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
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.

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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 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.
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.

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
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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 timeconsuming 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: 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. 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.=Fx

Zmg.

C(t)dt or F =

(4)

C(t)dt
0

In the absence of recirculation, 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. 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.
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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. T h e 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. T h e 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 typical 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).
T h e 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]. T h e theory and application have been reviewed by Hosie [641, Hamilton [58], and Burton
[16]. 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, 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]. Pathological 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-taggedalbumin, because Calibration 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-taggedalbumin 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.
T h e 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 positioned over the precordium. T h e 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. 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 3.2% 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].
T h e 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. However, 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.
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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, since this is the
method most frequently used at the present time. However, much of
the discussion also pertains to other indicator-dilution methods.
T h e recording apparatus for the dye-dilution curve includes a dye
densitometer and an amplifier-recorder system. Arterial blood is withdrawn at a constant rate (usually 20 to 40 cc. per minute) through a
cuvette in the densitometer. 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,
Moore, and Hamilton [72]. 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). Cardiac output is then obtained from formula 4.
T h e following aspects of this technique should be noted.
Sites of Injection and Sampling. T h e 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. T h e dilution of the dye in the large
left atrium results in a much lower peak concentration and a non-

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.
Recording Apparatus. T h e length and diameter of the catheter
connecting the sampling site to the densitometer should be kept minimal, 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.
Calculation and Calibration. T h e Stewart-Hamilton method for
determining the area under the dye curve utilizes the trapezoidal rule,
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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. T h e 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 nomogram 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 + l o % 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. T h e 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 calibrated, the computer will give a direct readout of cardiac output. T h e
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 timesharing 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
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deflection. Formula 4 is rewritten, including a factor of 60 to correct

for seconds to minutes:
F (litersimin.) =

60 sec./min. x I mg.

(5)

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

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. T h e 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. T h e 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 dyedilution 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]. T h e 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 .
T h e 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 thinwall 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. 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. 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.

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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 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%),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. T h e 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 correlated 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 1125as 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. T h e 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. T h e
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
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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.
T h e 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 indicatordilution 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). T h e 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 technician 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. T h e 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 sensitive 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
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event that blood flow appears effective as judged by other studies [1151.
T h e 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. T h e 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. T h e
convenience and expense of the method must therefore be a consideration. Outside of the well-equipped shock unit, the indicator-dilution
method has not achieved a place in routine monitoring, for obvious
reasons. T h e 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 C A R D I A C 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. T h e mean of a large number of reVOL.

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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 [ZO,
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 findings suggest that when congestive heart failure is present preoperatively,
cardiac output is likely to be decreased for the first few days after corrective 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 acidbase 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. However, since determination of cardiac output in low flow states is frequently in error [93], these values are of questionable accuracy. It is
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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.
T h e 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].
T h e 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, presumably 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 circulating 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]. T h e use of
ethacrynic acid markedly improved cardiac function in patients with
congestive heart failure refractory to other diuretics [ 1071. T h e 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 pharmacological assistance is required. Digitalis preparations must be used cautiously 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. LOWcardiac 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
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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 pulsecontour 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
offersinstantaneous 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 effectivenessof 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. T h e
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. T h e dosage of isoproterenol should be kept below 2 pg. per minute to avoid tachycardia and systemic vasodilatation.
T h e 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.
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