Indicator Dilution

Indicator Dilution Methods of Measuring Cardiac Output

Theoretically, the simplest method is to add the indicator substance at a known concentration and constant rate into the flow and to measure its concentration downstream. Providing that perfect mixing has occurred, the dilution factor gives the ratio of the two flows in the steady state. Stewart (1897), who was the first to use this principle for measuring cardiac output, infused sodium chloride over 10-15 s and measured the change in electrical resistance of the blood. When this had fallen to a steady level during the constant infusion he withdrew a blood sample and derived the dilution factor.

A more practical method is to add the indicator as a bolus and to measure the concentration time profile of the passage of this bolus at a point downstream. Typically the concentration rises to a rounded peak and falls away more slowly as the remaining indicator is washed out. Such a curve may be considered as a large number of elements of sufficiently short time duration that for each element the flow and concentration are effectively constant. The concentration of the marker multiplied by the flow and the time duration of each element gives the quantity of marker passed by that element. The sum of these quantities should therefore equal the total quantity of indicator added as the bolus. If the flow is constant for the duration of the curve, i.e. is the same for each of the elements, it may be calculated simply as the quantity of indicator injected divided by the total area under the dilution curve. The shape of the curve is unimportant providing that the total area can be found.
The bolus injection method of measuring cardiac output was first described by
Henriques (1913), who injected sodium thiocyanate and then withdrew arterial blood samples at 1 s intervals for in vitro colorimetric analysis using ferrous chloride. He identified the problem of the indicator starting to recirculate before the first pass was complete. See also Henriques - further details. White (1947) derived cardiac output from continuously recorded curves and the method was developed by Hamilton et al. (1932) and others for use in man.

Many different indicators have been tried but the most successful has been indocyanine green whose concentration curve can be measured in blood by light absorption. Like the Fick method, it is accurate but difficult to carry out. The densitometer, which measures indocyanine green concentration, has to be calibrated with samples of the individual patient's blood containing known concentrations of indocyanine green. This is time consuming. Other disadvantages are that the dye is very expensive, and if used repeatedly makes the patient green. A new variant of this method is that of pulse dye densitometry. Based on the principle of pulse oximetry, a photodetector is used to record the indocyanine green curve non-invasively. Imai et al (1997) found a considerable degree of error in some patients and that the agreement with thermodilution was less good at low cardiac outputs. Thermodilution, in which cold fluid (or sometimes heat) is injected, is now the most commonly used method.


Fegler first described the use of thermodilution for measuring cardiac output (Fegler, 1954). This method was then adapted for use in man by Branthwaite and Bradley (1968) at St. Thomas' Hospital and the method developed further by Ganz et al (1971) and others. There is now a huge literature on this subject. There are three slightly different thermodilution methods in clinical use, all of which use a thermal indicator (cold or heat) injected into the right side of the heart and detected either in the pulmonary arterial or arterial blood. By far the commonest clinical method of measuring cardiac output is by thermodilution using a Swan-Ganz catheter.

Cold thermodilution using a Swan-Ganz catheter

A Swan-Ganz catheter is inserted via a central vein (usually the internal jugular or subclavian) through the right atrium and ventricle so that its tip lies in a branch of the pulmonary artery. Cold dextrose is injected rapidly via one port of the catheter which ends at a side hole in the right atrium. The cold dextrose mixes with the blood in the right atrium and ventricle before passing into the pulmonary artery where the fall in temperature is sensed by a thermistor on the side of the catheter. Cardiac output is then calculated from the temperature-time curve. The usual clinical practice is to perform three or more measurements in rapid succession and to take the average of those which agree closely. For an excellent review of pulmonary artery catheterization see Gomez and Palazzo 1998.


It has been shown that there is usually good agreement between cardiac output measured by this method and cardiac output measured by Fick or indocyanine green. The method can be repeated many times at short intervals subject to avoiding excessive fluid loading. The Swan-Ganz catheter can also be used for measuring pulmonary artery pressures and (if fitted with an oximeter) mixed venous oxygen saturation.


There are occasions when thermodilution cardiac output is likely to be inaccurate (Fischer et al., 1978; Heerdt et al., 1992; Nishikawa and Dohi, 1993), but the main disadvantages are the catheter-associated morbidity and mortality. It has not been shown that the outcome in terms of patient survival is improved as a result of therapeutic intervention undertaken on the basis of information obtained from Swan-Ganz catheters. Connors et al., 1996 found that the mortality of 2184 intensive care patients who had Swan-Ganz catheters inserted was 24% greater than that of a group, matched for severity of illness, who did not. It was not clear from this study whether the excess mortality was due to complications directly attributable to the catheters or to an adverse response to treatment initiated on the basis of measurements made using the catheters. In an accompanying editorial, Dalen and Bone (1996) recommended that the FDA should issue a moratorium on the use of Swan-Ganz catheters unless an appropriately designed randomized controlled clinical trial is immediately undertaken. In a more recent study (Murdoch et al., 2000) of 4132 intensive care patients, 44% of whom had pulmonary artery catheters, the authors demonstrated no beneficial effect of pulmonary artery catheters but concluded that they did not cause an increase in mortality. Numerous complications resulting from Swan-Ganz catheters have been described (Buchbinder and Ganz, 1976; Barash et al., 1981; Boyd et al., 1983; Durand et al., 1995; Eidelmann et al., 1994; Horst et al., 1984; Gore et al., 1987; Kinirons and MacSullivan, 1996; Robin, 1985,1987,1988; Sykes, 1992; van Doorn et al., 1994 ). These include damage to the carotid and subclavian arteries, pneumothorax, dysrrhythmias including ventricular fibrillation, perforation of the atrium or ventricle, tamponade, damage to the tricuspid and pulmonary valves, knotting of the catheter, catheter transection and endocarditis.

Warm thermodilution using a Swan-Ganz catheter

This is a variant of thermodilution in which heat is introduced into the blood in the right ventricle, by passing a current through a heating coil wrapped around this part of the catheter (Yelderman et al.,1992,1992; Haller et al., 1995; Jakobsen et al., 1995; Lefrant et al., 1995). The rise in temperature which can safely be produced is very small and therefore a random series of pulses of heat is given and signal analysis used to derive the mean thermodilution curve (Yelderman, 1990). The advantage of this method over cold thermodilution is that since no fluid is injected the heat pulses can be continued indefinitely and repeated estimates of cardiac output obtained at intervals of a few minutes. Infusion of cold fluids will of course interfere with this method, but the main drawback is the need for an adapted Swan-Ganz catheter, which is bigger and stiffer than the normal Swan-Ganz catheter, and its attendant risks.

Transpulmonary Thermodilution

It is possible to inject the cold indicator on the right side of the heart and measure the fall in temperature this produces in the blood in the aorta and so derive cardiac output from this 'transpulmonary thermodilution' curve. First described by Fegler, this method is sometimes used in children too small for insertion of a Swan-Ganz catheter. A fine thermistor is inserted into the aorta via a femoral artery. The agreement with Fick and indocyanine green is generally good although experience with this device is at present limited. This method is also used in the Pulsion PiCCO system to provide calibration for the pulse contour analysis method.