1 Cardiovascular Physiology: A Primer
Thomas E. J. Gayeski, Brad L. Steenwyk, and Jack H. Crawford
1. The heart has a fibrous skeleton that provides an insertion site at each valvular ring. This fibrous structure also connects cardiac myocytes so that “stretch” or preload results in sarcomeres lengthening and not intercellular sliding.
2. Contractility changes as a result of myoplasmic Ca2+ concentration change during systole.
3. Relaxation following contraction is an active process requiring ATP consumption to pump Ca2+ into the sarcoplasmic reticulum as well across the sarcolemma.
4. The fundamental unit of tension development is the sarcomere.
5. The endocardium receives perfusion during systole while the epicardium receives blood flow throughout the cardiac cycle. The ventricular wall is more susceptible to endocardial infarction.
6. The external stroke volume work the ventricle does is to raise the pressure of a stroke volume from VEDP (right or left) to mean arterial pressure (pulmonary or systemic, respectively).
7. Oxygen or ATP consumption occurs during release of actin–myosin bonds during relaxation of this bond. The main determinants of myocardial oxygen consumption are heart rate, contractility, and wall tension.
8. The cardiovascular system regulates blood pressure and it is an example of a negative feedback loop control system. Sensors throughout the cardiovascular system all sense stretch.
9. Physiologic reserves are expansion factors allowing the cardiovascular system to maintain blood pressure. These reserves are heart rate (3-fold range), contractility, systemic vascular resistance (15-fold range), and venous capacitance (~1.5-fold range).
10. Utilizing the reserve of venous capacitance does not affect myocardial oxygen consumption.
AS A PHYSIOLOGIC PRIMER FOR CARDIAC ANESTHESIOLOGY, this chapter requires brevity and choices (or opinions)! Cardiac anatomy, physiology, pathology, and genomics are decades old, continue to evolve, and have a vast literature. Our focus is on presenting physiologic principles important to clinical management in the operating room. A detailed description and discussion of cardiac physiology can be found in 1. If these physiologic concepts are memorized and applied correctly, your patients will benefit from risk modification under your care. If they are understood, you will be able to apply them to the dynamic pathology present in the operating room and have a physiologic basis for being a consultant in cardiac anesthesiology.
I. Embryologic development of the heart.
A. The cardiovascular system begins to develop during week 3 as the primitive vascular system is formed from mesodermally derived endothelial tubes. Eventually at week 4, bilateral cardiogenic cords from paired endocardial heart tubes fuse into a single heart tube (primitive heart). This fusion initiates forward flow and is the start of the heart’s transport function.
B. The primitive heart evolves into four chambers: Bulbus cordis, ventricle, primordial atrium, and sinus venosus, eventually forming bulboventricular loop with the initial contraction occurs at 21 to 22 days. These contractions result in unidirectional blood flow in week 4.
C. From weeks 4 to 7 heart development enters a critical period as it divides into the four chambers of the adult heart, the basis of the fetal circulation.
D. The framework of the heart is a fibrous skeleton, composed of fibrin and elastin, forming four rings encircling the four valves of the heart as well as intermyocyte connections.
E. The fibrous skeleton:
1. Serves as an anchor for the insertion of the valve cusps
2. Resists overdistention of the annuli of the valves (resisting incompetence)
3. Provides a fixed insertion point for the muscular bundles of the ventricles
4. Minimizes intermyocyte sliding during ventricular filling and contraction
II. Electrical conduction
A. By breaking the atrial intermyocyte conduction of impulses, the fibrous skeleton blocks the direct spread of electrical conduction from the atria to the ventricles.
B. Because of this separation of the atrial myocyte conduction from ventricular myocytes, the AV nodal/purkinje system creates coordinated contraction between atria and ventricles.
C. Excitation–contraction coupling
1. A purkinje fiber action potential results in the coordinated contraction of a cardiac myocyte. There are five phases of an action potential and an integrated and complex change in Na+, K+, and Ca2+conductances and ion fluxes within these phases.
2. Excitation–contraction coupling starts when an action potential triggers the diffusion of Ca2+ ions across the sarcolemma through the Ca2+ release channels (ryanodine receptor channel). To shorten the time constant of this transmembrane flux, the T-tubule system markedly increases the surface area through which this flux of external Ca2+ occurs. In addition, the sarcoplasmic reticulum cisternae ensure rapid myoplasmic Ca2+ increase (Fig. 1.1).
3. The amount of Ca2+ transported across the sarcolemma is only about 1% of Ca2+ needed for contraction. However, this Ca2+ serves as a trigger for sarcoplasmic reticulum release of Ca2+ to create the Ca2+concentration needed for tension development.
4. The sarcoplasmic reticulum is a complex organelle responsible for the efficient cycling of calcium concentration during each heartbeat. The external Ca2+ crossing the sarcolemma triggers a graded release of internal Ca2+ from the sarcoplasmic reticulum. From relaxation to contraction, cytosolic Ca2+ concentration varies approximately 100-fold.
Figure 1.1 Relation of cardiac sarcoplasmic reticulum to surface membrane and myofibrils. The SRL and C overlie the myofilaments; they are shown separately for illustrative purposes. SL, sarcolemma; C, cisterna; T, transverse tubule; SRL, longitudinal sarcoplasmic reticulum; Z, Z disc.
5. Three very important proteins within the sarcoplasmic reticulum are responsible for controlling calcium flux: The Ca2+ release channel, the sarco-endoplasmic reticulum ATP-ase (SERCA-2), and the regulatory protein of SERCA-2 (phospholamban). Alterations within phospholamban are currently an active area of interest and may play a role in the development of heart failure and other cardiomyopathies (Maclennan, Nature Reviews Molecular Cell Biology 4, 566–577 [July 2003]).
6. The graded release of Ca2+, signaled by the trans-sarcolemmal Ca2+ flux and enhanced due to sarcoplasmic reticulum cisternae, is dependent on the amount of Ca2+ stored in the sarcoplasmic reticulum, the sympathetic tone (sarcolemma Ca2+ conductance), and the external Ca2+. Increased stores lead to increased release, resulting in increased tension development for a given sarcomere length =increased contractility.
7. Any increase in contractility via any drug is a consequence of increased myoplasmic Ca2+ concentration during systole! Ca2+ binds to troponin and results in a conformational change involving tropomyosin. This change allows actin and myosin to interact, resulting in shortening of a sarcomere (Fig. 1.2).
8. Similarly, a decrease in contractility is a result of decreased Ca2+ binding to troponin during systole. Its cause is attributable to decreased myoplasmic Ca2+ during systole or decreased Ca2+ binding to troponin. Myoplasmic Ca2+ is affected by inhalational agents, induction drugs, etc. A common clinical reason for decreased Ca2+–troponin affinity is intracellular acidosis.
9. Finally, for contraction to cease, Ca2+ must be removed from the myoplasm. Ca2+ is actively pumped into the sarcoplasmic reticulum as well as pumped across the sarcolemma. Depending on Ca2+ ion conductances in each of the sites, sarcoplasmic Ca2+ may be increased or decreased in the sarcoplasmic reticulum during this removal.
III. Cardiac myocyte
1. The fundamental unit of tension development is the sarcomere. The sarcomere is composed of myosin, the tropomyosin–actin–troponin complex, and a z-disc.
2. Each actin molecule contains a myosin-binding site as well as the site for tropomyosin–troponin chain to bind. Two actin molecule chains are intertwined and form an actin polymer. Combined with a tropomyosin–troponin complex bound within the grooves to the actin polymer chains, this complex is known as a thin filament. The thin filament spans a distance of approximately 2 μm.
3. The z-disc anchors the thin filaments in place in a regular pattern as schematized below. It is a strong meshwork of filaments forming a band that anchors the interdigitated thin filaments.
Figure 1.2 Schematic representation of actin–myosin dependence on Ca2+–troponin binding for tension development to occur. (From Honig C. Modern Cardiovascular Physiology. Boston/Toronto: Little, Brown and Company; 1981.)
4. Myosin molecules aggregate spontaneously forming the thick filaments. These filaments are approximately 1.6 μm. These thick filaments are held in place by M filaments and are interdigitated amongst the thin filaments. At the center of each thick filament is a zone that has no myosin “heads.” This absence explains the decrease in tension development if overstretching of the sarcomere were to occur. Each myosin head contains an ATP-ase and actin-binding site.
5. Together, troponin and tropomyosin and Ca2+ binding serve as regulatory proteins that allow actin and myosin to interact to result in shortening of the sarcomere length.
6. Each exposure of actin to myosin results in a shortening of sarcomere length. To allow for multiple shortenings to occur, actin–myosin binding is uncoupled. This ATP-consuming step, the relaxation phase, occurs because of the ATP-ase bound to myosin. This energy-dependent step, requiring oxygen consumption, occurs multiple times during a cardiac cycle.
7. Depending on preload, the sarcomere length, or the distance between z-discs, ranges from 1.8 to 2.2 μm.
IV. Organization of myocytes
A. A cardiac myocyte is approximately 12 μm long. Hence, each myocyte only has several (~6) sarcomeres in series from end to end of a myocyte.
B. As mentioned under embryology, collagen fibers link cardiac myocytes together. These collagen fiber links connect adjacent myocytes that hold all myocytes together allowing for a summation of the shortening of each myocyte into a concerted shortening of the ventricle.
C. This collagen structure also limits the cardiac myocyte from being overstretched, minimizing the risk of destroying a cell or limiting actin–myosin exposure through overstretching [1, p. 9].
D. Additional complexity is that from epicardium to endocardium, longitudinal alignment of the cardiac myocytes occurs in layers. Hence, shortening in each layer results in distortion between the layers.
E. This distortion results in partial occlusion of penetrating arteries arising from the surface vessels supplying blood to the inner layers of the myocardium.
F. Consequently, the endocardium is more vulnerable to ischemia than the epicardium because blood flow to the endocardium occurs primarily during systole while that to the epicardium occurs during the entire cardiac cycle.
V. Length–tension relationship
A. Consider this thought experiment. There is an idealized, single cardiac myocyte that is 12 μm long with 6 sarcomeres in series. All distances between Z-discs (sarcomere lengths) are equal for each of the 6 sarcomeres (12 μm = 6 * 2 μm). As the cardiac myocyte length changes, the length of each sarcomere changes proportionately. This single myocyte is suspended so that a strain gauge measures the tension that the myocyte generates at rest and during contraction.
1. The idealized myocyte is stretched between two fixed points.
2. The tension caused by the force of stretching the muscle at rest and created by the muscle during contraction is measured.
3. The muscle is stretched at rest over a range of 10.8 to 16.2 μm. Consequently, the sarcomere lengths vary between 1.8 and 2.7 μm as this myocyte contracts.
4. At each sarcomere length, two fixed myoplasmic Ca2+ concentrations are set within the cell: Zero concentration (rest) and a known value (contraction).
5. Myocyte tension is measured for both Ca2+ concentrations.
6. Plotting resting tension as a function of length results in a resting length–tension plot.
7. Recording peak tension as a function of myocyte length, a length–tension curve can be plotted for the given Ca2+ concentration as depicted in Figure 1.3.
1. In our idealized myocyte model, a measured amount of tension was required to stretch the sarcomere to a value between 1.9 and 2.6 μm. If we were to plot this passive tension resulting from passive stretch of the sarcomeres, there would be very little passive tension required to stretch the sarcomeres until around 2.2 μm. As the sarcomeres become stretched beyond 2.2 μm in intact cardiac muscle, the fibrous skeleton restricts further stretching resulting in a rapid change in pressure with very little change in volume (very low compliance).
2. This resting relationship between length and tension is the equivalent of ventricular compliance as will be discussed below.
Figure 1.3 Top three schematic diagrams represent actin (thick filaments penetrating Z disc) and myosin (thin filaments forming sheaf between Z disc) filaments at three sarcomere lengths 1.9, 2.2, and 2.8 μm. Bottom graph represents per cent of maximum tension development versus sarcomere length for strips of cardiac muscle. Note that fibrous cardiac skeleton inhibits sarcomere stretch from approaching a sarcomere length of 2.8 μm. (Modified from Honig C. Modern Cardiovascular Physiology. Boston/Toronto: Little, Brown and Company; 1981.)
1. For a given Ca2+ concentration, a fraction of troponin molecules will bind Ca2+ molecules.
2. This Ca2+ binding to each troponin results in a conformational change in its corresponding tropomyosin that allows an actin and myosin head pair, opposing each other and regulated by these tropomyosin molecules, to interact.
3. In addition to this conformational change, the percentage of the actin and myocytes heads opposed to each other is dependent on sarcomere length.
4. If one repeats the above mental experiment with a different known Ca2+ concentration, a new contracting length–tension curve is plotted.
5. For a range of Ca2+ concentrations in cardiac myocytes, a family of length–tension curves results.
6. Only through a change in myoplasmic Ca2+ concentration during contraction can contractility change.
D. Intracellular Ca2+ concentration
1. The range of myoplasmic Ca2+ concentrations during contraction varies depending upon Ca2+ fluxes across the sarcolemma at the initiation of contraction and the Ca2+ released from the sarcoplasmic reticulum.
2. The flux of Ca2+ across the sarcolemma is only ~1% of Ca2+ present during contraction. However, changes in this 1% result in changes in the amount of Ca2+ released from the sarcoplasmic reticulum.
3. The sarcoplasmic reticulum response is graded. The more the Ca2+ crossing the sarcolemma, the more the Ca2+ released from the sarcoplasmic reticulum.
4. Examples of increasing sarcolemmal Ca2+ flux include increasing epinephrine levels and increasing external Ca2+ concentration (a CaCl2 bolus).
5. Increased sarcoplasmic reticulum Ca2+ stores result from increased Ca2+ flux across the sarcolemma and increased heart rate (HR).
E. Oxygen consumption
1. Each interaction of actin and myosin results in a submicron shortening of the sarcomere. For the sarcomere to shorten 15%, many actin–myosin interactions take place.
2. Therefore, shortening requires a repetitive interaction of actin–myosin complexes.
3. Each interaction requires ATP for release of the actin–myosin head. It is relaxation of the actin–myosin interaction that requires energy and consumes oxygen.
4. Remember that the more actin–myosin cycles in a unit of time, the more the oxygen consumption!
VI. A heart chamber and external work
A. The chamber wall
1. To form a ventricular chamber, individual myocytes are joined together via collagen fibrin strands. This joining of myocytes, along a particular direction but not end to end, results in a sheet of muscle with myocytes oriented along a similar axis.
2. Several such layers form the ventricular wall. These layers insert on the valvular annuli.
3. Because of the electrical distribution of the signal through the purkinje system, the layers contract synchronously resulting in shortening of the muscle layers and a reduction in the volume of the chamber itself.
1. Atrial contraction contributes approximately 20% of the ventricular filling volume in a normal heart and may contribute even more when left-ventricular end-diastolic pressure (LVEDP) is increased. In addition to the volume itself, the rapid rate of ventricular volume addition resulting from atrial contraction may play a role in ventricular sarcomere lengthening.
1. For a given state of contractility (myoplasmic Ca2+ concentration), sarcomere length determines the wall tension the ventricle can achieve as discussed above. The aggregate shortening of the sarcomeres in the layers of cardiac myocytes results in wall tension that leads to ejection of blood into the aorta and pulmonary artery (PA).
2. The active range of sarcomere length is only 1.9 to 2.2 μm or ~15% of its length. Falling below 1.8 μm results from an empty ventricle and an empty heart cannot pump blood. The collagen fiber network inhibits the stretching of sarcomeres much above 2.2 μm. This integration of structure and function is important in permitting survival. If there were no skeleton, overstretch would lead to reduced emptying that would lead to more overstretch and no cardiac output (CO).
D. Preload and compliance
a. Where clinicians speak of preload, muscle physiologists think of sarcomere length. Clinician’s surrogate for initial sarcomere length is end-diastolic ventricular volume, and not ventricular pressure.
b. As discussed above, the sarcomere length determines how many actin–myosin heads interact for a given myoplasmic Ca2+ concentration at any instant.
c. Measuring sarcomere length is essentially impossible clinically. As a surrogate indirect estimate of sarcomere length, clinicians measure a chamber pressure during chamber diastole. This pressure measurement is the equivalent of the myocyte tension measurement above.
d. A more direct surrogate estimate of sarcomere length is chamber volume. As echocardiography is commonly available, estimates of volumes are direct estimates of preload and remove assumptions about chamber compliance that are necessary from the estimate when chamber pressure is used.
e. A plot of the relationship between chamber pressure and chamber volume results in a curve similar to the resting length tension curve for the myocyte.
f. The slope of this curve at any point (change in volume over the change in pressure at that point) is the compliance of the chamber at that point. The pressure–volume curve is nonlinear, and this slope varies depending on ventricular volume. Ventricles become much less compliant as sarcomere length surpasses 2.2 μm because of the collagen fiber skeleton.
g. Non-ischemic changes in compliance generally occur over long time periods. However, ischemia can change ventricular compliance very quickly. Thick ventricles, ventricles with scar formation, or ischemic ventricles have a lower compliance than normal ventricles. Less compliant ventricles require a higher pressure within them to have equal volume within them compared to a more compliant ventricle.
h. While preload is most commonly considered in the left ventricle, it is important in all four chambers. Congenital heart disease and cardiac tamponade can make that very apparent.
E. Ventricular work
1. For a sarcomere length between 1.9 and ~2.2 μm (preload) with a given systolic myoplasmic Ca2+ concentration (contractility), the cardiac myocyte will shorten, develop tension that increases with increased sarcomere length, and eject blood from the ventricle—a stroke volume (SV).
2. In ejecting this SV the ventricle performs external work. This external work is the raising of SV from LVEDP to the ventricular pressure in systole. In the absence of valvular heart disease, the systolic pressure and ventricular pressure in systole are closely matched by those in the aorta or PA for the respective ventricles.
3. Normal blood pressures (BPs) in the aorta and PA are not dependent on subject size and vary little amongst normal subjects. Normalizing SV to stroke volume index (SVI), SV divided by body surface area (BSA), the variability amongst subjects is small.
4. Formally, the external work of a ventricle is the area within the pressure volume loop seen in Figure 1.4. The definition of various points and intervals is defined in the legend. We estimate this indexed work for the left ventricle (LVSWI) by multiplying the SVI in milliliter times the difference in arterial mean pressure and ventricular pressure at the end of diastole (commonly estimated as atrial pressure or PA wedge pressure) times a constant (0.0136) to convert to clinical units:
LVSWI = SVI * (SBP mean − LVEDP) * 0.0136 (g m/m2)
Figure 1.4 Idealized pressure–volume loop. Area within the loop represents LVSW. Dividing SV (Point B minus Point A volumes) by BSA results in SVI. The area within this indexed loop is the LVSWI.
5. The normal resting values for SVI and LVSWI are ~50 mL/m2 and 50 g m/m2.
6. In performing this work, the efficiency of the ventricle, the ratio of external work done to energy consumed to do it, approaches that of a gasoline engine—only 10%. An astonishingly inefficient process given that our lives depend on it (and we cannot improve it)!
7. Since external work includes the product of pressure difference and SV, the amount of work does not distinguish between these two variables. Evidence suggests that the ventricles can do volume work somewhat more efficiently (require less oxygen) than pressure work. The reasoning relates to how many actin–myosin cycles are required to shorten a sarcomere to a given distance! The hypothesis is that it takes fewer actin–myosin cycles to shorten the same distance for volume work compared to pressure work. This principle may explain an underlying reason for success using vasodilators to treat heart failure.
F. Starling curve
1. For a given myoplasmic Ca2+ concentration (contractile state), varying the sarcomere length between 1.9 μm and less than 2.2 μm increases the amount of external work changes. For a ventricle with a normal compliance, a sarcomere length of 2.2 μm corresponds to one with an LVEDP of 10 mm Hg.
2. By plotting the relationship of ventricular pressure with left ventricular work index, a Starling curve is generated.
3. By changing the contractile state and replotting the same relationship, a new curve develops resulting in a family of Starling curves idealized in Figure 1.5.
G. Myocardial oxygen consumption
1. Except for very unusual circumstances, substrate for ATP and phosphocreatine (PCr) production is readily available. At any given moment the intracellular oxygen content is capable of keeping the heart contracting for seconds but the carbohydrate and lipid store can fuel the heart for almost an hour. Hence, capillary blood flow is crucial to maintain oxidative metabolism.
2. Myoglobin is an intracellular oxygen store. Its affinity for oxygen is between hemoglobin and cytochrome aa3. The maximum oxygen concentration required in mitochondria for maximal ATP production is 0.1 Torr! Myoglobin concentration is high enough to buffer interruptions in capillary flow only for seconds. Compared to high-energy phosphate buffers, this time buffer is small relative to ATP consumption rates. However, its intermediate oxygen affinity enhances unloading from the red cell into the myocyte and also serves to distribute oxygen within the cell.
3. Commonly, blood flow to regions of the heart limits oxygen delivery resulting in decreased. ATP production will result in reduced wall motion in that region—regional ischemic heart disease.
Figure 1.5 The Starling curve.
4. Capillaries are approximately 1 mm in length, so each capillary supplies multiple cardiac myocytes (12 μm in length) along its length. In contrast, skeletal muscle fiber is perhaps 15 cm long. Capillary length is the same—1 mm. Hence, each fiber has 150 capillaries in series to supply its entire length.
5. Capillary perfusion is organized into several capillaries supplied from a single higher-order arteriole. There are multiple levels of arteriolar structure. The lower-order, or initial, arterioles contribute to systemic vascular resistance (SVR) and the higher-order arterioles regulate regional blood flow distribution (at the local level). The intricacies are beyond the scope of this chapter.
6. This structure yields regions of perfusion on the scale of mm3 for the regional blood flow unit. Hence, the smallest volumes for “small vessel infarcts” should be of this order of magnitude. As the vessel occlusions become more proximal, the infarct size grows.
7. Because of the size of cardiac myocytes being small relative to the capillary and unit of importance of blood flow from ischemia, infarction only affects local zones. If the cardiac myocyte had a similar structure as skeletal muscle myocyte, the consequences of a local infarct would be more global.
8. Adequate production of ATP is dependent on mitochondrial function. Approximately 30% of cell volume is occupied by mitochondria. Given the substrate store and the ability to produce ATP within this volume, oxygen availability is the limiting factor for maintaining ATP availability. Mitochondria can maximally produce ATP when their cell PO2 is 0.1 Torr!
9. PCr is an intracellular buffer for ATP concentration. The cell readily converts ATP into PCr and vice versa. PCr is an important energy source and also serves to transport ATP between mitochondria and myosin ATP-ase.
10. Myosin ATP-ase activity is responsible for 75% of myocardial ATP consumption. The remaining 25% is being consumed by Ca2+ transport into the sarcoplasmic reticulum and across the sarcolemma.
11. Mitochondria play an evolving role in determining the response to ischemia. Intracellular signaling pathways in response to hypoxia may direct the cell to necrosis or even apoptosis.
VII. Control systems
A. The space program put man in space. As importantly, it brought many technical advances. In the world of systems development, control systems were an essential part. These systems allowed us to perform tasks in unexplored environments under unimagined conditions. To perform many tasks we required control systems. These systems in simplest concept permitted real-time sensing and adjustment of system outcomes through adjustment of system input and performance based on system outcome. This closed loop of an output affecting an input is referred to as a feedback loop.
B. Circulating levels of Ca2+, thyroid hormones, and antidiuretic hormone are only a few of the systems that utilize a negative feedback loop to maintain a “normal blood level.” A feedback loop is referred to as a negative feedback loop if a deviation from the desired level, called set point, is returned toward that level through the system response. Blood levels of all of the above protein moieties are controlled through negative feedback loop systems. In contrast, positive feedback loops increase the deviation from the normal level in response to a change. Outside of the physiology of the immune system, physiologic systems with positive feedback loops are generally pathologic. As considered below, perhaps the most studied biologic negative feedback loop is the cardiovascular system.
C. A simple example
1. A simple, manual system consists of a voltage source, a wall switch, and a light bulb. The system turns electrical energy into light through manually turning a light switch. A more complex system includes a light detector (sensor) that senses light level. If the ambient light level gets below a defined level, the controller turns the light bulb on and vice versa. This system automates light on and light off. A refinement of this automated system is one that keeps the light level constant below a defined light level (set point). In this system, light level is referred to as a regulated variable. If the light level is above the set point, the constant-light-level-system (CLLS) does not turn on the light. However, when the light level gets below this set point, the CLLS controls the amount of light coming from a light bulb such that the light level at the light sensor remains constant. This control requires that the output from the light bulb must vary. One way to vary the light output is to control the voltage (input) to the light bulb. This new variable output light bulb is referred to as an effector because it changes in response to system requirements. We will refer to the component of the system that regulates the voltage as the regulator. This CLLS system has a negative feedback loop because CLLS increases light output if natural (or artificial) light decreases and vice versa.
2. If regulating the light level becomes essential, the CLLS may become more complex. Outside disturbances such as snow and sleet will interfere with the sensing of ambient light. If system regulation requires adaptation to adjust for this disturbance, the system will require alteration.
3. The components of this CLLS consists of inputs to a light source (voltage), an effector that can vary light levels (light bulb), a sensor that detects the amount of light (a light detector), and a comparator that compares the signal from the sensor to a set point (the light level at which the system turns on or off). Finally, a controller varies the voltage to the light source in response to the signal from the sensor. The controller is the combination of the comparator and the regulator. Finally, the disturbances to the regulated variable as well as other systems impacting that variable are schematized (Fig. 1.6).
4. To be complete there are positive feedback systems as well. In a positive feedback system, the response of the system increases the difference between the regulated variable and a set point. When positive feedback occurs, the system frequently becomes unstable and usually leads to system failure. In physiology, typically pathology causes positive feedback. An example of this pathology is the response of the cardiovascular system to hypotension in the presence of coronary artery disease. Hypotension leads to an increase in HR and contractility that lead to more ischemia and more hypotension.
VIII. The cardiovascular system components
A. The simple control system model can be used to develop a model of the cardiovascular system. This model is useful if it predicts the system response to system disturbances. Modified from [1, p.249], components in Figure 1.6 can be broken down into sensor, controller, and effector functions. The following discussion will summarize concepts for each function.
Figure 1.6 Diagram of a control system with a feedback loop. If the system response to a disturbance is to return the regulated variable back to the original set point, the system is a negative feedback system. Many physiologic systems are negative feedback systems.
B. For the sensor functions, the two best characterized sensors—the baroreceptors in the carotid sinus and the volume and HR sensors in the right atrium—will be outlined in detail.
C. Regulation of a variable is defined as the variable remaining fixed despite changes in its determinants. The regulated variable in the cardiovascular system is primarily BP and occurs via a negative feedback loop.
D. Our survival requires a wide range of CO and SVR. Since BP changes only by perhaps ± 25% from our being asleep to maximal exercising, CO increasing is offset by SVR decreasing. The range for each is approximately 4 to 6-fold.
E. Individual organ survival is preserved as a consequence of system integration. It is noted from above that a well-conditioned subject can increase CO 4-fold while a sedentary person can only increase 2-fold. However, while running, his blood flow to skeletal muscle must be 100-fold greater than its minimum value. This apparent disparity—4-fold increase in CO but 100-fold increase to skeletal muscle—because blood flow to other organs is reduced.
F. The brain is the site of the comparator and integrator. Together the comparator and the regulator make up the controller. While anatomic sites for individual comparator and regulator functions are known, the specifics of interaction of these sites and regulation of control balance (what effector is utilized and how much) are largely unknown.
G. For this review, details of the sympathetic and parasympathetic outputs will not receive focus. As outputs from the controller, the nervous system signals recruit and derecruit the effectors in a predictable fashion through release of norepinephrine and acetylcholine as indicated in Figure 1.7.
H. The effectors of the cardiovascular system—heart, venous system, and arterial system— respond to changes in system demand. Fundamentally, the cardiovascular system must maintain BP in a normal range despite a wide range of demand, e.g., exercise or limitations of effector reserves such as dehydration and ischemic and valvular heart disease. To adapt, the effectors have a range over which they can expand their capacities. Each effector has an expandable range known as its physiologic reserve.
I. Effective feedback control requires functioning sensors, comparators, and effectors to have the desired effect—in this case regulation of BP. The understanding of complexities and capacities of the sensors, comparators, and effectors as well as system integration provides a clinical basis for reducing surgical and anesthetic risk.
IX. Stretch receptors: BP sensors
A. The simplified view of BP regulation presented herein is useful for organizing priorities in maintaining BP. Integration of BP regulation is more complex and requires meeting demands of competing organs.
Figure 1.7 This simplified representation omits input to the brain from sensors throughout the vascular tree and the ventricular chambers. As discussed in the text, there are multiple inputs to the brain not represented in this simplified view. Input to the brain includes signals from sensors (receptors) that monitor blood volume, CO, SVR, and HR. Input to the effectors occurs through the sympathetic and parasympathetic systems with neural transmitters indicated. NOR, norepinephrine; ACH, acetylcholine; S.A., sinoatrial.
B. Excepting the splanchnic circulation, organs are organized in parallel with either the aorta or PA as their source of BP.
C. As a consequence, blood flow to the individual organs can be locally adjusted or centrally integrated. This organization allows for individual independent organ perfusion as long as aortic or PA BP is maintained.
D. Additional sensor sites include systemic and pulmonary venous volumes, HR, SVR, and ventricular volumes. Experiments looking at cardiovascular system responses to isolated disturbance in these locations have demonstrated their existence.
Figure 1.8 The A fibers (stretch receptors) are located in the body of the atrium and fire during atrial contraction and sense atrial contraction rate or HR. The B fibers (stretch receptors) are located at the intersection of the inferior vena cava (IVC) and superior vena cava (SVC). Their neural signals occur during ventricular systole when the atria are filling. Hence, they sense atrial volume.
E. All known pressure-sensitive sensors in the cardiovascular system are stretch receptors. They respond to wall stretch and not container pressure. Hence, compliance of the receptor site impacts receptor response.
F. In addition to the volume of a chamber, the rate of change of that volume may be sensed and afferent signals are sent to the brain.
G. Consequently, depending on the sensor location, sensor signals provide data that reflect BP, venous capacitance, SVR, ventricular contractility, SV, HR, and other parameters. Most of the knowledge of these sensor sites is inferred from indirect experiments.
X. Atrial baroreceptors
A. Within the right atrium, there are receptors at the junction of the superior and inferior venae cavae with the atrium (B fibers) and in the body of this atrium (A fibers, Fig. 1.8). The corresponding impulses from the respective nerves are seen on the left. A fibers, seen in both atria, generate impulses during atrial contraction, indicating that they detect HR.
Figure 1.9 The nerve discharge frequency from the baroreceptor recording change from ~30 pulses/s to 80 pulses/s after the response reached a steady state. Note that there was a transient change during the rapid response phase as well.
B. B fibers are located only in the right atrium and impulses occur during systole when the atrium is filling. Maximum frequency of B fiber impulses occurs just prior to AV valve opening and this frequency is linearly proportional to right atrial volume. Hence, B fibers detect atrial volume. Hence, information necessary to infer CO is therefore available.
C. The B receptor impulse rates (volume receptor) have adrenal, pituitary, and renal effects. These effects form another negative feedback loop control system that regulates volume in the long term through the adrenal–pituitary–renal axis.
D. In addition to these B fiber signals, results from system-oriented whole animal experiments indicate that there are additional volume receptors throughout the cardiovascular system. Not surprisingly, large systemic veins, pulmonary veins, as well as right and left ventricles all have effects on the cardiovascular system that are volume dependent. The observed effects on CO, SVR, and BP clearly indicate that there is a predictable impact of these additional receptors on overall homeostasis.
XI. Arterial baroreceptors
A. The baroreceptors in the carotid sinus are the first described sensors of BP. Additional arterial baroreceptors have been discovered in the pulmonary and systemic arterial trees including a site in the proximal aorta!
B. “The carotid sinus baroreceptor monitors BP” is a rapid response to the common question of where BP is sensed. However, the details of what is sensed in this location are less frequently known [1, p. 246].
C. In Figure 1.9 a step change in mean BP from 50 to 330 mm Hg is plotted along with the neural discharge of the carotid sinus fiber. There is a change in the neural frequency reflecting the step change in BP and then a leveling to a steady-state discharge rate, indicating a signal correlating with mean BP.
D. In Figure 1.10, the relationship between neural impulses in a single neural fiber emanating from a carotid sinus nerve can be seen relative to the pulsatile “BP waveform” in the carotid body.
E. Signals related to contractility (upstroke of BP), SVR (the dichrotic notch in the peripheral circulation), and downstroke emanate from the carotid sinus nerve. Hence, the oscillatory shape of the BP waveform is detected and a signal sent to the brain controller.
Figure 1.10 Note that the upslope of arterial pressure (dP/dt), the downslope (SVR), and the notch (SVR) are reflected in the action potential frequency.
F. The aortic baroreceptor is located near or in the aortic arch. Infrequently, cardiac anesthesiologists can become acutely aware of its presence. When distorted secondary to the placement of any aortic clamp, the resulting aortic baroreceptor signal results in an acute and dramatic increase in BP. The presumed mechanism is that the clamp distorts the aortic baroreceptor. This distortion results in a signal that BP has precipitously fallen. Despite the fact that the carotid baroreceptor has no such indication, hypertension ensues—imperfect system integration. Immediately releasing the cross-clamp (when possible) promptly returns the BP to a more normal level (usually). When release is not feasible, short, rapid-acting intervention— pharmacologic or reverse Trendelenburg—is required. How does reverse Trendelenburg affect the pressure?
G. Cardiovascular effectors
1. BP is the product of CO, or HR times SV times SVR plus right atrial pressure (RA):
BP = (CO * SVR) + RA = (SV * HR *SVR) + RA (1)
2. Organ perfusion is dependent on the difference between arterial pressure and RA and organ resistance. For homeostasis, a focus on perfusion is important in our view of BP.
3. The organs in the body are in parallel and the SVR is dependent on the individual resistance in a simple but more complex way than I will cover here!
4. SV is dependent upon contractility, preload, and afterload [Eq. (1)]. Sympathetic tone sets contractility, preload, and SVR. The myoplasmic Ca2+ concentration, fraction of blood in the thorax versus total blood volume, and the SVR are all functions of sympathetic tone.
5. HR is dependent on the sympathetic tone as well.
XII. Effectors and physiologic reserves
A. The range that each of the effectors can contribute to maintaining BP through increasing CO or changing SVR in the face of everyday life requirements (sleeping to climbing a mountain) is referred to as physiologic reserve.
B. Knowing this range for each effector gives a framework to consider which reserves can be utilized to further increase CO or perhaps increase SVR.
C. This concept provides a framework for considering which effector is available to lower or raise BP. To have a clinical situation where additional physiologic reserve cannot be recruited (because of pathology or exceeding a range) will increase risk and jeopardize outcome.
1. A normal resting HR range is perhaps 60 beats per minute (bpm). A maximum attainable HR in a 25-yr old would be 220 as compared to 170 in a 55-yr old. Hence, an average expansion factor is ~2.5- to 3.5-fold.
2. The clinician must keep in mind that of the three main determinants of oxygen demand— HR, contractility, and wall tension—only HR correlated with ischemia in patients under anesthesia. Hence, this correlation tempers the use of this expansion factor.
E. Systemic vascular resistance
1. Within the systemic vascular tree, the organs in our body, recognizing the lung and liver as more complex circulations, emanate from the aorta or the PA. This arrangement is referred to as be parallel.
2. Because of the large diameters of the aorta and pulmonary artery, there is no physiologically important decrease in mean BP along either of their lengths. Consequently, each organ experiences the same mean BP. Through its own resistance, the organ determines the blood flow to it.
3. In normal life, organ blood flow requirement are met without compromising BP. Metabolic requirements (substrate supply, oxygen supply, and demand) are met despite the variability amongst organs for blood flow. The cardiovascular system maintains pressure through its effectors via central nervous system (CNS) control responding to local organ control of its resistance.
4. Looking at Equation (1), if BP is regulated, when SVR is high then CO must be proportionately lower and vice versa. What is the observed range of SVR? For a severely dehydrated person or one with a bad left ventricle, the cardiac index might be 33% of normal (1.2 LPM/M2 [Eq. (1)]). The corresponding SVR would be three times the normal value (3,600 dyne s/cm5 [Eq. (1)]). For a well-trained athlete who, during maximal exercise, would increase CO 7-fold, the SVR would be ~15% of normal (~200 dyne s/cm5 [Eq. (1)]).
1. Contractility is not a commonly measured clinical variable because of the difficulty in direct measurement and the impact of afterload and preload on its estimate. The clinician is left to estimate any changes. A consequence of an increase in contractility is the ability to increase wall tension in the left ventricle. This increased ability will lead to an increase in ejection rate and fraction under normal conditions. While there are differences in how trained and untrained healthy subjects achieve the increase, both increase ejection fraction (EF) from 60% to 80%. This 33% increase in EF contributes to a modest but important increase in CO.
G. Intravascular volume: Venous capacitance
1. Total blood volume can be estimated from body weight. In the ideal 70 kg person, an estimate of blood volume is 70 mL/kg or ~5 L. This blood volume is considered euvolemia.
2. The distribution of that volume between intrathoracic and extrathoracic (or systemic) volumes is roughly 30% and 70%, respectively.
3. In each of these two compartments, approximately one-third of the blood is in the arteries and capillaries and two-thirds are in the venous system.
4. The pulmonary veins hold 1,100 mL and the systemic veins hold 2,400 cc (almost half of the blood volume).
5. Relaxation of venous tone results in an increase in venous capacity for blood. If there is no change in blood volume, this results in a decrease in atrial filling pressures.
6. Returning those atrial filling pressures to their original values requires infusion of volume. The amount of intravascular volume added to return these pressures to their original values is referred to as the venous capacitance reserve.
7. In addition to the blood volume defined as euvolemia, the intrathoracic and extrathoracic compartments can expand their respective volumes by approximately 300 and 1,200 mL!
8. Thus, quantitatively, 1,500 mL of intravascular volume is an estimate of this venous capacitance reserve.
9. This reserve intravascular volume is added to a euvolemic blood volume (5 L in a 70 kg subject), and the total intravascular volume would be 6.5 L or a 30% increase.
10. Functionally, maintaining intrathoracic blood volume in the face of hemorrhage is an important task of the cardiovascular system. Maintenance of this blood volume results in maintenance of CO through shifting blood into the thorax and recruitment of HR and contractility.
11. In pathologic states resulting in chronically elevated right- or left-sided atrial pressures, venous dilation results in an increase in “euvolemic” blood volume.
12. Particularly in the systemic venous system, this increase in capacity can be large. While there is no experimental data, anecdotal observations of patients going on cardiopulmonary bypass clearly demonstrate this fact. However, the extent that the increased volumes can be recruited to maintain intrathoracic volume, the key to maintaining preload, is unknown.
13. Like hemorrhage, chronic diuresis leads to a contracted venous bed. Hence, caring for patients who are chronically or acutely made hypovolemic secondary to this management approach must include understanding the state of their venous volume status and its capacitance.
14. Worthy of note, chronic diuretic administration leads to venoconstriction. However, an acute dose of lasix will venodilate the patient with heart failure and actually lower intrathoracic blood volume due to the shift of blood into the dilated systemic veins.
H. Lymphatic circulation: A final reserve?
1. Lymphatic circulation occurs in interstitial space between the blood vessels and intracellular space. Clinically this system is rarely discussed but physiologically plays a vital role. For our purposes, its role in protection of organs from edema and recruitment of volume in times of high sympathetic tone—severe hemorrhage—will be discussed.
2. The characteristics of this space help prevent fluid accumulation in two ways—transport of fluid through the lymphatic conduits and its low compliance .
3. In interstitial space, the lymphatics are tented open by a collagen matrix. Because of this tenting, they are not compressed when the interstitium is edematous. Lymphatics increase their flow during edematous states.
4. Consequently, more fluid leaves the interstitium via lymphatic drainage when more fluid enters the lymphatics across the capillary.
5. The collagen matrix is a gel and this structure results in interstitial space having a low compliance. Consequently, fluid entering interstitial space raises interstitial pressure rapidly (low compliance) and the increase in interstitial pressure opposes further transudation of fluid across capillaries.
6. This increased interstitial pressure also increases lymphatic drainage.
7. This system does not only have water passing through it, but also proteins traverse this space with total proteins moving through it in ~24 hrs daily.
8. It is also dynamic during the convective transport of blood down a capillary. Exchange occurs as fluid leaves the capillary at the arteriole end and returns at the venous end. The expansion factor for this exchange is ~8-fold. Hence, crystalloid administration equilibrates across the vascular and interstitial volumes rapidly.
9. With severe hemorrhage with maximal sympathetic stimulation, interstitial and intracellular fluid may contribute up to 2.5 L of fluid to intravascular volume. While this recruitment of intracellular and interstitial fluid compensates for intravascular depletion acutely, this depletion, particularly of intracellular volume, does so at the expense of cell function, eventually leading to acidosis and compromise of cell function.
10. All three of these compartments—intracellular, interstitial, and intravascular—have a dynamic relationship with at least equilibrium being reached in minutes after volume administration, change in sympathetic tone, or administration of vasoactive drugs.
11. In summary, for major hemorrhage, consideration of volume resuscitation requirements must include intracellular, interstitial, and intravascular compartments. Particularly when sympathetic tone is abruptly altered (induction of anesthesia), the extent of circulatory collapse may be greater than anticipated as fluid within these compartments equilibrates at the new level of sympathetic tone.
I. Brain: The controller
1. It is beyond the scope of this chapter, and to an extent our knowledge, to detail the neural pathways, interactive signaling, and psychological influence to the cardiovascular system response. Hence, the controller, our brain, is considered a black box. In this view, this controller is designed to maintain BP assuming that all the effectors are recruitable.
2. Making the controller a black box may be justifiable on another level. After we describe the system integration, we must recognize that the pharmacology we utilize affects the integration of this system in direct and indirect effects on effectors and perhaps the controller and sensors as well. Other medications affect the ability of the CNS to stimulate responses through receptor or ganglion blockade. For anesthesiologists, in many situations, our clinical management must replace system integration. By understanding the pharmacology present and its effect on the cardiovascular system, clinical judgment dictates a plan to control BP regulation. This control responsibility must include temporizing and maintaining BP variability. Unable to rely on the cardiovascular system alone, the clinician manipulates the effector responses to maintain BP always cognizant of the need for physiologic reserves in the face of upcoming disturbances.
3. Understanding the comorbidities anticipates the limitations in physiologic reserves and their availability for recruitment during stress. Recognition of necessary compromises for adjustment of anesthetic approach reduces the risk of morbidity.
XIII. The cardiovascular system integration
A. The cardiovascular system response to physiologic stress is predictable and reproducible. In its simplest form, if BP is altered, the integrated system response—sensors, controller, and effectors—senses the alteration and returns BP toward the original set point. This negative feedback permits us to lead our lives without considering the consequences or preparing for the disturbances to this system. As each effector is recruited to regulate BP, it can contribute less to compensating for an additional stress. We take for granted the range and automaticity of this system response.
B. In healthy subjects, the utilization of their reserves to respond to recruitment is dependent on training levels, hydration status, and psychological state amongst others. In healthy subjects, their limits are set through a complex physio-psycho state that ends with not being able to go on—hitting the wall.
C. For patients, the response of effectors may be limited by effector pathology. The most common of these is ischemic heart disease.
D. To maintain blood in the face of hypotension the cardiovascular system responses are predictable.
1. Oxygen demand. HR and contractility will be increased. Each increases myocardial oxygen consumption. Wall tension will be decreased. Since HR is a primary determinant of the onset of ischemia under anesthesia, its elevation is a reason for concern and intervention.
2. Oxygen supply. Assuming no blood loss or alteration of oxygenation, increased HR leads to reduced diastolic time. Hence, endocardial perfusion time will be reduced. Reduced diastolic systemic pressure will most likely be greater than LVEDP reduction. Consequently perfusion pressure is reduced.
3. Intervention: The anesthesiologist will most likely administer neosynepherine in response. SVR will increase, and blood volume will shift from the systemic veins into the thoracic veins, increasing preload and leading to an increase in SV. BP will rise, HR will fall, contractility will be reduced, diastolic time lengthened, and perhaps coronary perfusion pressure will rise as well.
a. Response time required
(1) Responding to hypotension is an everyday occurrence for an anesthesia provider. Defining hypotension is somewhat difficult. Physiologists would arrive at a value of around a mean BP of 50 mm Hg for organ function. Hypotensive anesthesia challenges that value and data indicate that a sitting position is different from a supine one. A prevalent clinical definition is “±25% of the preoperative value.” Given anxiety, determining that preoperative value is not always easy. Clinicians face this dilemma and almost individually resolve it.
(2) As an aside, cardiac anesthesiologists in the post-bypass period are confronted with BP management in the patient who frequently has hypertension, renal insufficiency, peripheral vascular disease, and an aorta that has been (minimally) cannulated. Systolic pressures, frequently under 100 mm Hg, are the norm in this setting.
(3) If it is low, how long at the pressure will cause damage. If a neuron is without oxygen, the neuron has a lifespan of minutes. Given that reality, sacrificing all other organ functions to maintain BP is essential on the time scale of minutes.
(4) For the kidney, even renal insufficiency created during surgery can recover. Consequently, sacrificing renal perfusion is acceptable to protect the neuron.
(5) For a cardiac myocyte, the time constant is several minutes. The exact time constant is unclear for an individual cell but is certainly approaching an hour. After 4 hrs, the magic window for thrombolysis to be effective, 50% of myocytes will survive. Therefore, compromising myocardial oxygen supply and demand to preserve neurons is acceptable as a temporizing measure.
4. Neosynepherine administration elicits a very positive physiologic impact if we do not stop there. As the new controller, the anesthesia provider needs to consider why the hypotension occurred, if that reason is going to continue or get worse and how soon the remaining physiologic reserves can maintain homeostasis.
5. These considerations are crucial in determining the likelihood of long-term—the course of the operation and the early postoperative period—hemodynamic stability of the patient.
6. Frequently, volume management is key in this decision. Consider that if instead of administering neosynephrine above, a volume challenge was administered and the BP response was to increase, the oxygen demand and supply benefits would remain. However, instead of consuming physiologic reserves through neosynephrine use, the controller would be providing physiologic reserves through increased venous capacitance and decreased SVR.
a. Achieving the balance between the need for short-term intervention and long-term stability is the responsibility of the controller, the patient’s or the provider’s brain.
XIV. Effect of anesthesia providers and our pharmacology on the cardiovascular system
A. The surgical patient
1. White-coat hypertension is common. Some attribute this hypertension to the flight response necessary for survival! The perioperative period is certainly a time of increased anxiety for many patients. In the context of our cardiovascular system, the anxiety represents an input that most likely alters the response at the controller level—the brain. Since non–white-pant hypertension may contribute to cardiac-related complications perioperatively, a patient who is hypertensive in the preoperative area will be given an anxiolytic as the first step to determine if it is chronic or not.
2. If the anxiolysis reduces the BP to the normal range, we attribute the hypertension to anxiety and proceed. If it does not, we attribute it to an altered set point for BP and must consider the risks and benefits, as ill-defined as they are, before proceeding.
B. The anesthetic choice
1. For a healthy patient for low-risk surgery, our closed claims data conclude that anesthetic choice has little to no bearing on outcome. Low surgical risk in the setting of normal physiologic reserves protects homeostasis to the extent that the margin for error is great. Provocative statement—perhaps but the closed claims data base would support this view.
2. For the high-risk patient with comorbidities related to diabetes, ischemic or valvular heart disease for high-risk surgery, consideration of the status of their physiologic cardiac reserves becomes extremely important. The entire perioperative period subjects the patient to increased risk. Understanding the consequences of the patient’s pathology on their physiologic reserves and use of clinical management approaches to reduce the risk should influence the anesthetic choice.
3. In this chapter, we discussed physiologic reserves in the context of normal physiology. The principles related to ventricular function, determinants of myocardial oxygen consumption, and physiologic reserves apply in the pathologic situation as well.
4. Of all the physiologic reserves discussed, the physiologic reserve that is minimally affected by pathology during surgery and is not shown to affect outcomes adversely, except perhaps for gastrointestinal (GI) surgery and major trauma, is volume management to replenish or expand venous capacitance reserves. The principle that “An empty heart cannot pump blood!!!” is true. The number of patients resuscitated from hypovolemia is far greater than those who have incurred congestive heart failure due to too much fluid.
C. Treating the cause
1. When clinical signs and symptoms do not agree with clinical judgment and conclusions, more data are necessary. The two most useful monitors in the setting of unresponsive hypotension under general anesthesia are the PA catheter and the transesophageal echocardiography (TEE) examination.
2. The PA catheter has been touted and maligned as a monitoring tool. Rao et al.  demonstrated an improved outcome in patients undergoing surgery in the setting of a recent myocardial infarction. Using physiologic principles to guide management, Rao et al. demonstrated improved outcome in this high-risk group. A national survey demonstrated that clinicians did not understand the physiologic principles underlying the interventions in Rao’s study. The mere presence of a PA catheter has not been shown to improve outcome or “The yellow snake does no good when inserted .” While anecdotal experience does not refute data, using the data from the PA catheter to optimize the physiologic reserves available for perioperative optimization would be the parallel to Rao’s results for the high-risk setting of a recent acute myocardial infarction.
3. The TEE probe is the optimal tool for assessing ventricular volume status and regional wall motion abnormalities. An experienced echocardiographer can assess the volume status of the ventricle (intrathoracic blood volume) within a minute and almost as quickly assess ventricular systolic function. These two data elements provide immediate help in clinical management of the unresponsive hypotension. Particularly in a setting where ventricular compliance can change (ischemia, acidosis, and sepsis) so that filling pressures may not reflect volume status of the ventricles, TEE is an essential tool. As a tool, it can be used to assess the state of venous capacitance through Trendelenburg and reverse Trendelenburg manipulation during observation. Clearly with three-dimensional echocardiographic capabilities, CO becomes measurable. The available physiologic reserves are then known.
XV. Clinical examples to discuss
A. GI surgery: A special case?
1. In GI surgery, conservative fluid management is reported to improve surgical outcomes. While the studies are limited, the outcome improvement appears real  but controversial . Important to note when considering these data are that a bowel preparation and hydration the night before and the morning of surgery preoperatively are important parameters that may have led to reduced fluid administration intraoperatively.
2. When extrapolating these results to another operation, all interstitial spaces are not the same—specifically, the gut interstitial space is different from all other. GI function involves absorption from the GI tract. Interstitial fluid fluxes and a lymphatic system function are different from those in other organs. Globalizing fluid management from GI surgery and inferring that if the outcome improves for GI surgery due to fluid management is unsound.
3. Balancing the benefits and risks of surgery, fluid shifts, cardiac system perturbations with the risk of fluid administration, and its other benefits should be the focus.
XVI. Two examples emphasizing fluid management
A. A patient NPO for 12 hrs on a diuretic.
1. The patient is undergoing a 30-min herniorrhaphy.
2. The patient is on a diuretic for chronic hypertension.
3. In correcting volume deficit, the goal is to achieve euvolemia.
4. This 70 kg patient on a diuretic for hypertension is NPO overnight. The diuretic results in volume constriction—a guesstimate of 500 mL. Twelve hours of NPO results in sensible and insensible losses—guesstimate 1,250 mL.
5. The type and duration of surgery will result in insignificant fluid shifts.
6. The goal is euvolemia.
7. Insensible and sensible loss replacement—1,250 mL of crystalloid
a. Considerations: Nuance of the lactated ringer’s versus normal saline controversy, actual ionic content of losses. Both deemed inconsequential in this patient.
8. Chronic intravascular volume contraction—500 mL of the following:
a. Crystalloid administration of 1,500 mL infusion
(1) In the intraoperative period the presence of the chronic volume depletion will not be compensated for by the CNS controller and will have to be accommodated for by the anesthesia provider.
(2) While neosynephrine could be used,
(a) The postoperative pain medications will affect BP regulation and result in hypotension more likely.
(b) Nausea and vomiting are reduced in the hydrated patient.
9. Total fluid 2,750 mL—rounded to 3 L.
a. If recruiting the venous capacitance reserve of 1,500 mL were the goal, 4,500 mL of additional crystalloid would have been infused with a hypervolemic patient but with no change in atrial filling pressure.
b. Hence, an overinfusion of 500 mL of crystalloid would not be noticed in the cardiovascular system.
10. In this setting, how do we respond to “You gave too much fluid!!!!”
a. A proposed rationale response is “The patient had an insensible deficit of 1,250 mL based on NPO status, I guesstimated that he was volume constricted because of his diuretic for hypertension—~500 mL as he was well compensated when awake—and he became hypotensive on induction, consistent with that. Given that, and that the perioperative period will have less effective cardiovascular BP regulation, hypotension more likely, I estimated approximately 2,750 mL to get him euvolemic. If I erred, his physiologic reserve of 1,500 mL of intravascular volume would have accommodated ~5,000 more mL. He is not nauseated at the moment and I expect him to have a stable BP until his ambulatory discharge. Would you like me to order pain meds for the Phase 2 recovery.” Concise, factual, and true. Have fun with your knowledge and profession!
B. This same Patient, NPO for 12 hrs on a diuretic; involved in a motor vehicle accident outside the hospital entrance
1. Same 70 kg hypertensive patient on a diuretic is involved in an MVA on his way to the hospital.
2. Vital signs in the emergency room (ER) minutes after the accident
a. HR 180
b. BP 60/40
3. Conscious, Foley catheter in place, large-bore access available, monitored, no head or chest trauma
4. Hematocrit (HCT) 24
5. Clearly, this clinical operating room course will be difficult. Induction, further monitors, maintenance, etc. are important considerations. But in the ER, while other decisions and actions are going on, consider volume management alone.
6. Volume management
a. The goal of fluid replacement:
(1) From the above patient considerations, prior to accident, returning to euvolemia required 3 L.
(2) Ongoing and potential worsening of blood loss suggests that a goal of recruiting venous capacitance reserve (1,750 mL) through volume expansion is preferable—1,500 mL of additional venous capacity beyond euvolemia.
b. Estimating extent of hypovolemia and crystalloid replacement for achieving the goal:
(1) NPO times 12 hrs plus volume depletion from diuretic—3 L (from the above patient)
(2) Recruiting venous capacitance reserve of 1,500 mL—4.5 L of crystalloid
(3) Vital signs indicate at least a greater than 25% reduction in intrathoracic blood volume. The extrathoracic blood volume is reduced to maintain intrathoracic blood volume, and an estimate of overall intravascular volume approaching 40% is within reason (2 L of blood loss) requiring 6 L of crystalloid replacement.
(4) Interstitial and intracellular volume recruitment (up to 25%) into intravascular space compensates for blood loss in this situation as well—1.2 L of crystalloid.
(5) Total crystalloid administration for achieving the goal of euvolemia plus adding venous capacitance reserve assuming no ongoing blood loss is as follows:
Total crystalloid: 3 + 4.5 + 6 + 1.2 = ~15 L!!
(6) Concerning the actual volume resuscitation, various protocols advocate different combinations of colloid, crystalloid, fresh frozen plasma, platelets, packed red cell units as well as antifibrinolytics, platelet function enhancers, etc. Consideration of the fluids loss estimates from the individual compartments above combined with the intravascular volume, coagulation and oxygen carrying capacity issues in this case will drive ultimate fluids administered. Consideration of requirements of each of the compartments is necessary to restore intravascular volume and cell function ultimately.
c. Red cell mass and coagulation
(1) Clearly, red cell mass, commonly thought of in terms of HCT, and coagulation factors will also require consideration. There are protocols for RBC to fresh frozen plasma (FFP) ratios in trauma and this consideration is beyond the scope of this chapter.
(2) However, an estimate of RBC requirements based on red cell mass reveals the following:
(a) Initial HCT 24%
(b) Initial intravascular volume of 60% of normal (contraction of 40% volume)
(c) Desired goal of volume expansion to include euvolemia plus venous capacitance reserve: 5 5 L + ~1.5 L.
(d) This represents a 30% increase in intravascular volume or 130% of euvolemia.
(e) Your estimate without reading on of his HCT after 15 L of crystalloid
(f) The final HCT estimate calculation is as follows:
Final HCT = Initial HCT (24) * [Initial volume (0.6)/Final volume (1.3)]
(g) That value would be 11%.
(h) That HCT is too low. Setting a desired HCT, transfusing RBCs to reach it with the recognition of ongoing blood loss, and infusing FFP and platelets to correct coagulation deficiencies are dynamic considerations in trauma. Using physiologic principles outlined for volume managment, the anesthesiologist can guesstimate endpoints for product component requirements. In the face of continued bleeding, recalculating guesstimates and retesting hypotheses are essential to achieving hemodynamic and hemostatic stability.
The remainder of this book is focused on cardiac anesthesiology. The patients to whom it applies have significant pathology as it relates to the cardiovascular system. In this chapter, we reviewed patients with a normal, intact cardiovascular system. This model provides the building blocks for putting pathology into the context of the normal cardiovascular system. From the effect of hypertension on the sensors, to the effect of increased intra cranial pressure on the brain or the effect of HR and contractility in the presence of coronary artery disease, pathology impacts the desired response of the cardiovascular system. Consider the system effects as you apply your management of the anesthetic as the controller of this system. This individualization will provide a foundation for your choices and responses. In acting on principles, a reduction in morbidity and mortality may (can) be achieved (Rao).
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