Respiratory effects of pressure support ventilation in spontaneously breathing patients under anaesthesia: Randomised controlled trial.

BACKGROUND: Lung volume loss is a major risk factor for postoperative respiratory complications after general anaesthesia and mechanical ventilation. We hypothesise that spontaneous breathing without pressure support may enhance the risk for atelectasis development. Therefore, we aimed at characterising whether pressure support prevents changes in lung function in patients breathing spontaneously through laryngeal mask airway. METHODS: In this randomised controlled trial, adult female patients scheduled for elective gynaecological surgery in lithotomy position were randomly assigned to the continuous spontaneous breathing group (CSB, n = 20) or to the pressure support ventilation group (PSV, n = 20) in a tertiary university hospital. Lung function measurements were carried out before anaesthesia and 1 h postoperatively by a researcher blinded to the group allocation. Lung clearance index calculated from end-expiratory lung volume turnovers as primary outcome variable was assessed by the multiple-breath nitrogen washout technique (MBW). Respiratory mechanics were measured by forced oscillations to assess parameters reflecting the small airway function and respiratory tissue stiffness. RESULTS: MBW was successfully completed in 18 patients in both CSB and PSV groups. The decrease in end-expiratory lung volume was more pronounced in the CSB than that in the PSV group (16.6 ± 6.6 [95% CI] % vs. 7.6 ± 11.1%, p = .0259), with no significant difference in the relative changes of the lung clearance index (-0.035 ± 7.1% vs. -0.18 ± 6.6%, p = .963). The postoperative changes in small airway function and respiratory tissue stiffness were significantly lower in the PSV than in the CSB group (p < .05 for both). CONCLUSIONS: These results suggest that pressure support ventilation protects against postoperative lung-volume loss without affecting ventilation inhomogeneity in spontaneously breathing patients with increased risk for atelectasis development. TRIAL REGISTRATION: NCT02986269.

Lung recruitment by continuous negative extra-thoracic pressure support following one-lung ventilation: an experimental study.

Lung recruitment maneuvers following one-lung ventilation (OLV) increase the risk for the development of acute lung injury. The application of continuous negative extrathoracic pressure (CNEP) is gaining interest both in intubated and non-intubated patients. However, there is still a lack of knowledge on the ability of CNEP support to recruit whole lung atelectasis following OLV. We investigated the effects of CNEP following OLV on lung expansion, gas exchange, and hemodynamics. Ten pigs were anesthetized and mechanically ventilated with pressure-regulated volume control mode (PRVC; FiO2: 0.5, Fr: 30-35/min, VT: 7 mL/kg, PEEP: 5 cmH2O) for 1 hour, then baseline (BL) data for gas exchange (arterial partial pressure of oxygen, PaO2; and carbon dioxide, PaCO2), ventilation and hemodynamical parameters and lung aeration by electrical impedance tomography were recorded. Subsequently, an endobronchial blocker was inserted, and OLV was applied with a reduced VT of 5 mL/kg. Following a new set of measurements after 1 h of OLV, two-lung ventilation was re-established, combining PRVC (VT: 7 mL/kg) and CNEP (-15 cmH2O) without any hyperinflation maneuver and data collection was then repeated at 5 min and 1 h. Compared to OLV, significant increases in PaO2 (154.1 ± 13.3 vs. 173.8 ± 22.1) and decreases in PaCO2 (52.6 ± 11.7 vs. 40.3 ± 4.5 mmHg, p < 0.05 for both) were observed 5 minutes following initiation of CNEP, and these benefits in gas exchange remained after an hour of CNEP. Gradual improvements in lung aeration in the non-collapsed lung were also detected by electrical impedance tomography (p < 0.05) after 5 and 60 min of CNEP. Hemodynamics and ventilation parameters remained stable under CNEP. Application of CNEP in the presence of whole lung atelectasis proved to be efficient in improving gas exchange via recruiting the lung without excessive airway pressures. These benefits of combined CNEP and positive pressure ventilation may have particular value in relieving atelectasis in the postoperative period of surgical procedures requiring OLV.

Benefit of Flow-Controlled Over Pressure-Regulated Volume Control Mode During One-Lung Ventilation: A Randomized Experimental Crossover Study.

BACKGROUND: Application of a ventilation modality that ensures adequate gas exchange during one-lung ventilation (OLV) without inducing lung injury is of paramount importance. Due to its beneficial effects on respiratory mechanics and gas exchange, flow-controlled ventilation (FCV) may be considered as a protective alternative mode of traditional pressure- or volume-controlled ventilation during OLV. We investigated whether this new modality provides benefits compared with conventional ventilation modality for OLV. METHODS: Ten pigs were anaesthetized and randomly assigned in a crossover design to be ventilated with FCV or pressure-regulated volume control (PRVC) ventilation. Arterial partial pressure of oxygen (Pa o2 ), carbon dioxide (Pa co2 ), ventilation and hemodynamical parameters, and lung aeration measured by electrical impedance tomography were assessed at baseline and 1 hour after the application of each modality during OLV using an endobronchial blocker. RESULTS: Compared to PRVC, FCV resulted in increased Pa o2 (153.7 ± 12.7 vs 169.9 ± 15.0 mm Hg; P = .002) and decreased Pa co2 (53.0 ± 11.0 vs 43.2 ± 6.0 mm Hg; P < .001) during OLV, with lower respiratory elastance (103.7 ± 9.5 vs 77.2 ± 10.5 cm H 2 O/L; P < .001) and peak inspiratory pressure values (27.4 ± 1.9 vs 22.0 ± 2.3 cm H 2 O; P < .001). No differences in lung aeration or hemodynamics could be detected between the 2 ventilation modalities. CONCLUSIONS: The application of FCV in OLV led to improvement in gas exchange and respiratory elastance with lower ventilatory pressures. Our findings suggest that FCV may offer an optimal, protective ventilation modality for OLV.

Flow-controlled ventilation maintains gas exchange and lung aeration in a pediatric model of healthy and injured lungs: A randomized cross-over experimental study.

Flow-controlled ventilation (FCV) is characterized by a constant flow to generate active inspiration and expiration. While the benefit of FCV on gas exchange has been demonstrated in preclinical and clinical studies with adults, the value of this modality for a pediatric population remains unknown. Thus, we aimed at observing the effects of FCV as compared to pressure-regulated volume control (PRVC) ventilation on lung mechanics, gas exchange and lung aeration before and after surfactant depletion in a pediatric model. Ten anesthetized piglets (10.4 ± 0.2 kg) were randomly assigned to start 1-h ventilation with FCV or PRVC before switching the ventilation modes for another hour. This sequence was repeated after inducing lung injury by bronchoalveolar lavage and injurious ventilation. The primary outcome was respiratory tissue elastance. Secondary outcomes included oxygenation index (PaO2/FiO2), PaCO2, intrapulmonary shunt (Qs/Qt), airway resistance, respiratory tissue damping, end-expiratory lung volume, lung clearance index and lung aeration by chest electrical impedance tomography. Measurements were performed at the end of each protocol stage. Ventilation modality had no effect on any respiratory mechanical parameter. Adequate gas exchange was provided by FCV, similar to PRVC, with sufficient CO2 elimination both in healthy and surfactant-depleted lungs (39.46 ± 7.2 mmHg and 46.2 ± 11.4 mmHg for FCV; 36.0 ± 4.1 and 39.5 ± 4.9 mmHg, for PRVC, respectively). Somewhat lower PaO2/FiO2 and higher Qs/Qt were observed in healthy and surfactant depleted lungs during FCV compared to PRVC (p < 0.05, for all). Compared to PRVC, lung aeration was significantly elevated, particularly in the ventral dependent zones during FCV (p < 0.05), but this difference was not evidenced in injured lungs. Somewhat lower oxygenation and higher shunt ratio was observed during FCV, nevertheless lung aeration improved and adequate gas exchange was ensured. Therefore, in the absence of major differences in respiratory mechanics and lung volumes, FCV may be considered as an alternative in ventilation therapy of pediatric patients with healthy and injured lungs.

Novel ventilation techniques in children.

Extraordinary progress has been made during the past few decades in the development of anesthesia machines and ventilation techniques. With unprecedented precision and performance, modern machines for pediatric anesthesia can deliver appropriate mechanical ventilation for children and infants of all sizes and with ongoing respiratory diseases, ensuring very small volume delivery and compensating for circuit compliance. Along with highly accurate monitoring of the delivered ventilation, modern ventilators for pediatric anesthesia also have a broad choice of ventilation modalities, including synchronized and assisted ventilation modes, which were initially conceived for ventilation weaning in the intensive care setting. Despite these technical advances, there is still room for improvement in pediatric mechanical ventilation. There is a growing effort to minimize the harm of intraoperative mechanical ventilation of children by adopting the protective ventilation strategies that were previously employed only for prolonged mechanical ventilation. More than ever, the pediatric anesthesiologist should now recognize that positive-pressure ventilation is potentially a harmful procedure, even in healthy children, as it can contribute to both ventilator-induced lung injury and ventilator-induced diaphragmatic dysfunction. Therefore, careful choice of the ventilation modality and its parameters is of paramount importance to optimize gas exchange and to protect the lungs from injury during general anesthesia. The present report reviews the novel ventilation techniques used for children, discussing the advantages and pitfalls of the ventilation modalities available in modern anesthesia machines, as well as innovative ventilation modes currently under development or research. Several innovative strategies and devices are discussed. These novel modalities are likely to become part of the armamentarium of the pediatric anesthesiologist in the near future and are particularly relevant for challenging ventilation scenarios.

Variable Ventilation Is Equally Effective as Conventional Pressure Control Ventilation for Optimizing Lung Function in a Rabbit Model of ARDS.

BACKGROUND: Introducing mathematically derived variability (MVV) into the otherwise monotonous conventional mechanical ventilation has been suggested to improve lung recruitment and gas exchange. Although the application of a ventilation pattern based on variations in physiological breathing (PVV) is beneficial for healthy lungs, its value in the presence of acute respiratory distress syndrome (ARDS) has not been characterized. We therefore aimed at comparing conventional pressure-controlled ventilation with (PCS) or without regular sighs (PCV) to MVV and PVV at two levels of positive end-expiratory pressure (PEEP) in a model of severe ARDS. METHODS: Anesthetised rabbits (n = 54) were mechanically ventilated and severe ARDS (PaO2/FiO2 ≤ 150 mmHg) was induced by combining whole lung lavage, i.v. endotoxin and injurious ventilation. Rabbits were then randomly assigned to be ventilated with PVV, MVV, PCV, or PCS for 5 h while maintaining either 6 or 9 cmH2O PEEP. Ventilation parameters, blood gas indices and respiratory mechanics (tissue damping, G, and elastance, H) were recorded hourly. Serum cytokine levels were assessed with ELISA and lung histology was analyzed. RESULTS: Although no progression of lung injury was observed after 5 h of ventilation at PEEP 6 cmH2O with PVV and PCV, values for G (58.8 ± 71.1[half-width of 95% CI]% and 40.8 ± 39.0%, respectively), H (54.5 ± 57.2%, 50.7 ± 28.3%), partial pressure of carbon-dioxide (PaCO2, 43.9 ± 23.8%, 46.2 ± 35.4%) and pH (-4.6 ± 3.3%, -4.6 ± 2.2%) worsened with PCS and MVV. Regardless of ventilation pattern, application of a higher PEEP improved lung function and precluded progression of lung injury and inflammation. Histology lung injury scores were elevated in all groups with no difference between groups at either PEEP level. CONCLUSION: At moderate PEEP, variable ventilation based on a pre-recorded physiological breathing pattern protected against progression of lung injury equally to the conventional pressure-controlled mode, whereas mathematical variability or application of regular sighs caused worsening in lung mechanics. This outcome may be related to the excessive increases in peak inspiratory pressure with the latter ventilation modes. However, a greater benefit on respiratory mechanics and gas exchange could be obtained by elevating PEEP, compared to the ventilation mode in severe ARDS.

High inspired oxygen fraction impairs lung volume and ventilation heterogeneity in healthy children: a double-blind randomised controlled trial.

BACKGROUND: Although a high inspired oxygen fraction (FiO2) is commonly used in paediatric anaesthesia, the impact on postoperative lung function is unclear. We compared lung volume, ventilation heterogeneity, and respiratory mechanics in anaesthetised children randomised to receive low or high FiO2 intraoperatively. METHODS: In a double-blind randomised controlled trial, children scheduled for elective surgery were randomly assigned FiO2 100% (n=29) or FiO2 80% (n=29) during anaesthesia induction and emergence. During maintenance of anaesthesia, participants assigned FiO2=100% at induction/emergence received FiO2=80% (FiO2>0.8 group); those randomised to FiO2=80% at induction/emergence received FiO2=35% intraoperatively (FiO2 [0.8→0.35 group]). During spontaneous breathing, we measured the (i) functional residual capacity (FRC) and lung clearance index (ventilation inhomogeneity) by multiple-breath nitrogen washout; and (ii) airway resistance and respiratory tissue elastance by forced oscillations, before operation, after discharge from the recovery room, and 24 h after operation. Mean (95% confidence intervals) are reported. RESULTS: Fifty eight children (12.9 [12.3-13.5] yr) were randomised; 22/29 (high group) and 21/29 (low group) children completed serial multiple-breath nitrogen washout measurements. FRC decreased in the FiO2>0.8 group after discharge from recovery (-12.0 [-18.5 to -5.5]%; P=0.01), but normalised 24 h later. Ventilation inhomogeneity increased in both groups after discharge from recovery, but persisted in the FiO2>0.8 group 24 h after surgery (6.1 [2.5-9.8%]%; P=0.02). Airway resistance and respiratory elastance did not differ between the groups at any time point. CONCLUSIONS: FiO2>0.8 decreases lung volume in the immediate postoperative period, accompanied by persistent ventilation inhomogeneity. These data suggest that FiO2>0.8 should be avoided in anaesthetised children with normal lungs. CLINICAL TRIAL REGISTRATION: NCT02384616.

Cardiorespiratory Alterations Following Acute Normovolemic Hemodilution in a Pediatric and an Adult Porcine Model: A Prospective Interventional Study.

BACKGROUND: Acute normovolemic hemodilution (ANH) is considered as a blood-sparing intervention during the perioperative management. We aimed at comparing the cardiopulmonary consequences of ANH between adult pigs and weaned piglets to establish the effects of lowering hematocrit in these age groups, and thereby testing the hypothesis that difference in the age-related physiological behavior will be reflected in the cardiorespiratory changes following ANH. METHODS: ANH was achieved in anesthetized, mechanically ventilated adult minipigs and 5-week-old weaned piglets by stepwise blood withdrawal (10 mL/kg) with crystalloids replacement. Cardiorespiratory assessments consisted of measuring airway resistance, respiratory tissue elastance, effective lung volume, extravascular lung water, mean arterial pressure, pulmonary blood flow, and cardiac output. Respiratory and hemodynamic measurements were made at control conditions and following each ANH condition obtained with 5 to 7 steps. RESULTS: ANH induced immediate and progressive increases in airway resistance and tissue elastance in both groups, with more pronounced worsening in adults despite the similar decreases in hematocrit. The increases in extravascular lung water were significantly greater in the adult population with the differences in mean (DM) of 25.1% (95% confidence interval [CI], 5.3%-44.9%). Progressive ANH led to significant decreases in the DM of pulmonary blood flow (45.3%; 95% CI, 19.8%-70.8%) and mean arterial pressure (36.3%; 95% CI, 18.7%-53.9%) only in adults, whereas cardiac output increased significantly only in the piglets (DM, 51.6; 95% CI, 14.2%-89.0%). CONCLUSIONS: While ANH led to mild detrimental cardiorespiratory changes in weaned piglets, gradual developments of bronchoconstriction, lung tissue extravasation and stiffening, and deteriorations in systemic and pulmonary hemodynamics were observed in adults. ANH may exert age-dependent cardiorespiratory effect.

Synchrotron Imaging Shows Effect of Ventilator Settings on Intrabreath Cyclic Changes in Pulmonary Blood Volume.

Despite the importance of dynamic changes in the regional distributions of gas and blood during the breathing cycle for lung function in the mechanically ventilated patient, no quantitative data on such cyclic changes are currently available. We used a novel gated synchrotron computed tomography imaging to quantitatively image regional lung gas volume (Vg), tissue density, and blood volume (Vb) in six anesthetized, paralyzed, and mechanically ventilated rabbits with normal lungs. Images were repeatedly collected during ventilation and steady-state inhalation of 50% xenon, or iodine infusion. Data were acquired in a dependent and nondependent image level, at zero end-expiratory pressure (ZEEP) and 9 cm H2O (positive end-expiratory pressure), and a tidal volume (Vt) of 6 ml/kg (Vt1) or 9 ml/kg (Vt2) at an Inspiratory:Expiratory ratio of 0.5 or 1.7 by applying an end-inspiratory pause. A video showing dynamic decreases in Vb during inspiration is presented. Vb decreased with positive end-expiratory pressure (P = 0.006; P = 0.036 versus Vt1-ZEEP and Vt2-ZEEP, respectively), and showed larger oscillations at the dependent image level, whereas a 45% increase in Vt did not have a significant effect. End-inspiratory Vb minima were reduced by an end-inspiratory pause (P = 0.042, P = 0.006 at nondependent and dependent levels, respectively). Normalized regional Vg:Vb ratio increased upon inspiration. Our data demonstrate, for the first time, within-tidal cyclic variations in regional pulmonary Vb. The quantitative matching of regional Vg and Vb improved upon inspiration under ZEEP. Further study is underway to determine whether these phenomena affect intratidal gas exchange.

Pressure-regulated volume control vs. volume control ventilation in healthy and injured rabbit lung: An experimental study.

BACKGROUND: It is not well understood how different ventilation modes affect the regional distribution of ventilation, particularly within the injured lung. OBJECTIVES: We compared respiratory mechanics, lung aeration and regional specific ventilation ((Equation is included in full-text article.)) distributions in healthy and surfactant-depleted rabbits ventilated with pressure-regulated volume control (PRVC) mode with a decelerating inspiratory flow or with volume control (VC) mode. DESIGN: Randomised experimental study. ANIMALS AND INTERVENTIONS: New Zealand white rabbits (n = 8) were anaesthetised, paralysed and mechanically ventilated either with VC or PRVC mode (tidal volume: 7 ml kg; rate: 40 min; positive end-expiratory pressure (PEEP): 3 cmH2O), at baseline and after lung injury induced by lung lavage. MAIN OUTCOME MEASURES: Airway resistance (Raw), respiratory tissue damping (G) and elastance (H) were measured by low-frequency forced oscillations. Synchrotron radiation computed tomography during stable xenon wash-in was used to measure regional lung aeration and specific ventilation and the relative fraction of nonaerated, trapped, normally, poorly and hyperinflated lung regions. RESULTS: Lung lavage significantly elevated peak inspiratory pressure (PIP) (P < 0.001). PIP was lower on PRVC compared with VC mode (-12.7 ±â€Š1.7%, P < 0.001). No significant differences in respiratory mechanics, regional ventilation distribution, strain or blood oxygenation could be detected between the two ventilation modes. CONCLUSION: A decelerating flow pattern (PRVC) resulted in equivalent regional ventilation distribution, respiratory mechanics and gas exchange, in both normal and mechanically heterogeneous lungs with, however, a significantly lower peak pressure. Our data suggest that the lower PIP on PRVC ventilation was because of the decelerating flow pattern rather than the ventilation distribution.

Effect of surfactant on regional lung function in an experimental model of respiratory distress syndrome in rabbit.

We assessed the changes in regional lung function following instillation of surfactant in a model of respiratory distress syndrome (RDS) induced by whole lung lavage and mechanical ventilation in eight anaesthetized, paralyzed, and mechanically ventilated New Zealand White rabbits. Regional specific ventilation (sV̇) was measured by K-edge subtraction synchrotron computed tomography during xenon washin. Lung regions were classified as poorly aerated (PA), normally aerated (NA), or hyperinflated (HI) based on regional density. A functional category was defined within each class based on sV̇ distribution (High, Normal, and Low). Airway resistance (Raw), respiratory tissue damping (G), and elastance (H) were measured by forced oscillation technique at low frequencies before and after whole lung saline lavage-induced (100 ml/kg) RDS, and 5 and 45 min after intratracheal instillation of beractant (75 mg/kg). Surfactant instillation improved Raw, G, and H (P < 0.05 each), and gas exchange and decreased atelectasis (P < 0.001). It also significantly improved lung aeration and ventilation in atelectatic lung regions. However, in regions that had remained normally aerated after lavage, it decreased regional aeration and increased sV̇ (P < 0.001) and sV̇ heterogeneity. Although surfactant treatment improved both central airway and tissue mechanics and improved regional lung function of initially poorly aerated and atelectatic lung, it deteriorated regional lung function when local aeration was normal prior to administration. Local mechanical and functional heterogeneity can potentially contribute to the worsening of RDS and gas exchange. These data underscore the need for reassessing the benefits of routine prophylactic vs. continuous positive airway pressure and early "rescue" surfactant therapy in very immature infants.

Lung volume assessments in normal and surfactant depleted lungs: agreement between bedside techniques and CT imaging.

BACKGROUND: Bedside assessment of lung volume in clinical practice is crucial to adapt ventilation strategy. We compared bedside measures of lung volume by helium multiple-breath washout technique (EELVMBW,He) and effective lung volume based on capnodynamics (ELV) to those assessed from spiral chest CT scans (EELVCT) under different PEEP levels in control and surfactant-depleted lungs. METHODS: Lung volume was assessed in anaesthetized mechanically ventilated rabbits successively by measuring i) ELV by analyzing CO2 elimination traces during the application of periods of 5 consecutive alterations in inspiratory/expiratory ratio (1:2 to 1.5:1), ii) measuring EELVMBW,He by using helium as a tracer gas, and iii) EELVCT from CT scan images by computing the normalized lung density. All measurements were performed at PEEP of 0, 3 and 9 cmH2O in random order under control condition and following surfactant depletion by whole lung lavage. RESULTS: Variables obtained with all techniques followed sensitively the lung volume changes with PEEP. Excellent correlation and close agreement was observed between EELVMBW,He and EELVCT (r = 0.93, p < 0.0001). ELV overestimated EELVMBW,He and EELVCT in normal lungs, whereas this difference was not evidenced following surfactant depletion. These findings resulted in somewhat diminished but still significant correlations between ELV and EELVCT (r = 0.58, p < 0.001) or EELVMBW,He (0.76, p < 0.001) and moderate agreements. CONCLUSIONS: Lung volume assessed with bedside techniques allow the monitoring of the changes in the lung aeration with PEEP both in normal lungs and in a model of acute lung injury. Under stable pulmonary haemodynamic condition, ELV allows continuous lung volume monitoring, whereas EELVMBW,He offers a more accurate estimation, but intermittently.

Role of cellular effectors in the emergence of ventilation defects during allergic bronchoconstriction.

It is not known whether local factors within the airway wall or parenchyma may influence the emergence and spatial distribution of ventilation defects (VDs), thereby modulating the dynamic system behavior of the lung during bronchoconstriction. We assessed the relationship between the distribution of cellular effectors and the emergence of defects in regional ventilation distribution following allergen challenge. We performed high-resolution K-edge subtraction (KES) synchrotron imaging during xenon inhalation and measured the forced oscillatory input impedance in ovalbumin (OVA)-sensitized Brown-Norway rats (n = 12) at baseline and repeatedly following OVA challenge. Histological slices with best anatomic matching to the computed tomographic images were stained with a modified May-Grunwald Giemsa and immunohistochemical staining with monoclonal anti-rat CD68, in six rats. Slides were digitized and total cells and eosinophils were counted in the walls of bronchi and vessels randomly selected within and outside of VDs on the basis of xenon-KES images. Ventilated alveolar area decreased and ventilation heterogeneity, Newtonian resistance, tissue damping, and elastance increased following OVA challenge. Eosinophil, total cell, and CD68+ counts were significantly higher in the bronchial and vascular walls within vs. outside of the VDs. The minimal central airway diameters during OVA-induced bronchoconstriction were correlated with eosinophil (R = -0.85; P = 0.031) and total cell densities (R = -0.82; P = 0.046) in the airway walls within the poorly ventilated zones. Our findings suggest that allergic airway inflammation is locally heterogeneous and is topographically associated with the local emergence of VDs following allergen challenge.

Effect of positive end-expiratory pressure on regional ventilation distribution during mechanical ventilation after surfactant depletion.

BACKGROUND: Ventilator-induced lung injury occurs due to exaggerated local stresses, repeated collapse, and opening of terminal air spaces in poorly aerated dependent lung, and increased stretch in nondependent lung. The aim of this study was to quantify the functional behavior of peripheral lung units in whole-lung lavage-induced surfactant depletion, and to assess the effect of positive end-expiratory pressure. METHODS: The authors used synchrotron imaging to measure lung aeration and regional specific ventilation at positive end-expiratory pressure of 3 and 9 cm H2O, before and after whole-lung lavage in rabbits. Respiratory mechanical parameters were measured, and helium-washout was used to assess end-expiratory lung volume. RESULTS: Atelectatic, poorly, normally aerated, hyperinflated, and trapped regions could be identified using the imaging technique used in this study. Surfactant depletion significantly increased atelectasis (6.3±3.3 [mean±SEM]% total lung area; P=0.04 vs. control) and poor aeration in dependent lung. Regional ventilation was distributed to poorly aerated regions with high (16.4±4.4%; P<0.001), normal (20.7±5.9%; P<0.001 vs. control), and low (5.7±1.2%; P<0.05 vs. control) specific ventilation. Significant redistribution of ventilation to normally aerated nondependent lung regions occurred (41.0±9.6%; P=0.03 vs. control). Increasing positive end-expiratory pressure level to 9 cm H2O significantly reduced poor aeration and recruited atelectasis, but ventilation redistribution persisted (39.2±9.5%; P<0.001 vs. control). CONCLUSIONS: Ventilation of poorly aerated dependent lung regions, which can promote the local concentration of mechanical stresses, was the predominant functional behavior in surfactant-depleted lung. Potential tidal recruitment of atelectatic lung regions involved a smaller fraction of the imaged lung. Significant ventilation redistribution to aerated lung regions places these at risk of increased stretch injury.

Comparison of static end-expiratory and effective lung volumes for gas exchange in healthy and surfactant-depleted lungs.

BACKGROUND: Effective lung volume (ELV) for gas exchange is a new measure that could be used as a real-time guide during controlled mechanical ventilation. The authors established the relationships of ELV to static end-expiratory lung volume (EELV) with varying levels of positive end-expiratory pressure (PEEP) in healthy and surfactant-depleted rabbit lungs. METHODS: Nine rabbits were anesthetized and ventilated with a modified volume-controlled mode where periods of five consecutive alterations in inspiratory/expiratory ratio (1:2-1.5:1) were imposed to measure ELV from the corresponding carbon dioxide elimination traces. EELV and the lung clearance index were concomitantly determined by helium wash-out technique. Airway and tissue mechanics were assessed by using low-frequency forced oscillations. Measurements were collected at PEEP 0, 3, 6, and 9 cm H2O levels under control condition and after surfactant depletion by whole-lung lavage. RESULTS: ELV was greater than EELV at all PEEP levels before lavage, whereas there was no evidence for a difference in the lung volume indices after surfactant depletion at PEEP 6 or 9 cm H2O. Increasing PEEP level caused significant parallel increases in both ELV and EELV levels, decreases in ventilation heterogeneity, and improvement in airway and tissue mechanics under control condition and after surfactant depletion. ELV and EELV exhibited strong and statistically significant correlations before (r=0.84) and after lavage (r=0.87). CONCLUSIONS: The parallel changes in ELV and EELV with PEEP in healthy and surfactant-depleted lungs support the clinical value of ELV measurement as a bedside tool to estimate dynamic changes in EELV in children and infants.

Prevention of airway hyperresponsiveness induced by left ventricular dysfunction in rats.

BACKGROUND: The effectiveness of strategies for treatment of the altered static lung volume and against the development of bronchial hyperreactivity (BHR) following a left ventricular dysfunction (LVD) induced by myocardial ischaemia was investigated in a rat model of sustained postcapillary pulmonary hypertension. METHODS: Airway resistance (Raw) was identified from the respiratory system input impedance (Zrs) in four groups of rats. End-expiratory lung volume (EELV) was determined plethysmographically, and Zrs was measured under baseline conditions and following iv infusions of 2, 6 or 18 µg/kg/min methacholine. Sham surgery was performed in the rats in Group C, while the left interventricular coronary artery was ligated and Zrs and its changes following identical methacholine challenges were reassessed in the same rats 8 weeks later, during which no treatment was applied (Group I), or the animals were treated daily with a combination of an angiotensin enzyme converter inhibitor and a diuretic (enalapril and furosemide, Group IE), or a calcium channel blocker (diltiazem, Group ID). The equivalent dose of methacholine causing a 100% increase in Raw (ED50) was determined in each group. Diastolic pulmonary arterial pressure (PapD) was assessed by introducing a catheter into the pulmonary artery. RESULTS: The sustained presence of a LVD increased PapD in all groups of rats, with variable but significant elevations in Groups I (p=0.004), ID (p=0.013) and IE (p=0.006). A LVD for 8 weeks induced no changes in baseline Raw but elevated the EELV independently of the treatments. In Group I, BHR consistently developed following the LVD, with a significant decrease in ED50 from 10.0 ± 2.5 to 6.9 ± 2.5 µg/kg/min (p=0.006). The BHR was completely abolished in both Groups ID and IE, with no changes in ED50 (9.5 ± 3.6 vs. 10.7 ± 4.7, p=0.33 and 10.6 ± 2.1 vs. 9.8 ± 3.5 µg/kg/min p=0.56, respectively). CONCLUSIONS: These findings suggest that a LVD following coronary ischaemia consistently induces BHR. The more consistent efficacy of both treatment strategies in preventing BHR than in treating the adverse pulmonary vascular consequences suggests the benefit of both calcium channel blockade and ACE inhibition to counteract the airway susceptibility following a LVD.

Acute hemorrhagic shock decreases airway resistance in anesthetized rat.

We studied the relation between changes in pulmonary and systemic hemodynamics to those in the airway resistance, respiratory tissue mechanics, and thoracic gas volume (TGV) following acute hemorrhage and blood reinfusion in rats. Forced oscillation technique was used to measure airway resistance (Raw), respiratory tissue damping, and elastance at baseline and after stepwise 1-ml blood withdrawals up to 5 ml total, followed by stepwise reinfusion up to full restoration. Mean systemic (Pam) and pulmonary arterial pressures and suprarenal aortic blood flow were measured at each step. In supplemental animals, plethysmographic TGV, Pam, and respiratory mechanics measurements were performed. Blood volume loss (BVL) led to proportional decreases in Raw (66.5 ± 8.8 vs. 44.8 ± 9.0 cmH(2)O·s·l(-1) with 5 ml, P < 0.001), Pam, and aortic blood flow. In contrast, tissue damping increased significantly (1,070 ± 91 vs. 1,235 ± 105 cmH(2)O/l, P = 0.009 with 5 ml BVL), whereas tissue elastance did not change significantly. TGV significantly increased with acute BVL (3.7 ± 0.2 vs. 4.2 ± 0.2 ml, P = 0.01). Stepwise reinfusions produced opposite changes in the above parameters, with Raw reaching a higher value than baseline (P = 0.001) upon full volume restoration. Both adrenalin (P = 0.015) and noradrenalin levels were elevated (P = 0.010) after 5-ml blood withdrawal. Our data suggest that the decreases in Raw following BVL may be attributed to the following: 1) an increased TGV enhancing airway parenchymal tethering forces; and 2) an increase in circulating catecholamines. The apparent beneficial effect of a reduction in Raw in acute hemorrhagic shock is counteracted by an increase in dead space and the appearance of peripheral mechanical heterogeneities due to de-recruitment of the pulmonary vasculature.

Prevention of bronchial hyperreactivity in a rat model of precapillary pulmonary hypertension.

BACKGROUND: The development of bronchial hyperreactivity (BHR) subsequent to precapillary pulmonary hypertension (PHT) was prevented by acting on the major signalling pathways (endothelin, nitric oxide, vasoactive intestine peptide (VIP) and prostacyclin) involved in the control of the pulmonary vascular and bronchial tones. METHODS: Five groups of rats underwent surgery to prepare an aorta-caval shunt (ACS) to induce sustained precapillary PHT for 4 weeks. During this period, no treatment was applied in one group (ACS controls), while the other groups were pretreated with VIP, iloprost, tezosentan via an intraperitoneally implemented osmotic pump, or by orally administered sildenafil. An additional group underwent sham surgery. Four weeks later, the lung responsiveness to increasing doses of an intravenous infusion of methacholine (2, 4, 8 12 and 24 µg/kg/min) was determined by using the forced oscillation technique to assess the airway resistance (Raw). RESULTS: BHR developed in the untreated rats, as reflected by a significant decrease in ED50, the equivalent dose of methacholine required to cause a 50% increase in Raw. All drugs tested prevented the development of BHR, iloprost being the most effective in reducing both the systolic pulmonary arterial pressure (Ppa; 28%, p = 0.035) and BHR (ED50 = 9.9 ± 1.7 vs. 43 ± 11 µg/kg in ACS control and iloprost-treated rats, respectively, p = 0.008). Significant correlations were found between the levels of Ppa and ED50 (R = -0.59, p = 0.016), indicating that mechanical interdependence is primarily responsible for the development of BHR. CONCLUSIONS: The efficiency of such treatment demonstrates that re-establishment of the balance of constrictor/dilator mediators via various signalling pathways involved in PHT is of potential benefit for the avoidance of the development of BHR.

Changes in airway and respiratory tissue mechanics after cardiac surgery.

BACKGROUND: Because of the critical importance of the first postoperative week in the development of respiratory complications after cardiac surgery, the mechanical properties of the respiratory system in this period were followed up systematically. METHODS: The input impedance of the respiratory system (Zrs) was measured during spontaneous breathing in patients (n=35) undergoing cardiac surgery on the day before surgery to establish the baseline, and for six days thereafter. The airway resistance was inferred from the average of the resistive component of Zrs, while the changes in respiratory elastance were assessed from the imaginary part of Zrs by model fitting. An assessment was made of the impact on the postoperative changes of factors characteristic of the patients (gender, age, smoking, and obesity) or the surgery duration and the need or not for a cardiopulmonary bypass. RESULTS: Airway resistance increased immediately after extubation (peak rise on day 1, evening: 48+/-10%) and subsequently gradually decreased to the initial level, the recovery proving prolonged in obese patients. Postoperative elevation in elastance peaked later (day 2, evening: 83+/-14%), lasted longer, and was affected by both cardiopulmonary bypass (p<0.05) and obesity (p<0.005). CONCLUSIONS: These findings demonstrate the need for particular attention in the postoperative management of patients after cardiac surgery in order to reduce the immediate airway symptoms, and to take steps to maintain the lungs open during the critical postoperative days 2 and 3, especially in obese patients and (or) if the surgery involves the use of cardiopulmonary bypass.

Mechanisms for lung function impairment and airway hyperresponsiveness following chronic hypoxia in rats.

Although chronic normobaric hypoxia (CH) alters lung function, its potential to induce bronchial hyperreactivity (BHR) is still controversial. Thus the effects of CH on airway and tissue mechanics separately and changes in lung responsiveness to methacholine (MCh) were investigated. To clarify the mechanisms, mechanical changes were related to end-expiratory lung volume (EELV), in vivo results were compared with those in vitro, and lung histology was assessed. EELV was measured plethysmographically in two groups of rats exposed to 21 days of CH (11% O(2)) or to normoxia. Total respiratory impedance was measured under baseline conditions and following intravenous MCh challenges (2-18 microg x kg(-1) x min(-1)). The lungs were then excised and perfused, and the pulmonary input impedance was measured, while MCh provocations were repeated under a pulmonary capillary pressure of 5, 10, and 15 mmHg. Airway resistance, tissue damping, and elastance were extracted from the respiratory impedance and pulmonary input impedance spectra. The increases in EELV following CH were associated with decreases in airway resistance, whereas tissue damping and elastance remained unaffected. CH led to the development of severe BHR to MCh (206 +/- 30 vs. 95 +/- 24%, P < 0.001), which was not detectable when the same lungs were studied in vitro at any pulmonary capillary pressure levels maintained. Histology revealed pulmonary arterial vascular remodeling with overexpression of alpha-smooth muscle actin antibody in the bronchial wall. These findings suggest that, despite the counterbalancing effect of the increased EELV, BHR develops following CH, only in the presence of intact autonomous nervous system. Thus neural control plays a major role in the changes in the basal lung mechanics and responsiveness following CH.