve same effect on CO.
- Afterload reduction can be useful in failing heart.
- Vasodilation means hypotension may occur.
- Vasodilation is non-selective – skeletal muscle can ‘steal’ from other vascular beds.
- Tachyphylaxis after 72 hours.
- Dose: 2.5–20 μg/kg/min.
