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Departments of *Cardiology,
Cardio-Thoracic Surgery, and
Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands
Address correspondence and reprint requests to Paul Steendijk, PhD, Leiden University Medical Center, Department of Cardiology, PO Box 9600, 2300 RC Leiden, The Netherlands. Address e-mail to p.steendijk{at}lumc.nl
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Abstract |
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IMPLICATIONS: Pressure-volume loops provide on-line quantification of intrinsic systolic and diastolic myocardial function in a load-independent fashion. This study shows the feasibility of perioperative pressure-volume analysis by use of the conductance-catheter method. This method provides detailed data about the immediate effects of surgery and may be used to evaluate complex cardiac procedures.
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Introduction |
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Methods |
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After 2 mg of lorazepam as sublingual premedication 2 h before surgery, all patients received total IV anesthesia with target-controlled infusion of propofol, remifentanil, and sufentanil (3–5). The hypnotic state was monitored with a bispectral index monitor (Aspect Medical Systems, Newton, MA). The induction of anesthesia was started with a targeted concentration of propofol 1.5 µg/mL and remifentanil 3 ng/mL. Before intubation, the remifentanil-targeted concentration was increased to 9 ng/mL and the targeted propofol concentration to 2 µg/mL. A single dose of pancuronium bromide (0.1 mg/kg) was given to facilitate intubation. During surgery, the propofol concentration was adjusted between 1.5 and 2.0 µg/mL to maintain a bispectral index value less than 60. Remifentanil was titrated between 5 and 10 ng/mL in response to the patient’s hemodynamic reaction on surgical stimuli. Sufentanil was started at a targeted concentration of 0.1 ng/mL after the start of surgery to allow smooth transition of the patient’s analgesic state from the operating room to the intensive care unit (ICU). The patients were ventilated with an oxygen/air mixture (fraction of inspired oxygen, 40%) at a ventilatory rate of 12–15 breaths/min, and ventilatory volume was adjusted to maintain PaCO2 between 4.5 and 5.5 kPa (34–41 mm Hg). A thermal filament catheter was placed with its tip in the pulmonary artery via the right internal jugular vein for semicontinuous CO measurements (Edwards Lifesciences, Uden, The Netherlands). A multiplane TEE probe was inserted to monitor cardiac function and facilitate positioning of the conductance catheter perioperatively.
We used a 7F integrated pressure-conductance catheter (CD-Leycom, Zoetermeer, The Netherlands) incorporating a solid-state pressure sensor and 12 electrodes with an interelectrode spacing of 10 mm. A pigtail facilitates placement through the aortic valve and positioning within the LV apex (Fig. 1). The catheter is connected to a Leycom Cardiac Function Lab signal processor. Between the two most proximal and two most distal electrodes, a dual electric field (20 kHz; 30 µA) is generated (6). The remaining eight electrodes are used to measure five segmental volume signals. The user may select from three settings the best match with the LV long axis: by skipping electrodes 1 or 2, 1-cm segments may be converted to 2-cm segments, thereby extending the effective length of the catheter. The optimal setting is selected on the basis of inspection of the segmental volume signals. An aortic volume signal is easily distinguished from a ventricular signal because it resembles an aortic pressure signal and is out of phase with the ventricular volume signals. The segmental conductance values are summed to yield total conductance [G(t)] and, taking into account the specific resistivity of blood and the electrode spacing, converted to a time-varying volume signal, V(t), which follows through the equation:
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is a slope factor, L is the interelectrode spacing, rho is the specific resistivity of blood measured from a 5-mL blood sample by using a special four-electrode cuvette connected to the Cardiac Function Lab, and GP is the parallel conductance. G(t) is the sum of the conductance of the blood in the LV and GP. The latter results from the conductance of the ventricular wall, other cardiac chambers, and, to some extent, all electrically conductive structures outside the LV cavity. Baan et al. (1) devised a method to determine GP by injecting a small bolus (7 mL) of hypertonic saline solution (10%) in the distal port of the pulmonary artery catheter. The highly conductive saline transiently changes blood conductivity, which is measured only in the LV. By analyzing the conductance signal registered during passage of the bolus through the LV, GP can be determined (1). The correction volume (Vc) corresponding to GP can be determined as follows: equation
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After correction for GP, the volume signal is directly proportional to actual ventricular volume but generally underestimates true volume by a fixed factor. There are two main causes for this underestimation. First, there may be a mismatch between the measured segments and the LV long axis. Second, the conversion of conductance to volume assumes that the electric field is homogeneous within the cavity. In reality, this is not entirely the case, and the result is underestimation. The development of dual-field excitation (6) has substantially improved electric field homogeneity, but some underestimation remains, especially in large hearts. To correct for this underestimation, the factor was introduced, which is obtained by comparing conductance-derived stroke volume (SV) with an independent measure of SV. In most studies, is calculated by dividing SV of the conductance catheter by SV obtained by thermodilution: = SVconductance/SVthermodilution. In this study, we compare conductance values with the "stat" CO measurements recorded from a Vigilance® Continuous Cardiac Output Monitoring System (Edwards Lifesciences).
After bypass material was harvested, the pericardium was opened, and epicardial pacemaker leads were placed on the right atrium. A caval tourniquet was applied around the inferior cava to perform temporary preload reductions by caval vein occlusion. After systemic heparinization, a sheath (F8; Cordis, Roden, The Netherlands) was introduced into the ascending aorta for placement of the conductance catheter. Subsequently the conductance catheter was inserted into the LV and positioned along the long axis toward the LV apex. Catheter introduction and positioning were guided and verified by TEE and inspection of the segmental conductance signals. Positioning was aimed at locating the pigtail in the apex and locating the most proximal electrodes just above the aortic valve. Measurements were obtained if five segmental LV volume signals were obtained.
The protocol included measurements at a paced HR of 80 bpm before and after CPB. If the intrinsic rate was more than 80 bpm, the pacemaker was set slightly above the intrinsic rate. Pressure-volume loops were measured at steady-state and during transient vena caval occlusion (typical pressure decrease of 20 mm Hg within 5–10 s) to obtain systolic and diastolic pressure-volume relationships. Mechanical ventilation was interrupted to exclude the effects of respiration. Rho was measured just before data acquisition, both before and after CPB. Additional acquisitions (before and after CPB) were performed for determination of GP after the injection of 7 mL of 10% hypertonic saline solution through the distal port of the pulmonary artery catheter. Independent CO measurements by thermodilution were obtained during steady-state. The thermodilution catheter provides update measurements approximately every minute that indicate average CO over the preceding period. An analog signal reflecting the "stat" signal was recorded simultaneously with the pressure-volume signals for off-line calculation of .
Baseline hemodynamic data were calculated from steady-state pressure-volume loops: HR, end-systolic volume, end-diastolic volume (EDV), end-systolic pressure (ESP), end-diastolic pressure (EDP), CO, SV, stroke work (SW), maximal and minimal rate of LV pressure change (dP/dtMAX and dP/dtMIN), EF, and the relaxation time constant (Tau). Tau, reflecting the early active relaxation process, was calculated as the time constant of monoexponential pressure decay during isovolumic relaxation. The isovolumic period was defined as the period between the time point of dP/dtMIN and the time point at which dP/dt reached 10% of the dP/dtMIN value. Indices of systolic and diastolic function were derived from pressure-volume loops during caval vein occlusion. For systolic function, the ESP-volume relation (ESPVR), the dP/dtMAX-EDV relation, and the preload recruitable stroke work relation (PRSW; SW versus EDV) were determined, and for diastolic function, the chamber stiffness constant (CS) was determined. The systolic relationships were characterized by their slope and volume intercept. The slope of the ESPVR (Ees) and its volume intercept at a fixed systolic pressure of 75 mm Hg are indices of contractility that are largely independent of loading conditions (7,8). The ESPVR was determined by linear regression of ESP-volume points obtained during caval vein occlusion. Similarly, the PRSW slope was determined by plotting SW against EDV, and the same was done for the slope of the dP/dtMAX-EDV relation. The slopes of these two relationships also reflect contractility (9,10). CS was determined by exponential regression of the EDPVR by means of the following equation: equation
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where yo is the pressure asymptote and A is a constant.
Pre- and post-CPB data were compared by using paired Student’s t-tests. Statistical significance was assumed at P < 0.05. All data are presented as mean ± SD.
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Results |
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Rho measurements and assessment of Vc and were performed in each patient before and after CPB. Results are summarized in Table 2. Rho decreased significantly after CPB as expected because of hemodilution. Mean values of Vc and were not significantly altered after CPB but showed a substantial interindividual variability.
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Discussion |
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Previous studies have extensively shown that the conductance catheter can be applied to obtain pressure-volume relationships. Although most patient studies were performed in the catheterization laboratory, several groups have demonstrated feasibility of the technique in the operating room under various conditions (12–14). Consistent with these previous studies, our study demonstrates that perioperative pressure-volume measurements by the conductance catheter can be used to quantify detailed intrinsic systolic and diastolic function within an acceptable time window. Measurements were uncomplicated, and there were no technical difficulties during instrumentation, catheter placement and loading interventions.
New technical aspects of our study were the use of retrograde insertion of the conductance catheter by using TEE guidance compared with the transmitral approach used in previous studies in the operating room. Both approaches may have theoretical advantages and disadvantages. The transaortic approach provides a better match of the catheter position with the LV long axis. Compared with the anterograde placement, this provides a better registration of the volume changes, especially in the basal segments. In contrast, anterograde placement through the mitral valve may complicate interpretation of segmental volume signals because of changes in the mitral valve plane during ejection and filling. Conversely, with retrograde placement, eccentric (anteromedial) displacement of the catheter at the base of the heart may occur. The electric field is such that the measurement electrodes will move approximately parallel to the equipotential planes field, and thus the eccentric movement is unlikely to strongly influence the conductance signal. Another reason for using the transaortic approach is that we aim to apply this methodology in future studies to evaluate the effects of mitral valve surgery, in which case placement through the aortic valve is clearly preferable. Furthermore, we analyzed the changes in the calibration factors. As a disadvantage, substantial between-patient variability was found for calibration factors (rho, , and Vc), indicating the need for careful assessment of these factors in each individual patient. In addition, after CPB, rho and, to a lesser extent, and Vc were changed because of reduced hematocrit, fluid shifts, and possibly altered catheter position with reinsertion. Although the average and Vc were not significantly changed, substantial differences were present in individual patients, indicating that reassessment is required at the various stages of surgery. Besides influencing between- and within-patient variability, the calibration factors are important for determining the absolute accuracy of the conductance-derived volumes.
Calibration factors and Vc are both obtained by means of indicator-dilution methods: thermodilution and saline dilution, respectively. Thermodilution is widely used in the surgical setting, and the accuracy is generally found to be acceptable (15). In this study, we used "stat" continuous CO measurements with a thermal filament catheter that has accuracy comparable to that of the bolus injection method (16,17). The saline dilution method has been used extensively to obtain parallel conductance and was found to be accurate, with a slight tendency to underestimate the parallel conductance obtained by alternative methods (18). An important advantage of these indicator-dilution methods, compared with imaging modalities such as TEE, is that they do not require assumptions regarding the geometry of the ventricle. This may be relevant especially when comparing conditions in which geometrical changes would be anticipated, such as after ventricular reconstruction or mitral valve surgery. Furthermore, the inter- and intraobserver variability of indicator-dilution methods is limited.
Our main physiological findings were that systolic function was unchanged after CPB in these patients undergoing CABG, whereas early relaxation was improved and diastolic stiffness was increased. Previous pressure-volume studies comparing pre- and post-CPB cardiac function in patients undergoing CABG have shown conflicting data. Schreuder et al. (13) reported unchanged systolic function and increased diastolic stiffness, whereas Wallace et al. (14) found a decrease in systolic function but no changes in relaxation or diastolic stiffness. Both studies used cold cardioplegia, whereas our study was performed with warm-blood cardioplegic arrest, which may explain the preserved systolic function in our study as compared with the decrease found by Wallace et al. The unchanged systolic function found by Schreuder et al. may be attributed to their pre-CPB measurement being obtained at a temperature that was decreased to less than 35°C, which, according to a recent study, significantly reduces Ees by approximately 50% (19). Because the post-CPB measurements in Schreuder et al.’s study were performed at 37°C, this may have masked an actual reduction in systolic function.
With regard to diastolic function, all studies report an increase in diastolic stiffness, although in Wallace et al.’s study (14) this effect did not reach statistical significance. Also in the study of Schreuder et al. (13), the increase was less pronounced as compared with our study (39% increase versus 138%). However, Schreuder et al. described the EDPVR as linear, whereas we derived the diastolic stiffness constant from an exponential relation. The increase is most likely due to myocardial edema after CPB, because myocardial lymph flow has been shown to almost cease during cardioplegic arrest (20). De Hert et al. (21) have shown that a more rapid normalization of diastolic stiffness may be obtained by optimizing preload conditions before weaning from CPB. Furthermore, Allen et al. (22) demonstrated that increasing contractility by dobutamine infusion enhanced myocardial lymphatic function, thus speeding edema removal after CPB. Thus, when difficulty is encountered in weaning from CPB because of increased diastolic stiffness, inotropic support should be considered. However, it should be used with caution because it may adversely affect energetics, increase HR, and induce ischemia (23). In addition, several pharmacological substances added to the cardioplegia composition are associated with reduced edema formation (24–26). Remarkably, although diastolic stiffness was increased, early relaxation was improved in our study, as shown by the significantly reduced Tau. After revascularization, enhanced oxygen-dependent reuptake of calcium into the sarcoplasmic reticulum would be expected to improve active relaxation (27). Our findings are consistent with the results of Humphrey et al. (28), who demonstrated a reduced Tau after CPB in patients undergoing CABG. In contrast, De Hert et al. (21) found an increased Tau in a similar patient group. Differences may be due to the applied anesthetic and cardioplegic protocols that influence post-CPB relaxation directly or indirectly via changes in contractility or loading, which are tightly coupled with relaxation (23,29). Thus, unchanged or even increased Tau as found in some studies may be related to post-CPB changes in systolic function and/or loading conditions. In our study, EDV, ESP, dP/dtMAX, and Ees were not significantly altered after CPB, whereas De Hert et al. (21) reported a reduced dP/dtMAX, indicating a reduced contractile state.
As an alternative to invasive volume measurements, several groups have used TEE to obtain on-line area determination (30–33). This method is less invasive, but when used to construct pressure-area loops, it still requires a LV catheter for pressure measurements, and a loading intervention. Schmidlin et al. (33) tested whether pressure-area relations may be used as a surrogate for pressure-volume relations to detect changes in contractile state, and they concluded that pressure-area analysis provides the same changes as pressure-volume analysis. However, the calculations derived from area estimates have several limitations. During the cardiac cycle, through-plane motion of the LV complicates volume calculations when using short-axis area estimates. This effect is even more prominent during acute loading interventions. In contrast, the intraventricular placement of the conductance catheter provides on-line volume measurements of nearly the entire ventricle unaffected by translations or rotations of the heart within the thorax. In general, on-line area determination by TEE requires optimal image quality, and the stability and reproducibility of measurements are better at higher preload conditions because the effects of tracing errors are minimized (31). Area estimates derived during caval vein occlusion could become very small, thereby decreasing the precision of the digital echocardiographic quantification method for calculation of pressure-area relations. In addition, the precision is reduced in the presence of regional wall motion abnormalities (30). Conventional assessment of diastolic function by TEE (i.e., without simultaneous LV pressure measurement) has two disadvantages compared with the conductance-catheter method. First, assessment of both active and passive components requires two separate TEE views: the midpapillary esophageal long-axis view and transgastric short-axis view, respectively (32). Second, the active diastolic relaxation measured by mitral Doppler flow analysis is HR and load dependent.
In conclusion, the limitations of TEE are outweighed by its proven clinical value to visualize the endoventricular wall and to quantify segmental wall motion. Conversely, the important value of the conductance catheter is that it yields accurate, load-independent quantitative data on basic systolic and diastolic function. The possibility to measure these fundamental quantities in addition to the data provided by TEE may prove to be important in selected patient groups to evaluate new surgical techniques or anesthetic drugs or procedures. The physiological effects on systolic and diastolic function reported in this study will be useful reference data for future studies in patients with depressed LV function undergoing cardiac surgery.
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Acknowledgments |
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