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Comparison of impedance cardiography with indirect fick (CO2) method of measuring cardiac output in healthy children during exercise
hy Comparison of Impedance Cardiogra With Indirect Fwk (CO,) Method o 5 Cardiac Output in Healthy Measurin Chi f dren During Exercise Paul Pianosi,
MD, and Daniel
Garros,
MD
Electric bioimpedance has been used to measure cardiac output for decades. Improvements in modeling and microprocessor technology have spawned newer generations of such devices. This method would be especially useful in children, in whom the use of invasive methods is limited. We tested a device (ICG-M401, ASK ltd.) in 30 healthy children at 2 levels of exercise (0.5 and 1.5 W/kg), and compared impedance measurements of cardiac output (a,,) with carbon dioxide (CO,) rebreathing measurements of cardiac output (a,). The Q,co-oxygen uptake (VOZ) relation was expressed by &o = 3.8 + 4.6 VO2; r2 = 0.68. Mean + SD bias (Q,(;1Rs)was 0.14 -+ 1.05 L/min, not significantly different
from zero (95% confidence intenal -0.12 to + 0.44 11 min). All Qlc~ results were within ? 15% of the hypothetical mean value (Bland and Altman analysis). The largest deviation of QlcG from Qm was +30%, found in 1 of 57 paired determinations. Eighty percent of QKC values were within 220% of the QRs result. We conclude that impedance cardiography with the ICG-MI01 provided realistic and reliable estimates of cardiac output in healthy children during exercise. This, along with ik ease of operation and utility at rest and during exercise, make it both useful and attractive for clinic and research purposes. (Am J Cardiol 1996;77:745-749)
totally noninvasive technique for measuring cardiac output (Q) that does not require a great A deal of skill to perform, that can be done inexpen-
hospital personnel for this study (Table I). Participants and their parents signed informed consent. This study had received approval from the University of Manitoba Faculty of Medicine Committee for Use of Human Subjects in Research. Exercise protocol: Exercise was performed on an electrically braked cycle ergometer (Excalibur, Quinton Instruments, Seattle, Washington) at 2 work rates: 0.5 and 1.5 W/kg, chosen to span the range of work intensities from light to moderately heavy exercise. Subjects pedaled for 4 minutes before gas exchange measurements commenced, starting with blood gas sampling, followed by mixed expired gas collection for 2 minutes, and ending with duplicate CO1 rebreathing maneuvers. Total duration of work at each load was approximately 8 minutes. Apparatus: Expired ventilation was measured on a spirometer (Transferscreen II, Erich Jaeger Co., Wurzburg, Germany) equipped with a heated pneumotachograph, calibrated before and after tests by using a volumetric syringe. Mixed expired gases were collected in 60 L gas-collection bags and analyzed with zirconium oxide oxygen (0,) and infrared CO* analyzers (S-3A/l, CD-3A, respectively, Ametek Inc., Pittsburgh, Pennsylvania). End tidal CO;?could also be sampled at the mouth at a flow rate of 400 ml/min. Analyzers were calibrated with reference gases (room air [5% CO,, 15% 02, balance, nitrogen gas ( N2)] and 13% C02, balance 02) before and after testing. All signals were recorded in real time on a Gould thermal strip-chart recorder (TA2000, Cleveland, Ohio).
sively at the bedside or in the laboratory, repeatedly, and that doesn’t perturb the measured variable(s) , would be an invaluable asset in pediatric research and clinical medicine. Thoracic electric bioimpedante cardiography (ICG) offers such a technique.lm3 Different devices operating on this principle have been tested against “gold standard” methods of measuring cardiac output, with many reports affirming its utility,4-10 but some reports suggesting ICG output measurements were neither accurate nor reliable.1’-‘5 It is apparent from these studies that not all impedance devices performed alike. Some investigators found that ensemble averaging of the first time derivative of thoracic impedance improved accuracy.4-6 We tested a new device (ICG-M401, ASK Ltd., Budapest, Hungary) in healthy children during exercise by comparing im edance versus carbon dioxide (CO*) rebreathing ’ r measurements of cardiac output. We also examined the effects of hemoglobin concentration l7 and thoracic configuration I4 on the ICG measurement of Q.
METHODS Subjects:Thirty healthy children with normal spirometry were recruited from families and friends of From the Department of Pediatrics and Child Health, Children’s Hosof Medicine, University of Manitoba, pital of Winnipeg, and Facul Winnipeg, Canada. This stu fi’y was funded by a grant from the Children’s Hospital of Winnipeg Research Foundation and the Manitoba Medical Services Foundation. Manuscript received September 22, 1995; revised manuscript received November 14, 1995, and accepted November 15. Address for reprints: Paul Pianosi, MD, CN-503, Children’s Hospital, 840 Sherbrook Street, Winnipeg, MB, Canada, R3A 1 S 1
METHODS/IMPEDANCE
Measurement of cardiac output by carbon dioxide rebreathing: Arterialized capillary blood was obtained
from a finger warmed by wrapping in a heating pad. Samples were stored on ice, and analyzed within 20 CARDIOGRAPHY
IN EXERCISING
HEALTHY
CHllDREN
745
TABLE I Cardiac CO2 Rebreathing,
Output (L/min) by Impedance Cardiography Together With VOn at 0.5 and 1.5 W/kg
Variable VO:, (L/min) CO? rebreathing Electrical impedance Dye dilution* * Reference and
1.09
Values
data from Eriksson
L/min
in pubertal
are expressed
CO2 = carbon
dioxide;
and
0.5 W/kg
1.5 W/kg
0.64 it 0.21 6.49 + 1.64 6.68 -c 1.51 7.7 + 1 .o
1.21 + 0.45
et cP’ obtained
9.142 2.53 9.23 k 2.49 9.3 c 1.4 by dye dilution
at VO? 0.71
boys.
as mean
2 SD.
VO? = oxygen
uptake.
processed FIGURE 1. lbration of gmphii output of wodorms Ltd., Budapest, Hungary). The upper buce is the ektrocardiimm from the top is the first time derivative (dZ/dt), third tmce is the (PCG), and the lower trace is the merit value of dZ/dt is shown for 2 (2.21 and vertical lines are used to compute the (vet), and the qs2 interval, with
corrected mixed venous CO2 partial pressures I6 were converted to contents,” assuming a saturation of 97%. Impedance cardiography The ICG-M401 uses a tetrapolar lead system with paired inner electrodes placed on either side in the supraclavicular fossa just above the level of the suprasternal notch, and along the midaxillary line at the level of the xiphoid. The outer electrodes are placed 6 cm ce halad and caudad, respectively. Pregelled Red Dot%A(3M Co., St. Paul, Minnesota) was used for this purpose, and applied after the skin had been gently abraded with fine sandpaper and swabbed with alcohol. Leads for the electrocardiogram were placed on the right and left pectoral areas and on the right and left lower quadrants of the abdomen. The lead (I, II, or III) that gave the best definition of the QRS complex was used for computation purposes by the software program. Finally, the phonocardiogram was recorded by a proprietary microphone attached with double-sided adhesive placed along the left sternal border at a site where the second heart sound was loudest. We made our impedance measurements during free breathing due to difficulty in having children hold their breath on exercise, an approach justified by work done in adults. Sample waveforms processed by the device are shown in Figure 1. The software program used a by the ICG-MO1 (ASK modification of the Kubicek equa(ECG), second truce tion, based on empiric corrections phonocard’ for body habitus derived from
minutes on a Radiometer ABLSOO blood gas analyzer to measure pH and partial pressure of arterial COa. Hemoglobin (g/L) was also measured from these samples on a Radiometer Hemoximeter (OSM 3, Copenhagen, Denmark). The rebreathing bag was filled with an appropriate mixture of CO2 ( 10% to 15%) in 02, with the volume of the rebreathing mixture approximating the subject’s vital capacity. The subject was instructed to take 3 to 4 rapid, deep breaths, and then continue normal breathing pattern for approximately 15 seconds. End tidal CO* was continuously sampled at the mouth and the analog signal recorded on paper at 10 mm/s to capture a plateau in the CO2 concentration. This maneuver was attempted in duplicate with rl minute between each, and if both trials resulted in an equilibrium plateau, the mean mixed venous CO* partial pressure was used. Values for arterial and downstream 746
THE AMERICAN JOURNAL OF CARDIOLOGY”
VOL. 77
preliminary
studies that compared
impedance with direct Fick measurements of cardiac output in adults: SV = r($)(VET)(s) where SV = stroke volume (ml), r = blood resistivity (assumed constant at 135 R/cm), L = distance between inner electrodes (measured), Z, = baseline thoracic impedance (0)) VET = ventricular ejection time (seconds), and dZ/dt = maximal value of first time derivative of impedance. The 3 types of body habitus were ectomorph, mesomorph, and endomorph, which we defined for use in children as percent ideal weight for height <85%, 85% to 120%, and > 120%, respectively. Thoracic length was measured while the subject was seated on a stool after electrode placement, and verified later with the subject seated on the ergometer. The mean of these, to the nearest centimeter, was entered as “L” into the APRIL1, 1996
to 183)) and percent ideal body weight 103% (range 80% to 144%). 18 Thoracic dimensions were as follows: length 20.5 cm (range 16 to 26) and circumference 76 cm (range 59 to 90), giving a thoracic index of 0.70 (range 0.57 to 0.83). Thoracic length 14 averaged 13.1 + 0.8% of body height. Using thoracic index and chest cirQ (kmin -l) cumference as independent predictors, and the QICG/QRBratio as a de10 pendent variable, univariate analysis showed no influence of these factors on measurement of cardiac output by ICG. Mean hemoglobin concentration 6 was 140 g/L ( 124 to 1.59). Using hemoglobin concentration (to reflect hematocrit), we found a slight (r2 = 0.12), but statistically significant (p = 0.009), inverse relation between 2 QICG/QRB and hemoglobin. There was .25 .75 1.25 1.75 2.25 no relation between baseline thoracic impedance and age. 902 (I-min -l) Regression of cardiac output against VOZ for the 2 methods is ut (Q) measured by thoracic~elechic impedance and FIGURE 2. Piot of cardiic shown in Figure 2. In general, the reing versus oxygen uptake (VO3 in health exercising carbon dioxide (CO4 reb 3 area represents normal mnge in pubertal boys from crata of children. Stip lation for impedance measurements Eriksson et a P.20 had slightly higher intercept and lower slope than did the relation .for computations. Subjects underwent duplicate mea- rebreathing measurements. However, the values obsurement of chest circumference, and of anteropos- tained for slope by either method were clearly within terior and lateral chest diameters at the level of the the accepted range (see Discussion). Regression of xiphoid. The ratio of the latter 2 (thoracic index) was QICG on QRB showed excellent correlation (Figure 3). There were no differences between QicG and QRe calculated. Analysis: Each minute measurement of impedance in the 2-way analysis of variance. Comparison of cardiac output was made based on all cardiac cycles techniques by the method of Altman and Bland is over an g-second interval. Impedance measurements shown in Figure 4, which illustrates differences befrom the fourth or fifth to eighth minutes were av- tween results obtained by each technique about the eraged to provide a single value for heart rate and hypothetical average. Mean bias (Qicc-QRB) was cardiac output at that workload. Values obtained by 0.14 + 1.05 L/mm, not significantly different from both methods were regressed against 02 uptake zero (95% confidence interval -0.12 to +0.44 L/ ( VOZ) . Measurements of cardiac output were com- mm). All QIco results were within 2 15% of the hypared by regression of ICG cardiac output (Qico) on pothetical mean value. The largest deviation of Qicd rebreathing cardiac output (QRB) by the method of from QRBwas +30%, found in 1 of 57 paired meaBland and Altman ” and by 2-way analysis of vari- surements. Eighty percent of QicGvalues were within ance (method and workload). To test the appropri- 220% of the corresponding QRBresult. ateness of Kubicek’s equation and some of its theoretical foundations, we carried out regression of the DISCUSSION ratio of QIcc/QRe against thoracic index, chest cirThe analysis of Bland and Altman is ideal for this cumference, and hemoglobin concentration. study design because of the difficulty in selecting a standard method of measuring cardiac output in exercising children. In an attempt to add validity to our RESULTS We were unable to obtain a satisfactory plateau results, we chose to plot cardiac output calculated by in the mixed venous CO* partial pressure tracing in both methods as a function of O2 uptake, since there 2 subjects at the heavier workload; satisfactory pho- are few published reports on this relation obtained nocardiographic signals were not obtained in 1 per- by invasive measurements of cardiac output. Taken son at the heavier workload, casting doubt on the together, these data show the acceptability of ICG impedance measurement. These data were not in- estimates of cardiac output in healthy children during exercise. cluded in our analysis. Study subjects consisted of 14 boys and 16 girls Although we obtained Qicd at rest, we made no with a mean age of 12 years (range 8 to 17), weight attempt to do likewise by CO2 rebreathing. Be48 kg (range 27 to 80), height 156 cm (range 133 cause of the known inaccuracy of this method
o impedance
q
CO2 rebreathing
METHODS/IMPEDANCE
CARDIOGRAPHY IN EXERCISING HEALTHY CHllDREN
747
rupted exercise in some subjects. The ability to obtain accurate resting measurements and to obtain repeated measurements on exercise without perturbing the subject or unnecessarily prolonging the test make ICG a viable, attractive choice for this purpose. The magnitude of differences between Qrcc and QRB found in the present (I-min study compare quite favorably with reports comparing different methods of measuring cardiac output.2*3 The device used in the present study incorporated empirically derived correction factors for body hab6 itus (ectomorph, mesomorph, and en&G-1.11 +.875& domorph) because of the known effect of obesity on electric bioimpedance.** rG825 I I' I I These comparisons were derived from 3 simultaneous determinations of Q by 3 6 9 12 15 18 ICG and direct Fick methods per. QRB (I=min-1) formed (in adults) during development of the software program. Other FIGURE 3. Regression plot of ek&ic impedance (&J versus indid (carbon diox recognized potential confounding facide) Fick (m measuremen of cardiac output in indiiual heahhy children at 2 tors, such as hematocrit and configu~~i~wcise, showing the regression line /t&n line} and the line of identity ration of the thorax, did not seem to substantially influence the measurement of QIcc . We found that_ the_.effect when the arteriovenous CO2 content difference is of hemoglobin on the QICG/QRBamounted to this rasmall, *I small errors in measurement of arterial tio being 1.1 at the lower end of hemoglobin values, and mixed venous CO2 partial pressures, can lead and 0.95 at the upper end. Thus, use of a Kubicek to large errors in computation of QRB. In our ex- model of the thorax with a constant for blood resisperience, the technical difficulty in accurately es- tivity seems reasonable for this purpose. The issue timating mixed venous CO2 partial pressure was at of hematocrit has received considerable attention, least as great as that of obtaining a good-quality without emergence of a clear consensus.11*17s21 phonocardiographic signal. There have been few previous studies comparing Obtaining arterial CO2 partial pressure by blood ICG with other methods of measuring cardiac output sampling was more problematic, because this dis- in children.9~23-25Miles et a125found that systemic 3.0
1.0 &G
- hRB
(lamin
-1
FIGURE 4. Graphic mpresenbtion the difference between measure-
o.o
)
abscissa. /iorizond 52;~ -
-2.0 -3.0
I
I
2
4
6
mean of 748
of
I
I
I
8
10
12
(QicG + QR~)
THE AMERICAN JOURNAL OF CARDIOLOGY”
I
14
16
(I-min-l)
VOL. 77
APRIL1, 1996
lines indicate difference ar bias (6) and S
.
blood flow was accurately measured in a group of children with acyanotic congenital heart disease, but that direct Fick-measured pulmonary blood flow was significantly greater than systemic flow measured by either impedance or direct Fick methods in patients with left-to-right shunts. These investigators, using the Minnesota Impedance Cardiograph model 304B ( Surcom, Minneapolis, Minnesota), commented favorably on ICG.25 In contradistinction, Lababidi et a123compared results of dye-dilution measurements with those from a Minnesota Impedance Cardiograph model 202 (Kubicek equation) and found good correlation between the 2 methods in children aged 3 to 18 years, with and without shunts or valvular insufficiency. If one examines studies comparing Qlcc with other methods of measuring cardiac output during exercise, 5-15,26 all but 1 involved adult subjects.’ Several different impedance devices were used, rendering simple comparisons difficult. Nonetheless, there appears to be a tendency that devices which used the Sramek equation gave less satisfactory results than those that used the Kubicek equation. This reflects our own earlier experience with the NCCOM-3 (BoMed, Irvine, California) (unpublished observations), and the experience of others,27 but contradicts the conclusions reached by Fuller.2 In developing software algorithms for the ICGM401, data obtained by direct Fick measurements obtained mainly in adults with coronary artery disease were used to derive empiric correction factors related to body habitus. Whether these are suitable for use in children remains to be seen, but this underscores the need for further studies comparing ICG measurements in children with a more accepted standard such as the direct Fick method. Our initial findings pave the way for future studies in children undergoing catheterization for diagnosis and management of congenital heart disease, or in those in the intensive care unit. Having demonstrated the accuracy and validity of this device for measurement of cardiac output by ICG in healthy children during exercise, the possibility of applying the method to other pediatric disorders now exists. The recognized cardiotoxicity of cytotoxic agents can be monitored by periodic exercise testing with measurement of stroke volume. The ability to repeatedly measure cardiac output over short intervals will enable one to determine kinetics of the stroke volume response to exercise during the growth period, which will improve understanding of developmental aspects of exercise physiology. ICG holds the greatest promise in children in whom invasive cardiac output monitoring is seldom performed.
1. Penney BC. Theory and cardiac applications of electrical impedance measurements. CRC Crir Rev Biomed Eng 1986;13:227-281. 2. Fuller HD. The validity of cardiac output measurements by thoracic impedance: a meta-analysis. Clin Invest Med 1992;15:103-112. 3. Miles DS, Gotshall RW. Impedance cardiography: non-invasive assessment of human central hemodynamics at rest and during exercise. Exer Span Sci Rev 1989;17:231-263. 4. Pickett BR, Buell JC. Validity of cardiac output measurement by computer averaged impedance cardiography, and comparison with simultaneous thermodilution determinations. Am J Cardiol 1992;69: 1354- 1358. 5. Miyamoto Y, Takahashi M, Nakamura T, Hiura T, Mikami M. Continuous determination of cardiac output during exercise by the use of impedance plethysmography. Med Biol Eng Compur 1981;19:638-644. 6. Muzi M, Ebert TJ, Tristani FE, Jeutter DC, Barney JA, Smith JJ. Determination of cardiac output using ensemble-averaged impedance cardiograms. J Appl Physiol 1985;58:2OI-205. 7. Koon-Kang Teo, Hetherington MD, Haennel RG, Greenwood PV, Rossall RE, Kappagoda T. Cardiac output measured by impedance cardiography during maximal exercise tests. Cardiovasc Res 1985;19:737-743. 8. Denniston JC, Maher ST, Reeves JT, ‘Cruz JC, Cymerman A, Grover RF. Measurement of cardiac output by electrical impedance at rest and during exercise. J Appl Physiol 1976;40:91-95. 9. Edmunds AT, Godfrey S, Tooley M. Cardiac output measured by transthoracic impedance cardiography at rest, during exercise and at various lung volumes. Clin Sci 1982;63:107-113. 10. Moore R, Sansores R, Guimond V, Abboud R. Evaluation of cardiac output by thoracic electrical bioimpedance during exercise in normal subjects. Chesr 1992;102:448-455. 11. duQuesnay MC, Stoute GJ, Hughson RL. Cardiac output by impedance cardiography during breath holding and normal breathing. J Appl Physiol 1987;62:101-107. 12. Goldstein DS, Cannon RO III, Zimlichman R, Keiser HR. Clinical evaluation of impedance cardiography. Clin Physiol 1986;6:235-251. 13. Thomas SHL. Impedance cardiography using the Sramek-Bernstein method: accuracy and variability at rest and during exercise. Br J Clin Pharmm01 1992;34:467-476. 14. White SW, Quail AW, deLeeuw PW, Traugott FM, Brown WJ, Porges WL, Cottee DB. Impedance cardiography for cardiac output measurement: an evaluation of accuracy and limitations. Eur Hean J 1990; 11 (suppl 1):79-92. 15. Smith SA, Russell AE, West MJ, Chalmers J. Automated non-invasive measurement of cardiac output: comparison of electrical bioimpedance and carbon dioxide rebreathing techniques. Br Heart J 1988;59:292-298. 16. Jones NL. Clinical Exercise Testing. 3rd ed. Toronto: WB Saunders Co, 1989:189-195. 17. Quail AW, Traugott FM, Porges WL, White SW. Thoracic resistivity for stroke volume calculation in impedance cardiography. J Appl Physiol 1981;50:191-195, 18. McHardy GJR. Relationships between the differences in pressure and content of carbon dioxide in arterial and venous blood. Clin Sri 1967:32:299-309. 19. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1:307-310. 20. Eriksson BO, Grimby G, Saltin B. Cardiac output and arterial blood gases during exercise in pubertal boys. J Appl Physiol 1971;31:348-352. 21. Godfrey S, Davies CTM. Estimates of arterial PCOz and their effect on the calculated values of cardiac output and dead space on exercise. Clin Sci 1970;39:529-537. 22. Bernstein DP. A new stroke volume equation for thoracic electrical bioimpedance: theory and rationale. Crit Care Med 1986;14:904-909. 23. Lababidi Z, Ehmke DA, Dumin RE, Leaverton PE, Lauer RM. Evaluation of impedance cardiac output in children. Pediatrics 1971;47:870-879. 24. Introna RPS, Pmett JK, Crumrine RC, Cuadrado AR. Use of transthoracic bioimpedance to determine cardiac output in pediatric patients. Cn’t Care Med 1988:16:1101-1105. 25. Miles DS, Gotshall RW, Golden JC, Tuuri DT, Beckman RH III, Dillon T. Accuracy of electrical impedance cardiography for measuring cardiac output in children with congenital heart defects. Am J Cardiol 1988;61:612-616. 26. Wilson MF, Bong Hee Sung, Pincomb GA, Lovallo WR. Simultaneous measurement of stroke volume by impedance cardiography and nuclear ventriculography: comparisons at rest and exercise. Ann Biomed Eng 1989; 17:475 482. 27. Gotshall RW, Wood VC, Miles DS. Comparison of two impedance cardiographic techniques for measuring cardiac output. Ann Biomed Eng 1989;17:495-505.
METHODS/IMPEDANCE CARDIOGRAPHY IN EXERCISINGHEAlTHY CHILDREN 749
MD, and Daniel
Garros,
MD
Electric bioimpedance has been used to measure cardiac output for decades. Improvements in modeling and microprocessor technology have spawned newer generations of such devices. This method would be especially useful in children, in whom the use of invasive methods is limited. We tested a device (ICG-M401, ASK ltd.) in 30 healthy children at 2 levels of exercise (0.5 and 1.5 W/kg), and compared impedance measurements of cardiac output (a,,) with carbon dioxide (CO,) rebreathing measurements of cardiac output (a,). The Q,co-oxygen uptake (VOZ) relation was expressed by &o = 3.8 + 4.6 VO2; r2 = 0.68. Mean + SD bias (Q,(;1Rs)was 0.14 -+ 1.05 L/min, not significantly different
from zero (95% confidence intenal -0.12 to + 0.44 11 min). All Qlc~ results were within ? 15% of the hypothetical mean value (Bland and Altman analysis). The largest deviation of QlcG from Qm was +30%, found in 1 of 57 paired determinations. Eighty percent of QKC values were within 220% of the QRs result. We conclude that impedance cardiography with the ICG-MI01 provided realistic and reliable estimates of cardiac output in healthy children during exercise. This, along with ik ease of operation and utility at rest and during exercise, make it both useful and attractive for clinic and research purposes. (Am J Cardiol 1996;77:745-749)
totally noninvasive technique for measuring cardiac output (Q) that does not require a great A deal of skill to perform, that can be done inexpen-
hospital personnel for this study (Table I). Participants and their parents signed informed consent. This study had received approval from the University of Manitoba Faculty of Medicine Committee for Use of Human Subjects in Research. Exercise protocol: Exercise was performed on an electrically braked cycle ergometer (Excalibur, Quinton Instruments, Seattle, Washington) at 2 work rates: 0.5 and 1.5 W/kg, chosen to span the range of work intensities from light to moderately heavy exercise. Subjects pedaled for 4 minutes before gas exchange measurements commenced, starting with blood gas sampling, followed by mixed expired gas collection for 2 minutes, and ending with duplicate CO1 rebreathing maneuvers. Total duration of work at each load was approximately 8 minutes. Apparatus: Expired ventilation was measured on a spirometer (Transferscreen II, Erich Jaeger Co., Wurzburg, Germany) equipped with a heated pneumotachograph, calibrated before and after tests by using a volumetric syringe. Mixed expired gases were collected in 60 L gas-collection bags and analyzed with zirconium oxide oxygen (0,) and infrared CO* analyzers (S-3A/l, CD-3A, respectively, Ametek Inc., Pittsburgh, Pennsylvania). End tidal CO;?could also be sampled at the mouth at a flow rate of 400 ml/min. Analyzers were calibrated with reference gases (room air [5% CO,, 15% 02, balance, nitrogen gas ( N2)] and 13% C02, balance 02) before and after testing. All signals were recorded in real time on a Gould thermal strip-chart recorder (TA2000, Cleveland, Ohio).
sively at the bedside or in the laboratory, repeatedly, and that doesn’t perturb the measured variable(s) , would be an invaluable asset in pediatric research and clinical medicine. Thoracic electric bioimpedante cardiography (ICG) offers such a technique.lm3 Different devices operating on this principle have been tested against “gold standard” methods of measuring cardiac output, with many reports affirming its utility,4-10 but some reports suggesting ICG output measurements were neither accurate nor reliable.1’-‘5 It is apparent from these studies that not all impedance devices performed alike. Some investigators found that ensemble averaging of the first time derivative of thoracic impedance improved accuracy.4-6 We tested a new device (ICG-M401, ASK Ltd., Budapest, Hungary) in healthy children during exercise by comparing im edance versus carbon dioxide (CO*) rebreathing ’ r measurements of cardiac output. We also examined the effects of hemoglobin concentration l7 and thoracic configuration I4 on the ICG measurement of Q.
METHODS Subjects:Thirty healthy children with normal spirometry were recruited from families and friends of From the Department of Pediatrics and Child Health, Children’s Hosof Medicine, University of Manitoba, pital of Winnipeg, and Facul Winnipeg, Canada. This stu fi’y was funded by a grant from the Children’s Hospital of Winnipeg Research Foundation and the Manitoba Medical Services Foundation. Manuscript received September 22, 1995; revised manuscript received November 14, 1995, and accepted November 15. Address for reprints: Paul Pianosi, MD, CN-503, Children’s Hospital, 840 Sherbrook Street, Winnipeg, MB, Canada, R3A 1 S 1
METHODS/IMPEDANCE
Measurement of cardiac output by carbon dioxide rebreathing: Arterialized capillary blood was obtained
from a finger warmed by wrapping in a heating pad. Samples were stored on ice, and analyzed within 20 CARDIOGRAPHY
IN EXERCISING
HEALTHY
CHllDREN
745
TABLE I Cardiac CO2 Rebreathing,
Output (L/min) by Impedance Cardiography Together With VOn at 0.5 and 1.5 W/kg
Variable VO:, (L/min) CO? rebreathing Electrical impedance Dye dilution* * Reference and
1.09
Values
data from Eriksson
L/min
in pubertal
are expressed
CO2 = carbon
dioxide;
and
0.5 W/kg
1.5 W/kg
0.64 it 0.21 6.49 + 1.64 6.68 -c 1.51 7.7 + 1 .o
1.21 + 0.45
et cP’ obtained
9.142 2.53 9.23 k 2.49 9.3 c 1.4 by dye dilution
at VO? 0.71
boys.
as mean
2 SD.
VO? = oxygen
uptake.
processed FIGURE 1. lbration of gmphii output of wodorms Ltd., Budapest, Hungary). The upper buce is the ektrocardiimm from the top is the first time derivative (dZ/dt), third tmce is the (PCG), and the lower trace is the merit value of dZ/dt is shown for 2 (2.21 and vertical lines are used to compute the (vet), and the qs2 interval, with
corrected mixed venous CO2 partial pressures I6 were converted to contents,” assuming a saturation of 97%. Impedance cardiography The ICG-M401 uses a tetrapolar lead system with paired inner electrodes placed on either side in the supraclavicular fossa just above the level of the suprasternal notch, and along the midaxillary line at the level of the xiphoid. The outer electrodes are placed 6 cm ce halad and caudad, respectively. Pregelled Red Dot%A(3M Co., St. Paul, Minnesota) was used for this purpose, and applied after the skin had been gently abraded with fine sandpaper and swabbed with alcohol. Leads for the electrocardiogram were placed on the right and left pectoral areas and on the right and left lower quadrants of the abdomen. The lead (I, II, or III) that gave the best definition of the QRS complex was used for computation purposes by the software program. Finally, the phonocardiogram was recorded by a proprietary microphone attached with double-sided adhesive placed along the left sternal border at a site where the second heart sound was loudest. We made our impedance measurements during free breathing due to difficulty in having children hold their breath on exercise, an approach justified by work done in adults. Sample waveforms processed by the device are shown in Figure 1. The software program used a by the ICG-MO1 (ASK modification of the Kubicek equa(ECG), second truce tion, based on empiric corrections phonocard’ for body habitus derived from
minutes on a Radiometer ABLSOO blood gas analyzer to measure pH and partial pressure of arterial COa. Hemoglobin (g/L) was also measured from these samples on a Radiometer Hemoximeter (OSM 3, Copenhagen, Denmark). The rebreathing bag was filled with an appropriate mixture of CO2 ( 10% to 15%) in 02, with the volume of the rebreathing mixture approximating the subject’s vital capacity. The subject was instructed to take 3 to 4 rapid, deep breaths, and then continue normal breathing pattern for approximately 15 seconds. End tidal CO* was continuously sampled at the mouth and the analog signal recorded on paper at 10 mm/s to capture a plateau in the CO2 concentration. This maneuver was attempted in duplicate with rl minute between each, and if both trials resulted in an equilibrium plateau, the mean mixed venous CO* partial pressure was used. Values for arterial and downstream 746
THE AMERICAN JOURNAL OF CARDIOLOGY”
VOL. 77
preliminary
studies that compared
impedance with direct Fick measurements of cardiac output in adults: SV = r($)(VET)(s) where SV = stroke volume (ml), r = blood resistivity (assumed constant at 135 R/cm), L = distance between inner electrodes (measured), Z, = baseline thoracic impedance (0)) VET = ventricular ejection time (seconds), and dZ/dt = maximal value of first time derivative of impedance. The 3 types of body habitus were ectomorph, mesomorph, and endomorph, which we defined for use in children as percent ideal weight for height <85%, 85% to 120%, and > 120%, respectively. Thoracic length was measured while the subject was seated on a stool after electrode placement, and verified later with the subject seated on the ergometer. The mean of these, to the nearest centimeter, was entered as “L” into the APRIL1, 1996
to 183)) and percent ideal body weight 103% (range 80% to 144%). 18 Thoracic dimensions were as follows: length 20.5 cm (range 16 to 26) and circumference 76 cm (range 59 to 90), giving a thoracic index of 0.70 (range 0.57 to 0.83). Thoracic length 14 averaged 13.1 + 0.8% of body height. Using thoracic index and chest cirQ (kmin -l) cumference as independent predictors, and the QICG/QRBratio as a de10 pendent variable, univariate analysis showed no influence of these factors on measurement of cardiac output by ICG. Mean hemoglobin concentration 6 was 140 g/L ( 124 to 1.59). Using hemoglobin concentration (to reflect hematocrit), we found a slight (r2 = 0.12), but statistically significant (p = 0.009), inverse relation between 2 QICG/QRB and hemoglobin. There was .25 .75 1.25 1.75 2.25 no relation between baseline thoracic impedance and age. 902 (I-min -l) Regression of cardiac output against VOZ for the 2 methods is ut (Q) measured by thoracic~elechic impedance and FIGURE 2. Piot of cardiic shown in Figure 2. In general, the reing versus oxygen uptake (VO3 in health exercising carbon dioxide (CO4 reb 3 area represents normal mnge in pubertal boys from crata of children. Stip lation for impedance measurements Eriksson et a P.20 had slightly higher intercept and lower slope than did the relation .for computations. Subjects underwent duplicate mea- rebreathing measurements. However, the values obsurement of chest circumference, and of anteropos- tained for slope by either method were clearly within terior and lateral chest diameters at the level of the the accepted range (see Discussion). Regression of xiphoid. The ratio of the latter 2 (thoracic index) was QICG on QRB showed excellent correlation (Figure 3). There were no differences between QicG and QRe calculated. Analysis: Each minute measurement of impedance in the 2-way analysis of variance. Comparison of cardiac output was made based on all cardiac cycles techniques by the method of Altman and Bland is over an g-second interval. Impedance measurements shown in Figure 4, which illustrates differences befrom the fourth or fifth to eighth minutes were av- tween results obtained by each technique about the eraged to provide a single value for heart rate and hypothetical average. Mean bias (Qicc-QRB) was cardiac output at that workload. Values obtained by 0.14 + 1.05 L/mm, not significantly different from both methods were regressed against 02 uptake zero (95% confidence interval -0.12 to +0.44 L/ ( VOZ) . Measurements of cardiac output were com- mm). All QIco results were within 2 15% of the hypared by regression of ICG cardiac output (Qico) on pothetical mean value. The largest deviation of Qicd rebreathing cardiac output (QRB) by the method of from QRBwas +30%, found in 1 of 57 paired meaBland and Altman ” and by 2-way analysis of vari- surements. Eighty percent of QicGvalues were within ance (method and workload). To test the appropri- 220% of the corresponding QRBresult. ateness of Kubicek’s equation and some of its theoretical foundations, we carried out regression of the DISCUSSION ratio of QIcc/QRe against thoracic index, chest cirThe analysis of Bland and Altman is ideal for this cumference, and hemoglobin concentration. study design because of the difficulty in selecting a standard method of measuring cardiac output in exercising children. In an attempt to add validity to our RESULTS We were unable to obtain a satisfactory plateau results, we chose to plot cardiac output calculated by in the mixed venous CO* partial pressure tracing in both methods as a function of O2 uptake, since there 2 subjects at the heavier workload; satisfactory pho- are few published reports on this relation obtained nocardiographic signals were not obtained in 1 per- by invasive measurements of cardiac output. Taken son at the heavier workload, casting doubt on the together, these data show the acceptability of ICG impedance measurement. These data were not in- estimates of cardiac output in healthy children during exercise. cluded in our analysis. Study subjects consisted of 14 boys and 16 girls Although we obtained Qicd at rest, we made no with a mean age of 12 years (range 8 to 17), weight attempt to do likewise by CO2 rebreathing. Be48 kg (range 27 to 80), height 156 cm (range 133 cause of the known inaccuracy of this method
o impedance
q
CO2 rebreathing
METHODS/IMPEDANCE
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rupted exercise in some subjects. The ability to obtain accurate resting measurements and to obtain repeated measurements on exercise without perturbing the subject or unnecessarily prolonging the test make ICG a viable, attractive choice for this purpose. The magnitude of differences between Qrcc and QRB found in the present (I-min study compare quite favorably with reports comparing different methods of measuring cardiac output.2*3 The device used in the present study incorporated empirically derived correction factors for body hab6 itus (ectomorph, mesomorph, and en&G-1.11 +.875& domorph) because of the known effect of obesity on electric bioimpedance.** rG825 I I' I I These comparisons were derived from 3 simultaneous determinations of Q by 3 6 9 12 15 18 ICG and direct Fick methods per. QRB (I=min-1) formed (in adults) during development of the software program. Other FIGURE 3. Regression plot of ek&ic impedance (&J versus indid (carbon diox recognized potential confounding facide) Fick (m measuremen of cardiac output in indiiual heahhy children at 2 tors, such as hematocrit and configu~~i~wcise, showing the regression line /t&n line} and the line of identity ration of the thorax, did not seem to substantially influence the measurement of QIcc . We found that_ the_.effect when the arteriovenous CO2 content difference is of hemoglobin on the QICG/QRBamounted to this rasmall, *I small errors in measurement of arterial tio being 1.1 at the lower end of hemoglobin values, and mixed venous CO2 partial pressures, can lead and 0.95 at the upper end. Thus, use of a Kubicek to large errors in computation of QRB. In our ex- model of the thorax with a constant for blood resisperience, the technical difficulty in accurately es- tivity seems reasonable for this purpose. The issue timating mixed venous CO2 partial pressure was at of hematocrit has received considerable attention, least as great as that of obtaining a good-quality without emergence of a clear consensus.11*17s21 phonocardiographic signal. There have been few previous studies comparing Obtaining arterial CO2 partial pressure by blood ICG with other methods of measuring cardiac output sampling was more problematic, because this dis- in children.9~23-25Miles et a125found that systemic 3.0
1.0 &G
- hRB
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FIGURE 4. Graphic mpresenbtion the difference between measure-
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lines indicate difference ar bias (6) and S
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blood flow was accurately measured in a group of children with acyanotic congenital heart disease, but that direct Fick-measured pulmonary blood flow was significantly greater than systemic flow measured by either impedance or direct Fick methods in patients with left-to-right shunts. These investigators, using the Minnesota Impedance Cardiograph model 304B ( Surcom, Minneapolis, Minnesota), commented favorably on ICG.25 In contradistinction, Lababidi et a123compared results of dye-dilution measurements with those from a Minnesota Impedance Cardiograph model 202 (Kubicek equation) and found good correlation between the 2 methods in children aged 3 to 18 years, with and without shunts or valvular insufficiency. If one examines studies comparing Qlcc with other methods of measuring cardiac output during exercise, 5-15,26 all but 1 involved adult subjects.’ Several different impedance devices were used, rendering simple comparisons difficult. Nonetheless, there appears to be a tendency that devices which used the Sramek equation gave less satisfactory results than those that used the Kubicek equation. This reflects our own earlier experience with the NCCOM-3 (BoMed, Irvine, California) (unpublished observations), and the experience of others,27 but contradicts the conclusions reached by Fuller.2 In developing software algorithms for the ICGM401, data obtained by direct Fick measurements obtained mainly in adults with coronary artery disease were used to derive empiric correction factors related to body habitus. Whether these are suitable for use in children remains to be seen, but this underscores the need for further studies comparing ICG measurements in children with a more accepted standard such as the direct Fick method. Our initial findings pave the way for future studies in children undergoing catheterization for diagnosis and management of congenital heart disease, or in those in the intensive care unit. Having demonstrated the accuracy and validity of this device for measurement of cardiac output by ICG in healthy children during exercise, the possibility of applying the method to other pediatric disorders now exists. The recognized cardiotoxicity of cytotoxic agents can be monitored by periodic exercise testing with measurement of stroke volume. The ability to repeatedly measure cardiac output over short intervals will enable one to determine kinetics of the stroke volume response to exercise during the growth period, which will improve understanding of developmental aspects of exercise physiology. ICG holds the greatest promise in children in whom invasive cardiac output monitoring is seldom performed.
1. Penney BC. Theory and cardiac applications of electrical impedance measurements. CRC Crir Rev Biomed Eng 1986;13:227-281. 2. Fuller HD. The validity of cardiac output measurements by thoracic impedance: a meta-analysis. Clin Invest Med 1992;15:103-112. 3. Miles DS, Gotshall RW. Impedance cardiography: non-invasive assessment of human central hemodynamics at rest and during exercise. Exer Span Sci Rev 1989;17:231-263. 4. Pickett BR, Buell JC. Validity of cardiac output measurement by computer averaged impedance cardiography, and comparison with simultaneous thermodilution determinations. Am J Cardiol 1992;69: 1354- 1358. 5. Miyamoto Y, Takahashi M, Nakamura T, Hiura T, Mikami M. Continuous determination of cardiac output during exercise by the use of impedance plethysmography. Med Biol Eng Compur 1981;19:638-644. 6. Muzi M, Ebert TJ, Tristani FE, Jeutter DC, Barney JA, Smith JJ. Determination of cardiac output using ensemble-averaged impedance cardiograms. J Appl Physiol 1985;58:2OI-205. 7. Koon-Kang Teo, Hetherington MD, Haennel RG, Greenwood PV, Rossall RE, Kappagoda T. Cardiac output measured by impedance cardiography during maximal exercise tests. Cardiovasc Res 1985;19:737-743. 8. Denniston JC, Maher ST, Reeves JT, ‘Cruz JC, Cymerman A, Grover RF. Measurement of cardiac output by electrical impedance at rest and during exercise. J Appl Physiol 1976;40:91-95. 9. Edmunds AT, Godfrey S, Tooley M. Cardiac output measured by transthoracic impedance cardiography at rest, during exercise and at various lung volumes. Clin Sci 1982;63:107-113. 10. Moore R, Sansores R, Guimond V, Abboud R. Evaluation of cardiac output by thoracic electrical bioimpedance during exercise in normal subjects. Chesr 1992;102:448-455. 11. duQuesnay MC, Stoute GJ, Hughson RL. Cardiac output by impedance cardiography during breath holding and normal breathing. J Appl Physiol 1987;62:101-107. 12. Goldstein DS, Cannon RO III, Zimlichman R, Keiser HR. Clinical evaluation of impedance cardiography. Clin Physiol 1986;6:235-251. 13. Thomas SHL. Impedance cardiography using the Sramek-Bernstein method: accuracy and variability at rest and during exercise. Br J Clin Pharmm01 1992;34:467-476. 14. White SW, Quail AW, deLeeuw PW, Traugott FM, Brown WJ, Porges WL, Cottee DB. Impedance cardiography for cardiac output measurement: an evaluation of accuracy and limitations. Eur Hean J 1990; 11 (suppl 1):79-92. 15. Smith SA, Russell AE, West MJ, Chalmers J. Automated non-invasive measurement of cardiac output: comparison of electrical bioimpedance and carbon dioxide rebreathing techniques. Br Heart J 1988;59:292-298. 16. Jones NL. Clinical Exercise Testing. 3rd ed. Toronto: WB Saunders Co, 1989:189-195. 17. Quail AW, Traugott FM, Porges WL, White SW. Thoracic resistivity for stroke volume calculation in impedance cardiography. J Appl Physiol 1981;50:191-195, 18. McHardy GJR. Relationships between the differences in pressure and content of carbon dioxide in arterial and venous blood. Clin Sri 1967:32:299-309. 19. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1:307-310. 20. Eriksson BO, Grimby G, Saltin B. Cardiac output and arterial blood gases during exercise in pubertal boys. J Appl Physiol 1971;31:348-352. 21. Godfrey S, Davies CTM. Estimates of arterial PCOz and their effect on the calculated values of cardiac output and dead space on exercise. Clin Sci 1970;39:529-537. 22. Bernstein DP. A new stroke volume equation for thoracic electrical bioimpedance: theory and rationale. Crit Care Med 1986;14:904-909. 23. Lababidi Z, Ehmke DA, Dumin RE, Leaverton PE, Lauer RM. Evaluation of impedance cardiac output in children. Pediatrics 1971;47:870-879. 24. Introna RPS, Pmett JK, Crumrine RC, Cuadrado AR. Use of transthoracic bioimpedance to determine cardiac output in pediatric patients. Cn’t Care Med 1988:16:1101-1105. 25. Miles DS, Gotshall RW, Golden JC, Tuuri DT, Beckman RH III, Dillon T. Accuracy of electrical impedance cardiography for measuring cardiac output in children with congenital heart defects. Am J Cardiol 1988;61:612-616. 26. Wilson MF, Bong Hee Sung, Pincomb GA, Lovallo WR. Simultaneous measurement of stroke volume by impedance cardiography and nuclear ventriculography: comparisons at rest and exercise. Ann Biomed Eng 1989; 17:475 482. 27. Gotshall RW, Wood VC, Miles DS. Comparison of two impedance cardiographic techniques for measuring cardiac output. Ann Biomed Eng 1989;17:495-505.
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