- Email: [email protected]
Haemodynamics and cardiovascular shock
BASIC SCIENCE
Haemodynamics and cardiovascular shock
of intravenous fluid to a shocked patient is best achieved under pressure and through a short, wide cannula.
Hannah Bawdon
(where P ¼ pressure gradient across the length of the tube, r ¼ radius, h ¼ fluid viscosity and L ¼ tube length). Turbulent flow occurs in uneven tubes, with sharp angles or sudden changes in tube diameter. Laminar flow can also become turbulent at high fluid velocities. Flow is tumultuous, having eddy currents and a flat flow profile (Figure 1). Consequently, turbulent flow is less efficient and so requires a greater change in pressure or tube radius to achieve the same increase in fluid flow. Turbulent flow is proportional to radius2 and Opressure gradient, but inversely proportional to tube length and density of fluid. Reynolds’ number (Re) can be used to predict when fluid flow will become turbulent. This is a dimensionless number, calculated by Re ¼ v r d/h. (v ¼ velocity, r ¼ fluid density, d ¼ diameter of tube, h ¼ fluid viscosity). Re less than 2000 predicts laminar flow, whereas Re over 2000 is most commonly turbulent. Resistance is that which impairs fluid flow. For laminar flow, it is defined mathematically as:
Flow ¼ Pr 4 p=8hL
Michael Reay
Abstract Haemodynamics is the study of blood flow around the body. The factors influencing haemodynamics are complex and include cardiac output, circulating blood volume, vessel diameter, resistance and blood viscosity. These, in turn, are interlinked and affected by factors such as exercise, posture, disease, drugs and obesity. In this article we shall explore the physiology and control of blood flow and pressure in health, moving on then to look at what happens when control mechanisms break down, resulting in cardiovascular shock.
Keywords Flow; haemodynamics; pathophysiology; shock
Flow Flow is the amount of fluid moving past a point per unit time. In general, flow through a tube may be described as either laminar or turbulent. Laminar flow typically occurs in a smooth tube with constant diameter and no sharp bends. Flow is smooth, with fluid behaving like a series of concentric layers (laminae) that slide past each other. The flow profile is parabolic; velocity is greatest in the centre of the tube, and progressively reduces towards the periphery due to the effects of friction. The very outermost layer of fluid has a velocity approaching zero (Figure 1). Suspended particles (including blood cells) tend to gravitate towards the centre of flow, in a process known as ‘axial streaming’. When considering the factors which affect laminar flow, it is helpful to think of a bag of fluid attached via a giving set to an intravenous cannula. If you want to infuse fluid faster you might squeeze the bag; this increases the driving pressure gradient across the system, with a proportional increase in fluid flow. Use of a larger bore cannula or giving set will allow fluid to run faster, and in fact this effect is more significant because flow is proportional to radius,4 that is, doubling the radius will result in a 16-fold increase in fluid flow. Conversely, increasing the length of the tube or the viscosity of the fluid reduces the maximum flow rate possible. This is all summarized in the Hagene Poiseuille equation below, and is the reason why rapid infusion
Resistance ¼ pressure=flow Using the HagenePoiseuille equation above, we can see that increasing fluid viscosity or tube length increases flow resistance, whereas increasing tube diameter has the opposite effect (again, this is proportional to radius4). Blood flow and resistance Blood obeys the laws outlined above, with flow being a mixture of laminar and turbulent in different parts of the body. A third type, bolus flow, occurs at capillary level. Laminar blood flow: as previously stated, this is most efficient and occurs throughout the body. There is minimal friction between layers which glide past each other smoothly. Axial streaming of blood cells to the centre of flow creates a marginal plasma layer next to the vessel wall; this further reduces friction which is of particular relevance in small vessels. Turbulent blood flow: large diameter vessels with high velocity flow and low viscosity blood (e.g. in anaemia) encourage turbulence. Stenoses and points where vessels branch are also significant, as they create friction and take energy away from the system.
Hannah Bawdon BDS MFDSRCS(Eng) MB BCh FRCA is a Specialty Trainee (ST3) in Anaesthetics at University Hospital Birmingham, Birmingham, UK. Conflicts of interest: none declared.
Bolus flow: red blood cells are larger than the cross-sectional diameter of some capillaries. They therefore need to deform to pass through, and do this in boluses, with pockets of plasma between cells (Figure 1). Friction between red blood cells and the endothelium increase resistance to flow in these vessels, although gaseous exchange between plasma and the tissues is improved.1
Michael Reay MBBS FRCA FFICM is a Consultant in Anaesthesia and Intensive Care at Russells Hall Hospital, Dudley, West Midlands, UK. Conflict of interests: none declared.
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such as noradrenaline and vasopressin, and stimulation of a1-adrenergic receptors cause vasoconstriction, whereas stimulation of b2-adrenergic receptors result in vasodilation. Increased intravascular pressure is thought to be accompanied by contraction of muscle in the vessel wall, reducing diameter and therefore flow; this is the myogenic theory of autoregulation.
Laminar, turbulent & bolus flow
Laminar flow
Control of heart rate The sinoatrial (SA) node generates an intrinsic rate of approximately 110 beats/minute (bpm). Further control is a balance between the activities of the parasympathetic nervous systemvagal tone slows the SA and atrioventricular (AV) nodes, and sympathetic cardioaccelerator fibres, which arise from the sympathetic chain at levels T1-T5, speeding up SA node automaticity and AV nodal transmission.
Turbulent flow
BOLUS FLOW Pockets off plasma
Control of stroke volume The volume of blood (in ml) ejected from the left ventricle with each contraction is determined by the preload, afterload, cardiac contractility and ventricular function.
RBC RBCs
Figure 1
Preload: the preload is the end-diastolic ventricular wall tension. Wall tension determines the initial length of the cardiac muscle fibre before contraction begins, and is the prime determinant of contractile force. This relationship is illustrated by Starling’s law (Figure 2). As neither variable are easy to measure, wall tension is commonly substituted by left ventricular end-diastolic volume (LVEDV, as increased volume is associated with increased wall tension), and contractility by stroke volume. Note that even the normal heart reaches an LVEDV at which it cannot increase stroke volume any further without an increase in sympathetic tone. At higher volumes, the curve for the failing heart starts to slope downwards; this represents excessive muscle fibre stretch such that contractile filaments barely overlap and can no longer initiate effective contractions. Clinically, preload is often estimated by central venous pressure (CVP) for the right ventricle, and pulmonary artery occlusion pressure (PAOP) for the left
Resistance to whole body blood flow is predominantly at the level of the small arteries and arterioles; these are known as the ‘resistance vessels’. Circulatory pressures therefore drop significantly at arteriolar level. Resistance is low in the venous circulation, a state necessary to maintain cardiac output at lower venous pressures. For any organ, flow ¼ perfusion pressure/resistance. Perfusion pressure is defined as mean arterial e venous pressure, but also depends on local pressures within the capillary circulation. Blood flow to an organ can be improved, either by increasing the perfusion pressure or reducing resistance in local arterioles.
Control of cardiac output and blood pressure Total flow across the circulation (i.e. cardiac output) depends on the peripheral resistance. Assuming laminar flow: Total Peripheral Resistance TPR
The Frank-Starling law
Mean Arterial Pressure ðMAPÞCentral Venous Pressure ðCVPÞ ¼ Cardiac Output ðCOÞ
Starling law During exercise
In health, CVP is usually discounted as its contribution is minimal. The equation can therefore be rearranged to give us: Stroke volume
Increased contractility
MAP ¼ CO TPR Cardiac output is equal to heart rate stroke volume. Thus, mean arterial pressure is affected by anything which alters peripheral resistance, heart rate or stroke volume.
Heart failure
Cardiogenic shock
Control of peripheral resistance As already stated, small arteries and arterioles form the ‘resistance vessels’. Minimal changes across the group effect large changes in overall resistance. Key influences include locally produced substances, which predominantly cause vasodilation, for example CO2, Hþ, lactic acid, histamine (think of substances produced during exercise or anaphylaxis). Circulating hormones
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Normal Decreased contractility
Left ventricular end-diastolic volume
Figure 2
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ventricle. The failing heart might be seen as a worsening stroke volume/cardiac output in response to a fluid challenge.
Cardiopulmonary receptors: receptors located at the junctions of large veins and the atria convey information about circulating blood volume, again via the vagus nerves. One example of their action is the Bainbridge reflex, in which a rapid increase in atrial pressure triggers a reflex tachycardia; its full significance is unknown, although it is thought to contribute to respiratory sinus arrhythmia.
Afterload is the cardiac muscle fibre tension generated in systole before fibre shortening occurs. It is the ‘load’ which the ventricle must overcome before it can eject a stroke volume. Whilst not truly analogous, it is often taken to be systemic vascular resistance, as the two are closely linked. Afterload is also increased by outflow obstruction, for example aortic stenosis, and greater LVEDV, as increased muscle fibre tension needs to be generated to produce an adequate contractile pressure. Laplace’s law describes this relationship for a sphere (an approximation of ventricular cardiac muscle), as follows:
Chemoreceptors: peripheral chemoreceptors respond to the hypoxia and acidosis associated with tissue hypoperfusion. They stimulate a sympathetic outflow which vasoconstricts peripheral and splanchnic vessels, aiming to raise the blood pressure and maintain perfusion of vital organs.
P ¼ 2T=R
Cushing’s reflex: this is a response to brainstem hypoxia secondary to raised intracranial pressure. A massive sympathetic outflow endeavours to restore cerebral perfusion, resulting in generalized vasoconstriction, hypertension and a reflex bradycardia.
(where P ¼ pressure generated across the wall, T ¼ tension in the wall, and R ¼ radius of the sphere). The effect of increased afterload is a reduction in stroke volume, but increase in myocardial work (and therefore oxygen demand), which is clearly bad for a struggling heart. Afterload may be reduced by using vasodilator drugs.
Shock Shock is a state characterized by insufficient tissue perfusion to meet the metabolic demands of the body. It is a physiological derangement rather than a diagnosis. A number of different pathophysiological processes can all result in a similar clinical picture of refractory hypotension, tissue hypoxia and acidosis; these are discussed below, and also in ‘Management of the circulation on ICU’ on pp 543e551 of this issue. Whatever the cause, compensatory mechanisms initially act to preserve a degree of organ perfusion. When these mechanisms fail, tissues rapidly become critically starved of oxygen and nutrients, and toxic metabolites build up. This results in organ dysfunction which, if allowed to progress unchecked, leads to a spiralling decline of irreversible multi-organ failure and subsequent death. It is therefore essential that shock is identified and treated promptly. Again, whatever the cause of shock, initial treatment has the same aim e to restore tissue oxygenation and perfusion. This is best achieved with a generic ABC approach, together with treatments specific to the cause identified.
Contractility is a measure of the intrinsic ability of cardiac muscle to do work (contract). It is interpreted in the context of a given preload and afterload, i.e. increased force of contraction achieved with the same degree of cardiac filling and systemic vascular resistance. Myocardial contraction is due to interaction between intracellular actin and myosin, in a process requiring calcium. Increased contractility (called ‘positive inotropy’) increases the force and rate of contraction (via mechanisms which increase intracellular calcium), together with the stroke volume. Of course, nothing is quite that straightforward; increasing the rate of contraction beyond a certain point ultimately compromises diastolic ventricular filling and therefore LVEDV, which tends to decrease stroke volume. The effect of changes in contractility is demonstrated on the Starling curve in Figure 2. Ventricular function: normal myocardium contracts in a coordinated, concentric fashion. Damaged tissue manifests as areas of akinetic or dyskinetic muscle, with associated reduction in contractile efficiency.
Oxygen delivery This refers to the amount of oxygen delivered to the tissues per unit time. It is calculated by:
Reflex control of haemodynamics A number of reflexes exist to maintain cardiovascular parameters within limits required for organ perfusion, preventing wide fluctuations. Receptors (discussed below) transmit impulses via the vagus or glossopharyngeal nerves, synapsing in the nucleus tractus solitarius of the brainstem. From here, impulses project to areas including other regions of the brainstem, the cortex, and hypothalamus. The efferent arc of these reflexes is via the parasympathetic and sympathetic systems.
Oxygen delivery ðDO2 Þ ¼ cardiac output arterial oxygen content And is therefore dependent on both pulmonary oxygenation and all the factors affecting cardiac output that are outlined above. Arterial oxygen content is primarily determined by the amount of haemoglobin and its oxygen binding capacity. Dissolved oxygen usually contributes very little. This is summarized in the equation below:
Baroreceptors: these stretch receptors are located in the walls of the carotid sinus and aortic arch, and fire in response to vessel distension, particularly when the rate of pressure rise is rapid. The afferent limb of the reflex is via glossopharyngeal and vagus nerves. Baroreceptors are only useful for short-term blood pressure control, as more prolonged hypertension rapidly resets their firing threshold.
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Oxygen content ðml=dl bloodÞ ¼ ðHb SaO2 1:34Þ þ ðPaO2 0:0225Þ (SaO2 ¼ oxygen saturation of arterial blood, PaO2 ¼ partial pressure of oxygen in arterial blood, in kPa).
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These equations underline the importance of a systematic approach to resuscitation of the shocked patient. Oxygen delivery to the tissues may need to be treated by means of respiratory care (to improve oxygenation in the lungs), cardiovascular support (to improve cardiac output and blood pressure) and potentially also blood transfusion (to improve the oxygen carrying capacity of blood in an anaemic patient). See also the article ‘Mechanisms of Hypoxaemia’ on pp 505e511 of this issue for further related detail.
inevitable knock-on effect on cardiac output. Examples include sepsis, neurogenic shock and anaphylaxis. In sepsis, infective agents, most commonly bacteria, trigger the release of pro-inflammatory cytokines and nitric oxide. The consequences of this include vasodilation and leakage of plasma from blood vessels into surrounding tissues. The signs of shock are warm peripheries, tachycardia, hypotension, manifestations of poor organ perfusion and signs of the infective source. Treatment should be as per Surviving Sepsis Campaign guidelines,2 updated recommendations are available via the campaign website.3 The campaign advocates early recognition of sepsis, resuscitation and source control using care bundles. Resuscitation is guided by parameters such as CVP, mixed venous oxygen saturation, mean arterial pressure, urine output and haematocrit. This is collectively referred to as ‘early goal-directed therapy’ and should involve early escalation to critical care facilities when required. Neurogenic shock can occur following spinal cord injury. Loss of sympathetic innervation results in unopposed parasympathetic effects on blood vessels, resulting in massive peripheral vasodilation and reduced SVR. Treatment follows generic ABC principles, together with spine stabilization. Vasopressors may be needed initially, to overcome vasodilation, increasing venous return and blood pressure. Anaphylactic shock is similar to septic shock, in that mast cell degranulation releases substances including histamine which increase capillary permeability and cause vasodilation. This results in relative hypovolaemia and peripheral oedema. As well as supportive measures, specific treatment includes removal of the allergenic source and administration of adrenaline as a firstline measure, followed by use of chlorpheniramine and hydrocortisone to prevent rebound reactions.
Classification of shock Pathophysiologically, there are three main categories of shock; hypovolaemic, vasodilatory and cardiogenic. The key clinical findings in each of these are summarized in Table 1 and outlined in the subsequent sections. Other categories are described in texts, but can be considered combinations or variations of these three. Hypovolaemic shock: this occurs when fluid, which may be blood or plasma, is acutely lost from the intravascular space. Examples include acute haemorrhage (of any cause), gastrointestinal losses (e.g. diarrhoea and vomiting, especially in children) and severe burns. Loss of intravascular volume results in decreased venous return, which reduces LVEDV, stroke volume and therefore cardiac output (see Starling curve, Figure 2). Physiological responses attempt to compensate for poor perfusion by increasing cardiac output. With ongoing losses, further compensation eventually becomes impossible and tissue metabolism is affected (Figure 3). High levels of circulating catecholamines and other vasoactive hormones result in tachycardia and peripheral vasoconstriction, together with vasoconstriction in the renal, splanchnic and skeletal circulations. This presents clinically as cool peripheries, prolonged capillary refill time, decreased urine output and agitation or reduced level of consciousness. Remember that young fit people can maintain relatively normal physiological parameters until significant fluid loss has occurred. However, once compensatory mechanisms are exhausted, their decline may be dramatic. Low blood pressure in a young adult suffering from trauma is a bad sign and needs prompt attention. This may need to include surgical intervention to arrest any causative bleeding.
Contractility/cardiogenic: this may be due to either loss of contractility or mechanical impairment to blood flow. Examples include myocardial infarction, arrhythmias and valvular heart disease. Reduced contractility and reduced cardiac output result in reduced organ perfusion. The body responds in a similar way as to hypovolaemia, with increased circulating catecholamine levels causing tachycardia and vasoconstriction. Patients have cool, clammy peripheries and evidence of poor organ perfusion, but with a normal intravascular volume. Pump failure results in raised jugular venous pressure (JVP) or CVP. Peripheral vasoconstriction increases afterload, which puts additional strain on a struggling myocardium.
Vasodilatory shock: the unifying problem in this category is a precipitous fall in systemic vascular resistance (SVR), which reduces blood pressure and compromises preload, having the
Categories of shock Type
Hypovolaemic Vasodilatory Cardiogenic
Basic bedside monitoring
Advanced cardiac output monitoring
HR
BP
JVP
Peripheral temperature
CVP
SṽO2
Cardiac index
SVR
[ [ [/Y
Y Y Y
Y Y [
Y [/Y Y
Y Y [
Y [/Y Y
Y [/Y Y
[ Y [
SṽO2 ¼ mixed venous oxygen saturations. Cardiac index ¼ cardiac output/body surface area. BP, blood pressure; CVP, central venous pressure; HR, heart rate; JVP, jugular venous pressure; SVR, systemic vascular resistance.
Table 1
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Pathogenesis of hypovolaemic shock Decreased intravascular fluid volume
Decreased cardiac output
Splenic discharge
Antidiuretic hormone (ADH) release
Interstitial fluid shift
Increased intravascular volume
Aldosterone release
Increased catecholamine release
Increased heart rate Increased stroke volume
Increased cardiac output
Continued fluid loss
Decreased cardiac output
Decreased systematic and pulmonary pressures
Decreased tissue perfusion
Impaired cellular metabolism Reproduced with kind permission from Dr Bryan Bledsoe http://www.bryanbledsoe.com/handouts
Figure 3
Venous return and CVP4
intrapericardial or intraabdominal pressure may cause a decrease in venous return and subsequent decrease in preload, however it may also lead to an increase in CVP. Even though there lacks robust evidence supporting the relationship of CVP and circulating volume, volume responsiveness may still indicate a relative hypovolaemic state. It is therefore still a recognized monitor of volume assessment.5
CVP is the measurement of venous blood pressure within a central vein (usually internal jugular or subclavian) that reflects the pressure within the right atrium which correlates to venous return or preload. It can be monitored continuously by placement of a central venous catheter. With the patient supine, the normal CVP is approximately 5 cm of water (1 cm of water ¼ 0.75 mmHg). Patients with low CVP have either volume deficit or peripheral pooling from vasodilatation resulting in relative hypovolaemia. If fluid restores the CVP and raises blood pressure the cause of shock is the most likely hypovolaemia. If repeated fluid boluses fail to restore blood pressure and CVP, the cause is the most likely vasodilatory failure. Alternatively a state of shock with a raised CVP indicates possible cardiac failure.
Venous return and mixed venous saturation6e9 Mixed venous saturation (SvO2) is the oxygen saturation of blood in the proximal pulmonary artery. It reflects the balance of oxygen supply and demand averaged across the entire body. Venous saturation from the superior vena cava (ScvO2) is usually 2e5% less than the SvO2, due to the higher oxygen content of venous blood from the kidneys. SvO2 is an indicator of the amount of oxygen extracted from microcirculatory beds, which is high in states of shock, thus reducing SvO2. The normal SvO2 is 70%; an ScvO2 less than 65%
Limitations with CVP and volume assessment CVP is the venous blood pressure within the intrathoracic and intraabdominal vena cavae. An increase in intrathoracic,
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is indicative of shock. Improving SvO2 with fluid resuscitation, inotropes or a combination of both correlates with an improvement in cardiac index. SvO2 is reduced in all three pathophysiological variants of shock. It has to be used in context with other measurements (e.g. CVP), in order to distinguish between them. As a continuous or series of measurements, SvO2 helps to assess treatment response. There is evidence to indicate that SvO2 less than 65% is associated with a higher incidence of postoperative complications. Using SvO2 to guide resuscitation improves outcome.
treatment of shock may be life saving, involving early detection and a focus towards correction of altered physiology. Further management is directed by determining which of the three pathophysiological mechanisms predominates. A
REFERENCES 1 Prothero J, Burton AC. The physics of blood flow in capillaries. 1. The nature of the motion. Biophys J 1961; 1: 565e79. 2 Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008; 36: 296e327. 3 http://www.survivingsepsis.org/guidelines/Pages/default.aspx. Accessed 29th April 2012 4 MacLean LD, Duff JH. The use of central venous pressure as a guide to volume replacement in shock. Chest 1965; 48: 199e205. 5 Magder S. Central venous pressure monitoring. Curr Opin Crit Care 2006; 12: 219e27. 6 Muir L, Kirby BJ, King AJ, Miller HC. Mixed venous oxygen saturation in relation to cardiac output in myocardial infarction. Br Med J 1970; 4: 276e8. 7 Krauss XH, Verdouw PD, Hughenholtz PG, Nauta J. On-line monitoring of mixed venous oxygen saturation after cardiothoracic surgery. Thorax 1975; 636e43. 8 Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345: 1368e77. 9 Shepherd SJ, Pearse RM. Role of central and mixed venous oxygen saturation measurement in perioperative care. Anesthesiol 2009; 111: 649e56.
Invasive cardiac monitoring Invasive cardiac monitors measure cardiac output directly using either the thermodilution or Doppler principles. Thermodilution principle This measures the rate of change of temperature when cold saline is injected into the right atrium. A time/temperature curve is plotted. The degree of change in temperature is directly proportional to the cardiac output. Once cardiac output is determined then SVR is calculated. PA catheters and PiCCO use this principle. Doppler principle The blood velocity through a specified point, e.g. aorta in oesophageal doppler, causes a ‘Doppler shift’ in the frequency of the returning ultrasound waves, which can be used to calculate flow velocity. If the cross section area at that point is known, the volume flowing i.e. stroke volume (SV) and CO can be calculated. Doppler ultrasound is non-invasive, accurate and inexpensive.
Conclusions
FURTHER READING Spoors C, Kiff K, eds. Training in anaesthesia: the essential curriculum. Chapter 10: cardiovascular system. Oxford University Press, 2010.
In this article we have explored the physiology and control of blood flow and pressure in health and disease. The prompt
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Ó 2012 Elsevier Ltd. All rights reserved.
Haemodynamics and cardiovascular shock
of intravenous fluid to a shocked patient is best achieved under pressure and through a short, wide cannula.
Hannah Bawdon
(where P ¼ pressure gradient across the length of the tube, r ¼ radius, h ¼ fluid viscosity and L ¼ tube length). Turbulent flow occurs in uneven tubes, with sharp angles or sudden changes in tube diameter. Laminar flow can also become turbulent at high fluid velocities. Flow is tumultuous, having eddy currents and a flat flow profile (Figure 1). Consequently, turbulent flow is less efficient and so requires a greater change in pressure or tube radius to achieve the same increase in fluid flow. Turbulent flow is proportional to radius2 and Opressure gradient, but inversely proportional to tube length and density of fluid. Reynolds’ number (Re) can be used to predict when fluid flow will become turbulent. This is a dimensionless number, calculated by Re ¼ v r d/h. (v ¼ velocity, r ¼ fluid density, d ¼ diameter of tube, h ¼ fluid viscosity). Re less than 2000 predicts laminar flow, whereas Re over 2000 is most commonly turbulent. Resistance is that which impairs fluid flow. For laminar flow, it is defined mathematically as:
Flow ¼ Pr 4 p=8hL
Michael Reay
Abstract Haemodynamics is the study of blood flow around the body. The factors influencing haemodynamics are complex and include cardiac output, circulating blood volume, vessel diameter, resistance and blood viscosity. These, in turn, are interlinked and affected by factors such as exercise, posture, disease, drugs and obesity. In this article we shall explore the physiology and control of blood flow and pressure in health, moving on then to look at what happens when control mechanisms break down, resulting in cardiovascular shock.
Keywords Flow; haemodynamics; pathophysiology; shock
Flow Flow is the amount of fluid moving past a point per unit time. In general, flow through a tube may be described as either laminar or turbulent. Laminar flow typically occurs in a smooth tube with constant diameter and no sharp bends. Flow is smooth, with fluid behaving like a series of concentric layers (laminae) that slide past each other. The flow profile is parabolic; velocity is greatest in the centre of the tube, and progressively reduces towards the periphery due to the effects of friction. The very outermost layer of fluid has a velocity approaching zero (Figure 1). Suspended particles (including blood cells) tend to gravitate towards the centre of flow, in a process known as ‘axial streaming’. When considering the factors which affect laminar flow, it is helpful to think of a bag of fluid attached via a giving set to an intravenous cannula. If you want to infuse fluid faster you might squeeze the bag; this increases the driving pressure gradient across the system, with a proportional increase in fluid flow. Use of a larger bore cannula or giving set will allow fluid to run faster, and in fact this effect is more significant because flow is proportional to radius,4 that is, doubling the radius will result in a 16-fold increase in fluid flow. Conversely, increasing the length of the tube or the viscosity of the fluid reduces the maximum flow rate possible. This is all summarized in the Hagene Poiseuille equation below, and is the reason why rapid infusion
Resistance ¼ pressure=flow Using the HagenePoiseuille equation above, we can see that increasing fluid viscosity or tube length increases flow resistance, whereas increasing tube diameter has the opposite effect (again, this is proportional to radius4). Blood flow and resistance Blood obeys the laws outlined above, with flow being a mixture of laminar and turbulent in different parts of the body. A third type, bolus flow, occurs at capillary level. Laminar blood flow: as previously stated, this is most efficient and occurs throughout the body. There is minimal friction between layers which glide past each other smoothly. Axial streaming of blood cells to the centre of flow creates a marginal plasma layer next to the vessel wall; this further reduces friction which is of particular relevance in small vessels. Turbulent blood flow: large diameter vessels with high velocity flow and low viscosity blood (e.g. in anaemia) encourage turbulence. Stenoses and points where vessels branch are also significant, as they create friction and take energy away from the system.
Hannah Bawdon BDS MFDSRCS(Eng) MB BCh FRCA is a Specialty Trainee (ST3) in Anaesthetics at University Hospital Birmingham, Birmingham, UK. Conflicts of interest: none declared.
Bolus flow: red blood cells are larger than the cross-sectional diameter of some capillaries. They therefore need to deform to pass through, and do this in boluses, with pockets of plasma between cells (Figure 1). Friction between red blood cells and the endothelium increase resistance to flow in these vessels, although gaseous exchange between plasma and the tissues is improved.1
Michael Reay MBBS FRCA FFICM is a Consultant in Anaesthesia and Intensive Care at Russells Hall Hospital, Dudley, West Midlands, UK. Conflict of interests: none declared.
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such as noradrenaline and vasopressin, and stimulation of a1-adrenergic receptors cause vasoconstriction, whereas stimulation of b2-adrenergic receptors result in vasodilation. Increased intravascular pressure is thought to be accompanied by contraction of muscle in the vessel wall, reducing diameter and therefore flow; this is the myogenic theory of autoregulation.
Laminar, turbulent & bolus flow
Laminar flow
Control of heart rate The sinoatrial (SA) node generates an intrinsic rate of approximately 110 beats/minute (bpm). Further control is a balance between the activities of the parasympathetic nervous systemvagal tone slows the SA and atrioventricular (AV) nodes, and sympathetic cardioaccelerator fibres, which arise from the sympathetic chain at levels T1-T5, speeding up SA node automaticity and AV nodal transmission.
Turbulent flow
BOLUS FLOW Pockets off plasma
Control of stroke volume The volume of blood (in ml) ejected from the left ventricle with each contraction is determined by the preload, afterload, cardiac contractility and ventricular function.
RBC RBCs
Figure 1
Preload: the preload is the end-diastolic ventricular wall tension. Wall tension determines the initial length of the cardiac muscle fibre before contraction begins, and is the prime determinant of contractile force. This relationship is illustrated by Starling’s law (Figure 2). As neither variable are easy to measure, wall tension is commonly substituted by left ventricular end-diastolic volume (LVEDV, as increased volume is associated with increased wall tension), and contractility by stroke volume. Note that even the normal heart reaches an LVEDV at which it cannot increase stroke volume any further without an increase in sympathetic tone. At higher volumes, the curve for the failing heart starts to slope downwards; this represents excessive muscle fibre stretch such that contractile filaments barely overlap and can no longer initiate effective contractions. Clinically, preload is often estimated by central venous pressure (CVP) for the right ventricle, and pulmonary artery occlusion pressure (PAOP) for the left
Resistance to whole body blood flow is predominantly at the level of the small arteries and arterioles; these are known as the ‘resistance vessels’. Circulatory pressures therefore drop significantly at arteriolar level. Resistance is low in the venous circulation, a state necessary to maintain cardiac output at lower venous pressures. For any organ, flow ¼ perfusion pressure/resistance. Perfusion pressure is defined as mean arterial e venous pressure, but also depends on local pressures within the capillary circulation. Blood flow to an organ can be improved, either by increasing the perfusion pressure or reducing resistance in local arterioles.
Control of cardiac output and blood pressure Total flow across the circulation (i.e. cardiac output) depends on the peripheral resistance. Assuming laminar flow: Total Peripheral Resistance TPR
The Frank-Starling law
Mean Arterial Pressure ðMAPÞCentral Venous Pressure ðCVPÞ ¼ Cardiac Output ðCOÞ
Starling law During exercise
In health, CVP is usually discounted as its contribution is minimal. The equation can therefore be rearranged to give us: Stroke volume
Increased contractility
MAP ¼ CO TPR Cardiac output is equal to heart rate stroke volume. Thus, mean arterial pressure is affected by anything which alters peripheral resistance, heart rate or stroke volume.
Heart failure
Cardiogenic shock
Control of peripheral resistance As already stated, small arteries and arterioles form the ‘resistance vessels’. Minimal changes across the group effect large changes in overall resistance. Key influences include locally produced substances, which predominantly cause vasodilation, for example CO2, Hþ, lactic acid, histamine (think of substances produced during exercise or anaphylaxis). Circulating hormones
SURGERY 30:10
Normal Decreased contractility
Left ventricular end-diastolic volume
Figure 2
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ventricle. The failing heart might be seen as a worsening stroke volume/cardiac output in response to a fluid challenge.
Cardiopulmonary receptors: receptors located at the junctions of large veins and the atria convey information about circulating blood volume, again via the vagus nerves. One example of their action is the Bainbridge reflex, in which a rapid increase in atrial pressure triggers a reflex tachycardia; its full significance is unknown, although it is thought to contribute to respiratory sinus arrhythmia.
Afterload is the cardiac muscle fibre tension generated in systole before fibre shortening occurs. It is the ‘load’ which the ventricle must overcome before it can eject a stroke volume. Whilst not truly analogous, it is often taken to be systemic vascular resistance, as the two are closely linked. Afterload is also increased by outflow obstruction, for example aortic stenosis, and greater LVEDV, as increased muscle fibre tension needs to be generated to produce an adequate contractile pressure. Laplace’s law describes this relationship for a sphere (an approximation of ventricular cardiac muscle), as follows:
Chemoreceptors: peripheral chemoreceptors respond to the hypoxia and acidosis associated with tissue hypoperfusion. They stimulate a sympathetic outflow which vasoconstricts peripheral and splanchnic vessels, aiming to raise the blood pressure and maintain perfusion of vital organs.
P ¼ 2T=R
Cushing’s reflex: this is a response to brainstem hypoxia secondary to raised intracranial pressure. A massive sympathetic outflow endeavours to restore cerebral perfusion, resulting in generalized vasoconstriction, hypertension and a reflex bradycardia.
(where P ¼ pressure generated across the wall, T ¼ tension in the wall, and R ¼ radius of the sphere). The effect of increased afterload is a reduction in stroke volume, but increase in myocardial work (and therefore oxygen demand), which is clearly bad for a struggling heart. Afterload may be reduced by using vasodilator drugs.
Shock Shock is a state characterized by insufficient tissue perfusion to meet the metabolic demands of the body. It is a physiological derangement rather than a diagnosis. A number of different pathophysiological processes can all result in a similar clinical picture of refractory hypotension, tissue hypoxia and acidosis; these are discussed below, and also in ‘Management of the circulation on ICU’ on pp 543e551 of this issue. Whatever the cause, compensatory mechanisms initially act to preserve a degree of organ perfusion. When these mechanisms fail, tissues rapidly become critically starved of oxygen and nutrients, and toxic metabolites build up. This results in organ dysfunction which, if allowed to progress unchecked, leads to a spiralling decline of irreversible multi-organ failure and subsequent death. It is therefore essential that shock is identified and treated promptly. Again, whatever the cause of shock, initial treatment has the same aim e to restore tissue oxygenation and perfusion. This is best achieved with a generic ABC approach, together with treatments specific to the cause identified.
Contractility is a measure of the intrinsic ability of cardiac muscle to do work (contract). It is interpreted in the context of a given preload and afterload, i.e. increased force of contraction achieved with the same degree of cardiac filling and systemic vascular resistance. Myocardial contraction is due to interaction between intracellular actin and myosin, in a process requiring calcium. Increased contractility (called ‘positive inotropy’) increases the force and rate of contraction (via mechanisms which increase intracellular calcium), together with the stroke volume. Of course, nothing is quite that straightforward; increasing the rate of contraction beyond a certain point ultimately compromises diastolic ventricular filling and therefore LVEDV, which tends to decrease stroke volume. The effect of changes in contractility is demonstrated on the Starling curve in Figure 2. Ventricular function: normal myocardium contracts in a coordinated, concentric fashion. Damaged tissue manifests as areas of akinetic or dyskinetic muscle, with associated reduction in contractile efficiency.
Oxygen delivery This refers to the amount of oxygen delivered to the tissues per unit time. It is calculated by:
Reflex control of haemodynamics A number of reflexes exist to maintain cardiovascular parameters within limits required for organ perfusion, preventing wide fluctuations. Receptors (discussed below) transmit impulses via the vagus or glossopharyngeal nerves, synapsing in the nucleus tractus solitarius of the brainstem. From here, impulses project to areas including other regions of the brainstem, the cortex, and hypothalamus. The efferent arc of these reflexes is via the parasympathetic and sympathetic systems.
Oxygen delivery ðDO2 Þ ¼ cardiac output arterial oxygen content And is therefore dependent on both pulmonary oxygenation and all the factors affecting cardiac output that are outlined above. Arterial oxygen content is primarily determined by the amount of haemoglobin and its oxygen binding capacity. Dissolved oxygen usually contributes very little. This is summarized in the equation below:
Baroreceptors: these stretch receptors are located in the walls of the carotid sinus and aortic arch, and fire in response to vessel distension, particularly when the rate of pressure rise is rapid. The afferent limb of the reflex is via glossopharyngeal and vagus nerves. Baroreceptors are only useful for short-term blood pressure control, as more prolonged hypertension rapidly resets their firing threshold.
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Oxygen content ðml=dl bloodÞ ¼ ðHb SaO2 1:34Þ þ ðPaO2 0:0225Þ (SaO2 ¼ oxygen saturation of arterial blood, PaO2 ¼ partial pressure of oxygen in arterial blood, in kPa).
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These equations underline the importance of a systematic approach to resuscitation of the shocked patient. Oxygen delivery to the tissues may need to be treated by means of respiratory care (to improve oxygenation in the lungs), cardiovascular support (to improve cardiac output and blood pressure) and potentially also blood transfusion (to improve the oxygen carrying capacity of blood in an anaemic patient). See also the article ‘Mechanisms of Hypoxaemia’ on pp 505e511 of this issue for further related detail.
inevitable knock-on effect on cardiac output. Examples include sepsis, neurogenic shock and anaphylaxis. In sepsis, infective agents, most commonly bacteria, trigger the release of pro-inflammatory cytokines and nitric oxide. The consequences of this include vasodilation and leakage of plasma from blood vessels into surrounding tissues. The signs of shock are warm peripheries, tachycardia, hypotension, manifestations of poor organ perfusion and signs of the infective source. Treatment should be as per Surviving Sepsis Campaign guidelines,2 updated recommendations are available via the campaign website.3 The campaign advocates early recognition of sepsis, resuscitation and source control using care bundles. Resuscitation is guided by parameters such as CVP, mixed venous oxygen saturation, mean arterial pressure, urine output and haematocrit. This is collectively referred to as ‘early goal-directed therapy’ and should involve early escalation to critical care facilities when required. Neurogenic shock can occur following spinal cord injury. Loss of sympathetic innervation results in unopposed parasympathetic effects on blood vessels, resulting in massive peripheral vasodilation and reduced SVR. Treatment follows generic ABC principles, together with spine stabilization. Vasopressors may be needed initially, to overcome vasodilation, increasing venous return and blood pressure. Anaphylactic shock is similar to septic shock, in that mast cell degranulation releases substances including histamine which increase capillary permeability and cause vasodilation. This results in relative hypovolaemia and peripheral oedema. As well as supportive measures, specific treatment includes removal of the allergenic source and administration of adrenaline as a firstline measure, followed by use of chlorpheniramine and hydrocortisone to prevent rebound reactions.
Classification of shock Pathophysiologically, there are three main categories of shock; hypovolaemic, vasodilatory and cardiogenic. The key clinical findings in each of these are summarized in Table 1 and outlined in the subsequent sections. Other categories are described in texts, but can be considered combinations or variations of these three. Hypovolaemic shock: this occurs when fluid, which may be blood or plasma, is acutely lost from the intravascular space. Examples include acute haemorrhage (of any cause), gastrointestinal losses (e.g. diarrhoea and vomiting, especially in children) and severe burns. Loss of intravascular volume results in decreased venous return, which reduces LVEDV, stroke volume and therefore cardiac output (see Starling curve, Figure 2). Physiological responses attempt to compensate for poor perfusion by increasing cardiac output. With ongoing losses, further compensation eventually becomes impossible and tissue metabolism is affected (Figure 3). High levels of circulating catecholamines and other vasoactive hormones result in tachycardia and peripheral vasoconstriction, together with vasoconstriction in the renal, splanchnic and skeletal circulations. This presents clinically as cool peripheries, prolonged capillary refill time, decreased urine output and agitation or reduced level of consciousness. Remember that young fit people can maintain relatively normal physiological parameters until significant fluid loss has occurred. However, once compensatory mechanisms are exhausted, their decline may be dramatic. Low blood pressure in a young adult suffering from trauma is a bad sign and needs prompt attention. This may need to include surgical intervention to arrest any causative bleeding.
Contractility/cardiogenic: this may be due to either loss of contractility or mechanical impairment to blood flow. Examples include myocardial infarction, arrhythmias and valvular heart disease. Reduced contractility and reduced cardiac output result in reduced organ perfusion. The body responds in a similar way as to hypovolaemia, with increased circulating catecholamine levels causing tachycardia and vasoconstriction. Patients have cool, clammy peripheries and evidence of poor organ perfusion, but with a normal intravascular volume. Pump failure results in raised jugular venous pressure (JVP) or CVP. Peripheral vasoconstriction increases afterload, which puts additional strain on a struggling myocardium.
Vasodilatory shock: the unifying problem in this category is a precipitous fall in systemic vascular resistance (SVR), which reduces blood pressure and compromises preload, having the
Categories of shock Type
Hypovolaemic Vasodilatory Cardiogenic
Basic bedside monitoring
Advanced cardiac output monitoring
HR
BP
JVP
Peripheral temperature
CVP
SṽO2
Cardiac index
SVR
[ [ [/Y
Y Y Y
Y Y [
Y [/Y Y
Y Y [
Y [/Y Y
Y [/Y Y
[ Y [
SṽO2 ¼ mixed venous oxygen saturations. Cardiac index ¼ cardiac output/body surface area. BP, blood pressure; CVP, central venous pressure; HR, heart rate; JVP, jugular venous pressure; SVR, systemic vascular resistance.
Table 1
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Pathogenesis of hypovolaemic shock Decreased intravascular fluid volume
Decreased cardiac output
Splenic discharge
Antidiuretic hormone (ADH) release
Interstitial fluid shift
Increased intravascular volume
Aldosterone release
Increased catecholamine release
Increased heart rate Increased stroke volume
Increased cardiac output
Continued fluid loss
Decreased cardiac output
Decreased systematic and pulmonary pressures
Decreased tissue perfusion
Impaired cellular metabolism Reproduced with kind permission from Dr Bryan Bledsoe http://www.bryanbledsoe.com/handouts
Figure 3
Venous return and CVP4
intrapericardial or intraabdominal pressure may cause a decrease in venous return and subsequent decrease in preload, however it may also lead to an increase in CVP. Even though there lacks robust evidence supporting the relationship of CVP and circulating volume, volume responsiveness may still indicate a relative hypovolaemic state. It is therefore still a recognized monitor of volume assessment.5
CVP is the measurement of venous blood pressure within a central vein (usually internal jugular or subclavian) that reflects the pressure within the right atrium which correlates to venous return or preload. It can be monitored continuously by placement of a central venous catheter. With the patient supine, the normal CVP is approximately 5 cm of water (1 cm of water ¼ 0.75 mmHg). Patients with low CVP have either volume deficit or peripheral pooling from vasodilatation resulting in relative hypovolaemia. If fluid restores the CVP and raises blood pressure the cause of shock is the most likely hypovolaemia. If repeated fluid boluses fail to restore blood pressure and CVP, the cause is the most likely vasodilatory failure. Alternatively a state of shock with a raised CVP indicates possible cardiac failure.
Venous return and mixed venous saturation6e9 Mixed venous saturation (SvO2) is the oxygen saturation of blood in the proximal pulmonary artery. It reflects the balance of oxygen supply and demand averaged across the entire body. Venous saturation from the superior vena cava (ScvO2) is usually 2e5% less than the SvO2, due to the higher oxygen content of venous blood from the kidneys. SvO2 is an indicator of the amount of oxygen extracted from microcirculatory beds, which is high in states of shock, thus reducing SvO2. The normal SvO2 is 70%; an ScvO2 less than 65%
Limitations with CVP and volume assessment CVP is the venous blood pressure within the intrathoracic and intraabdominal vena cavae. An increase in intrathoracic,
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is indicative of shock. Improving SvO2 with fluid resuscitation, inotropes or a combination of both correlates with an improvement in cardiac index. SvO2 is reduced in all three pathophysiological variants of shock. It has to be used in context with other measurements (e.g. CVP), in order to distinguish between them. As a continuous or series of measurements, SvO2 helps to assess treatment response. There is evidence to indicate that SvO2 less than 65% is associated with a higher incidence of postoperative complications. Using SvO2 to guide resuscitation improves outcome.
treatment of shock may be life saving, involving early detection and a focus towards correction of altered physiology. Further management is directed by determining which of the three pathophysiological mechanisms predominates. A
REFERENCES 1 Prothero J, Burton AC. The physics of blood flow in capillaries. 1. The nature of the motion. Biophys J 1961; 1: 565e79. 2 Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008; 36: 296e327. 3 http://www.survivingsepsis.org/guidelines/Pages/default.aspx. Accessed 29th April 2012 4 MacLean LD, Duff JH. The use of central venous pressure as a guide to volume replacement in shock. Chest 1965; 48: 199e205. 5 Magder S. Central venous pressure monitoring. Curr Opin Crit Care 2006; 12: 219e27. 6 Muir L, Kirby BJ, King AJ, Miller HC. Mixed venous oxygen saturation in relation to cardiac output in myocardial infarction. Br Med J 1970; 4: 276e8. 7 Krauss XH, Verdouw PD, Hughenholtz PG, Nauta J. On-line monitoring of mixed venous oxygen saturation after cardiothoracic surgery. Thorax 1975; 636e43. 8 Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345: 1368e77. 9 Shepherd SJ, Pearse RM. Role of central and mixed venous oxygen saturation measurement in perioperative care. Anesthesiol 2009; 111: 649e56.
Invasive cardiac monitoring Invasive cardiac monitors measure cardiac output directly using either the thermodilution or Doppler principles. Thermodilution principle This measures the rate of change of temperature when cold saline is injected into the right atrium. A time/temperature curve is plotted. The degree of change in temperature is directly proportional to the cardiac output. Once cardiac output is determined then SVR is calculated. PA catheters and PiCCO use this principle. Doppler principle The blood velocity through a specified point, e.g. aorta in oesophageal doppler, causes a ‘Doppler shift’ in the frequency of the returning ultrasound waves, which can be used to calculate flow velocity. If the cross section area at that point is known, the volume flowing i.e. stroke volume (SV) and CO can be calculated. Doppler ultrasound is non-invasive, accurate and inexpensive.
Conclusions
FURTHER READING Spoors C, Kiff K, eds. Training in anaesthesia: the essential curriculum. Chapter 10: cardiovascular system. Oxford University Press, 2010.
In this article we have explored the physiology and control of blood flow and pressure in health and disease. The prompt
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