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Cardiac Performance During Anesthesia and Operation*
Cardiac Performance During Anesthesia and Operation ~ RICHARD A. THEYE, M.D.
The fundamental function of the heart is to pump blood through a system of connected tubes. In this chapter, the conceptual basis for regulating the rate of output from this pump (cardiac output) will be developed. Also, the manner in which cardiac output is altered by anesthesia, unreplaced blood loss, and increased airway pressure will be discussed. Of course there are other potent forces capable of altering cardiac performance during anesthesia and operation: a complete list would include hypoxia, hypercarbia, arrhythmias, countless drugs, coronary-artery dise9,se, and abnormalities of valvular function. Although these additional circumstances will not be discussed, they must not be forgotten.
TERMS AND ANALYTIC TECHNIQUES
Certain terms are commonly used to describe the functions of the cardiovascular system. The flow through the systemic vascular bed (systemic flow) is equal to left ventricular output. Left and right ventricular outputs are necessarily equal, as are pulmonary and systemic flow rates except in certain unsteady states of short duration and in the presence of intracardiac or systemic-pulmonary shunts. Cardiac output is used ordinarily to indicate left or right ventricular output. Thus, for all practical purposes, values for left or right ventricular output and for systemic or pulmonary flow rates are interchangeable and equal to cardiac output. Cardiac output, the volume output of either ventricle per unit of time, is the product of stroke volume and heart rate. When cardiac output and stroke volume are expressed relative to body surface area (in square meters), the terms "cardiac index" and "stroke index" are used. For example, a normal adult man of 1.8 sq.m. body surface might have a cardiac output of 6.3 L. per min., cardiac index of 3.5 L. per min. per sq.m., heart rate of
* This investigation was supported in part by Research Grant H-4881 from the National Institutes of Health, Public Health Service.
841
842
RICHARD
A.
(mg. /
RADIAL _--+---....:- - - - -ARTERY
------------
THEYE
L.)
0
5
10
Signal
5 mg. Indocyanine Green into Left Atrium
Base Line==~~==============~============~============= Figure 1. Dye curve recorded from radial artery following left atrial injection of 5 mg. indocyanine green. (Note appearance of dye in approximately 4 seconds with rapid increase in concentration. After reaching peak, dye concentration rapidly decreases. Recirculation of injected dye prevents complete return to base line.) Curve resulting from right atrial injection of dye would have smaller maximal deflection and be more spread out but would yield same calculated value for cardiac output. (Reproduced with permission from: Theye, R. A. and Kirklin, J. W.: Physiologic Studies Early After Repair of Tetralogy of Fallot. Circulation 28:42-51 [July] 1963.)
75 beats per min., stroke volume of 84 mI., and stroke index of 47 mI. per sq.m. Cardiac output can be measured by a variety of techniques. 5 • 11 The classic methods utilize the Fick relationship: C ardiacoupu t t
=
oxygen uptake . . (arterIal - ffilxed venous) OJ content
This approach is of limited applicability to anesthetized subjects because of the technical problems of analyzing blood and gas in the presence of gaseous anesthetic agents. Techniques for gas chromatography show promise of removing this barrier. In the meantime, dye-dilution techniques have been widely applied to the measurement of cardiac output in anesthetized man, both in the laboratory and in the operating room. In this approach, a known amount of indicator is injected as "centrally" as possible and the time course of change in concentration of this indicator in arterial blood is recorded. Common indicators include indocyanine green, Evans blue, isotopically tagged albumin, and cold saline. The most common application includes injection of indocyanine green via a catheter passed to the right
CARDIAC PERFORMANCE DURING ANESTHESIA AND OPERATION
843
atrium and sampling from a peripheral artery through a densitometer.9 A typical dye curve obtained in this manner is illustrated in Figure 1. Knowledge of the amount of dye injected and the calibration curve of the instrument would permit calculation of cardiac output from this curve. ll
INTERREACTION OF FACTORS
The manner in which cardiac output is controlled in intact man is not fully understood. Some prefer to regard the heart as passive in this regardpumping whatever volume of blood it receives. The primary determinant of cardiac output then would be the rate of venous return as influenced by peripheral vascular factors.2 For our purposes, however, it is more convenient to think of the heart as having an active influence on cardiac output and performing along lines suggested by Starling and extended by Sarnoff. The basic concept in this approach is Starling's "Law of the Heart," which states that the amount of energy released with ventricular systole is a direct function of ventricular end-diastolic fiber length. Since neither the amount of energy released nor the end-diastolic fiber length is easily measured, the usefulness of this expression is limited except after certain modifications. When the pressure in the artery receiving blood from the ventricle is unchanged, stroke volume can be substituted for energy released with ventricular systole. When myocardial distensibility is unchanged and pericardial-sac pressure is near zero and constant, mean atrial pressure can be substituted for ventricular end-diastolic fiber length. Under these conditions, the "Law of the Heart" is the direct relationship between stroke volume and mean atrial pressure-both of which are familiar and readily measured. The graphic description of the relationship between stroke volume and mean atrial pressure has come to be called a ventricular-function curve. Extension of the relationship to cardiac output requires only that consideration of the heart rate be included. Typical curves for the right and left ventricles are illustrated in Figures 2 and 3. In these forms the relationships are physiologically valid but have little utility, since they describe the response of the ventricle to variations in atrial pressure under a single, unchanging condition of myocardial distensibility and contractility. Sarnoff has suggested that ventricular performance could be described better by a family of ventricular function curves-each having the same general shape, but with the slope depending on the state of the myocardium. Within this context, increased myocardial contractility is defined as increased release of energy at a given fiber length and is represented by a shift of the curve to the left-that is, a greater stroke volume for the same atrial pressure or the same stroke volume for a lower atrial pressure. In the same fashion decreased contractility is represented by a shift of the
844
RICHARD
A
THEYlf
100~----------------------~
Rt. ventricle
80 Figure 2. Ventricular-function curve for right ventricle, illustrating direct relationship between right ventricular stroke volume and right atrial pressure. This is direct extension of Starling's law of the heart assuming no change in pulmonary-artery pressure and in myocardial distensibility and contractility.
20
00
6
8
Rt. atr i a I pressure -mm. Hg 100
Lt. ve n t ric I e 80
Figure 3. Ventricular-funetion curve for left ventricle. Stroke volume and atrial pressure are directly related. Note that (1) slope of this curve is flatter than that for right ventricle (Fig. 2) and (2) for equivalent stroke volumes, left ventricle requires higher filling pressures than right. These differences are based, presumably, on lesser distensibility of left ventricle.
-..:
e:I
.,
e: ....I::>
60
:::,
....,
'"
40
... .....
I::>
\I)
20
0
0
2
4
6
8
10
Lt. atrial pressure - mm. Hg
curve to the right. A family of curves for the right ventricle is illustrated in Figure 4. Ordinarily this form of analysis ignores altered distensibility as a basis for altered function. This is partly because of the difficulties in measurement of ventricular end-diastolic volume but also partly because of lack of agreement on definition of terms. For example, if distensibility is increased, a given atrial or filling pressure results in a greater fiber length-which for a given state of contractility would result in a greater energy release. Accordingly, a shift of the curve to the left is attributed more correctly to
845
CARDIAC PERFORMANCE DURING ANESTHESIA AND OPERATION
increased contractility or distensibility, or both, than to increased contractilityalone. For the sake of convenience only, this point will be ignored from here on and a shift in a ventricular-function curve will be interpreted only as a change in contractility. Further information on these matters is available in several textbooks. 3 • 7 In this form of analysis it is necessary to consider the right or left heart (atrium and ventricle) and attached artery as a separate entity. Right atrial pressure, right ventricular stroke volume, and pulmonaryartery pressure are pertinent to the analysis of right ventricular function alone, as are left atrial pressure, left ventricular stroke volume, and aortic pressure to the analysis of left ventricular function. Failure to recognize the need for such a separation has led to confusion in the past, particularly in attempting to evaluate left ventricular function from knowledge of right atrial pressure. In addition, the influence of circumstances external to the heart must be kept clearly in mind at all times. For example, atrial pressure (mean) is used as an index of ventricular end-diastolic filling pressure and hence of the degree of distention and fiber-lengthening of the ventricle. What one actually needs for these purposes, however, is the transmural pressurethat is, the difference between the pressure inside and that outside the ventricle at end-diastole (Fig. 5). The mean pressure outside the ventricle in the pericardial sac is ordinarily negative though nearly zero during spontaneous respiration; but it increases with opening of the chest, institution of positive-pressure breathing, pneumothorax, pericardial tamponade, and so on. Under these circumstances, increases of atrial pressure are
.'.'
100r-------------~--------~
Rt. ventricle
.'
••••••
.'
80 Figure 4. Family of ventricular-function curves for right ventricle. Normal curve (solid line) is centrally placed. To left is curve (dotted line) of increased contractility. To right is curve (dashed line) of decreased contractility. Equivalent stroke volumes are observed at lower atrial pressures as contractility increases.
// l
l
! I/
l
! I .I I l I l I
20
//
//
!
: !
Normal /
I
I
I
I Contractility inc rea sed --.-~ decreased - - -
O~----~-----L----~----~
o
2
4
6
Rt. atrial pressure - mm. Hg
8
846 Pressure
RICHARD
Relations
of Venous
A.
THEYE
System
Figure 5. Diagram emphasizing filling characteristics of right ventricle. Although peripheral venous, central venous, right atrial, and right ventricular end-diastolic pressures all reflect (in progressively greater degree) the filling pressure of the right ventricle, true filling pressure is difference between pressure inside ventricle and that outside (in pericardial sac) at end-diastole. This is termed transmural or effective filling pressure.
not necessarily accompanied by an increase in transmural or effective filling pressure; and one must either measure the other pressure variable (intrapericardial) or limit interpretation. The other external circumstance requiring consideration is a change in pulmonary-artery or aortic pressure. So long as the pressure in the artery receiving blood from a ventricle is unchanged, stroke volume is a useful index of the amount of energy released with ventricular systole. But obviously, more energy is required to eject a given stroke volume into an artery filled with blood at a pressure of 150 mm. Hg than at, say, 100 mm. Hg. Evaluation of ventricular performance in this circumstance-a change of large magnitude in arterial pressure-is difficult; but it can be approached by conversion of stroke volume to units of work: 8 Work
=
stroke volume X (mean arterial - mean atrial) pressure
EFFECTS OF SPECIAL CONDITIONS
Anesthesia
The influence of anesthesia and operation on cardiac performance is readily presented through the use of ventricular function curves. All potent general anesthetic agents are direct myocardial depressants. 6 That means that anesthetic agents, per se, cause reduction in myocardial contractility. Figure 6 represents this effect as a shift in the ventricular-function curve from the normal position to the right. This has been demonstrated repeat-
847
CARDIAC PERFORMANCE DURING ANESTHESIA AND OPERATION
edly in isolated heart-lung preparations wherein the addition of an anesthetic agent-whether ethyl ether, cyclopropane, halothane, or thiopental -results in a smaller stroke volume at the same atrial pressure or the same stroke volume at a higher atrial pressure. The degree of depression of myocardial contractility in these preparations was similar with all agents at equivalent anesthetic dosage levels and increased progressively as concentration of agent was increased. In intact animals, however-including man-both ethyl ether! and cyclopropane 6 produce increases of sympathetic nervous system activity. Increased sympathetic activity and consequent elevated catecholamine levels are known to shift the curve to the left. 8 As a result of this circumstance, ventricular function in intact man under the influence of only ethyl ether or cyclopropane is ordinarily not depressed at light surgical levels of anesthesia and may indeed be stimulated. 6 The ability of reflex release of catecholamines (or sympathetic stimulation) with these agents to antagonize the direct myocardial depressant effects of the agents per se is illustrated in Figure 7. Catecholamine levels are not known to be elevated with halothane and are elevated only slightly, if at all, with thiopental. The anestheticinduced reduction in myocardial contractility accordingly remains unopposed with these agents. It is believed that this is the major reason why cardiac output usually is higher during light levels of anesthesia with ether or cyclopropane than at similar levels with halothane or thiopental. At deep levels of anesthesia, however, this reflex compensatory mechanism is less effective and myocardial contractility and cardiac output are greatly reduced with all anesthetic agents. 100r-----------------------~
Rt. ventricle
80 -..:
/
E: I
II>
Figure 6. Right ventricularfunction curves illustrating direct depressant effect of anesthetic agents on heart. Note that this effect would result in lower stroke volume at any given atrial pressure.
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~
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.....'-
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/
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/
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1 Direct effect 1 of anesthetic 1
6 Rt. a trio I pre s sur e - m m. H 9
8
848
RICHARD
A.
THEYE
100r-------------------------~
Rt. ventricle Normal
80 Figure 7. Right ventricularfunction curves illustrating effects of opposing forces operative during anesthesia with agents which give rise to increased sympathetic nervous system activity. The latter force, which increases myocardial contractility, is in opposition to the direct depressant effect of the anesthetic agent per se.
60 Anesthetic ag en t
40
20
O~----~----~----L---~
o
4
6
8
Rt. atrial pressure - mm. Hg
Loss of Blood Unreplaced blood loss alters cardiac performance primarily by reducing the blood volume and thereby the effective ventricular filling pressure. Since this phenomenon is dealt with in detail elsewhere (p. 845) only a few remarks are necessary here. When blood is lost without compensatory hemodilution or changes in venous distensibility, venous (including atrial) pressure falls. Stroke volume necessarily decreases unless myocardial contractility increases (shifting the ventricular-function curve to the left). As stroke volume decreases, cardiac output falls unless heart rate increases. In actual practice, however, with unreplaced blood loss some compensation through these agencies does ordinarily take place-particularly in light levels of anesthesia with ether or cyclopropane. For example, in a study of response to unreplaced blood loss during surgery for varicose veins,lO stroke volume and cardiac output were maintained despite reductions of 8 to 34 per cent in blood volume and associated significant reductions in atrial pressure (Fig. 8). Eventually, though-if the blood loss continues and the deficit in blood volume increases-cardiac output falls and the patient is said to be in shock. The mechanisms to compensate for slow, steady loss appear to be more adequate than those available to compensate for acute loss of the same magnitude. The response to replacement of whole blood is illustrated in Figure 9.
Increased Airway Pressure The influence of increased airway pressure on cardiac output is achieved primarily through the mechanical effects of the transmitted
CARDIAC PERFORMANCE DURING ANESTHESIA AND OPERATION
849
pressure itself.4.12 With the chest wall intact, increased airway pressure leads to increased intrathoracic and hence to increased pericardial-sac pressures. Ventricular diastolic filling is thereby impeded. To keep the effective (transmural) filling pressure unchanged, atrial pressure would have to increase at least as much as pericardial-sac pressure increased (Fig. 5). Although some increase in atrial pressure occurs (Fig. 10), it is limited by the natural impedance of the atrial wall and by the momentary reduction in venous return which accompanies an abrupt increase of pressure in the right atrium and the intrathoracic great veins. This reduction in venous return persists until peripheral venous pressure increases sufficiently to restore the previous gradient between peripheral and central veins. Initially the increased peripheral venous pressure is accompanied or accomplished by an increase in peripheral venous blood volume and a corresponding decrease in central venous blood volume. This redistribution of blood volume is less pronounced in the presence of active, effective peripheral venomotor mechanisms and exerts less deleterious effects in the presence of normovolemia. The other compensatory mechanism of importance in responding to 40
A •
STROKE INOEX
A •
VENOUS PRESSURE
o • CARDIAC
OUTPUT
t }
20
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...J
0
~
C!:
0
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-60~--~~--~~--~----~--
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• MEAN find S.E. of MEAN
__- L____-L____~__~
5
7
9
hours Figure 8. Hemodynamics during ether anesthesia, unreplaced blood loss, and varicose-vein surgery. These average values were observed in 10 patients with reductions in blood volume of 8 to 34 per cent. Note the maintenance of stroke volume despite significant, progressive reduction in atrial pressure. Presumably myocardial contractility was increasing during this period.
850
RICHARD
A.
THEYE
36
32
Cardiac index =4.85 L./min.lm 2
~
28
~
24
~ ~
20
~
16
Q) ~
§
~
Cardiac index = 2.18 L.lmin.lm2
12 Right atrium 8
4
o
200
400
600
800
1000
1200
1400
Blood transfusion in ml.
Figure 9. Response of atrial pressures and cardiac output to transfusion of 1400 m!. heparinized blood. Observations were made following closure of atrial septal defect in young adult. Note great increase in cardiac output following transfusion and elevation of atrial pressures. Greater increase in left atrial pressure is believed to result from lesser distensibility of left ventricle. (Reproduced with permission from: Theye, R. A. and Moffitt, E. A.: Blood TransfUl~ion Therapy During Anesthesia and Operation. Anesth. & Analg. 41:354-359 [May-Junej1962.)
an increase in airway pressure is, of course, an increase in myocardial contractility. In anesthetized man, this is most likely available at light levels of ether or cyclopropane anesthesia. For all of these reasons, small increases in mean airway pressure ordinarily are tolerated with ease by healthy, normovolemic patients lightly anesthetized with ether or cyclopropane. In the presence of preexisting heart disease or hypovolemia, large increases of airway pressure may lead to serious reductions in cardiac output, particularly during deep thiopental or halothane anesthesia.
SUMMARY
Cardiac performance during anesthesia and operation has been presented through the medium, primarily, of ventricular-function curves. All
Figure 10. Influence of increased airway pressure on cardiac output during halothane anesthesia. Observations (Theye, R. A. and Tuohy, G. F.: Unpublished data.) were made during controlled ventilation halothane anesthesia, and surgery for varicose veins. Airway pressure was elevated artificially by maintaining rebreathing bag in anesthetic circuit overfilled and distended during 3D-minute period indicated.
potent anesthetic agents are direct depressants of myocardial contractility. At high concentrations, all anesthetic agents are associated with significant reductions in cardiac output. At lighter levels of anesthesia with ether or cyclopropane, this direct myocardial depressant effect is largely compensated for by the reflex stimulation of the sympathetic nervous system. Unreplaced blood loss may cause reduction of cardiac output through hypovolemia and consequent reduction of ventricular filling pressure. Increased airway pressure can reduce cardiac output by impeding venous return and restricting ventricular diastolic filling.
REFERENCES 1. Brewster, W. R., Jr., Isaacs, J. P. and Waino-Andersen, Thorkild: Depressant effect
of ether on myocardium of the dog and its modification by reflex release of epinephrine and nor-epinephrine. Am. J. Physiol. 175:399-414 (Dec.) 1953. 2. Guyton, A. C.: Symposium on regulation of performance of heart: Determination of cardiac output by equating venous return curves with cardiac response curves. Physiol. Rev. 35:123-129 (Jan.) 1955. 3. Hamilton, W. F. and Dow, Philip: Handbook of Physiology: A Critical, Compre-
852
4. 5. 6. 7. 8. 9. 10. 11. 12.
RICHARD
A.
THEYE
hensive Presentation of Physiological Knowledge and Concepts. Section 2: Circulation. Washington, D. C., American Physiological Society, 1963, vol. 2, 1786 pp. Maloney, J. V., Jr., Elam, J. 0., Handford, S. W., Balla, G. A., Eastwood, D. W., Brown, E. S. and Ten Pas, R. H.: Importance of negative pressure phase in mechanical respirators. J.A.M.A. 152:212-216 (May 16) 1953. Payne, J. P. and Armstrong, P. J.: Measurement of cardiac output. Brit. J. Anaesth. 34:637-645 (Sept.) 1962. Price, H. L.: Circulatory actions of general anesthetic agents and the homeostatic roles of epinephrine and norepinephrine in man. Clin. Pharmacol. & Therap. 2:163-176 (March-April) 1961. Rushmer, R. F.: Cardiovascular Dynamics. 2nd Ed. Philadelphia, W. B. Saunders Company, 1961, 503 pp. Sarnoff, S. J.: Symposium on regulation of performance of heart: Myocardial contractility as described by ventricular function curves; observations on Starling's law of the heart. Physiol. Rev. 35:107-122 (Jan.) 1955. Theye, R. A., Rehder, Kai, Quesada, R. S. and Fowler, W. S.: Measurement of cardiac output by an indicator-dilution method. Anesthesiology 25:71-74 (Jan.Feb.) 1964. Theye, R. A. and Tuohy, G. F.: Hemodynamics and blood volume during operation with ether anesthesia and unreplaced blood loss. Anesthesiology 25:6-14 (Jan.Feb.) 1964. Wade, O. L. and Bishop, J. M.: Cardiac Output and Regional Blood Flow. Oxford, Blackwell Scientific Publications, 1962. Whittenberger, J. L.: Artificial respiration. Physiol. Rev. 35:611-628 (July) 1955.
The fundamental function of the heart is to pump blood through a system of connected tubes. In this chapter, the conceptual basis for regulating the rate of output from this pump (cardiac output) will be developed. Also, the manner in which cardiac output is altered by anesthesia, unreplaced blood loss, and increased airway pressure will be discussed. Of course there are other potent forces capable of altering cardiac performance during anesthesia and operation: a complete list would include hypoxia, hypercarbia, arrhythmias, countless drugs, coronary-artery dise9,se, and abnormalities of valvular function. Although these additional circumstances will not be discussed, they must not be forgotten.
TERMS AND ANALYTIC TECHNIQUES
Certain terms are commonly used to describe the functions of the cardiovascular system. The flow through the systemic vascular bed (systemic flow) is equal to left ventricular output. Left and right ventricular outputs are necessarily equal, as are pulmonary and systemic flow rates except in certain unsteady states of short duration and in the presence of intracardiac or systemic-pulmonary shunts. Cardiac output is used ordinarily to indicate left or right ventricular output. Thus, for all practical purposes, values for left or right ventricular output and for systemic or pulmonary flow rates are interchangeable and equal to cardiac output. Cardiac output, the volume output of either ventricle per unit of time, is the product of stroke volume and heart rate. When cardiac output and stroke volume are expressed relative to body surface area (in square meters), the terms "cardiac index" and "stroke index" are used. For example, a normal adult man of 1.8 sq.m. body surface might have a cardiac output of 6.3 L. per min., cardiac index of 3.5 L. per min. per sq.m., heart rate of
* This investigation was supported in part by Research Grant H-4881 from the National Institutes of Health, Public Health Service.
841
842
RICHARD
A.
(mg. /
RADIAL _--+---....:- - - - -ARTERY
------------
THEYE
L.)
0
5
10
Signal
5 mg. Indocyanine Green into Left Atrium
Base Line==~~==============~============~============= Figure 1. Dye curve recorded from radial artery following left atrial injection of 5 mg. indocyanine green. (Note appearance of dye in approximately 4 seconds with rapid increase in concentration. After reaching peak, dye concentration rapidly decreases. Recirculation of injected dye prevents complete return to base line.) Curve resulting from right atrial injection of dye would have smaller maximal deflection and be more spread out but would yield same calculated value for cardiac output. (Reproduced with permission from: Theye, R. A. and Kirklin, J. W.: Physiologic Studies Early After Repair of Tetralogy of Fallot. Circulation 28:42-51 [July] 1963.)
75 beats per min., stroke volume of 84 mI., and stroke index of 47 mI. per sq.m. Cardiac output can be measured by a variety of techniques. 5 • 11 The classic methods utilize the Fick relationship: C ardiacoupu t t
=
oxygen uptake . . (arterIal - ffilxed venous) OJ content
This approach is of limited applicability to anesthetized subjects because of the technical problems of analyzing blood and gas in the presence of gaseous anesthetic agents. Techniques for gas chromatography show promise of removing this barrier. In the meantime, dye-dilution techniques have been widely applied to the measurement of cardiac output in anesthetized man, both in the laboratory and in the operating room. In this approach, a known amount of indicator is injected as "centrally" as possible and the time course of change in concentration of this indicator in arterial blood is recorded. Common indicators include indocyanine green, Evans blue, isotopically tagged albumin, and cold saline. The most common application includes injection of indocyanine green via a catheter passed to the right
CARDIAC PERFORMANCE DURING ANESTHESIA AND OPERATION
843
atrium and sampling from a peripheral artery through a densitometer.9 A typical dye curve obtained in this manner is illustrated in Figure 1. Knowledge of the amount of dye injected and the calibration curve of the instrument would permit calculation of cardiac output from this curve. ll
INTERREACTION OF FACTORS
The manner in which cardiac output is controlled in intact man is not fully understood. Some prefer to regard the heart as passive in this regardpumping whatever volume of blood it receives. The primary determinant of cardiac output then would be the rate of venous return as influenced by peripheral vascular factors.2 For our purposes, however, it is more convenient to think of the heart as having an active influence on cardiac output and performing along lines suggested by Starling and extended by Sarnoff. The basic concept in this approach is Starling's "Law of the Heart," which states that the amount of energy released with ventricular systole is a direct function of ventricular end-diastolic fiber length. Since neither the amount of energy released nor the end-diastolic fiber length is easily measured, the usefulness of this expression is limited except after certain modifications. When the pressure in the artery receiving blood from the ventricle is unchanged, stroke volume can be substituted for energy released with ventricular systole. When myocardial distensibility is unchanged and pericardial-sac pressure is near zero and constant, mean atrial pressure can be substituted for ventricular end-diastolic fiber length. Under these conditions, the "Law of the Heart" is the direct relationship between stroke volume and mean atrial pressure-both of which are familiar and readily measured. The graphic description of the relationship between stroke volume and mean atrial pressure has come to be called a ventricular-function curve. Extension of the relationship to cardiac output requires only that consideration of the heart rate be included. Typical curves for the right and left ventricles are illustrated in Figures 2 and 3. In these forms the relationships are physiologically valid but have little utility, since they describe the response of the ventricle to variations in atrial pressure under a single, unchanging condition of myocardial distensibility and contractility. Sarnoff has suggested that ventricular performance could be described better by a family of ventricular function curves-each having the same general shape, but with the slope depending on the state of the myocardium. Within this context, increased myocardial contractility is defined as increased release of energy at a given fiber length and is represented by a shift of the curve to the left-that is, a greater stroke volume for the same atrial pressure or the same stroke volume for a lower atrial pressure. In the same fashion decreased contractility is represented by a shift of the
844
RICHARD
A
THEYlf
100~----------------------~
Rt. ventricle
80 Figure 2. Ventricular-function curve for right ventricle, illustrating direct relationship between right ventricular stroke volume and right atrial pressure. This is direct extension of Starling's law of the heart assuming no change in pulmonary-artery pressure and in myocardial distensibility and contractility.
20
00
6
8
Rt. atr i a I pressure -mm. Hg 100
Lt. ve n t ric I e 80
Figure 3. Ventricular-funetion curve for left ventricle. Stroke volume and atrial pressure are directly related. Note that (1) slope of this curve is flatter than that for right ventricle (Fig. 2) and (2) for equivalent stroke volumes, left ventricle requires higher filling pressures than right. These differences are based, presumably, on lesser distensibility of left ventricle.
-..:
e:I
.,
e: ....I::>
60
:::,
....,
'"
40
... .....
I::>
\I)
20
0
0
2
4
6
8
10
Lt. atrial pressure - mm. Hg
curve to the right. A family of curves for the right ventricle is illustrated in Figure 4. Ordinarily this form of analysis ignores altered distensibility as a basis for altered function. This is partly because of the difficulties in measurement of ventricular end-diastolic volume but also partly because of lack of agreement on definition of terms. For example, if distensibility is increased, a given atrial or filling pressure results in a greater fiber length-which for a given state of contractility would result in a greater energy release. Accordingly, a shift of the curve to the left is attributed more correctly to
845
CARDIAC PERFORMANCE DURING ANESTHESIA AND OPERATION
increased contractility or distensibility, or both, than to increased contractilityalone. For the sake of convenience only, this point will be ignored from here on and a shift in a ventricular-function curve will be interpreted only as a change in contractility. Further information on these matters is available in several textbooks. 3 • 7 In this form of analysis it is necessary to consider the right or left heart (atrium and ventricle) and attached artery as a separate entity. Right atrial pressure, right ventricular stroke volume, and pulmonaryartery pressure are pertinent to the analysis of right ventricular function alone, as are left atrial pressure, left ventricular stroke volume, and aortic pressure to the analysis of left ventricular function. Failure to recognize the need for such a separation has led to confusion in the past, particularly in attempting to evaluate left ventricular function from knowledge of right atrial pressure. In addition, the influence of circumstances external to the heart must be kept clearly in mind at all times. For example, atrial pressure (mean) is used as an index of ventricular end-diastolic filling pressure and hence of the degree of distention and fiber-lengthening of the ventricle. What one actually needs for these purposes, however, is the transmural pressurethat is, the difference between the pressure inside and that outside the ventricle at end-diastole (Fig. 5). The mean pressure outside the ventricle in the pericardial sac is ordinarily negative though nearly zero during spontaneous respiration; but it increases with opening of the chest, institution of positive-pressure breathing, pneumothorax, pericardial tamponade, and so on. Under these circumstances, increases of atrial pressure are
.'.'
100r-------------~--------~
Rt. ventricle
.'
••••••
.'
80 Figure 4. Family of ventricular-function curves for right ventricle. Normal curve (solid line) is centrally placed. To left is curve (dotted line) of increased contractility. To right is curve (dashed line) of decreased contractility. Equivalent stroke volumes are observed at lower atrial pressures as contractility increases.
// l
l
! I/
l
! I .I I l I l I
20
//
//
!
: !
Normal /
I
I
I
I Contractility inc rea sed --.-~ decreased - - -
O~----~-----L----~----~
o
2
4
6
Rt. atrial pressure - mm. Hg
8
846 Pressure
RICHARD
Relations
of Venous
A.
THEYE
System
Figure 5. Diagram emphasizing filling characteristics of right ventricle. Although peripheral venous, central venous, right atrial, and right ventricular end-diastolic pressures all reflect (in progressively greater degree) the filling pressure of the right ventricle, true filling pressure is difference between pressure inside ventricle and that outside (in pericardial sac) at end-diastole. This is termed transmural or effective filling pressure.
not necessarily accompanied by an increase in transmural or effective filling pressure; and one must either measure the other pressure variable (intrapericardial) or limit interpretation. The other external circumstance requiring consideration is a change in pulmonary-artery or aortic pressure. So long as the pressure in the artery receiving blood from a ventricle is unchanged, stroke volume is a useful index of the amount of energy released with ventricular systole. But obviously, more energy is required to eject a given stroke volume into an artery filled with blood at a pressure of 150 mm. Hg than at, say, 100 mm. Hg. Evaluation of ventricular performance in this circumstance-a change of large magnitude in arterial pressure-is difficult; but it can be approached by conversion of stroke volume to units of work: 8 Work
=
stroke volume X (mean arterial - mean atrial) pressure
EFFECTS OF SPECIAL CONDITIONS
Anesthesia
The influence of anesthesia and operation on cardiac performance is readily presented through the use of ventricular function curves. All potent general anesthetic agents are direct myocardial depressants. 6 That means that anesthetic agents, per se, cause reduction in myocardial contractility. Figure 6 represents this effect as a shift in the ventricular-function curve from the normal position to the right. This has been demonstrated repeat-
847
CARDIAC PERFORMANCE DURING ANESTHESIA AND OPERATION
edly in isolated heart-lung preparations wherein the addition of an anesthetic agent-whether ethyl ether, cyclopropane, halothane, or thiopental -results in a smaller stroke volume at the same atrial pressure or the same stroke volume at a higher atrial pressure. The degree of depression of myocardial contractility in these preparations was similar with all agents at equivalent anesthetic dosage levels and increased progressively as concentration of agent was increased. In intact animals, however-including man-both ethyl ether! and cyclopropane 6 produce increases of sympathetic nervous system activity. Increased sympathetic activity and consequent elevated catecholamine levels are known to shift the curve to the left. 8 As a result of this circumstance, ventricular function in intact man under the influence of only ethyl ether or cyclopropane is ordinarily not depressed at light surgical levels of anesthesia and may indeed be stimulated. 6 The ability of reflex release of catecholamines (or sympathetic stimulation) with these agents to antagonize the direct myocardial depressant effects of the agents per se is illustrated in Figure 7. Catecholamine levels are not known to be elevated with halothane and are elevated only slightly, if at all, with thiopental. The anestheticinduced reduction in myocardial contractility accordingly remains unopposed with these agents. It is believed that this is the major reason why cardiac output usually is higher during light levels of anesthesia with ether or cyclopropane than at similar levels with halothane or thiopental. At deep levels of anesthesia, however, this reflex compensatory mechanism is less effective and myocardial contractility and cardiac output are greatly reduced with all anesthetic agents. 100r-----------------------~
Rt. ventricle
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Figure 6. Right ventricularfunction curves illustrating direct depressant effect of anesthetic agents on heart. Note that this effect would result in lower stroke volume at any given atrial pressure.
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848
RICHARD
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80 Figure 7. Right ventricularfunction curves illustrating effects of opposing forces operative during anesthesia with agents which give rise to increased sympathetic nervous system activity. The latter force, which increases myocardial contractility, is in opposition to the direct depressant effect of the anesthetic agent per se.
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Loss of Blood Unreplaced blood loss alters cardiac performance primarily by reducing the blood volume and thereby the effective ventricular filling pressure. Since this phenomenon is dealt with in detail elsewhere (p. 845) only a few remarks are necessary here. When blood is lost without compensatory hemodilution or changes in venous distensibility, venous (including atrial) pressure falls. Stroke volume necessarily decreases unless myocardial contractility increases (shifting the ventricular-function curve to the left). As stroke volume decreases, cardiac output falls unless heart rate increases. In actual practice, however, with unreplaced blood loss some compensation through these agencies does ordinarily take place-particularly in light levels of anesthesia with ether or cyclopropane. For example, in a study of response to unreplaced blood loss during surgery for varicose veins,lO stroke volume and cardiac output were maintained despite reductions of 8 to 34 per cent in blood volume and associated significant reductions in atrial pressure (Fig. 8). Eventually, though-if the blood loss continues and the deficit in blood volume increases-cardiac output falls and the patient is said to be in shock. The mechanisms to compensate for slow, steady loss appear to be more adequate than those available to compensate for acute loss of the same magnitude. The response to replacement of whole blood is illustrated in Figure 9.
Increased Airway Pressure The influence of increased airway pressure on cardiac output is achieved primarily through the mechanical effects of the transmitted
CARDIAC PERFORMANCE DURING ANESTHESIA AND OPERATION
849
pressure itself.4.12 With the chest wall intact, increased airway pressure leads to increased intrathoracic and hence to increased pericardial-sac pressures. Ventricular diastolic filling is thereby impeded. To keep the effective (transmural) filling pressure unchanged, atrial pressure would have to increase at least as much as pericardial-sac pressure increased (Fig. 5). Although some increase in atrial pressure occurs (Fig. 10), it is limited by the natural impedance of the atrial wall and by the momentary reduction in venous return which accompanies an abrupt increase of pressure in the right atrium and the intrathoracic great veins. This reduction in venous return persists until peripheral venous pressure increases sufficiently to restore the previous gradient between peripheral and central veins. Initially the increased peripheral venous pressure is accompanied or accomplished by an increase in peripheral venous blood volume and a corresponding decrease in central venous blood volume. This redistribution of blood volume is less pronounced in the presence of active, effective peripheral venomotor mechanisms and exerts less deleterious effects in the presence of normovolemia. The other compensatory mechanism of importance in responding to 40
A •
STROKE INOEX
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VENOUS PRESSURE
o • CARDIAC
OUTPUT
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hours Figure 8. Hemodynamics during ether anesthesia, unreplaced blood loss, and varicose-vein surgery. These average values were observed in 10 patients with reductions in blood volume of 8 to 34 per cent. Note the maintenance of stroke volume despite significant, progressive reduction in atrial pressure. Presumably myocardial contractility was increasing during this period.
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36
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Cardiac index =4.85 L./min.lm 2
~
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12 Right atrium 8
4
o
200
400
600
800
1000
1200
1400
Blood transfusion in ml.
Figure 9. Response of atrial pressures and cardiac output to transfusion of 1400 m!. heparinized blood. Observations were made following closure of atrial septal defect in young adult. Note great increase in cardiac output following transfusion and elevation of atrial pressures. Greater increase in left atrial pressure is believed to result from lesser distensibility of left ventricle. (Reproduced with permission from: Theye, R. A. and Moffitt, E. A.: Blood TransfUl~ion Therapy During Anesthesia and Operation. Anesth. & Analg. 41:354-359 [May-Junej1962.)
an increase in airway pressure is, of course, an increase in myocardial contractility. In anesthetized man, this is most likely available at light levels of ether or cyclopropane anesthesia. For all of these reasons, small increases in mean airway pressure ordinarily are tolerated with ease by healthy, normovolemic patients lightly anesthetized with ether or cyclopropane. In the presence of preexisting heart disease or hypovolemia, large increases of airway pressure may lead to serious reductions in cardiac output, particularly during deep thiopental or halothane anesthesia.
SUMMARY
Cardiac performance during anesthesia and operation has been presented through the medium, primarily, of ventricular-function curves. All
Figure 10. Influence of increased airway pressure on cardiac output during halothane anesthesia. Observations (Theye, R. A. and Tuohy, G. F.: Unpublished data.) were made during controlled ventilation halothane anesthesia, and surgery for varicose veins. Airway pressure was elevated artificially by maintaining rebreathing bag in anesthetic circuit overfilled and distended during 3D-minute period indicated.
potent anesthetic agents are direct depressants of myocardial contractility. At high concentrations, all anesthetic agents are associated with significant reductions in cardiac output. At lighter levels of anesthesia with ether or cyclopropane, this direct myocardial depressant effect is largely compensated for by the reflex stimulation of the sympathetic nervous system. Unreplaced blood loss may cause reduction of cardiac output through hypovolemia and consequent reduction of ventricular filling pressure. Increased airway pressure can reduce cardiac output by impeding venous return and restricting ventricular diastolic filling.
REFERENCES 1. Brewster, W. R., Jr., Isaacs, J. P. and Waino-Andersen, Thorkild: Depressant effect
of ether on myocardium of the dog and its modification by reflex release of epinephrine and nor-epinephrine. Am. J. Physiol. 175:399-414 (Dec.) 1953. 2. Guyton, A. C.: Symposium on regulation of performance of heart: Determination of cardiac output by equating venous return curves with cardiac response curves. Physiol. Rev. 35:123-129 (Jan.) 1955. 3. Hamilton, W. F. and Dow, Philip: Handbook of Physiology: A Critical, Compre-
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4. 5. 6. 7. 8. 9. 10. 11. 12.
RICHARD
A.
THEYE
hensive Presentation of Physiological Knowledge and Concepts. Section 2: Circulation. Washington, D. C., American Physiological Society, 1963, vol. 2, 1786 pp. Maloney, J. V., Jr., Elam, J. 0., Handford, S. W., Balla, G. A., Eastwood, D. W., Brown, E. S. and Ten Pas, R. H.: Importance of negative pressure phase in mechanical respirators. J.A.M.A. 152:212-216 (May 16) 1953. Payne, J. P. and Armstrong, P. J.: Measurement of cardiac output. Brit. J. Anaesth. 34:637-645 (Sept.) 1962. Price, H. L.: Circulatory actions of general anesthetic agents and the homeostatic roles of epinephrine and norepinephrine in man. Clin. Pharmacol. & Therap. 2:163-176 (March-April) 1961. Rushmer, R. F.: Cardiovascular Dynamics. 2nd Ed. Philadelphia, W. B. Saunders Company, 1961, 503 pp. Sarnoff, S. J.: Symposium on regulation of performance of heart: Myocardial contractility as described by ventricular function curves; observations on Starling's law of the heart. Physiol. Rev. 35:107-122 (Jan.) 1955. Theye, R. A., Rehder, Kai, Quesada, R. S. and Fowler, W. S.: Measurement of cardiac output by an indicator-dilution method. Anesthesiology 25:71-74 (Jan.Feb.) 1964. Theye, R. A. and Tuohy, G. F.: Hemodynamics and blood volume during operation with ether anesthesia and unreplaced blood loss. Anesthesiology 25:6-14 (Jan.Feb.) 1964. Wade, O. L. and Bishop, J. M.: Cardiac Output and Regional Blood Flow. Oxford, Blackwell Scientific Publications, 1962. Whittenberger, J. L.: Artificial respiration. Physiol. Rev. 35:611-628 (July) 1955.