Simultaneous determination of the accuracy and precision of closed-circuit cardiac output rebreathing techniques.

Foreign and soluble gas rebreathing methods are attractive for determining cardiac output (Q(c)) because they incur less risk than traditional invasive methods such as direct Fick and thermodilution. We compared simultaneously obtained Q(c) measurements during rest and exercise to assess the accuracy and precision of several rebreathing methods. Q(c) measurements were obtained during rest (supine and standing) and stationary cycling (submaximal and maximal) in 13 men and 1 woman (age: 24 +/- 7 yr; height: 178 +/- 5 cm; weight: 78 +/- 13 kg; Vo(2max): 45.1 +/- 9.4 ml.kg(-1).min(-1); mean +/- SD) using one-N(2)O, four-C(2)H(2), one-CO(2) (single-step) rebreathing technique, and two criterion methods (direct Fick and thermodilution). CO(2) rebreathing overestimated Q(c) compared with the criterion methods (supine: 8.1 +/- 2.0 vs. 6.4 +/- 1.6 and 7.2 +/- 1.2 l/min, respectively; maximal exercise: 27.0 +/- 6.0 vs. 24.0 +/- 3.9 and 23.3 +/- 3.8 l/min). C(2)H(2) and N(2)O rebreathing techniques tended to underestimate Q(c) (range: 6.6-7.3 l/min for supine rest; range: 16.0-19.1 l/min for maximal exercise). Bartlett's test indicated variance heterogeneity among the methods (P < 0.05), where CO(2) rebreathing consistently demonstrated larger variance. At rest, most means from the noninvasive techniques were +/-10% of direct Fick and thermodilution. During exercise, all methods fell outside the +/-10% range, except for CO(2) rebreathing. Thus the CO(2) rebreathing method was accurate over a wider range (rest through maximal exercise), but was less precise. We conclude that foreign gas rebreathing can provide reasonable Q(c) estimates with fewer repeat trials during resting conditions. During exercise, these methods remain precise but tend to underestimate Q(c). Single-step CO(2) rebreathing may be successfully employed over a wider range but with more measurements needed to overcome the larger variability.     

Non-invasive assessment of cardiac output and stroke volume in patients during exercise. Evaluation of a CO2-rebreathing method

A one-step CO2 rebreathing method for the determination of cardiac output and stroke volume (SV) has been evaluated by comparison with the direct Fick technique during recumbent exercise (10-90 W) in 13 patients. In an initial analysis, the influence of different rebreathing times and of correction for haemoglobin concentration was studied. The best correlation with the direct Fick technique was obtained with the longest analysis time, i.e. 21 s, and correction for variations in haemoglobin concentration further improved the correlation. Consequently, an analysis time of 21 s and correction for haemoglobin have been used. At low cardiac outputs, the CO2-rebreathing method overestimated the flow compared to the Fick technique. The correlation between the methods, however, was so good that a valid estimate of cardiac output could be obtained from the CO2 rebreathing method with appropriate corrections (Cardiac output, CO2 method = 2.7 + 0.77. Cardiac output, Fick; r = 0.91; Residual Standard deviation (SD res) = 0.77 l X min-1). Stroke volumes measured with the CO2 rebreathing method did not differ significantly from those obtained with the direct Fick technique, although there was a tendency to overestimate stroke volume with the CO2 rebreathing method (SV, CO2 method = 12 + 0.89 X SV, Fick; r = 0.82; SD res = 11 ml).     

Measuring stroke volume of the ascending aorta with an extravascular Doppler ultrasound probe in comparison with aortic thermodilution]

Currently, no reliable minimally invasive method of measuring cardiac output continuously in neonates and children undergoing cardiac surgery is available. An extravascular Doppler probe was used to measure cardiac output in 15 New Zealand White rabbits (average weight 3.5 kg, range 2.5-4.5 kg). The results obtained were compared with cardiac outputs determined using the aortic thermodilution principle. The mean cardiac outputs measured with the extravascular Doppler probe was 0.37 +/- 0.01 l/min as compared with 0.39 +/- 0.01 l/min with aortic thermodilution. Regression analysis revealed a close correlation (r = 0.973) between the two techniques. The extravascular Doppler techniques is an option for continuous and reliable cardiac output measurement in small animals used in surgical experiments (open chest models) and in neonates or children during surgical repair of complicated congenital heart conditions.     

Determination of cardiac output using ensemble-averaged impedance cardiograms

Although impedance cardiography provides safe and reliable noninvasive estimates of stroke volume in humans, its usefulness is limited by the necessity for subjects to be apneic and motionless. In an effort to circumvent this restriction we studied the validity of ensemble-averaging of impedance data in exercising normal subjects and in intensive-care patients. The correlation coefficient (r value) between 128 ensemble-averaged and standard hand-digitized determinations of stroke volume index from the same records taken during rest and exercise in six normal male subjects was +0.97 (P less than 0.001). The r value for ensemble-averaged stroke volume indices during free breathing and breath hold in the same subjects was +0.92 (P less than 0.001), suggesting that breath hold did not significantly affect the stroke volume estimation. In 14 freely breathing hospital intensive-care patients the r value between simultaneous thermodilution cardiac output readings and ensemble-averaged impedance determinations was +0.87 (P less than 0.01). The results indicate that ensemble-averaging of transthoracic impedance data provides waveforms from which reliable estimates of cardiac output can be made during normal respiration in healthy human subjects at rest and exercise and in critically ill patients.     

An improved rebreathing method for measuring mixed venous carbon dioxide tension and its clinical application.

The mixed venous carbon dioxide tension (PVCO2) can be measured at the bedside by a rebreathing equilibrium technique that is quick, simple and noninvasive. Only one brief period of rebreathing is required. The technique is accurate even when the lungs are not normal, and gives a graphic record that allows verification of the accuracy of the estimate. The PVCO2 is affected mainly by changes in alveolar ventilation and cardiac output. It can be measured instead of the arterial carbon dioxide tension (PACO2) to follow changes in alveolar ventilation when the cardiac output is normal (PaCO2 = 0.8 PVCO2). When the cardiac output is abnormal, measurement of both PaCO2 and PvCO2 is useful in determining how much the cardiac output is reduced. Consideration of the relation between oxygen consumption and carbon dioxide production suggests that the equation PaCO2 = 0.8 PVCO2 - 12 indicates a reduction in cardiac output that may impair the oxygen supply to tissues. Simple corrections can be applied to allow for variations in arterial oxygen saturation and hemoglobin concentration that will affect this relationship.     

Estimation of cardiac output by the CO2 rebreathing method during tethered swimming

The reproducibility of cardiac output (Q) estimated by the CO2 rebreathing method during tethered swimming was studied in five highly trained college swimmers. The reproducibility of the CO2 rebreathing method for estimations of Q during tethered swimming was similar to the reproducibility reported for the CO2 rebreathing method, direct Fick method, or dye-dilution method during either cycling or treadmill walking. All duplicate estimates of Q by the CO2 rebreathing method were within 15% of one another. A comparison was made between the Q's estimated by the CO2 rebreathing method during tethered swimming and previously published data on Q determined by the dye-dilution method during free swimming in a flune. At any given oxygen uptake, Q obtained by the CO2 rebreathing method during tethered swimming was not significantly different from the Q obtained by the dye-dilution method during flume swimming. Estimates of Q by the CO2 rebreathing method made during high intensities of tethered swimming were reproducible and appear to be valid.     

Cardiac output by rebreathing in patients with cardiopulmonary diseases

Noninvasive estimates of cardiac output by rebreathing soluble gases (Qc) can be unreliable in patients with cardiopulmonary diseases because of uneven distribution of ventilation to lung gas volume and pulmonary blood flow. To evaluate this source of error, we compared rebreathing Qc with invasive measurements of cardiac output performed by indicator-dilution methods (COID) in 39 patients with cardiac or pulmonary diseases. In 16 patients with normal lung volumes and 1-s forced expiratory volumes (FEV1), Qc measured with acetylene [Qc(C2H2)] overestimated COID insignificantly by 2 +/- 9% (SD). In subjects with mild to moderate obstructive lung disease, Qc(C2H2) slightly overestimated COID by 6 +/- 15% (P = 0.11). In patients with restrictive disease or combined obstructive and restrictive disease, Qc(C2H2) underestimated COID significantly by 9 +/- 14% (P less than 0.04). The magnitude of the discrepancy between Qc and COID correlated with size of the volume rebreathed and an index of uneven ventilation calculated from helium mixing during rebreathing that determined a dead space to inspired volume ratio (VRD/VI). Rebreathing volumes less than 40% of the predicted FEV or VRD/VI of 0.4 or greater identified all subjects with a discrepancy between Qc(C2H2) and COID of 20% or greater.     

Reduced submaximal leg blood flow after high-intensity aerobic training.

This study evaluated the hypothesis that active muscle blood flow is lower during exercise at a given submaximal power output after aerobic conditioning as a result of unchanged cardiac output and blunted splanchnic vasoconstriction. Eight untrained subjects (4 men, 4 women, 23-31 yr) performed high-intensity aerobic training for 9-12 wk. Leg blood flow (femoral vein thermodilution), splanchnic blood flow (indocyanine green clearance), cardiac output (acetylene rebreathing), whole body O(2) uptake (VO(2)), and arterial-venous blood gases were measured before and after training at identical submaximal power outputs (70 and 140 W; upright 2-leg cycling). Training increased (P < 0.05) peak VO(2) (12-36%) but did not significantly change submaximal VO(2) or cardiac output. Leg blood flow during both submaximal power outputs averaged 18% lower after training (P = 0.001; n = 7), but these reductions were not correlated with changes in splanchnic vasoconstriction. Submaximal leg VO(2) was also lower after training. These findings support the hypothesis that aerobic training reduces active muscle blood flow at a given submaximal power output. However, changes in leg and splanchnic blood flow resulting from high-intensity training may not be causally linked.     

Measurement of cardiac output during exercise by open-circuit acetylene uptake.

Noninvasive measurement of cardiac output (QT) is problematic during heavy exercise. We report a new approach that avoids unpleasant rebreathing and resultant changes in alveolar PO(2) or PCO(2) by measuring short-term acetylene (C(2)H(2)) uptake by an open-circuit technique, with application of mass balance for the calculation of QT. The method assumes that alveolar and arterial C(2)H(2) pressures are the same, and we account for C(2)H(2) recirculation by extrapolating end-tidal C(2)H(2) back to breath 1 of the maneuver. We correct for incomplete gas mixing by using He in the inspired mixture. The maneuver involves switching the subject to air containing trace amounts of C(2)H(2) and He; ventilation and pressures of He, C(2)H(2), and CO(2) are measured continuously (the latter by mass spectrometer) for 20-25 breaths. Data from three subjects for whom multiple Fick O(2) measurements of QT were available showed that measurement of QT by the Fick method and by the C(2)H(2) technique was statistically similar from rest to 90% of maximal O(2) consumption (VO(2 max)). Data from 12 active women and 12 elite male athletes at rest and 90% of VO(2 max) fell on a single linear relationship, with O(2) consumption (VO(2)) predicting QT values of 9.13, 15.9, 22.6, and 29.4 l/min at VO(2) of 1, 2, 3, and 4 l/min. Mixed venous PO(2) predicted from C(2)H(2)-determined QT, measured VO(2), and arterial O(2) concentration was approximately 20-25 Torr at 90% of VO(2 max) during air breathing and 10-15 Torr during 13% O(2) breathing. This modification of previous gas uptake methods, to avoid rebreathing, produces reasonable data from rest to heavy exercise in normal subjects.     

Comparison of two noninvasive techniques for estimating cardiac output during exercise

This study presents the comparison of two different noninvasive techniques for the estimation of cardiac output (Q). The two techniques used were transthoracic impedance plethysmography (Z) and the indirect Fick CO2 rebreathing (RB) method. Paired estimates of Q were made on 60 different male subjects at rest and during graded increments of work on a cycle ergometer. The mean resting Q as measured by the Z technique (COZ) was 7.46 +/- 0.35 and 5.96 +/- 0.43 l/min using the RB (CORB) technique. At 200 W the mean COZ was 18.67 +/- 0.72 l/min and the CORB was 23.73 +/- 0.84 l/min. Both the techniques were linearly correlated (R) with O2 consumption; i.e., RZ = 0.752, RRB = 0.855. The difference between these two R values is statistically significant (P less than 0.001). A linear relationship was found between the Z and RB techniques at all work loads (R = 0.75). This study suggests that both techniques are equally as reliable over a large range of work loads, with the Z technique being the simplest and most efficient to implement. It was also found that lung volume had no effect on the calculated COZ.     

Modelflow underestimates cardiac output in heat-stressed individuals

An estimation of cardiac output can be obtained from arterial pressure waveforms using the Modelflow method. However, whether the assumptions associated with Modelflow calculations are accurate during whole body heating is unknown. This project tested the hypothesis that cardiac output obtained via Modelflow accurately tracks thermodilution-derived cardiac outputs during whole body heat stress. Acute changes of cardiac output were accomplished via lower-body negative pressure (LBNP) during normothermic and heat-stressed conditions. In nine healthy normotensive subjects, arterial pressure was measured via brachial artery cannulation and the volume-clamp method of the Finometer. Cardiac output was estimated from both pressure waveforms using the Modeflow method. In normothermic conditions, cardiac outputs estimated via Modelflow (arterial cannulation: 6.1 ± 1.0 l/min; Finometer 6.3 ± 1.3 l/min) were similar with cardiac outputs measured by thermodilution (6.4 ± 0.8 l/min). The subsequent reduction in cardiac output during LBNP was also similar among these methods. Whole body heat stress elevated internal temperature from 36.6 ± 0.3 to 37.8 ± 0.4°C and increased cardiac output from 6.4 ± 0.8 to 10.9 ± 2.0 l/min when evaluated with thermodilution (P < 0.001). However, the increase in cardiac output estimated from the Modelflow method for both arterial cannulation (2.3 ± 1.1 l/min) and Finometer (1.5 ± 1.2 l/min) was attenuated compared with thermodilution (4.5 ± 1.4 l/min, both P < 0.01). Finally, the reduction in cardiac output during LBNP while heat stressed was significantly attenuated for both Modelflow methods (cannulation: -1.8 ± 1.2 l/min, Finometer: -1.5 ± 0.9 l/min) compared with thermodilution (-3.8 ± 1.19 l/min). These results demonstrate that the Modelflow method, regardless of Finometer or direct arterial waveforms, underestimates cardiac output during heat stress and during subsequent reductions in cardiac output via LBNP.     

Noninvasive cardiac output estimation: a preliminary study

 The availability of a simple-to-use, automatic measurement system for noninvasive flow estimation is imperative, given the clinical demand for an acceptable noninvasive procedure rather than the standard invasive procedure of thermodilution. A method for calculating cardiac output from noninvasively derived pressure pulses has been developed, and the results of a preliminary evaluation study on post-cardiac surgery patients for whom invasive flow measures were readily available for comparison are provided in this report. The proposed method relies on fast Fourier transform (FFT) analysis of pulses measured externally at the carotid and femoral pressure points. A transfer function of the aorta is computed from digitally filtered pulse measurements, and a tapered model of the aorta is parametrically adapted using a simplex optimization algorithm so that its transfer function matches that derived experimentally. An aortic input impedance term is obtained from the optimized model and utilized along with the carotid pulse (analogous to input voltage) to compute aortic flow. In addition to its automation, attractive features of this method include the requirement for relatively few pulses for analysis as well as considerable resistance to noise artifact. For 59 data records collected from 54 post-cardiac surgery patients, the average flow measurements computed over several pulses compare well with the standard, invasive method of thermodilution. Preliminary results also indicate a strong potential for tracking changes in cardiac output over time, and invite further use of the method in monitoring hemodynamically unstable patients. Received: 18 February 1997 / Accepted in revised form: 12 May 1997     

Cardiac output in exercise by impedance cardiography during breath holding and normal breathing

Estimation of cardiac output by impedance cardiography (QZ) in exercise during normal breathing (NB) has been limited by motion artifact. Our objective was to obtain readable impedance cardiograms on five subjects during upright cycle exercise at 0, 50, 100, 150, and 200 W to permit comparisons of QZ during NB, expiratory breath hold (EXP) and inspiratory breath hold (INSP). Q was also determined using an equilibration CO2 rebreathing method [Q(RB)]. QZ during NB exceeded EXP QZ at 100, 150, and 200 W, and exceeded INSP QZ at 100 W (P less than 0.05). The low EXP QZ values were due to a significantly lower stroke volume at 100, 150, and 200 W (P less than 0.05). For the INSP QZ at 100 W, heart rate was lower than during EXP (P less than 0.05). Regression of QZ (NB) against Q(RB) resulted in a linear relationship (r = 0.93) over the range of Q = 7-26 1/min. The slope of the regression differed significantly from 1.0 (P less than 0.05). We conclude that QZ values obtained during EXP or INSP should not be assumed to represent QZ during NB, at least at work rates greater than 50 W. A consequence of the linear relationship between QZ(NB) and Q(RB) over the range of 0-200 W is that estimates of CO2 rebreathing cardiac output can be obtained by impedance cardiography if QZ is adjusted using an appropriate empirical factor.     

Calculation of volumes and systolic indices of heart ventricle from Halobatrachus didactylus: echocardiographic noninvasive method

The purpose of this work is to calculate end-systolic and end-diastolic volumes of Halobatrachus didactylus ventricles, from two-dimensional (2D) echocardiographic images, comparing four different linear methods, and to derive systolic indices of ventricular function-fractional shortening, ejection fraction, stroke volume, and cardiac output independent of the Fick principle. Echocardiography provided high resolution images of cardiac structures and allowed accurate linear measurements. The Simpson algorithm proved to be the best method of calculating ventricle volumes. As a corollary, ventricular mass can be derived from echocardiographic volume data. This noninvasive method promises wide utilization in experimental comparative cardiovascular biology.     

Continuous cardiac output monitoring in humans by invasive and noninvasive peripheral blood pressure waveform analysis.

We present an evaluation of a novel technique for continuous (i.e., automatic) monitoring of relative cardiac output (CO) changes by long time interval analysis of a peripheral arterial blood pressure (ABP) waveform in humans. We specifically tested the mathematical analysis technique based on existing invasive and noninvasive hemodynamic data sets. With the former data set, we compared the application of the technique to peripheral ABP waveforms obtained via radial artery catheterization with simultaneous thermodilution CO measurements in 15 intensive care unit patients in which CO was changing because of disease progression and therapy. With the latter data set, we compared the application of the technique to noninvasive peripheral ABP waveforms obtained via a finger-cuff photoplethysmography system with simultaneous Doppler ultrasound CO measurements made by an expert in 10 healthy subjects during pharmacological and postural interventions. We report an overall CO root-mean-squared normalized error of 15.3% with respect to the invasive hemodynamic data set and 15.1% with respect to the noninvasive hemodynamic data set. Moreover, the CO errors from the invasive and noninvasive hemodynamic data sets were only mildly correlated with mean ABP (rho = 0.41, 0.37) and even less correlated with CO (rho = -0.14, -0.17), heart rate (rho = 0.04, 0.19), total peripheral resistance (rho = 0.38, 0.10), CO changes (rho = -0.26, -0.20), and absolute CO changes (rho = 0.03, 0.38). With further development and successful prospective testing, the technique may potentially be employed for continuous hemodynamic monitoring in the acute setting such as critical care and emergency care.     

Changes in cardiac output during sustained maximal ventilation in humans

To determine the increment in cardiac output and in O2 consumption (Vo2) from quiet breathing to maximal sustained ventilation, Vo2 and cardiac output were measured using an acetylene rebreathing technique in five subjects. Cardiac output and Vo2 were measured multiple times in each subject at rest and during sustained maximal ventilation. During maximal ventilation subjects breathed 5% CO2 to prevent hypocapnia. The increase in cardiac output from rest to maximal breathing was taken as an estimate of respiratory muscle blood flow and was used to calculate the arteriovenous O2 content difference across the respiratory muscles from the Fick equation. Cardiac output increased by 4.3 +/- 1.0 l/min (mean +/- SD), from 5.6 +/- 0.7 l/min at rest to 9.9 +/- 1.1 l/min, during maximal ventilations ranging from 127 to 193 l/min. Vo2 increased from 312 +/- 29 to 723 +/- 69 ml/min during maximal ventilation. O2 extraction across the respiratory muscles during maximal breathing was 9.6 +/- 1.0 vol% (range 8.5 to 10.7 vol%). These values suggest an upper limit of respiratory muscle blood flow of 3-5 l/min during unloaded maximal sustained ventilation.     

Cardiac output measurement in mice by thermodilution

Traditional methods for measuring cardiac output in mice are invasive and traumatic. The authors discuss using the less-invasive thermodilution method, which is widely accepted in humans and other animals.     

Labeled carbon dioxide (C18O2): an indicator gas for phase II in expirograms.

Carbon dioxide labeled with 18O (C18O2) was used as a tracer gas for single-breath measurements in six anesthetized, mechanically ventilated beagle dogs. C18O2 is taken up quasi-instantaneously in the gas-exchanging region of the lungs but much less so in the conducting airways. Its use allows a clear separation of phase II in an expirogram even from diseased individuals and excludes the influence of alveolar concentration differences. Phase II of a C18O2 expirogram mathematically corresponds to the cumulative distribution of bronchial pathways to be traversed completely in the course of exhalation. The derivative of this cumulative distribution with respect to respired volume was submitted to a power moment analysis to characterize volumetric mean (position), standard deviation (broadness), and skewness (asymmetry) of phase II. Position is an estimate of dead space volume, whereas broadness and skewness are measures of the range and asymmetry of functional airway pathway lengths. The effects of changing ventilatory patterns and of changes in airway size (via carbachol-induced bronchoconstriction) were studied. Increasing inspiratory or expiratory flow rates or tidal volume had only minor influence on position and shape of phase II. With the introduction of a postinspiratory breath hold, phase II was continually shifted toward the airway opening (maximum 45% at 16 s) and became steeper by up to 16%, whereas skewness showed a biphasic response with a moderate decrease at short breath holding and a significant increase at longer breath holds. Stepwise bronchoconstriction decreased position up to 45 +/- 2% and broadness of phase II up to 43 +/- 4%, whereas skewness was increased up to twofold at high-carbachol concentrations. Under all circumstances, position of phase II by power moment analysis and dead space volume by the Fowler technique agreed closely in our healthy dogs. Overall, power moment analysis provides a more comprehensive view on phase II of single-breath expirograms than conventional dead space volume determinations and may be useful for respiratory physiology studies as well as for the study of diseased lungs.     

Respiratory measurements of cardiac output: from elegant idea to useful test.

The measurement of cardiac output was first proposed by Fick, who published his equation in 1870. Fick's calculation called for the measurement of the contents of oxygen or CO2 in pulmonary arterial and systemic arterial blood. These values could not be determined directly in human subjects until the acceptance of cardiac catheterization as a clinical procedure in 1940. In the meanwhile, several attempts were made to perfect respiratory methods for the indirect determination of blood-gas contents by respiratory techniques that yielded estimates of the mixed venous and pulmonary capillary gas pressures. The immediate uptake of nonresident gases can be used in a similar way to calculate cardiac output, with the added advantage that they are absent from the mixed venous blood. The fact that these procedures are safe and relatively nonintrusive makes them attractive to physiologists, pharmacologists, and sports scientists as well as to clinicians concerned with the physiopathology of the heart and lung. This paper outlines the development of these techniques, with a discussion of some of the ways in which they stimulated research into the transport of gases in the body through the alveolar membrane.     

Investigations concerning the application of the cross-correlation method in cardiac output measurements

ABSTRACT: BACKGROUND: In spite of numerous non-invasive examinations the "gold clinical standard" of cardiac output measurements is the invasive pulmonary artery catheterization by means of the Swan-Ganz catheter and the application of the thermodilution method to estimate the blood flow. The results obtained by means of thermodilution are sensitive to many physical and biological disturbances. The unreliability of this method amounts to 20-45% and depends on the given variant of the method. Therefore some other method, more accurate and resistant to disturbances, was looked for. This paper presents a new approach to cardiac output measurements, based on cross-correlation signal analysis. The goal of investigations was to verify experimentally the application of the cross-correlation method of cardiac output measurements. RESULTS: In 99.2% of the examined cases the extreme of the cross-correlation function was easy to be estimated by numerical algorithms. In 0,8% of the remaining cases (with a plateau region adjacent to the maximum point) numerical detection of the extreme was inaccurate. The typical unreliability of the investigated method amounted o 5.1% (9.8% in the worst case). Investigations performed on a physical model revealed that the unreliability of cardiac output measurements by means of the cross-correlation method is 3-5 times better than in the case of thermodilution. CONCLUSIONS: The performed investigations and theoretical analysis have shown, that the cross-correlation method may be applied in cardiac output measurements. This kind of measurements seems to be more accurate and disturbance-resistant than clinically applied thermodilution.