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COLLECTIVE REVIEW

Cardiac Output
Clinical Monitoring and Management
Joseph S. Carey, M.D., and Richard K. Hughes, M.D.

M

ore than any other single clinical advance in recent years,
operative procedures on the heart have focused attention on
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. T h e 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. T h e use of a tight-fitting face mask
for collection purposes might influence the patient’s 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.
T h e 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

T h e 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 Flow (Cardiac Output) cc./min. =
C.O. cc./min. =

Total O2 uptake (cc./min.)
cc. O2given up/ 100 cc. blood ’

(1)

O2 uptake
x 100,
A-V 0, difference

(2)

300
C.O. cc./min. = -x 100.

5

For this determination, a sampling of arterial oxygen content, mixed
venous oxygen content, 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. T h e limitations of this method are
VOL.

7,

NO. 2, FEB.,

1969

151

and an average concentration of 6 mg. in practice the blood containing the indicator recirculates and contaminates the downslope of the curve (A in Fig. However. The continuous analysis of this concentration produces an indicator-dilution curve (Fig. this technique was used by Cournand and associates [3 11 in performing their original studies of hemodynamics in clinical shock. C(t)dt or F = (4) + 0 C(t)dt 0 In the absence of recirculation. 1). (A) Actual curve contaminated by recirculation. 152 T H E ANNALS OF THORACIC SURGERY . and on-line computer analysis. The total amount of indicator (I mg. A technique analogous to the Fick principle is the rapid injection of an indicator into the circulation. per liter is recorded over a 10-second period in the arterial blood. The cardiac output would thus be 6 liters per minute. The total flow (F)is related to the concentration recorded at the sampling site in the following manner: T h e 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. 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. 1). *Thus. and the timeconsuming analysis of expired air and blood oxygen concentrations. 1). the concentration curve would gradually diminish at an exponential rate as new blood flowed into the system and replaced the blood containing the indicator (B in Fig. then one liter of blood must have flowed by during that 10-second period. if 6 mg. as follows: Zmg.=Fx 2 Zmg. of dye is injected into the right atrium. Ordinarily. Nevertheless. (B) Ideal curve that would be recorded if recirculation did not occur.) injected is equal to the summation of all the increments of concentration multiplied by the flow rate. With the availability of continuous recording of arterial and venous oxygen saturation and expired oxygen concentration.CAREY AND HUGHES the difficulty of obtaining accurate samples of expired air in acutely ill patients. an instantaneous estimation of cardiac output may be possible in the future. ~~ FZG. with downstream analysis of its dilution concentration. the need for sampling of pulmonary artery blood. 1.

T h e theory and application have been reviewed by Hosie [641.COLLECTIVE REVIEW: Cardiac Output the first portion of the downslope occurs before recirculation occurs. indocyanine green dye. Indocyanine green is rapidly removed from the circulation by the liver [66]. Electrical conductivity is measured by a small conductivity cell placed distal to the site of injection of a small volume of saline. T h e determination of cardiac output by this technique (as well as the electrical conductivity method) has the attractive advantage of the absence of recirculation. It is necessary for the indicator to be perfectly mixed in its dilution volume in order to insure an exponential washout of the indicator. A typical indicator-dilution curve is recorded. saline. during rapidly repeated injections. when the concentration curve is plotted on log paper. NO. 7. 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. some green dye will accumulate and may produce an error of up to 11% in calibration curves [39]. sampling in pulmonary artery or aorta). and Burton [16]. This technique has received considerable attention in recent years. 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. 1121. 84. T h e change in temperature of the blood after injection of saline may be recorded as an indicator-dilution (thermodilution) curve. so that hemoglobin saturation does not affect the density of the blood. This line may then be extended to the baseline and the integration (summation) procedure performed. Colored dyes are detected in the arterial blood by withdrawal through a densitometer. These curves are difficult to calibrate. the downslope (before recirculation) will form a straight line with a slope related to this constant. and does not accumulate significantly as does Evans blue dye. primarily as a means of measuring ventricular volume [97]. Hamilton [58]. T h e indicator must not in itself stimulate the cardiovascular system and should be easy to detect in the arterial blood. However. which detects the absorption of light by the dye at a specific wavelength. and various radioactive labeled substances are most frequently used. T h e assumption of this extrapolation is that the exponential rate of decay is a negative constant.. Saline has been used as an indicator by recording changes in temperature or electrical conductivity of blood after its infusion [16. If there is at least one ventricle between the injection and sampling sites. 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. 2. Evans blue dye. 58. FEB. since the temperature change (or change in electrical conductivity) is soon dissipated in the vascular beds distal to VOL. mixing is usually adequate. 1 9 6 9 153 . and thus.

Nevertheless.35. Further refinements of this technique may be expected in the future.4% average difference when compared to the Fick method. a count rate meter. However. 781. an electronic amplifier.CAREY AND HUGHES the recording site.2% average variation between paired cardiac output determinations by radiocardiography. a photomultiplier system. positioning of the collimator. T h e indicator-dilution curve recorded by isotope dilution is not as smooth as the dye-dilution curve. a method has been developed by which the integration procedure may be performed without extrapolation of the downslope [51]. perhaps because of the insulating effect of air in the lungs [64]. 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. the dependence on this equilibration may lead to error when radiocardiography is used to measure cardiac output. 75. Pathological conditions like pulmonary edema and pulmonary vascular or parenchymal disease may cause considerable error. 154 T H E ANNALS OF THORACIC SURGERY . Since it is well known that the measurement of blood volume by I131-taggedalbumin in acutely ill patients is frequently in error due to improper mixing of the indicator. and an 8. because Calibration may be accomplished by allowing the indicator to completely equilibrate with the circulation. and thermodilution has not as yet found a place in the monitoring of the seriously ill patient. This makes the calculation by integration of the curve somewhat more difficult. In addition. some of which are discussed below. T h e equipment required for radiocardiography includes a crystal scintillation counter. and amounts of intervening tissue. since the only significant external radiation resulting from internally located radioisotopes comes from gamma rays. A collimating shield is used to avoid pickup of radioactive scatter when the counter is positioned over the precordium. since contamination by isotope in adjacent vessels may occur. the equilibration count over the heart covers a larger field of radiation than the original recording of the first pass of indicator. The most commonly used isotope is I131-taggedalbumin. Gamma-emitting isotopes must be used. The injection and sampling sites must thus be relatively close together. as pointed out by Conn [28]. 36. These results compare favorably with those obtained by comparison of the dye-dilution with Fick techniques [57]. Various radioactive substances have been used as indicators for the recording of dilution curves [28. T h e system may be “focused” in order to reduce to a minimum the errors due to radioactive scatter. and because of its passage through each ventricle a double-peaked curve is recorded. and an electronic recorder. 50-52. T h e disadvantages of equipment required and potential errors due to positioning and anatomical variations are offset by the advantage that arterial cannulation is avoided. Kloster and his associates [75] obtained a 3.

NO. Cardiac output is then obtained from formula 4. T h e more peripheral the site of injection. 2. This will result in a curve with a lower peak concentration and a more gradual washout. and Hamilton [72]. Moore. 7.COLLECTIVE REVlEW: Cardiac Output CALCULATION OF CARDIAC O U T P U T FROM INDICA TOR-DILUTION CURVES T h e procedure for the calculation of cardiac output by the dyedilution technique will now be described in detail. T h e dilution of the dye in the large left atrium results in a much lower peak concentration and a non- FIG. Delayed washout from the left atrium results in nonexponential downslope of curve (B). T h e area under the curve is determined by measuring the concentration at specific time intervals on the replotted curve (B in Fig. 1). Arterial blood is withdrawn at a constant rate (usually 20 to 40 cc. However. much of the discussion also pertains to other indicator-dilution methods. T h e dye curve is recorded on a linear recorder. T h e classic method of deriving cardiac output from indicatordilution curves was proposed by Stewart and refined by Kinsman. When the washout is gradual. Sites of Injection and Sampling. since this is the method most frequently used at the present time. 1969 155 .. Effect of injection site on dye-dilution curve. VOL. FEB. 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 greater will be the dilution volume of the dye. the downslope of the curve is more likely to be contaminated by recirculation [93]. 2. T h e recording apparatus for the dye-dilution curve includes a dye densitometer and an amplifier-recorder system. 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. per minute) through a cuvette in the densitometer. T h e following aspects of this technique should be noted.

These considerations are not of practical importance unless on-line computer analysis of dye curves is used. Pulsations at the sampling site may be minimized by using stiff tubing and withdrawal rates of 20 to 40 cc. In the normal circulation. per minute. particularly if more peripheral arteries. it is necessary to bring the injection and sampling sites closer together. Variability in the linearity and response times of dye densitometers has been noted [110]. gradual washout of dye. Chronic lung disease may also result in errors in dye curve recording. Although this technique may be useful for studying the normal or exercise circulation under specific conditions. peripheral vein injection sites will give reasonable results. However. Such curves are impossible to integrate accurately. an accurate dye curve may not be obtained unless injection is made into the ascending aorta. such as the radial. This somewhat reduces the problems of excessive dilution that occur in patients with cardiac enlargement. T h e Stewart-Hamilton method for determining the area under the dye curve utilizes the trapezoidal rule. 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. Recording Apparatus.CAREY AND HUGHES exponential. so that for some studies with rapidly repeated injections. When multiple-sample calibration is used. where nonlinearity can introduce a significant error. when circulation time is delayed. Although the Stewart-Hamilton theory assumes continuous flow. it is not accurate in low flow states and thus probably not useful in acutely ill patients. Therefore. This may be most pronounced when sampling is performed with an earpiece densitometer. a correction factor must be used [39]. 156 THE ANNALS OF THORACIC SURGERY . without delayed circulation time or enlargement of the cardiac chambers. T h e length and diameter of the catheter connecting the sampling site to the densitometer should be kept minimal. Response time can diminish with accumulation of background dye. Calculation and Calibration. as when cardiac output is low. Dye curves are affected by peripheral sampling sites to some degree. which samples the dye as it passes through the pinna of the ear [99]. When cardiac enlargement as well as low cardiac output is present. 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. due to variations in transit time across the lungs [92]. under conditions of low flow and cardiopulmonary disease. are used [5]. in order to reduce errors due to streaming of dyed blood in the tubing [29]. central injection into the great veins or right atrium is necessary in order to avoid contamination of the downslope by recirculation. linearity is necessarily checked. pulsatile flow at peripheral sites generally does not produce a significant error.

A visual curve-fitting technique was used by Gorten and Hughes [51]. NO. Other investigators [8.4%. This method was shown to agree within + l o % of 90% of curves calculated by the Stewart-Hamilton formula. T h e downslope of the curve prior to valve replacement is prolonged and probably contaminated by early recirculation. 9 11 have investigated the assumption that the area of a dye-dilution curve can be estimated from the first part of the curve. 2. 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. 3. This formula agrees well with the Stewart-Hamilton method. the area is determined by adding the points and multiplying the sum by the time interval. 51. requiring the logarithmic replot of the downslope and estimation of the remainder of the downslope back to zero concentration. This method gives a mean difference of 2. VOL. and mitral insufficiency. T h e method of Williams and associates [126] breaks the curve into several smaller areas and sums them by simple arithmetic. Eflects of delayed washout and early recirculation on dye-dilution curve.. Figure 3 illustrates cardiac output curves taken before and after mitral valve replacement in a patient with low cardiac output.4% when compared to the Stewart-Hamilton calculation. 1261. 1969 157 . 7. a large heart. Delayed washout allows early recirculation and nonexponential downslope of curve (A). and Boyett and his associates [12]. This is a somewhat laborious process. FEB. 37. When initial and final concentration values are zero (as in the replotted 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. A nomogram combining planimetry with a formula for estimating the area under the downslope for use at the bedside has also been devised [27]. and then summed [69]. 62. as a result of FIG.COLLECTIVE REVIEW: Cardiac Output in which concentration points are marked at time intervals (usually one second). Several shortcuts that avoid replotting have been devised to estimate the area under the curve with varying degrees of accuracy [12. 27. having a standard deviation of differences of 1. 21.

Because ideal curves are not usually obtained in low flow states. however. and flat. less accurate results are obtained. 1101. utilizing a simple formula and noting only the peak concentration and peak concentration time. or the forward triangle method of Hetzel et al. with most differences between manual and computer results varying between *5%. and obtained a mean difference of t-9% in the normal range of cardiac output. When properly calibrated. The formulas employed are usually variations of the short forms mentioned above. A concentration curve is plotted and the result obtained as milligrams per liter per millimeter recorder 158 T H E ANNALS OF THORACIC SURGERY . After valve replacement. the downslope is steeper and may readily be calculated. assuming exponential washout [48. 1041. 481. sampling variations. distortion due to baseline shifts. [62]. Flat curves with delayed washout may. Slightly better results were obtained with a Lexington computer by Glassman and his associates [48]. These low-cost computers are essentially integrating devices that contain a compensating circuit to perform an automatic estimation of the area under the downslope. the computer will give a direct readout of cardiac output.CAREY AND HUGHES delayed washout from the left atrium caused by mitral insufficiency. With attention to methodological details. With less sophisticated instrumentation. In the absence of such facilities. it is unlikely that these low-cost computers will offer sufficient advantage over arithmetic calculations to make them useful in patient monitoring. and little time is saved because external recording of the dye curve and computer output is still required. sophisticated on-line computer analysis of dye curves may be practical where timesharing computer facilities are available. Dalby and his associates [32] compared the Sanborn computer to a planimetric method. With the use of sophisticated analysis. such as is now commercially available. This curve could not be calculated by the Stewart-Hamilton method. Computers may be used to replot automatically the downslope and estimate the area under the dye-dilution curve. be calculated by Dow’s method [37]. 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. In the opinion of Wood’s group at the Mayo Clinic [126]. irregular curves may be removed and accurate computation performed 1291. These results are not as accurate as arithmetical methods that avoid replotting. these workers believed that arithmetical techniques were simpler and more accurate. errors due to mitral and aortic regurgitation can be minimized [103. The main problem with low-cost computers is the inability of the instrument to calculate accurately low and high curves [7. T h e theory and circuitry of on-line computation of cardiac output have been described [59. 761.

where rapid changes in hematocrit. For detection of VOL.) = 2 60 sec. (6) Stroke volume (SF') equals a constant ( K ) . Formula 4 is rewritten. x I mg. which are described by central arterial pulse contour. forward flow occurs during diastole as well as systole [123]./liter/mm. and other factors may occur./min. Warner's formula for calculation of stroke volume is SV = dPmd (1 + Sa/Da). it is necessary to sterilize the withdrawal equipment and calibration apparatus in order to reinfuse the blood when frequent dye curves are performed. x CF mg. T h e procedure of Weil and his associates uses semiautomated equipment for rapid and accurate calibration. FEB. Pulse rate times stroke volume gives cardiac output.. times the square root of the mean distending pressure ( ~ m d )times . 1969 159 . Flow relates to pressure and resistance. 7. 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.COLLECTIVE REVIEW: Cardiac Output deflection. 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. one plus systolic (Sa) over diastolic (Da) pressure [121]. Therefore. they distend during systole and contract during diastole. 2. (5) C ( t ) dt mm. NO. A simplified sterile procedure for performing the calibration has been described by Weil and his associates [124]. As these authors point out.-sec.which relates to aortic volume and is obtained from one determination of cardiac output by the dyedilution method. Stroke volume consists of forward flow during systole and diastole. T h e relationship between pulse pressure and stroke volume is well known [58. 1011. Warner and associates have developed a practical method for computer analysis of pulse contour in order to determine cardiac output [121-1231. It is important to mix the dye-blood mixture carefully in recording the calibration curve. allowing frequent calibration by permitting reinfusion of calibration samples. background dye concentration. Enlarging on this concept. frequent calibration is necessary in the clinical setting. including a factor of 60 to correct for seconds to minutes: F (litersimin. Since arteries are elastic tubes. Since a considerable volume of blood is required for the sampling of arterial blood for dye curves and their calibration. 0 where C F is the calibration factor obtained from the calibration curve.

CAREY AND HUGHES the degree of change of cardiac output. exercise. Sorenson Research Corp. All or part of the data can be retrieved subsequently from the magnetic disks or by review of the printout. The catheter is attached to a pressure transducer. 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. T h e agreement was +9%. The constant (K) is derived. Sampling of multiple beats is particularly important for patients with arrhythmias. the arterial catheter is left in as long as two weeks for monitoring.98 or better . and body pressurization [121]. calibration by the dye-dilution method is not essential. 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. stored. systemic vascular resistance. stroke volume. Substations may be used in the operating rooms. During a few seconds.. and animal research laboratories. The analog-to-digital converter samples the aortic pulse wave 200 times per second for 16 beats in order to derive mean values. Salt Lake City. After calibration.long size 19 Teflon catheter* is passed percutaneously through a thinwall size 18 needle into the radial artery and advanced in or near the aortic arch. and mean arterial pressure are displayed on a memory oscilloscope at the bedside substation. T h e technique of monitoring acutely ill patients has been described by Warner and his associates [122]. Significant complications do not occur. and during changes of pulse rate from 60 to 240 with pacemaker-induced rates after creation of complete heart block [53]. and anesthesia. the pressure-pulse program is called. *CAP Infusor. diastolic. Utah. atropine. Cardiac output is immediately calculated by the computer. and applied to future computations of cardiac output by the computer. since pulse volume is often so variable. cardiac catheterization laboratories. infusion of drugs (metaraminol. On occasion. 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. The correlation coefficient of the pressure-pulse method and flowmeter studies was 0. A specially designed 100-cm. neostigmine). Data can also be measured automatically by the computer at preset intervals. A similar catheter is passed percutaneously into a central vein. tilt. heart rate. 160 THE ANNALS OF THORACIC SURGERY . intensive care units. calculations are performed and cardiac output. T h e 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. duration of systole. and the constant ( K ) can be estimated. exercise. systolic.

a good cardiac output. NO. Central venous pressure correlates poorly with cardiac output. Although no studies have been performed comparing the volume of the radial pulse to stroke index. and direct correlation with cardiac output was fair in one clinical study [2]. Monitoring of the A-V oxygen difference has therefore been used to estimate indirectly cardiac output [113. 7. An indicatordilution 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%). 1271. but again any level of cardiac output may be present at a given blood volume. 1271. but observation of changes is very helpful in evaluating cardiac function [43. 751. Mixed venous oxygen saturation is indirectly related to cardiac output. FEB. 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]. 951.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 patient with a strong. A mean variance of +19% to 234% was obtained when this technique was compared to cardiac output measured by the Fick method [58].. 2. VOL. 1969 161 . Measurement of serum lactic acid may therefore be helpful in evaluating the circulatory state of acutely ill patients. However. Central venous pressure and blood volume are readily monitored in acutely ill patients.the technique of multiple samples is not justified if continuous recording of the indicator-dilution curve is available. full radial pulse is likely to have a good stroke output and. A correlation coefficient between actual (measured by dye dilution) and estimated cardiac output of .68 was obtained. and the A-V oxygen difference may be normal in spite of low cardiac output. 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. Lactic acid is elevated in the majority of patients in shock [15. Correction of blood volume deficits correlated with a rise in cardiac output in most postoperative cardiac surgical patients [9. with a mean variance of +24%. 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. These results were considered sufficiently inaccurate that the method could not be recommended for bedside use. T h e presence of excess lactic acid in the blood may be indicative of hypoxic acidosis secondary to poor tissue perfusion. many patients have a reduced oxygen uptake. assuming adequate heart rate. 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.

This counter requires careful positioning and has not yet been used for patient monitoring. It allows the patient some freedom of motion. but placement of the catheter in the aorta was required for sampling. gives the physician qualitative information that is adequate in the majority of situations in which instrumentation for measurement of cardiac output is unavailable. Although placement of a catheter in the pulmonary artery is required. Khalil and his associates [7 11 have described a local thermodilution technique in which a thermister catheter was passed into the pulmonary artery. Cardiac output was derived from the resulting thermodilution curve. Reflected sound waves have been used as a means for determining changes in ventricular volume. Monitoring of these parameters in the clinical setting. Two other single-catheter thermodilution techniques for measuring blood flow have been described [47. and the temperature change was recorded by the thermister in the pulmonary artery. and brain. 861. 1203 have described a fiberoptic catheter for use in detecting dye-dilution curves directly from a densitometer at the end of the catheter. and the apparatus is simple and inexpensive. T h e method agreed well with the Fick technique. lightweight precordial counter for use in recording radioisotope dilution curves. the delay of external sampling systems was avoided. was used to record radioisotope dilution curves of dogs by Hernandez and his associates [61]. sampling. 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 162 THE ANNALS OF THORACIC SURGERY . Because of internal sampling. and simple integration of the curve allowed direct on-line computation of cardiac output. and recirculation problems. these techniques may provide simple and inexpensive monitoring devices for postoperative patients. skin. NEW TECHNIQUES Gorten [50] has described a small. since they avoid injection. placed in the esophagus. Hugenholtz and his associates [65. skin blanching. This counter may be fixed to the chest and avoids the need for lead shielding and collimation by using 1125as the indicator. T h e method agreed well with cardiac output determination by the Fick method. A miniature scintillation counter. in addition to other easily measured variables mentioned previously. and mental alertness are related to the perfusion of the kidneys. A portion of the catheter in the right atrium heated the blood by direct contact. one of which has been used in pediatric patients [86].CAREY AND HUGHES Urine output. and it may be useful in a restless postoperative patient. This technique avoids injection of indicator.

A more convenient instrument is now available* that incorporates a disposable cuvette. is stable [85]. Calculation can readily be performed by the use of simple formulas that avoid replotting. a densitometer. but have not yet been adopted to the monitoring of acutely ill patients. 3). but reinfusion of curve samples as well as calibration samples is easily accomplished. APPRAISAL OF TECHNIQUES At the present time. Calif. T h e instrumentation is relatively simple and may be handled by one person. since accuracy in low flow States is not achieved by relatively unsophisticated instruments. Determination of cardiac output from indicator-dilution curves in low flow states requires careful positioning of injection and sampling sites. 671. 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.and is rapidly removed by the liver [66]. knowledge of the limitations of the recording apparatus. FEB. At the present time. 2. Reasonable agreement with stroke volume as determined by the Fick principle has been obtained with these methods. the best available techniques for monitoring cardiac output in the seriously ill patient are variations of the indicatordilution technique and pulse-contour methods. the dye most commonly used.. True exponential washout of the indicator from its dilution volume is the exception rather than the rule in low flow states [93]. and careful calibration and calculation of the dilution curves. This *Cardiodensitometer. T h e majority of these techniques have been used in the cardiac catheterization laboratory. Dye-dilution curves are relatively easy to record in acutely ill patients when proper attention is paid to the limitations of the method. when injections can be made directly into the heart and sampling accomplished through a peripheral artery (Figs. 1969 163 . Beckman Instruments. NO. From the recorded tracing (echocardiogram). 7. Its effect on the density of blood is not influenced by hemoglobin saturation. and this factor must be considered in performing calculations. Indocyanine green. This method is particularly suited to intraoperative measurements.COLLECTIVE REVIEW: Cardiac Output waves (ultrasound) to record motion of the walls of the heart [40. With refinements of instrumentation. VOL. and a recorder with an integrating circuit. changes in ventricular volume may be calculated. Palo Alto. and the instrumentation has the advantage of being completely free of intravascular components. 2. although it is usually necessary for a physician to make the injection while a technician records the curve. this may be possible in the future. Dye curves require withdrawal of arterial blood through a cuvette for sampling.

a sensitive finger on the radial pulse may be as reliable as the most sophisticated computer analysis of pulse contour. It is thus particularly suited to postoperative monitoring. it is preferable to keep the dilution volume to a minimum by approximating the injection and sampling sites. By allowing peripheral injection and central. The radioisotope-dilution technique avoids arterial sampling by counting directly over the heart. Radioisotope curves are somewhat more time-consuming. the radioisotope technique may be preferable to the dye-dilution method for postoperative monitoring. dye curves should be used. the product of pulse pressure (as recorded in the arm) and heart rate gives a rough estimate of cardiac output. because they require a 15-minute delay before the equilibration concentration is recorded. about $5. peripheral injections give better curves with radioisotopes than with dye. described by Herd and associates [60]. and acid-base balance. Finally. urine output. because the recorded curve contains two concentration peaks (as the indicator passes through each ventricle). This method is relatively new. and the tracing is slightly more irregular. Nevertheless. [I 221 is well worth a trial. the pulse-contour method of Warner et al. As discussed above. Central injection is therefore not a necessity with the radioisotope technique. utilizes simple electrical circuits that multiply the difference between mean and diastolic aortic pressure by heart rate. Determination of the area under the radioisotope-dilution curve also takes slightly longer than for the dye curve. When more frequent measurements are required. Determination of cardiac output from pulse-contour analysis offers the only available continuous monitoring of cardiac output. such as mental alertness. since peripheral sampling is usually used for dye curves. Indeed.CAREY AND HUGHES instrument is particularly suited for bedside use because of its size and stability. which simplifies calculation of the area under the curve. are easy to obtain and usually reflect the effectiveness of blood flow. A less elaborate pulse-contour method. This method may be used for continuous monitoring of cardiac output without the need for on-line computer analysis. it has been suggested that the number obtained by cardiac output measurement is in itself unnecessary in the 164 THE ANNALS OF THORACIC SURGERY . when the finger is attached on-line to a well-programmed human brain.000. the convenience of the disposable cuvette. As a result of central sampling. where time-sharing facilities for on-line computer analysis are available. and the integrating circuit. external sampling. T h e cost of the equipment for the performance of radioisotope or dye-dilution curves is essentially the same. Radioisotope-dilution curves may be recorded 5 to 6 times in one day. Other simple measurements. and its accuracy has yet to be proved in the variety of clinical settings where monitoring of cardiac output is desirable. Progressively simplifying the basic assumption that the pressure pulse is proportional to the stroke volume.

It appears likely that for routine monitoring of cardiac output some variation of the pulse-contour technique will become the procedure of choice. the indicator-dilution method has not achieved a place in routine monitoring. However. T h e superimposition of surgical trauma. FEB. that cardiac output be monitored in acutely ill patients in general and in postoperative cardiac surgical patients in particular. the information produced by pulse-contour analysis is instantaneously available for use to nurses. but not essential.5 and 4. With the increasing availability of time-sharing facilities for computer analysis. 1969 165 . it appears desirable. and other unknown variables may alter the homeostatic balance of such a patient so that a new level of blood flow may be required. anesthesia. since the clinician wishes to restore the homeostatic balance of his critically ill patient. a reasonably well-performed indicator-dilution cardiac output determination can be very helpful. urine output. since the only technical procedure required is placement of a catheter in or near the aortic arch. events occurring in the past are readily reviewed. in the absence of highly competent technical personnel. not as accurate as the observations of the experienced clinician. On the other hand. for obvious reasons. In the light of the foregoing discussion. Indeed. this should include the return of normal blood pressure and cardiac output as well as normal acid-base balance and urine output. M A N A G E M E N T OF LOW C A R D I A C O U T P U T Normal cardiac output varies between 2. This method provides the necessary spontaneity and simplicity required of monitoring devices. 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. As described by Warner et al. directional changes in cardiac output may not be immediately signaled by changes in secondary variables.5 liters per minute per square meter of body surface.COLLECTIVE REVIEW: Cardiac Output event that blood flow appears effective as judged by other studies [1151. [122]. and acid-base balance. most preoperative patients with acquired heart disease have low cardiac output and normal blood pressure. and with storage of data. as a spot check in the difficult situation. Furthermore. 7. T h e mean of a large number of reVOL. It is well known that cardiac output can be quite low while all other parameters are in the normal range. Borderline clinical studies may not reflect low cardiac output. 2. T h e results are not as immediately available and. T h e convenience and expense of the method must therefore be a consideration.. monitoring by this technique could be made available by telephone connection even to remote areas. Outside of the well-equipped shock unit. NO. prosthetic valve replacement. T h e same has been said of blood pressure.

In spite of this imbalance. poor perfusion of extremities. since determination of cardiac output in low flow states is frequently in error [93].2 and 3. below which progressive metabolic acidosis developed [22. These findings suggest that when congestive heart failure is present preoperatively. This suggests that oxygen consumption is reduced. Rastelli and Kirklin [98] and Mundth and his associates [88] found that acidbase balance and oxygen saturation usually remained normal. cardiac output is likely to be decreased for the first few days after corrective surgery. when congestive heart failure has usually been present preoperatively [75]. 1061.8 [119]. Because of a compensatory reduction in oxygen requirements. suggesting a physiological response to increased metabolic demands. with most studies revealing a mean between 3. Assuming that the metabolic demands of the patient are increased by the operation. However.CAREY AND HUGHES ported measurements in normals using the Fick and dye methods was 3. oliguria. The point at which cardiac output becomes critically low is difficult to identify. cardiac output is usually increased. 941. cardiac output is usually elevated [ZO. After noncardiac operations.2 liters per minute per square meter. it is difficult to attach an adequate or inadequate label to a given value of cardiac output. This effect is most pronounced after mitral valve replacement. 981. may be self-perpetuating. cyanosis. prolonged inadequate cardiac output may have deleterious effects on hepatic and renal function [88]. Mental confusion after surgery may be associated with low cardiac output [l 11 and may indicate inadequate cerebral perfusion. Blood pressure and urine output may remain normal by virtue of compensatory autonomic and renal adjustments. Immediately after aortic valve replacement. However. After open cardiac operations.6 liters per minute per square meter. by reducing coronary blood flow. It is 166 THE ANNALS OF THORACIC SURGERY . except when long-standing congestive heart failure has been present [75]. the imbalance between available cardiac output and energy requirements is exaggerated. Reduction in oxygen requirements may be a metabolic compensation that protects patients with long-standing cardiac disease from developing metabolic acidosis. 24. In the absence of the full-blown syndrome of hypotension. these values are of questionable accuracy. Some patients have preoperative levels of cardiac output in this range without metabolic acidosis. It is important to remember that the heart itself has high metabolic requirements and that low cardiac output. Rising creatinine and bilirubin are signs of inadequate hepatic and renal blood flow. 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. 23. and metabolic acidosis. metabolic acidosis may not develop. Studies during cardiopulmonary bypass identified a critical flow rate of 1.

Patients VOL. The changes in body composition that occur before and after intracardiac operations were reviewed by Kirklin and Pacific0 [74]. a decreased pC0. 42. 901 tend to decrease cardiac output. causes an increase. This effect may be due to a decrease in pulmonary vascular resistance as a result of better expansion of the lungs and improved oxygenation. Experimentally. since both pulmonary collapse and hypoxia are known to increase pulmonary vascular resistance [lo. and acid-base balance. 1171. 83. acidosis itself has little effect on the heart [6.41. and respiratory assistance is often necessary. However. Therefore. 96. NO. A paradoxical reduction in central venous pressure may occur when respiratory assistance is provided to these patients. 891..2 and 2. 891. pulmonary compliance is decreased. There is evidence to suggest that metabolic acidosis accompanies low cardiac output [24. 24.2 liters per minute per square meter is incompatible with life. 18. probably due to changes in intracellular and extracellular potassium concentration 144. preferably with intermittent monitoring of arterial blood gases. while a rise in pC0. Patients with signs of low cardiac output have improved with respiratory assistance alone [77].COLLECTIVE REVIEW: Cardiac Output likely that a cardiac output of less than 1. 1171 and increased intrathoracic pressure [30. 1051 and increased circulating catecholamines [83. 75. particularly in the critical early postoperative period when cardiopulmonary. 941. presumably due to release of catecholamines [701. T h e importance of maintaining adequate ventilation to circulatory homeostasis in the early postoperative period is well known [23. ventilation. respiratory assistance must be used with care. 1969 167 . but other studies have not substantiated this finding [9. Arrhythmias are more common in the presence of acid-base abnormalities. It is important to remember that hyperventilation [70. 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]. T h e first line of defense against low cardiac output is restoration of normal blood volume. In the presence of long-standing pulmonary hypertension. FEU. rather than the rise that usually occurs with positive pressure assistance. 1051. Litwak and his associates [80] suggested that blood volume deficits were due to sequestration of blood.0 liters per minute per square meter will be deleterious to the patient and should be treated. 2. 331. The circulatory effects of respiratory alkalosis and acidosis are fairly consistent. a rise in pC0. 881. Several authors have pointed out the importance of maintaining high atrial pressures in postoperative cardiac surgical patients [74. may adversely affect cardiac performance when pH remains constant [6. 541. 34. Generally. 74. renal. It is also likely that values between 1. causes a decrease in cardiac output [96. 7. and hepatic complications are likely to occur.

/min. and normal fluid and electrolyte balance was not restored until 2 to 6 weeks after surgery. LOWcardiac output in postoperative patients is almost always accompanied by high systemic vascular resistance. as a result of sodium retention and excessive fluid intake. and worsened by the procedure. and slow nodal rhythm are common after intracardiac operations. These arrhythmias are best treated by pacing. In the acute situation. 1071. as a result of inappropriate secretion of antidiuretic hormone [125]. This agent must be used with caution because of potassium loss that occurs during the marked diuresis that it produces (up to 40 ml. Sodium excretion may be impaired before operation. The beneficial effect of atrial and ventricular pacing on cardiac output in postoperative patients has been demonstrated [46. These changes were exaggerated by operation with cardiopulmonary bypass. and when low doses of isoproterenol are used (1 to 2 pg. bradycardia. 113. or when other measures have failed. It may therefore be necessary to maintain salt and water restriction for several weeks after operation. the clinical experience with this agent is considerable [88. preferably by atrial stimulation.79]. The hemodynamic effects 168 THE ANNALS OF THORACIC SURGERY . Various degrees of heart block. T h e same effect has been observed in postoperative patients [19].) systemic vasodilatation is rarely a problem. In the early postoperative period. serum values for these ions were usually decreased. chloride. 14. and cardiac output may increase up to 60% with atrial pacing [46]. may cause increased pulmonary vascular resistance and cellular metabolic dysfunction as a result of dilutional effects.) in postoperative patients [19]. Digitalis preparations must be used cautiously in the early postoperative period. From the foregoing discussion it is apparent that a variety of means are available for the treatment of low cardiac output before pharmacological assistance is required. T h e use of ethacrynic acid markedly improved cardiac function in patients with congestive heart failure refractory to other diuretics [ 1071. The importance of atrial contraction to ventricular filling is well known [13. 1141. and free water [73. arrhythmias or heart block frequently prevent the physician from maintaining the optimal inotropic effect of digitalis. Although total exchangeable sodium and potassium were increased./min. the accumulation of extracellular and intracellular fluid. but full digitalization is preferable to inadequate amounts of digitalis. However. 1021.CAREY AND HUGHES 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. isoproterenol is the inotropic agent of choice. Although few studies of the effects of isoproterenol in postoperative patients have been performed. the use of ethacrynic acid may be beneficial in promoting the excretion of sodium. Although most diuretics cause little effect on the postoperative patient.68.

Dopamine. and hemorrhage) are somewhat variable [17. Computer analysis of curves may be inaccurate. but its effect is somewhat short-lived and accumulation may occur with excessive dosage. 1111. SUMMARY A review of currently available methods for monitoring of cardiac output reveals that both the indicator-dilution technique and the pulsecontour method are applicable to acutely ill patients. are preventable. calibrate. and damage to the coronary arteries by coronary perfusion cannulas. Cardiac tamponade is not uncommon. it is usually not used unless isoproterenol fails. increases systemic vascular resistance. but only rarely does persistent hypotension occur when it is used in low dosages for the treatment of postoperative cardiac surgical patients. 1969 169 . such as ligation of the left coronary circumflex artery. 81. 87. Radioisotope-dilution curves are slightly more difficult to record. particularly in low flow states. Dye-dilution studies are readily performed and perhaps offer the most accurate measurement of cardiac output when proper attention is given to methodological details. the treatment of low cardiac output may eventually rest with cardiac assistance by mechanical means or by total heart replacement. When treating low cardiac output in postoperative patients. Glucagon infusion has caused modest increases in cardiac output in postoperative patients.COLLECTIVE REVIEW: Cardiac Output of isoproterenol in other low flow states (myocardial infarction. 2. a catecholamine with inotropic effects analogous to isoproterenol. Epinephrine has been used with good results in low cardiac output syndrome [25]. 831. even when the pericardium has not been closed. Other anatomical causes. 7. Massively enlarged hearts with very low preoperative cardiac output may be beyond repair. NO. VOL. In such cases. like other vasopressors. the physician must be alert for anatomical causes of myocardial dysfunction. Calcium is a powerful inotropic agent that is also useful in acute situations. and calculate. sepsis.. Neither method offersinstantaneous display. but because this agent. 55. Dysfunction of prosthetic valves is a frequent cause of fatal low cardiac output syndrome [loo]. particularly when the observer is experienced in those variables that most accurately reflect the effectivenessof blood flow. but do not require central injection or withdrawal of arterial blood for sampling. FEB. Dopamine increases the renal excretion of sodium [49]. and may be of benefit when other inotropic agents have failed [112a]. coronary air embolus. and the number of determinations is limited by the need for indicator injection. Clinical estimation of cardiac output by indirect studies is adequate in most cases. This effect may provide additional benefit to patients in congestive heart failure. causes less systemic vasodilatation and tachycardia [49. unless sophisticated curve analysis is used.

Moran. He should also be fully aware of preventable causes of low cardiac output that occur during operation. K. Cardiac hemodynamics immediately following mitral valve surgery. J. Aksnes. G. 2. 5. A. E.. and Dimond. and Scannell... 15:213. T. Amer. J. and output between 1. M. Cappelen. Scand. M. J. Clinical experience with the use of computers for calculation of cardiac output. 17:91. Benchimol.. Appl. chloride. Acta Chir. 170 THE ANNALS OF THORACIC SURGERY . R. 357(Suppl. B. C. B. V. Atrial or ventricular pacing may be beneficial in slow arrhythmias. Cardiac output and regional femoral blood flow in early postoperative period after heart surgery.. Areas of dyedilution curves sampled from central and peripheral sites. Surg. Austen. Wegner. and Day. but simpler analysis by electrical circuits may be possible. P. ventilation. Corning. 7. H. G.):299. 212:54. Aerospace Med. T h e method is as yet unproved in a variety of clinical settings. Sanders. and Hall. A. with a range of 2.. Normal cardiac output is approximately 3. Baue.. E.. Proper attention to blood volume.0 may be deleterious to vital organ function if allowed to persist. Cardiac output below 1. J. C.5. W.. Akre. G.. R. T h e surgeon should be constantly on the alert for treatable anatomical causes of low cardiac output. Agress. and free water..5 to 4. E. 1966. J.. but at the present time it appears to offer the most promise as a means for monitoring cardiac output in the acutely ill patient. Thorac. 51:468. Computer analysis by time-sharing facilities is most accurate. W. Mori. For inotropic stimulation. E. J. may be accomplished by salt and water restriction and the use of ethacrynic acid when necessary to promote excretion of sodium. 1962. Cardiol. J. particularly in patients with long-standing congestive heart failure. A. J. E. 6.. per minute to avoid tachycardia and systemic vasodilatation. Moran. S. Cardiovasc.. Tragus. Bassingthwaighte. 51:461. J. Edwards. Avoidance of fluid overload.. 1967. A. Physiol.. Sanders. M. G. W.. T. B. M. Austen.6 liters per minute per square meter. T h e dosage of isoproterenol should be kept below 2 pg. H. Full digitalization is preferable but difficult to accomplish in the early postoperative period. Corning. 1967..CAREY AND HUGHES 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. Thorac. 1965. J. Physiol. D. Measurement of the stroke volume by the vibrocardiogram. Surg. ]. 1966.2 and 2. C. W.. H.2 liters per minute per square meter is probably incompatible with life. 1966. Effects of NaCl and N a H C 0 3 in shock with metabolic acidosis.. Cardiovasc. C. 38: 1248. P. and Wood. A. G. Fremont. 3. 4. Amer. Cardiac hemodynamics immediately following aortic valve surgery. I. G. and Parking. and Scannell. and acid-base balance will improve cardiac output in many cases. calcium and isoproterenol are the most commonly used agents. REFERENCES 1.

R. R. 1965. Mohr.. H. Circulation 356uppl. Coffin. Amer. 26. and Gillespie. Surg. Carvalho. J. Clowes. and Frahm. Surg. O. W. A. Thorac.COLLECTIVE REVIEW: Cardiac Output 8.. G.. 1968. A. J. R... A. 12. J . Cooper. and Beheler. 1967. 2. Effects of acidosis on cardiovascular function in surgical patients. 28. Studies of Starling’s law of the heart: IV. Circulation 24:633. M. R. Berry. W.. Burton. Carey.. A. J. A. J. 1960. and Del Guercio. Hemodynamic studies in open pneumothorax. Obstet. 20. M. Amer. Clark. 23.. Tomin. and Simeone. Carey. L. I):78. Benchimol.. 1960. J. Cardiouasc. K. and Kloster. 1964. Schweikert. Clark. D. W. S. F.. NO. H. K. Physiol. L.. and Ryan. J. 1965. Blood volume. Circulation 35: 327. Konitaxis. M. Carey. and Goshgarian.. 29. G. G. M. J. H. K.. A. Gynec.. and Weil. 13. and Troell.. 1961. and Lillehei. M ed. and Britz. G.. 1966. W. L. A method for the rapid computation of indicator-dilution downslope areas. Braunwald. J. H. Dimond. S. 64: 160. E. A qualitative study of the “azygos factor” during vena caval occlusion in the dog. 1964. J. O. 1966. Nomograms for the rapid calculation of cardiac output at the bedside. W. Norlander. Res. Ankeney. 9. 1966. E. Cardiol. Cohn. 52:422. 99:227. R. 154:524. 27. Cardiovasc. 19:526.. C. T. L.. L. T. Rev. 1963. R. I n preparation. 164:109. R. Circ. W. C. Cardiovascular function in shock: Responses to volume loading and isoproterenol infusion. D. Observations on the postoperative circulation. Effects of acute hypoxia on pressure. 1954.. A. 1954. II):65. L. F. 15. S. T. H.. Yao. A. T h e relationship of postoperative acidosis to pulmonary and cardiovascular function. S. flow and resistance in pulmonary vascular bed. Physiol. Gynec.. and Roberts. Carlsten. 10:505. H. Circulation 366uppl. H. 1964. A. Blachly. 204:597. and Shoemaker. J. T.. S. C. Relations of cardiac output to postcardiotomy delirium.. D.. Miller. G. M. 25. Surg.. Control of fluid and electrolyte retention with ethacrynic acid after intracardiac operations. Broder. Surg. Clowes. Surg. M.. Becker. C. Monson... FEB. Brockman.. S. Extracorporeal maintenance of circulation. Chicago: Year Book. 1963. Surg. Del Guercio. 21. Clowes. Surg. Science 143: 1457. L. 12: 119. Cohen. 17. Stowe. P. F. McLaughlin. 12:131. Use of external counting technics in studies of the circulation. G. J. 24. 19. Obstet. M. and Lacy. Amer. G. D.. Lab. B. W. Brown. Alichneiwicz. 16. E. and Morrow.. 40:826. Cardiouasc. J. Excess lactate: An index of reversibility of shock in human patients. 11. central venous pressure and cardiac output in the management of open heart patients. J... 22. Amer. Conn. VOL. A. 1961. M. R. 1962. D. G. L. A. Observations on the hemodynamic functions of the left atrium in man. 1969 171 . Berger. and Hughes. 1963. G. T h e forward triangle formula for calculations of cardiac output: T h e indicator dilution technique. and Stoik. Boyett. 18. Surgery 58:404. Rapid method for determination of cardiac output by indicator dilution techniques. W. Polanzak.. Thorac. W. Res. Physiol.. 10. E. A. P. J. J.. L. 14. S. Physiology and Biophysics of the Circulation. Hughes.. Removal of distortion from indicator-dilution curves with analog computer. Sabga. 98:225. J.7.. Circ. Dynamic function of atrial contraction in regulation of cardiac performance. A. R.. M. Thorac.. Experimental study and clinical use of epinephrine for treatment of low cardiac output syndrome. 39:1. Appl. Clin. Arnold.. 55:538. G. E. E. J. D. 1967.

Harvey. 1963. and Cournand. R. Surg. R. S. and Sloman. Noble. Quantitative radiocardiography: I. Lewis... A.. Werko. P. W. 31. Stan Meet. 1:287. Mayo Clin. Amer. Res. Rochester. Theoretical considerations. and Roe. 11.. A hemodynamic comparison of atrial and ventricular pacing in postoperative cardiac surgical patient. W. 36:77. Cardiovasc.. 22:177. W. Friesen. 1960. P.. A comparison of computer and planimetry cardiac output determinations. 35. Rev. Dow. Circulation time and blood volume as means to estimate the cardiac output. and Ganz. B. 174. J. C.. B. M. F. Surgery 13:964.. M. D. J. Starr. L. Fishman. Physiol. L. 35:745.. I. 43. 32:591. J. H. J... Appl. Res. Surgery 56: 44. Circulation 26: 183.. Fronek. Circulation 35: 1092. R. Goldberg. and Young. R. Richardson.. I. McDonald. Cardiouasc. Dynamics of the Pulmonary Circulation. E. J.. 2: 1255. E. D. W. W. Section 2:Circulation. E. B. J. O.. 38. L. Dalby. Guintini. A. and Richardson. Thorac. Surg. and Harvey. J. Acta Cardiol. Christlieb. C .. Hutchinson. M. 36. Lewis. D. 40. D. D. F. Bradley. L. Frick. 1964. 207: 1112. A. N. 32. Physiologic studies of effects of intermittent positive pressure breathing on cardiac output in man. H. 42. 1963. F. Littlefield. Physiol. Herr. Estimations of cardiac output and central blood volume by dye dilution. R.. Q... 47. Dewall.. Bassingthwaighte. 44. Feigenbaum. Controlled atrial hypertension: A method for supporting cardiac output following open heart surgery. F. Edwards. F. D. Cardiouasc. 37. with an empirical formula for certain troublesome curves. L.. Durand. Surg. 1967. Dow. A.. W.. 1948.. W. Cardiovasc. 55:271. Technique and analysis of curves. Zaky. 1956. A. and Lillehei. Flemma. J.). Ames. 39. J. A. G. Fishman. R. Gregerson. L.. P. L. Use of ultrasound to measure left ventricular stroke volume. H. H. W. A. Thung. A.. Handbook of Physiology. Donato. Physiol. 48. R. N. 1966. Surg. J. 1967.. 1943. H. Cardiol. 1964. Gott. Thorac.... V. 45. C. M. Varco. and Muller. E. T. Fermoso. Aust. 1968. Sutterer. Studies of the circulation in clinical shock. W. 8: 175. Woodson.. 33. E.. 1962.. The metabolic effects of mechanical ventilation and respiratory alkalosis in postoperative patients. Rochester. and Kassebaum. Breed. 172 T H E ANNALS OF THORACIC SURGERY .. B. Circ.. Thorac. J.. Glassman. Measurement of flow in single blood vessels including cardiac output by local thermodilution. and Herrera. In W. 1960. D. S. Hamilton (Ed.. Read. D. and Wood. Med. 1963. 1962. 7:399. B. L. Use of sympathomimetic amines in heart failure.. G. V. C. 45:80. 1955. M. Lauson. K. The management of the severely ill patient after open heart surgery. J. 34. 52:777. Amer. R. Durand. R. J. Circulation 26: 174... 1956.. J. A. J. Quantitative radiocardiography: 11... Warden. Amer. Damman. L. Thorac. I. L. J. G. P. 152:162. Physiol. C. W. 41. 49. J . M. J .. and Richards.. Comparison of cardiac output calculation by manual and analogue computer methods. A. (Basel) 18:227. Total body perfusion for open cardiotomy using the bubble oxygenator: Physiologic responses in man. G.. Cournand. Blood level of indocyanine green in the dog during multiple dye curves and its effect on instrument calibration.. Motley. 46. H. Dimensional relationships in dye dilution curves from humans and dogs. Baliff. 1968.CAREY AND HUGHES 30. H. Parker. R. C. Riley. and Nasser. M. Vol. T. Cournand. R. P. J. Proc. H. Washington: American Physiological Society.. R. L... and Guyton. 1967. Donato. Mechanism of decrease in cardiac output caused by opening in the chest.

Hugenholtz. and Hughes. M.). J. 1969 173 . 1967.. Amer.. Res. R.M. Pietras. Stauffer. Goldring. Gorten.. D. Online determination of cardiac output by fiberoptics. 63. 48: 898. S. Proc. A. Applications of ultrasound in cardiology and cardiovascular physiology. Amer. A method for the clinical determination of cardiac output. Leclair. A. I. and Hamilton. W. 10:491.. 21: 1864. Weber. Circ. D. Loeb. R. A small. 202: 1124. 22:362. 1967. M. Kinsman.. Hara. 5:482. Hunton. E. Q. Hepatic removal of indocyanine green. G. Baltimore: Williams & Wilkins. J . 52.. H. J. Physiol. Philadelphia: Saunders. Khalil. Hamilton (Ed. Staf Meet. R. Ter-Pogossian. F. 1968. and Wood. Aortic pulse contour calculation of cardiac output. Gorten. A study of the techniques and sources of error in the clinical application of the external counting method of estimating cardiac output. Kelman. R. 1963. H. N.. Joyner. 71. L.. J. C. J. R. Res.. Res. 1961. Pp. 55. J. 51. H. Surg. P. Hetzel. Studies on the circulation. Measurement of cardiac output by two methods in dogs. Moore. Gunnar. W... F. Holm. Appl. B. C. H. G. Appl. 1929. A p p l . Graves.. Physiol. 89:322.. Handbook of Physiology. B. J. Hemodynamic studies before and after cardioversion. Best and W. N.. 191:87P. Sci. Bollman. On line computation of cardiac output from dye dilution curves. Guyton. Wilson. J. 1966. H. H. D.. M. Circulatory Physiology: Cardiac Output and Its Regulation. Minzel. 299. 67:383. 12:379. Thorac. and Guyton. J.. M. R. Physiol. and Belleville.. J. I n C.. C. and Stauffer.. and Gamble. Thermal dilution technics. 68. S. C. 1962. M. Estimation of cardiac output from first part of arterial dye dilution curves. Ramirez. Vol. Kelman.. Scand.. 1964. Gorten. 1967. L. W. 238:274. W.. I: Injection method: Physical and mathematical considerations. 1967. 70. New technique for determining cardiac output with use of a miniature esophageal scintillation counter. 18:543. I n W.. Physiol. 1958. Acta Chir. Measurement of the Cardiac Output. R.. Polanzi. Section 2: Circulation. T h e influence of artificial ventilation on cardiac output in the anesthetized human. 72. 1959. Kahn. J. J. and Underwood. A.A. 69. and Hoffman. H. 20:1365. 133:62. A. Hamilton. 65. P. R. Ineffectiveness of isoproterenol in shock due to acute myocardial infarction. Physiological Basis of Medical Practice. Reliable extrapolation of indicator dilution curves without replotting. 67. 2. 54. Cardiovasc. Med. B. R. Appl. 59. C.. R. W.). T. S. M. Taylor (Eds. H. and Reid. Klein. A. P. Heart J . J . Cardiovasc. J. K. and Schlobohm. Physiol. J. Errors in the processive of dye dilution curves. J .COLLECTIVE REVIEW: Cardiac Output 50. Circulation 35:55. 58. J. and Prys-Roberts. Gregg. 1967. E. Measurement of cardiac output by thermal dilution and direct Fick methods in dogs. Arner. W. Herd. A. Swan. S. R. M. NO. J. FEB. and Christiansen. Regulation of Pressure and Flow in the Systemic and Pulmonary Circulation. Washington: American Physiological Society. Arellano. W. Circ. H.. 21:1131. D. N. Hamilton. J. 64... Physiol. J.. C. J. C. 551-584. R. 7. 1965.. W. 66. R.. A. and Eichling. 1967. Circ. Hernandez. Mayo Clin. R. F. Circulation 36(Suppl. J ... Appl. J. Hosie. H. and Simon. 56. F. Physiol. Sorenson. J. D.. 1964. 1962. 60. 53. 57. J. E. F. VOL. L. Anesthesiology 29:580. G.. L. Richardson. C.. Dis. 1960. Progr. 13:92. J .. A. 61. J. and Sloan. M. 1966. 11):145. 1966. L. W. 62.A. 1963. and Tobin. lightweight precordial counter for determination of cardiac output. J. H. 1963. 35:752. P. Arterial pressure pulse contours during hemorrhage in anesthetized dogs. Wagner.

L. J.. R. Appl. 87. E. W. Amer. 1967. J.. 86.. Frasher.CAREY AND HUGHES 73. J. Amer. Oriol. Physiol. D. McDonald. Kirkendall.. D. J . Theory and design of an “on-line” cardiac output computer. Med.. M. E. Litwak.. 85. Postoperative care following open heart operations. A. The effect in man of changes in intrathoracic pressure on cardiac output. 1968. A... 88. Appl. Quantitative radiocardiography. Circulation 33:538. D. C. J... E. and Gunther. 77. J. Amer. and Swan. Kuhn. Morgan. A. D. 91.. A.. L. A. R. R. 1962. Keller. Amer. D. using Dow’s formula. B. Cardiol. W. Physiol. Electrical conductivity method for estimating right ventricular output and mathematical model. and Tuttle. Clinical pharmacology of furosemide and ethacrynic acid. J. Lewis. Anthonisen. 22: 147. Circulatory effects of intermittent positive pressure ventilation. N. R. Hyman. Valet. Morse. J. and Pacifico. H. J. H. Circulation 26:761. Med. 1967. Canad. Gadboys. and McGregor. W. K. New Eng. J. A. C.. LeFemine. on cardiac performance in conscious dogs. 1967. 75:589. C. L. E. and Stein. Kloster. L. 79. and McGregor. 1965. H. Goldberg. Heart J. Maronde. B. J. Serial cardiac output and blood volume studies following cardiac valve replacement. Thorac. Cardiol. 52:209... 1963. D. 74. and Sobin. 1967. Amer. J. B. L. W. New Eng. L. Lukban. M. Starr. Oriol. Wintershied. P. Indicator dilution methods in estimation of cardiac output in clinical shock. and renal plasma flow. L. Routine use of controlled ventilation. Slonim. J. Circulation 26: 189. A. Dopamine in the treatment of hypotension and shock. W. Circulation 36(Suppl.. and Harken. Effect of isoproterenol in shock associated with myocardial infarction. ‘74 THE ANNALS OF THORACIC SURGERY . Clin. Amer.. The effects of a narcotic level of carbon dioxide on plasma potassium and respiration of cats. Cardiol. Appl.. C. C. 89.. S. M. Donato.. R. R. L. Wisoff. 111: Results and validation of theory and method.. and Smith. 75. Cardiovasc. 43: 203. 22:588. L.. L. 1968. 82.. 76. 83. Heart J. 56:484. Danzig. Harvey.. H. L. 1968. 80. G. Crawford.. Thorac. 11):192. S. Cardiovasc. Pharmacol. 1966. Support of myocardial performance after open cardiac operations by rate augmentation. W. Noble. H. 1949.. Effect of intracardiac operations upon congestive heart failure and body composition. J. 1962. 23:784. I. M.. 1964. L. Physiol. MacCannell. 22: 183. E. A. Thorac. S. G. J. 275: 1389. 1966. Progressive hepatic and renal failure associated with low cardiac output following open heart surgery. Limitations of indicator dilution methods in estimation of cardiac output in chronic lung disease. 1968... Surg.. A. Effects of dopamine in man: Augmentation of sodium excretion.. 22162. Physiol. MacKay. G. Surg. W. glomerular filtration rate. 75:66. 93. Effect of changes in PaCOz and PaO. 90. A. Meyer. F. and Sakirurai.. S.. M. J. 1966. A. B.. 1967. I.. Surg. and Cudkowicz. Phenomenon of sequestration and desequestration. L. 92. Oriol.. R. Guintini. Mundth. O’Neill. McNay. Invest. and Cournand. Determination of cardiac output.. Litwak. I. 84. B. Goldsmith. W. R. 20:826. H. 1968. M.. R. W. J. A.. Physiol. Cardiovasc.. Kunz. 53:275. D. 1967. J. and Goldberg. and Gadboys. McNay. Northwest Med. 151:469. Bristow. Trenchard. A. J.. Kirklin. 43:1116. J. H.. 1968. 78. C. L. 268: 1377. 67:149. L. D. Homologous blood syndrome during extracorporeal circulation in man: 11. and Austen. I n vitro instability of a commonly used tricarbocyanine dye. C. and Guz. and Mason. S. McCord. and Griswold. M.. 81. Mitchie. M. F. J..

Appl. Fox. Surgery 57:414. E. E. J. Cardiovasc. and O’Connor. 1967. Thompson. 6:142. 1967. Trinkle. Arch. Rushmer.. Res. E. Gott. L. N. 111. H. G. W. 34:570. Amer. F. Roberts. 97... S. W. J... Peretz. Circ. Samet. Validity of indicator dilution determination of cardiac output in patients with aortic regurgitation. Circulation 33:410. Carey. Causes of early postoperative death following cardiac valve replacement.. Cardiovasc. FEB. 7. and Bristow. Sinclair. Philadelphia: Saunders. Bernstein. 113.. S. Thorac. 6): 183. D. and Wood.. H. McGregor. Surg. 104. K. T h e relationship of hypercapnia to ventricular fibrillation. Printen. W. J. Hemodynamic patterns after acute anesthetized and unanesthetized trauma. W.. W.. H. C. P. Samet. 22260. Physiol. Young. 99. 102. and Harris. W. Surg. Oriol. Appl. J .. Electrical calibration for the saline-dilution method for cardiac output. Studies on cardiac arrest. R. March.. C. Geddes. J. A. 1967. H.. Siegal. Reed. Significance of atrial contribution to ventricular filling. Cardiol. H. Physiol. Bernstein.. E. J. K. McIntosh. Reproducibility of results obtained with indicator dilution technique for estimating cardiac output in man. F. McK. R. Eiseman. E. C.. D.. H. Amer. K.. C. and Hoff. S. 1966.. Cardiol. Wiegand... J. C. H. NO. J.. W. Surg.. S. Monson. H. J. 1968. 100. and Gifford. Rapaport. 101.. Sleeper. and MacLean. Spencer. D.. Circ. 1964. Cent. Rastelli.. 1967. Validity of indicator dilution cardiac output determination in patients with mitral regurgitation. B. Assisted circulation for cardiac failure following intracardiac surgery with cardiopulmonary bypass.. P.. VOL. Shoemaker. 1962. R.. Med. 1965. Duff. Surgery 55:299. J. 110... K. 109. Hemodynamic state early after prosthetic replacement of mitral valve. Castillo. and Wood. Efficacy of ethacrynic acid in patients with refractory congestive heart failure resistant to meralluride. and McGregor. Allen. 11:712. and Elston.. Treatment with isoproterenol and metaraminol. 1954. 16:669.. Circulation 35: 1084. 1968. and Dossetor. P. J . 11:803.. N. J. L. H. and Rossi. Sellers.. 49:56... G. 1966. 95. Cardiovascular Dynamics. L. W. W.. J . L.. Physiologic studies upon prolonged cardiopulmonary by-pass with the pump-oxygenator with particular reference to (1) acid base balance (2) siphon caval drainage. W.. I. Weirich. M. Thorac. Use of dichromatic earpiece densitometry for determination of cardiac output. Parmley. Circulation 34:448. 2. J. Res. Use of computer for calculating cardiac output. J . 1967. J. and Levine. D. Circulation 38(Suppl. 28:447. 23:373. H. C. and Castillo.. C. Circulation 34:609. A. I. 54:422.. Paneth. Estimation of left ventricular residual volume in the dog by a thermodilution technique. B. J. Lacticacidosis: A clinically significant aspect of shock. 112. Ass. Res. Apparent dye dilution curves produced by injection of transparent solutions. 105. and Lillehei. Cardiovasc. L. P. K. F. J . Canad. J . M. J. Cardiovasc. and Morrow. 90:673. H. 98. W.. 1969 175 . 1961. Samet. A... M. Clinico-pathologic correlations in 64 patients studied at necropsy. W. C. C.. Influence of hyperventilation on cardiac output and renal blood flow. A. B. and Schenk.. Surg. 15:195. C. McDonald. Sinclair. D. Smith. J. H. Kjartansson. E. R. 1966. Hemodynamic studies in cardiogenic shock. Sonnenblick.. J. Surg. 112a. D. Thorac. Thorac. and Matloff. 96. Smith.. 1968. C. O. W. J. B. W. G. M. Bull. Hemodynamic effects of glucagon after prosthetic valve replacement. 108.. (Chicago) 95:492. Read. D. J. and Kirklin. Delin. 1961. 1967. Pollock.. 1962. 1965. J. Amato. and Bernstein. 107. R. Sutterer. V. W. 103.COLLECTIVE REVIEW:Cardiac Output 94. 1965. C. 106. Sealy.

L. The pathogenesis and treatment of hyponatremia in congestive heart failure. Williams. P. H. and Fine. J . Thorac. A. E. H. and Hugenholtz. 1953. 1967. W. M e d . 1962. 116. 115. R. Wilson. A. H. and Marbach. 22:822. Anesthesiology 26:49.. R. 11):68. The role of computers in medical research. and Wood. J. R. A. Computer-based monitoring of cardiovascular functions in postoperative patients. 1966. B. 176 T H E ANNALS OF THORACIC SURGERY . Circulation 37(Suppl.. 123. 1968. H. Surg. J . Amer. Physiol. C. Borun. Personal communication. J. Wagner. Arch. Fiberoptic-dye dilution method for measurement of cardiac output. Taber. 118. M. Pp. Circulation 37:694.. 117. J. Barr.. P. 21 :695. Gamble. A p p l . Milde. 127. Anesthesiology 27:778. F. J. 25:558. Theye.. and Wood. M. 1966. B. 196: 944. Wade. APPI. G. P.. Surg. 1963. H. Repeating dispenser for calibration of dye-dilution curves. 24. E.. H. 120. R. Warner. 1-50. 46: 57.. Erythrocyte volumes after perfusion with homologous blood. R. C. Morales. J . 4: 12. C. J.. Physiol. 1965.: Blackwell. W. G. R. Quantitation of beat-to-beat changes in stroke volume from the aortic pulse contour in man. Theye.. 125. L. Oxford.. R. J. F. Eng. 119.. Sept. A. and Hanenson.. Theye. J.CAREY AND HUGHES 114. Theye.. (Chicago) 91:92. Effect of hypocapnia on cardiac output during anesthesia.. E. 121. R. J. J. H. 5:495. A. Connolly. Rational approach to management of clinical shock. Cardiac Output and Regional Blood Flow. Tomkins. 126. Warner. 124. 1966. H. Swan. Gardner. G. A. G. 1968. and Bishop. 122. Comparison with the direct Fick and angiocardiographic methods. N. Surg. P. R.. R.. Weil. D. R. Physiol. and Toronto. A p p l . Albers... E. R. J. Ann. H.. and Tuohy. T h e value of venous oxygen levels during general anesthesia.A. 1968. Cardiovasc. Thorac. 1965.A. A method for the calculation of the areas under dye-dilution curves. D. M.. Myocardial necrosis and the postoperative low cardiac output syndrome. 1967.. 0. and Kirklin. W. Grossman. H.. R. E.M. Weston. J. O’Donovan. and Michenfelder. Warner. 1958. J. R. J. E.