849

Review Article The role of the vasculature in regulating venous return

Eric Jacobsohn MB CHB PKCPC,* and : historical Robin Chorn ~Sc MB CHB FKCPC,"~ Michael O'Connor MD* and graphical approach

Purpose: To review the physiology of cardiac output regulation by the peripheral vasculature. This will enable the clinician to understand and manage the complex circulatory changes in various forms of shock, and in other common altered circulatory states encountered in anaesthetic practice. Source: Articles were obtained from a Medline review (I 966 to present; search terms: shock, venous retum, car- diac output) and a hand search (Index Medicus). Other sources include review articles, personal files, and textbooks. Principal fmdings: At steady state, cardiac output is equal to venous retum 0/R). Venous return depends on mean systemic pressure (PMs), which is the pressure in the peripheral vasculature driving blood flow to the , (Pg~), and the resistance to venous return (Rv). When considering VR, P~ is the downstream pressure to VR, and not simply an indirect measure of the volume status. The pressure gradient forVR is, therefore, PMs - Pp~, and in a system obeying Ohm's Law, VR = Shock and other altered circulatory states cause changes in both VR and cardiac function. The circulation can be con- veniently described by a venous return and a cardiac output curve. By drawing these curves for each clinical situation, a clear understanding of the altered circulatory state is obtained, and treatment options can be dearly defined. Conclusion: The peripheral circulation controls cardiac output in many clinical conditions. Manipulation of the peripheral circulation is as important to the successful treatment of shock and other altered circulatory states, as is the manipulation of cardiac output.

Objectff : Revoir la physiologie de la regulation vasculaire p&iph6rique du d6bit cardiaque. Ceci devrait permettre au clinicien de comprendre et de prendre en charge les changements circulatoires complexes survenant dam les 6tats de choc et autres 6tats d'instabilit6 circulatoire rencontres en anesth6sie. Source : Les articles ont 6t6 compil6s grace ~ un survol de Medline (de 1966 jusqu'~ maintenant ; mots-cl6s : choc, retour veineux, d6bit cardiaque) et une recherche manuelle (Index Medicus). Des artides de revue, des dossiers per- sonnels et des manuels ont aussi 6t6 utilis6s. Principales constatations : ~, 1'6tat d'Equilibre, le debit cardiaque est Egal au retour veineux (RV). Le RV depend de ta pression systolique moyenne (PsM) laquelle est constituEe de la pression vasculaire p&iphEriques qui am6ne le sang au coeur, la pression auriculaire droite (PAD) et la resistance au retour veineux (Rv). Si on examine le RV, on con- state que la P~ est la pression d'aval du RV et non simplement une mesure indirecte de la volEmie. Le gradient de la pression pour RV est donc PsM-P~ et ce syst6me obEit ~ la Ioi d'Ohm, RV = PsM-PAR Le choc et les autres Etats d'instabilitE circulatoire modifient ~ la fois le RV et la fonction cardiaque. II est commode de representer la circulation par une courbe du retour veineux et du debit cardiaque. Le trace de ces courbes pour cha- tune des situations cliniques permet de mieux comprendre rEtat d'instabilitE circulatoire et d'acc6der ~, des options thErapeutiques clairement dEfiNes. Conclusion : Dans plusieurs situations cliniques, la circulation p&iph&ique contr61e le d6bit cardiaque. La manipu- lation de la circulation p~riphErique constitue un traitement important du choc et des autres Etats d'instabilitE circula- toire au m~me titre que la manipulation du debit cardiaque.

From the Dcpartment of Anesthesia and Critical Care, University of Chicago, Chicago, IL* and The Department of Anesthesia, University of Southern California, Los Angeles, CAt Address correspondence to: Dr. Eric Jacobsohn, Department of Anesthesia and Section of Critical Care Medicine, University of Manitoba, HealthSeienccs Centre, GH723-820 Sherbrook Street, Winnipeg, Manitoba, R3A 1R9 Canada. Acceptedfor publication April 27, 1997.

CAN J ANAESTH 1997 / 44:8 / pp 849-867 850 CANADIAN IOURNAL OF ANAESTHESIA

PHYSIOLOGY OF VENOUS RETURN AND RADITIONALLY, cardiac output is dis- CARDIAC OUTPUT REGULATION cussed ha terms of the factors that govern History and circulatory models cardiac function, which include , Circulatory model of Weber T , rate, rh,,~hm, and contractility. Circulatory model of Starling and Bayliss ~e this perspective is helpful in dealing ~4th patients Circulatory model of Starr and Rawson whose circulatory function is limited by diseased , Circulatory model of Guyton it is incomplete. Under normal circumstances, cardiac The multiple circuit circulatory model output is controlled by the peripheral vasculature, Integration of cardiac function and venous return which is as energetic at returning blood to the heart as the heart is at pumping blood to the periphery: The VENOUS RETURN AND CARDIAC OUTPUT importance of the systemic vasculature in regulation of IN PATHOPHYSIOLOGICAL STATES Shock the cardiac output is not immediately apparent when considering the above determinants of cardiac output. Hypovolaemic shock However, preload is the force distending the heart at ('ardioeenic shock Distributive shock end , and is dependent on the interaction of the Obstructive shock heart and the amount of blood returning to the heart from the peripheral vasculature. Tl-fis review will exam- Spinal shock Mixed ine the factors that regulate venous return (VR), and the importance of VR in the control of the cardiac out- Miscellaneous put in both physiologic and pathophysiologic condi- Venous return and cardiac output in other com- tions. This will enable the clinician to understand clearly mon clinical situations and manage the haemodynamic changes in the many Cardiopulmonarv bypass forms of shock and other altered circulatory states. Pregnan~ 7be effect of volatile ana,'sthetic agents on circulatory PHYSIOLOGY OF VENOUS RETURN AND function CARDIAC OUTPUT REGULATION BY THE CONCLUSION VASCULATURE History and circulatory models To understand the concept of the regulation of cardiac output by the peripheral circulation, it is important to analyse the mathematical and experimental models that have led to the current knowledge of the circulation.

Circulatory model of Weber Much of our knowledge about the behaviour of the cir- culation has its origins in the work of WeberJ He con- structed a model of the circulation by using a portion of small intestine and connecting the two cut ends (Figure 1). The pressure in the fluid-filled system was measured during a no-flow state, and was called the l~drostatic mean pressure. When the system was com- pressed and flow was present, pressures at several points around the system were measured, and the average of these pressures calculated. This was called the ~.droki- netic mean pressure. Weber established that the hydro- static mean pressure and the hydrokinetic mean pressure were equal, He concluded that the pump caused a reduction in pressure on the venous side and an increase FIGURE I Weber's circulatory model. The cut ends of a loop on the arterial side. He established that the mean pres- of intestine are sewn together and valves t~shioncd tt~ allow flow sure in the model could only be increased by distending as indicated. The sponge represents the microcirculation. Pressures are measured at several points in the fluid-filled circuit, both at the tubes through the addition of" more fluid. He pro- rest ~hydrostatic mean pressure) and while being intermittently posed that that system mimicked the human circulation, com[,a'r (hydrokinefic mean pressure). but did not go on to explore this in humans. Jacobsohn etal.: CARDIAC OUTPUT REGULATION 851

Circulatory model of Starling and Bayliss with the . They then measured the The haemodynamic importance of these findings was pressure (PMs) at this neutral point in a dog model further studied by Bayliss and Starling in 1894. 2 They (Figure 2). The dogs were anaesthetized with morphhae, were embarrassed that the importance of Weber's find- and cannulae were placed in the femoral vein, femoral ings in 1850 had gone unrecognized for so many years. artery, portal vein, inferior vena cava, and aorta. The They stated that "the experimental results that we wish vagal nerves were exposed in the neck and the cervical to bring forward are largely such as might be predicted spines of the dogs were severed to induce complete sym- by anyone with a knowledge of elementary principles of pathectomy. The circulation was then arrested by vagal the circulation. Our justification in bringing them for- stimulation. There could be no reflex ward, however, is that they have not been so predicted, after the arrest due to the induced sympathectomy. The and it was only after obtaining the results that we asked experiment showed that, upon cessation of the circula- ourselves why they had not occurred to us before. In tion, the pressure in the femoral artery, portal vein, fact, they seem to be part of a forgotten or disregarded femoral vein, aorta and IVC equilibrated at a pressure of chapter in the physiology of circulation." They reasoned approximately 7 mmHG. They concluded that this was that, if blood were at a standstill, the pressure every- the PMS in a sympathectomized dog. where in the system would be equal, that is the pressure in the arteries and the veins would be at Weber's hydro- Circulatory model of Starr and Rawson static mean pressure. If the heart now began to pump, The importance of these studies and Ps~s were disre- pressure in the arteries would increase and pressure in garded for another 50 yr, until 1940, when Starr and the veins decrease. There must be a neutral point where Rawson 4 developed a mechanical model to simulate pressure would not change as flow commenced. They congestive (Figure 3). They hypothesized reasoned that the point at which pressure neither increased nor decreased must lie on the venous side of the capillaries. 3 They noted that "what does fall from the arteries through the capillaries and back to the heart is the energy level at any point. The total energy is the sum of the hydrostatic and kinetic energies. Because of the large capillary bed, the flow is slow there and hence the kinetic energy is low, and the hydrostatic energy is high. In the veins, the kinetic energy is high and the hydro- static pressure is low. Therefore, it follows that with the inaugtu'ation of the circulation, the point where the pressure is neither raised nor lowered must lie on the venous side of the capillaries." They went on to call this pressure mean systemic pressure (PMs), which was syn- onymous with the hydrostatic mean pressure previously described by Weber. They cautioned not to confuse PMs

HEART STOPPED BY VA GAL STIMULATION

5O

ARTERIAL 40 IS PRESSURE PRESSURE ' ~,~T*'~'L ~ ~.~ VENOUS FIGURE 3 Starr and Rawson's cardiac failure model. Arterial (mmHg) 30 a "~'~ (mmHg) portions, made from thick walled rubber tubing, are shown as hca~' ~eUORAL~ 4 lines. Vcnous portions, made from flexible tubing, are shown as light lines. Capillary beds consist of tubes filled with glass beads. I0 Manometers are connected at several points around the circuit, and a flowmeter is also present. This model could mimic many different o! circulatory states, including congestive heart failure. They showcd TIME (rain) that an increase in (PMs) does not occur as a result of heart failure, FIGURE 2 Baylissand Starling's experiment to measure PMs in a but was a compensatory mechanism for the heart failure. (Note: dog. When the circulation is arrested, the arterial and venous pres- Starr and Rawson renamed PMs, and called it the general static pres- sure equilibrate at the PMs" sure. However, in this review, we will call it PMs to avoid confusion.) 852 CANADIAN JOURNAL OF ANAESTHESIA

that the PMS was the pressure driving venous return to Therefore, it is reasonable to conclude that cardiac out- the heart. They postulated that PMs was increased in put is not controlled by the heart alone. Guy'con6,7, congestive heart failure as a compensatory mechanism emphasized the special importance of the peripheral cir- for decreased cardiac contractility. In their model, they culatory factors that affect the venous return and control could alter volumes, pressure, flows, and make the the cardiac output. He first developed a mathematical individual chambers fail. They showed that, in this analysis of the (Figure 5), and subse- mechanical model of congestive heart failure, PMS was quently tested the analysis in well designed animal exper- increased, not as a result of a failing heart, but as a iments. He postulated that the factors in the peripheral compensatory mechanism. circulation that were important in the regulation of car- They then measured PMS in 64 hospitalized patients diac output were: who had died from various causes,s It was measured with- 1) the PMS; 2) the capacitance of the veins, C; 3) the in 30 min of death by inserting a needle into the heart or resistance to venous return, Rv; and 4) the peripheral a great veha. In patients dying of prolonged congestive distribution of blood flow. heart failure, PMS averaged 20 cm H20 (Figure 4). In He postulated that the PMs was the driving pressure patients dying without heart failure, it averaged 10.6 cm for venous blood flow from the peripher2? to the heart. H20. Because the increased pressure was present after Although the previous models of the circulation had death, they concluded that the increase in PMS represent- defined similar pressures, the concept that the PMS (or ed a reflex circulatory response to compensate for the its equivalent in earlier models) was the driving force poor cardiac function, and was not the result of passive congestion behind the failing heart. They postulated that this increase in PMS improved cardiac output, but did not propose a mechanism. The explanation of how an increased I~MSimproves cardiac output would come from Guyton.

Single circuit circulatory model of Guyton When curves depicting the relationship between mean right atrial pressure (P~) and cardiac output are exam- ined (Frank-Starling curves), it is clear that, within the normal range of cardiac function, cardiac output can RI C:3 vary considerably, while PV,A varies only slightly. P3

1: zU~ a0 ,,%

v fs 0o . m wO ~ "

al Cases with Cases with slighl Cases without Cases without prolonged brief congestion peripheral congestion congeslion congestion or cardiac abnormality FIGURE 5 Model for Guyton's mathematical analysis of the circula- Cases with organic cardiac abnormality lion. C 3 = the capacitance of the arterial tree; P3 = arterial pressure; 1Ls = arterial and arteriolar resis~ace; C 2 and P2 = capacitance and FIGURE 4 Starr and Rawson's measurement Of PMs in humans mean pressure respectively of the capillary and venular storage pool of soon after death. The crossbars indicate average values. Mean pres- the blood; IL~ = resistance from this venous storage pool to the major sure in patients with organic heart disease and prolonged conges- veins; C l and P1 = capacitance and mean pressure of the major veins; tion is higher than in patients without congestion or cardiac R 1 = resistaalce to blood flow from the veins to the fight atrium; abnormalities. The high PMS that persists after death confirms that PP,A = fight atrial pressure; C is the capacitance of the entire circulatory it a compensatory mechanism for congestive heart failure. system. Jacobsohn et al.: CARDIAC OUTPUT REGULATION 853 for blood from the periphery to the heart, had not venous flow from periphery to the heart. It is easy to been explored. He derived the following mathemati- imagine what will happen when the pump in this cal analysis for VR: model is stopped: PRA will increase to PMs and arterial Equation 1 pressure (P) will decrease to PMs' Flow through the system does not influence the reservoir pressure (PMs), VR = PMS - P~ that is, cardiac output has no effect on PMs. ~a R, c,. (R,. ~) %. (~. ~. ~) c~ increased flow in the system can only result from an increase in the reservoir pressure (PMs) or a decrease in C the PRA" In this model, flow from the reservoir to the When the circulatory system is divided in "n" portions pump is represented by the following equation: instead of three portions, the formula becomes: Equation 4 Equation 2 Flow in system (cardiac output) = VR = PMs - P~ VR = PMs - P~

R, c,. (R,. ~) c~...... (_~. ~q. % ....~) c~ The PMs (the pressure in the reservoir) is analogous to C the pressure in the circulation during a no-flow state (PMs)' .The pressure in the reservoir is dependent on As the value of "n" in the preceding formula three factors: 1) the total volume of fluid in the reser- approaches infinity, this formula approaches absolute voir, V; 2) the capacitance of the reservoir, C; and 3) validity for a system of distensible tubes. the unstressed volume of the reservoir, V 0. The numerator in both these formulae is the differ- ence between two pressures, and this may therefore be called the pressure gradient for venous return. It repre- sents the difference between the pressure in the venous capacitance vessels (PMs), and the Pv~. On the other hand, the denominator in each instance is dependent upon the resistance and capacitance of the different portions of the peripheral circulatory system. The denominator may be considered to be the resistance to venous return (Rv). The veins which primarily deter- mine R v include large central veins such as the venae cava, which are passively affected, and peripheral large- and medium-sized veins which can be passively affect- ed or can be responsive to autonomic stimulation and vasoactive mediators. 8 A general formula for this rela- tionship can therefore be expressed as follows: Equation 3 Ra ~ Rv VR = Pressure gradient for VR R~ Guyton's single circuit model of the circulation is shown in Figure 6. 9 The reservoir in the model repre- sents the venous capacitance vessels, and the height of the fluid colunm in the reservoir represents the PMs' The venous system is 40 times more compliant than the arterial circulation and is by far the biggest com- partment in the peripheral circulation. The PMs is .~ I determined by the volume in this compartment and FIGURE 6 Guyton's single circuit model of the circulation. by the compliance of this compartment. Because the Blood from the capacitancevessels (the cylinder) flows through arterial pressure generated by the heart is not trans- the Rv to the RA. Flow is proportional to the pressure gradient mitted to the veins, the presence or absence of flow in Rv (flow = VR = CO = PMs " P~/Rv)" V = total volume in the reservoir (capacitance vessels); V0 = the unstressed volume; R^ = the the system has no effect on PMs" The pressure in the arterial resistance; ILl = the venous resistance;PA = file mean arterial reservoir (PMs) is, therefore, the driving pressure for pressure; PPL = pleural pressure C = capacitanceof the veins. 854 CANADIAN JOURNAL OF ANAESTHESIA

Equation 5 10- V-Vo Pres = PMS = Compliance of the reservoir r 8- "I- PMs 1) The pressure in the reservoir can be changed by E E s- adding or subtracting volume. This would be analo- v gous to increasing or decreasing the volume of blood 4- in the veins. CJO

2) The compliance of the reservoir can be measured n 2- by dividing the pressure change by the volume change. If the reservoir were a narrow cylinder (small 0 ! I capacitance), its compliance would be low, and the 0 4 6 small volume change would cause a large pressure Volume (liter) change. Conversely, if the reservoir were wide (large capacitance), its compliance would be large, and a sim- FIGURE 7 Stylizedpressure-volume relationship of the human ilar change in volume would cause a much smaller vasculature. V0 = volume in the circulation before there is any increase in pressure. V is the total circulatingvolume. change in pressure. These situations would be analo- gous to increasing or decreasing the capacitance of the veins by venodilation or venoconstriction.

3) The unstressed volume (Vo) is the volume that exists and temporarily stopped; however, the intraluminal ha the reservoir before there is an increase in pressure. pressure in the veins immediately rises to PMS' Since Inclusion of the V o is necessary for the reservoir to PMS is greater than the pressure surrounding the veins, mimic the vasculamre, as a certain volume of blood has the veins open, and flow would resume. However, to be present in the veins before pressure will be exert- when the veins open and flow resumes, the negative ed on the walls of the veins. Decreasing V o can increase P~ would again be transmitted, and the veins would the pressure in the reservoir. Hence, decreasing V o of again collapse. A cyclical repetition of this process the veins can maintain the PMS at normal levels in the would result in a fluttering effect. The net effect is to setting of a decreased intravascular volume. It is esti- set the pressure gradient for venous return at PMS- Ps, mated that 70-80% of the in a human is where Ps is the pressure surrounding the great unstressed. Therefore, in an average sized adult, extrathoracic veins. If the pressure surrounding the approximately 1.5 L of blood (30% x 5 L = the stressed veins is atmospheric, the maximum flow is reached at volume) is the amount that actually contributes to the an atrial transmural pressure of zero. Therefore, VR PMS" PMS has been measured to be approximately 8 (flow) obeys Ohm's Law when Pw 20, but the veins mmHg in normovolaemic humans (Figure 7). 1~ The act as a Starling resistor when PRA < 0. compliance of the human venular bed can be derived to The equation for VR is shown graphically in be 0.187 L.mmHg-! (1.5 L + 8 mmHg). Therefore, Figure 8. The intercepts the infusing one litre of fluid acutely would increase the PMS abscissa at a PV,A equal to the PMS (VR = 0 when PeA = by 5.3 mmHG. PMS)" The inverse of the slope of the line is the R v. At Right atrial pressures below atmospheric pressure a P~ < 0, flow is limited by collapse of the extratho- can occur due to contraction of the respiratory mus- racic veins. Guyton called the relationship between the cles. To illustrate this in the model (Figure 6), the PRA and the flow the venous return curve. He tested heart is surrounded by a box, representing the thorax the hypothesis of venous return in an animal modell 6 and pleural pressure (PPL)" Outside the thorax, the Anaesthetized dogs were connected to cardiopul- veins are surrounded by pressure that is approximate- monary bypass (CPB) (Figure 9). The variables that ly equal to atmospheric pressure. Therefore, when a affect VR in the mathematical model were individual- negative PPL is generated by a strong respiratory ly varied. The results (Figures 10, 11) show that: a) effort, the negative pressure that is transmitted to the when other factors remain constant, VR is approxi- right atrium is also transmitted to the great extratho- mately proportional to the PMS -- PRA, the pressure dif- racic veins. As the pressure in the extrathoracic veins ference being the pressure gradient for venous return; becomes negative, the veins collapse because they are b) the increase in the VR due to an increase in PMS is surrounded by a positive atmospheric pressure in the not absolutely proportional to the pressure gradient, abdomen. Vqhen they collapse, flow is instantaneously as an increase in volume is associated with decreases in Jacobsohn et al.: CARDIAC OUTPUT REGULATION 855

VENO~I RL~URN (CARDIACOtnlPtfl lUmP) 8.0 10- 7.0 VR. CO,, Pm'P~ Rv Y E s.ot ~~ / 4.0 ~ .

, w i i 0 1 2 3 4 S 6 ? 8 I) 10 11 10 RIGHT ATRIAL I~ESSURE (mmHgI PMS(mrnHg)

FIGURE 8 Venous return curve. Note that the P~as is the point FIGURE 10 Results of Guyton's experiments. The relationship at which the graph intersects the abscissa (pressure axis). The VR of Pm and VR at different levels of P~. The graphs confirm the reaches a maximum at a Pm of 0 due to the collapsibility of the VR equation; flow = 0 when Pm- PMs. major veins. The inverse of the slope of the line is R v.

~0 co.blo~l Inlmdon 140

| L0J PRAandPMS'0'] ~ "*'~'~'-.~.~.~l "O's

o s lOO 15 20 25 3o 35 4o Time(mtn) FIGURE 9 Guyton's experimental design. Blood drains to the oxy- FIGURE 11 Results of Guyton's experiments. The relationship genator and is returned to the aorta by a variable propulsion pump. between Pro, PMs, cardiac output, and the arterial pressure. Manometers are placed at various points in the circulation. The exter- These graphs illustrate the parallel changes that occur in these nal roller pump is an ancillary device to allow rapid equilibration of the parameters following blood infusion; arterial pressure and cardiac venous and arterial pressures when the circulation is arrested. All the output increase when blood is infused. Causes of the increase in variables of VK and cardiac output can be independently varied, and cardiac output are an increase in the gradient for VR, and a the mathematical relationship can then be tested. SVC = superior vena decrease in R v (because of the increase in size of the veins and cava; AO - aorta; PA = ; IVC = inferior vena tara. haemodihirion).

the K v (larger diameter of the veins and haemodilu- Mechanisms by which R v increase include constriction tion); and c) the upper limit to the P~ is the PMs" of the conducting veins, a change in the viscosity of Figure 12 shows how changes in the PMS affect VtL the blood (polycythaemia), or redistribution of blood An increase in the total volume, a decrease in Vo, or a from vascular beds with fast time constants to vascular decrease in the capacitance, can cause a right shift of beds with slow time constants. The time constant (z) the VR curve. Similarly, a decrease in total volume, an of a vascular bed is determined by the volume of the increase in Vo, and an increase in the capacitance, can vascular bed divided by the flow through the bed. The cause a parallel left shift of the VR curve. Changes in venous circulation is enormous and very variable. It the Rw change the slope of the VK curve (Figure 13). contains venous beds such as the renal venous bed 856 CANADIAN JOURNAL OF ANAESTHESIA which have low volumes and high flows, and hence cult model was developed, which has a splanchnic and a fast time constants (zf). It also includes the venous non-splanchnic circuit (Figure 14). 9 The mathematical plexus of the skin which has an enormous volume and equations derived for the multiple circuit model are com- very slow flow, and hence a slow time constant (Zs).ll plex and beyond the scope of this review. However, analy- The fraction of blood distributed to zf and ~ is called sis of the multiple circuit model shows that P~ has a Fr and F s respectively. A redistribution of blood from much greater effect on VR than left atrial pressure. 9 This to ~ units will have an effect on the venous return is not surprising, as the systemic vasculature has a capaci- curve similar to that of decrease in R v (Figure 13). tance 7-10 times that of the pulmonary vasculature and, therefore, dominates physiological control of the venous The multiple circuit circulatory model circulationJ 2 It is reasonable to use a single circuit model The preceding single circuit model of the circulation does of the circulation to explain the behaviour of the circula- llot have a pulmonary circuit or a cardiac compliance, nor tion as a whole. For a flail explanation and derivation of does it allow for changes in the surrounding pressure on the multiple circuit model, readers are referred to an the compliant regions of the vasculature. A multiple cir- excellent review by Sylvester et al. 9

VENOUS RETURN (CARDIAC OUTPUT) Cns (llmln.)

10

1" P~s

Normal

$ PMS

10 RIGHT ATRIAL PRESSURE (mmHg)

FIGURE 12 Changes in the PMS' A decrease in PMS moves the curve to the left, and an increase moves the curve to the fight. C = venous capacitance; V = total volume of the system.

10-

,LRv, l"Ff, SF,

Normal

FIGURE 14 Muldple circuit model of the circulafon. Blood from TRy, SF~, 1`F, the splanchnic and the non-splanclmic circuit flows into the fight heart (which has a compliance, Cr) , from where it is then ptmlped into the VENOUS RETURN pulmonary circuit. The pulmonary circuit has an arterial and venous (CAROIAC OUTPUT (I/rain.) o..[ resistance (Rap and R~,), separated by a compliance, Cp. Since most of the complian&: of the pulmonary vasculature is thought to reside in alveolar vessels, the pressure surrounding Cp is the alveolar pressure, 0 10 P~. From the pulmonary circuit, blood flows into the left side of the RIGHT ATRIAL PRESSURE (mmHg) heart, which has a compliance CL, from which it is pumped into the FIGURE 13 The effect of changes in the R v and the fractional systemic vascu[ature. The left and fight sides of the heart are sur- distribution of blood flow. A decrease in R v or an increase in F r rounded by a pressure, Ph, which can be thought of as the pressure have the effect of increasing the slope of the venous return curve. resulting from a combination of PpL and the pressure exerted by physi- Increasing R v and increasing F s has the opposite effect. cal contact bet~veen the heart and its surrounding structures. Jacobsohn et al.: CARDIAC OUTPUT REGULATION 857

Cardiac function and its relationship to lation, c) failure to deliver the circulated oxygen at the venous return cellular level, and d) failure of cells to utilize the deliv- Cardiac fimction is traditionally represented by the ered oxygen. The classification of shock has under- Frank-Starling cardiac function curves, which are depen- gone many changes over the years, and continues to dent on , contractility, and afterload (Figure evolve) s06,17 The summary below and Table I is a syn- 15). The intersection of the cardiac function curves and thesis of many of these classifications, and is a practi- the abscissa (pressure axis) occurs at a negative value cal approach to the differential diagnosis of shock. because the transmuralfilling pressure is P~ relative to 1. Hypovolaemic shock: the pressure surrounding the heart, which is the pleural a) Haemorrhagic: pressure (PvL)' In Figure 15, PVL is --3 mmHg; the trans- 1) Observed mural filling pressure (PeA - Pw) is zero when PeA is 2) Occult -3 mmHg. b) Non-haemorrhagic: One of Guyton's major contributions to the tmder- 1) Absolute or standing of cardiac output regulation was that the 2) Relative fluid deficit venous return and cardiac function curves could be rep- resented on the same graph (Figure 16). t3 In a steady 2. Cardiogenic shock: state, VR and cardiac output must be equal; large differ- a) Myocardial (RV and/or LV) ences between cardiac output and VR would result in b) Val~alar the accumulation of blood in one of the compartments c) Conduction and lead to the cessation of the circulation. At any time, d) Pericardial (also considered in 4) cardiac output is determined by the intersection point of 3. Distributive shock: This describes those forms of the VR and the cardiac function curves. The intersection shock that have in common vasodilatation and represents the momentary pumping ability of the heart altered distribution of blood flow. The pathophysiol- (rate, rhythm, contractility, afterload) and the character- ogy is often complex, and involves absolute or rela- istics of the circulation (V, Vo, C, Rv). tive hypovolaemia, changes ha the distribution of blood flow, and changes in cardiac function. Cardiac VENOUS RETURN AND CARDIAC OUTPUT IN output may be elevated, normal or decreased, and PATHOPHYSIOLOGICAL STATES depends on the indk~idual clinical situation. Shock a) Septic shock Shock is an acute clinical syndrome initiated by hypop- b) Systemic Inflammatory Response Syndrome erfusion, resulting in organ system dysfunction. 14 (SIRS) Hypoperfusion can result from either a) an inadequate c) Acute adrenal insufficiency oxygen content of the blood, b) an inadequate circu- d) Anaphylaxis e) Thiamine deficiency (Beri-Beri) 4. Obstructive shock: This describes those Forms of shock in which the major impediment is a mechan- CARDIAC OUTPUT (VENOUS RETURN) (I/rain.) ical obstruction to blood flow. This can be either: ...... 1' --:,7:-Systolic FuncUon...... a) Obstruction to venous return 10- b) Obstruction to cardiac ejection #o Dia,eJtollsFunr 5. Spinal shock: This is the result of either an I Normol / anatomical or chemical interruption (anaesthetic) of sympathetic activity from the spinal cord. The two components of spinal shock include: " $ SystolicFunction oe a) vasodilatation below the level of the spinal cord lesion

I I b) Depressed cardiac function if the lesion involves -5 I 10 the cardiac sympathetic nerve supply (T1-T4). RIGHT ATRIAL PRESSURE (mmHg) FIGURE 15 Cardiacfunction curves. Contractility,heart rate, 6. Miscellaneous: rhythm .'rod afterload determine the position of curve. The curves Metabolic intersect the abscissa at negativevalue because the transmural pres- Poisons sure is zero at this pressure (see text). Note that pure diastolicdys- function causes a parallel right-shiftof the curve. 7. Mixed: A combination of one or more of the above. 858 CANADIAN JOURNAL OF ANAESTHESIA

TABLE I Classification of shock CARDIAC OUTPUT 1. Hypovolaemic shock (VENOUS(Vmln.) RETURN) A) Haemorrhagic: 10- Occult Observed B) Non-haemorrhagic Absolute: fluid deficit (renal, GI, skin losses) ~ d,o,,,o,r Normal Relative: fluid redistribution (, drugs) Normal 2. Cardiogenic shock A) Myocardialfailure: (Systolic and~or diastolic; RV and/or LV) 1) Ischaemia/infarction 4.0 2) Myopathy: restrictive/obstructive/infiltrative/hypertrophic 3) Drug induced 4) Metabolic: ~,PO42-, r 2+, ?H § /" '" 5) tafterload: ooovl LV: I"BP, HOCM, AS RV: PHT, PE, HPV, PEEP, 0 3.5 8.5 I0 TPaw, ARDS,~PO2, i"H§ RIGHT ATRIAL PRESSURE (mmHg) ?CO2 6) Myocardial rupture (septum or freewall) FIGURE 16 Venous return and cardiac output plotted on the 7) Myocardial contusion same graph. At steady state, an individual has a unique VR and a B) Valvular unique cardiac function. The thin fine shows the cardiac output 1) Acute valvular insufficiency and P~ for this particular situation (cardiac output is 4 L.min-] at a) Infectious Psa = 3.5 mmHg and P~as = 8.5 mmHg). Cardiac output can be b) Traumatic changed by either changing the , the venous c) Ruptured papillary muscle return curve, or both. 2) Valvular stenosis/obstruction a) Thrombus (especially prosthetic valve) b) Myoxma c) Infection d) Stenotic valve C) Conduction The ultimate purpose of understanding the interac- 1) Brady-dysrhythmias 2) Tachy-dysrhythmias tion between VR and cardiac function is to be able to D) Pericardial Tamponade approach the therapy of shock and other altered circu- Infectious, traumatic, neoplastic, metabolic, collagen vascular latory states in a rational manner. Since cardiogenic 3. Distributive shock A) septic and obstructive shock are principally due to cardiac 1) Bacterial 3) Viral function abnormalities, our therapy should be focused 2) Fungal 4) Other infections B) SIRS on optimizing pre-load, inotropy, afterload, and heart 1) Burns 3) Major tissue injury rate. On the other hand, when approaching hypo- 2) Pancreatitis 4) Hepatic failure volaemic and distributive shock, our therapy is focused C) Acute adrenal insufficiency D) Anaphylaxis on abnormalities on the VR and cardiac output. Shock E) Thiamin deficiency (Beri-Beri) categories 1-5 will therefore be analysed in terms of 4. Obstructive shock changes in cardiac output and venous return: A) Obstruction to venous return 1) Pericardial tamponade 2) TIntrathoracic pressure: Hypovolaemic shock a) Tension pneumothorax The pathophysiological changes associated with hypov- b) TPaw olemia are shown in Figure 17. The compensatory c) ?PEEP 3) IVC obstruction (~intraabdominal pressure) mechanisms in hypovolaemic shock include an increase a) Positioning/pressure c) Thrombus in intrinsic catecholamine release, which causes the car- b) Tumours d) Pregnancy diac function curve to move to the left, and the venous B) Obstruction to cardiac ejection (LV or RV) 1) Massive PE (blood, tumour, air, amniotic) return curve to the right. There are several mechanisms 2) Dynamic RV or LV obstruction that increase venous return, and these include: 3) Fixed RV or LV obstruction 5. Spinal shock 1. A decrease in the capacitance of the venous reser- Anatomical or anaesthetic voir due to venoconstriction. This will cause an A) Vasodilatation below the cord lesion B) Cardiac depression (lesions above T4) increase in PMs and will cause a right shift of the 6. Miscellaneous causes venous return curve, ls,I9 Metabolic: thyroid storm, severe myxoedema, phaeochromocytoma Poisons: CO, CN and Iron 2. A decrease in V o. Studies by Rothe and cowork- 7. MIXED: Combination of above ers have shown that catecholamine release shifts HOCM=hypertrophic obstructive cardiomyopathy; AS=aortic stcno- the blood volume from the unstressed compart- sis; PHT=pulmonary ; HPV=hypoxic pulmonary vas- constriction; PE=pulmonary embolus; Paw=airway pressure; ment to the stressed compartment. 2~ This IVC=inferior vena cava; ARDS=aduh respiratory distress syndrome. enables the patient to maintain a normal BP, car- Jacobsohn et al.: CARDIAC OUTPUT REGULATION 859

CARDIACOUTPUT What would be the effect of epinephrine in haemor- (VENOUSRETURN) (I.min".) rhagic shock? Activation of 0t-adrenergic receptors ha the Haemodilution ($ Rv) ] periphery would result in a decrease in Vo .24 This would 10-~-~k ,,".... ,,.,...... T Cardiac Function increase the PMS, PRa, and cardiac output. However, this Normal L N-/d'SS ...... Normal assumes that the venous ~x-receptors were not already Phen~lephrlne ITPus.l' DRv~~' maximally activated by the patient's intrinsic cate- cholamine release. If they were already maximally stimu- lated, there would be little benefit from epinephrine. Hypovolaamla (.LPIsl ~_~ ~'%~ ...... $Cardiac Function The net effect of epinephrine on R v is nfinimal, as the and 13 stimulation have opposing effects. 2s-27 Epinephrine would further shift the cardiac output curve upwards, and the net effect will depend on the stage of shock. In early shock, there will be minimal effect, as car- -5 0 10 RIGHTATRIAl. PRESSURI: (mmHg) diac output is not the limiting effect, but in late hypo- volaemic shock, epinephrine may be beneficial. FIGURE 17 Hypovolaemicshock. A: Normal intersectionof the curves. B: Acute reduction in PMS' C: Left shift of the cardiac function curve due to compensatorycatecholarnine release. D: Resuscitation Cardiogenic shock (Figures 18, 19) with crystalloid.The venous rcturn curve shows a decreasedR v due to Cardiogenic shock can result from either myocardial haemodilution. E: Resuscitationwith phenylephrine.There is an dysfunction, valvular dysfunction, conduction distur- increase in Rv because ofvenoconstriction.F: Refractoryhypovolaemic bances, or pericardial pathology. Shock caused by peri- shock. This occurs ,aftersevere, prolongedhypovolaemia, and is associ- ated with acidosis and cardiac depression. In this situation an cardial pathology, although cardiac in aetiology, is best such as dopamine or epinephrine, may be beneficial(see text). considered a form of obstructive shock, and will be dealt with in that section. We will use cardiogenic shock due to ischaemia as the model in this section. The effect ofcardiogenic shock is shown in Figures 18 and 19. Therapeutically, clinicians have a wide variety diac output and PV,A in initial stages of hypo- of options for dealing with cardiogenic shock. volaemic shock, but leaves the patient with However, in order to optimize treatment of cardio- decreased reserve. Further blood loss would result genic shock, each intervention has to be analysed in in a decreased PMS, PR~, and cardiac output. terms of its effect on VR and cardiac function. Volume infusion has a small beneficial effect on cardiac output 3. An increase in precapillary resistance or decrease by improving VR. This occurs by increasing PMs and in postcapillary resistance results in the movement moving the venous return curve to the right. of fluid from interstitial space into the intravascu- However, there is a high price in terms of pulmonary lar space, increasing the PMS .23 This fluid move- oedema formation, as the patient functions at an ment also produces a drop in haematocrit; this increased filling pressure. Vasoactive drugs are the does not occur in the early stages of haemorrhage mainstay in the treatment of cardiogenic shock. Their and is more important as a long term adaptation, effects on the circulation are complex, the net effect as in the case of slow bleeding. The effect of a being a balance between the overall effect on the car- decrease in haematocrit is to decrease R v. diac function (rate, rhythm, contractility, afterload), Treating tmcomplicated hypovolaemic shock with and their effect on the VR. volume moves the venous return curve towards its nor- Dopamine and dobutamine are the two most com- mal position and, therefore, restores PMS, PV.A,and car- monly used in the treatment of cardiogenic diac output. Pharmacological interventions, such as the shock. There are important and substantial differences administration of vasoconstrictors and inotropes, are between these agents in the treatment of cardiogenic much less effective than giving ~]uid. 24 Phenylephfine, a shock (Table II). 28-30 The differences are accounted pure 0t-adrenergic agonist, also decreases V o and for predominandy by the different effect on VR and increases PMS" However, phenylephrine increases the R v afterload. At higher doses, dopamine is a 131, g2 and by causing constriction of the conducting veins. a-agonist, but the a effects predominate (Figure 18). Therefore, ha hypovolaemic shock, if PMS was restored In this regard, the cti effect ofdopamine are similar to with a fluid infusion or with an infusion of phenyle- administering volume, and sometimes madesirable. phrine, cardiac output would be higher with fluid infu- The 13I effect of dopamine moves the cardiac output sion because an infusion of crystalloid would decrease curve upwards, although its c~ effect increases afterload the Rv, whereas the R v is increased with phenylephfine. and decreases the beneficial effect on contractility. In 860 CANADIAN JOURNAL OF ANAESTHESIA

Dopamlne ( T Pus) Dobutamine (J.Rv) Compen*atlon {~ o 10" Compensation ~PMS) ~ Normal ..... Normal Normal %% ,,~""~'~'" Normal ...... Dopemlne \ .. - ,Oobutamlne CARDIACOUTPUT (CARUlACOUTRUr) VENOUSRETURN i# ****.o (I/rain) ,l/mln.) / "~w ~'~.,ar Failur. ../ .." .....- .\\\ :: \~

-5 10 -5 0 10 RIGHTATRIAL PRESSURE (rrtmHg) RIGHTATRIAL PRESSURE (mmHg) FIGURE 18 Cardiogenic shock and the effect ofdopamine. FIGURE 19 Cardiogenic shock and the effect ofdobutamine. A: Normal intersection of the curves. B: Depressed cardiac A: Normal intersection of the curves. B: Depressed cardiac func- function. There is predominantly systolic failure, but some tion. There is mainly systolic failure, but some diastolic dysfunc- diastolic dysfunction is also present. Increased PeA results. tion is also present. Increased PeA results. C: Compensation C: Compensation through catecholaminc release. Vcnoconstriction through catecholamine release. Venoconstriction moves the moves the venous return curve to the right. The patient venous return curve to the right. The patient functions at a higher functions at a higher PMs and PeA. D: Effect ofdopamine as PMs and PeA" D: Effect ofdobutamiue as a restdt of its action on a result of its action on cardiac function and VR (see text). cardiac function and venous return (see text). Dobutamine Dopamine further increases PMS and shifts the cardiac function increases cardiac output by improving contractilit3, , as well as curve upwards. Cardiac output increases and PRA may decrease improving the VR by decreasing Kv. Unlike dopamine, PMs is not slightly. Dopamine does not change R.v due to its effect on increased - in fact, PMs may decrease when dobutamine is started both the and f~-adrenergic receptors. due to an unopposed f~l effect (venodilatation). A judicious vol- ume infusion may be required when dobutamine is initiated.

addition, the beneficial effect on cardiac output may Pv~- In patients with no ability to increase contractili- be nainimizcd by the tachycardia, which can reduce ty, dobutamine may decrease , accom- diastolic time and myocardial . The net effect panied by a small increase in cardiac output. This may is a result of the effect on cardiac output and VR vari- compromise vital organ perfusion. This may be offset ables, and will vary from patient to patient. by judicious fluid administration when dobutamine Dobutamine (Figure 19) has predominant B 1 therapy is initiated. effect, and has no ct effect. This causes an increase in The effect of the selective phosphodiesterase III contractility, a decrease in afterload, and a decrease in inhibitors is similar to that ofdobutamine, except that the R v (through venodilatation). The beneficial effects tachycardia and rate-related increased oxygen con- of dobutamine on contractility and afterload may, as sumption and ischaemia are less. sl They cause an with dopamine, be offset by an increase in heart rate upward shift in the cardiac function curve through and increased myocardial oxygen consumption. The afterload reduction and increased contractility. In decrease in R v will be associated with increased VR addition, they may improve diastolic dysfunction and and cardiac output for any combination of PMs and cause a leftward shift of the cardiac function curve, s2

TABLE II Sumnaary of the pharmacological receptor selectivity for the commonly used adrenergic drugs Catccholaminc DA- 1 B1 g2 ct 1 c~2 Dopamine* 1-4+ 0-3+ 0-2+ 0-3+ 0-1+ Dobutamine 0 3+ 1+ 0-1+ 0 Norepinephrine 0 2+ 1+ 3+ 3+ Epinephrine 0 3+ 3+ 3+ 3+ Isoproterenol 0 3+ 3+ 0 0

*Dopamine pharmacological effects are dose related and varies bet~veen patients. Low doses (1-3 pg.kg- 1 .rain- 1 ) stimulate primarily the DA-1 and DA-2 receptors; high doses (>15 pg.kg-l.min -l) produce predominantly 0~-adrcnergic stimulation. 0-4 = degree of stimulation. Jacobsohn et al.: CARDIAC OUTPUT REGULATION 861

Phosphodiesterase III inhibitors probably decrease R v VENOUS RETURN (CARDIAC OUTPUT) due to intense vasodilatation,aa As with dobutamine, (I/rain.) Resuscitated Sepsis (1 Rv) they may cause severe hypotension in patients in car- Afterloed Reduction diogenic shock if the overall increase in cardiac output ..**.#** ...... from Sepsis is offset by the decrease in the afterload. Afterload reduction is desirable in the setting of ****~ o Normal cardiogenic shock, as it allows an increase in cardiac Normal output without the associated increase in myocardial Unresuscltatad Se oxygen consumption. Excessive afterload reduction is ( J. PMS, ~Rv) / Cardiac undesirable and may be hazardous. con- '" "" " Depression verting enzyme inhibitors increase cardiac output by reducing afterload and decreasing Rv.a4 The net effect I is similar to that of dobutamine, although the 0 10 increased cardiac output is due to afterload reduction RIGHT ATRIAL PRESSURE (mmHg) increased VR. FIGURE 20 Septic shock. A: Normal intersection of the curves. B: Acute sepsis, with no fluid resuscitation. Cardiac function may be Distributive shock normal, but because of the severe venodilatation, rite Ps~s may be Distributive shock is a term that is used to describe decreased. R v is decreased. C: Volume resuscitated septic patient. those forms of shock that have in common severe PMs is normal, R v is reduced (see text), and cardiac output is vasodilatation (arterial and venous) and altered distri- increased. D: Classic high output sepsis. Profound afterload reduc- tion (arteriodilatation) offsets any contractile depression due to the bution of blood flow. Examples of distributive shock septic mediators (see text). E: Severe myocardial depression due to include septic shock, as systemic inflammatory the septic mediators, not offset by afterload reduction (see text). response syndrome (SIRS), anaphylaxis,36~~ acute Even though R v is reduced, cardiac output is depressed. F: Profound adrenal insufficiency,4t-44 and Beri-Beri. 4s The haemo- sepsis with cardiac depression and no volume resuscitation. dynanaic pattern in distributive shock varies according to the particular clinical situation. Using sepsis as a model for distributive shock, sev- eral clinical scenarios may occur (Figure 20). If active venodilatation is part of sepsis, R v and PMs will studies have shown an increase in muscle blood flow decrease. The net effect on VR will depend on the bal- in sepsis, which supports this hypothesis. 49,s~ ance between a low R v and PMs; a dominant decrease About 10% of patients who become septic have car- in K v would increase VR, while a dominant decrease diac dysfunction, as evidenced by a normal or low car- in PMs would decrease VR. Ifvenodilatation is associ- diac output, sl Furthermore, even in those patients ated with significant arteriodilatation, then cardiac presenting with an elevated cardiac output, there is output could also increase. In some cases of septic usually impaired contractile function, with ventricular shock, contractility becomes severely depressed, either dilatation and a reduction in the . due to inherent mediators of sepsis or as a result of However, because the heart is dilated, oxygen debt; abnormalities in cardiac function rather changes little, and cardiac output is elevated because than VR will then determine cardiac output. This of an increase in heart rate. The depressed ejection occurs particularly in the late stages of sepsis. The clin- fraction and ventricular dilatation are probably related ical presentation in a particular patient is related to the to myocardial depressant factors released during sep- age of the patient, the pathogen involved, and the sis. s2,s3 In addition to systolic dysfunction, some dias- released vasoactive mediators. Although there is pro- tolic dysfunction also occurs during sepsis, s4,s5 found venodilatation in most acutely septic patients, in The therapeutic options in septic shock are partly some cases, despite this, and in the absence of volume determined by the volume status of the patient, and resuscitation, PMs may remain normal. 46,47 This may whether the patient has low or high cardiac output be explained by a decrease in Vo.l~ The reasons why sepsis, s6 An important goal of therapy is to maintain VR is usually increased in high output sepsis remains cardiac output, tissue oxygen delivery, and perfusiou speculative. The time constant of the splanchnic vas- pressure to vital organs. As the stressed volume is an culature may decrease, which would decrease Rv.4S important determinant of VR, volume resuscitation is There may also be an increase in the fractional blood crucial. Because of the severe vasodilatation and ongo- flow to portions of the non-splanchnic bed, which ing capillary leak, patients may require between four have fast time constants for venous drainage. Some and eight liters of fluid to normalize PMS ,and to 862 CANADIAN JOURNAL OF ANAESTHESIA

increase cardiac output. Another option is to increase CARDIAC OUTPUT (VENOUS RETURN) PMS by using norepinephrine rather than giving large I/mln. volume infusions. The a-1 effect decrease V o and increases the stressed volume. 24 The t~1 effects will augment myocardial function. However, the net effect Normal L ~,~ on cardiac function will depend on the effect on con- 'oN / tractility, heart rate, and the increased afterload. The effect of high dose dopamine are similar to that of norepinephrine, s7 Phenylephrine increases arterial I .N( -" pressure and Rv, and is therefore only useful to increase the cerebral and the coronary perfusion pres- sures in patients with high output sepsis. Many 0 lO PPL patients with sepsis or other causes of distributive RIGHT ATRIAL PRESSURE (mmHg) shock progress to ARDS. sS,s9 The evolution of ARDS FIGURE 21 Obstructive shock due to a tension pneumothorax. complicates haemodynamic management, as it makes A: Normal intersection of the curves. B: Tension pneumothorax. the infusion of volume relatively unattractive. 6~ The cardiac function curve is depressed and moved to the right Therapy with dopamine to increase PMS may be prefer- (see text). The 1Lr is increased because of compression of the con- able to volume infusions. ducting veins as they enter the thorax. The PMS is increased because of intense catecholamine release. Venous return plateaus at Poe" Obstructive shock C: Improved contractility. The effect of an inotrope, as well as that of the intrinsic catecholamine release, does not cause an increase The pathophysiological changes in tension pneumoth- in cardiac output. This is due to the limitation in VR and the orax are shown in Figure 21. The cardiovascular effect position/shape of the cardiac function and venous return curves. of a tension pneumothorax is to limit VR by increas- D: Volume infusion causes a slight increase in cardiac output. ing the pressure in the thorax. The equation for VR becomes PMS - PVL, because PPL is greater than P~ (see Guyton model). Decreasing the P~ below PL will not increase VR; the VR curve will plateau at a point a similar effect on the position of the cardiac ftmction greater than zero. In an acute tension pneumothorax, curve as a tension pneumothorax. The equation for there is an acute decrease in cardiac output, and a venous return becomes PMS - PPer' where Pver is pericar- compensatory intense catecholamine release. This will dial pressure. Use of an inotrope to increase contractil- have the effect of increasing PMS" The increase in PVL ity does not lead to an increase in the cardiac output, as increases R v by compression of the large conducting the VR curve is flat and the cardiac function curve is veins, but this is somewhat offset by hypoxaemia, moved to the fight. Definitive treatment is to decrease which has been shown to decrease R v in a dog the Pver tO reestablish a normal gradient for VR. model. 6],62 In addition, the cardiac function curve Another form of obstructive shock that is of particu- moves down and to the right. The rightward move lar importance to anaesthetists is IVC compression, as occurs because the transmural filling pressure is zero this may occur during intra-abdominal surgery and dur- when PRA is equal to PPL, which is high. The depres- ing the prone position (Figure 22). The definitive treat- sion of the cardiac function curve is caused by an ment is to decrease R v by refieving the pressure on the increase in the pulmonary due to conducting vein. lung volume loss and hypoxaemia. 63 The only success- ful way to treat a tension pneumothorax is to reduce Spinal shock (Figure 23) PVL immediately. This is accomplished with an emer- Spinal shock occurs as a consequence of an anatomical gency needle thoracostomy, followed by placement of or pharmacological transection of the spinal cord a tube thoracostomy. The use of an inotrope will not (spinal or epidural anaesthesia). ~-66 The haemody- increase cardiac output, as the limitation is the VR and namic consequences are determined by the level of the right shift of the cardiac function curve. cord transection. The higher the transection, the The haemodynamic changes in pericardial tampon- greater the loss of sympathetic tone, the greater the ade result from obstruction to VR, and are similar to degree ofvenodilatation, and the greater the decrease those of a tension pneumothorax. As the pressure in PMS and cardiac output. Transect_ions above the around the heart is increased, it becomes the limiting level of T 4 cause a cardiac sympathectomy and a pressure for VI~ Transmural filling pressure is zero depressed cardiac function curve. Spinal cord lesions when PRA is equal to pericardial pressure. This will have below T 4 are associated with normal contractility, and Jacobsohn et al.: CARDIAC OUTPUT REGULATION 863

VENOUS RETURN with transections above T 4 require therapy to improve (CARDIAC OUTPUT) I/rain. o~..o. .. Compensation contractility and to increase the PMs" Sometimes tem- .,,,'~" ..- Normal 10 porary pacing may be required for persistent bradycar- Normal dia in high spinal cord lesions. Moderate fluid resuscitation and drugs with inotropic and peripheral vasoconstricting effects are desirable. Dopamine or

T Volumei'l'PMsI T Rv norepinephrine are good choices, as they improve Com~ns~do. I re.~,TRv 1 venous tone and improve cardiac contractility. Comloresslon IT Rv 1 Other common conditions with altered circulatory states encountered in anaesthesia and critical care

-5 Cardiopulmonary bypass (Figure 24) RIGHT ATRIAL PRESSURE (mmHg) Cardiopulmonary bypass (CPB) is a practical demon- stration of the VR physiology. 6z,68 During CPB, the FIGURE 22 Obstructive shock due to IVC compression. A: Normal intersection of the curves. B: Increased Rv. In the venous blood returns from the patient to the venous acute situation, cardiac output decreases because of a decrease in reservoir through siphonage. A variable propulsion VR. The increased Rv is due to direct compression of the veins pump then pumps the venous blood through an oxy- and an increase in intra-abdominal pressure. C: Compensation genator back to the aorta. The flow from the peripher- due to catecholamine release. Intense venoconstriction increases al vasculature to the right atrium is dependent on the PMs, and shifts the cardiac function curve upward. However, there is only a small increase in cardiac output. D: Volume gradient for VR, that is, PMs - P~' During CPB, P~ is resuscitation causes a small increase in PMs and cardiac output. determined by the flow from the right atrium to the venous reservoir. Flow from the right atrium to the reservoir occurs by siphonage, and is dependent on the size of the cannula and venous return lines, the degree VENOUS RETUR'I.) [ (CARDIAC OUTPU of siphonage (the height between the patient and file venous reservoir), and the resistance in the lines 10 -f- ,. ~ .... Normal between right atrium and the reservoir. The pressure at Normal | ~ (and RestJscltsted) L ~176176 . .... Dopamlne the tip of the cannula (P~) can therefore be decreased to a maximum of zero by allowing complete siphonage. " .* ... Cardiac "~'A ." .. -""" Sympnthectomy Excess siphonage would create a negative pressure, and ,"~ .* .*" (lesion aboveT4) ,L PUS .* C .*" cause collapse of the right atrium around the cannula. P~ can be increased by partially occluding the clamp .. on the venous return line. At a constant reservoir level, flow during CPB is therefore determined by the venous

.4, o ep.* 'j.::5' ~ . o' " N return. Flow during CPB can be increased by maximiz- ing VR by completely opening the venous return line 10 and thereby minimizing P~. During bypass, PMs can RIGHT ATRIAL PRESSURE ImmRg) also be altered. The volume of the venous reservoir can FIGURE 23 Spinal shock. A: Normal intersection of the curves. be transfused into the patient, increasing PMs" The gra- B: In a cervical cord transection or high spinal/epidural anaesthetic, dient for VR from the patient to the right atrium would the cardiac output is decreased, in part due a cardiac sympathecto- therefore be increased. In addition, maximum flow can my. There is also profound peripheral venodilatation due to the be increased by minimizing R v. sympathectomy(decrease in PMs)' C: Treatment of a cervical cord transection with dopamine and volume resuscitation. D: Spinal cord lesion below "-1"4 . Cardiac function is normal. Volume infusion will Pregnancy increase PMs and restore a normal circulation in this patient. The haemodynamic changes of pregnancy are impor- tant, as aberrations can cause profound effects on uterine blood flow and fetal well being. Despite an increase in blood volume of 40% above pre-pregnant are treated with volume or with a vasopressor (such as levels, the parturient at term remains susceptible to phenylephrine).. Using large volumes to restore the hypotension, especially during major conduction PMs in these patients may be undesirable. Spinal cord anaesthesia. 69,7~ Partial inferior vena caval and aortic transections above T 4 represent a combination of occlusion by the gravid uterus is present in the decreased contractility and decreased VR. Patients majority of patients lying in the supine position 864 CANADIAN JOURNAL OF ANAESTHESIA

(Figure 22). This impedes VR and cardiac output by The effect of halothane and isoflurane on circulatory increasing R v. Hypotension may result in some function patients. In addition to hypotension, there is an The effects ofinhalational anaesthetics on the VR curve increase in uterine venous pressure, further decreas- remain to be determined. Most studies document the ing uterine blood flow. However, in most parturi- effect of inhalational agents on the equilibrium point ents, an increase in resting sympathetic tone (increase only (Figure 25). 7] Volatile anaesthetics produce a in PMs) compensates for the effect of caval compres- dose-dependent increase in the P~, with the effect sion, and the blood pressure is usually maintained. being more marked with halothane than isoflurane.72 However, when sympathetic tone is abolished acute- Halothane causes a depression of the cardiac function ly (spinal or epidural anaesthesia), an acute decrease curve. This is due to its direct negative inotropic effect, in blood pressure may occur. If the spinal or epidur- without compensatory increase in heart rate. Because al results in a high block, the cardiac sympathetics halothane has a minimal effect on the overall systemic may be affected and the cardiac function curve will vascular resistance, the VR curve probably remains in a be depressed. This may make an already compro- near normal position. Like halothane, isoflurane is also mised situation (due to decreased VR) much worse, a direct negative inotrope, but it is also a patent and profound hypotension may result. Most of these vasodilator. The afterload reduction (arteriodilatation) haemodynamic changes can be prevented by volume and increased heart rate that occur with isoflurane off- loading, proper positioning, and judicious dosing of set the direct negative inotropic effect; the cardiac func- the anaesthetic. t_ion curve is therefore depressed less than with halothane. In addition, isoflurane causes venodilatation, and this probably leads to a decrease in R v. This will also decrease PMs, but this is minimized by volume infu- sion prior to and during induction of anaesthesia. The c decreased g~v wotfld offset the effect on cardiac output depression. The net result is that isoflurane causes a

CARDIAC OUTPUT Patient circuit (VENOUS RETURN) (Pmin.)

lO- tsoflurane (~ PMS,~Rv~ ~, ***''" ...... Normal Cannula Cannula II II Normal p***~ ~ Isoflurane (and Halothane) v* .#~ ,*** ~ - - - - Halothano Veno~s return control j .~176

~,PB circuit ~ ~176o149 =~149 I 0 10 Arterle] RIGHT ATRIAL PRESSURE (rnrnHg) Pump Oxygenalor FIGURE 25 Effect ofhalothane and isoflurane. A: Normal intersection of the curves. B: The effect of halothane. Halothane causes a decrease in cardiac systolic function and has minimal effect on VR. There is also some diastolic dysfunction. Patients who receive halothane function at a higher P~ and lower cardiac FIGURE 24 Cardiopulmonary bypass. The determinants of flow output. C: The effect of isoflurane. Patients receiving isoflurane during CPB depend on patient factors (P~as, P~, Rv), as well as CPB function at a minimally reduced cardiac output, but at a higher circuit factors (P~, the flow characteristics of the venous return can- P~. Isoflurane causes less depression of the cardiac ftmction curve nula mad lines, ,'rod the degree of siphonage). Some of these factors because of afterload reduction. Because it is a venodilator, it are interdependent, e.g., P~ in the arrested heart is dependent on reduces R x, and PMs. The reduction in PMs is minimized in clinical the characteristics of flow in the venous rcturn line, and PMs can be situations by administration of volume prior to inducing anaesthe- increased by transfusing the contents of the reservoir into the patient. sia. A small degree of diastolic dysfunction is also present. Jacobsohn et aL: CARDIAC OUTPUT REGULATION 865 small increase in PRA, and cardiac output is only mini- 8 Bressack MA, Raffin TA. Importance of venous return, mally depressed. With both isoflurane and halothane, venous resistance, and mean circulatory pressure in the there is a small right-shift of the cardiac function curve. physiology :rod management of shock. Chest 1987; 92: This is because volatile agents produce varying degrees 906-12. of in diastolic dysftmction. 73,74 9 SylvesterJT, Goldberg HS, Permutt S. The role of the vasculature in the regulation of cardiac output. Clin Conclusion Chest Med 1983; 4: 111-26. In analyzing circulatory function, physicians focus much 10 Magder S. Shock physiology. In: Pblsky MR, Dhainaut JF of their attention on the performance of the heart. This (Eds.). Pathophysiological Foundations of Critical Care. serves them well when managing patients with diseased Baltimore, MD: William and Wilkens, 1993: 140-59. hearts, but leaves them disadvantaged when managing 11 Permutt S, Caldini P. Regulation of the cardiac output patients with compromised circulations. The observa- by the circuit: venous return. In: Boan J, Noordegraff tion by Starling and Bayliss in 1894, that "the venous A, Raines J (Eds.). Cardiovascular System Dynamics. circulation was an important but disregarded chapter in Cambridge, MA, London: MIT Press, 1978: 465-79. the physiology of circulation, ''3 still holds true today. 12 GreenJF. Circulatory mechanics. In: Ftmdamental However, by studying dae concepts developed by Cardiovascular and Pulmonary Physiology. Weber, Starling, Starr and Guyton, physicians can Philadelphia, PA: Lea and Febiger, 1982: 101-10. enh~mce their tmderstanding of the circulation in many 13 Guyton A, Jones C, Coleman T. Circulatory Physiology: pathophysiological states, and overcome the dominance Cardiac Output and its Regulation. Philadelphia, WB of the cardiac function in thinking about the circulation. Saunders, 1973. 14 Wally ICR, Wood LD. Shock. In: Hall JB, Schmidt GA, Acknowledgments Wood LD (Eds.). Principles of Critical Care. New We wish to acknowledge Wanda Quinn for her assis- York: McGraw-Hill, 1992: 1393-416. tance in the preparation of this manuscript. 15 Blalock A. Experimental shock. The cause of the low blood pressure produced by muscle injury. Arch Surg References 1930; 20: 959. 1 WeberE. The law of pulsatile flow and its application to 16 Cournand A, Riley iLL> Bradley SE, et al. 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