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Department of Anesthesiology, Universitaetsklinikum der RWTH Aachen, Aachen, Germany
Address correspondence and reprint requests to Dr. Rolf Dembinski, Klinik fuer Anaesthesiologie, Universitaetsklinikum der RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany. Address e-mail to rolf.dembinski{at}post.rwth-aachen.de
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Abstract |
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A/
) distribution were performed at the onset of ALI and after 2, 4, 8, and 12 h. The main result was an improvement of oxygenation because of a decrease of pulmonary shunt and an increase of areas with normal A/ ratios during PSV (P < 0.005). However, during CMV, a more pronounced reduction of shunt was observed compared with PSV (P < 0.005). We conclude that, in this model of ALI, PSV improves gas exchange because of a reduction of A/ inequality. However, improvements in A/ distribution may be more effective with CMV than with PSV. IMPLICATIONS: Assisted spontaneous breathing may have beneficial effects on gas exchange in acute lung injury. We tested this hypothesis for pressure support ventilation in an animal model of acute lung injury. Our results demonstrate that pressure support does not necessarily provide better gas exchange than controlled mechanical ventilation.
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Introduction |
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A/ ) ratios, and increased dead space ventilation ( D/ T) may further impair gas exchange. Thus, hypoxemia is refractory to high inspiratory oxygen fractions. Compared with the passive movement of the diaphragm during controlled mechanical ventilation (CMV), the activity of the diaphragm during spontaneous breathing is accompanied by a more pronounced movement in the posterior regions of the lung (5,6). Therefore, it has been suggested that, in ARDS, the preservation of some degree of spontaneous breathing may be beneficial for the distribution of A/ because of an alveolar recruitment of otherwise atelectatic posterior lung units (7–10). Putensen et al. (11) demonstrated that, in patients with ARDS, partial ventilatory support for 1 h may result in an improvement of pulmonary gas exchange because of a redistribution of A/ when spontaneous breathing is possible throughout the respiratory cycle. In contrast, pressure support ventilation (PSV) providing mechanical assistance for each respiratory effort did not reveal improvements in A/ distribution or gas exchange when compared with CMV in this study. However, the prolonged effects of PSV in comparison to CMV remain unknown, which might be particularly interesting because it has been shown that airway pressure release ventilation might take some time to reveal the beneficial effects on gas exchange in patients with ARDS (12). This study was performed to determine whether long-term PSV may increase oxygenation because of an improvement in A/ distribution. |
Methods |
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In 20 female pigs weighing 30 ± 2 kg (mean ± SD), anesthesia was induced with 5 mg/kg thiopental and maintained with continuous infusion of 5–10 mg · kg-1 · h-1 thiopental and 8–12 µg · kg-1 · h-1 fentanyl. Animals were positioned supine, intubated with an 8.0- to 9.0-mm inside diameter endotracheal tube (Mallinckroth, Athlone, Ireland), and submitted to volume CMV (Evita; Dräger, Lübeck, Germany) with a respiratory rate (RR) of 20 min-1, a tidal volume (VT) of 10 mL/kg, an inspiratory/expiratory time ratio of 1:2, and a positive end-expiratory pressure (PEEP) of 5 cm H2O. The inspiratory oxygen fraction (FIO2) was kept at 1.0. A 16-gauge arterial catheter (Vygon, Ecouen, France) and an 8.5F venous sheath (Arrow Deutschland GmbH, Erding, Germany) were inserted percutaneously into femoral vessels. A right heart catheter (model AH-05050, 7.5F; Arrow Deutschland GmbH) was positioned in a pulmonary artery under transduced pressure guidance. The blood temperature, determined by means of the pulmonary artery catheter, was maintained at 36.7° ± 0.9°C during the experiment by using an infrared warming lamp and a warming pad. A continuous infusion of 4–5 mL · kg-1 · h-1 of a balanced electrolyte solution was administered for adequate hydration.
Data Acquisition
All hemodynamic measurements were taken in the supine position with zero reference level at the midchest. Central venous pressure (CVP), mean arterial blood pressure (MAP), mean pulmonary artery pressure, and pulmonary capillary wedge pressure were transduced (pvb; Medizintechnik, Kirchseeon, Germany) and recorded (AS/3 Compact; Datex-Ohmeda, Achim, Germany). Cardiac output (CO) was measured by using standard thermodilution techniques and expressed as the mean of three measurements at end-expiration of different respiratory cycles. Heart rate (HR) was traced by the blood pressure curve. Systemic (SVR) and pulmonary vascular resistance were determined by using standard formulas.
Blood samples were collected simultaneously in duplicate, and analysis of arterial and mixed venous blood gases (PO2, PCO2), hemoglobin (Hb), and oxygen saturation (HbO2) was performed immediately. Blood gases were determined by using standard blood gas electrodes (ABL 510; Radiometer Copenhagen, Denmark). The variables Hb, HbaO2, and HbvO2 were measured via species-specific spectroscopy (OSM 3; Radiometer Copenhagen). Venous admixture ( VA/ T) was calculated by using the secondary variables arterial (CaO2), mixed venous (CvO2), and arterial capillary oxygen content (CcO2) as described recently (13). Also, oxygen delivery (DO2) and consumption (O2) were calculated. The data were presented as the mean of each measurement taken in duplicate.
A/ distributions were analyzed by using the multiple inert gas elimination technique (14). Briefly, two blood samples were taken to determine blood gas coefficients for six inert gases (sulfur hexafluoride, ethane, cyclopropane, enflurane, ether, and acetone) in duplicate for each animal. Then, 45 min before the first blood sampling for A/ calculation, an isotonic saline solution equilibrated with these 6 inert gases was infused into a peripheral vein at a constant rate of 4 mL/min. Samples of arterial and mixed venous blood and mixed expired gas were collected simultaneously at each study point during several respiratory cycles by using glass syringes (Popper & Sons Inc., Hannover, Germany) and analyzed immediately by using gas chromatography (GC 14 B; Shimadzu, Duisburg, Germany) with Porapak® T packed columns (Agilent Technologies, Waldbronn, Germany). Sulfur hexafluoride was examined by using the electron capture detector, whereas the other five gases were examined by using the flame ionization detector. The expiratory tubing and the mixing box for the expired gas samples were heated above body temperature to avoid a loss of the more soluble gases in condensed vapor. All samples were taken in duplicate. For each inert gas, retention (the ratio of the gas concentration in arterial to that in mixed venous blood) and excretion (the ratio of the gas concentration in expired gas to that in mixed venous blood) were calculated, and A/ distributions were estimated by using the individual blood gas coefficients of each animal. The duplicate samples were processed separately, resulting in two A/ distributions for each condition investigated in this study. The presented data were the mean values of A/ distributions taken in duplicate.
Shunt ( S/ T) was defined as the fraction of pulmonary blood flow ( T) perfusing unventilated alveoli (A/ = 0). Low A/ regions were defined as those with A/ ratios between 0.005 and 0.1, normal A/ regions as those with A/ ratios between 0.1 and 10, and high A/ regions as those with A/ ratios between 10 and 100. Data for perfusion distribution were presented in percent of total pulmonary blood flow and expressed as low, normal, and high. Accordingly, D/ T was defined as the fraction of gas entering unperfused lung units (A/ > 100), and ventilation of normal A/ areas was described as normal. The position of the distributions was also described by the mean A/ ratio for perfusion and ventilation (mean , meanA) and their dispersion by the log standard deviation of both perfusion (log SD ) and ventilation (log SDA).
Experimental Protocol
Baseline measurements, including hemodynamics and blood gas analyses, were performed when animal preparation was completed to confirm physiologic circulatory conditions. Then, acute lung injury (ALI) was induced by surfactant depletion caused by repeated lung lavage as described previously (13,15). The experimental protocol was started when a PaO2 < 100 mm Hg was achieved for >1 h. Subsequently, animals were randomized by a toss-up procedure to receive PSV (n = 10) with a PSV level set to achieve VT > 4 mL/kg and an RR < 40 min-1, or CMV (n = 10) with a VT = 10 mL/kg and an RR = 20 min-1. PEEP was adjusted to 10 cm H2O in both groups. In the CMV group, animals were sedated with thiopental and fentanyl and paralyzed with 0.2–0.4 mg · kg-1 · h-1 pancuronium whereas sedation without muscle relaxation in the PSV group was reduced to allow spontaneous breathing activity with continuous infusion of 2–5 mg · kg-1 · h-1 thiopental and 6–8 µg · kg-1 · h-1 fentanyl. Measurements, including determination of hemodynamics, blood gases, and A/ distribution, were performed after the induction of ALI and after 2, 4, 8, and 12 h. At the end of the experiments, the animals were killed with IV potassium chloride in deep sedation.
All values were expressed as means ± SD. Variables were statistically analyzed (SigmaStat for Windows 5.0; Jandel, San Rafael, CA) by using two-way analysis of variance (ANOVA) for repeated measures to compare values after 2, 4, 8, and 12 h with ALI values within each group and corresponding values between both groups. Because the values for S/ T and low were not normally distributed, these variables were analyzed within the groups by using the Friedman’s ANOVA on ranks and between the groups with the Mann-Whitney ranked sum test. Statistical analyses were followed by the Student-Newman-Keuls test for all pairwise comparisons when ANOVA revealed significant results. P values < 0.05 were considered significant.
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Results |
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Whereas the respiratory settings were fixed in the CMV group, ventilation variables in the PSV group were significantly different: RR and E increased whereas VT decreased after 2 h until the end of the study when compared with ALI and with corresponding values in the CMV group (P < 0.005). Ventilator settings and respiratory mechanics are demonstrated in Table 1.
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VA/ T were more pronounced with CMV than with PSV (P < 0.005). The secondary variables DO2 and O2 remained unchanged over the entire study period.
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A/ distribution data was confirmed by calculating the residual sum of squares (16). In 80% of the experimental runs, the residual sum of squares was <5.3 and in 92% <10.6. Analyses of A/ distributions revealed changes in A/ distribution (P < 0.005): In the PSV group, D/ T increased and normal decreased. In contrast, ventilation distribution in the CMV group remained unchanged. In both groups, normal increased and S/ T decreased but the reduction of S/ T in the CMV group exceeded those obtained with PSV (see Fig. 1). In the CMV group, a decrease in mean was observed for the entire study period.
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Discussion |
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A/ distribution during PSV. However, CMV with equal PEEP levels exceeded these improvements in gas exchange because of a more pronounced reduction of pulmonary shunt.
In patients with ARDS, the distribution of A/ is characterized by increased shunt, small amounts of low, and reduced blood flow to lung areas with a normal A/ ratio. Furthermore, D/ T is increased (2,4). Accordingly, comparable mean values for A/ distributions have been revealed in this study because of experimental ALI induced by repeated lung lavage.
In the present study, CMV and PSV with a PEEP level of 10 cm H2O improved pulmonary gas exchange significantly after 2 hours. In contrast, CMV with a PEEP level of 5 cm H2O did not result in an increase of PaO2 but caused death after 4 hours in a previous study using the same model of lung injury (17). Therefore, it seems likely that the improvement in gas exchange with CMV in this study was mainly caused by an alveolar recruitment attributable to the implementation of a PEEP level of 10 cm H2O, as has been demonstrated in clinical trials (2,18). The same effect of alveolar recruitment in otherwise nonventilated lung regions may be responsible for the improvement in the PSV group.
Spontaneous breathing activity with PSV did not cause an additional improvement in gas exchange, and A/ distribution was somewhat worse when compared with CMV. These effects may be explained by different mechanisms.
First, in some animals, the implementation of spontaneous breathing was difficult to perform: rapid changes in the drive of breathing caused changes in RR and VT that were difficult to adjust in time. However, these problems were mainly present in the beginning of the study period and may have influenced primarily the measurements after 2 hours but not those after 4, 8, and 12 hours.
Second, regarding the fast RR of the animals, a VT of approximately 4 mL/kg was adjusted to avoid excessively high E. As a consequence, lower VT may have resulted in decreased gas exchange because of a reduced alveolar ventilation and recruitment and an increased D/ T when compared with CMV. In fact, a A/ distribution analysis revealed a decrease in normal and an increase in D/ T with PSV, whereas S/ T was lower during CMV. However, actual recommendations of respirator settings in ARDS frequently include ventilation with low VT to limit ventilator-induced lung injury (19), and negative effects seem to be negligible. However, different T are a common finding when comparing CMV and PSV in clinical settings (20). Thus, the setting used in this study reflects the clinical situation and is therefore suitable to compare both ventilator strategies.
Third, the uncoupling of spontaneous and mechanical breaths may be a predisposing factor for beneficial effects not only for a short time but also for long-term spontaneous breathing in ALI. As Putensen et al. (11) suggested, an improvement of A/ distribution probably takes place only during spontaneous breathing without inspiratory mechanical support but not during PSV with inspiratory mechanical support of each breath. This hypothesis is supported by the present study for long-term PSV in experimental lung injury.
The differences of A/ distribution between PSV and CMV were quantitative but also qualitative, at least in some animals. Thus, CMV caused a reduction in mean and, at least in some animals, a marked blood flow redistribution from shunt areas to low A/ regions. As an example, A/ distribution of 1 animal at ALI and 12 h is demonstrated in Figure 2. Comparable increases in low were obtained in four pigs of the CMV group but not in the PSV group. These changes did not reach statistical significance for the CMV group, but regarding the significant decrease of mean , there is evidence that during CMV, shunt decreased not only for the benefit of blood flow to areas with normal but also to those with low A/ ratio. Probably, CMV did not recruit atelectatic lung regions continuously throughout the whole respiratory cycle but mainly during end-inspiration, whereas partial alveolar collapse resulted during expiration. According to this assumption, a higher PEEP level would have resulted in continuous recruitment and further improved pulmonary gas exchange, as revealed recently by Foti et al. (21) in patients with ARDS (21). They demonstrated that periodic lung recruitment maneuvers at low PEEP levels are less effective than continuous high PEEP levels without recruitment maneuvers. Thus, the results in the CMV group may have been caused by a comparable mechanism of tidal recruitment in some animals. Compared with PSV, recruitment during CMV is probably more pronounced but results in low A/ areas as well. In contrast, lung recruitment with PSV seems to be less effective but more homogenous because of lower T and airway pressures resulting in higher amounts of shunt instead of low.
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O2 demonstrated that even the faster RR during spontaneous breathing does not necessarily result in an increased oxygen consumption. In conclusion, compared with CMV, spontaneous breathing activity with PSV does not provide beneficial short-term or long-term effects on gas exchange in this animal model of ALI. Whether other respiratory modes allowing spontaneous breathing during mechanical ventilation may improve gas exchange over time needs to be determined in long-term evaluations.
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Acknowledgments |
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Footnotes |
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