Continuous estimation of respiratory system compliance and airway resistance during pressure-controlled ventilation without end-inspiration occlusion.

BACKGROUND: Assessing mechanical properties of the respiratory system (Cst) during mechanical ventilation necessitates an end-inspiration flow of zero, which requires an end-inspiratory occlusion maneuver. This lung model study aimed to observe the effect of airflow obstruction on the accuracy of respiratory mechanical properties during pressure-controlled ventilation (PCV) by analyzing dynamic signals. METHODS: A Hamilton C3 ventilator was attached to a lung simulator that mimics lung mechanics in healthy, acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD) models. PCV and volume-controlled ventilation (VCV) were applied with tidal volume (VT) values of 5.0, 7.0, and 10.0 ml/kg. Performance characteristics and respiratory mechanics were assessed and were calibrated by virtual extrapolation using expiratory time constant (RCexp). RESULTS: During PCV ventilation, drive pressure (DP) was significantly increased in the ARDS model. Peak inspiratory flow (PIF) and peak expiratory flow (PEF) gradually declined with increasing severity of airflow obstruction, while DP, end-inspiration flow (EIF), and inspiratory cycling ratio (EIF/PIF%) increased. Similar estimated values of Crs and airway resistance (Raw) during PCV and VCV ventilation were obtained in healthy adult and mild obstructive models, and the calculated errors did not exceed 5%. An underestimation of Crs and an overestimation of Raw were observed in the severe obstruction model. CONCLUSION: Using the modified dynamic signal analysis approach, respiratory system properties (Crs and Raw) could be accurately estimated in patients with non-severe airflow obstruction in the PCV mode.

The Effect of Recruitment Maneuver on Static Lung Compliance in Patients Undergoing General Anesthesia for Laparoscopic Cholecystectomy: A Single-Centre Prospective Clinical Intervention Study.

Background and Objectives: The aim of this study was to examine whether the use of an alveolar recruitment maneuver (RM) leads to a significant increase in static lung compliance (Cstat) and an improvement in gas exchange in patients undergoing laparoscopic cholecystectomy. Material and Methods: A clinical prospective intervention study was conducted. Patients were divided into two groups according to their body mass index (BMI): normal-weight (group I) and pre-obese and obese grade I (group II). Lung mechanics were monitored (Cstat, dynamic compliance-Cdin, peak pressure-Ppeak, plateau pressure-Pplat, driving pressure-DP) alongside gas exchange, and hemodynamic changes (heart rate-HR, mean arterial pressure-MAP) at six time points: T1 (induction of anesthesia), T2 (formation of pneumoperitoneum), T3 (RM with a PEEP of 5 cm H2O), T4 (RM with a PEEP of 7 cm H2O), T5 (desufflation), and T6 (RM at the end). The RM was performed by increasing the peak pressure by +5 cm of H2O at an equal inspiration-to-expiration ratio (I/E = 1:1) and applying a PEEP of 5 and 7 cm of H2O. Results: Out of 96 patients, 33 belonged to group I and 63 to group II. An increase in Cstat values occurred after all three RMs. At each time point, the Cstat value was measured higher in group I than in group II. A higher increase in Cstat was observed in group II after the second and third RM. Cstat values were higher at the end of the surgical procedure compared to values after the induction of anesthesia. The RM led to a significant increase in PaO2 in both groups without changes in HR or MAP. Conclusions: During laparoscopic cholecystectomy, the application of RM leads to a significant increase in Cstat and an improvement in gas exchange. The prevention of atelectasis during anesthesia should be initiated immediately after the induction of anesthesia, using protective mechanical ventilation and RM.

Effect of decreasing PEEP on hyperinflation and collapse in COVID-19: A computed tomography study.

BACKGROUND: High positive end-expiratory pressure (PEEP>10 cmH2O) is commonly used in mechanically ventilated hypoxemic patients with COVID-19. However, some epidemiological and physiological studies indirectly suggest that using a lower PEEP may primarily and beneficially decrease lung hyperinflation in this population. Herein we directly quantified the effect of decreasing PEEP from 15 to 10 cmH2O on lung hyperinflation and collapse in mechanically ventilated patients with COVID-19. METHODS: Twenty mechanically ventilated patients with COVID-19 underwent a lung computed tomography (CT) at PEEP of 15 and 10 cmH2O. The effect of decreasing PEEP on lung hyperinflation and collapse was directly quantified as the change in the over-aerated (density below -900 HU) and non-aerated (density above -100 HU) lung volumes. The net response to decreasing PEEP was computed as the sum of the change in those two compartments and expressed as the change in the "pathologic" lung volume. If the pathologic lung volume decreased (i.e., hyperinflation decreased more than collapse increased) when PEEP was decreased, the net response was considered positive; otherwise, it was considered negative. RESULTS: On average, the ratio of arterial tension to inspiratory fraction of oxygen (PaO2:FiO2) in the overall study population was 137 (119-162) mmHg. In 11 (55%) patients, the net response to decreasing PEEP was positive. Their over-aerated lung volume decreased by 159 (98-186) mL, while the non-aerated lung volume increased by only 58 (31-91) mL. In nine (45%) patients, the net response was negative. Their over-aerated lung volume decreased by 46 (18-72) mL, but their non-aerated lung volume increased by 107 (44-121) mL. CONCLUSION: In 20 patients with COVID-19 the net response to decreasing PEEP, as assessed with lung CT, was variable. In approximately half of them it was positive (and possibly beneficial), with a decrease in hyperinflation larger than the increase in collapse.

A vagal reflex evoked by airway closure.

Airway integrity must be continuously maintained throughout life. Sensory neurons guard against airway obstruction and, on a moment-by-moment basis, enact vital reflexes to maintain respiratory function1,2. Decreased lung capacity is common and life-threatening across many respiratory diseases, and lung collapse can be acutely evoked by chest wall trauma, pneumothorax or airway compression. Here we characterize a neuronal reflex of the vagus nerve evoked by airway closure that leads to gasping. In vivo vagal ganglion imaging revealed dedicated sensory neurons that detect airway compression but not airway stretch. Vagal neurons expressing PVALB mediate airway closure responses and innervate clusters of lung epithelial cells called neuroepithelial bodies (NEBs). Stimulating NEBs or vagal PVALB neurons evoked gasping in the absence of airway threats, whereas ablating NEBs or vagal PVALB neurons eliminated gasping in response to airway closure. Single-cell RNA sequencing revealed that NEBs uniformly express the mechanoreceptor PIEZO2, and targeted knockout of Piezo2 in NEBs eliminated responses to airway closure. NEBs were dispensable for the Hering-Breuer inspiratory reflex, which indicated that discrete terminal structures detect airway closure and inflation. Similar to the involvement of Merkel cells in touch sensation3,4, NEBs are PIEZO2-expressing epithelial cells and, moreover, are crucial for an aspect of lung mechanosensation. These findings expand our understanding of neuronal diversity in the airways and reveal a dedicated vagal pathway that detects airway closure to help preserve respiratory function.

Pressure-volume mechanics of inflating and deflating intact whole organ porcine lungs.

Pressure-volume curves of the lung are classical measurements of lung function and are impacted by changes in lung structure due to disease or shifts in air-delivery volume or cycling rate. Diseased and preterm infant lungs have been found to show heterogeneous behavior which is highly frequency dependent. This breathing rate dependency has motivated the exploration of multi-frequency oscillatory ventilators to deliver volume oscillation with optimal frequencies for various portions of the lung to provide more uniform air distribution. The design of these advanced ventilators requires the examination of lung function and mechanics, and an improved understanding of the pressure-volume response of the lung. Therefore, to comprehensively analyze whole lung organ mechanics, we investigate six combinations of varying applied volumes and frequencies using ex-vivo porcine specimens and our custom-designed electromechanical breathing apparatus. Lung responses were evaluated through measurements of inflation and deflation slopes, static compliance, peak pressure and volume, as well as hysteresis, energy loss, and pressure relaxation. Generally, we observed that the lungs were stiffer when subjected to faster breathing rates and lower inflation volumes. The lungs exhibited greater inflation volume dependencies compared to frequency dependencies. This study's reported response of the lung to variations of inflation volume and breathing rate can help the optimization of conventional mechanical ventilators and inform the design of advanced ventilators. Although frequency dependency is found to be minimal in normal porcine lungs, this preliminary study lays a foundation for comparison with pathological lungs, which are known to demonstrate marked rate dependency.

Characterization of compliance phenotypes in COVID-19 acute respiratory distress syndrome.

BACKGROUND: Coronavirus disease 2019-associated acute respiratory distress syndrome (COVID-19 ARDS) seems to differ from the "classic ARDS", showing initial significant hypoxemia in the face of relatively preserved compliance and evolving later in a scenario of poorly compliant lungs. We tested the hypothesis that in patients with COVID-19 ARDS, the initial value of static compliance of respiratory system (Crs) (1) depends on the previous duration of the disease (i.e., the fewer days of illness, the higher the Crs and vice versa) and (2) identifies different lung patterns of time evolution and response to prone positioning. METHODS: This was a single-center prospective observational study. We enrolled consecutive mechanically ventilated patients with a diagnosis of COVID-19 who met ARDS criteria, admitted to intensive care unit (ICU). Patients were divided in four groups based on quartiles of initial Crs. Relationship between Crs and the previous duration of the disease was evaluated. Respiratory parameters collected once a day and during prone positioning were compared between groups. RESULTS: We evaluated 110 mechanically ventilated patients with a diagnosis of COVID-19 who met ARDS criteria admitted to our ICUs. Patients were divided in groups based on quartiles of initial Crs. The median initial Crs was 41 (32-47) ml/cmH2O. No association was found between the previous duration of the disease and the initial Crs. The Crs did not change significantly over time within each quartile. Positive end-expiratory pressure (PEEP) and driving pressure were respectively lower and greater in patients with lower Crs. Prone positioning significantly improved PaO2/FiO2 in the 4 groups, however it increased the Crs significantly only in patients in lower quartile of Crs. CONCLUSIONS: In our cohort, the initial Crs is not dependent on the previous duration of COVID-19 disease. Prone positioning improves oxygenation irrespective to initial Crs, but it ameliorates respiratory mechanics only in patients with lower Crs.

Determining optimal positive end-expiratory pressure and tidal volume in children by intratidal compliance: a prospective observational study.

BACKGROUND: Limited data exist regarding optimal intraoperative ventilation strategies for the paediatric population. This study aimed to determine the optimal combination of PEEP and tidal volume (VT) based on intratidal compliance profiles in healthy young children undergoing general anaesthesia. METHODS: During anaesthesia, infants (1 month-1 yr), toddlers (1-3 yr), and children (3-6 yr) were assigned serially to four ventilator settings: PEEP 8 cm H2O/VT 8 ml kg-1 (PEEP8/VT8), PEEP 10 cm H2O/VT 5 ml kg-1 (PEEP10/VT5), PEEP 10 cm H2O/VT 8 ml kg-1 (PEEP10/VT8), and PEEP 12 cm H2O/VT 5 ml kg-1 (PEEP12/VT5). The primary outcome was intratidal compliance profile, classified at each ventilator setting as horizontal (indicative of optimal alveolar ventilatory conditions), increasing, decreasing, or combinations of increasing/decreasing/horizontal compliance. Secondary outcomes were peak inspiratory, plateau, and driving pressures. RESULTS: Intratidal compliance was measured in 15 infants, 13 toddlers, and 15 children (15/43 [35%] females). A horizontal compliance profile was most frequently observed with PEEP10/VT5 (60.5%), compared with PEEP10/VT8, PEEP8/VT8, and PEEP12/VT5 (23.3-34.9%; P<0.001). Decreasing compliance profiles were most frequent when VT increased to 8 ml kg-1, PEEP increased to 12 cm H2O, or both. Plateau airway pressures were lower at PEEP8/VT8 (16.9 cm H2O [2.2]) and PEEP10/VT5 (16.7 cm H2O [1.7]), compared with PEEP10/VT8 (19.5 cm H2O [2.1]) and PEEP12/VT5 (19.0 cm H2O [2.0]; P<0.001). Driving pressure was lowest with PEEP10/VT5 (4.6 cm H2O), compared with other combinations (7.0 cm H2O [2.0]-9.5 cm H2O [2.1]; P<0.001). CONCLUSIONS: VT 5 ml kg-1 combined with 10 cm H2O PEEP may reduce atelectasis and overdistension, and minimise driving pressure in the majority of mechanically ventilated children <6 yr. The effect of these PEEP and VT settings on postoperative pulmonary complications in children undergoing surgery requires further study. CLINICAL TRIAL REGISTRATION: NCT04633720.

mTORC1 is a mechanosensor that regulates surfactant function and lung compliance during ventilator-induced lung injury.

The acute respiratory distress syndrome (ARDS) is a highly lethal condition that impairs lung function and causes respiratory failure. Mechanical ventilation (MV) maintains gas exchange in patients with ARDS but exposes lung cells to physical forces that exacerbate injury. Our data demonstrate that mTOR complex 1 (mTORC1) is a mechanosensor in lung epithelial cells and that activation of this pathway during MV impairs lung function. We found that mTORC1 is activated in lung epithelial cells following volutrauma and atelectrauma in mice and humanized in vitro models of the lung microenvironment. mTORC1 is also activated in lung tissue of mechanically ventilated patients with ARDS. Deletion of Tsc2, a negative regulator of mTORC1, in epithelial cells impairs lung compliance during MV. Conversely, treatment with rapamycin at the time MV is initiated improves lung compliance without altering lung inflammation or barrier permeability. mTORC1 inhibition mitigates physiologic lung injury by preventing surfactant dysfunction during MV. Our data demonstrate that, in contrast to canonical mTORC1 activation under favorable growth conditions, activation of mTORC1 during MV exacerbates lung injury and inhibition of this pathway may be a novel therapeutic target to mitigate ventilator-induced lung injury during ARDS.

Pulmonary Function Tests in Very Low Birth Weight Infants Screened for Pulmonary Hypertension: A Pilot Study.

OBJECTIVE: To compare pulmonary function tests (PFTs), specifically respiratory system resistance (Rrs) and compliance (Crs), in very low birth weight (VLBW) infants with and without pulmonary hypertension. STUDY DESIGN: Infants were included who underwent PFTs at 34-38 weeks postmenstrual age (PMA) as part of our pulmonary hypertension screening guidelines for infants born at ≤1500 g requiring respiratory support at ≥34 weeks PMA. One pediatric cardiologist reviewed and estimated right ventricular or pulmonary arterial pressure and defined pulmonary hypertension as an estimated pulmonary arterial pressure or right ventricular pressure greater than one-half the systemic pressure. Rrs and Crs were measured with the single breath occlusion technique and functional residual capacity with the nitrogen washout method according to standardized criteria. RESULTS: Twelve VLBW infants with pulmonary hypertension and 39 without pulmonary hypertension were studied. Those with pulmonary hypertension had significantly lower birth weight and a trend toward a lower gestational age. There were no other demographic differences between the groups. The infants with pulmonary hypertension had significantly higher Rrs (119 vs 78 cmH2O/L/s; adjusted P = .012) and significantly lower Crs/kg (0.71 vs 0.92 mL/cmH2O/kg; P = .04). CONCLUSIONS: In this pilot study of VLBW infants screened for pulmonary hypertension at 34-38 weeks PMA, those with pulmonary hypertension had significantly increased Rrs and decreased Crs compared with those without pulmonary hypertension. Additional studies are needed to further phenotype infants with evolving BPD and pulmonary hypertension.

An appraisal of respiratory system compliance in mechanically ventilated covid-19 patients.

BACKGROUND: Heterogeneous respiratory system static compliance (CRS) values and levels of hypoxemia in patients with novel coronavirus disease (COVID-19) requiring mechanical ventilation have been reported in previous small-case series or studies conducted at a national level. METHODS: We designed a retrospective observational cohort study with rapid data gathering from the international COVID-19 Critical Care Consortium study to comprehensively describe CRS-calculated as: tidal volume/[airway plateau pressure-positive end-expiratory pressure (PEEP)]-and its association with ventilatory management and outcomes of COVID-19 patients on mechanical ventilation (MV), admitted to intensive care units (ICU) worldwide. RESULTS: We studied 745 patients from 22 countries, who required admission to the ICU and MV from January 14 to December 31, 2020, and presented at least one value of CRS within the first seven days of MV. Median (IQR) age was 62 (52-71), patients were predominantly males (68%) and from Europe/North and South America (88%). CRS, within 48 h from endotracheal intubation, was available in 649 patients and was neither associated with the duration from onset of symptoms to commencement of MV (p = 0.417) nor with PaO2/FiO2 (p = 0.100). Females presented lower CRS than males (95% CI of CRS difference between females-males: - 11.8 to - 7.4 mL/cmH2O p < 0.001), and although females presented higher body mass index (BMI), association of BMI with CRS was marginal (p = 0.139). Ventilatory management varied across CRS range, resulting in a significant association between CRS and driving pressure (estimated decrease - 0.31 cmH2O/L per mL/cmH20 of CRS, 95% CI - 0.48 to - 0.14, p < 0.001). Overall, 28-day ICU mortality, accounting for the competing risk of being discharged within the period, was 35.6% (SE 1.7). Cox proportional hazard analysis demonstrated that CRS (+ 10 mL/cm H2O) was only associated with being discharge from the ICU within 28 days (HR 1.14, 95% CI 1.02-1.28, p = 0.018). CONCLUSIONS: This multicentre report provides a comprehensive account of CRS in COVID-19 patients on MV. CRS measured within 48 h from commencement of MV has marginal predictive value for 28-day mortality, but was associated with being discharged from ICU within the same period. Trial documentation: Available at https://www.covid-critical.com/study . TRIAL REGISTRATION: ACTRN12620000421932.

Emergency 3-Dimensional-Printed Devices for Splitting Ventilators in Lungs With Different Compliances: An In Vitro Study.

Ventilator shortages occurred due to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This in vitro study evaluated the effectiveness of 3-dimensional (3D)-printed splitters and 3D-printed air flow limiters (AFL) in delivering appropriate tidal volumes (TV) to lungs with different compliances. Groups were divided according to the size of the AFL: AFL-4 was a 4-mm device, AFL-5 a 5-mm device, AFL-6 a 6-mm device, and no limiter (control). A ventilator was split to supply TV to 2 artificial lungs with different compliances. The AFL improved TV distribution.

Positive End-Expiratory Pressure, Pleural Pressure, and Regional Compliance during Pronation: An Experimental Study.

Rationale: The physiological basis of lung protection and the impact of positive end-expiratory pressure (PEEP) during pronation in acute respiratory distress syndrome are not fully elucidated. Objectives: To compare pleural pressure (Ppl) gradient, ventilation distribution, and regional compliance between dependent and nondependent lungs, and investigate the effect of PEEP during supination and pronation. Methods: We used a two-hit model of lung injury (saline lavage and high-volume ventilation) in 14 mechanically ventilated pigs and studied supine and prone positions. Global and regional lung mechanics including Ppl and distribution of ventilation (electrical impedance tomography) were analyzed across PEEP steps from 20 to 3 cm H2O. Two pigs underwent computed tomography scans: tidal recruitment and hyperinflation were calculated. Measurements and Main Results: Pronation improved oxygenation, increased Ppl, thus decreasing transpulmonary pressure for any PEEP, and reduced the dorsal-ventral pleural pressure gradient at PEEP < 10 cm H2O. The distribution of ventilation was homogenized between dependent and nondependent while prone and was less dependent on the PEEP level than while supine. The highest regional compliance was achieved at different PEEP levels in dependent and nondependent regions in supine position (15 and 8 cm H2O), but for similar values in prone position (13 and 12 cm H2O). Tidal recruitment was more evenly distributed (dependent and nondependent), hyperinflation lower, and lungs cephalocaudally longer in the prone position. Conclusions: In this lung injury model, pronation reduces the vertical pleural pressure gradient and homogenizes regional ventilation and compliance between the dependent and nondependent regions. Homogenization is much less dependent on the PEEP level in prone than in supine positon.

Lung ultrasound score as an indicator of dynamic lung compliance during veno-venous extra-corporeal membrane oxygenation.

Decisions on weaning from veno-venous extra-corporeal membrane oxygenation (VV-ECMO) requires the ability to maintain adequate gas exchange and work of breathing with reductions in ECMO pump flow and fresh gas flow. Testing of the readiness to wean the patient from ECMO however may vary dependent upon local protocols and clinical judgment. This study sought to validate the use of the LUS-score during VV-ECMO against the changes in chest x-ray infiltrates, dynamic lung compliance (CLdyn) and VV-ECMO settings (as standard measures of native lung function and the level of ECMO support) during the ECMO cycle. This prospective cohort study of 10 patients on VV-ECMO compared the LUS score (range 0-36) within 48-h, day 5 and day 10 of commencement of ECMO (or on the day of ECMO decannulation) to dynamic lung compliance, Murray Lung Injury Score and ECMO settings. Seven Male and three Female patients were included (average age 37 years (SD 14.8) and weight 71 Kg (SD 16.9). Median (IQR) duration of ECMO, ICU and hospital length of stay was 7.5 days (5.2-19.0), 12.5 days (8.5-22.7), 19.0 days (12.1- 36.1), respectively. There was a strong negative association between LUS-score and dynamic lung compliance (rs(33) = -0.66, p < .001) providing some validation on the use of the LUS score as a potential surrogate measure of lung aeration and lung mechanics during VV-ECMO weaning.

Acute respiratory distress syndrome (ARDS) caused by the novel coronavirus disease (COVID-19): a practical comprehensive literature review.

INTRODUCTION: The exponential growth of SARS-CoV-2 virus transmission during the first months of 2020 has placed substantial pressure on most health systems around the world. The complications derived from the novel coronavirus disease (COVID-19) vary due to comorbidities, sex and age, with more than 50% of the patients requiring some level of intensive care developing acute respiratory distress syndrome (ARDS). The authors carried out an extensive and comprehensive literature review on SARS-CoV-2 infection, the clinical, pathological, and radiological presentation as well as the current treatment strategies. AREAS COVERED: Various complications caused by SARS-CoV-2 infection have been identified, the most lethal being the acute respiratory distress syndrome, caused most likely by the presence of severe immune cell response and the concomitant alveolus inflammation. The new treatment strategies are updated, and the analysis of the physiopathology is included in this review. EXPERT OPINION: ARDS is one of the most frequent complications in patients with COVID-19. Information regarding the etiology and physiopathology are still unfolding and for the prevention and amelioration, good clinical management, adequate ventilatory support and the use of systemic corticoids seem to be the most efficient way to reduce mortality and to reduce hospital lengths.

T-piece resuscitators: can they provide safe ventilation in a low compliant newborn lung?

BACKGROUND: T-piece resuscitators (TPRs) are used for primary newborn resuscitation in birthing and emergency rooms worldwide. A recent study has shown spikes in peak inflation pressure (PIP) over set values with two brands of TPRs inbuilt into infant warmer/resuscitation platforms. We aimed to compare delivered ventilation between two TPR drivers with inflation pressure spikes to a standard handheld TPR in a low test lung compliance (Crs), leak-free bench test model. METHODS: A single operator provided positive pressure ventilation to a low compliance test lung model (Crs 0.2-1 mL/cmH2O) at set PIP of 15, 25, 35 and 40 cmH2O. Two TPR devices with known spikes (Draeger Resuscitaire, GE Panda) were compared with handheld Neopuff (NP). Recommended settings for positive end-expiratory pressure (5 cmH2O), inflation rate of 60/min and gas flow rate 10 L/min were used. RESULTS: 2293 inflations were analysed. Draeger and GE TPR drivers delivered higher mean PIP (Panda 18.9-49.5 cmH2O; Draeger 21.2-49.2 cmH2O and NP 14.8-39.9 cmH2O) compared with set PIP and tidal volumes (TVs) compared with the NP (Panda 2.9-7.8 mL; Draeger 3.8-8.1 mL; compared with NP 2.2-6.0 mL), outside the prespecified acceptable range (±10% of set PIP and ±10% TV compared with NP). CONCLUSION: The observed spike in PIP over set values with Draeger and GE Panda systems resulted in significantly higher delivered volumes compared with the NP with identical settings. Manufacturers need to address these differences. The effect on patient outcomes is unknown.

Functional respiratory imaging identifies redistribution of pulmonary blood flow in patients with COVID-19.

An increasing observation is that some patients with COVID-19 have normal lung compliance but significant hypoxaemia different from typical acute respiratory distress syndrome (ARDS). We hypothesised that changes in pulmonary blood distribution may be partially responsible and used functional respiratory imaging on CT scans to calculate pulmonary blood volume. We found that patients with COVID-19 had significantly reduced blood volume in the smaller calibre blood vessels (here defined as <5 mm2 cross-sectional area) compared with matched ARDS patients and healthy controls. This suggests that using high levels of PEEP may not alone be enough to oxygenate these patients and that additional management strategies may be needed.

Evidence of Air Trapping During Ex Vivo Lung Perfusion: A Swine Experimental Lung Imaging and Mechanics Study.

Ex vivo lung perfusion (EVLP) allows the ventilation and perfusion of lungs to evaluate their viability for transplantation. The aim of this study is to compare the mechanical, morphologic and functional properties of lungs during EVLP with values obtained in vivo to guide a safe mechanical ventilation strategy. Lungs from 5 healthy pigs were studied in vivo and during 4 hours of EVLP. Lung compliance, airway resistance, gas exchange, and hemodynamic parameters were collected at positive end-expiratory pressure (PEEP) of 5 cm H2O. Computed tomography was performed at PEEP 0, PEEP 5, and total lung capacity (TLC). Lung pressure-volume (PV) curves were performed from PEEP 0 to TLC. Lung compliance decreased during EVLP (53 ± 5 mL/cm H2O vs 29 ± 7 mL/cm H2O, P < .05), and the PV curve showed a lower inflection point. Gas content (528 ± 118 mL vs 892 ± 402 mL at PEEP 0) and airway resistance (25 ± 5 vs 44 ± 9 cmH2O/L∗s-1, P < .05) were higher during EVLP. Alveolar dead space (5% ± 2% vs 17% ± 6%, P < .05) and intrapulmonary shunt (9% ± 2% vs 28% ± 13%, P < .05) increased ex vivo compared to in vivo, while the partial pressure of oxygen to inspired oxygen fraction ratio (PO2/FiO2) did not differ (468 ± 52 mm Hg vs 536 ± 14 mm Hg). In conclusion, during EVLP lungs show signs of air trapping and bronchoconstriction, resulting in low compliance and increased alveolar dead space. Intrapulmonary shunt is high despite oxygenation levels acceptable for transplantation.

Haemodynamic characteristics of COVID-19 patients with acute respiratory distress syndrome requiring mechanical ventilation. An invasive assessment using right heart catheterization.

AIMS: Interstitial pneumonia due to coronavirus disease 2019 (COVID-19) is often complicated by severe respiratory failure. In addition to reduced lung compliance and ventilation/perfusion mismatch, a blunted hypoxic pulmonary vasoconstriction has been hypothesized, that could explain part of the peculiar pathophysiology of the COVID-19 cardiorespiratory syndrome. However, no invasive haemodynamic characterization of COVID-19 patients has been reported so far. METHODS AND RESULTS: Twenty-one mechanically-ventilated COVID-19 patients underwent right heart catheterization. Their data were compared both with those obtained from non-mechanically ventilated paired control subjects matched for age, sex and body mass index, and with pooled data of 1937 patients with 'typical' acute respiratory distress syndrome (ARDS) from a systematic literature review. Cardiac index was higher in COVID-19 patients than in controls [3.8 (2.7-4.5) vs. 2.4 (2.1-2.8) L/min/m2 , P < 0.001], but slightly lower than in ARDS patients (P = 0.024). Intrapulmonary shunt and lung compliance were inversely related in COVID-19 patients (r = -0.57, P = 0.011) and did not differ from ARDS patients. Despite this, pulmonary vascular resistance of COVID-19 patients was normal, similar to that of control subjects [1.6 (1.1-2.5) vs. 1.6 (0.9-2.0) WU, P = 0.343], and lower than reported in ARDS patients (P < 0.01). Pulmonary hypertension was present in 76% of COVID-19 patients and in 19% of control subjects (P < 0.001), and it was always post-capillary. Pulmonary artery wedge pressure was higher in COVID-19 than in ARDS patients, and inversely related to lung compliance (r = -0.46, P = 0.038). CONCLUSIONS: The haemodynamic profile of COVID-19 patients needing mechanical ventilation is characterized by combined cardiopulmonary alterations. Low pulmonary vascular resistance, coherent with a blunted hypoxic vasoconstriction, is associated with high cardiac output and post-capillary pulmonary hypertension, that could eventually contribute to lung stiffness and promote a vicious circle between the lung and the heart.

Prone position in ARDS patients: why, when, how and for whom.

In ARDS patients, the change from supine to prone position generates a more even distribution of the gas-tissue ratios along the dependent-nondependent axis and a more homogeneous distribution of lung stress and strain. The change to prone position is generally accompanied by a marked improvement in arterial blood gases, which is mainly due to a better overall ventilation/perfusion matching. Improvement in oxygenation and reduction in mortality are the main reasons to implement prone position in patients with ARDS. The main reason explaining a decreased mortality is less overdistension in non-dependent lung regions and less cyclical opening and closing in dependent lung regions. The only absolute contraindication for implementing prone position is an unstable spinal fracture. The maneuver to change from supine to prone and vice versa requires a skilled team of 4-5 caregivers. The most frequent adverse events are pressure sores and facial edema. Recently, the use of prone position has been extended to non-intubated spontaneously breathing patients affected with COVID-19 ARDS. The effects of this intervention on outcomes are still uncertain.