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*Institute of Anesthesiology and Intensive Therapy,
Division of Cardiac Surgery, and
Department of Medical Informatics and Engineering, University of Szeged, Szeged, Hungary
Address correspondence and reprint requests to Zoltán Hantos, PhD, Department of Medical Informatics and Engineering, University of Szeged, PO Box 427, H-6701 Szeged, Hungary. Address e-mail to hantos{at}dmi.u-szeged.hu
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Abstract |
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IMPLICATIONS: We observed that cardiopulmonary bypass deteriorates lung function by inducing a heterogeneous airway constriction, whereas no such effects were observed in patients undergoing cardiac surgery without bypass. The impairment in parenchymal mechanics, which was obtained in both groups, may result from peripheral airway closure and/or be a consequence of mediator release.
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Introduction |
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Whereas studies involving use of the end-inflation occlusion technique (10) have revealed consistent increases in respiratory elastance (Ers) (7–9,11,12), the findings relating to changes in the end-inspiratory airway (Rmin) or tissue resistances (Rti) after CPB are far less uniform. Rmin or Rti has been reported to be decreased (5) or unchanged (8,12) after CPB, whereas CPB leads to the onset of an intrinsic positive end-expiratory pressure (PEEP), indicating an increase in airway resistance (Raw) (9,11,13). Furthermore, measurements made in the frequency and tidal volume ranges of normal breathing have revealed increases in pulmonary elastance and resistance after CPB (14,15), whereas these adverse changes were not observed with off-pump coronary artery bypass grafting surgery (OPCAB) (15).
Studies in which the respiratory or lung impedance is partitioned into airway and tissue components allow an evaluation of the responses of the respiratory tissues to various stimuli (16–19). Because the airway and tissue mechanical responses may dissociate (17), the changes (or the lack of response) in the overall mechanical variables may lead to false conclusions concerning the mechanical status of the respiratory system and the loci of the changes. The goal of this study was to characterize the effects of CPB on the airway and tissue mechanics separately. We compared the changes in the mechanical properties of the airways and respiratory tissues in three groups of anesthetized, paralyzed patients undergoing elective cardiac surgery, not using CPB or using CPB, with or without the administration of dopamine (DA). The study groups were designed to form homogeneous cohorts regarding the anesthetic management, in particular the administration of bronchoactive drugs (adrenoreceptor agonists, volatile anesthetics, calcium channel blockers, and so on). The airway and tissue mechanical properties were separated via a model-based evaluation of the low-frequency respiratory impedance spectra (Zrs) (16–19). In an attempt to characterize the underlying mechanisms responsible for the changes in respiratory mechanics, we measured the amount of extravascular lung water (EVLW) (19) in a smaller cohort of the study population before and after CPB.
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Methods |
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The patients were ventilated with a Siemens Servo 900C ventilator (Siemens-Elema) in volume-controlled, constant-flow mode by setting the inspiratory/expiratory ratio to 
1:3 and the end-inspiratory pause to 10% of the total cycle and by applying a PEEP of 2 cm H2O. A fraction of oxygen in the inspired air of 0.5–0.8 and a tidal volume of 10 mL/kg were applied, and the ventilatory frequency was adjusted to maintain a normal PaCO2 level. In the CPB group, mechanical ventilation was stopped during cardioplegic cardiac arrest without applying a positive airway pressure. Before the declamping of the aorta, the lungs were inflated three to five times to a peak airway pressure of 30 cm H2O to facilitate the removal of gas emboli from the heart and to reexpand the lungs. Ventilation was restored before the patient was weaned from CPB. To exclude the potential biasing effects of positive inotropic drugs, the patients in the major study populations were selected so that no such drugs were involved.
In a small cohort of the CPB group (n = 5), a transpulmonary arterial thermodilution system (PiCCO; Pulsion Medical System, Munich, Germany) was used to measure EVLW (20). A fiberoptic thermistor catheter was inserted into the femoral artery. The thermal indicator bolus was injected into the right atrium via a central venous catheter. The monitor determined the mean transit time of the thermal indicator and calculated EVLW. EVLW and Zrs were measured at the same time.
The equipment used for the impedance measurements (Fig. 1) is a modification of the low-frequency forced-oscillation setup applied in animal experiments (16,17). Two collapsible latex tube segments (A and B) were clamped alternately to switch the ET tube from the respirator to the oscillatory device and back as follows: during mechanical ventilation, A was open and B was closed. Before the oscillatory measurements, the lungs were inflated to a pressure of approximately 30 cm H2O to standardize the volume history. Segment B was then opened for a few ventilatory cycles before data acquisition to equilibrate the pressures in the lungs and the loudspeaker chambers. In the resulting apneic period, small-amplitude (<1 cm H2O) pseudorandom pressure excitations were introduced into the trachea. The forcing signal contained 30 integer-multiple components of the fundamental frequency 0.2 Hz, in the frequency range 0.2–6 Hz.
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) was measured with a 28-mm-inner diameter screen pneumotachograph connected to a differential pressure transducer (ICS Model 33NA002D; ICSensors, Miltipas, CA). To exclude the ET tube impedance from our measurements, we measured tracheal pressure (Ptr) with an identical pressure transducer through a 1.5-mm-outer diameter polyethylene catheter furnished with several lateral holes at the tip that was positioned 1.5–2 cm over the distal end of the ET tube. Four to 6 recordings, each 15 s long, were collected at end-expiration, both immediately before the skin incision and at the end of the operation, just before removal of the surgical preparation. At least 2-min periods of mechanical ventilation were interposed between the successive Zrs measurements. The electrical signals of the transducers were low-pass filtered at 25 Hz and digitized at a rate of 256 Hz by the analog-to-digital board of a personal computer. The transfer function between the transducers was determined by exposing the sensors with their connecting tubing to the same oscillatory pressure fluctuation, to take into account the differences in the frequency responses and to correct the impedances accordingly.
The mechanical impedance of the respiratory system was calculated from the Ptr and signals (Zrs = Ptr/). The impedance spectra were calculated by fast Fourier transformation by using a 5-s time window and 95% overlapping. The impedance curves were ensemble-averaged for each patient and condition.
At low oscillation frequencies, the airways and the parenchyma exhibit distinctly different frequency dependencies, which allows the separation of the mechanical properties of the two compartments (16–19). The airways can be described by a frequency-independent Raw and airway inertance (Iaw), whereas both the parenchymal resistance and reactance change roughly inversely with increasing frequency (16–19). These characteristics can be used to separate the airway and parenchymal properties by fitting a model containing a frequency-independent Raw and Iaw connected in series with a constant-phase tissue compartment (16) representing tissue damping (G) and elastance (H): equation
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where Rrs and Xrs are the respiratory resistance and reactance, respectively; j is the imaginary unit; 
is the angular frequency; and 
is expressed as = 2/
arctan(H/G). The model was fitted to each impedance spectrum by minimizing the absolute differences between the measured and the modeled impedance data. Impedance data points coinciding with the heart rate and its harmonics had low reproducibility and were therefore excluded from the model fit. Tissue hysteresivity (
) values were calculated as = G/H (21).
The values are reported as means ± SE. The Kolmogorov-Smirnov test was used to test data for normality. Two-way repeated-measures analyses of variance (ANOVAs) with the presence or absence of CPB as the first variable and the time of the measurement (before or after the surgery) as the second variable were used to estimate the effects of CPB on the mechanical conditions of the lungs. Another two-way repeated-measures ANOVA, with the administration of DA as the first factor and the time of the measurement as the second factor, was applied to assess the effect of DA on the changes in lung mechanics during surgery. Pairwise comparisons were performed by using Student-Newman-Keuls multiple comparison procedures. Statistical significance was accepted at the P < 0.05 level.
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Results |
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after CPB (18.3% ± 10.4%) was not statistically significant. In contrast with the significant increase in Raw in the CPB patients, a marked and statistically significant decrease was observed in Raw (-40.6% ± 9.2%) in the CPB-DA group. In the latter group, the small decreases in G (-3.5% ± 8.1%) were associated with moderate increases in H (18.3% ± 5.3%). The opposite changes in G and H resulted in a decreased (-18.7% ± 5.2%). The patients in the OPCAP group showed no statistically significant change in Raw (11.8% ± 7.9%), Iaw (8.1% ± 18.0%), or (4.9% ± 3.7%), whereas G (60.0% ± 10.4%) and H (54.6% ± 9.5%) increased significantly.
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(P < 0.05); i.e., the changes in these variables were significantly influenced by the presence or absence of CPB during cardiac surgery. Highly significant interactions were observed between the effects of DA and time (before or after surgery) in Raw (P < 0.000001), Iaw (P < 0.05), G (P < 0.02), and (P < 0.01), demonstrating that the administration of DA affected the changes in the mechanical variables significantly during cardiac surgery requiring CPB. There was no difference (P = 0.6) between the EVLW values measured before (540.4 ± 60.5 mL) and after (544.8 ± 21.4 mL) CPB. |
Discussion |
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In this study, we enrolled patients with coronary artery disease and aortic or mitral valve diseases. Because patients with poor ejection fraction and high left ventricular end-diastolic pressure were omitted from the study population, it can be expected that the pulmonary circulation was not markedly affected by the cardiac disorder. Therefore, it may be anticipated that changes in lung mechanics were not due to altered pulmonary hemodynamics associated with postcapillary congestion (6).
The mechanical properties of the respiratory system at the usual range for spontaneous breathing frequency are determined to a comparable degree by the airways and the respiratory tissues (16–19,22). Small-amplitude low-frequency forced oscillations and fitting of the constant-phase model (16) to the impedance spectra provide a noninvasive technique for study of the airway and tissue mechanical variables separately. Because the changes in the respiratory system were expected to affect both the airway and tissue compartments, the forced oscillation method at low frequencies was considered an appropriate and sensitive technique with which to characterize the CPB-induced changes in the lungs.
The pulmonary and chest wall contributions to Rrs and the total Ers have been reported to be approximately equal in adult humans (7,22). Although the tissue variables G and H combine the mechanical properties of the lungs and the chest wall, the earlier finding that the chest wall elastance and resistance were unchanged after cardiac surgery (7) suggests that the lungs are responsible for the changes observed in this study. Nevertheless, the constancy of the chest wall variables blunts the increases observed in G and H after CPB.
Without the administration of adrenergic drugs, CPB induced significant increases in Raw that were associated with significant, but highly variable, decreases in Iaw. In contrast, these adverse changes in airway mechanics were not detectable in the OPCAB patients. Because the resistance and inertance are inversely related to the fourth and second power, respectively, of the radius of an airway, a decrease in the overall airway diameter is expected to increase both Raw and Iaw; this was not the case in the CPB patients. This controversial behavior of the airway variables can be interpreted in terms of inhomogeneous narrowing of the peripheral airways, which not only influences Rrs, but also alters the frequency dependence of Xrs, leading to biased estimates of Iaw (16), a mechanism confirmed by studies in which different resident gases were used during induced bronchoconstriction (18,19). According to previous studies (16,18,19), the increase in Raw after CPB is a result of inhomogeneous peripheral airway constriction, whereas the mechanisms involved in the airway narrowing remain speculative. Incomplete reopening of the peripheral lung after the standardizing volume excursion, distortions in lung configuration persisting temporarily after the closure of the chest, and uneven mucus deposition may all have led to increases in Raw. Because these factors existed in both the CPB and the OPCAP groups and because there was no change in the airway variables in the latter population, it seems more likely that a mechanism related specifically to the CPB was responsible for the adverse changes in the bronchial tree. This finding also agrees with the results of a recent study that reported impaired oxygenation and lung mechanics in CPB patients, whereas it demonstrated that OPCAB surgery had no measurable detrimental effects on the lungs (15). As concerns the potential mechanisms responsible for the adverse changes after CPB, the systemic inflammatory reaction induced by the extracorporeal circulation (23) might have led to airway narrowing via mucosal thickening or the release of bronchoactive contractile mediators.
Measurements of the flow and the sudden decrease in airway opening pressure after an end-inspiratory occlusion were used previously to estimate the changes in airway mechanics after CPB (5,8,12). In contrast with our findings, the authors who applied this technique demonstrated either a decrease (5) or no change (8,12) in Rmin immediately after cardiac surgery. In other studies, evaluation of the alveolar pressure during end-expiratory occlusions with a simple bedside respiratory monitor pointed to the appearance of an intrinsic PEEP (9,11,13). This was interpreted as a marker of increased Raw after CPB, which agrees with our results on Raw. The discrepancies between the results of the previous studies and the present ones can most probably be attributed to the different lung volumes at which the measurements were performed. It is apparent that the studies that suggested a decrease or no change in Raw were made at end-inspiration (5,8,12), whereas the measurements of intrinsic PEEP were made and the current forced oscillatory data were collected at end-expiration, where the likelihood of partial closure of the airways is enhanced.
We found significant increases in the respiratory tissue variables G and H in both the CPB and OPCAB groups. Because the increases in G exceeded those in H, the restrictive changes in the lung periphery may have been accompanied by other mechanisms. Smooth muscle constrictor drugs induce larger increases in Rti than in elastance (24). This phenomenon is attributed to the altered coupling between the resistive and elastic properties at the elementary level of the parenchyma and is therefore considered an intrinsic response of the lung tissue (21). However, inhomogeneous peripheral airway constriction increases the frequency-dependent component of pulmonary resistance, which is then readily accounted for by an artifactually increased value of G estimated from the fitting of the four-variable single-compartment model (16,18,19).
Although all the above-mentioned mechanisms may have coexisted in our measurements in both the CPB and the OPCAB groups, their respective roles were probably not equally important. Intrinsic changes in parenchymal viscoelastic properties may result from edema development or from the liberation of constrictor mediators acting mainly on the parenchymal contractile apparatus. The lack of change in EVLW indicates that edema did not develop, although this observation is based on measurements in a subgroup of CPB patients only. The liberation of mediators altering the parenchymal mechanics does not seem likely either, because the perioperative increases in the tissue variables in the CPB and OPCAB groups were similar, whereas the release of mediators is expected to occur primarily in the former patients. Restrictive processes were highly probable in our subjects, because the development of atelectasis with a subsequent decrease in functional residual capacity (FRC) toward the closing capacity is consistently observed after cardiac surgery with CPB (2–4), during anesthesia in the supine position, and during intermittent positive-pressure ventilation (25,26). Indeed, this is in agreement with the increases in H and the proportional parts in G. The excessive increase in G can then be attributed to ventilation inhomogeneities and regarded as a virtual tissue change associated with another artifactual change, i.e., the reduction in Iaw (16,18,19).
The increase in H observed in this study after CPB fits in well with the increases of 16%–35% determined in Ers with the end-inflation occlusion method (EIOM) (8,9,11,12). By contrast, the even more marked increases in G are at variance with the unchanged Rti values obtained with the EIOM (8,12). The explanation for this discrepancy may lie in the different lung volumes at which G and Rti are estimated, which impose different conditions on airway closure. Both G and Rti reflect not only tissue viscoelasticity, but also time constant inequalities; nevertheless, G was estimated with small-amplitude oscillations around the FRC level, whereas Rti was derived from the transient response to the end-inspiratory occlusion, i.e., at an airway opening pressure level of 8–12 cm H2O, where the peripheral airway homogeneity was restored. In turn, the values of Ers correspond to the tidal excursion and hence reflect the elastic resistances at early inspiration, which are different before and after CPB. Therefore, unlike G and H, the resistive and elastic variables derived from the EIOM do not relate to the same inflation level of the respiratory system. Our study design, however, revealed that adverse changes in tissue mechanical variables may be a consequence of the anesthesia and intermittent positive-pressure ventilation, rather than the CPB itself.
Cardiac anesthesia often requires the administration of bronchoactive drugs, such as positive inotropic drugs. These drugs may affect the adverse changes induced by CPB. Therefore, the patients who received DA after CPB were assigned to a third group (CPB-DA). The marked decrease in Raw in these patients can be attributed to a substantial decrease in the bronchial tone, which was significantly higher in this population at the beginning of the surgery. The decreased bronchial tone may have resulted in a more homogeneous ventilation of the lung periphery, which is likely to be reflected in the decreased G and (18). The slight but uniform increases in H can be attributed to a lung volume loss, which may result from the elevated diaphragm. These findings indicate that the administration of DA may prevent some of the detrimental effects of CPB on the airways, although future studies involving patient groups with similar initial mechanical conditions are necessary to confirm this finding.
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Conclusions |
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Acknowledgments |
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The authors are grateful to Medial Ltd., Budapest, Hungary, for their generous support providing the PiCCO equipment.
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