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Background: Mechanical ventilation with variable tidal volumes (V-VCV) has the potential to improve lung function during general anesthesia. We tested the hypothesis that V-VCV compared to conventional volume-controlled ventilation (C-VCV) would improve intraoperative arterial oxygenation and respiratory system mechanics in patients undergoing thoracic surgery under one-lung ventilation (OLV)., Methods: Patients were randomized to V-VCV (n = 39) or C-VCV (n = 39). During OLV tidal volume of 5 mL/kg predicted body weight (PBW) was used. Both groups were ventilated with a positive end-expiratory pressure (PEEP) of 5 cm H 2 O, inspiration to expiration ratio (I:E) of 1:1 (during OLV) and 1:2 during two-lung ventilation, the respiratory rate (RR) titrated to arterial pH, inspiratory peak-pressure ≤ 40 cm H 2 O and an inspiratory oxygen fraction of 1.0., Results: Seventy-five out of 78 Patients completed the trial and were analyzed (dropouts were excluded). The partial pressure of arterial oxygen (PaO 2 ) 20 min after the start of OLV did not differ among groups (V-VCV: 25.8 ± 14.6 kPa vs C-VCV: 27.2 ± 15.3 kPa; mean difference [95% CI]: 1.3 [-8.2, 5.5], P = 0.700). Furthermore, intraoperative gas exchange, intraoperative adverse events, need for rescue maneuvers due to desaturation and hypercapnia, incidence of postoperative pulmonary and extra-pulmonary complications, and hospital free days at day 30 after surgery did not differ between groups., Conclusions: In thoracic surgery patients under OLV, V-VCV did not improve oxygenation or respiratory system mechanics compared to C-VCV. Ethical Committee: EK 420092019., Trial Registration: at the German Clinical Trials Register: DRKS00022202 (16.06.2020)., Competing Interests: Declaration of competing interest M.G.A. received consultation fees from Dräger, Ambu, GE Healthcare, and ZOLL. M.G.A. and T.K. were granted a patent on variable pressure support ventilation and might indirectly benefit from this publication. All other authors have disclosed that they do not have any conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: During one-lung ventilation (OLV), positive end-expiratory pressure (PEEP) can improve lung aeration but might overdistend lung units and increase intrapulmonary shunt. The authors hypothesized that higher PEEP shifts pulmonary perfusion from the ventilated to the nonventilated lung, resulting in a U-shaped relationship with intrapulmonary shunt during OLV., Methods: In nine anesthetized female pigs, a thoracotomy was performed and intravenous lipopolysaccharide infused to mimic the inflammatory response of thoracic surgery. Animals underwent OLV in supine position with PEEP of 0 cm H2O, 5 cm H2O, titrated to best respiratory system compliance, and 15 cm H2O (PEEP0, PEEP5, PEEPtitr, and PEEP15, respectively, 45 min each, Latin square sequence). Respiratory, hemodynamic, and gas exchange variables were measured. The distributions of perfusion and ventilation were determined by IV fluorescent microspheres and computed tomography, respectively., Results: Compared to two-lung ventilation, the driving pressure increased with OLV, irrespective of the PEEP level. During OLV, cardiac output was lower at PEEP15 (5.5 ± 1.5 l/min) than PEEP0 (7.6 ± 3 l/min) and PEEP5 (7.4 ± 2.9 l/min; P = 0.004), while the intrapulmonary shunt was highest at PEEP0 (PEEP0: 48.1% ± 14.4%; PEEP5: 42.4% ± 14.8%; PEEPtitr: 37.8% ± 11.0%; PEEP15: 39.0% ± 10.7%; P = 0.027). The relative perfusion of the ventilated lung did not differ among PEEP levels (PEEP0: 65.0% ± 10.6%; PEEP5: 68.7% ± 8.7%; PEEPtitr: 68.2% ± 10.5%; PEEP15: 58.4% ± 12.8%; P = 0.096), but the centers of relative perfusion and ventilation in the ventilated lung shifted from ventral to dorsal and from cranial to caudal zones with increasing PEEP., Conclusions: In this experimental model of thoracic surgery, higher PEEP during OLV did not shift the perfusion from the ventilated to the nonventilated lung, thus not increasing intrapulmonary shunt., (Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.)

A promising therapeutic option for the treatment of critical-size mandibular defects is the implantation of biodegradable, porous structures that are produced patient-specifically by using additive manufacturing techniques. In this work, degradable poly(DL-lactide) polymer (PDLLA) was blended with different mineral phases with the aim of buffering its acidic degradation products, which can cause inflammation and stimulate bone regeneration. Microparticles of CaCO 3 , SrCO 3 , tricalcium phosphates (α-TCP, β-TCP), or strontium-modified hydroxyapatite (SrHAp) were mixed with the polymer powder following processing the blends into scaffolds with the Arburg Plastic Freeforming 3D-printing method. An in vitro degradation study over 24 weeks revealed a buffer effect for all mineral phases, with the buffering capacity of CaCO 3 and SrCO 3 being the highest. Analysis of conductivity, swelling, microstructure, viscosity, and glass transition temperature evidenced that the mineral phases influence the degradation behavior of the scaffolds. Cytocompatibility of all polymer blends was proven in cell experiments with SaOS-2 cells. Patient-specific implants consisting of PDLLA + CaCO 3 , which were tested in a pilot in vivo study in a segmental mandibular defect in minipigs, exhibited strong swelling. Based on these results, an in vitro swelling prediction model was developed that simulates the conditions of anisotropic swelling after implantation.

Study Objective: We aimed to characterize intra-operative mechanical ventilation with low or high positive end-expiratory pressure (PEEP) and recruitment manoeuvres (RM) regarding intra-tidal recruitment/derecruitment and overdistension using non-linear respiratory mechanics, and mechanical power in obese surgical patients enrolled in the PROBESE trial., Design: Prospective, two-centre substudy of the international, multicentre, two-arm, randomized-controlled PROBESE trial., Setting: Operating rooms of two European University Hospitals., Patients: Forty-eight adult obese patients undergoing abdominal surgery., Interventions: Intra-operative protective ventilation with either PEEP of 12 cmH 2 O and repeated RM (HighPEEP+RM) or 4 cmH 2 O without RM (LowPEEP)., Measurements: The index of intra-tidal recruitment/de-recruitment and overdistension (%E 2 ) as well as airway pressure, tidal volume (V T ), respiratory rate (RR), resistance, elastance, and mechanical power (MP) were calculated from respiratory signals recorded after anesthesia induction, 1 h thereafter, and end of surgery (EOS)., Main Results: Twenty-four patients were analyzed in each group. PEEP was higher (mean ± SD, 11.7 ± 0.4 vs. 3.7 ± 0.6 cmH 2 O, P < 0.001) and driving pressure lower (12.8 ± 3.5 vs. 21.7 ± 6.8 cmH 2 O, P < 0.001) during HighPEEP+RM than LowPEEP, while V T and RR did not differ significantly (7.3 ± 0.6 vs. 7.4 ± 0.8 ml∙kg -1 , P = 0.835; and 14.6 ± 2.5 vs. 15.7 ± 2.0 min -1 , P = 0.150, respectively). %E 2 was higher in HighPEEP+RM than in LowPEEP following induction (-3.1 ± 7.2 vs. -12.4 ± 10.2%; P < 0.001) and subsequent timepoints. Total resistance and elastance (13.3 ± 3.8 vs. 17.7 ± 6.8 cmH 2 O∙l∙s -2 , P = 0.009; and 15.7 ± 5.5 vs. 28.5 ± 8.4 cmH 2 O∙l, P < 0.001, respectively) were lower during HighPEEP+RM than LowPEEP. Additionally, MP was lower in HighPEEP+RM than LowPEEP group (5.0 ± 2.2 vs. 10.4 ± 4.7 J∙min -1 , P < 0.001)., Conclusions: In this sub-cohort of PROBESE, intra-operative ventilation with high PEEP and RM reduced intra-tidal recruitment/de-recruitment as well as driving pressure, elastance, resistance, and mechanical power, as compared with low PEEP., Trial Registration: The PROBESE study was registered at www., Clinicaltrials: gov, identifier: NCT02148692 (submission for registration on May 23, 2014)., Competing Interests: Declaration of Competing Interest MGA received consultation fees from Ambu (Ballerup, Denmark), Dräger Medical (Lübeck, Germany), ZOLL (Minneapolis, MN, USA), Lungpacer (Vancouver, B.C., Canada) and Merck (London, UK). The other authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Mechanical ventilation is a life-saving therapy in several clinical situations, promoting gas exchange and providing rest to the respiratory muscles. However, mechanical ventilation may cause hemodynamic instability and pulmonary structural damage, which is known as ventilator-induced lung injury (VILI). The four main injury mechanisms associated with VILI are as follows: barotrauma/volutrauma caused by overstretching the lung tissues; atelectrauma, caused by repeated opening and closing of the alveoli resulting in shear stress; and biotrauma, the resulting biological response to tissue damage, which leads to lung and multi-organ failure. This narrative review elucidates the mechanisms underlying the pathogenesis, progression, and resolution of VILI and discusses the strategies that can mitigate VILI. Different static variables (peak, plateau, and driving pressures, positive end-expiratory pressure, and tidal volume) and dynamic variables (respiratory rate, airflow amplitude, and inspiratory time fraction) can contribute to VILI. Moreover, the potential for lung injury depends on tissue vulnerability, mechanical power (energy applied per unit of time), and the duration of that exposure. According to the current evidence based on models of acute respiratory distress syndrome and VILI, the following strategies are proposed to provide lung protection: keep the lungs partially collapsed (SaO 2  > 88%), avoid opening and closing of collapsed alveoli, and gently ventilate aerated regions while keeping collapsed and consolidated areas at rest. Additional mechanisms, such as subject-ventilator asynchrony, cumulative power, and intensity, as well as the damaging threshold (stress-strain level at which tidal damage is initiated), are under experimental investigation and may enhance the understanding of VILI., (© 2023. The Author(s).)

Background: Mechanical ventilation (MV) is a life supporting therapy but may also cause lung damage. This phenomenon is known as ventilator-induced lung injury (VILI). A potential pathomechanisms of ventilator-induced lung injury may be the stretch-induced production and release of cytokines and pro-inflammatory molecules from the alveolar epithelium. Yes-associated protein (YAP) might be regulated by mechanical forces and involved in the inflammation cascade. However, its role in stretch-induced damage of alveolar cells remains poorly understood. In this study, we explored the role of YAP in the response of alveolar epithelial type II cells (AEC II) to elevated cyclic stretch in vitro . We hypothesize that Yes-associated protein activates its downstream targets and regulates the interleukin-6 (IL-6) expression in response to 30% cyclic stretch in AEC II. Methods: The rat lung L2 cell line was exposed to 30% cyclic equibiaxial stretch for 1 or 4 h. Non-stretched conditions served as controls. The cytoskeleton remodeling and cell junction integrity were evaluated by F-actin and Pan-cadherin immunofluorescence, respectively. The gene expression and protein levels of IL-6, Yes-associated protein, Cysteine-rich angiogenic inducer 61 (Cyr61/CCN1), and connective tissue growth factor (CTGF/CCN2) were studied by real-time polymerase chain reaction (RT-qPCR) and Western blot, respectively. Verteporfin (VP) was used to inhibit Yes-associated protein activation. The effects of 30% cyclic stretch were assessed by two-way ANOVA. Statistical significance as accepted at p < 0.05. Results: Cyclic stretch of 30% induced YAP nuclear accumulation, activated the transcription of Yes-associated protein downstream targets Cyr61/CCN1 and CTGF/CCN2 and elevated IL-6 expression in AEC II after 1 hour, compared to static control. VP (2 µM) inhibited Yes-associated protein activation in response to 30% cyclic stretch and reduced IL-6 protein levels. Conclusion: In rat lung L2 AEC II, 30% cyclic stretch activated YAP, and its downstream targets Cyr61/CCN1 and CTGF/CCN2 and proinflammatory IL-6 expression. Target activation was blocked by a Yes-associated protein inhibitor. This novel YAP-dependent pathway could be involved in stretch-induced damage of alveolar cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ran, Müller, Brunssen, Huhle, Scharffenberg, Schnabel, Koch, Gama de Abreu, Morawietz, Ferreira and Wittenstein.)

Background . Global and regional transpulmonary pressure (P L ) during one-lung ventilation (OLV) is poorly characterized. We hypothesized that global and regional P L and driving P L (ΔP L ) increase during protective low tidal volume OLV compared to two-lung ventilation (TLV), and vary with body position. Methods . In sixteen anesthetized juvenile pigs, intra-pleural pressure sensors were placed in ventral, dorsal, and caudal zones of the left hemithorax by video-assisted thoracoscopy. A right thoracotomy was performed and lipopolysaccharide administered intravenously to mimic the inflammatory response due to thoracic surgery. Animals were ventilated in a volume-controlled mode with a tidal volume (V T ) of 6 mL kg -1 during TLV and of 5 mL kg -1 during OLV and a positive end-expiratory pressure (PEEP) of 5 cmH 2 O. Global and local transpulmonary pressures were calculated. Lung instability was defined as end-expiratory P L <2.9 cmH 2 O according to previous investigations. Variables were acquired during TLV (TLVsupine), left lung ventilation in supine (OLVsupine), semilateral (OLVsemilateral), lateral (OLVlateral) and prone (OLVprone) positions randomized according to Latin-square sequence. Effects of position were tested using repeated measures ANOVA. Results . End-expiratory P L and ΔP L were higher during OLVsupine than TLVsupine. During OLV, regional end-inspiratory P L and ΔP L did not differ significantly among body positions. Yet, end-expiratory P L was lower in semilateral (ventral: 4.8 ± 2.9 cmH 2 O; caudal: 3.1 ± 2.6 cmH 2 O) and lateral (ventral: 1.9 ± 3.3 cmH 2 O; caudal: 2.7 ± 1.7 cmH 2 O) compared to supine (ventral: 4.8 ± 2.9 cmH 2 O; caudal: 3.1 ± 2.6 cmH 2 O) and prone position (ventral: 1.7 ± 2.5 cmH 2 O; caudal: 3.3 ± 1.6 cmH 2 O), mainly in ventral ( p ≤ 0.001) and caudal ( p = 0.007) regions. Lung instability was detected more often in semilateral (26 out of 48 measurements; p = 0.012) and lateral (29 out of 48 measurements, p < 0.001) as compared to supine position (15 out of 48 measurements), and more often in lateral as compared to prone position (19 out of 48 measurements, p = 0.027). Conclusion . Compared to TLV, OLV increased lung stress. Body position did not affect stress of the ventilated lung during OLV, but lung stability was lowest in semilateral and lateral decubitus position., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wittenstein, Scharffenberg, Yang, Bluth, Kiss, Schultz, Rocco, Pelosi, Gama de Abreu and Huhle.)

Background: Variable ventilation recruits alveoli in atelectatic lungs, but it is unknown how it compares with conventional recruitment manoeuvres., Objectives: To test whether mechanical ventilation with variable tidal volumes and conventional recruitment manoeuvres have comparable effects on lung function., Design: Randomised crossover study., Setting: University hospital research facility., Animals: Eleven juvenile mechanically ventilated pigs with atelectasis created by saline lung lavage., Interventions: Lung recruitment was performed using two strategies, both with an individualised optimal positive-end expiratory pressure (PEEP) associated with the best respiratory system elastance during a decremental PEEP trial: conventional recruitment manoeuvres (stepwise increase of PEEP) in pressure-controlled mode) followed by 50 min of volume-controlled ventilation (VCV) with constant tidal volume, and variable ventilation, consisting of 50 min of VCV with random variation in tidal volume., Main Outcome Measures: Before and 50 min after each recruitment manoeuvre strategy, lung aeration was assessed by computed tomography, and relative lung perfusion and ventilation (0% = dorsal, 100% = ventral) were determined by electrical impedance tomography., Results: After 50 min, variable ventilation and stepwise recruitment manoeuvres decreased the relative mass of poorly and nonaerated lung tissue (percent lung mass: 35.3 ± 6.2 versus 34.2 ± 6.6, P  = 0.303); reduced poorly aerated lung mass compared with baseline (-3.5 ± 4.0%, P  = 0.016, and -5.2 ± 2.8%, P  < 0.001, respectively), and reduced nonaerated lung mass compared with baseline (-7.2 ± 2.5%, P  < 0.001; and -4.7 ± 2.8%, P  < 0.001 respectively), while the distribution of relative perfusion was barely affected (variable ventilation: -0.8 ± 1.1%, P  = 0.044; stepwise recruitment manoeuvres: -0.4 ± 0.9%, P  = 0.167). Compared with baseline, variable ventilation and stepwise recruitment manoeuvres increased Pa O 2 (172 ± 85mmHg, P  = 0.001; and 213 ± 73 mmHg, P  < 0.001, respectively), reduced Pa CO 2 (-9.6 ± 8.1 mmHg, P  = 0.003; and -6.7 ± 4.6 mmHg, P  < 0.001, respectively), and decreased elastance (-11.4 ± 6.3 cmH 2 O, P  < 0.001; and -14.1 ± 3.3 cmH 2 O, P  < 0.001, respectively). Mean arterial pressure decreased during stepwise recruitment manoeuvres (-24 ± 8 mmHg, P  = 0.006), but not variable ventilation., Conclusion: In this model of lung atelectasis, variable ventilation and stepwise recruitment manoeuvres effectively recruited lungs, but only variable ventilation did not adversely affect haemodynamics., Trial Registration: This study was registered and approved by Landesdirektion Dresden, Germany (DD24-5131/354/64)., (Copyright © 2023 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Background: Patient-ventilator asynchrony during mechanical ventilation may exacerbate lung and diaphragm injury in spontaneously breathing subjects. We investigated whether subject-ventilator asynchrony increases lung or diaphragmatic injury in a porcine model of acute respiratory distress syndrome (ARDS)., Methods: ARDS was induced in adult female pigs by lung lavage and injurious ventilation before mechanical ventilation by pressure assist-control for 12 h. Mechanically ventilated pigs were randomised to breathe spontaneously with or without induced subject-ventilator asynchrony or neuromuscular block (n=7 per group). Subject-ventilator asynchrony was produced by ineffective, auto-, or double-triggering of spontaneous breaths. The primary outcome was mean alveolar septal thickness (where thickening of the alveolar wall indicates worse lung injury). Secondary outcomes included distribution of ventilation (electrical impedance tomography), lung morphometric analysis, inflammatory biomarkers (gene expression), lung wet-to-dry weight ratio, and diaphragmatic muscle fibre thickness., Results: Subject-ventilator asynchrony (median [interquartile range] 28.8% [10.4] asynchronous breaths of total breaths; n=7) did not increase mean alveolar septal thickness compared with synchronous spontaneous breathing (asynchronous breaths 1.0% [1.6] of total breaths; n=7). There was no difference in mean alveolar septal thickness throughout upper and lower lung lobes between pigs randomised to subject-ventilator asynchrony vs synchronous spontaneous breathing (87.3-92.2 μm after subject-ventilator asynchrony, compared with 84.1-95.0 μm in synchronised spontaneous breathing;). There were also no differences between groups in wet-to-dry weight ratio, diaphragmatic muscle fibre thickness, atelectasis, lung aeration, or mRNA expression levels for inflammatory cytokines pivotal in ARDS pathogenesis., Conclusions: Subject-ventilator asynchrony during spontaneous breathing did not exacerbate lung injury and dysfunction in experimental porcine ARDS., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Oxygen is one of the most commonly used drugs by anesthesiologists. The World Health Organization (WHO) gave recommendations regarding perioperative oxygen administration, but the practice of oxygen use in anesthesia, critical emergency, and intensive care medicine remains unclear., Methods: We conducted an online survey among members of the European Society of Anaesthesiology and Intensive Care (ESAIC). The questionnaire consisted of 46 queries appraising the perioperative period, emergency medicine and in the intensive care, knowledge about current recommendations by the WHO, oxygen toxicity, and devices for supplemental oxygen therapy., Results: Seven hundred ninety-eight ESAIC members (2.1% of all ESAIC members) completed the survey. Most respondents were board-certified and worked in hospitals with > 500 beds. The majority affirmed that they do not use specific protocols for oxygen administration. WHO recommendations are unknown to 42% of respondents, known but not followed by 14%, and known and followed by 24% of them. Respondents prefer inspiratory oxygen fraction (FiO 2 ) ≥80% during induction and emergence from anesthesia, but intraoperatively < 60% for maintenance, and higher FiO 2 in patients with diseased than non-diseased lungs. Postoperative oxygen therapy is prescribed more commonly according to peripheral oxygen saturation (SpO 2 ), but shortage of devices still limits monitoring. When monitoring is used, SpO 2  ≤ 95% is often targeted. In critical emergency medicine, oxygen is used frequently in patients aged ≥80 years, or presenting with respiratory distress, chronic obstructive pulmonary disease, myocardial infarction, and stroke. In the intensive care unit, oxygen is mostly targeted at 96%, especially in patients with pulmonary diseases., Conclusions: The current practice of perioperative oxygen therapy among respondents does not follow WHO recommendations or current evidence, and access to postoperative monitoring devices impairs the individualization of oxygen therapy. Further research and additional teaching about use of oxygen are necessary., (© 2022. The Author(s).)

Background: Atelectasis is one of the most common respiratory complications in patients undergoing open abdominal surgery. Peripheral oxygen saturation (SpO 2 ) and forced vital capacity (FVC) are bedside indicators of postoperative respiratory dysfunction. The aim of this study was to describe the changes in lung aeration, using quantitative analysis of magnetic resonance imaging (MRI) and the diagnostic accuracy of SpO 2 and FVC to detect postoperative atelectasis., Methods: Post-hoc analysis of a randomized trial conducted at a University Hospital in Dresden, Germany. Patients undergoing pre- and postoperative lung MRI were included. MRI signal intensity was analyzed quantitatively to define poorly and nonaerated lung compartments. Postoperative atelectasis was defined as nonaerated lung volume above 2% of the total lung volume in the respective MRI investigation., Results: This study included 45 patients, 27 with and 18 patients without postoperative atelectasis. Patients with atelectasis had higher body mass index (p = .024), had more preoperative poorly aerated lung volume (p = .049), a lower preoperative SpO 2 (p = .009), and a lower preoperative FVC (p = .029). The amount of atelectasis correlated with preoperative SpO 2 (Spearman's ρ = -.51, p < .001) and postoperative SpO 2 (ρ = -.60, p < .001), and with preoperative FVC (ρ = -.29, p = .047) and postoperative FVC (ρ = -.40, p = .006). A postoperative SpO 2  ≤ 94% had 74% sensitivity and 78% specificity to detect atelectasis, while postoperative FVC ≤ 50% had 56% sensitivity and 100% specificity to detect atelectasis., Conclusion: SpO 2 and FVC correlated with the amount of postoperative non-aerated lung volume, showing acceptable diagnostic accuracy in bedside detection of postoperative atelectasis., (© 2022 Acta Anaesthesiologica Scandinavica Foundation.)

Rationale: Diaphragm dysfunction is frequently observed in critically ill patients with difficult weaning from mechanical ventilation. Objectives: To evaluate the effects of temporary transvenous diaphragm neurostimulation on weaning outcome and maximal inspiratory pressure. Methods: Multicenter, open-label, randomized, controlled study. Patients aged ⩾18 years on invasive mechanical ventilation for ⩾4 days and having failed at least two weaning attempts received temporary transvenous diaphragm neurostimulation using a multielectrode stimulating central venous catheter (bilateral phrenic stimulation) and standard of care (treatment) ( n  = 57) or standard of care (control) ( n  = 55). In seven patients, the catheter could not be inserted, and in seven others, pacing therapy could not be delivered; consequently, data were available for 43 patients. The primary outcome was the proportion of patients successfully weaned. Other endpoints were mechanical ventilation duration, 30-day survival, maximal inspiratory pressure, diaphragm-thickening fraction, adverse events, and stimulation-related pain. Measurements and Main Results: The incidences of successful weaning were 82% (treatment) and 74% (control) (absolute difference [95% confidence interval (CI)], 7% [-10 to 25]), P  = 0.59. Mechanical ventilation duration (mean ± SD) was 12.7 ± 9.9 days and 14.1 ± 10.8 days, respectively, P  = 0.50; maximal inspiratory pressure increased by 16.6 cm H 2 O and 4.8 cm H 2 O, respectively (difference [95% CI], 11.8 [5 to 19]), P  = 0.001; and right hemidiaphragm thickening fraction during unassisted spontaneous breathing was +17% and -14%, respectively, P  = 0.006, without correlation with changes in maximal inspiratory pressure. Serious adverse event frequency was similar in both groups. Median stimulation-related pain in the treatment group was 0 (no pain). Conclusions: Temporary transvenous diaphragm neurostimulation did not increase the proportion of successful weaning from mechanical ventilation. It was associated with a significant increase in maximal inspiratory pressure, suggesting reversal of the course of diaphragm dysfunction. Clinical trial registered with www.clinicaltrials.gov (NCT03096639) and the European Database on Medical Devices (CIV-17-06-020004).

Background: Mechanical ventilation (MV) may initiate or worsen lung injury, so-called ventilator-induced lung injury (VILI). Although different mechanisms of VILI have been identified, research mainly focused on single ventilator parameters. The mechanical power (MP) summarizes the potentially damaging effects of different parameters in one single variable and has been shown to be associated with lung damage. However, to date, the association of MP with pulmonary neutrophilic inflammation, as assessed by positron-emission tomography (PET), has not been prospectively investigated in a model of clinically relevant ventilation settings yet. We hypothesized that the degree of neutrophilic inflammation correlates with MP. Methods: Eight female juvenile pigs were anesthetized and mechanically ventilated. Lung injury was induced by repetitive lung lavages followed by initial PET and computed tomography (CT) scans. Animals were then ventilated according to the acute respiratory distress syndrome (ARDS) network recommendations, using the lowest combinations of positive end-expiratory pressure and inspiratory oxygen fraction that allowed adequate oxygenation. Ventilator settings were checked and adjusted hourly. Physiological measurements were conducted every 6 h. Lung imaging was repeated 24 h after first PET/CT before animals were killed. Pulmonary neutrophilic inflammation was assessed by normalized uptake rate of 2-deoxy-2-[ 18 F]fluoro-D-glucose (K iS ), and its difference between the two PET/CT was calculated (ΔK iS ). Lung aeration was assessed by lung CT scan. MP was calculated from the recorded pressure-volume curve. Statistics included the Wilcoxon tests and non-parametric Spearman correlation. Results: Normalized 18 F-FDG uptake rate increased significantly from first to second PET/CT ( p = 0.012). ΔK iS significantly correlated with median MP (ρ = 0.738, p = 0.037) and its elastic and resistive components, but neither with median peak, plateau, end-expiratory, driving, and transpulmonary driving pressures, nor respiratory rate (RR), elastance, or resistance. Lung mass and volume significantly decreased, whereas relative mass of hyper-aerated lung compartment increased after 24 h ( p = 0.012, p = 0.036, and p = 0.025, respectively). Resistance and PaCO 2 were significantly higher ( p = 0.012 and p = 0.017, respectively), whereas RR, end-expiratory pressure, and MP were lower at 18 h compared to start of intervention. Conclusions: In this model of experimental acute lung injury in pigs, pulmonary neutrophilic inflammation evaluated by PET/CT increased after 24 h of MV, and correlated with MP., Competing Interests: MG received consultation fees from Dräger, Ambu, GE Healthcare, and ZOLL. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Scharffenberg, Wittenstein, Ran, Zhang, Braune, Theilen, Maiello, Benzi, Bluth, Kiss, Pelosi, Rocco, Schultz, Kotzerke, Gama de Abreu and Huhle.)

High-flow nasal cannula oxygen therapy (HFNCOT) system consists of an air/oxygen supply system capable of delivering up to 100% humidified and heated oxygen at a flow rate of up to 80 L/min. The system includes a blender, active humidifier, single heated tube, and nasal cannula. HFNCOT has many physiological advantages compared with other standard oxygen therapies, such as anatomical dead space washout, more constant fraction of inspired oxygen, positive end-expiratory (PEEP) effect, supplement of adequate humidification and maintenance of muco-ciliary function. HFNCOT is mostly used for hypoxemic acute respiratory failure, although it also has other indications. HFNCOT is a common choice of physicians as its technology makes it more silent and comfortable. Though HFNCOT is used in many clinical settings, there is a lack of publications addressing devices and initial settings. We present a review on HFNCOT, with focus on device and application methodology.

Background: The incidence of hypoxemia during one-lung ventilation (OLV) is as high as 10%. It is also partially determined by the distribution of perfusion. During thoracic surgery, different body positions are used, such as the supine, semilateral, lateral, and prone positions, with such positions potentially influencing the distribution of perfusion. Furthermore, hypovolemia can impair hypoxic vasoconstriction. However, the effects of body position and hypovolemia on the distribution of perfusion remain poorly defined. We hypothesized that, during OLV, the relative perfusion of the ventilated lung is higher in the lateral decubitus position and that hypovolemia impairs the redistribution of pulmonary blood flow. Methods: Sixteen juvenile pigs were anesthetized, mechanically ventilated, submitted to a right-sided thoracotomy, and randomly assigned to one of two groups: (1) intravascular normovolemia or (2) intravascular hypovolemia, as achieved by drawing ~25% of the estimated blood volume ( n = 8/group). Furthermore, to mimic thoracic surgery inflammatory conditions, Escherichia coli lipopolysaccharide was continuously infused at 0.5 μg kg -1 h -1 . Under left-sided OLV conditions, the animals were further randomized to one of the four sequences of supine, left semilateral, left lateral, and prone positioning. Measurements of pulmonary perfusion distribution with fluorescence-marked microspheres, ventilation distribution by electrical impedance tomography, and gas exchange were then performed during two-lung ventilation in a supine position and after 30 min in each position and intravascular volume status during OLV. Results: During one-lung ventilation, the relative perfusion of the ventilated lung was higher in the lateral than the supine position. The relative perfusion of the non-ventilated lung was lower in the lateral than the supine and prone positions and in semilateral compared with the prone position. During OLV, the highest arterial partial pressure of oxygen/inspiratory fraction of oxygen (PaO 2 / F I O 2 ) was achieved in the lateral position as compared with all the other positions. The distribution of perfusion, ventilation, and oxygenation did not differ significantly between normovolemia and hypovolemia. Conclusions: During one-lung ventilation in endotoxemic pigs, the relative perfusion of the ventilated lung and oxygenation were higher in the lateral than in the supine position and not impaired by hypovolemia., Competing Interests: MG received consultation fees from Dräger, Ambu, GE Healthcare, and ZOLL. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wittenstein, Scharffenberg, Ran, Zhang, Keller, Tauer, Theilen, Chai, Ferreira, Müller, Bluth, Kiss, Schultz, Rocco, Pelosi, Gama de Abreu and Huhle.)

Background: Lung recruitment manoeuvres and positive end-expiratory pressure (PEEP) can improve lung function during general anaesthesia. Different recruitment manoeuvre strategies have been described in large international trials: in the protective ventilation using high vs. low PEEP (PROVHILO) strategy, tidal volume (VT) was increased during volume-controlled ventilation; in the individualised peri-operative open-lung approach vs. standard protective ventilation in abdominal surgery (iPROVE) strategy, PEEP was increased during pressure-controlled ventilation., Objectives: To compare the effects of the PROVHILO strategy and the iPROVE strategy on respiratory and haemodynamic variables., Design: Randomised crossover study., Setting: University hospital research facility., Animals: A total of 20 juvenile anaesthetised pigs., Interventions: Animals were assigned randomly to one of two sequences: PROVHILO strategy followed by iPROVE strategy or vice-versa (n = 10/sequence). In the PROVHILO strategy, VT was increased stepwise by 4 ml kg-1 at a fixed PEEP of 12 cmH2O until a plateau pressure of 30 to 35 cmH2O was reached. In the iPROVE strategy, at fixed driving pressure of 20 cmH2O, PEEP was increased up to 20 cmH2O followed by PEEP titration according to the lowest elastance of the respiratory system (ERS)., Main Outcome Measures: We assessed regional transpulmonary pressure (Ptrans), respiratory system mechanics, gas exchange and haemodynamics, as well as the centre of ventilation (CoV) by electrical impedance tomography., Results: During recruitment manoeuvres with the PROVHILO strategy compared with the iPROV strategy, dorsal Ptrans was lower at end-inspiration (16.3 ± 2.7 vs. 18.6 ± 3.1 cmH2O, P = 0.001) and end-expiration (4.8 ± 2.6 vs. 8.8 ± 3.4 cmH2O, P  < 0.001), and mean arterial pressure (MAP) was higher (77 ± 11 vs. 60 ± 14 mmHg, P < 0.001). At 1 and 15 min after recruitment manoeuvres, ERS was higher in the PROVHILO strategy than the iPROVE strategy (24.6 ± 3.9 vs. 21.5 ± 3.4 and 26.7 ± 4.3 vs. 24.0 ± 3.8 cmH2O l-1; P  < 0.001, respectively). At 1 min, PaO2 was lower in PROVHILO compared with iPROVE strategy (57.1 ± 6.1 vs. 59.3 ± 5.1 kPa, P = 0.013), but at 15 min, values did not differ. CoV did not differ between strategies., Conclusion: In anaesthetised pigs, the iPROVE strategy compared with the PROVHILO strategy increased dorsal Ptrans at the cost of lower MAP during recruitment manoeuvres, and decreased ERS thereafter, without consistent improvement of oxygenation or shift of the CoV., Trial Registration: This study was registered and approved by the Landesdirektion Dresden, Germany (DD24-5131/338/28)., (Copyright © 2021 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Background: Variable assisted mechanical ventilation has been shown to improve lung function and reduce lung injury. However, differences between extrinsic and intrinsic variability are unknown., Objective: To investigate the effects of neurally adjusted ventilatory assist (NAVA, intrinsic variability), variable pressure support ventilation (Noisy PSV, extrinsic variability) and conventional pressure-controlled ventilation (PCV) on lung and diaphragmatic function and damage in experimental acute respiratory distress syndrome (ARDS)., Design: Randomised controlled animal study., Setting: University Hospital Research Facility., Subjects: A total of 24 juvenile female pigs., Interventions: ARDS was induced by repetitive lung lavage and injurious ventilation. Animals were randomly assigned to 24 h of either: 1) NAVA, 2) Noisy PSV or 3) PCV (n=8 per group). Mechanical ventilation settings followed the ARDS Network recommendations., Measurements: The primary outcome was histological lung damage. Secondary outcomes were respiratory variables and patterns, subject-ventilator asynchrony (SVA), pulmonary and diaphragmatic biomarkers, as well as diaphragmatic muscle atrophy and myosin isotypes., Results: Global alveolar damage did not differ between groups, but NAVA resulted in less interstitial oedema in dorsal lung regions than Noisy PSV. Gas exchange and SVA incidence did not differ between groups. Compared with Noisy PSV, NAVA generated higher coefficients of variation of tidal volume and respiratory rate. During NAVA, only 40.4% of breaths were triggered by the electrical diaphragm signal. The IL-8 concentration in lung tissue was lower after NAVA compared with PCV and Noisy PSV, whereas Noisy PSV yielded lower type III procollagen mRNA expression than NAVA and PCV. Diaphragmatic muscle fibre diameters were smaller after PCV compared with assisted modes, whereas expression of myosin isotypes did not differ between groups., Conclusion: Noisy PSV and NAVA did not reduce global lung injury compared with PCV but affected different biomarkers and attenuated diaphragmatic atrophy. NAVA increased the respiratory variability; however, NAVA yielded a similar SVA incidence as Noisy PSV., Trial Registration: This trial was registered and approved by the Landesdirektion Dresden, Germany (AZ 24-9168.11-1/2012-2).

Background: Continuous external negative pressure (CENP) during positive pressure ventilation can recruit dependent lung regions. We hypothesised that CENP applied regionally to the thorax or the abdomen only, increases the caudal end-expiratory transpulmonary pressure depending on positive end-expiratory pressure (PEEP) in lung-injured pigs. Eight pigs were anesthetised and mechanically ventilated in the supine position. Pressure sensors were placed in the left pleural space, and a lung injury was induced by saline lung lavages. A CENP shell was placed at the abdomen and thorax (randomised order), and animals were ventilated with PEEP 15, 7 and zero cmH 2 O (15 min each). On each PEEP level, CENP of - 40, - 30, - 20, - 10 and 0 cmH 2 O was applied (3 min each). Respiratory and haemodynamic variables were recorded. Electrical impedance tomography allowed assessment of centre of ventilation., Results: Compared to positive pressure ventilation alone, the caudal transpulmonary pressure was significantly increased by CENP of ≤ 20 cmH 2 O at all PEEP levels. CENP of - 20 cmH 2 O reduced the mean airway pressure at zero PEEP (P = 0.025). The driving pressure decreased at CENP of ≤ 10 at PEEP of 0 and 7 cmH 2 O (P < 0.001 each) but increased at CENP of - 30 cmH 2 O during the highest PEEP (P = 0.001). CENP of - 30 cmH 2 O reduced the mechanical power during zero PEEP (P < 0.001). Both elastance (P < 0.001) and resistance (P < 0.001) were decreased at CENP ≤ 30 at PEEP of 0 and 7 cmH 2 O. Oxygenation increased at CENP of ≤ 20 at PEEP of 0 and 7 cmH 2 O (P < 0.001 each). Applying external negative pressure significantly shifted the centre of aeration towards dorsal lung regions irrespectively of the PEEP level. Cardiac output decreased significantly at CENP -20 cmH 2 O at all PEEP levels (P < 0.001). Effects on caudal transpulmonary pressure, elastance and cardiac output were more pronounced when CENP was applied to the abdomen compared with the thorax., Conclusions: In this lung injury model in pigs, CENP increased the end-expiratory caudal transpulmonary pressure. This lead to a shift of lung aeration towards dependent zones as well as improved respiratory mechanics and oxygenation, especially when CENP was applied to the abdomen as compared to the thorax. CENP values ≤ 20 cmH 2 O impaired the haemodynamics.

Background: Flow-controlled ventilation (FCV) allows expiratory flow control, reducing the collapse of the airways during expiration. The performance of FCV during one-lung ventilation (OLV) under intravascular normo- and hypovolaemia is currently unknown. In this explorative study, we hypothesised that OLV with FCV improves PaO 2 and reduces mechanical power compared to volume-controlled ventilation (VCV). Sixteen juvenile pigs were randomly assigned to one of two groups: (1) intravascular normovolaemia (n = 8) and (2) intravascular hypovolaemia (n = 8). To mimic inflammation due to major thoracic surgery, a thoracotomy was performed, and 0.5 μg/kg/h lipopolysaccharides from Escherichia coli continuously administered intravenously. Animals were randomly assigned to OLV with one of two sequences (60 min per mode): (1) VCV-FCV or (2) FCV-VCV. Variables of gas exchange, haemodynamics and respiratory signals were collected 20, 40 and 60 min after initiation of OLV with each mechanical ventilation mode. The distribution of ventilation was determined using electrical impedance tomography (EIT)., Results: Oxygenation did not differ significantly between modes (P = 0.881). In the normovolaemia group, the corrected expired minute volume (P = 0.022) and positive end-expiratory pressure (PEEP) were lower during FCV than VCV. The minute volume (P ≤ 0.001), respiratory rate (P ≤ 0.001), total PEEP (P ≤ 0.001), resistance of the respiratory system (P ≤ 0.001), mechanical power (P ≤ 0.001) and resistive mechanical power (P ≤ 0.001) were lower during FCV than VCV irrespective of the volaemia status. The distribution of ventilation did not differ between both ventilation modes (P = 0.103)., Conclusions: In a model of OLV in normo- and hypovolemic pigs, mechanical power was lower during FCV compared to VCV, without significant differences in oxygenation. Furthermore, the efficacy of ventilation was higher during FCV compared to VCV during normovolaemia.

Background: Mechanical ventilation with variable tidal volumes (V T ) may improve lung function and reduce ventilator-induced lung injury in experimental acute respiratory distress syndrome (ARDS). However, previous investigations were limited to less than 6 h, and control groups did not follow clinical standards. We hypothesised that 24 h of mechanical ventilation with variable V T reduces pulmonary inflammation (as reflected by neutrophil infiltration), compared with standard protective, nonvariable ventilation., Methods: Experimental ARDS was induced in 14 anaesthetised pigs with saline lung lavage followed by injurious mechanical ventilation. Pigs (n=7 per group) were randomly assigned to using variable V T or nonvariable V T modes of mechanical ventilation for 24 h. In both groups, ventilator settings including positive end-expiratory pressure and oxygen inspiratory fraction were adjusted according to the ARDS Network protocol. Pulmonary inflammation (primary endpoint) and perfusion were assessed by positron emission tomography using 2-deoxy-2-[ 18 F]fluoro-d-glucose and 68 Gallium ( 68 Ga)-labelled microspheres, respectively. Gas exchange, respiratory mechanics, and haemodynamics were quantified. Lung aeration was determined using CT., Results: The specific global uptake rate of 18 F-FDG increased to a similar extent regardless of mode of mechanical ventilation (median uptake for variable V T =0.016 min -1 [inter-quartile range, 0.012-0.029] compared with median uptake for nonvariable V T =0.037 min -1 [0.008-0.053]; P=0.406). Gas exchange, respiratory mechanics, haemodynamics, and lung aeration and perfusion were similar in both variable and nonvariable V T ventilatory modes., Conclusion: In a porcine model of ARDS, 24 h of mechanical ventilation with variable V T did not attenuate pulmonary inflammation compared with standard protective mechanical ventilation with nonvariable V T ., (Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Introduction: An ageing population and steady increase in the rates of neoplasms and chronic degenerative diseases poses a challenge for societies and their healthcare systems. Because of the recent and continued advances in therapies, such as the development and widespread use of non-invasive ventilation (NIV), survival rates have increased for these pathologies. For patients with end-stage chronic respiratory diseases, the use of NIV following the onset of acute or severe chronic respiratory failure is a valid option when intubation has been excluded., Evidence Acquisition: The following electronic databases were searched from their inception to January 2000 to December 2017: MEDLINE, EMBASE, CINHAIL, CENTRAL (Cochrane Central register of Controlled Trials), DARE (Database of Abstracts of Reviews of Effectiveness), the Cochrane Database of Systematic Reviews, ACP Journal Club database., Evidence Synthesis: The available evidence strongly supports the use of NIV in patients presenting with an exacerbation of chronic obstructive pulmonary disease, as well end-stage neuromuscular disease. Few studies support the use of NIV in end-stage interstitial lung disease and in morbid obesity patients. In patients with cancer has been recommend offering NIV as palliative care to improve dyspnea., Conclusions: The decision regarding the treatment should be made by the patient, ideally before reaching the terminal stage and after having a frank dialogue with healthcare professionals and family members.

PET imaging with 18 F-FDG followed by mathematic modeling of the pulmonary uptake rate (K i ) is the gold standard for assessment of pulmonary inflammation in experimental studies of acute respiratory distress syndrome (ARDS). However, dynamic PET requires long imaging and allows the assessment of only 1 cranio-caudal field of view (∼15 cm). We investigated whether static 18 F-FDG PET/CT and analysis of SUV or standardized uptake ratios (SUR stat , uptake time-corrected ratio of 18 F-FDG concentration in lung tissue and blood plasma) might be an alternative to dynamic 18 F-FDG PET/CT and Patlak analysis for quantification of pulmonary inflammation in experimental ARDS. Methods: ARDS was induced by saline lung lavage followed by injurious mechanical ventilation in 14 anesthetized pigs (29.5-40.0 kg). PET/CT imaging sequences were acquired before and after 24 h of mechanical ventilation. K i and the apparent volume of distribution were calculated from dynamic 18 F-FDG PET/CT scans using the Patlak analysis. Static 18 F-FDG PET/CT scans were obtained immediately after dynamic PET/CT and used for calculations of SUV and SUR stat Mean K i values of the whole imaged field of view and of 5 ventro-dorsal lung regions were compared with corresponding SUV and SUR stat values, respectively, by means of linear regression and concordance analysis. The variability of the 18 F-FDG concentration in blood plasma (arterial input function) was analyzed. Results: Both for the whole imaged field of view and ventro-dorsal subregions, K i was linearly correlated with SUR stat ( r 2 ≥ 0.84), whereas K i -SUV correlations were worse ( r 2 ≤ 0.75). The arterial input function exhibited an essentially invariant shape across all animals and time points and can be described by an inverse power law. Compared with K i , SUR stat and SUV tracked the same direction of change in regional lung inflammation in 98.6% and 84.3% of measurements, respectively. Conclusion: The K i -SUR stat correlations were considerably stronger than the K i -SUV correlations. The good K i -SUR stat correlations suggest that static 18 F-FDG PET/CT and SUR stat analysis provides an alternative to dynamic 18 F-FDG PET/CT and Patlak analysis, allowing the assessment of inflammation of whole lungs, repeated measurements within the period of 18 F-FDG decay, and faster data acquisition., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Electrical impedance tomography (EIT) with indicator dilution may be clinically useful to measure relative lung perfusion, but there is limited information on the performance of this technique., Methods: Thirteen pigs (50-66 kg) were anaesthetised and mechanically ventilated. Sequential changes in ventilation were made: (i) right-lung ventilation with left-lung collapse, (ii) two-lung ventilation with optimised PEEP, (iii) two-lung ventilation with zero PEEP after saline lung lavage, (iv) two-lung ventilation with maximum PEEP (20/25 cm H 2 O to achieve peak airway pressure 45 cm H 2 O), and (v) two-lung ventilation under unilateral pulmonary artery occlusion. Relative lung perfusion was assessed with EIT and central venous injection of saline 3%, 5%, and 10% (10 ml) during breath holds. Relative perfusion was determined by positron emission tomography (PET) using 68 Gallium-labelled microspheres. EIT and PET were compared in eight regions of equal ventro-dorsal height (right, left, ventral, mid-ventral, mid-dorsal, and dorsal), and directional changes in regional perfusion were determined., Results: Differences between methods were relatively small (95% of values differed by less than 8.7%, 8.9%, and 9.5% for saline 10%, 5%, and 3%, respectively). Compared with PET, EIT underestimated relative perfusion in dependent, and overestimated it in non-dependent, regions. EIT and PET detected the same direction of change in relative lung perfusion in 68.9-95.9% of measurements., Conclusions: The agreement between EIT and PET for measuring and tracking changes of relative lung perfusion was satisfactory for clinical purposes. Indicator-based EIT may prove useful for measuring pulmonary perfusion at bedside., (Copyright © 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Objectives: To determine the impact of positive end-expiratory pressure during mechanical ventilation with and without spontaneous breathing activity on regional lung inflammation in experimental nonsevere acute respiratory distress syndrome., Design: Laboratory investigation., Setting: University hospital research facility., Subjects: Twenty-four pigs (28.1-58.2 kg)., Interventions: In anesthetized animals, intrapleural pressure sensors were placed thoracoscopically in ventral, dorsal, and caudal regions of the left hemithorax. Lung injury was induced with saline lung lavage followed by injurious ventilation in supine position. During airway pressure release ventilation with low tidal volumes, positive end-expiratory pressure was set 4 cm H2O above the level to reach a positive transpulmonary pressure in caudal regions at end-expiration (best-positive end-expiratory pressure). Animals were randomly assigned to one of four groups (n = 6/group; 12 hr): 1) no spontaneous breathing activity and positive end-expiratory pressure = best-positive end-expiratory pressure - 4 cm H2O, 2) no spontaneous breathing activity and positive end-expiratory pressure = best-positive end-expiratory pressure + 4 cm H2O, 3) spontaneous breathing activity and positive end-expiratory pressure = best-positive end-expiratory pressure + 4 cm H2O, 4) spontaneous breathing activity and positive end-expiratory pressure = best-positive end-expiratory pressure - 4 cm H2O., Measurements and Main Results: Global lung inflammation assessed by specific [F]fluorodeoxyglucose uptake rate (median [25-75% percentiles], min) was decreased with higher compared with lower positive end-expiratory pressure both without spontaneous breathing activity (0.029 [0.027-0.030] vs 0.044 [0.041-0.065]; p = 0.004) and with spontaneous breathing activity (0.032 [0.028-0.043] vs 0.057 [0.042-0.075]; p = 0.016). Spontaneous breathing activity did not increase global lung inflammation. Lung inflammation in dorsal regions correlated with transpulmonary driving pressure from spontaneous breathing at lower (r = 0.850; p = 0.032) but not higher positive end-expiratory pressure (r = 0.018; p = 0.972). Higher positive end-expiratory pressure resulted in a more homogeneous distribution of aeration and regional transpulmonary pressures at end-expiration along the ventral-dorsal gradient, as well as a shift of the perfusion center toward dependent zones in the presence of spontaneous breathing activity., Conclusions: In experimental mild-to-moderate acute respiratory distress syndrome, positive end-expiratory pressure levels that stabilize dependent lung regions reduce global lung inflammation during mechanical ventilation, independent from spontaneous breathing activity.

Aim: We compared 68 Gallium ( 68 Ga)- and fluorescence-labeled microspheres for measurement of pulmonary perfusion distribution in anesthetized pigs without lung injury., Methods: In two mechanically ventilated pigs, the distribution of pulmonary perfusion was marked in vivo with 68 Ga- and fluorescence-labeled microspheres in supine and prone position. After each injection, the distribution of 68 Ga-labeled microspheres was measured in vivo with positron emission tomography/ computed tomography (PET/CT) in the position in which microspheres were injected and vice versa. The distribution of fluorescence-labeled microspheres was measured ex vivo . Perfusion distributions were compared between methods and postures within four lung regions and along the ventro-dorsal gradient. After each injection of 68 Ga-labeled microspheres, changes in ventro-dorsal perfusion gradients induced by repositioning were compared for volume- and mass-normalized PET/CT measurements., Results: Regional and gradient analyses of in vivo and ex vivo measurements, respectively, consistently revealed higher pulmonary perfusion in dorsal than ventral regions in supine positioned animals. Both methods showed more pronounced perfusion gradients in supine compared to prone position. Changes in animal position were associated with alterations in the ventro-dorsal perfusion gradient when volume-, but not mass-normalization was conducted for PET/CT data., Conclusions: Ex vivo fluorescence- and in vivo 68 Ga-labeled microspheres measurements revealed similar perfusion distributions. Mass-normalized perfusion measurements by 68 Ga-labeled microspheres and PET/CT were not affected by positioning artifacts., Competing Interests: The authors report no conflicts of interest. The authors alone were responsible for the content and writing of the paper., (Schattauer GmbH.)