Accuracy of Cardiac Output Computers - NCBI

Accuracy of Cardiac Output Computers JOSEPH S. CAREY,* M.D., HERBERT WILLIAMSON, *" CALVIN R. ScoTr,* * B.S. From the Thoracic Surgical Research Laboratory, Wadsworth Hospital, Veterans Administration Center, Los Angeles, California, and the Department of Surgery, UCLA Schoool of Medicine, Los Angeles, California

THE application of computer technology to clinical medicine has led to the development of several new technics for the estimation of cardiac output. These include pulse contour analysis 9 and on-line computation of dye-dilution curves.6 Pulse contour analysis offers the great advantage of providing results in essentially "real-time," but it requires assumptions concerning the distensibility of the systemic arterial tree, which might itself vary with certain therapeutic interventions. The dye-dilution technic has become the standard by which other methods are measured, because of its well-established applicability to the nonsteady state of acute disease. Previous investigations have studied the accuracy of consecutive or paired determinations by this technic.8 Calculation of the same dye curve by various methods has also been reported.' The present study was designed to evaluate the performance of various dye-dilution recording systems, particularly two commercially available cardiac output "computers." These "computers" were intended for bedside use, but little data exist concerning accuracy of applicability to acutely ill patients.5 7 In anesthetized dogs, the same injection of dye was simultaneously recorded by a "cardiac output computer" (Lexington Instruments, Waltham, Mass.), a "cardioSubmitted for publication October 5, 1970 'Veterans Administration Center and UCLA School of Medicine, Los Angeles. " Veterans Administration Center, Los Angeles.

762

densitometer" (Beckman Instruments, Palo Alto, Calif.), and a standard logarthmic replotting technic. In additional studies, the Lexington computer was tested by coupling it to an electronic system which simulated a curve with a known true value. The Beckman cardiodensitometer was further evaluated in a model circulatory system with a known flow. In all studies, the standard replotting technic, using the Gilford densitometer with a photographic recorder, was used as the point of reference for other methods. Methods Instrumentation and Calculations Lexington Computer. This is an analog computer which has two basic functions: 1) integration of the signal from the densitometer, which continously sums the area under the dye curve, and 2) prediction of the area under the downslope portion of the curve. At any point in time during the exponential decay portion of the curve, the output of the computer gives a constant number which is the sum of the area under the previously integrated portion of the curve plus the predicted area under the remainder of the curve. This is possible because as the downslope progressess, the previously recorded area increases while the predicted area decreases by an equal amount. When the densitometer-computer system has been previously calibrated to a known flow, cardiac output may be readily determined by recording the magnitude of the computer output from the dye curve

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ACCURACY OF CARDIAC OUTPUT COMPUTERS

and comparing it to that of the known flow. Calibration is accomplished by drawing non dye-bearing blood through the densitometer and setting the computer meter and recorder to zero. A single dye-bearing sample of blood, which is proportional to a known cardiac output, is then drawn through the densitometer. The computer meter is set to the known flow and the deflection noted on the recorder. Multiple sample calibration may be performed by recording the computer deflections for several known concentrations of dye in blood. A calibration curve may then be drawn. The Lexington computer is a calculating instrument only. It requires a densitometer, recorder, and withdrawal pump to complete the apparatus necessary to measure cardiac output. In these studies, Gilford densitometers and withdrawal pumps (Gilford Instrument Laboratories, Oberlin, Ohio) and an Electronics for Medicine photographic recorder (Electronics for Medicine Co., White Plains, N. Y.) were used. Cardiodensitometer. This instrument is a self-contained apparatus for the determination of cardiac output, requiring only a withdrawal pump. Blood is drawn through a disposable couvette, and the dye curve is recorded on a direct-writing strip chart on top of the instrument. An integrating circuit continously records the area under the curve. The area under the downslope is estimated by assuming a proportionality constant between the area under two chosen points on the exponential part of the downslope and the area under the remaining portion which would be recorded in the absence of recirculation. A three-point calibration procedure is performed with three known dye-bearing samples of blood. Standard Replot. All dye curves recorded from the Gilford or Beckman densitometers were manually marked at 0.5 second intervals to a point on the down-

763 slope just prior to the recirculation phase. The area under the curve was calculated off-line by a digital computer which estimated the area under the curve by a similar process as the Lexington computer, using the manually digitized points instead of the analog signal. A three-point calibration procedure was used, and cardiac output was calculated from the standard Stewart-Hamilton equation.

Experimental Procedure Mongrel dogs weighing between 15 and 23 Kg. were anesthetized with sodium pentobarbital. Ventilation was controlled by an intratracheal tube and a Harvard respirator. Two equal length polyethylene catheters were placed in the abdominal aorta through the femoral arteries. Another catheter was passed into the superior vena cava through the external jugular vein. Indocyanine green (3 mg.) was injected into the superior vena cava followed by a 5 ml. saline flush. Using separate pumps set to withdraw blood at identical rates (40 ml./min.), the arterial dye concentration was simultaneously sampled by two densitometers. The output of the densitometers was recorded by the computer, the cardio-densitometer and by the EM recorder. In each experiment, three curves were rapidly recorded using the Gilford and Beckman densitometers, with the computer coupled to the Gilford. Calibration was then performed by drawing three dyebearing samples simultaneously through each recording system. In some experiments, the computer was coupled to the Beckman densitometer and three additional curves were recorded, followed by another calibration procedure. In other experiments, a similar procedure was followed using two Gilford densitometers. Simulated Curves Dye dilution curves

were simulated on analog computer (Electronics Associates Inc., Model TR 20). An electrical cir-

an

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CAREY, WILLIAMSON AND SCOTT

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Results Lexington Computer. The Lexington

STANDARD REPLOT L/min

FIG. 1. Simultaneous calculation of the output of a Gilford densitometer by Lexington computer and standard replotting technics (anesthetized dogs). Single point calibration was used.

cuit capable of generating

a reproducible or without a

"dye-dilution curve," with "recirculation" phase was used. Rise and fall times of the artificial curve could be varied, and a calibration signal was incorporated into the circuit. The area under the curve was calculated simultaneously by the Lexington computer and by an integrator. The output of the integrator was measured with a digital voltmeter. From the reading of the voltmeter, the true value of the generated curve was determined (in the absence of recirculation). The error of the integrator system in repeated measurements was less than 1%o. Using this reproducible artificial curve, the Lexington calculation was compared to the standard replot (manual digitizing) technic for curves varying between 2.0 and 5.2 liters per minute. A model circulatory system was used to test the Gilford and Beckman densitometers against a known flow. In this system, dye was injected upstream from a pump and mixing chamber, and sampled downstream from the mixing chamber. The system was primed with 2,000 ml. of dog or human blood and flow was varied between 2.0 and 4.5 liters per minute. Because dye accumulated in this in vitro system, a maximum of six cardiac output curves were recorded in each experiment.

computer was calibrated (as recommended by the manufacturer) with a single dye-inblood sample. The results of multiple determinations (using the Gilford densitometer) are plotted against the standard replot of the same curve in Figure 1. A random, wide distribution (standard deviation of the per cent error 21.3%o) was observed. When the same curves were corrected to three-point calibration (Fig. 2), using three dye-in-blood mixtures and drawing a calibration curve, the results improved (standard deviation 9.3%o), but a net positive error was observed (+11%o). When the Lexington was used with the Beckman densitometer (Fig. 3) a random distribution of per cent difference was observed, and the standard deviation of the difference was 8.0%o. The necessity for using three-point calibration is illustrated in Figure 4. In Figure 4a, the calibration curve is linear and passes through zero. The use of any point on the curve, referenced to zero, will give the same slope in millimeters of deflection per milligram per liter as will the use of all three sample points. If the curve does not pass through zero, the use of any one 5.0

PERCENT ERROR -10 TO +29 (SD 9.3%)

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calibration.

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ACCURACY OF CARDIAC OUTPUT COMPUTERS

point on the curve, referenced to zero, will result in a different slope than that of the curve. When the calibration curve passes above zero (Fig. 4b) the calibration factor will be overestimated and cardiac output will be overestimated. When the curve passes below zero, the reverse occurs. These factors account for the improved results noted when three-point calibration was used. The Lexington computer accurately calculated the electronically simulated curves (Fig. 5). The scatter about the line of identity was random, and the standard deviation of the difference was 3.5%. The results obtained by standard replot were also consistent, but a slight net positive error was noted (+6.7%). Beckman Cardiodensitometer. When the same curve was recorded by the Beckman and Gilford systems, nearly all values obtained by the Beckman were lower than those of the Gilford (Fig. 6). Similar results were found in the model circulatory system (Fig. 7), where values ranging from -6 to -37% (mean -22%) of true flow were recorded with the Beckman. The slope of the individual studies was similar to true flow, however, indicating that individual variations were accurately represented. Gilford System. Two identical Gilford densitometers were used to record the same curve on the same recorder (Fig. 8). A random scatter about the line of identity was observed (range of differences -20 to +15%). In the model circulatory system (Fig. 9), the Gilford system also showed random scatter (range of difference -20 to +19%), and the individual studies showed a similar slope as that of the true flow, again indicating that flow variations were accurately represented.

Discussion Performance of Lexington Computer. The accuracy of this instrument, like that of all computers, is a function of its input.

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765

PERCENT ERROR -16 TO +19 (SD 8.0%)

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case, the dye-dilution be no more accurate than the information produced by the photodensitometer and its calibration. The data from in vivo studies reveal that a nonlinear densitometer introduces a systematic error into the single-point calibration technic. This negates the possibility of direct readout by this type of cardiac output computer since the readout meter can only be calibrated to one known flow. If the densitometer is known to be consistently linear, direct readout may be possible. In most cases, however, a three-point calibration curve would be preferable. The data from the electronically simulated curves indicate that the cardiac out-

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information. The inherent variability of dye-dilution curves, however, underscores the need for built-in data checks when performing in vivo measurements. Thus the time saved in calculation is lost when it is necessary to use triplepoint calibration, to control baseline recorder drift, and to compensate for background dye concentration. The results of in vivo studies reported here are similar to those reported by others. Delby and associates,8 using a Sanborn cardiac output computer and Waters denreceives

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CAREY, WILLIAMSON AND SCOTT

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Fic. 4. Calibration curves using three samples of dye-in-blood mixtures. Lower curve fails to pass through zero. Thus, the use of zero + one calibration point will introduce a positive or negative error into the calibration factor, depending on whether the true curve passes above or below zero. Such errors caused the wide scatter of results seen in Figure 1.

sitometer, reported a per cent error of 8.9%o (S.D.) when computer results were compared to a planimeter method. Sinclair and associates,7 using a Lexington computer and Gilford densitometer, reported per cent differences ranging between -19.0 and +11.7%. Neither in their data, nor in that of Glassman and associates,5 who also used the Lexington computer, was there evidence of the net positive error found in the present experiments. Benchimol and

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associates,. however, also reported a net positive error (+8%) when computer calculations were compared to standard replotting. Several methods have been devised for calculating the area under the indicator dilution curve which do not require logarithmic replotting. Williams and associates 10 reported an arithmetic method which was quite accurate (standard deviation of the difference 1.4%) when compared to the standard replotting technic. A nomogram devised by Cohn and Del Guercio 2 also compared favorably to standard replotting (mean difference 2.4%). These methods are less complicated and apparently more accurate than computer technic. Beckman Cardiodensitometer. This instrument simplifies considerably the technical aspects of performing cardiac output by the dye dilution technic. All the necessary equipment, except a withdrawal pump, is provided. Calculation is rapidly performed, since the area under the curve is determined by an integrator. Estimates of the downslope area by the ratio method proved to be very accurate in these studies as compared to standard replotting methods (correlation coefficient 0.99). The results, however appear to show a systemati-

KNOWN FLOW

Fic. 5. Calculation of electronically simulated curves having a "known flow" by Lexington computer and standard replotting technics. Per cent error = mean + standard deviation.

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ACCURACY OF CARDIAC OUTPUT COMPUTERS

-

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PERCENT ERROR -20 TO +15 (SD 10.5%)

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FIG. 8. Simultaneous recording of dye curve by identical Gilford densitometers, using standard

from Gilford and Beckman densitometers, using standard replotting technic (anesthetized dogs).

replotting technic (anesthetized dogs).

cally negative error when compared to those obtained by the Gilford system, in both the animal studies and in the model circulatory system. This error may be related to the hydraulic characteristics of the couvette used in this instrument. Dynamic changes in dye concentration during the recording of the curve may not be accurately reflected by this particular couvette. This problem was discussed by Fox and associates,4 who originally developed indocyanine green for use in the performance of dye dilution curves. The recorder included in the Beckman cardiodensitometer was apparently not at fault. In the stud-

simultaneously recorded by another (EM) recorder, and there was no significant difference between the two resulting calculations. Accuracy of Dye-dilution Cardiac Output Determinations. Direct comparison between two Gilford densitometers sampling simultaneously from different arterial sites produced an 8% error (standard deviation of the per cent difference) in these studies. Slightly better results were reported by Sleeper and associates 8 who used carefully matched Gilford densitometers and an Electronics for Medicine recorder. In their

ies shown in Figure 3, the Beckman

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PERCENT

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19715 Ann. Surg. 174Nov.No. CAREY, WILLIAMSON AND SCOTTCAE,Vol.

studies, two densitometers sampling from the same site resulted in a 6% error (two standard deviations of the per cent difference). Benchimol and associates 1 noted that simply replotting the same curve could produce a variation of up to 16%. Because of this variability, many investigators believe that computer calculation offers no significant advantage to the method.6' 10 The present studies support this conclusion. These studies indicate that instrumentation currently available for determining cardiac output by the dye-dilution technic may produce errors which are not indicated by their manufacturers. Cardiac output "computers" may produce accurate results only when great care is exercised and potential technical problems are recognized and controlled. Better quality control is necessary for instrumentation which is intended for use in seriously ill patients. The dye-dilution technic is relatively cumbersome and in general is rather inaccurate. Better methods are required to answer the need for cardiovascular monitoring of the acutely ill patient. In the light of the present studies, simpler technics should be considered,^ such as the pulse contour method, which may be at least as accurate as the dye-dilution method.

than simple arithmetic methods, and a net positive error (+ 11%) was evident. The Beckman cardiodensitometer was simple to use and showed reproducible results, but a net negative error (-22%) was apparent. These studies suggest a need for better quality control and improved methodology in instrumentation intended for the cardiovascular monitoring of acutely- ill patients. Acknowledgments

Summary The accuracy of two commercially available cardiac output computers was evaluated by recording simultaneously a single dye injection in anesthetized dogs or in a model circulatory system, and by the use of an electronically simulated "dye-curve." The Lexington computer accurately calculated simulated curves, but required threepoint calibration for in vivo studies. Direct comparison of computer calculation to standard 'methods showed less accuracy

ods. Cir. Res., 1:287, 1967. 6. Hara, H. H. and Belleville, J. W.: On Line Computation of Cardiac Output from Dye Dilution Curves. Circ. Res., 12:379, 1963. 7. Sinclair, S., Duff, J. H. and MacLean, L. D.: Use of Computers for Calculating Cardiac Output. Surgery, 57:414, 1965. 8. Sleeper, J. C., Thompson, H. K., McIntosh, H. D. and Elston, R. C.: Reproducibility of

The authors appreciate the assistance of Emi Nakamura and Erich Pfeiffer, Ph.D., of the Veterans Administration Western Research Support Center, Sepulveda, California, in the performance of this study.

References 1. Benchimol, A., Akre, P. R. and Dimond, E. G.: Clinical Experience with the Use of Computers for Calculation of Cardiac Output. Amer. J. Cardiol., 15:213, 1965. 2. Cohn, J. D. and Del Guercio, L. R. M.: Nomogram for the Rapid Calculation of Cardiac Output at the Bedside. Ann. Surg., 164:109, 1966. 3. Dalby, L., McDonald, R. and Sloman, G.: A Comparison of Computer and Planimetry Cardiac Output Determinations. Med. J. Aust., 2:1255, 1967. 4. Fox, I. J., Sutterer, W. F. and Wood, E. H.: Dynamic Response Characteristics of Systems for Continuous Recording of Concentration Changes in a Flowing Liquid (for

example, indicator-dilution curves). J. Appl. Physiol., 11:390, 1957. 5. Glassman, E., Baliff, R. and Herrera, C.: Comparison of Cardiac Output Calculation by Manual and Analogue Computer Meth-

Results Obtained with Indicator Dilution Technique for Estimating Cardiac Output in Man. Circ. Res., 11:712, 1962. 9. Warner, H. R.: The Role of Computers in Medical Research. JAMA, 166:944, 1966. 10. Williams, J. C. P., O'Donovan, P. B. and Wood, E. H.: A Method for the Calculation of the Areas under Dye-dilution Curves. J. Appl. Physiol., 21:695, 1966.