Poly(dl-lactide) Polymer Blended with Mineral Phases for Extrusion 3D Printing-Studies on Degradation and Biocompatibility.

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 CaCO3, SrCO3, tricalcium phosphates (α-TCP, ß-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 CaCO3 and SrCO3 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 + CaCO3, 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.

Effects of positive end-expiratory pressure on pulmonary perfusion distribution and intrapulmonary shunt during one-lung ventilation in pigs A randomized crossover study.

BACKGROUND: During one-lung ventilation (OLV), positive end-expiratory pressure (PEEP) can improve lung aeration, but might over-distend lung units and increase intrapulmonary shunt. We hypothesized that higher PEEP shifts pulmonary perfusion from the ventilated to the non-ventilated 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 cmH2O, 5 cmH2O, titrated to best respiratory system compliance, and 15 cmH2O (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 i.v. 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. CONCLUSION: In this experimental model of thoracic surgery, higher PEEP during OLV did not shift the perfusion from the ventilated to the non-ventilated lung, thus not increasing intrapulmonary shunt. TRIAL REGISTRATION: This study was registered and approved by the Landesdirektion Dresden, Germany (25-5131/496/33).

Comparative effects of variable versus conventional volume-controlled one-lung ventilation on gas exchange and respiratory system mechanics in thoracic surgery patients: A randomized controlled clinical trial.

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 H2O, 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 H2O 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 (PaO2) 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).

Respiratory mechanics and mechanical power during low vs. high positive end-expiratory pressure in obese surgical patients - A sub-study of the PROBESE randomized controlled trial.

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 cmH2O and repeated RM (HighPEEP+RM) or 4 cmH2O without RM (LowPEEP). MEASUREMENTS: The index of intra-tidal recruitment/de-recruitment and overdistension (%E2) as well as airway pressure, tidal volume (VT), 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 cmH2O, P < 0.001) and driving pressure lower (12.8 ± 3.5 vs. 21.7 ± 6.8 cmH2O, P < 0.001) during HighPEEP+RM than LowPEEP, while VT 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). %E2 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 cmH2O∙l∙s-2, P = 0.009; and 15.7 ± 5.5 vs. 28.5 ± 8.4 cmH2O∙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).

Modulation of the hippo-YAP pathway by cyclic stretch in rat type 2 alveolar epithelial cells-a proof-of-concept study.

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.

Distribution of transpulmonary pressure during one-lung ventilation in pigs at different body positions.

Background. Global and regional transpulmonary pressure (PL) during one-lung ventilation (OLV) is poorly characterized. We hypothesized that global and regional PL and driving PL (ΔPL) 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 (VT) of 6 mL kg-1 during TLV and of 5 mL kg-1 during OLV and a positive end-expiratory pressure (PEEP) of 5 cmH2O. Global and local transpulmonary pressures were calculated. Lung instability was defined as end-expiratory PL<2.9 cmH2O 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 PL and ΔPL were higher during OLVsupine than TLVsupine. During OLV, regional end-inspiratory PL and ΔPL did not differ significantly among body positions. Yet, end-expiratory PL was lower in semilateral (ventral: 4.8 ± 2.9 cmH2O; caudal: 3.1 ± 2.6 cmH2O) and lateral (ventral: 1.9 ± 3.3 cmH2O; caudal: 2.7 ± 1.7 cmH2O) compared to supine (ventral: 4.8 ± 2.9 cmH2O; caudal: 3.1 ± 2.6 cmH2O) and prone position (ventral: 1.7 ± 2.5 cmH2O; caudal: 3.3 ± 1.6 cmH2O), 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.

Variable ventilation versus stepwise lung recruitment manoeuvres for lung recruitment: A comparative study in an experimental model of atelectasis.

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 ±â€Š6.2 versus 34.2 ±â€Š6.6, P  = 0.303); reduced poorly aerated lung mass compared with baseline (-3.5 ±â€Š4.0%, P  = 0.016, and -5.2 ±â€Š2.8%, P  < 0.001, respectively), and reduced nonaerated lung mass compared with baseline (-7.2 ±â€Š2.5%, P  < 0.001; and -4.7 ±â€Š2.8%, P  < 0.001 respectively), while the distribution of relative perfusion was barely affected (variable ventilation: -0.8 ±â€Š1.1%, P  = 0.044; stepwise recruitment manoeuvres: -0.4 ±â€Š0.9%, P  = 0.167). Compared with baseline, variable ventilation and stepwise recruitment manoeuvres increased Pa O 2 (172 ±â€Š85mmHg, P  = 0.001; and 213 ±â€Š73 mmHg, P  < 0.001, respectively), reduced Pa CO 2 (-9.6 ±â€Š8.1 mmHg, P  = 0.003; and -6.7 ±â€Š4.6 mmHg, P  < 0.001, respectively), and decreased elastance (-11.4 ±â€Š6.3 cmH 2 O, P  < 0.001; and -14.1 ±â€Š3.3 cmH 2 O, P  < 0.001, respectively). Mean arterial pressure decreased during stepwise recruitment manoeuvres (-24 ±â€Š8 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).

Effect of patient-ventilator asynchrony on lung and diaphragmatic injury in experimental acute respiratory distress syndrome in a porcine model.

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.

Practice of oxygen use in anesthesiology - a survey of the European Society of Anaesthesiology and Intensive Care.

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 (FiO2) ≥80% during induction and emergence from anesthesia, but intraoperatively < 60% for maintenance, and higher FiO2 in patients with diseased than non-diseased lungs. Postoperative oxygen therapy is prescribed more commonly according to peripheral oxygen saturation (SpO2), but shortage of devices still limits monitoring. When monitoring is used, SpO2 ≤ 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.

Changes in lung aeration and respiratory function after open abdominal surgery: A quantitative magnetic resonance imaging study.

BACKGROUND: Atelectasis is one of the most common respiratory complications in patients undergoing open abdominal surgery. Peripheral oxygen saturation (SpO2 ) 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 SpO2 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 SpO2 (p = .009), and a lower preoperative FVC (p = .029). The amount of atelectasis correlated with preoperative SpO2 (Spearman's ρ = -.51, p < .001) and postoperative SpO2 (ρ = -.60, p < .001), and with preoperative FVC (ρ = -.29, p = .047) and postoperative FVC (ρ = -.40, p = .006). A postoperative SpO2 ≤ 94% had 74% sensitivity and 78% specificity to detect atelectasis, while postoperative FVC ≤ 50% had 56% sensitivity and 100% specificity to detect atelectasis. CONCLUSION: SpO2 and FVC correlated with the amount of postoperative non-aerated lung volume, showing acceptable diagnostic accuracy in bedside detection of postoperative atelectasis.

Mechanical Power Correlates With Lung Inflammation Assessed by Positron-Emission Tomography in Experimental Acute Lung Injury in Pigs.

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-[18F]fluoro-D-glucose (KiS), and its difference between the two PET/CT was calculated (ΔKiS). 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 18F-FDG uptake rate increased significantly from first to second PET/CT (p = 0.012). ΔKiS 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 PaCO2 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.

Effects of Body Position and Hypovolemia on the Regional Distribution of Pulmonary Perfusion During One-Lung Ventilation in Endotoxemic Pigs.

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 (PaO2/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.

Effects of two stepwise lung recruitment strategies on respiratory function and haemodynamics in anaesthetised pigs: A randomised crossover study.

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 ±â€Š2.7 vs. 18.6 ±â€Š3.1 cmH2O, P = 0.001) and end-expiration (4.8 ±â€Š2.6 vs. 8.8 ±â€Š3.4 cmH2O, P  < 0.001), and mean arterial pressure (MAP) was higher (77 ±â€Š11 vs. 60 ±â€Š14 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 ±â€Š3.9 vs. 21.5 ±â€Š3.4 and 26.7 ±â€Š4.3 vs. 24.0 ±â€Š3.8 cmH2O l-1; P  < 0.001, respectively). At 1 min, PaO2 was lower in PROVHILO compared with iPROVE strategy (57.1 ±â€Š6.1 vs. 59.3 ±â€Š5.1 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).

High-Flow Nasal Oxygen Therapy in Acute Hypoxemic Respiratory Failure: Concise Review on Technology and Initial Methodology.

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.

The role of non-invasive ventilation in weaning and decannulating critically ill patients with tracheostomy: A narrative review of the literature.

INTRODUCTION: Invasive mechanical ventilation (IMV) is associated with several complications. Placement of a long-term airway (tracheostomy) is also associated with short and long-term risks for patients. Nevertheless, tracheostomies are placed to help reduce the duration of IMV, facilitate weaning and eventually undergo successful decannulation. METHODS: We performed a narrative review by searching PubMed, Embase and Medline databases to identify relevant citations using the search terms (with synonyms and closely related words) "non-invasive ventilation", "tracheostomy" and "weaning". We identified 13 publications comprising retrospective or prospective studies in which non-invasive ventilation (NIV) was one of the strategies used during weaning from IMV and/or tracheostomy decannulation. RESULTS: In some studies, patients with tracheostomies represented a subgroup of patients on IMV. Most of the studies involved patients with underlying cardiopulmonary comorbidities and conditions, and primarily involved specialized weaning centres. Not all studies provided data on decannulation, although those which did, report high success rates for weaning and decannulation when using NIV as an adjunct to weaning patient off ventilatory support. However, a significant percentage of patients still needed home NIV after discharge. CONCLUSIONS: The review supports a potential role for NIV in weaning patients with a tracheostomy either off the ventilator and/or with its decannulation. Additional research is needed to develop weaning protocols and better characterize the role of NIV during weaning.

PEEP in thoracic anesthesia: pros and cons.

Protective ventilation includes a strategy with low tidal volume, Plateau pressure, driving pressure, positive end-expiratory pressure (PEEP), and recruitment maneuvers on the ventilated lung. The rationale for the application of PEEP during one-lung ventilation (OLV) is that PEEP may contribute to minimize atelectrauma, preventing airway closure and alveolar collapse and improving the ventilation/perfusion to the ventilated lung. However, in case of high partial pressure of oxygen the application of PEEP may cause increased pulmonary vascular resistance, thus diverting blood flow to the non-ventilated lung, and worsening ventilation/perfusion. Further, PEEP may be associated with higher risk of hemodynamic impairment, increased need for fluids and vasoactive drugs. Positive effects on outcome have been reported by titrating PEEP according to driving pressure, targeted to obtain the optimum respiratory as well as pulmonary system compliance. This may vary according to the method employed for titration and should be performed individually for each patient. In summary, the potential for harm combined with the lack of evidence for improved outcome suggest that PEEP must be judiciously used during OLV even when titrated to a safe target, and only as much as necessary to maintain an appropriate gas exchange under low protective tidal volumes and driving pressures.

Continuous external negative pressure improves oxygenation and respiratory mechanics in Experimental Lung Injury in Pigs - A pilot proof-of-concept trial.

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 cmH2O (15 min each). On each PEEP level, CENP of - 40, - 30, - 20, - 10 and 0 cmH2O 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 cmH2O at all PEEP levels. CENP of - 20 cmH2O 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 cmH2O (P < 0.001 each) but increased at CENP of - 30 cmH2O during the highest PEEP (P = 0.001). CENP of - 30 cmH2O 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 cmH2O. Oxygenation increased at CENP of ≤ 20 at PEEP of 0 and 7 cmH2O (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 cmH2O 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 cmH2O impaired the haemodynamics.

Comparative effects of flow vs. volume-controlled one-lung ventilation on gas exchange and respiratory system mechanics in pigs.

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 PaO2 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.