Benefits of intratracheal and extrathoracic high-frequency percussive ventilation in a model of capnoperitoneum.

Abdominal inflation with CO2 is used to facilitate laparoscopic surgeries, however, providing adequate mechanical ventilation in this scenario is of major importance during anesthesia management. We characterized high-frequency percussive ventilation (HFPV) in protecting from the gas exchange and respiratory mechanical impairments during capnoperitoneum. In addition, we aimed to assess the difference between conventional pressure-controlled mechanical ventilation (CMV) and HFPV modalities generating the high-frequency signal intratracheally (HFPVi) or extrathoracally (HFPVe). Anesthetized rabbits (n = 16) were mechanically ventilated by random sequences of CMV, HFPVi, and HFPVe. The ventilator superimposed the conventional waveform with two high-frequency signals (5 Hz and 10 Hz) during intratracheal HFPV (HFPVi) and HFPV with extrathoracic application of oscillatory signals through a sealed chest cuirass (HFPVe). Lung oxygenation index ([Formula: see text]/[Formula: see text]), arterial partial pressure of carbon dioxide ([Formula: see text]), intrapulmonary shunt (Qs/Qt), and respiratory mechanics were assessed before abdominal inflation, during capnoperitoneum, and after abdominal deflation. Compared with CMV, HFPVi with additional 5-Hz oscillations during capnoperitoneum resulted in higher [Formula: see text]/[Formula: see text], lower [Formula: see text], and decreased Qs/Qt. These improvements were smaller but remained significant during HFPVi with 10 Hz and HFPVe with either 5 or 10 Hz. The ventilation modes did not protect against capnoperitoneum-induced deteriorations in respiratory tissue mechanics. These findings suggest that high-frequency oscillations combined with conventional pressure-controlled ventilation improved lung oxygenation and CO2 removal in a model of capnoperitoneum. Compared with extrathoracic pressure oscillations, intratracheal generation of oscillatory pressure bursts appeared more effective. These findings may contribute to the optimization of mechanical ventilation during laparoscopic surgery.NEW & NOTEWORTHY The present study examines an alternative and innovative mechanical ventilation modality in improving oxygen delivery, CO2 clearance, and respiratory mechanical abnormalities in a clinically relevant experimental model of capnoperitoneum. Our data reveal that high-frequency oscillations combined with conventional ventilation improve gas exchange, with intratracheal oscillations being more effective than extrathoracic oscillations in this clinically relevant translational model.

Changes in lung mechanics and ventilation-perfusion match: comparison of pulmonary air- and thromboembolism in rats.

BACKGROUND: Pulmonary air embolism (AE) and thromboembolism lead to severe ventilation-perfusion defects. The spatial distribution of pulmonary perfusion dysfunctions differs substantially in the two pulmonary embolism pathologies, and the effects on respiratory mechanics, gas exchange, and ventilation-perfusion match have not been compared within a study. Therefore, we compared changes in indices reflecting airway and respiratory tissue mechanics, gas exchange, and capnography when pulmonary embolism was induced by venous injection of air as a model of gas embolism or by clamping the main pulmonary artery to mimic severe thromboembolism. METHODS: Anesthetized and mechanically ventilated rats (n = 9) were measured under baseline conditions after inducing pulmonary AE by injecting 0.1 mL air into the femoral vein and after occluding the left pulmonary artery (LPAO). Changes in mechanical parameters were assessed by forced oscillations to measure airway resistance, lung tissue damping, and elastance. The arterial partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2) were determined by blood gas analyses. Gas exchange indices were also assessed by measuring end-tidal CO2 concentration (ETCO2), shape factors, and dead space parameters by volumetric capnography. RESULTS: In the presence of a uniform decrease in ETCO2 in the two embolism models, marked elevations in the bronchial tone and compromised lung tissue mechanics were noted after LPAO, whereas AE did not affect lung mechanics. Conversely, only AE deteriorated PaO2, and PaCO2, while LPAO did not affect these outcomes. Neither AE nor LPAO caused changes in the anatomical or physiological dead space, while both embolism models resulted in elevated alveolar dead space indices incorporating intrapulmonary shunting. CONCLUSIONS: Our findings indicate that severe focal hypocapnia following LPAO triggers bronchoconstriction redirecting airflow to well-perfused lung areas, thereby maintaining normal oxygenation, and the CO2 elimination ability of the lungs. However, hypocapnia in diffuse pulmonary perfusion after AE may not reach the threshold level to induce lung mechanical changes; thus, the compensatory mechanisms to match ventilation to perfusion are activated less effectively.

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.

Expiratory high-frequency percussive ventilation: a novel concept for improving gas exchange.

BACKGROUND: Although high-frequency percussive ventilation (HFPV) improves gas exchange, concerns remain about tissue overdistension caused by the oscillations and consequent lung damage. We compared a modified percussive ventilation modality created by superimposing high-frequency oscillations to the conventional ventilation waveform during expiration only (eHFPV) with conventional mechanical ventilation (CMV) and standard HFPV. METHODS: Hypoxia and hypercapnia were induced by decreasing the frequency of CMV in New Zealand White rabbits (n = 10). Following steady-state CMV periods, percussive modalities with oscillations randomly introduced to the entire breathing cycle (HFPV) or to the expiratory phase alone (eHFPV) with varying amplitudes (2 or 4 cmH2O) and frequencies were used (5 or 10 Hz). The arterial partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2) were determined. Volumetric capnography was used to evaluate the ventilation dead space fraction, phase 2 slope, and minute elimination of CO2. Respiratory mechanics were characterized by forced oscillations. RESULTS: The use of eHFPV with 5 Hz superimposed oscillation frequency and an amplitude of 4 cmH2O enhanced gas exchange similar to those observed after HFPV. These improvements in PaO2 (47.3 ± 5.5 vs. 58.6 ± 7.2 mmHg) and PaCO2 (54.7 ± 2.3 vs. 50.1 ± 2.9 mmHg) were associated with lower ventilation dead space and capnogram phase 2 slope, as well as enhanced minute CO2 elimination without altering respiratory mechanics. CONCLUSIONS: These findings demonstrated improved gas exchange using eHFPV as a novel mechanical ventilation modality that combines the benefits of conventional and small-amplitude high-frequency oscillatory ventilation, owing to improved longitudinal gas transport rather than increased lung surface area available for gas exchange.

Seasonal changes in proportion of cardiac surgeries associated with diabetes, smoking and elderly age.

BACKGROUND: Seasonal variations in the ambient temperature may affect the exacerbation of cardiovascular diseases. Our primary objective was to evaluate the seasonality of the monthly proportion of cardiac surgeries associated with diabetes, smoking and/or elderly age at a tertiary-care university hospital in East-Central Europe with a temperate climate zone. As a secondary objective, we also assessed whether additional factors affecting small blood vessels (smoking, aging, obesity) modulate the seasonal variability of diabetes. METHODS: Medical records were analyzed for 9838 consecutive adult patients who underwent cardiac surgery in 2007-2018. Individual seasonal variations of diabetes, smoking, and elderly patients were analyzed monthly, along with the potential risk factors for cardiovascular complication. We also characterized whether pairwise coexistence of diabetes, smoking, and elderly age augments or blunts the seasonal variations. RESULTS: Seasonal variations in the monthly proportion of cardiac surgeries associated with diabetes, smoking and/or elderly age were observed. The proportion of cardiac surgeries of non-elderly and smoking patients with diabetes peaked in winter (amplitude of change as [peak-nadir]/nadir: 19.2%, p<0.02), which was associated with increases in systolic (6.1%, p<0.001) and diastolic blood pressures (4.4%, p<0.05) and serum triglyceride levels (27.1%, p<0.005). However, heart surgery in elderly patients without diabetes and smoking was most frequently required in summer (52.1%, p<0.001). Concomitant occurrence of diabetes and smoking had an additive effect on the requirement for cardiac surgery (107%, p<0.001), while the simultaneous presence of older age and diabetes or smoking eliminated seasonal variations. CONCLUSIONS: Scheduling regular cardiovascular control in accordance with periodicities in diabetes, elderly, and smoking patients more than once a year may improve patient health and social consequences. TRIAL REGISTRATION: NCT03967639.

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.

Exaggerated Ventilator-Induced Lung Injury in an Animal Model of Type 2 Diabetes Mellitus: A Randomized Experimental Study.

Although ventilator-induced lung injury (VILI) often develops after prolonged mechanical ventilation in normal lungs, pulmonary disorders may aggravate the development of adverse symptoms. VILI exaggeration can be anticipated in type 2 diabetes mellitus (T2DM) due to its adverse pulmonary consequences. Therefore, we determined whether T2DM modulates VILI and evaluated how T2DM therapy affects adverse pulmonary changes. Rats were randomly assigned into the untreated T2DM group receiving low-dose streptozotocin with high-fat diet (T2DM, n = 8), T2DM group supplemented with metformin therapy (MET, n = 8), and control group (CTRL, n = 8). In each animal, VILI was induced by mechanical ventilation for 4 h with high tidal volume (23 ml/kg) and low positive end-expiratory pressure (0 cmH2O). Arterial and venous blood samples were analyzed to measure the arterial partial pressure of oxygen (PaO2), oxygen saturation (SaO2), and the intrapulmonary shunt fraction (Qs/Qt). Airway and respiratory tissue mechanics were evaluated by forced oscillations. Lung histology samples were analyzed to determine injury level. Significant worsening of VILI, in terms of PaO2, SaO2, and Qs/Qt, was observed in the T2DM group, without differences in the respiratory mechanics. These functional changes were also reflected in lung injury score. The MET group showed no difference compared with the CTRL group. Gas exchange impairment without significant mechanical changes suggests that untreated diabetes exaggerates VILI by augmenting the damage of the alveolar-capillary barrier. Controlled hyperglycemia with metformin may reduce the manifestations of respiratory defects during prolonged mechanical ventilation.

Invasive and non-invasive assessment of macro- and micro-circulatory effects of vasopressors during sevoflurane anesthesia in a pediatric experimental model: A randomized trial.

BACKGROUND: While non-invasive assessment of macro- and micro-circulation has the promise to optimize anesthesia management, evidence is lacking for the relationship between invasive and non-invasive measurements of cardiac output and microcirculatory indices. AIMS: We aimed to compare the abilities of non-invasive techniques to detect changes in macro- and micro-circulation following deep anesthesia and subsequent restoration of the compromised hemodynamic by routinely used vasopressors in a randomized experimental study. METHODS: A 20%-25% drop in mean arterial pressure was induced by sevoflurane in anesthetized mechanically ventilated just-weaned piglets (n = 12) prior to the administration of vasopressors in random order (dopamine, ephedrine, noradrenaline, and phenylephrine). Simultaneous transpulmonary thermodilution cardiac output assessment with the invasive pulse index continuous contour (PiCCO) method was compared with non-invasive estimates obtained with electrical conductivity (ICON) and echo Doppler (Cardio Q). Changes in microcirculation were characterized by sublingual red blood cell velocity, jugular cerebral venous oxygen saturation, and arterial lactate. MAIN OUTCOME MEASURES: Cardiac output indices obtained by invasive and non-invasive methods. RESULTS: Changes in cardiac output measured invasively and non-invasively correlated significantly after sevoflurane (r = .78, p = .003 and r = .76, p = .006 between PiCCO and ICON or Cardio Q, respectively). Following the administration of vasopressors, invasive and non-invasive cardiac output assessments were unrelated with significant correlations observed only between PiCCO and ICON after dopamine and ephedrine. Sevoflurane-induced hypotension decreased jugular cerebral venous oxygen saturation significantly and was recovered by all vasopressors. Sevoflurane and vasopressors had no effect on red blood cell velocity, which increased only after dopamine. No consistent changes in lactate were observed during the study period. CONCLUSIONS: The results of this study suggest that non-invasive cardiac output measurements may not accurately reflect changes in macrocirculation after hemodynamic optimization by vasopressors. Due to the incoherence between macro- and micro-circulation, monitoring microcirculation is essential to guide patient management.

Effect of body position on the redistribution of regional lung aeration during invasive and non-invasive ventilation of COVID-19 patients.

Severe COVID-19-related acute respiratory distress syndrome (C-ARDS) requires mechanical ventilation. While this intervention is often performed in the prone position to improve oxygenation, the underlying mechanisms responsible for the improvement in respiratory function during invasive ventilation and awake prone positioning in C-ARDS have not yet been elucidated. In this prospective observational trial, we evaluated the respiratory function of C-ARDS patients while in the supine and prone positions during invasive (n = 13) or non-invasive ventilation (n = 15). The primary endpoint was the positional change in lung regional aeration, assessed with electrical impedance tomography. Secondary endpoints included parameters of ventilation and oxygenation, volumetric capnography, respiratory system mechanics and intrapulmonary shunt fraction. In comparison to the supine position, the prone position significantly increased ventilation distribution in dorsal lung zones for patients under invasive ventilation (53.3 ± 18.3% vs. 43.8 ± 12.3%, percentage of dorsal lung aeration ± standard deviation in prone and supine positions, respectively; p = 0.014); whereas, regional aeration in both positions did not change during non-invasive ventilation (36.4 ± 11.4% vs. 33.7 ± 10.1%; p = 0.43). Prone positioning significantly improved the oxygenation both during invasive and non-invasive ventilation. For invasively ventilated patients reduced intrapulmonary shunt fraction, ventilation dead space and respiratory resistance were observed in the prone position. Oxygenation is improved during non-invasive and invasive ventilation with prone positioning in patients with C-ARDS. Different mechanisms may underly this benefit during these two ventilation modalities, driven by improved distribution of lung regional aeration, intrapulmonary shunt fraction and ventilation-perfusion matching. However, the differences in the severity of C-ARDS may have biased the sensitivity of electrical impedance tomography when comparing positional changes between the protocol groups.Trial registration: ClinicalTrials.gov (NCT04359407) and Registered 24 April 2020, https://clinicaltrials.gov/ct2/show/NCT04359407 .

Sevoflurane and Hypercapnia Blunt the Physiological Variability of Spontaneous Breathing: A Comparative Interventional Study.

Background: Although spontaneous breathing is known to exhibit substantial physiological fluctuation that contributes to alveolar recruitment, changes in the variability of the respiratory pattern following inhalation of carbon dioxide (CO2) and volatile anesthetics have not been characterized. Therefore, we aimed at comparing the indices of breathing variability under wakefulness, sleep, hypercapnia and sedative and anesthetic concentrations of sevoflurane. Methods: Spontaneous breathing pattern was recorded on two consecutive days in six rabbits using open whole-body plethysmography under wakefulness and spontaneous sleep and following inhalation of 5% CO2, 2% sevoflurane (0.5 MAC) and 4% (1 MAC) sevoflurane. Tidal volume (VT), respiratory rate (RR), minute ventilation (MV), inspiratory time (TI) and mean inspiratory flow (VT/TI) were calculated from the pressure fluctuations in the plethysmograph. Means and coefficients of variation were calculated for each measured variable. Autoregressive model fitting was applied to estimate the relative contributions of random, correlated, and oscillatory behavior to the total variance. Results: Physiological sleep decreased MV by lowering RR without affecting VT. Hypercapnia increased MV by elevating VT. Sedative and anesthetic concentrations of sevoflurane increased VT but decreased MV due to a decrease in RR. Compared to the awake stage, CO2 had no effect on VT/TI while sevoflurane depressed significantly the mean inspiratory flow. Compared to wakefulness, the variability in VT, RR, MV, TI and VT/TI were not affected by sleep but were all significantly decreased by CO2 and sevoflurane. The variance of TI originating from correlated behavior was significantly decreased by both concentrations of sevoflurane compared to the awake and asleep conditions. Conclusions: The variability of spontaneous breathing during physiological sleep and sevoflurane-induced anesthesia differed fundamentally, with the volatile agent diminishing markedly the fluctuations in respiratory volume, inspiratory airflow and breathing frequency. These findings may suggest the increased risk of lung derecruitment during procedures under sevoflurane in which spontaneous breathing is maintained.

Lung and chest wall mechanical properties in metformin-treated and untreated models of type 2 diabetes.

The adverse respiratory consequences of type 2 diabetes mellitus (T2DM) may reflect compromised lung function and/or alterations of the chest wall because of skeletal muscle stiffening. We assessed the separate contributions of these compartments to respiratory complications in diabetes and explored the effects of metformin on respiratory abnormalities. Experiments were performed in untreated rats (control, n = 7), high-fat diet-fed rats receiving streptozotocin (T2DM, n = 7), and metformin-treated diabetic rats (MET, n = 6). Newtonian resistance, tissue damping, and elastance were separately assessed for lung and chest wall components by measuring the esophageal pressure during forced oscillations at low (0 cmH2O), medium (3 cmH2O), and high positive end-expiratory pressure (PEEP) (6 cmH2O). Tissue hysteresivity was calculated as damping/elastance. Blood gas parameters were used to assess gas exchange, and lung histology was performed to characterize collagen expression. T2DM at low PEEP compromised airway and lung tissue mechanics in association with gas-exchange defects and collagen overexpression. Abnormal chest wall mechanics in T2DM was indicated only by decreased tissue hysteresivity. No difference in lung or chest wall mechanics, gas exchange, or lung histology was observed between the MET and control groups. These findings suggest the primary involvement of the pulmonary system in the respiratory consequences of T2DM, with chest wall properties only disturbed by a shift toward the dominance of elastic forces at low PEEP. The adequacy of metformin to treat the adverse respiratory consequences of diabetes was also revealed, in addition to its well-established beneficial effects on other organs.NEW & NOTEWORTHY The present study examined the contributions of the lungs and chest wall to respiratory complications in a rat model of diabetes and clarified the effects of metformin on these changes. At low positive end-expiratory pressure, type 2 diabetes was linked to dysfunctional airway and lung tissue mechanics in relation with gas-exchange defects and collagen overexpression, whereas decreased tissue hysteresivity was manifested in the chest wall abnormalities. Metformin treated all adverse respiratory consequences of diabetes.

Respiratory consequences of obesity and diabetes / Az elhízás és a cukorbetegség légzorendszeri következményei

Összefoglaló. Bevezetés: A cukorbetegségben no a simaizmok tónusa, és megváltozik az elasztin és a kollagén szerkezete. Mivel a tüdoszövetben ezek a strukturális elemek meghatározóak, a cukorbetegség várhatóan módosítja a légutak és a tüdoszövet mechanikai és funkcionális viselkedését. Célkituzés: Vizsgálatunk során diabetesben szenvedo, elhízott és nem elhízott betegeink körében tanulmányoztuk a légzésmechanikai elváltozásokat és a gázcserefunkciót. Módszer: Elektív szívsebészeti beavatkozásra kerülo, normál testalkatú betegeket diabetesben nem szenvedo (n = 80), illetve cukorbeteg (n = 35) csoportokra osztottuk. További két betegcsoportba elhízott és nem cukorbeteg (n = 47), valamint elhízott és diabetesben szenvedo (n = 33) betegek kerültek. A légzorendszer mechanikai tulajdonságait kényszerített oszcillációs technikával határoztuk meg, mellyel a légúti ellenállás (Raw), valamint a szöveti csillapítás (G) és rugalmasság (H) tényezoi jellemezhetok. Volumetriás kapnográfia segítségével a kapnogram 3. fázisának meredekségét és a légzési térfogat különbözo ventilációs/perfúziós illeszkedési zavaraiból adódó holttérfrakciókat határoztuk meg. Az intrapulmonalis shuntfrakciót és az oxigenizációs indexet (PaO2/FiO2) artériás és centrális vénás vérgázmintákból határoztuk meg. Eredmények: A megfelelo kontrollcsoportokhoz hasonlítva a cukorbetegség önmagában is növelte az Raw (7,4 ± 5 vs. 3,0 ± 1,7 H2Ocm.s/l), a G (11,3 ± 4,9 vs. 6,2 ± 2,4 H2Ocm/l) és a H (32,3 ± 12,0 vs. 25,1± 6,9 H2Ocm/l) értékét (p<0,001 mindegyik betegcsoportnál), de ez nem járt együtt a gázcserefunckció romlásával. Hasonló patológiás elváltozásokat észleltünk elhízás során a légzésmechanikában és az alveolaris heterogenitásban, amelyek azonban a gázcsere hatékonyságát is rontották. Következtetés: Cukorbetegségben a légzésmechanika romlását a fokozott hypoxiás pulmonalis vasoconstrictio ellensúlyozni képes, ezzel kivédve az intrapulmonalis shunt növekedését és az oxigenizációs képesség romlását. Orv Hetil. 2022; 163(2): 63-73. INTRODUCTION: While sustained hyperglicemia affects the smooth muscle tone and the elastin-collagen network, the effect of diabetes mellitus on the function and structure of the airways and the lung parenchyma has not been characterized, and the confounding influence of obesity has not been elucidated. OBJECTIVE: To reveal the separate and additive roles of diabetes mellitus and obesity on the respiratory function. METHOD: Non-obese mechanically ventilated patients were categorized as control non-diabetic (n = 80) and diabetic (n = 35) groups. Obese patients with (n = 33) or without (n = 47) associated diabetes were also enrolled. Forced oscillation technique was applied to measure airway resistance (Raw), tissue damping (G), and tissue elastance (H). Capnography was utilized to determine phase 3 slopes and ventilation dead space parameters. Arterial and central venous blood samples were analyzed to assess intrapulmonary shunt fraction (Qs/Qt) and the lung oxygenation index (PaO2/FiO2). RESULTS: Diabetes without obesity increased the Raw (7.4 ± 5 cmH2O.s/l vs. 3.0 ± 1.7 cmH2O.s/l), G (11.3 ± 4.9 cmH2O/l vs. 6.2 ± 2.4 cmH2O/l), and H (32.3 ± 12.0 cmH2O/l vs. 25.1 ± 6.9 cmH2O/l, (p<0.001 for all), compared with the corresponding control groups. Capnographic phase 3 slope was increased in diabetes without significant changes in PaO2/FiO2 or Qs/Qt. While similar detrimental changes in respiratory mechanics and alveolar heterogeneity were observed in obese patients without diabetes, these alterations also compromised gas exchange. CONCLUSION: The intrinsic mechanical abnormalities in the airways and lung tissue induced by diabetes are counterbalanced by hypoxic pulmonary vasoconstriction, thereby maintaining intrapulmonary shunt fraction and oxygenation ability of the lungs. Orv Hetil. 2022; 163(2): 63-73.

Dopamine Reverses Lung Function Deterioration After Cardiopulmonary Bypass Without Affecting Gas Exchange.

OBJECTIVE: To investigate the effects of dopamine on the adverse pulmonary changes after cardiopulmonary bypass. DESIGN: A prospective, nonrandomized clinical investigation. SETTING: A university hospital. PARTICIPANTS: One hundred fifty-seven patients who underwent elective cardiac surgery that required cardiopulmonary bypass. INTERVENTIONS: Fifty-two patients were administered intravenous infusion of dopamine (3 µg/kg/min) for five minutes after weaning from cardiopulmonary bypass; no intervention was applied in the other 105 patients. MEASUREMENTS AND MAIN RESULTS: Measurements were performed under general anesthesia and mechanical ventilation before cardiopulmonary bypass, after cardiopulmonary bypass, and after the intervention. In each protocol stage, forced oscillatory lung impedance was measured to assess airway and tissue mechanical changes. Mainstream capnography was performed to assess ventilation- and/or perfusion-matching by calculating the normalized phase-3 slopes of the time and volumetric capnograms and the physiologic deadspace. Arterial and central venous blood samples were analyzed to characterize lung oxygenation and intrapulmonary shunt. After cardiopulmonary bypass, dopamineinduced marked improvements in airway resistance and tissue damping, with relatively small decreases in lung tissue elastance. These changes were associated with decreases in the normalized phase-3 slopes of the time and volumetric capnograms. The inotrope had no effect on physiologic deadspace, intrapulmonary shunt, or lung oxygenation. CONCLUSION: Dopamine reversed the complex detrimental lung mechanical changes induced by cardiopulmonary bypass and alleviated ventilation heterogeneities without affecting the physiologic deadspace or intrapulmonary shunt. Therefore, dopamine has a potential benefit on the gas exchange abnormalities after weaning from cardiopulmonary bypass.

Obesity and diabetes: similar respiratory mechanical but different gas exchange defects.

Diabetes mellitus increases smooth muscle tone and causes tissue remodeling, affecting elastin and collagen. Although the lung is dominated by these elements, diabetes is expected to modify the airway function and respiratory tissue mechanics. Therefore, we characterized the respiratory function in patients with diabetes with and without associated obesity. Mechanically ventilated patients with normal body shapes were divided into the control nondiabetic (n = 73) and diabetic (n = 31) groups. The other two groups included obese patients without diabetes (n = 43) or with diabetes (n = 30). The mechanical properties of the respiratory system were determined by forced oscillation technique. Airway resistance (Raw), tissue damping (G), and tissue elastance (H) were assessed by forced oscillation. Capnography was applied to determine phase 3 slopes and dead space indices. The intrapulmonary shunt fraction (Qs/Qt) and the lung oxygenation index (PaO2/FIO2) were estimated from arterial and central venous blood samples. Compared with the corresponding control groups, diabetes alone increased the Raw (7.6 ± 6 cmH2O.s/l vs. 3.1 ± 1.9 cmH2O.s/l), G (11.7 ± 5.5 cmH2O/l vs. 6.5 ± 2.8 cmH2O/l), and H (31.5 ± 11.8 cmH2O/l vs. 24.2 ± 7.2 cmH2O/l (P < 0.001 for all). Diabetes increased the capnographic phase 3 slope, whereas PaO2/FIO2 or Qs/Qt was not affected. Obesity alone caused similar detrimental changes in respiratory mechanics and alveolar heterogeneity, but these alterations also compromised gas exchange. We conclude that diabetes-induced intrinsic mechanical abnormalities are counterbalanced by hypoxic pulmonary vasoconstriction, which maintained intrapulmonary shunt fraction and oxygenation ability of the lungs.

Use of capnography to verify emergency ventilator sharing in the COVID-19 era.

Exacerbation of COVID-19 pandemic may lead to acute shortage of ventilators, which may require shared use of ventilator as a lifesaving concept. Two model lungs were ventilated with one ventilator to i) test the adequacy of individual tidal volumes via capnography, ii) assess cross-breathing between lungs, and iii) offer a simulation-based algorithm for ensuring equal tidal volumes. Ventilation asymmetry was induced by placing rubber band around one model lung, and the uneven distribution of tidal volumes (VT) was counterbalanced by elevating airflow resistance (HR) contralaterally. VT, end-tidal CO2 concentration (ETCO2), and peak inspiratory pressure (Ppi) were measured. Unilateral LC reduced VT and elevated ETCO2 on the affected side. Under HR, VT and ETCO2 were re-equilibrated. In conclusion, capnography serves as simple, bedside method for controlling the adequacy of split ventilation in each patient. No collateral gas flow was observed between the two lungs with different time constants. Ventilator sharing may play a role in emergency situations.

Physiologically variable ventilation in a rabbit model of asthma exacerbation.

BACKGROUND: Mechanical ventilation during status asthmaticus is challenging and increases the risk of severe complications. We recently reported the value of physiologically variable ventilation (PVV) in healthy and acutely injured lungs. We investigated whether PVV provides benefits compared with pressure-controlled ventilation (PCV) in an experimental model of severe acute asthma. METHODS: Allergen-sensitised rabbits were anaesthetised and randomised to either PCV (n=10) or PVV (n=12) during sustained bronchoconstriction induced by allergen and cholinergic stimuli for 6 h. The PVV pattern was generated from pre-recorded spontaneous breathing. Ventilation parameters, oxygenation index (PaO2/FiO2), and respiratory mechanics were measured hourly. Histological injury and inflammation were quantified after 6 h of ventilation. RESULTS: PVV resulted in lower driving pressures (13.7 cm H2O [12.5-14.9], mean [95% confidence interval]), compared with pressure-controlled ventilation (17.6 cm H2O [15.4-19.8]; P=0.002). PVV improved PaO2/FiO2 (PVV: 55.1 kPa [52-58.2]; PCV: 45.6 kPa [39.3-51.9]; P=0.018) and maintained tissue elastance (PVV: +8.7% [-0.6 to 18]; PCV: -11.2% [-17.3 to -5.1]; P=0.03). PVV resulted in less lung injury as assessed by lower histological injury score (PVV: 0.65 [0.62-0.65]; PCV: 0.71 [0.69-0.73]; P=0.003), cell count (PVV: 247 104 ml-1 [189-305]; PCV: 447 104 ml-1 [324-570]; P=0.005), and protein concentration in bronchoalveolar lavage fluid (PVV: 0.14 µg ml-1 [0.10-0.18]; PCV: 0.21 µg ml-1 [0.15-0.27]; P=0.035). CONCLUSIONS: Applying physiological variable ventilation in a model of asthma exacerbation led to improvements in gas exchange, ventilatory pressures, and respiratory tissue mechanics, and reduced lung injury. A global reduction in lung shear stress and recruitment effects may explain the benefits of PVV in status asthmaticus.

Lung volume dependence of respiratory function in rodent models of diabetes mellitus.

BACKGROUND: Diabetes mellitus causes the deterioration of smooth muscle cells and interstitial matrix proteins, including collagen. Collagen and smooth muscle cells are abundant in the lungs, but the effect of diabetes on airway function and viscoelastic respiratory tissue mechanics has not been characterized. This study investigated the impact of diabetes on respiratory function, bronchial responsiveness, and gas exchange parameters. METHODS: Rats were allocated randomly to three groups: a model of type 1 diabetes that received a high dose of streptozotocin (DM1, n = 13); a model of type 2 diabetes that received a low dose of streptozotocin with a high-fat diet (DM2, n = 14); and a control group with no treatment (C, n = 14). Forced oscillations were applied to assess airway resistance (Raw), respiratory tissue damping (G), and elastance (H). The arterial partial pressure of oxygen to the inspired oxygen fraction (PaO2/FiO2) and intrapulmonary shunt fraction (Qs/Qt) were determined from blood gas samples at positive end-expiratory pressures (PEEPs) of 0, 3, and 6 cmH2O. Lung responsiveness to methacholine was also assessed. Collagen fibers in lung tissue were quantified by histology. RESULTS: The rats in groups DM1 and DM2 exhibited elevated Raw, G, H, and Qs/Qt, compromised PaO2/FiO2, and diminished airway responsiveness. The severity of adverse tissue mechanical change correlated with excessive lung collagen expression. Increased PEEP normalized the respiratory mechanics, but the gas exchange abnormalities remained. CONCLUSIONS: These findings indicate that diabetes reduces airway and lung tissue viscoelasticity, resulting in alveolar collapsibility that can be compensated by increasing PEEP. Diabetes also induces persistent alveolo-capillary dysfunction and abnormal adaptation ability of the airways to exogenous constrictor stimuli.