Prone position in intubated, mechanically ventilated patients with COVID-19: a multi-centric study of more than 1000 patients.

BACKGROUND: Limited data are available on the use of prone position in intubated, invasively ventilated patients with Coronavirus disease-19 (COVID-19). Aim of this study is to investigate the use and effect of prone position in this population during the first 2020 pandemic wave. METHODS: Retrospective, multicentre, national cohort study conducted between February 24 and June 14, 2020, in 24 Italian Intensive Care Units (ICU) on adult patients needing invasive mechanical ventilation for respiratory failure caused by COVID-19. Clinical data were collected on the day of ICU admission. Information regarding the use of prone position was collected daily. Follow-up for patient outcomes was performed on July 15, 2020. The respiratory effects of the first prone position were studied in a subset of 78 patients. Patients were classified as Oxygen Responders if the PaO2/FiO2 ratio increased ≥ 20 mmHg during prone position and as Carbon Dioxide Responders if the ventilatory ratio was reduced during prone position. RESULTS: Of 1057 included patients, mild, moderate and severe ARDS was present in 15, 50 and 35% of patients, respectively, and had a resulting mortality of 25, 33 and 41%. Prone position was applied in 61% of the patients. Patients placed prone had a more severe disease and died significantly more (45% vs. 33%, p < 0.001). Overall, prone position induced a significant increase in PaO2/FiO2 ratio, while no change in respiratory system compliance or ventilatory ratio was observed. Seventy-eight % of the subset of 78 patients were Oxygen Responders. Non-Responders had a more severe respiratory failure and died more often in the ICU (65% vs. 38%, p = 0.047). Forty-seven % of patients were defined as Carbon Dioxide Responders. These patients were older and had more comorbidities; however, no difference in terms of ICU mortality was observed (51% vs. 37%, p = 0.189 for Carbon Dioxide Responders and Non-Responders, respectively). CONCLUSIONS: During the COVID-19 pandemic, prone position has been widely adopted to treat mechanically ventilated patients with respiratory failure. The majority of patients improved their oxygenation during prone position, most likely due to a better ventilation perfusion matching. TRIAL REGISTRATION: clinicaltrials.gov number: NCT04388670.

Use of low-molecular weight heparin, transfusion and mortality in COVID-19 patients not requiring ventilation.

It is still debated whether prophylactic doses of low-molecular- weight heparin (LMWH) are always effective in preventing Venous Thromboembolism (VTE) and mortality in COVID-19. Furthermore, there is paucity of data for those patients not requiring ventilation. We explored mortality and the safety/efficacy profile of LMWH in a cohort of Italian patients with COVID-19 who did not undergo ventilation. From the initial cohort of 422 patients, 264 were enrolled. Most (n = 156, 87.7%) received standard LMWH prophylaxis during hospitalization, with no significant difference between medical wards and Intensive Care Unit (ICU). Major or not major but clinically relevant hemorrhages were recorded in 13 (4.9%) patients: twelve in those taking prophylactic LMWH and one in a patient taking oral anticoagulants (p: n.s.). Thirty-nine patients (14.8%) with median age 75 years. were transfused. Hemoglobin (Hb) at admission was significantly lower in transfused patients and Hb at admission inversely correlated with the number of red blood cells units transfused (p < 0.001). In-hospital mortality occurred in 76 (28.8%) patients, 46 (24.3%) of whom admitted to medical wards. Furthermore, Hb levels at admittance were significantly lower in fatalities (g/dl 12.3; IQR 2.4 vs. 13.3; IQR 2.8; Mann-Whitney U-test; p = 0.001). After the exclusion of patients treated by LMWH intermediate or therapeutic doses (n = 32), the logistic regression showed that prophylaxis significantly and independently reduced mortality (OR 0.31, 95% CI 0.13-0.85). Present data show that COVID-19 patients who do not require ventilation benefit from prophylactic doses of LMWH.

SARS-CoV-2 pneumonia succesfully treated with cpap and cycles of tripod position: a case report.

BACKGROUND: Pneumonia induced by 2019 Coronavirus (COVID-19) is characterized by hypoxemic respiratory failure that may present with a broad spectrum of clinical phenotypes. At the beginning, patients may have normal lung compliance and be responsive to noninvasive ventilatory support, such as CPAP. However, the transition to more severe respiratory failure - Severe Acute Respiratory Syndrome (SARS-CoV-2), necessitating invasive ventilation is often abrupt and characterized by a severe V/Q mismatch that require cycles of prone positioning. The aim of this case is to report the effect on gas exchange, respiratory mechanics and hemodynamics of tripod (or orthopneic sitting position) used as an alternative to prone position in a patient with mild SARS-CoV-2 pneumonia ventilated with helmet CPAP. CASE PRESENTATION: A 77-year-old awake and collaborating male patient with mild SARS-CoV-2 pneumonia and ventilated with Helmet CPAP, showed sudden worsening of gas exchange without dyspnea. After an unsuccessful attempt of prone positioning, we alternated three-hours cycles of semi-recumbent and tripod position, still keeping him in CPAP. Arterial blood gases (PaO2/FiO2, PaO2, SaO2, PaCO2 and A/a gradient), respiratory (VE, VT, RR) and hemodynamic parameters (HR, MAP) were collected in the supine and tripod position. Cycles of tripod position were continued for 3 days. The patient had a clinically important improvement in arterial blood gases and respiratory parameters, with stable hemodynamic and was successfully weaned and discharged to ward 10 days after pneumonia onset. CONCLUSIONS: Tripod position during Helmet CPAP can be applied safely in patients with mild SARS-CoV-2 pneumonia, with improvement of oxygenation and V/Q matching, thus reducing the need for intubation.

Effects of Positive End-Expiratory Pressure in "High Compliance" Severe Acute Respiratory Syndrome Coronavirus 2 Acute Respiratory Distress Syndrome.

OBJECTIVES: Clinical observation suggests that early acute respiratory distress syndrome induced by the severe acute respiratory syndrome coronavirus 2 may be "atypical" due to a discrepancy between a relatively unaffected static respiratory system compliance and a significant hypoxemia. This would imply an "atypical" response to the positive end-expiratory pressure. DESIGN: Single-center, unblinded, crossover study. SETTING: ICU of Bari Policlinico Academic Hospital (Italy), dedicated to care patients with confirmed diagnosis of novel coronavirus disease 2019. PATIENTS: Eight patients with early severe acute respiratory syndrome coronavirus 2 acute respiratory distress syndrome and static respiratory compliance higher than or equal to 50 mL/cm H2O. INTERVENTIONS: We compared a "lower" and a "higher" positive end-expiratory pressure approach, respectively, according to the intervention arms of the acute respiratory distress syndrome network and the positive end-expiratory pressure setting in adults with acute respiratory distress syndrome studies. MEASUREMENTS AND MAIN RESULTS: Patients were ventilated with the acute respiratory distress syndrome network and, subsequently, with the ExPress protocol. After 1 hour of ventilation, for each protocol, we recorded arterial blood gas, respiratory mechanics, alveolar recruitment, and hemodynamic variables. Comparisons were performed with analysis of variance for repeated measures or Friedman test as appropriate. Positive end-expiratory pressure was increased from 9 ± 3.5 to 17.7 ± 1.7 cm H2O (p < 0.01). Alveolar recruitment was 450 ± 111 mL. Static respiratory system compliance decreased from 58.3 ± 7.6 mL/cm H2O to 47.4 ± 14.5 mL/cm H2O (p = 0.018) and the "stress index" increased from 0.97 ± 0.03 to 1.22 ± 0.07 (p < 0.001). The PaO2/FIO2 ratio increased from 131 ± 22 to 207 ± 41 (p < 0.001), and the PaCO2 increased from 45.9 ± 12.7 to 49.8 ± 13.2 mm Hg (p < 0.001). The cardiac index went from 3.6 ± 0.4 to 2.9 ± 0.6 L/min/m (p = 0.01). CONCLUSIONS: Our data suggest that the "higher" positive end-expiratory pressure approach in patients with severe acute respiratory syndrome coronavirus 2 acute respiratory distress syndrome and high compliance improves oxygenation and lung aeration but may result in alveolar hyperinflation and hemodynamic alterations.

LPS removal reduces CD80-mediated albuminuria in critically ill patients with Gram-negative sepsis.

LPS-induced sepsis is a leading cause of acute kidney injury (AKI) in critically ill patients. LPS may induce CD80 expression in podocytes with subsequent onset of proteinuria, a risk factor for progressive chronic kidney disease (CKD) frequently observed after AKI. This study aimed to investigate the therapeutic efficacy of LPS removal in decreasing albuminuria through the reduction of podocyte CD80 expression. Between January 2015 and December 2017, 70 consecutive patients with Gram-negative sepsis-induced AKI were randomized to either have coupled plasma filtration and adsorption (CPFA) added to the standard care ( n = 35) or not ( n = 35). To elucidate the possible relationship between LPS-induced renal damage, proteinuria, and CD80 expression in Gram sepsis, a swine model of LPS-induced AKI was set up. Three hours after LPS infusion, animals were treated or not with CPFA for 6 h. Treatment with CPFA significantly reduced serum cytokines, C-reactive protein, procalcitonin, and endotoxin levels in patients with Gram-negative sepsis-induced AKI. CPFA significantly lowered also proteinuria and CD80 urinary excretion. In the swine model of LPS-induced AKI, CD80 glomerular expression, which was undetectable in control pigs, was markedly increased at the podocyte level in LPS-exposed animals. CPFA significantly reduced LPS-induced proteinuria and podocyte CD80 expression in septic pigs. Our data indicate that LPS induces albuminuria via podocyte expression of CD80 and suggest a possible role of timely LPS removal in preventing the maladaptive repair of the podocytes and the consequent increased risk of CKD in sepsis-induced AKI.

Valve mediated hemodynamics and their association with distal ascending aortic diameter in bicuspid aortic valve subjects.

PURPOSE: Valve mediated hemodynamics have been postulated to contribute to pathology of the ascending aorta (AAo). The objective of this study is to assess the association of aortic valve morphology and hemodynamics with downstream AAo size in subjects with bicuspid aortic valve (BAV) disease. MATERIALS AND METHODS: Four-dimensional flow MRI at 1.5 or 3 Tesla was used to evaluate the hemodynamics in the proximal AAo of 52 subjects: size-matched controls with tricuspid aortic valves (n = 24, mid ascending aorta [MAA] diameter = 38.0 ± 4.9 mm) and BAV patients with aortic dilatation (n = 14 right and left coronary leaflet fusion [RL]-BAV, MAA diameter = 38.1 ± 5.3 mm; n = 14 right and noncoronary leaflet fusion [RN]-BAV, MAA diameter = 36.5 ± 6.6 mm). A validated semi-automated technique was used to evaluate hemodynamic metrics (flow angle, flow displacement, and jet quadrant) and valve morphology (orifice circularity) for all subjects. Regression analysis of these metrics to AAo diameter was performed. RESULTS: RN-BAV subjects displayed a stronger correlation between hemodynamic metrics in the proximal AAo with diameter in the distal AAo compared with size-matched tricuspid aortic valve (TAV) controls and RL-BAV subjects. The distal AAo diameter was found to be strongly correlated to the upstream flow displacement (R2adjusted = 0.75) and flow angle (R2adjusted = 0.66) measured at the sino-tubular junction (STJ). Orifice circularity was also strongly correlated (R2adjusted = 0.53) to the distal AAo diameter in RN-BAV subjects. For TAV controls and RL-BAV subjects, correlations were weaker (R2adjusted < 0.2). CONCLUSION: Hemodynamics in the STJ were strongly correlated to the distal AAo diameter for the RN-BAV subjects. Hemodynamic metrics were more strongly correlated to the downstream aortic size when compared with valve morphology metrics. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:246-254.

Respiratory System Mechanics During Low Versus High Positive End-Expiratory Pressure in Open Abdominal Surgery: A Substudy of PROVHILO Randomized Controlled Trial.

BACKGROUND: In the 2014 PROtective Ventilation using HIgh versus LOw positive end-expiratory pressure (PROVHILO) trial, intraoperative low tidal volume ventilation with high positive end-expiratory pressure (PEEP = 12 cm H2O) and lung recruitment maneuvers did not decrease postoperative pulmonary complications when compared to low PEEP (0-2 cm H2O) approach without recruitment breaths. However, effects of intraoperative PEEP on lung compliance remain poorly understood. We hypothesized that higher PEEP leads to a dominance of intratidal overdistension, whereas lower PEEP results in intratidal recruitment/derecruitment (R/D). To test our hypothesis, we used the volume-dependent elastance index %E2, a respiratory parameter that allows for noninvasive and radiation-free assessment of dominant overdistension and intratidal R/D. We compared the incidence of intratidal R/D, linear expansion, and overdistension by means of %E2 in a subset of the PROVHILO cohort. METHODS: In 36 patients from 2 participating centers of the PROVHILO trial, we calculated respiratory system elastance (E), resistance (R), and %E2, a surrogate parameter for intratidal overdistension (%E2 > 30%) and R/D (%E2 < 0%). To test the main hypothesis, we compared the incidence of intratidal overdistension (primary end point) and R/D in higher and lower PEEP groups, as measured by %E2. RESULTS: E was increased in the lower compared to higher PEEP group (18.6 [16…22] vs 13.4 [11.0…17.0] cm H2O·L; P < .01). %E2 was reduced in the lower PEEP group compared to higher PEEP (-15.4 [-28.0…6.5] vs 6.2 [-0.8…14.0] %; P < .05). Intratidal R/D was increased in the lower PEEP group (61% vs 22%; P = .037). The incidence of intratidal overdistension did not differ significantly between groups (6%). CONCLUSIONS: During mechanical ventilation with protective tidal volumes in patients undergoing open abdominal surgery, lung recruitment followed by PEEP of 12 cm H2O decreased the incidence of intratidal R/D and did not worsen overdistension, when compared to PEEP ≤2 cm H2O.

Peep titration based on the open lung approach during one lung ventilation in thoracic surgery: a physiological study.

BACKGROUND: During thoracic surgery in lateral decubitus, one lung ventilation (OLV) may impair respiratory mechanics and gas exchange. We tested a strategy based on an open lung approach (OLA) consisting in lung recruitment immediately followed by a decremental positive-end expiratory pressure (PEEP) titration to the best respiratory system compliance (CRS) and separately quantified the elastic properties of the lung and the chest wall. Our hypothesis was that this approach would improve gas exchange. Further, we were interested in documenting the impact of the OLA on partitioned respiratory system mechanics. METHODS: In thirteen patients undergoing upper left lobectomy we studied lung and chest wall mechanics, transpulmonary pressure (PL), respiratory system and transpulmonary driving pressure (ΔPRS and ΔPL), gas exchange and hemodynamics at two time-points (a) during OLV at zero end-expiratory pressure (OLVpre-OLA) and (b) after the application of the open-lung strategy (OLVpost-OLA). RESULTS: The external PEEP selected through the OLA was 6 ± 0.8 cmH2O. As compared to OLVpre-OLA, the PaO2/FiO2 ratio went from 205 ± 73 to 313 ± 86 (p = .05) and CL increased from 56 ± 18 ml/cmH2O to 71 ± 12 ml/cmH2O (p = .0013), without changes in CCW. Both ΔPRS and ΔPL decreased from 9.2 ± 0.4 cmH2O to 6.8 ± 0.6 cmH2O and from 8.1 ± 0.5 cmH2O to 5.7 ± 0.5 cmH2O, (p = .001 and p = .015 vs OLVpre-OLA), respectively. Hemodynamic parameters remained stable throughout the study period. CONCLUSIONS: In our patients, the OLA strategy performed during OLV improved oxygenation and increased CL and had no clinically significant hemodynamic effects. Although our study was not specifically designed to study ΔPRS and ΔPL, we observed a parallel reduction of both after the OLA. TRIAL REGISTRATION: TRN: ClinicalTrials.gov , NCT03435523 , retrospectively registered, Feb 14 2018.

Comparison Between Doppler-Echocardiography and Uncalibrated Pulse Contour Method for Cardiac Output Measurement: A Multicenter Observational Study.

OBJECTIVES: Echocardiography and pulse contour methods allow, respectively, noninvasive and less invasive cardiac output estimation. The aim of the present study was to compare Doppler echocardiography with the pulse contour method MostCare for cardiac output estimation in a large and nonselected critically ill population. DESIGN: A prospective multicenter observational comparison study. SETTING: The study was conducted in 15 European medicosurgical ICUs. PATIENTS: We assessed cardiac output in 400 patients in whom an echocardiographic evaluation was performed as a routine need or for cardiocirculatory assessment. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One echocardiographic cardiac output measurement was compared with the corresponding MostCare cardiac output value per patient, considering different ICU admission categories and clinical conditions. For statistical analysis, we used Bland-Altman and linear regression analyses. To assess heterogeneity in results of individual centers, Cochran Q, and the I statistics were applied. A total of 400 paired echocardiographic cardiac output and MostCare cardiac output measures were compared. MostCare cardiac output values ranged from 1.95 to 9.90 L/min, and echocardiographic cardiac output ranged from 1.82 to 9.75 L/min. A significant correlation was found between echocardiographic cardiac output and MostCare cardiac output (r = 0.85; p < 0.0001). Among the different ICUs, the mean bias between echocardiographic cardiac output and MostCare cardiac output ranged from -0.40 to 0.45 L/min, and the percentage error ranged from 13.2% to 47.2%. Overall, the mean bias was -0.03 L/min, with 95% limits of agreement of -1.54 to 1.47 L/min and a relative percentage error of 30.1%. The percentage error was 24% in the sepsis category, 26% in the trauma category, 30% in the surgical category, and 33% in the medical admission category. The final overall percentage error was 27.3% with a 95% CI of 22.2-32.4%. CONCLUSIONS: Our results suggest that MostCare could be an alternative to echocardiography to assess cardiac output in ICU patients with a large spectrum of clinical conditions.

Impact of prolonged assisted ventilation on diaphragmatic efficiency: NAVA versus PSV.

BACKGROUND: Prolonged controlled mechanical ventilation depresses diaphragmatic efficiency. Assisted modes of ventilation should improve it. We assessed the impact of pressure support ventilation versus neurally adjusted ventilator assist on diaphragmatic efficiency. METHOD: Patients previously ventilated with controlled mechanical ventilation for 72 hours or more were randomized to be ventilated for 48 hours with pressure support ventilation (n =12) or neurally adjusted ventilatory assist (n = 13). Neuro-ventilatory efficiency (tidal volume/diaphragmatic electrical activity) and neuro-mechanical efficiency (pressure generated against the occluded airways/diaphragmatic electrical activity) were measured during three spontaneous breathing trials (0, 24 and 48 hours). Breathing pattern, diaphragmatic electrical activity and pressure time product of the diaphragm were assessed every 4 hours. RESULTS: In patients randomized to neurally adjusted ventilator assist, neuro-ventilatory efficiency increased from 27 ± 19 ml/µV at baseline to 62 ± 30 ml/µV at 48 hours (p <0.0001) and neuro-mechanical efficiency increased from 1 ± 0.6 to 2.6 ± 1.1 cmH2O/µV (p = 0.033). In patients randomized to pressure support ventilation, these did not change. Electrical activity of the diaphragm, neural inspiratory time, pressure time product of the diaphragm and variability of the breathing pattern were significantly higher in patients ventilated with neurally adjusted ventilatory assist. The asynchrony index was 9.48 [6.38- 21.73] in patients ventilated with pressure support ventilation and 5.39 [3.78- 8.36] in patients ventilated with neurally adjusted ventilatory assist (p = 0.04). CONCLUSION: After prolonged controlled mechanical ventilation, neurally adjusted ventilator assist improves diaphragm efficiency whereas pressure support ventilation does not. TRIAL REGISTRATION: ClinicalTrials.gov study registration: NCT02473172, 06/11/2015.

Physiological Effects of the Open Lung Approach in Patients with Early, Mild, Diffuse Acute Respiratory Distress Syndrome: An Electrical Impedance Tomography Study.

BACKGROUND: To test the hypothesis that in early, mild, acute respiratory distress syndrome (ARDS) patients with diffuse loss of aeration, the application of the open lung approach (OLA) would improve homogeneity in lung aeration and lung mechanics, without affecting hemodynamics. METHODS: Patients were ventilated according to the ARDS Network protocol at baseline (pre-OLA). OLA consisted in a recruitment maneuver followed by a decremental positive end-expiratory pressure trial. Respiratory mechanics, gas exchange, electrical impedance tomography (EIT), cardiac index, and stroke volume variation were measured at baseline and 20 min after OLA implementation (post-OLA). Esophageal pressure was used for lung and chest wall elastance partitioning. The tomographic lung image obtained at the fifth intercostal space by EIT was divided in two ventral and two dorsal regions of interest (ROIventral and ROIDorsal). RESULTS: Fifteen consecutive patients were studied. The OLA increased arterial oxygen partial pressure/inspired oxygen fraction from 216 ± 13 to 311 ± 19 mmHg (P < 0.001) and decreased elastance of the respiratory system from 29.4 ± 3 cm H2O/l to 23.6 ± 1.7 cm H2O/l (P < 0.01). The driving pressure (airway opening plateau pressure - total positive end-expiratory pressure) decreased from 17.9 ± 1.5 cm H2O pre-OLA to 15.4 ± 2.1 post-OLA (P < 0.05). The tidal volume fraction reaching the dorsal ROIs increased, and consequently the ROIVentral/Dorsal impedance tidal variation decreased from 2.01 ± 0.36 to 1.19 ± 0.1 (P < 0.01). CONCLUSIONS: The OLA decreases the driving pressure and improves the oxygenation and lung mechanics in patients with early, mild, diffuse ARDS. EIT is useful to assess the impact of OLA on regional tidal volume distribution.

Cardiovascular magnetic resonance compatible physical model of the left ventricle for multi-modality characterization of wall motion and hemodynamics.

BACKGROUND: The development of clinically applicable fluid-structure interaction (FSI) models of the left heart is inherently challenging when using in vivo cardiovascular magnetic resonance (CMR) data for validation, due to the lack of a well-controlled system where detailed measurements of the ventricular wall motion and flow field are available a priori. The purpose of this study was to (a) develop a clinically relevant, CMR-compatible left heart physical model; and (b) compare the left ventricular (LV) volume reconstructions and hemodynamic data obtained using CMR to laboratory-based experimental modalities. METHODS: The LV was constructed from optically clear flexible silicone rubber. The geometry was based off a healthy patient's LV geometry during peak systole. The LV phantom was attached to a left heart simulator consisting of an aorta, atrium, and systemic resistance and compliance elements. Experiments were conducted for heart rate of 70 bpm. Wall motion measurements were obtained using high speed stereo-photogrammetry (SP) and cine-CMR, while flow field measurements were obtained using digital particle image velocimetry (DPIV) and phase-contrast magnetic resonance (PC-CMR). RESULTS: The model reproduced physiologically accurate hemodynamics (aortic pressure = 120/80 mmHg; cardiac output = 3.5 L/min). DPIV and PC-CMR results of the center plane flow within the ventricle matched, both qualitatively and quantitatively, with flow from the atrium into the LV having a velocity of about 1.15 m/s for both modalities. The normalized LV volume through the cardiac cycle computed from CMR data matched closely to that from SP. The mean difference between CMR and SP was 5.5 ± 3.7%. CONCLUSIONS: The model presented here can thus be used for the purposes of: (a) acquiring CMR data for validation of FSI simulations, (b) determining accuracy of cine-CMR reconstruction methods, and

Lung protection during non-invasive synchronized assist versus volume control in rabbits.

INTRODUCTION: Experimental work provides insight into potential lung protective strategies. The objective of this study was to evaluate markers of ventilator-induced lung injury after two different ventilation approaches: (1) a "conventional" lung-protective strategy (volume control (VC) with low tidal volume, positive end-expiratory pressure (PEEP) and paralysis), (2) a physiological approach with spontaneous breathing, permitting synchrony, variability and a liberated airway. For this, we used non-invasive Neurally Adjusted Ventilatory Assist (NIV-NAVA), with the hypothesis that liberation of upper airways and the ventilator's integration with lung protective reflexes would be equally lung protective. METHODS: In this controlled and randomized in vivo laboratory study, 25 adult White New Zealand rabbits were studied, including five non-ventilated control animals. The twenty animals with aspiration-induced lung injury were randomized to ventilation with either VC (6 mL/kg, PEEP 5 cm H2O, and paralysis) or NIV-NAVA for six hours (PEEP = zero because of leaks). Markers of lung function, lung injury, vital signs and ventilator parameters were assessed. RESULTS: At the end of six hours of ventilation (n = 20), there were no significant differences between VC and NIV-NAVA for vital signs, PaO2/FiO2 ratio, lung wet-to-dry ratio and broncho-alveolar Interleukin 8 (Il-8). Plasma IL-8 was higher in VC (P <0.05). Lung injury score was lower for NIV-NAVA (P = 0.03). Dynamic lung compliance recovered after six hours in NIV-NAVA but not in VC (P <0.05). During VC, peak pressures increased from 9.2 ± 2.4 cm H2O (hour 1) to 12.3 ± 12.3 cm H2O (hour 6) (P <0.05). During NIV-NAVA, the tracheal end-expiratory pressure was similar to the end-expiratory pressure during VC. Two animals regurgitated during NIV-NAVA, without clinical consequences, and survived the protocol. CONCLUSIONS: In experimental acute lung injury, NIV-NAVA is as lung-protective as VC 6 ml/kg with PEEP.

Machine-Learning-Accelerated Simulations for the Design of Airbag Constrained by Obstacles at Rest.

Predicting airbag deployment geometries is an important task for airbag and vehicle designers to meet safety standards based on biomechanical injury risk functions. This prediction is also an extraordinarily complex problem given the number of disciplines and their interactions. State-of-the-art airbag deployment geometry simulations (including time history) entail large, computationally expensive numerical methods such as finite element analysis (FEA) and computational fluid dynamics (CFD), among others. This complexity results in exceptionally large simulation times, making thorough exploration of the design space prohibitive. This paper proposes new parametric simulation models which drastically accelerate airbag deployment geometry predictions while maintaining the accuracy of the airbag deployment geometry at reasonable levels; these models, called herein machine learning (ML)-accelerated models, blend physical system modes with data-driven techniques to accomplish fast predictions within a design space defined by airbag and impactor parameters. These ML-accelerated models are evaluated with virtual test cases of increasing complexity: from airbag deployments against a locked deformable obstacle to airbag deployments against free rigid obstacles; the dimension of the tested design spaces is up to six variables. ML training times are documented for completeness; thus, airbag design explorers or optimization engineers can assess the full budget for ML-accelerated approaches including training. In these test cases, the ML-accelerated simulation models run three orders of magnitude faster than the high-fidelity multi-physics methods, while accuracies are kept within reasonable levels within the design space.

Awake Craniotomy in Conscious Sedation: The Role of A2 Agonists.

BACKGROUND: In Awake Craniotomy (AC), α2-agonists and remifentanil (clonidine and dexmedetomidine) are used in the preoperative phase and throughout the procedure to combine monitored anesthesia care and local anesthesia. The study aims were to specify the key role of α2-agonists administered and to evaluate complication presence/absence in anesthesiologic management. METHODS: 42 patients undergoing AC in 3 different centers in the south of Italy (Foggia, San Giovanni Rotondo, and Bari) were recruited. Our protocol involves analgo-sedation by administering Dexmedetomidine and Remifentanil in continuous intravenous infusion, allowing the patient to be sedated and in comfort but contactable and spontaneously breathing. During pre-surgery, the patient is premedicated with intramuscular clonidine (2 µg/kg). In the operating setting, Dexmedetomidine in infusion and Remifentanil in Target Controlled Infusion for effect are started. At the end of the surgical procedure, the infusion of drugs was suspended. RESULTS: There were no intraoperative side effects. The mean duration of interventions was 240 ± 62 min. The average quantity of Remifentanil and Dexmedetomidine infused during interventions were 4.2 ± 1.3 mg and 1.0 ± 0.3 mg, respectively. No significant side effects were described in the post-operative phase. A total of 86% of patients and 93% of surgeons were totally satisfied. CONCLUSIONS: Synergy between opioid drugs and α2 agonists plays a fundamental role in ensuring procedure success.

Successful Versus Failed Transition From Controlled Ventilation to Pressure Support Ventilation in COVID-19 Patients: A Retrospective Cohort Study.

OBJECTIVES: In patients with COVID-19 respiratory failure, controlled mechanical ventilation (CMV) is often necessary during the acute phases of the disease. Weaning from CMV to pressure support ventilation (PSV) is a key objective when the patient's respiratory functions improve. Limited evidence exists regarding the factors predicting a successful transition to PSV and its impact on patient outcomes. DESIGN: Retrospective observational cohort study. SETTING: Twenty-four Italian ICUs from February 2020 to May 2020. PATIENTS: Mechanically ventilated ICU patients with COVID-19-induced respiratory failure. INTERVENTION: The transition period from CMV to PSV was evaluated. We defined it as "failure of assisted breathing" if the patient returned to CMV within the first 72 hours. MEASUREMENTS AND MAIN RESULTS: Of 1260 ICU patients screened, 514 were included. Three hundred fifty-seven patients successfully made the transition to PSV, while 157 failed. Pao2/Fio2 ratio before the transition emerged as an independent predictor of a successful shift (odds ratio 1.00; 95% CI, 0.99-1.00; p = 0.003). Patients in the success group displayed a better trend in Pao2/Fio2, Paco2, plateau and peak pressure, and pH level. Subjects in the failure group exhibited higher ICU mortality (hazard ratio 2.08; 95% CI, 1.42-3.06; p < 0.001), an extended ICU length of stay (successful vs. failure 21 ± 14 vs. 27 ± 17 d; p < 0.001) and a longer duration of mechanical ventilation (19 ± 18 vs. 24 ± 17 d, p = 0.04). CONCLUSIONS: Our study emphasizes that the Pao2/Fio2 ratio was the sole independent factor associated with a failed transition from CMV to PSV. The unsuccessful transition was associated with worse outcomes.

Individualised, perioperative open-lung ventilation strategy during one-lung ventilation (iPROVE-OLV): a multicentre, randomised, controlled clinical trial.

BACKGROUND: It is uncertain whether individualisation of the perioperative open-lung approach (OLA) to ventilation reduces postoperative pulmonary complications in patients undergoing lung resection. We compared a perioperative individualised OLA (iOLA) ventilation strategy with standard lung-protective ventilation in patients undergoing thoracic surgery with one-lung ventilation. METHODS: This multicentre, randomised controlled trial enrolled patients scheduled for open or video-assisted thoracic surgery using one-lung ventilation in 25 participating hospitals in Spain, Italy, Turkey, Egypt, and Ecuador. Eligible adult patients (age ≥18 years) were randomly assigned to receive iOLA or standard lung-protective ventilation. Eligible patients (stratified by centre) were randomly assigned online by local principal investigators, with an allocation ratio of 1:1. Treatment with iOLA included an alveolar recruitment manoeuvre to 40 cm H2O of end-inspiratory pressure followed by individualised positive end-expiratory pressure (PEEP) titrated to best respiratory system compliance, and individualised postoperative respiratory support with high-flow oxygen therapy. Participants allocated to standard lung-protective ventilation received combined intraoperative 4 cm H2O of PEEP and postoperative conventional oxygen therapy. The primary outcome was a composite of severe postoperative pulmonary complications within the first 7 postoperative days, including atelectasis requiring bronchoscopy, severe respiratory failure, contralateral pneumothorax, early extubation failure (rescue with continuous positive airway pressure, non-invasive ventilation, invasive mechanical ventilation, or reintubation), acute respiratory distress syndrome, pulmonary infection, bronchopleural fistula, and pleural empyema. Due to trial setting, data obtained in the operating and postoperative rooms for routine monitoring were not blinded. At 24 h, data were acquired by an investigator blinded to group allocation. All analyses were performed on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT03182062, and is complete. FINDINGS: Between Sept 11, 2018, and June 14, 2022, we enrolled 1380 patients, of whom 1308 eligible patients (670 [434 male, 233 female, and three with missing data] assigned to iOLA and 638 [395 male, 237 female, and six with missing data] to standard lung-protective ventilation) were included in the final analysis. The proportion of patients with the composite outcome of severe postoperative pulmonary complications within the first 7 postoperative days was lower in the iOLA group compared with the standard lung-protective ventilation group (40 [6%] vs 97 [15%], relative risk 0·39 [95% CI 0·28 to 0·56]), with an absolute risk difference of -9·23 (95% CI -12·55 to -5·92). Recruitment manoeuvre-related adverse events were reported in five patients. INTERPRETATION: Among patients subjected to lung resection under one-lung ventilation, iOLA was associated with a reduced risk of severe postoperative pulmonary complications when compared with conventional lung-protective ventilation. FUNDING: Instituto de Salud Carlos III and the European Regional Development Funds.

Effects of recruitment maneuver and positive end-expiratory pressure on respiratory mechanics and transpulmonary pressure during laparoscopic surgery.

BACKGROUND: The authors tested the hypothesis that during laparoscopic surgery, Trendelenburg position and pneumoperitoneum may worsen chest wall elastance, concomitantly decreasing transpulmonary pressure, and that a protective ventilator strategy applied after pneumoperitoneum induction, by increasing transpulmonary pressure, would result in alveolar recruitment and improvement in respiratory mechanics and gas exchange. METHODS: In 29 consecutive patients, a recruiting maneuver followed by positive end-expiratory pressure 5 cm H(2)O maintained until the end of surgery was applied after pneumoperitoneum induction. Respiratory mechanics, gas exchange, blood pressure, and cardiac index were measured before (T(BSL)) and after pneumoperitoneum with zero positive end-expiratory pressure (T(preOLS)), after recruitment with positive end-expiratory pressure (T(postOLS)), and after peritoneum desufflation with positive end-expiratory pressure (T(end)). RESULTS: Esophageal pressure was used for partitioning respiratory mechanics between lung and chest wall (data are mean ± SD): on T(preOLS), chest wall elastance (E(cw)) and elastance of the lung (E(L)) increased (8.2 ± 0.9 vs. 6.2 ± 1.2 cm H(2)O/L, respectively, on T(BSL); P = 0.00016; and 11.69 ± 1.68 vs. 9.61 ± 1.52 cm H(2)O/L on T(BSL); P = 0.0007). On T(postOLS), both chest wall elastance and E(L) decreased (5.2 ± 1.2 and 8.62 ± 1.03 cm H(2)O/L, respectively; P = 0.00015 vs. T(preOLS)), and Pao(2)/inspiratory oxygen fraction improved (491 ± 107 vs. 425 ± 97 on T(preOLS); P = 0.008) remaining stable thereafter. Recruited volume (the difference in lung volume for the same static airway pressure) was 194 ± 80 ml. Pplat(RS) remained stable while inspiratory transpulmonary pressure increased (11.65 + 1.37 cm H(2)O vs. 9.21 + 2.03 on T(preOLS); P = 0.007). All respiratory mechanics parameters remained stable after abdominal desufflation. Hemodynamic parameters remained stable throughout the study. CONCLUSIONS: In patients submitted to laparoscopic surgery in Trendelenburg position, an open lung strategy applied after pneumoperitoneum induction increased transpulmonary pressure and led to alveolar recruitment and improvement of E(cw) and gas exchange.