7 the annals of thoracic surgery volume 7 issue 2 1969 [doi 10.1016%2fs0003-4975%2810%2966161-9]...

COLLECTIVE REVIEW

Cardiac Output Clinical Monitoring and Management

Joseph S. Carey, M.D., and Richard K. Hughes, M.D.

ore than any other single clinical advance in recent years, operative procedures on the heart have focused attention on M the need for more accurate evaluation of the ability of the

heart to provide adequate blood flow. A high percentage of patients in whom open cardiac procedures are performed have low cardiac output preoperatively, and valvular repair usually does not immediately restore normal myocardial function [3, 4, 74, 971. Thus, Zow cardiac output syndrome has become a clinical entity. The diagnosis has generally rested on recognition of the effects of low cardiac output rather than its direct measurement. Treatment of low cardiac output is also empirical and usually rests on the monitoring of variables influenced by cardiac output. There are many easily measured variables directly or indirectly related to cardiac output, such as blood pressure, pulse, urine output, arterial and venous blood gases, and various clinical signs. Taken together, such studies yield valuable information, but they do not always accurately reflect cardiac output.

Many techniques have been developed for the estimation of cardiac output, but not all are applicable to bedside monitoring. This is because all measurements of cardiac output are indirect estimations based on various mathematical and physical assumptions. As such, they contain inherent errors that must be determined and minimized. Certain techniques are not applicable when the assumptions cannot be met in a given physiological setting. For example, the determination of cardiac

From the Division of Thoracic Surgery, Veterans Administration Center, and the UCLA School of Medicine, Los Angeles, Calif., and the University of Utah College of Medicine, Salt Lake City, Utah.

Address reprint requests to Dr. Carey, Division of Thoracic Surgery, Veterans Administration Center, Los Angeles, Calif. 90073.

150 THE ANNALS OF THORACIC SURGERY

COLLECTIVE REVIEW: Cardiac Output

output by the Fick principle, in which expired air is collected and analyzed, is inaccurate unless all expired air is collected; such a collection would be difficult to perform in a patient who could not maintain a mouthpiece in proper position. The use of a tight-fitting face mask for collection purposes might influence the patients breathing pattern and in itself produce a change in oxygen uptake. Similarly, measurement of aortic flow by flowmeter requires implantation by thoracotomy and would require open removal subsequently.

The methods that have been used in seriously ill or postoperative patients have generally been variations of the Fick principle, the indicator-dilution technique, or the pulse-contour method. The purpose in this review is to consider the practical aspects of these and other techniques in evaluating the acutely ill patient, and to review briefly the management of patients with low cardiac output. For more detailed analysis of the subject, several textbooks and reviews are available [l6, 56, 58, 101, 1191.

T H E FICK PRINCIPLE A N D T H E INDICATOR-DILUTION TECHNIQUE

The Fick principle is based on the fact that during its passage through the peripheral tissues, a certain amount of oxygen is taken up from the blood. If the volume of oxygen taken up from every 100 cc. of blood during one passage through the tissues is determined, and the total volume of oxygen taken up by the body during a certain period of time is known, then the number of 100 cc. increments that must have passed by during that time can be calculated. Thus, if 5 cc. of oxygen is given up by 100 cc. of blood, and 300 cc. of oxygen is taken up in one minute, then 60 increments of 100 cc., or 6 liters, must have flowed through the tissues during that minute, as is shown by the following formulas:

Total O2 uptake (cc./min.) cc. O2 given up/ 100 cc. blood

Total Flow (Cardiac Output) cc./min. = (1)

O2 uptake C.O. cc./min. = x 100, (2) A-V 0, difference

300 5

C.O. cc./min. = - x 100.

For this determination, venous oxygen content,

a sampling of arterial oxygen content, mixed and volume of oxygen taken up by the lungs

is required. Mixed venous blood must be drawn from the -pulmonary artery, and a three-minute sample of expired air is required for accurate determination of oxygen uptake. The limitations of this method are

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the difficulty of obtaining accurate samples of expired air in acutely ill patients, the need for sampling of pulmonary artery blood, and the time- consuming analysis of expired air and blood oxygen concentrations. Nevertheless, this technique was used by Cournand and associates [3 11 in performing their original studies of hemodynamics in clinical shock. With the availability of continuous recording of arterial and venous oxygen saturation and expired oxygen concentration, and on-line computer analysis, an instantaneous estimation of cardiac output may be possible in the future.

A technique analogous to the Fick principle is the rapid injection of an indicator into the circulation, with downstream analysis of its dilution concentration. The continuous analysis of this concentration produces an indicator-dilution curve (Fig. 1). The total flow (F) is related to the concentration recorded at the sampling site in the following manner: The amount of indicator passing the site during any interval of time (d t ) is equal to the average concentration [ C ( t ) ] recorded during that time multiplied by the total rate of flow. The total amount of indicator (I mg.) injected is equal to the summation of all the increments of concentration multiplied by the flow rate, as follows:

Zmg. Z m g . = F x 2 C(t)dt or F =

0 C(t)dt

0

(4) +

In the absence of recirculation, the concentration curve would grad- ually diminish at an exponential rate as new blood flowed into the system and replaced the blood containing the indicator (B in Fig. 1). However, in practice the blood containing the indicator recirculates and contaminates the downslope of the curve (A in Fig. 1). Ordinarily,

~~

FZG. 1. Indicator-dilution curve obtained by continuous sampling of femoral artery blood after injection of indocyanine green dye into the right atrium of a patient with normal cardiac output. (A) Actual curve contaminated by recirculation. (B) Ideal curve that would be recorded if recirculation did not occur.

*Thus, if 6 mg. of dye is injected into the right atrium, and an average concentration of 6 mg. per liter is recorded over a 10-second period in the arterial blood, then one liter of blood must have flowed by during that 10-second period. The cardiac output would thus be 6 liters per minute.



the first portion of the downslope occurs before recirculation occurs, and the remainder of the downslope can be extrapolated by plotting the logarithm of the first part of the descending portion of the curve against time. The assumption of this extrapolation is that the exponential rate of decay is a negative constant, and thus, when the concentration curve is plotted on log paper, the downslope (before recirculation) will form a straight line with a slope related to this constant. This line may then be extended to the baseline and the integration (summation) procedure performed.

It is necessary for the indicator to be perfectly mixed in its dilution volume in order to insure an exponential washout of the indicator. If there is at least one ventricle between the injection and sampling sites, mixing is usually adequate. The indicator must not in itself stimulate the cardiovascular system and should be easy to detect in the arterial blood. Evans blue dye, indocyanine green dye, saline, and various radioactive labeled substances are most frequently used. Colored dyes are detected in the arterial blood by withdrawal through a densitometer, which detects the absorption of light by the dye at a specific wavelength. Indocyanine green is preferred because it absorbs light at a wavelength (805 mp) at which reduced hemoglobin and oxygenated hemoglobin have the same absorption characteristics, so that hemoglobin saturation does not affect the density of the blood. Indocyanine green is rapidly removed from the circulation by the liver [66], and does not accumulate significantly as does Evans blue dye. However, during rapidly repeated injections, some green dye will accumulate and may produce an error of up to 11% in calibration curves [39].

Saline has been used as an indicator by recording changes in temperature or electrical conductivity of blood after its infusion [16, 58, 84, 1121. Electrical conductivity is measured by a small conductivity cell placed distal to the site of injection of a small volume of saline. A typi- cal indicator-dilution curve is recorded. These curves are difficult to calibrate, and saline may be lost or electrical conductivity of the blood itself may change unless the injection and sampling sites are close together (injection in right or left ventricle, sampling in pulmonary artery or aorta).

The change in temperature of the blood after injection of saline may be recorded as an indicator-dilution (thermodilution) curve. This technique has received considerable attention in recent years, primarily as a means of measuring ventricular volume [97]. The theory and application have been reviewed by Hosie [641, Hamilton [58], and Burton [16]. The determination of cardiac output by this technique (as well as the electrical conductivity method) has the attractive advantage of the absence of recirculation, since the temperature change (or change in electrical conductivity) is soon dissipated in the vascular beds distal to

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the recording site. The injection and sampling sites must thus be relatively close together. Nevertheless, cardiac output has been determined by thermodilution from injections on the right side of the heart and sampling on the left with reasonable accuracy in normal patients, perhaps because of the insulating effect of air in the lungs [64]. Patho- logical conditions like pulmonary edema and pulmonary vascular or parenchymal disease may cause considerable error, and thermodilution has not as yet found a place in the monitoring of the seriously ill patient.

Various radioactive substances have been used as indicators for the recording of dilution curves [28,35, 36, 50-52, 75, 781. Gamma-emitting isotopes must be used, since the only significant external radiation resulting from internally located radioisotopes comes from gamma rays. The most commonly used isotope is I131-tagged albumin, because Cali- bration may be accomplished by allowing the indicator to completely equilibrate with the circulation. Since it is well known that the measurement of blood volume by I131-tagged albumin in acutely ill patients is frequently in error due to improper mixing of the indicator, the dependence on this equilibration may lead to error when radiocardiography is used to measure cardiac output. In addition, as pointed out by Conn [28], the equilibration count over the heart covers a larger field of radiation than the original recording of the first pass of indicator, since contamination by isotope in adjacent vessels may occur.

The equipment required for radiocardiography includes a crystal scintillation counter, a photomultiplier system, an electronic amplifier, a count rate meter, and an electronic recorder. A collimating shield is used to avoid pickup of radioactive scatter when the counter is posi- tioned over the precordium. The system may be focused in order to reduce to a minimum the errors due to radioactive scatter, positioning of the collimator, and amounts of intervening tissue. The disadvantages of equipment required and potential errors due to positioning and anatomical variations are offset by the advantage that arterial cannula- tion is avoided. Kloster and his associates [75] obtained a 3.2% average variation between paired cardiac output determinations by radiocardiography, and an 8.4% average difference when compared to the Fick method. These results compare favorably with those obtained by comparison of the dye-dilution with Fick techniques [57].

The indicator-dilution curve recorded by isotope dilution is not as smooth as the dye-dilution curve, and because of its passage through each ventricle a double-peaked curve is recorded. This makes the calculation by integration of the curve somewhat more difficult. How- ever, a method has been developed by which the integration procedure may be performed without extrapolation of the downslope [51]. Further refinements of this technique may be expected in the future, some of which are discussed below.


COLLECTIVE REVlEW: Cardiac Output

CALCULATION OF CARDIAC OUTPUT FROM INDICA TOR-DILUTION CURVES

The procedure for the calculation of cardiac output by the dye- dilution technique will now be described in detail, since this is the method most frequently used at the present time. However, much of the discussion also pertains to other indicator-dilution methods.

The recording apparatus for the dye-dilution curve includes a dye densitometer and an amplifier-recorder system. Arterial blood is with- drawn at a constant rate (usually 20 to 40 cc. per minute) through a cuvette in the densitometer. The dye curve is recorded on a linear recorder. The classic method of deriving cardiac output from indicator- dilution curves was proposed by Stewart and refined by Kinsman, Moore, and Hamilton [72]. The area under the curve is determined by measuring the concentration at specific time intervals on the replotted curve (B in Fig. 1). Cardiac output is then obtained from formula 4.

The more peripheral the site of injection, the greater will be the dilution volume of the dye. This will result in a curve with a lower peak concentration and a more gradual washout. When the washout is gradual, the downslope of the curve is more likely to be contaminated by recirculation [93]. Figure 2 illustrates the difference between dye curves recorded from the femoral artery after injection of dye into the ascending aorta and left atrium in a patient with a large left atrium. The dilution of the dye in the large left atrium results in a much lower peak concentration and a non-

The following aspects of this technique should be noted. Sites of Injection and Sampling.

FIG. 2. Effect of injection site on dye-dilution curve. Indicator-dilution curves obtained during operation by continuous sampling of femoral artery blood after injection of indocyanine green dye in (A) the ascending aorta and (B) the left atrium of a patient with mitral stenosis and a large left atrium. Delayed washout from the left atrium results in nonexponential downslope of curve (B).

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exponential, gradual washout of dye. Such curves are impossible to integrate accurately. In the normal circulation, without delayed circulation time or enlargement of the cardiac chambers, peripheral vein injection sites will give reasonable results. However, when circulation time is delayed, as when cardiac output is low, central injection into the great veins or right atrium is necessary in order to avoid contamination of the downslope by recirculation. When cardiac enlargement as well as low cardiac output is present, an accurate dye curve may not be obtained unless injection is made into the ascending aorta. Chronic lung disease may also result in errors in dye curve recording, due to variations in transit time across the lungs [92]. Therefore, under conditions of low flow and cardiopulmonary disease, it is necessary to bring the injection and sampling sites closer together.

Dye curves are affected by peripheral sampling sites to some degree, particularly if more peripheral arteries, such as the radial, are used [5]. This is because variations in local circulation time due to vasospasm may result in sampling delay and produce spurious recording of the actual dye concentration. This may be most pronounced when sampling is performed with an earpiece densitometer, which samples the dye as it passes through the pinna of the ear [99], Although this technique may be useful for studying the normal or exercise circulation under specific conditions, it is not accurate in low flow states and thus probably not useful in acutely ill patients. In low flow states it is therefore preferable to utilize the femoral artery or aorta for sampling. One of the advantages of the radioactive isotope dilution technique is that sampling is made directly over the heart. This somewhat reduces the problems of excessive dilution that occur in patients with cardiac enlargement.

The length and diameter of the catheter connecting the sampling site to the densitometer should be kept mini- mal, in order to reduce errors due to streaming of dyed blood in the tubing [29]. Pulsations at the sampling site may be minimized by using stiff tubing and withdrawal rates of 20 to 40 cc. per minute. Although the Stewart-Hamilton theory assumes continuous flow, pulsatile flow at peripheral sites generally does not produce a significant error.

Variability in the linearity and response times of dye densitometers has been noted [110]. When multiple-sample calibration is used, linearity is necessarily checked. Response time can diminish with accumulation of background dye, so that for some studies with rapidly repeated injections, a correction factor must be used [39]. These considerations are not of practical importance unless on-line computer analysis of dye curves is used, where nonlinearity can introduce a significant error.

The Stewart-Hamilton method for determining the area under the dye curve utilizes the trapezoidal rule,

Recording Apparatus.

Calculation and Calibration.



in which concentration points are marked at time intervals (usually one second), and then summed [69]. When initial and final concentration values are zero (as in the replotted curve), the area is determined by adding the points and multiplying the sum by the time interval. This is a somewhat laborious process, requiring the logarithmic replot of the downslope and estimation of the remainder of the downslope back to zero concentration. Several shortcuts that avoid replotting have been devised to estimate the area under the curve with varying degrees of accuracy [12, 21, 27, 51, 1261. The method of Williams and associates [126] breaks the curve into several smaller areas and sums them by simple arithmetic. This formula agrees well with the Stewart-Hamilton method, having a standard deviation of differences of 1.4%. A nomo- gram combining planimetry with a formula for estimating the area under the downslope for use at the bedside has also been devised [27]. This method gives a mean difference of 2.4% when compared to the Stewart-Hamilton calculation. A visual curve-fitting technique was used by Gorten and Hughes [51], and Boyett and his associates [12]. Other investigators [8, 37, 62, 9 11 have investigated the assumption that the area of a dye-dilution curve can be estimated from the first part of the curve. This method was shown to agree within +lo% of 90% of curves calculated by the Stewart-Hamilton formula, and within *15% of all curves [91]. This relative lack of accuracy may be counterbalanced in curves obtained in low flow states by the inaccuracy of the replotting technique in estimating the area of these curves [931. Figure 3 illustrates cardiac output curves taken before and after mitral valve replacement in a patient with low cardiac output, a large heart, and mitral insufficiency. The downslope of the curve prior to valve replacement is prolonged and probably contaminated by early recirculation, as a result of

FIG. 3. Eflects of delayed washout and early recirculation on dye-dilution curve. Indicator-dilution curves obtained during operation by continuous sampling of femoral artery blood after injection of indocyanine green dye into the left atrium of a patient with mitral insuficiency and low cardiac output (A) before and (B) after valve replacement. Delayed washout allows early recirculation and nonexponential downslope of curve (A).

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delayed washout from the left atrium caused by mitral insufficiency. This curve could not be calculated by the Stewart-Hamilton method. After valve replacement, the downslope is steeper and may readily be calculated. Flat curves with delayed washout may, however, be calculated by Dows method [37], or the forward triangle method of Hetzel et al. [62], utilizing a simple formula and noting only the peak concentration and peak concentration time. With attention to methodological details, errors due to mitral and aortic regurgitation can be minimized [103, 1041.

Computers may be used to replot automatically the downslope and estimate the area under the dye-dilution curve. When properly cali- brated, the computer will give a direct readout of cardiac output. The theory and circuitry of on-line computation of cardiac output have been described [59, 761. With the use of sophisticated analysis, distortion due to baseline shifts, sampling variations, and flat, irregular curves may be removed and accurate computation performed 1291. With less sophisticated instrumentation, such as is now commercially available, less accurate results are obtained. These low-cost computers are essentially integrating devices that contain a compensating circuit to perform an automatic estimation of the area under the downslope, assuming exponential washout [48, 1101. The formulas employed are usually variations of the short forms mentioned above. Dalby and his associates [32] compared the Sanborn computer to a planimetric method, and obtained a mean difference of t-9% in the normal range of cardiac output. Slightly better results were obtained with a Lexington computer by Glassman and his associates [48], with most differences between manual and computer results varying between *5%. These results are not as accurate as arithmetical methods that avoid replotting, and little time is saved because external recording of the dye curve and computer output is still required. The main problem with low-cost computers is the inability of the instrument to calculate accurately low and high curves [7, 481. Because ideal curves are not usually obtained in low flow states, it is unlikely that these low-cost computers will offer sufficient advantage over arithmetic calculations to make them useful in patient monitoring. In the opinion of Woods group at the Mayo Clinic [126], sophisticated on-line computer analysis of dye curves may be practical where time- sharing computer facilities are available. In the absence of such facilities, these workers believed that arithmetical techniques were simpler and more accurate.

Calibration of dye-dilution curves is accomplished by passing several known concentrations of dye-blood mixture through the densitometer and recording the output at identical gain settings to those used for recording the cardiac output curve. A concentration curve is plotted and the result obtained as milligrams per liter per millimeter recorder



deflection. Formula 4 is rewritten, including a factor of 60 to correct for seconds to minutes:

F (litersimin.) = (5) 60 sec./min. x I mg.

2 C ( t ) dt mm.-sec. x CF mg./liter/mm. 0

where C F is the calibration factor obtained from the calibration curve. It is important to mix the dye-blood mixture carefully in recording the calibration curve, and to use several points in order to correct visually for nonlinearity that may result from technical errors in preparing and recording the deflections of dye-blood calibration samples. A simplified sterile procedure for performing the calibration has been described by Weil and his associates [124]. Since a considerable volume of blood is required for the sampling of arterial blood for dye curves and their calibration, it is necessary to sterilize the withdrawal equipment and calibration apparatus in order to reinfuse the blood when frequent dye curves are performed. The procedure of Weil and his associates uses semiautomated equipment for rapid and accurate calibration, allowing frequent calibration by permitting reinfusion of calibration samples. As these authors point out, frequent calibration is necessary in the clinical setting, where rapid changes in hematocrit, background dye concentration, and other factors may occur.

PULSE-CONTOUR METHOD

Moment-to-moment determinations of cardiac output in experimental and clinical settings can be obtained by analysis of central arterial pulse contour. The relationship between pulse pressure and stroke volume is well known [58, 1011. Enlarging on this concept, Warner and associates have developed a practical method for computer analysis of pulse contour in order to determine cardiac output [121-1231.

Stroke volume consists of forward flow during systole and diastole. Since arteries are elastic tubes, they distend during systole and contract during diastole. Therefore, forward flow occurs during diastole as well as systole [123]. Flow relates to pressure and resistance, which are described by central arterial pulse contour. Warner's formula for calculation of stroke volume is

SV = dPmd (1 + Sa/Da). (6) Stroke volume (SF') equals a constant ( K ) , which relates to aortic volume and is obtained from one determination of cardiac output by the dye- dilution method, times the square root of the mean distending pressure ( ~ m d ) , times one plus systolic (Sa) over diastolic (Da) pressure [121]. Pulse rate times stroke volume gives cardiac output. For detection of

-

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the degree of change of cardiac output, calibration by the dye-dilution method is not essential, and the constant ( K ) can be estimated.

Derivation of cardiac output from central arterial pulse contour has been compared to simultaneous dye-dilution determinations and direct Fick calculations of cardiac output in humans at rest, exercise, tilt, and body pressurization [121]. The agreement was +9%. Cardiac output determined by the pressure-pulse method was compared in dogs with direct measurements from a previously placed electromagnetic flowmeter around the ascending aorta at conditions of rest, exercise, infusion of drugs (metaraminol, atropine, neostigmine), and anesthesia, and during changes of pulse rate from 60 to 240 with pacemaker-induced rates after creation of complete heart block [53]. The correlation coefficient of the pressure-pulse method and flowmeter studies was 0.98 or better .

The technique of monitoring acutely ill patients has been described by Warner and his associates [122]. A specially designed 100-cm.- long size 19 Teflon catheter* is passed percutaneously through a thin- wall size 18 needle into the radial artery and advanced in or near the aortic arch. The catheter is attached to a pressure transducer. A similar catheter is passed percutaneously into a central vein. The arterial transducer is connected to the input of a computer substation from which data are sent over frequency modulation telephone lines to a Control Data 3200 computer. One calibration of cardiac output is obtained by the dye-dilution method. Cardiac output is immediately calculated by the computer. The constant (K) is derived, stored, and applied to future computations of cardiac output by the computer. After calibration, the pressure-pulse program is called. The analog-to-digital converter samples the aortic pulse wave 200 times per second for 16 beats in order to derive mean values. Sampling of multiple beats is particularly important for patients with arrhythmias, since pulse volume is often so variable. During a few seconds, calculations are performed and cardiac output, stroke volume, heart rate, duration of systole, systemic vascular resistance, systolic, diastolic, and mean arterial pressure are displayed on a memory oscilloscope at the bedside substation. These data are also printed on paper and recorded on magnetic disks for instant recall at the substation in order to review past trends in a time sequence. Data can also be measured automatically by the computer at preset intervals. All or part of the data can be retrieved subsequently from the magnetic disks or by review of the printout. On occasion, the arterial catheter is left in as long as two weeks for monitoring. Significant complications do not occur. Substations may be used in the operating rooms, intensive care units, cardiac catheterization laboratories, and animal research laboratories.

*CAP Infusor, Sorenson Research Corp., Salt Lake City, Utah.


COLLECTIVE REVIEW: Curdiuc Output

CLINICAL ESTIMATION OF CARDIAC O U T P U T

Frick [45] estimated cardiac output from blood volume and circulation time. A correlation coefficient between actual (measured by dye dilution) and estimated cardiac output of .68 was obtained, with a mean variance of +24%. These results were considered sufficiently inaccurate that the method could not be recommended for bedside use. Holm and his associates [63] utilized a somewhat more elaborate method in which samples of arterial blood were drawn every two to three seconds for about one minute after the injection of II3l albumin. An indicator- dilution curve was constructed from which cardiac output could be calculated. Although the apparatus was simple and the results agreed well with actual flow in model experiments (mean variance as%), the technique of multiple samples is not justified if continuous recording of the indicator-dilution curve is available.

Multiplication of the pulse pressure (assumed to be equal to stroke index) by the heart rate may provide a rough clinical estimation of cardiac output. A mean variance of +19% to 234% was obtained when this technique was compared to cardiac output measured by the Fick method [58]. A corollary to the estimation of stroke index from pulse pressure is that the volume of the palpated radial pulse will also reflect stroke index. Although no studies have been performed comparing the volume of the radial pulse to stroke index, a patient with a strong, full radial pulse is likely to have a good stroke output and, assuming adequate heart rate, a good cardiac output.

Mixed venous oxygen saturation is indirectly related to cardiac output. When oxygen uptake and arterial oxygen content remain constant, a reduction in cardiac output will be accompanied by a reduction in mixed venous oxygen content [118]. Monitoring of the A-V oxygen difference has therefore been used to estimate indirectly cardiac output [113, 1271. However, many patients have a reduced oxygen uptake, and the A-V oxygen difference may be normal in spite of low cardiac output. The presence of excess lactic acid in the blood may be indicative of hypoxic acidosis secondary to poor tissue perfusion. Lactic acid is elevated in the majority of patients in shock [15, 951, and direct correlation with cardiac output was fair in one clinical study [2]. Measurement of serum lactic acid may therefore be helpful in evaluating the circulatory state of acutely ill patients.

Central venous pressure and blood volume are readily monitored in acutely ill patients. Central venous pressure correlates poorly with cardiac output, but observation of changes is very helpful in evaluating cardiac function [43, 1271. Correction of blood volume deficits correla- ted with a rise in cardiac output in most postoperative cardiac surgical patients [9, 751, but again any level of cardiac output may be present at a given blood volume.

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Urine output, skin blanching, and mental alertness are related to the perfusion of the kidneys, skin, and brain. Monitoring of these parameters in the clinical setting, in addition to other easily measured variables mentioned previously, gives the physician qualitative information that is adequate in the majority of situations in which instrumentation for measurement of cardiac output is unavailable.

NEW TECHNIQUES

Gorten [50] has described a small, lightweight precordial counter for use in recording radioisotope dilution curves. This counter may be fixed to the chest and avoids the need for lead shielding and collimation by using 1125 as the indicator. It allows the patient some freedom of motion, and it may be useful in a restless postoperative patient. A miniature scintillation counter, placed in the esophagus, was used to record radioisotope dilution curves of dogs by Hernandez and his associates [61]. This counter requires careful positioning and has not yet been used for patient monitoring.

Khalil and his associates [7 11 have described a local thermodilution technique in which a thermister catheter was passed into the pulmonary artery. A portion of the catheter in the right atrium heated the blood by direct contact, and the temperature change was recorded by the thermister in the pulmonary artery. Cardiac output was derived from the resulting thermodilution curve. This technique avoids injection of indicator, and the apparatus is simple and inexpensive. The method agreed well with cardiac output determination by the Fick method. Two other single-catheter thermodilution techniques for measuring blood flow have been described [47, 861, one of which has been used in pediatric patients [86]. Although placement of a catheter in the pulmonary artery is required, these techniques may provide simple and inexpensive monitoring devices for postoperative patients, since they avoid injection, sampling, and recirculation problems.

Hugenholtz and his associates [65, 1203 have described a fiberoptic catheter for use in detecting dye-dilution curves directly from a densitometer at the end of the catheter. Because of internal sampling, the delay of external sampling systems was avoided, and simple integration of the curve allowed direct on-line computation of cardiac output. The method agreed well with the Fick technique, but placement of the catheter in the aorta was required for sampling.

Reflected sound waves have been used as a means for determining changes in ventricular volume. Agress and his associates [l] have described the recording of low frequency vibrations from a precordial microphone (vibrocardiogram) from which stroke volume could be calculated. Other workers have utilized reflected high-frequency sound



waves (ultrasound) to record motion of the walls of the heart [40, 671. From the recorded tracing (echocardiogram), changes in ventricular volume may be calculated. Reasonable agreement with stroke volume as determined by the Fick principle has been obtained with these methods, and the instrumentation has the advantage of being completely free of intravascular components.

The majority of these techniques have been used in the cardiac catheterization laboratory, but have not yet been adopted to the monitoring of acutely ill patients. With refinements of instrumentation, this may be possible in the future.

APPRAISAL OF TECHNIQUES

At the present time, the best available techniques for monitoring cardiac output in the seriously ill patient are variations of the indicator- dilution technique and pulse-contour methods. Determination of cardiac output from indicator-dilution curves in low flow states requires careful positioning of injection and sampling sites, knowledge of the limitations of the recording apparatus, and careful calibration and calculation of the dilution curves. True exponential washout of the indicator from its dilution volume is the exception rather than the rule in low flow states [93], and this factor must be considered in performing calculations.

Dye-dilution curves are relatively easy to record in acutely ill patients when proper attention is paid to the limitations of the method. Indocyanine green, the dye most commonly used, is stable [85], and is rapidly removed by the liver [66]. Its effect on the density of blood is not influenced by hemoglobin saturation. Dye curves require withdrawal of arterial blood through a cuvette for sampling, but reinfusion of curve samples as well as calibration samples is easily accomplished. This method is particularly suited to intraoperative measurements, when injections can be made directly into the heart and sampling accomplished through a peripheral artery (Figs. 2, 3). The instrumentation is relatively simple and may be handled by one person, although it is usually necessary for a physician to make the injection while a tech- nician records the curve. Calculation can readily be performed by the use of simple formulas that avoid replotting. At the present time, computer analysis of dye curves does not appear to offer a significant timesaving advantage in the calculation of the area under the curve unless sophisticated analysis is performed, since accuracy in low flow States is not achieved by relatively unsophisticated instruments. A more convenient instrument is now available* that incorporates a disposable cuvette, a densitometer, and a recorder with an integrating circuit. This

*Cardiodensitometer. Beckman Instruments, Palo Alto, Calif.

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instrument is particularly suited for bedside use because of its size and stability, the convenience of the disposable cuvette, and the integrating circuit, which simplifies calculation of the area under the curve.

The radioisotope-dilution technique avoids arterial sampling by counting directly over the heart. As a result of central sampling, peripheral injections give better curves with radioisotopes than with dye, since peripheral sampling is usually used for dye curves. Central injection is therefore not a necessity with the radioisotope technique. As discussed above, it is preferable to keep the dilution volume to a minimum by approximating the injection and sampling sites. By allowing peripheral injection and central, external sampling, the radioisotope technique may be preferable to the dye-dilution method for postoperative monitoring. Radioisotope-dilution curves may be recorded 5 to 6 times in one day. When more frequent measurements are required, dye curves should be used. Radioisotope curves are somewhat more time-consuming, because they require a 15-minute delay before the equilibration concentration is recorded. Determination of the area under the radioisotope-dilution curve also takes slightly longer than for the dye curve, because the recorded curve contains two concentration peaks (as the indicator passes through each ventricle), and the tracing is slightly more irregular. The cost of the equipment for the performance of radioisotope or dye-dilution curves is essentially the same, about $5,000.

Determination of cardiac output from pulse-contour analysis offers the only available continuous monitoring of cardiac output. It is thus particularly suited to postoperative monitoring. This method is relatively new, and its accuracy has yet to be proved in the variety of clinical settings where monitoring of cardiac output is desirable. Nevertheless, where time-sharing facilities for on-line computer analysis are available, the pulse-contour method of Warner et al. [ I 221 is well worth a trial.

A less elaborate pulse-contour method, described by Herd and associates [60], utilizes simple electrical circuits that multiply the difference between mean and diastolic aortic pressure by heart rate. This method may be used for continuous monitoring of cardiac output without the need for on-line computer analysis. Progressively simplifying the basic assumption that the pressure pulse is proportional to the stroke volume, the product of pulse pressure (as recorded in the arm) and heart rate gives a rough estimate of cardiac output. Finally, a sensi- tive finger on the radial pulse may be as reliable as the most sophisticated computer analysis of pulse contour, when the finger is attached on-line to a well-programmed human brain.

Other simple measurements, such as mental alertness, urine output, and acid-base balance, are easy to obtain and usually reflect the effectiveness of blood flow. Indeed, it has been suggested that the number obtained by cardiac output measurement is in itself unnecessary in the



event that blood flow appears effective as judged by other studies [1151. The same has been said of blood pressure. However, since the clinician wishes to restore the homeostatic balance of his critically ill patient, this should include the return of normal blood pressure and cardiac output as well as normal acid-base balance and urine output. It is well known that cardiac output can be quite low while all other parameters are in the normal range. Indeed, most preoperative patients with acquired heart disease have low cardiac output and normal blood pressure, urine output, and acid-base balance. The superimposition of surgical trauma, prosthetic valve replacement, anesthesia, and other unknown variables may alter the homeostatic balance of such a patient so that a new level of blood flow may be required. Borderline clinical studies may not reflect low cardiac output. Furthermore, directional changes in cardiac output may not be immediately signaled by changes in secondary variables.

In the light of the foregoing discussion, it appears desirable, but not essential, that cardiac output be monitored in acutely ill patients in general and in postoperative cardiac surgical patients in particular. The convenience and expense of the method must therefore be a considera- tion. Outside of the well-equipped shock unit, the indicator-dilution method has not achieved a place in routine monitoring, for obvious reasons. The results are not as immediately available and, in the absence of highly competent technical personnel, not as accurate as the observations of the experienced clinician. On the other hand, as a spot check in the difficult situation, a reasonably well-performed indicator-dilution cardiac output determination can be very helpful.

It appears likely that for routine monitoring of cardiac output some variation of the pulse-contour technique will become the procedure of choice. As described by Warner et al. [122], the information produced by pulse-contour analysis is instantaneously available for use to nurses; and with storage of data, events occurring in the past are readily reviewed. Such information significantly improves the effectiveness of the clinician as well as the quality of immediate patient care by allowing review of pertinent events that might have gone unnoticed. This method provides the necessary spontaneity and simplicity required of monitoring devices. With the increasing availability of time-sharing facilities for computer analysis, monitoring by this technique could be made available by telephone connection even to remote areas, since the only technical procedure required is placement of a catheter in or near the aortic arch.

M A N A G E M E N T OF LOW CARDIAC O U T P U T

Normal cardiac output varies between 2.5 and 4.5 liters per minute per square meter of body surface. The mean of a large number of re-

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ported measurements in normals using the Fick and dye methods was 3.6 liters per minute per square meter, with most studies revealing a mean between 3.2 and 3.8 [119].

After noncardiac operations, cardiac output is usually elevated [ Z O , 23, 24, 1061, suggesting a physiological response to increased metabolic demands. After open cardiac operations, cardiac output is low in the early postoperative period and usually does not return to preoperative levels until 24 to 48 hours after surgery [75, 981. This effect is most pronounced after mitral valve replacement, when congestive heart failure has usually been present preoperatively [75]. Immediately after aortic valve replacement, cardiac output is usually increased, except when long-standing congestive heart failure has been present [75]. These find- ings suggest that when congestive heart failure is present preoperatively, cardiac output is likely to be decreased for the first few days after correc- tive surgery.

Assuming that the metabolic demands of the patient are increased by the operation, the imbalance between available cardiac output and energy requirements is exaggerated. In spite of this imbalance, Rastelli and Kirklin [98] and Mundth and his associates [88] found that acid- base balance and oxygen saturation usually remained normal. This suggests that oxygen consumption is reduced. Reduction in oxygen requirements may be a metabolic compensation that protects patients with long-standing cardiac disease from developing metabolic acidosis.

The point at which cardiac output becomes critically low is difficult to identify. Because of a compensatory reduction in oxygen requirements, metabolic acidosis may not develop. Blood pressure and urine output may remain normal by virtue of compensatory autonomic and renal adjustments. In the absence of the full-blown syndrome of hypotension, oliguria, cyanosis, poor perfusion of extremities, and metabolic acidosis, it is difficult to attach an adequate or inadequate label to a given value of cardiac output. However, prolonged inadequate cardiac output may have deleterious effects on hepatic and renal function [88]. Rising creatinine and bilirubin are signs of inadequate hepatic and renal blood flow. Mental confusion after surgery may be associated with low cardiac output [l 11 and may indicate inadequate cerebral perfusion. It is important to remember that the heart itself has high metabolic requirements and that low cardiac output, by reducing coronary blood flow, may be self-perpetuating.

Studies during cardiopulmonary bypass identified a critical flow rate of 1.2 liters per minute per square meter, below which progressive metabolic acidosis developed [22, 941. Some patients have preoperative levels of cardiac output in this range without metabolic acidosis. How- ever, since determination of cardiac output in low flow states is frequently in error [93], these values are of questionable accuracy. It is



likely that a cardiac output of less than 1.2 liters per minute per square meter is incompatible with life. It is also likely that values between 1.2 and 2.0 liters per minute per square meter will be deleterious to the patient and should be treated, particularly in the critical early postoperative period when cardiopulmonary, renal, and hepatic complications are likely to occur.

The first line of defense against low cardiac output is restoration of normal blood volume, ventilation, and acid-base balance. Several authors have pointed out the importance of maintaining high atrial pressures in postoperative cardiac surgical patients [74, 75, 881. Litwak and his associates [80] suggested that blood volume deficits were due to sequestration of blood, but other studies have not substantiated this finding [9, 74, 1151. It is more likely that deficits occurring in spite of normal measured blood balance are due to loss of plasma and electrolyte solutions used during pump priming and transfusion therapy [74].

The importance of maintaining adequate ventilation to circulatory homeostasis in the early postoperative period is well known [23, 24, 331. Patients with signs of low cardiac output have improved with respiratory assistance alone [77]. In the presence of long-standing pulmonary hypertension, pulmonary compliance is decreased, and respiratory assistance is often necessary. A paradoxical reduction in central venous pressure may occur when respiratory assistance is provided to these patients, rather than the rise that usually occurs with positive pressure assistance. This effect may be due to a decrease in pulmonary vascular resistance as a result of better expansion of the lungs and improved oxygenation, since both pulmonary collapse and hypoxia are known to increase pulmonary vascular resistance [lo, 18, 42, 541. It is important to remember that hyperventilation [70, 96, 1171 and increased intrathoracic pressure [30,41, 901 tend to decrease cardiac output. Therefore, respiratory assistance must be used with care, preferably with intermittent monitoring of arterial blood gases.

The circulatory effects of respiratory alkalosis and acidosis are fairly consistent. Generally, a decreased pC0, causes a decrease in cardiac output [96, 1171, while a rise in pC0, causes an increase, presum- ably due to release of catecholamines [701. However, a rise in pC0, may adversely affect cardiac performance when pH remains constant [6, 891. There is evidence to suggest that metabolic acidosis accompanies low cardiac output [24, 34, 941. Experimentally, acidosis itself has little effect on the heart [6, 891. Arrhythmias are more common in the presence of acid-base abnormalities, probably due to changes in intracellular and extracellular potassium concentration 144, 83, 1051 and increased circu- lating catecholamines [83, 1051.

The changes in body composition that occur before and after intracardiac operations were reviewed by Kirklin and Pacific0 [74]. Patients

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with congestive heart failure before operation were distinguished from those without congestive heart failure by the presence of a high blood volume and increased extracellular fluid volume and total body water. Although total exchangeable sodium and potassium were increased, serum values for these ions were usually decreased. These changes were exaggerated by operation with cardiopulmonary bypass, and normal fluid and electrolyte balance was not restored until 2 to 6 weeks after surgery. Sodium excretion may be impaired before operation, as a result of inappropriate secretion of antidiuretic hormone [125], and worsened by the procedure. It may therefore be necessary to maintain salt and water restriction for several weeks after operation. In the early postoperative period, the accumulation of extracellular and intracellular fluid, as a result of sodium retention and excessive fluid intake, may cause increased pulmonary vascular resistance and cellular metabolic dysfunction as a result of dilutional effects. Although most diuretics cause little effect on the postoperative patient, the use of ethacrynic acid may be beneficial in promoting the excretion of sodium, chloride, and free water [73, 1071. This agent must be used with caution because of potassium loss that occurs during the marked diuresis that it produces (up to 40 ml./min.) in postoperative patients [19]. The use of ethacrynic acid markedly improved cardiac function in patients with congestive heart failure refractory to other diuretics [ 1071. The same effect has been observed in postoperative patients [19].

The beneficial effect of atrial and ventricular pacing on cardiac output in postoperative patients has been demonstrated [46,79]. Various degrees of heart block, bradycardia, and slow nodal rhythm are common after intracardiac operations. These arrhythmias are best treated by pacing, preferably by atrial stimulation. The importance of atrial contraction to ventricular filling is well known [13, 14,68, 1021, and cardiac output may increase up to 60% with atrial pacing [46].

From the foregoing discussion it is apparent that a variety of means are available for the treatment of low cardiac output before pharmaco- logical assistance is required. Digitalis preparations must be used cau- tiously in the early postoperative period, but full digitalization is preferable to inadequate amounts of digitalis. However, arrhythmias or heart block frequently prevent the physician from maintaining the optimal inotropic effect of digitalis. In the acute situation, or when other measures have failed, isoproterenol is the inotropic agent of choice. Although few studies of the effects of isoproterenol in postoperative patients have been performed, the clinical experience with this agent is considerable [88, 113, 1141. LOW cardiac output in postoperative patients is almost always accompanied by high systemic vascular resistance, and when low doses of isoproterenol are used (1 to 2 pg./min.) systemic vasodilatation is rarely a problem. The hemodynamic effects



of isoproterenol in other low flow states (myocardial infarction, sepsis, and hemorrhage) are somewhat variable [17, 55, 87, 1111, but only rarely does persistent hypotension occur when it is used in low dosages for the treatment of postoperative cardiac surgical patients. Calcium is a powerful inotropic agent that is also useful in acute situations, but its effect is somewhat short-lived and accumulation may occur with excessive dosage. Dopamine, a catecholamine with inotropic effects analogous to isoproterenol, causes less systemic vasodilatation and tachycardia [49, 81, 831. Dopamine increases the renal excretion of sodium [49]. This effect may provide additional benefit to patients in congestive heart failure. Epinephrine has been used with good results in low cardiac output syndrome [25], but because this agent, like other vasopressors, increases systemic vascular resistance, it is usually not used unless isoproterenol fails. Glucagon infusion has caused modest increases in cardiac output in postoperative patients, and may be of benefit when other inotropic agents have failed [112a].

When treating low cardiac output in postoperative patients, the physician must be alert for anatomical causes of myocardial dysfunction. Cardiac tamponade is not uncommon, even when the pericardium has not been closed. Dysfunction of prosthetic valves is a frequent cause of fatal low cardiac output syndrome [loo]. Other anatomical causes, such as ligation of the left coronary circumflex artery, coronary air embolus, and damage to the coronary arteries by coronary perfusion cannulas, are preventable. Massively enlarged hearts with very low preoperative cardiac output may be beyond repair. In such cases, the treatment of low cardiac output may eventually rest with cardiac assistance by mechanical means or by total heart replacement.

SUMMARY

A review of currently available methods for monitoring of cardiac output reveals that both the indicator-dilution technique and the pulse- contour method are applicable to acutely ill patients. Dye-dilution studies are readily performed and perhaps offer the most accurate measurement of cardiac output when proper attention is given to methodological details. Radioisotope-dilution curves are slightly more difficult to record, calibrate, and calculate, but do not require central injection or withdrawal of arterial blood for sampling. Neither method offers instantaneous display, and the number of determinations is limited by the need for indicator injection. Computer analysis of curves may be inaccurate, particularly in low flow states, unless sophisticated curve analysis is used.

Clinical estimation of cardiac output by indirect studies is adequate in most cases, particularly when the observer is experienced in those variables that most accurately reflect the effectiveness of blood flow.

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Estimation of cardiac output by pulse-contour analysis offers the only instantaneous display of blood flow and does not require technical personnel for its performance once a catheter has been placed in or near the aortic arch. Computer analysis by time-sharing facilities is most accurate, but simpler analysis by electrical circuits may be possible. The method is as yet unproved in a variety of clinical settings, but at the present time it appears to offer the most promise as a means for monitoring cardiac output in the acutely ill patient.

Normal cardiac output is approximately 3.6 liters per minute per square meter, with a range of 2.5 to 4.5. Cardiac output below 1.2 liters per minute per square meter is probably incompatible with life, and output between 1.2 and 2.0 may be deleterious to vital organ function if allowed to persist. Proper attention to blood volume, ventilation, and acid-base balance will improve cardiac output in many cases. Atrial or ventricular pacing may be beneficial in slow arrhythmias. Avoidance of fluid overload, particularly in patients with long-standing congestive heart failure, may be accomplished by salt and water restriction and the use of ethacrynic acid when necessary to promote excretion of sodium, chloride, and free water. Full digitalization is preferable but difficult to accomplish in the early postoperative period. For inotropic stimulation, calcium and isoproterenol are the most commonly used agents. The dosage of isoproterenol should be kept below 2 pg. per minute to avoid tachycardia and systemic vasodilatation.

The surgeon should be constantly on the alert for treatable anatomical causes of low cardiac output. He should also be fully aware of preventable causes of low cardiac output that occur during operation.

REFERENCES

1. Agress, C. M., Wegner, S., Fremont, R. P., Mori, I., and Day, D. J. Mea- surement of the stroke volume by the vibrocardiogram. Aerospace Med. 38: 1248, 1967.

2. Aksnes, E. G., Cappelen, C., and Hall, K. V. Cardiac output and regional femoral blood flow in early postoperative period after heart surgery. Acta Ch ir. Scand. 357(Suppl.) : 299, 1966.

3. Austen, W. G., Corning, H. B., Moran, J. M., Sanders, C. A., and Scannell, J. G. Cardiac hemodynamics immediately following aortic valve surgery. J. Thorac. Cardiovasc. Surg. 51:461, 1966.

4. Austen, W. G., Corning, H. B., Moran, J. M., Sanders, C. A., and Scannell, J. G. Cardiac hemodynamics immediately following mitral valve surgery. J. Thorac. Cardiovasc. Surg. 51:468, 1966.

5. Bassingthwaighte, J. B., Edwards, A. W. T., and Wood, E. H. Areas of dye- dilution curves sampled from central and peripheral sites. ]. Appl . Physiol. 17:91, 1962.

6. Baue, A. E., Tragus, E. T., and Parking, W. M. Effects of NaCl and NaHC03 in shock with metabolic acidosis. Amer. J. Physiol. 212:54, 1967.

7. Benchimol, A., Akre, P. R., and Dimond, E. G. Clinical experience with the use of computers for calculation of cardiac output. Amer. J. Cardiol. 15:213, 1965.



8. Benchimol, A., Dimond, E. G., Carvalho, F. R., and Roberts, M. W. The forward triangle formula for calculations of cardiac output: The indicator dilution technique. Amer. J . Cardiol. 12: 119, 1963.

9. Berger, R. L., Polanzak, M. L., and Ryan, T. J. Blood volume, central venous pressure and cardiac output in the management of open heart patients. Circulation 366uppl. II):65, 1967.

10. Berry, W. B., McLaughlin, J. S., Clark, W. D., and Morrow, A. G. Effects of acute hypoxia on pressure, flow and resistance in pulmonary vascular bed. Surgery 58:404, 1965.

11. Blachly, P. H., and Kloster, F. E. Relations of cardiac output to postcar- diotomy delirium. J. Thorac. Cardiovasc. Surg. 52:422, 1966.

12. Boyett, J. D., Stowe, D. E., Becker, L. H., and Britz, W. E. Rapid method for determination of cardiac output by indicator dilution techniques. J. Lab. Clin. Med. 64: 160, 1964.

13. Braunwald, E., and Frahm, C. J. Studies of Starlings law of the heart: IV. Observations on the hemodynamic functions of the left atrium in man. Circulation 24:633, 1961.

14. Brockman, S. K. Dynamic function of atrial contraction in regulation of cardiac performance. Amer. J. Physiol. 204:597, 1963.

15. Broder, G., and Weil, M. Excess lactate: An index of reversibility of shock in human patients. Science 143: 1457, 1964.

16. Burton, A. C. Physiology and Biophysics of the Circulation. Chicago: Year Book, 1965.

17. Carey, J. S., Brown, R. S., Mohr, P. A., Monson, D. O., Yao, S. T., and Shoemaker, W. C. Cardiovascular function in shock: Responses to volume loading and isoproterenol infusion. Circulation 35: 327, 1967.

18. Carey, J. S., and Hughes, R. K. Hemodynamic studies in open pneumo- thorax. J. Thorac. Cardiouasc. Surg. 55:538, 1968.

19. Carey, J. S., Miller, T. A., and Goshgarian, G. Control of fluid and electrolyte retention with ethacrynic acid after intracardiac operations. In prep- aration.

20. Carlsten, A., Norlander, O., and Troell, L. Observations on the postoperative circulation. Surg. Gynec. Obstet. 99:227, 1954.

21. Clark, R. G., and Stoik, M. W. A method for the rapid computation of indicator-dilution downslope areas. J. Appl . Physiol. 19:526, 1964.

22. Clowes, G. H. A. Extracorporeal maintenance of circulation. Physiol. Rev. 40:826, 1960.

23. Clowes, G. H. A., Alichneiwicz, A., Del Guercio, L. R. M., and Gillespie, D. The relationship of postoperative acidosis to pulmonary and cardiovascular function. J. Thorac. Cardiouasc. Surg. 39:1, 1960.

24. Clowes, G. H. A., Sabga, G. A., Konitaxis, A., Tomin, R., Hughes, M., and Simeone, F. A. Effects of acidosis on cardiovascular function in surgical patients. Amer. Surg. 154:524, 1961.

25. Coffin, L. H., Ankeney, J. L., and Beheler, E. M. Experimental study and clinical use of epinephrine for treatment of low cardiac output syndrome. Circulation 356uppl. I):78, 1966.

26. Cohen, M., and Lillehei, C. W. A qualitative study of the azygos factor during vena caval occlusion in the dog. Surg. Gynec. Obstet. 98:225, 1954.

27. Cohn, J. D., and Del Guercio, L. R. M. Nomograms for the rapid calculation of cardiac output at the bedside. Amer. Surg. 164:109, 1966.

28. Conn, H. L. Use of external counting technics in studies of the circulation. Circ. Res. 10:505, 1962.

29. Cooper, J. K., Schweikert, J. R., Arnold, T. G., and Lacy, W. W. Removal of distortion from indicator-dilution curves with analog computer. Circ. Res. 12:131, 1963.

VOL. 7, NO. 2, FEB., 1969 171

CAREY AND HUGHES

30.

31.

32.

33.

34.

35.

36.

37.

38.

39.

40.

41.

42.

43.

44.

45.

46.

47.

48.

49.

172

Cournand, A., Motley, H. L., Werko, L., and Richardson, D. W. Physio- logic studies of effects of intermittent positive pressure breathing on cardiac output in man. Amer. J. Physiol. 152:162, 1948. Cournand, A., Riley, R. L., Bradley, S. E., Breed, E. S., Noble, R. P., Lauson, H. D., Gregerson, M. I., and Richards, D. W. Studies of the circulation in clinical shock. Surgery 13:964, 1943. Dalby, L., McDonald, R., and Sloman, G. A comparison of computer and planimetry cardiac output determinations. Med. J . Aust. 2: 1255, 1967. Damman, J. F., Thung, N., Christlieb, I. I., Littlefield, J. B., and Muller, W. H. The management of the severely ill patient after open heart surgery. J. Thorac. Cardiouasc. Surg. 45:80, 1963. Dewall, R. A., Warden, H. E., Gott, V. L., Read, R. C., Varco, R. L., and Lillehei, C. W. Total body perfusion for open cardiotomy using the bubble oxygenator: Physiologic responses in man. J. Thorac. Surg. 32:591, 1956. Donato, L., Guintini, C., Lewis, M. L., Durand, J., Rochester, D. F., Harvey, R. M., and Cournand, A. Quantitative radiocardiography: I. Theoretical considerations. Circulation 26: 174, 1962. Donato, L., Rochester, D. F., Lewis, M. L., Durand, J., Parker, J. O., and Harvey, R. M. Quantitative radiocardiography: 11. Technique and analysis of curves. Circulation 26: 183, 1962. Dow, P. Dimensional relationships in dye dilution curves from humans and dogs, with an empirical formula for certain troublesome curves. J. Appl . Physiol. 7:399, 1955. Dow, P. Estimations of cardiac output and central blood volume by dye dilution. Physiol. Rev. 36:77, 1956. Edwards, A. W. T., Bassingthwaighte, J. B., Sutterer, W. F., and Wood, E. H. Blood level of indocyanine green in the dog during multiple dye curves and its effect on instrument calibration. Proc. Stan Meet. Mayo Clin. 35:745, 1960. Feigenbaum, H., Zaky, M. B., and Nasser, W. K. Use of ultrasound to measure left ventricular stroke volume. Circulation 35: 1092, 1967. Fermoso, J. D., Richardson, T. Q., and Guyton, A. C. Mechanism of decrease in cardiac output caused by opening in the chest. Amer. J. Physiol. 207: 11 12, 1964. Fishman, A. P. Dynamics of the Pulmonary Circulation. In W. F. Hamilton (Ed.), Handbook of Physiology. Section 2:Circulation, Vol. 11. Washington: American Physiological Society, 1963. P. 174. Fishman, N. H., Hutchinson, J. C., and Roe, B. B. Controlled atrial hypertension: A method for supporting cardiac output following open heart surgery. J. Thorac. Cardiouasc. Surg. 52:777, 1966. Flemma, R. J., and Young, W. G. The metabolic effects of mechanical ventilation and respiratory alkalosis in postoperative patients. Surgery 56: 44, 1964. Frick, M. Circulation time and blood volume as means to estimate the cardiac output. Acta Cardiol. (Basel) 18:227, 1963. Friesen, W. G., Woodson, R. D., Ames, A. W., Herr, R. H., Starr, A., and Kassebaum, D. G. A hemodynamic comparison of atrial and ventricular pacing in postoperative cardiac surgical patient. J . Thorac. Cardiovasc. Surg. 55:271, 1968. Fronek, A., and Ganz, V. Measurement of flow in single blood vessels including cardiac output by local thermodilution. Circ. Res. 8: 175, 1960. Glassman, E., Baliff, R., and Herrera, C . Comparison of cardiac output calculation by manual and analogue computer methods. Cardiovasc. Res. 1:287, 1967. Goldberg, L. J. Use of sympathomimetic amines in heart failure. Amer. J. Cardiol. 22:177, 1968.

T H E ANNALS OF THORACIC SURGERY


50. Gorten, R. J. A small, lightweight precordial counter for determination of cardiac output. J . Appl . Physiol. 20:1365, 1965.

51. Gorten, R. J., and Hughes, H. M. Reliable extrapolation of indicator dilution curves without replotting. Amer. Heart J . 67:383, 1964.

52. Gorten, R. J., and Stauffer, J. C. A study of the techniques and sources of error in the clinical application of the external counting method of estimating cardiac output. Amer. J . Med. Sci. 238:274, 1959.

53. Graves, C. L., Stauffer, W. M., Klein, R. L., and Underwood, P. S. Aortic pulse contour calculation of cardiac output. Anesthesiology 29:580, 1968.

54. Gregg, D. E. Regulation of Pressure and Flow in the Systemic and Pulmo- nary Circulation. In C. H. Best and W. B. Taylor (Eds.), Physiological Basis of Medical Practice. Baltimore: Williams & Wilkins, 1961. P. 299.

55. Gunnar, R. M., Loeb, H. S., Pietras, R. J., and Tobin, J. R. Ineffectiveness of isoproterenol in shock due to acute myocardial infarction. J.A.M.A. 202: 1124, 1967.

56. Guyton, A. C. Circulatory Physiology: Cardiac Output and Its Regulation. Philadelphia: Saunders, 1963.

57. Hamilton, F. N., Minzel, J. C., and Schlobohm, R. M. Measurement of cardiac output by two methods in dogs. J. Appl . Physiol. 22:362, 1967.

58. Hamilton, W. F. Measurement of the Cardiac Output. In W. F. Hamilton (Ed.), Handbook of Physiology. Section 2: Circulation, Vol. I. Washington: American Physiological Society, 1962. Pp. 551-584.

59. Hara, H. H., and Belleville, J. W. On line computation of cardiac output from dye dilution curves. Circ. Res. 12:379, 1963.

60. Herd, J. A., Leclair, N. R., and Simon, W. Arterial pressure pulse con- tours during hemorrhage in anesthetized dogs. J. Appl . Physiol. 21: 1864, 1966.

61. Hernandez, A., Goldring, D., Ter-Pogossian, M., and Eichling, J. New technique for determining cardiac output with use of a miniature esopha- geal scintillation counter. Circulation 35:55, 1967.

62. Hetzel, P. S., Swan, J. J. C., Ramirez, D. E., Arellano, A. A., and Wood, E. H. Estimation of cardiac output from first part of arterial dye dilution curves. J . Appl . Physiol. 13:92, 1958.

63. Holm, H. H., Sorenson, B. L., and Christiansen, J. A method for the clinical determination of cardiac output. Acta Chir. Scand. 133:62, 1967.

64. Hosie, K. F. 65. Hugenholtz, P. G., Wagner, H. R., Polanzi, M. L., and Gamble, W. J. On-

line determination of cardiac output by fiberoptics. Circulation 36(Suppl. 11): 145, 1967.

66. Hunton, D. B., Bollman, J. L., and Hoffman, H. N. Hepatic removal of indocyanine green. Proc. Staf Meet. Mayo Clin. 35:752, 1960.

67. Joyner, C. R., and Reid, J. M. Applications of ultrasound in cardiology and cardiovascular physiology. Progr. Cardiovasc. Dis. 5:482, 1963.

68. Kahn, D. R., Wilson, W. S., Weber, W., and Sloan, H. Hemodynamic studies before and after cardioversion. J . Thorac. Cardiovasc. Surg. 48: 898, 1964.

69. Kelman, G. R. Errors in the processive of dye dilution curves. Circ. Res. 18:543, 1966.

70. Kelman, G. R., and Prys-Roberts, C. The influence of artificial ventilation on cardiac output in the anesthetized human. J . Physiol. 191:87P, 1967.

71. Khalil, A. A., Richardson, T. Q., and Guyton, A. C. Measurement of cardiac output by thermal dilution and direct Fick methods in dogs. J. Appl . Physiol. 21:1131, 1966.

72. Kinsman, J. M., Moore, J. W., and Hamilton, W. F. Studies on the circulation. I: Injection method: Physical and mathematical considerations. Arner. J. Physiol. 89:322, 1929.

Thermal dilution technics. Circ. Res. 10:491, 1962.

VOL. 7, NO. 2, FEB., 1969 173

CAREY AND HUGHES

73.

74.

75.

76.

77.

78.

79.

80.

81.

82.

83.

84.

85.

86.

87.

88.

89.

90.

91.

92.

93.

74

Kirkendall, W. M., and Stein, J. H. Clinical pharmacology of furosemide and ethacrynic acid. Amer. J. Cardiol. 22162, 1968. Kirklin, J. W., and Pacifico, A. D. Effect of intracardiac operations upon congestive heart failure and body composition. Amer. J. Cardiol. 22: 183, 1968. Kloster, F. E., Bristow, J. D., Starr, A., McCord, C. W., and Griswold, H. E. Serial cardiac output and blood volume studies following cardiac valve replacement. Circulation 33:538, 1966. Kunz, A. L., and Smith, C. W. Theory and design of an on-line cardiac output computer. J . Appl. Physiol. 23:784, 1967. LeFemine, A. A., and Harken, D. Postoperative care following open heart operations. Routine use of controlled ventilation. J. Thorac. Cardiovasc. Surg. 52:209, 1966. Lewis, M. L., Guintini, C., Donato, L., Harvey, R. M., and Cournand, A. Quantitative radiocardiography. 111: Results and validation of theory and method. Circulation 26: 189, 1962. Litwak, R. S., Kuhn, L., Gadboys, H. L., Lukban, S. B., and Sakirurai, H. Support of myocardial performance after open cardiac operations by rate augmentation. J. Thorac. Cardiovasc. Surg. 56:484, 1968. Litwak, R. S., Slonim, R., Wisoff, B. G., and Gadboys, H. L. Homologous blood syndrome during extracorporeal circulation in man: 11. Phenomenon of sequestration and desequestration. New Eng. J. Med. 268: 1377, 1963. McDonald, R. H., Goldberg, L. I., McNay, J. L., and Tuttle, E. P. Effects of dopamine in man: Augmentation of sodium excretion, glomerular filtra- tion rate, and renal plasma flow. J. Clin. Invest. 43:1116, 1964. MacCannell, K. L., McNay, J. L., Meyer, M. B., and Goldberg, L. I. Dop- amine in the treatment of hypotension and shock. New Eng. J. Med. 275: 1389, 1966. MacKay, J. L. The effects of a narcotic level of carbon dioxide on plasma potassium and respiration of cats. Amer. J. Physiol. 151:469, 1949. Maronde, R. F., Frasher, W., Hyman, C., and Sobin, S. Electrical conductivity method for estimating right ventricular output and mathematical model. Amer. Heart J. 75:66, 1968. Mitchie, D. D., Goldsmith, R. S., and Mason, A. D. In vitro instability of a commonly used tricarbocyanine dye. Circulation 26:761, 1962. Morgan, B. C., Crawford, E. W., Wintershied, L. C., and Gunther, W. G. Circulatory effects of intermittent positive pressure ventilation. Northwest Med. 67:149, 1968. Morse, B. W., Danzig, R., and Swan, H. J. C. Effect of isoproterenol in shock associated with myocardial infarction. Circulation 36(Suppl. 11): 192, 1967. Mundth, E. D., Keller, A. R., and Austen, W. G. Progressive hepatic and renal failure associated with low cardiac output following open heart surgery. J. Thorac. Cardiovasc. Surg. 53:275, 1967. Noble, M. I. M., Trenchard, D., and Guz, A. Effect of changes in PaCOz and PaO, on cardiac performance in conscious dogs. J. Appl. Physiol. 22: 147, 1967. ONeill, A., Valet, L., and Cudkowicz, L. The effect in man of changes in intrathoracic pressure on cardiac output. Canad. J. Physiol. Pharmacol. 43: 203, 1965. Oriol, A. Determination of cardiac output, using Dows formula. J. Appl . Physiol. 22:588, 1967. Oriol, A., Anthonisen, N., and McGregor, M. Limitations of indicator dilution methods in estimation of cardiac output in chronic lung disease. Amer. Heart J. 75:589, 1968. Oriol, A., and McGregor, M. Indicator dilution methods in estimation of cardiac output in clinical shock. Amer. J. Cardiol. 20:826, 1967.

THE ANNALS OF THORACIC SURGERY


94.

95.

96.

97.

98.

99.

100.

101. 102.

103.

104.

105.

106.

107.

108.

109.

110.

111.

112.

Paneth, M., Sellers, R., Gott, V. L., Weirich, W. L., Allen, P., Read, R. C., and Lillehei, C. W. Physiologic studies upon prolonged cardiopulmonary by-pass with the pump-oxygenator with particular reference to (1) acid base balance (2) siphon caval drainage. J . Thorac. Cardiovasc. Surg. 34:570, 1967. Peretz, D. I., McGregor, M., and Dossetor, B. M. Lacticacidosis: A clini- cally significant aspect of shock. Canad. Med. Ass. J . 90:673, 1967. Pollock, L., McDonald, K. E., Kjartansson, K. B., Delin, N. A., and Schenk, W. G. Influence of hyperventilation on cardiac output and renal blood flow. Surgery 55:299, 1964. Rapaport, E., Wiegand, B. D., and Bristow, J. D. Estimation of left ventricular residual volume in the dog by a thermodilution technique. Circ. Res. 11:803, 1962. Rastelli, G. C., and Kirklin, J. W. Hemodynamic state early after prosthetic replacement of mitral valve. Circulation 34:448, 1966. Reed, J. H., and Wood, E. H. Use of dichromatic earpiece densitometry for determination of cardiac output. J. Appl. Physiol. 23:373, 1967. Roberts, W. C., and Morrow, A. G. Causes of early postoperative death following cardiac valve replacement. Clinico-pathologic correlations in 64 patients studied at necropsy. J . Thorac. Cardiovasc. Surg. 54:422, 1967. Rushmer, R. F. Samet, P., Bernstein, W. H., and Levine, S. Significance of atrial contribu- tion to ventricular filling. Amer. J . Cardiol. 15:195, 1965. Samet, P., Bernstein, W. H., and Castillo, C. Validity of indicator dilution cardiac output determination in patients with mitral regurgitation. Circula- tion 33:410, 1966. Samet, P., Castillo, C., and Bernstein, W. H. Validity of indicator dilution determination of cardiac output in patients with aortic regurgitation. Circu- lation 34:609, 1966. Sealy, W. C., Young, W. C., and Harris, J. S. Studies on cardiac arrest. The relationship of hypercapnia to ventricular fibrillation. J. Thorac. Surg. 28:447, 1954. Shoemaker, W. C., Printen, K. J., Amato, J. J., Monson, D. O., Carey, J. S., and OConnor, K. Hemodynamic patterns after acute anesthetized and unanesthetized trauma. Arch. Surg. (Chicago) 95:492, 1967. Siegal, W., and Gifford, R. W. Efficacy of ethacrynic acid in patients with refractory congestive heart failure resistant to meralluride. Amer. J . Cardiol. 22260, 1968. Sinclair, J. D., Sutterer, W. F., Fox, I. J., and Wood, E. H. Apparent dye dilution curves produced by injection of transparent solutions. J. Appl . Physiol. 16:669, 1961. Sinclair, S., Duff, J. H., and MacLean, L. D. Use of computer for calcu- lating cardiac output. Surgery 57:414, 1965. Sleeper, J. C., Thompson, H. H., McIntosh, H. D., and Elston, R. C. Re- producibility of results obtained with indicator dilution technique for estimating cardiac output in man. Circ. Res. 11:712, 1962. Smith, H. J., Oriol, A., March, J., and McGregor, M. Hemodynamic studies in cardiogenic shock. Treatment with isoproterenol and metaraminol. Cir- culation 35: 1084, 1967. Smith, McK., Geddes, L. A., and Hoff, H. E. Electrical calibration for the saline-dilution method for cardiac output. Cardiovasc. Res. Cent. Bull. 6:142. 1968.

Cardiovascular Dynamics. Philadelphia: Saunders, 1961.

112a. Sonnenblick, E., Parmley, W., and Matloff, J.

113. Spencer, F. C., Eiseman, B., Trinkle, J. K., and Rossi, N.

Hemodynamic effects of glucagon after prosthetic valve replacement. Circulation 38(Suppl. 6): 183, 1968.

Assisted circulation for cardiac failure following intracardiac surgery with cardiopulmonary bypass. J . Thorac. Cardiovasc. Surg. 49:56, 1965.

VOL. 7, NO. 2, FEB., 1969 175

CAREY AND HUGHES

114. Taber, R. E., Morales, A. R., and Fine, G. Myocardial necrosis and the postoperative low cardiac output syndrome. Ann. Thorac. Surg. 4: 12, 1967.

115. Theye, R. A. Personal communication, Sept. 24, 1968. 116. Theye, R. A., and Kirklin, J. W. Erythrocyte volumes after perfusion with

homologous blood. J . Thorac. Cardiovasc. Surg. 46: 57, 1963. 117. Theye, R. A., Milde, J. H., and Michenfelder, J. D. Effect of hypocapnia

on cardiac output during anesthesia. Anesthesiology 27:778, 1966. 118. Theye, R. A., and Tuohy, G. F. The value of venous oxygen levels during

general anesthesia. Anesthesiology 26:49, 1965. 119. Wade, 0. L., and Bishop, J. M. Cardiac Output and Regional Blood Flow.

Oxford, Eng.: Blackwell, 1962. Pp. 1-50. 120. Wagner, H. R., Gamble, W. J., Albers, W. H., and Hugenholtz, P. G.

Fiberoptic-dye dilution method for measurement of cardiac output. Com- parison with the direct Fick and angiocardiographic methods. Circulation 37:694, 1968.

121. Warner, H. R. The role of computers in medical research. J.A.M.A. 196: 944, 1966.

122. Warner, H. R., Gardner, R. M., and Toronto, A. F. Computer-based monitoring of cardiovascular functions in postoperative patients. Circulation 37(Suppl. 11): 68, 1968.

123. Warner, H. R., Swan, H. J. C., Connolly, D. C., Tomkins, R. G., and Wood, E. H. Quantitation of beat-to-beat changes in stroke volume from the aortic pulse contour in man. J . Appl . Physiol. 5:495, 1953.

124. Weil, M. H., Barr, J., and Marbach, E. P. Repeating dispenser for calibration of dye-dilution curves. J. APPI. Physiol. 22:822, 1967.

125. Weston, R. E., Grossman, J., Borun, E. R., and Hanenson, L. B. The pathogenesis and treatment of hyponatremia in congestive heart failure. Amer. J . Med. 25:558, 1958.

126. Williams, J. C. P., ODonovan, P. B., and Wood, E. H. A method for the calculation of the areas under dye-dilution curves. J. Appl . Physiol. 21 :695, 1966.

Rational approach to management of clinical shock. Arch. Surg. (Chicago) 91:92, 1965.

127. Wilson, J. N.


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