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Considering accuracy/precision cut-offs of 5 ± 8 mmHg and cut-off values for inter-class correlation coefficients (ICC=0.37...1, from DIN EN ISO 81060-2), absolute and relative errors in time independent measurement of blood pressure changes with non-invasive intermittent devices (NiBP) are derived mathematically for mean arterial blood pressure range of 40-180 mmHg. As a clinically relevant value for change of arterial blood pressure 20% of the baseline blood pressure is considered. The mean ratio between the change of BP measured by the NiBP and measured by the invasive reference device (TE%) were proposed as quality measure for the evaluation of NiBP device tracking capability. The proposed measure TE%is theoretically independent of absolute accuracy but depends on precision and ICC of a device. NiBP devices show considerable maximum TE% of 41% in tracking mean blood pressure changes respectively. In 10% of the measurements in the low blood pressure range TE% exceeding 100%. The mean 50th/90th TE% percentile over the whole blood pressure range were 25/61%, respectively. Furthermore, TE% was relatively insensitive to assumed blood pressure range but sensitive to ICC. NiBP devices have high relative error in tracking blood pressure changes that make those devices not well-suited for tracking blood pressure changes. The proposed tracking error allows the definition of reasonable accuracy/precision requirements of NBP devices.

Optimal fluid management is critical during mechanical ventilation to mitigate lung damage. Under normovolemia and protective ventilation, pulmonary tensile stress during pressure-support ventilation (PSV) results in comparable lung protection to compressive stress during pressure-controlled ventilation (PCV) in experimental acute lung injury (ALI). It is not yet known whether tensile stress can lead to comparable protection to compressive stress in ALI under a liberal fluid strategy (LF). A conservative fluid strategy (CF) was compared with LF during PSV and PCV on lungs and kidneys in an established model of ALI. Twenty-eight male Wistar rats received endotoxin intratracheally. After 24 h, they were treated with CF (minimum volume of Ringer's lactate to maintain normovolemia and mean arterial pressure ≥70 mmHg) or LF (~4 times higher than CF) combined with PSV or PCV (V

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.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.Seven hundred ninety-eight ESAIC members (2.1% of all ESAIC members) completed the survey. Most respondents were board-certified and worked in hospitals withgt; 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 (FiOsub2/sub) ≥80% during induction and emergence from anesthesia, but intraoperativelylt; 60% for maintenance, and higher FiOsub2/subin patients with diseased than non-diseased lungs. Postoperative oxygen therapy is prescribed more commonly according to peripheral oxygen saturation (SpOsub2/sub), but shortage of devices still limits monitoring. When monitoring is used, SpOsub2/sub ≤ 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.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.

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

Background Postoperative pulmonary complications (PPCs) are a major cause of morbidity and mortality after open abdominal surgery. Optimized perioperative lung expansion may minimize the synergistic factors responsible for the multiple-hit perioperative pulmonary dysfunction. This ongoing study will assess whether an anesthesia-centered bundle focused on perioperative lung expansion results in decreased incidence and severity of PPCs after open abdominal surgery. Methods Prospective multicenter randomized controlled pragmatic trial in 750 adult patients with at least moderate risk for PPCs undergoing prolonged (≥2 hour) open abdominal surgery. Participants are randomized to receive either a bundle intervention focused on perioperative lung expansion or usual care. The bundle intervention includes preoperative patient education, intraoperative protective ventilation with individualized positive end-expiratory pressure to maximize respiratory system compliance, optimized neuromuscular blockade and reversal management, and postoperative incentive spirometry and early mobilization. Primary outcome is the distribution of the highest PPC severity by postoperative day 7. Secondary outcomes include the proportion of participants with: PPC grades 1–2 through POD 7; PPC grades 3–4 through POD 7, 30 and 90; intraoperative hypoxemia, rescue recruitment maneuvers, or cardiovascular events; and any major extrapulmonary postoperative complications. Additional secondary and exploratory outcomes include individual PPCs by POD 7, length of postoperative oxygen therapy or other respiratory support, hospital resource use parameters, Patient-Reported Outcomes Measurements (PROMIS®) questionnaires for dyspnea and fatigue collected before and at days 7, 30 and 90 after surgery, and plasma concentrations of lung injury biomarkers (IL6, IL-8, RAGE, CC16, Ang-2) analyzed from samples obtained before, end of, and 24 hours after surgery. Discussion Participant recruitment for this study started January 2020; results are expected in 2024. At the conclusion of this trial, we will determine if this anesthesia-centered strategy focused on perioperative lung expansion reduces lung morbidity and healthcare utilization after open abdominal surgery. Trial registration ClinicalTrial.gov NCT04108130.

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

In this study a physiological closed-loop system for arterial CO2 partial pressure control was designed and comprehensively tested using a set of models of the respiratory CO2 gas exchange. The underlying preclinical data were collected from 12 pigs in presence of severe changes in hemodynamic and pulmonary condition. A minimally complex nonlinear state space model of CO2 gas exchange was identified post hoc in different lung conditions. The control variable was measured noninvasively using the endtidal CO2 partial pressure. For the simulation study the output signal of the controller was defined as the alveolar minute volume set value of an underlying adaptive lung protective ventilation mode. A linearisation of the two-compartment CO2 gas exchange model was used for the design of a model predictive controller (MPC). It was augmented by a tube based controller suppressing prediction errors due to model uncertainties. The controller was subject to comparative testing in interaction with each of the CO2 gas exchange models previously identified on the preclinical study data. The performance was evaluated for the system response towards the following five tests in comparison to a PID controller: recruitment maneuver, PEEP titration maneuver, stepwise change in the CO2 production, breath-hold maneuver and a step in the reference signal. A root mean square error of 2.69 mmHg between arterial CO2 partial pressure and the reference signal was achieved throughout the trial. The reference-variable response of the model predictive controller was superior regarding overshoot and settling time.

The indicator dilution method (IDM) is one approach to measure pulmonary perfusion using Electrical Impedance Tomography (EIT). To be able to calculate perfusion parameters and to increase robustnes, it is necessary to approximate and then to separate the components of the measured signals. The component referring to the passage of the injected bolus through the pixels can be modeled as a gamma variate function, its parameters are often determined using nonlinear optimization algorithms. In this paper, we introduce a linear approach that enables higher robustnes and faster computation, and compare the linear and nonlinear fitting approach on data of an animal study.

Background Mechanical ventilation with low tidal volumes has the potential to mitigate ventilation-induced lung injury, yet the clinical effect of tidal volume size on myocardial function has not been clarified. This cross-sectional study investigated whether low tidal volume ventilation has beneficial effects on myocardial systolic and diastolic function compared to intermediate tidal volume ventilation. Methods Forty-two mechanically ventilated patients without acute respiratory distress syndrome (ARDS) underwent transthoracic echocardiography after more than 24 h of mechanical ventilation according to the Protective Ventilation in Patients without ARDS (PReVENT) trial comparing a low versus intermediate tidal volume strategy. The primary outcome was left ventricular and right ventricular myocardial performance index as measure for combined systolic and diastolic function, with lower values indicating better myocardial function and a right ventricular myocardial performance index greater than 0.54 regarded as the abnormality threshold. Secondary outcomes included specific systolic and diastolic parameters. Results One patient was excluded due to insufficient acoustic windows, leaving 21 patients receiving low tidal volumes with a tidal volume size (mean ± SD) of 6.5 ± 1.8 ml/kg predicted body weight, while 20 patients were subjected to intermediate tidal volumes receiving a tidal volume size of 9.5 ± 1.6 ml/kg predicted body weight (mean difference, −3.0 ml/kg; 95% CI, −4.1 to −2.0; P < 0.001). Right ventricular dysfunction was reduced in the low tidal volume group compared to the intermediate tidal volume group (myocardial performance index, 0.41 ± 0.13 vs. 0.64 ± 0.15; mean difference, −0.23; 95% CI, −0.32 to −0.14; P < 0.001) as was left ventricular dysfunction (myocardial performance index, 0.50 ± 0.17 vs. 0.63 ± 0.19; mean difference, −0.13; 95% CI, −0.24 to −0.01; P = 0.030). Similarly, most systolic parameters were superior in the low tidal volume group compared to the intermediate tidal volume group, yet diastolic parameters did not differ between both groups. Conclusions In patients without ARDS, intermediate tidal volume ventilation decreased left ventricular and right ventricular systolic function compared to low tidal volume ventilation, although without an effect on diastolic function. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Background Pneumoperitoneum for laparoscopic surgery is associated with a rise of driving pressure. The authors aimed to assess the effects of positive end-expiratory pressure (PEEP) on driving pressure at varying intraabdominal pressure levels. It was hypothesized that PEEP attenuates pneumoperitoneum-related rises in driving pressure. Methods Open-label, nonrandomized, crossover, clinical trial in patients undergoing laparoscopic cholecystectomy. “Targeted PEEP” (2 cm H2O above intraabdominal pressure) was compared with “standard PEEP” (5 cm H2O), with respect to the transpulmonary and respiratory system driving pressure at three predefined intraabdominal pressure levels, and each patient was ventilated with two levels of PEEP at the three intraabdominal pressure levels in the same sequence. The primary outcome was the difference in transpulmonary driving pressure between targeted PEEP and standard PEEP at the three levels of intraabdominal pressure. Results Thirty patients were included and analyzed. Targeted PEEP was 10, 14, and 17 cm H2O at intraabdominal pressure of 8, 12, and 15 mmHg, respectively. Compared to standard PEEP, targeted PEEP resulted in lower median transpulmonary driving pressure at intraabdominal pressure of 8 mmHg (7 [5 to 8] vs. 9 [7 to 11] cm H2O; P = 0.010; difference 2 [95% CI 0.5 to 4 cm H2O]); 12 mmHg (7 [4 to 9] vs.10 [7 to 12] cm H2O; P = 0.002; difference 3 [1 to 5] cm H2O); and 15 mmHg (7 [6 to 9] vs.12 [8 to 15] cm H2O; P < 0.001; difference 4 [2 to 6] cm H2O). The effects of targeted PEEP compared to standard PEEP on respiratory system driving pressure were comparable to the effects on transpulmonary driving pressure, though respiratory system driving pressure was higher than transpulmonary driving pressure at all intraabdominal pressure levels. Conclusions Transpulmonary driving pressure rises with an increase in intraabdominal pressure, an effect that can be counterbalanced by targeted PEEP. Future studies have to elucidate which combination of PEEP and intraabdominal pressure is best in term of clinical outcomes. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Pressure-support ventilation may worsen lung damage due to increased dynamic transpulmonary driving pressure. The authors hypothesized that, at the same tidal volume (VT) and dynamic transpulmonary driving pressure, pressure-support and pressure-controlled ventilation would yield comparable lung damage in mild lung injury. Methods Male Wistar rats received endotoxin intratracheally and, after 24 h, were ventilated in pressure-support mode. Rats were then randomized to 2 h of pressure-controlled ventilation with VT, dynamic transpulmonary driving pressure, dynamic transpulmonary driving pressure, and inspiratory time similar to those of pressure-support ventilation. The primary outcome was the difference in dynamic transpulmonary driving pressure between pressure-support and pressure-controlled ventilation at similar VT; secondary outcomes were lung and diaphragm damage. Results At VT = 6 ml/kg, dynamic transpulmonary driving pressure was higher in pressure-support than pressure-controlled ventilation (12.0 ± 2.2 vs. 8.0 ± 1.8 cm H2O), whereas static transpulmonary driving pressure did not differ (6.7 ± 0.6 vs. 7.0 ± 0.3 cm H2O). Diffuse alveolar damage score and gene expression of markers associated with lung inflammation (interleukin-6), alveolar-stretch (amphiregulin), epithelial cell damage (club cell protein 16), and fibrogenesis (metalloproteinase-9 and type III procollagen), as well as diaphragm inflammation (tumor necrosis factor-α) and proteolysis (muscle RING-finger-1) were comparable between groups. At similar dynamic transpulmonary driving pressure, as well as dynamic transpulmonary driving pressure and inspiratory time, pressure-controlled ventilation increased VT, static transpulmonary driving pressure, diffuse alveolar damage score, and gene expression of markers of lung inflammation, alveolar stretch, fibrogenesis, diaphragm inflammation, and proteolysis compared to pressure-support ventilation. Conclusions In the mild lung injury model use herein, at the same VT, pressure-support compared to pressure-controlled ventilation did not affect biologic markers. However, pressure-support ventilation was associated with a major difference between static and dynamic transpulmonary driving pressure; when the same dynamic transpulmonary driving pressure and inspiratory time were used for pressure-controlled ventilation, greater lung and diaphragm injury occurred compared to pressure-support ventilation.

The term high-frequency ventilation (HFV) is used to describe different techniques of mechanical ventilation that use respiratory rates of 60 or more breaths per minute, tidal volumes equal to or less than the dead space, as well as lower peak airway pressures, lower transpulmonary pressure, and increased functional reserve capacity compared with conventional mechanical ventilation. There is a wide range of indications for HFV in thoracic surgery, such as rigid bronchoscopy, airway stenosis, imaging, stereotactic procedures and catheter ablation, treatment of bronchopleural fistula, and respiratory therapy after cardiac surgery. Contraindications for HFV are extreme adiposity, severe obstructive pulmonary disease, and an increased risk of aspiration whenever an open ventilation system is used as during high-frequency jet ventilation. HFV offers many benefits for thoracic procedures, such as increased surgical visibility, decreased conflict of space within the airways, decreased gas leak because of lower airway pressure when a major bronchopleural fistula is present and minimizing movements associated with normal tidal volume for imaging and radiation purposes, and a quasi-static surgical field. The complication rates of HFV are relatively low when patients are selected carefully, contraindications are excluded, the team is well trained, and backup strategies are available. This chapter will describe the different types and the use of HFV in thoracic procedures.

Hypoxaemia is a potential life-threatening yet common complication in the peri-operative and periprocedural patient (e.g. during an invasive procedure at risk of deterioration of gas exchange, such as bronchoscopy). The European Society of Anaesthesiology (ESA) and the European Society of Intensive Care Medicine (ESICM) developed guidelines for the use of noninvasive respiratory support techniques in the hypoxaemic patient in the peri-operative and periprocedural period. The panel outlined five clinical questions regarding treatment with noninvasive respiratory support techniques [conventional oxygen therapy (COT), high flow nasal cannula, noninvasive positive pressure ventilation (NIPPV) and continuous positive airway pressure (CPAP)] for hypoxaemic patients with acute peri-operative/periprocedural respiratory failure. The goal was to assess the available literature on the various noninvasive respiratory support techniques, specifically studies that included adult participants with hypoxaemia in the peri-operative/periprocedural period. The literature search strategy was developed by a Cochrane Anaesthesia and Intensive Care trial search specialist in close collaboration with the panel members and the ESA group methodologist. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to assess the level of evidence and to grade recommendations. The final process was then validated by both ESA and ESICM scientific committees. Among 19 recommendations, the two grade 1B recommendations state that: in the peri-operative/periprocedural hypoxaemic patient, the use of either NIPPV or CPAP (based on local expertise) is preferred to COT for improvement of oxygenation; and that the panel suggests using NIPPV or CPAP immediately post-extubation for hypoxaemic patients at risk of developing acute respiratory failure after abdominal surgery. Electronic supplementary material The online version of this article (10.1007/s00134-020-05948-0) contains supplementary material, which is available to authorized users.

BACKGROUND: In the Protective Ventilation in Cardiac Surgery (PROVECS) randomized, controlled trial, an open-lung ventilation strategy did not improve postoperative respiratory outcomes after on-pump cardiac surgery. In this prespecified subanalysis, the authors aimed to assess the regional distribution of ventilation and plasma biomarkers of lung epithelial and endothelial injury produced by that strategy. METHODS: Perioperative open-lung ventilation consisted of recruitment maneuvers, positive end-expiratory pressure (PEEP) = 8 cm H(2)O, and low-tidal volume ventilation including during cardiopulmonary bypass. Control ventilation strategy was a low-PEEP (2 cm H(2)O) low-tidal volume approach. Electrical impedance tomography was used serially throughout the perioperative period (n = 56) to compute the dorsal fraction of ventilation (defined as the ratio of dorsal tidal impedance variation to global tidal impedance variation). Lung injury was assessed serially using biomarkers of epithelial (soluble form of the receptor for advanced glycation end-products, sRAGE) and endothelial (angiopoietin-2) lung injury (n = 30). RESULTS: Eighty-six patients (age = 64 ± 12 yr; EuroSCORE II = 1.65 ± 1.57%) undergoing elective on-pump cardiac surgery were studied. Induction of general anesthesia was associated with ventral redistribution of tidal volumes and higher dorsal fraction of ventilation in the open-lung than the control strategy (0.38 ± 0.07 vs. 0.30 ± 0.10; P = 0.004). No effect of the open-lung strategy on the dorsal fraction of ventilation was noted at the end of surgery after median sternotomy closure (open-lung = 0.37 ± 0.09 vs. control = 0.34 ± 0.11; P = 0.743) or in extubated patients at postoperative day 2 (open-lung = 0.63 ± 0.18 vs. control = 0.59 ± 0.11; P > 0.999). Open-lung ventilation was associated with increased intraoperative plasma sRAGE (7,677 ± 3,097 pg/ml vs. 6,125 ± 1,400 pg/ml; P = 0.037) and had no effect on angiopoietin-2 (P > 0.999). CONCLUSIONS: In cardiac surgery patients, open-lung ventilation provided larger dorsal lung ventilation early during surgery without a maintained benefit as compared with controls at the end of surgery and postoperative day 2 and was associated with higher intraoperative plasma concentration of sRAGE suggesting lung overdistension.

In patients with uninjured lungs, increasing evidence indicates that tidal volume (VT) reduction improves outcomes in the intensive care unit (ICU) and in the operating room (OR). However, the degree to which this evidence has translated to clinical changes in ventilator settings for patients with uninjured lungs is unknown. To clarify whether ventilator settings have changed, we searched MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science for publications on invasive ventilation in ICUs or ORs, excluding those on patients 25% of patients with acute respiratory distress syndrome (ARDS). Our primary end point was temporal change in VT over time. Secondary end points were changes in maximum airway pressure, mean airway pressure, positive end-expiratory pressure, inspiratory oxygen fraction, development of ARDS (ICU studies only), and postoperative pulmonary complications (OR studies only) determined using correlation analysis and linear regression. We identified 96 ICU and 96 OR studies comprising 130,316 patients from 1975 to 2014 and observed that in the ICU, VT size decreased annually by 0.16 mL/kg (-0.19 to -0.12 mL/kg) (P < .001), while positive end-expiratory pressure increased by an average of 0.1 mbar/y (0.02-0.17 mbar/y) (P = .017). In the OR, VT size decreased by 0.09 mL/kg per year (-0.14 to -0.04 mL/kg per year) (P < .001). The change in VTs leveled off in 1995. Other intraoperative ventilator settings did not change in the study period. Incidences of ARDS (ICU studies) and postoperative pulmonary complications (OR studies) also did not change over time. We found that, during a 39-year period, from 1975 to 2014, VTs in clinical studies on mechanical ventilation have decreased significantly in the ICU and in the OR.

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.

Patients undergoing thoracic surgery are at high risk for pulmonary and extra pulmonary complications, and may develop impairment of gas exchange during surgery and in the postoperative period. This review focuses on the potential benefits of high-flow nasal cannula (HFNC) oxygen therapy in those patients.HFNC oxygen therapy can be used pre, intra and postoperatively. However, evidence for the use of HFNC oxygen therapy is still limited. Most trials investigated the effects of HFNC oxygen therapy in the postoperative period only, with promising beneficial effects. Preoperative HFNC oxygen therapy might be an alternative to conventional techniques, and allows continuous oxygenation during the apneic time of laryngoscopy. In certain patients, thoracic surgery might be performed in awake and nonintubated patients who are breathing spontaneously. Under these conditions, HFNC oxygen therapy might be considered for respiratory support by experienced anesthesiologists. In the postoperative period, HFNC oxygen therapy can prevent escalation of respiratory management and has the potential to reduce the length of hospital stay. Throughout the perioperative period, close monitoring of patients receiving HFNC oxygen therapy is key, and intubation criteria to avoid delayed intubation should be defined a priori to prevent harm.HFNC oxygen therapy is a promising tool in the perioperative care of thoracic surgical patients, when properly set, performed by experienced staff and closely monitored.

Objectives To determine whether driving pressure and expiratory flow limitation are associated with the development of postoperative pulmonary complications (PPCs) in cardiac surgery patients. Design Prospective cohort study. Setting University Hospital San Raffaele, Milan, Italy. Participants Patients undergoing elective cardiac surgery. Measurements and Main Results The primary endpoint was the occurrence of a predefined composite of PPCs. The authors determined the association among PPCs and intraoperative ventilation parameters, mechanical power and energy load, and occurrence of expiratory flow limitation (EFL) assessed with the positive end-expiratory pressure test. Two hundred patients were enrolled, of whom 78 (39%) developed one or more PPCs. Patients with PPCs, compared with those without PPCs, had similar driving pressure (mean difference [MD] –0.1 [95% confidence interval (CI), –1.0 to 0.7] cmH2O, p = 0.561), mechanical power (MD 0.5 [95% CI, –0.3 to 1.1] J/m, p = 0.364), and total energy load (MD 95 [95% CI, –78 to 263] J, p = 0.293), but they had a higher incidence of EFL (51% v 38%, p = 0.005). Only EFL was associated independently with the development of PPCs (odds ratio 2.46 [95% CI, 1.28-4.80], p = 0.007). Conclusions PPCs occurred frequently in this patient population undergoing cardiac surgery. PPCs were associated independently with the presence of EFL but not with driving pressure, total energy load, or mechanical power.

Background: Patients with coronavirus disease 2019 (COVID-19) may need hospitalization for supplemental oxygen, and some need intensive care unit (ICU) admission for escalation of care. Practice of adjunctive and supportive treatments remain uncertain and may vary widely between countries, within countries between hospitals, and possibly even within ICUs. We aim to investigate practice of adjunctive and supportive treatments, and their associations with outcome, in critically ill COVID-19 patients.Methods: The 'PRactice of Adjunctive Treatments in Intensive Care Unit Patients with Coronavirus Disease 2019' (PRoAcT-COVID) study is a national, observational study to be undertaken in a large set of ICUs in The Netherlands. The PRoAcT-COVID includes consecutive ICU patients, admitted because of COVID-19 to one of the participating ICUs during a 3-month period. Daily follow-up lasts 28 days. The primary endpoint is a combination of adjunctive treatments, including types of oxygen support, ventilation, rescue therapies for hypoxemia refractory to supplementary oxygen or during invasive ventilation, other adjunctive and supportive treatments, and experimental therapies. We will also collect tracheostomy rate, duration of invasive ventilation and ventilator-free days and alive at day 28 (VFD-28), ICU and hospital length of stay, and the mortality rates in the ICU, hospital and at day 90.Discussion: The PRoAcT-COVID study is an observational study combining high density treatment data with relevant clinical outcomes. Information on treatment practices, and their associations with outcomes in COVID-19 patients in highly and urgently needed. The results of the PRoAcT-COVID study will be rapidly available, and circulated through online presentations, such as webinars and electronic conferences, and publications in peer-reviewed journals-findings will also be presented at a dedicated website. At request, and after agreement of the PRoAcT-COVID steering committee, source data will be made available through local, regional and national anonymized datasets.Trial registration: The PRoAcT-COVID study is registered at clinicaltrials.gov (study identifier NCT04719182).

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.

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 and/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 12h. Mechanically ventilated pigs were randomised to spontaneously breath with, or without, induced subject-ventilator asynchrony, or neuromuscular blockade (n=7/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 ratio and diaphragmatic muscle fibre thickness. RESULTS Mean alveolar septal thickness was similar in pigs randomised to subject-ventilator asynchrony (mean (SD):29.5% (10.8) asynchronous breaths of total breaths; n=7) compared to synchronous spontaneous breathing (asynchronous breaths 1.8% (2.9) of total breaths; n=7). There was no difference in mean alveolar septal thickness throughout upper and lower lungs lobes between pigs randomised to subject-ventilator asynchrony versus synchronous spontaneous breathing (87.3-92.2μm after subject-ventilator asynchrony, compared to 84.1-95.0 μm in synchronised spontaneous breathing; P=0.956). There were also no differences between groups in wet-to-dry ratio, diaphragmatic muscle fibre thickness, atelectasis, lung aeration, and mRNA expression levels for inflammatory cytokines pivotal in ARDS pathogenesis. CONCLUSION Subject-ventilator asynchrony during spontaneous breathing did not exacerbate lung injury and dysfunction in experimental ARDS.

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.

Mechanical ventilation (MV) may lead to ventilator-induced diaphragm dysfunction (VIDD). VIDD is associated with difficult MV weaning and longer MV duration. Mitigating VIDD may thus improve outcomes in patients on prolonged MV. We conducted a preliminary multicenter, open label, randomized controlled trial of temporary transvenous diaphragm neurostimulation (TTDN) using a multi-electrode stimulating central venous catheter (Lungpacer Diaphragm Pacing Therapy System) in difficult-to-wean MV patients. Patients on MV for >96 hours with at least two failed spontaneous breathing trials and satisfying readiness to wean criteria were randomized (1:1) to TTDN (up to 120 stimulations per day; up to 30 days) or standard of care (SoC). Outcomes assessed included the proportion of patients successfully weaned, MV duration, 30-day survival, and maximal inspiratory pressure (MIP). 112 patients were randomized (57 TTDN; 55 SoC). TTDN was successfully delivered in 75% of cases. The frequency of serious adverse events was similar in both groups. For TTDN and SoC, respectively, the incidence of successful weaning was 82% and 74% (p=0.586); MV duration was 12.7±9.9 and 14.1±10.8 days (p=0.498); 30-day survival was 93% and 85% (p=0.216); MIP increased by 17±3 cmH2O vs. 5±2 cmH2O (p=0.001), with a significant stimulation dose-response relationship in TTDN patients. TTDN is feasible and safe in difficult to wean patients. A significant diaphragm-related improvement in MIP was achieved independent of patients9 cooperation.This study will help define the patient population and effect size to appropriately power future studies for clinical efficacy.

Background: Intraoperative mechanical ventilation may influence postoperative pulmonary complications (PPCs). Current practice during thoracic surgery is not well described. Methods: This is a post-hoc analysis of the prospective multicenter cross-sectional LAS VEGAS study focusing on patients who underwent thoracic surgery. Consecutive adult patients receiving invasive ventilation during general anesthesia were included in a one-week period in 2013. Baseline characteristics, intraoperative and postoperative data were registered. PPCs were collected as composite endpoint until the 5th postoperative day. Patients were stratified into groups based on the use of one lung ventilation (OLV) or two lung ventilation (TLV), endoscopic vs. non-endoscopic approach and ARISCAT score risk for PPCs. Differences between subgroups were compared using χ2 or Fisher exact tests or Student’s t-test. Kaplan–Meier estimates of the cumulative probability of development of PPC and hospital discharge were performed. Cox-proportional hazard models without adjustment for covariates were used to assess the effect of the subgroups on outcome. Results: From 10,520 patients enrolled in the LAS VEGAS study, 302 patients underwent thoracic procedures and were analyzed. There were no differences in patient characteristics between OLV vs. TLV, or endoscopic vs. open surgery. Patients received VT of 7.4 ± 1.6 mL/kg, a PEEP of 3.5 ± 2.4 cmH2O, and driving pressure of 14.4 ± 4.6 cmH2O. Compared with TLV, patients receiving OLV had lower VT and higher peak, plateau and driving pressures, higher PEEP and respiratory rate, and received more recruitment maneuvers. There was no difference in the incidence of PPCs in OLV vs. TLV or in endoscopic vs. open procedures. Patients at high risk had a higher incidence of PPCs compared with patients at low risk (48.1% vs. 28.9%; hazard ratio, 1.95; 95% CI 1.05–3.61; p = 0.033). There was no difference in the incidence of severe PPCs. The in-hospital length of stay (LOS) was longer in patients who developed PPCs. Patients undergoing OLV, endoscopic procedures and at low risk for PPC had shorter LOS. Conclusion: PPCs occurred frequently and prolonged hospital LOS following thoracic surgery. Proportionally large tidal volumes and high driving pressure were commonly used in this sub-population. However, large RCTs are needed to confirm these findings. Trial registration: This trial was prospectively registered at the Clinical Trial Register (www.clinicaltrials.gov; NCT01601223; registered May 17, 2012.)

Background: Outcome prediction in acute respiratory distress syndrome (ARDS) is challenging, especially in patients with severe hypoxemia. The aim of the current study was to determine the prognostic capacity of changes in PaO 2 /FiO 2 , dead space fraction (V D /V T ) and respiratory system driving pressure (ΔP RS ) induced by the first prone position (PP) session in patients with ARDS. Methods: This was a post hoc analysis of the conveniently-sized ‘Molecular Diagnosis and Risk Stratification of Sepsis’ study (MARS). The current analysis included ARDS patients who were placed in the PP. The primary endpoint was the prognostic capacity of the PP-induced changes in PaO 2 /FiO 2 , V D /V T , and ΔP RS for 28-day mortality. PaO 2 /FiO 2 , V D /V T , and ΔP RS was calculated using variables obtained in the supine position before and after completion of the first PP session. Receiving operator characteristic curves (ROC) were constructed, and sensitivity, specificity positive and negative predictive value were calculated based on the best cutoffs. Results: Ninety patients were included; 28-day mortality was 46%. PP-induced changes in PaO 2 /FiO 2 and V D /V T were similar between survivors vs. non-survivors [+83 (+24 to +137) vs. +58 (+21 to +113) mmHg, and –0.06 (–0.17 to +0.05) vs. –0.08 (–0.16 to +0.08), respectively]. PP-induced changes in ΔP RS were different between survivors vs. non-survivors [–3 (–7 to 2) vs. 0 (–3 to +3) cmH 2 O; P=0.03]. The area under the ROC of PP-induced changes in ΔP RS for mortality, however, was low [0.63 (95% confidence interval (CI), 0.50 to 0.75]; PP-induced changes in ΔP RS had a sensitivity and specificity of 76% and 56%, and a positive and negative predictive value of 60% and 73%. Conclusions: Changes in PaO 2 /FiO 2 , V D /V T , and ΔP RS induced by the first PP session have poor prognostic capacities for 28-day mortality in ARDS patients.

Respiratory mechanics describe the lung function through pressure and flow and the interplay between the two during the respiratory cycle. Derived indices are volume, compliance and resistance (Hess, Respir Care 59(11):1773–1794, 2014). Thoracic surgery in most cases requires the separation of the lungs in order to allow surgery of or near one lung and ventilation of the other lung, while the perfusion to the non-ventilated lung is continued. This has profound implications for the gas exchange and respiratory mechanics.

Purpose: Mechanical power (MP) may unify variables known to be related to development of ventilator-induced lung injury. The aim of this study is to examine the association between MP and mortality in critically ill patients receiving invasive ventilation for at least 48 h. Methods: This is an analysis of data stored in the databases of the MIMIC–III and eICU. Critically ill patients receiving invasive ventilation for at least 48 h were included. The exposure of interest was MP. The primary outcome was in-hospital mortality. Results: Data from 8207 patients were analyzed. Median MP during the second 24 h was 21.4 (16.2–28.1) J/min in MIMIC-III and 16.0 (11.7–22.1) J/min in eICU. MP was independently associated with in-hospital mortality [odds ratio per 5 J/min increase (OR) 1.06 (95% confidence interval (CI) 1.01–1.11); p = 0.021 in MIMIC-III, and 1.10 (1.02–1.18); p = 0.010 in eICU]. MP was also associated with ICU mortality, 30-day mortality, and with ventilator-free days, ICU and hospital length of stay. Even at low tidal volume, high MP was associated with in-hospital mortality [OR 1.70 (1.32–2.18); p < 0.001] and other secondary outcomes. Finally, there is a consistent increase in the risk of death with MP higher than 17.0 J/min. Conclusion: High MP of ventilation is independently associated with higher in-hospital mortality and several other outcomes in ICU patients receiving invasive ventilation for at least 48 h.

Postoperative pulmonary complications (PPCs) occur frequently and are associated with substantial morbidity and mortality. Evidence suggests that reduction of PPCs can be accomplished by using lung-protective ventilation strategies intraoperatively, but a consensus on perioperative management has not been established. We sought to determine recommendations for lung protection for the surgical patient at an international consensus development conference. Seven experts produced 24 questions concerning preoperative assessment and intraoperative mechanical ventilation for patients at risk of developing PPCs. Six researchers assessed the literature using questions as a framework for their review. The modified Delphi method was utilised by a team of experts to produce recommendations and statements from study questions. An expert consensus was reached for 22 recommendations and four statements. The following are the highlights: (i) a dedicated score should be used for preoperative pulmonary risk evaluation; and (ii) an individualised mechanical ventilation may improve the mechanics of breathing and respiratory function, and prevent PPCs. The ventilator should initially be set to a tidal volume of 6-8 ml kg-1 predicted body weight and positive end-expiratory pressure (PEEP) 5 cm H2O. PEEP should be individualised thereafter. When recruitment manoeuvres are performed, the lowest effective pressure and shortest effective time or fewest number of breaths should be used. ispartof: BJA: British Journal of Anaesthesia vol:123 issue:6 pages:898-913 ispartof: location:England status: Published online

Background The authors hypothesized that low tidal volume (VT) would minimize ventilator-induced lung injury regardless of the degree of mechanical power. The authors investigated the impact of power, obtained by different combinations of VT and respiratory rate (RR), on ventilator-induced lung injury in experimental mild acute respiratory distress syndrome (ARDS). Methods Forty Wistar rats received Escherichia coli lipopolysaccharide intratracheally. After 24 h, 32 rats were randomly assigned to be mechanically ventilated (2 h) with a combination of different VT (6 ml/kg and 11 ml/kg) and RR that resulted in low and high power. Power was calculated as energy (ΔP,L2/E,L) × RR (ΔP,L = transpulmonary driving pressure; E,L = lung elastance), and was threefold higher in high than in low power groups. Eight rats were not mechanically ventilated and used for molecular biology analysis. Results Diffuse alveolar damage score, which represents the severity of edema, atelectasis, and overdistension, was increased in high VT compared to low VT, in both low (low VT: 11 [9 to 14], high VT: 18 [15 to 20]) and high (low VT: 19 [16 to 25], high VT: 29 [27 to 30]) power groups. At high VT, interleukin-6 and amphiregulin expressions were higher in high-power than in low-power groups. At high power, amphiregulin and club cell protein 16 expressions were higher in high VT than in low VT. Mechanical energy and power correlated well with diffuse alveolar damage score and interleukin-6, amphiregulin, and club cell protein 16 expression. Conclusions In experimental mild ARDS, even at low VT, high mechanical power promoted ventilator-induced lung injury. To minimize ventilator-induced lung injury, low VT should be combined with low power.

Summary Aim: We compared 68Gallium (68Ga)- 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 68Ga- and fluorescence-labeled microspheres in supine and prone position. After each injection, the distribution of 68Ga-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 68Ga-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 68Ga-labeled microspheres measurements revealed similar perfusion distributions. Mass-normalized perfusion measurements by 68Ga-labeled microspheres and PET/CT were not affected by positioning artifacts.

Harmful effects of spontaneous breathing have been shown in experimental severe acute respiratory distress syndrome (ARDS). However, in the clinical setting, spontaneous respiration has been indicated only in mild ARDS. To date, no study has compared the effects of spontaneous assisted breathing with those of fully controlled mechanical ventilation at different levels of positive end-expiratory pressure (PEEP) on lung injury in ARDS.To compare the effects of assisted pressure support ventilation (PSV) with pressure-controlled ventilation (PCV) on lung function, histology and biological markers at two different PEEP levels in mild ARDS in rats.Randomised controlled experimental study.Basic science laboratory.Thirty-five Wistar rats (weight ± SD, 310 ± 19) g received Escherichia coli lipopolysaccharide (LPS) intratracheally. After 24 h, the animals were anaesthetised and randomly allocated to either PCV (n=14) or PSV (n=14) groups. Each group was further assigned to PEEP = 2 cmH2O or PEEP = 5 cmH2O. Tidal volume was kept constant (≈6 ml kg). Additional nonventilated animals (n=7) were used as a control for postmortem analysis.Ventilatory and mechanical parameters, arterial blood gases, diffuse alveolar damage score, epithelial integrity measured by E-cadherin tissue expression, and biological markers associated with inflammation (IL-6 and cytokine-induced neutrophil chemoattractant, CINC-1) and type II epithelial cell damage (surfactant protein-B) were evaluated.In both PCV and PSV, peak transpulmonary pressure was lower, whereas E-cadherin tissue expression, which is related to epithelial integrity, was higher at PEEP = 5 cmH2O than at PEEP = 2 cmH2O. In PSV, PEEP = 5 cmH2O compared with PEEP = 2 cmH2O was associated with significantly reduced diffuse alveolar damage score [median (interquartile range), 11 (8.5 to 13.5) vs. 23 (19 to 26), P = 0.005] and expressions of IL-6 and CINC-1 (P = 0.02 for both), whereas surfactant protein-B mRNA expression increased (P = 0.03). These changes suggested less type II epithelial cell damage at a PEEP of 5 cmH2O. Peak transpulmonary pressure correlated positively with IL-6 [Spearman's rho (ρ) = 0.62, P = 0.0007] and CINC-1 expressions (ρ = 0.50, P = 0.01) and negatively with E-cadherin expression (ρ = -0.67, P = 0.0002).During PSV, PEEP of 5 cmH2O, but not a PEEP of 2 cmH2O, reduced lung damage and inflammatory markers while maintaining epithelial cell integrity.

Background Studies in patients receiving invasive ventilation show important differences in use of low tidal volume (VT) ventilation (LTVV) between females and males. The aims of this study were to describe temporal changes in VT and to determine what factors drive the sex difference in use of LTVV. Methods and findings This is a posthoc analysis of 2 large longitudinal projects in 59 ICUs in the United States, the ‘Medical information Mart for Intensive Care III’ (MIMIC III) and the ‘eICU Collaborative Research DataBase’. The proportion of patients under LTVV (median VT < 8 ml/kg PBW), was the primary outcome. Mediation analysis, a method to dissect total effect into direct and indirect effects, was used to understand which factors drive the sex difference. We included 3614 (44%) females and 4593 (56%) males. Median VT declined over the years, but with a persistent difference between females (from median 10.2 (9.1 to 11.4) to 8.2 (7.5 to 9.1) ml/kg PBW) vs. males (from median 9.2 [IQR 8.2 to 10.1] to 7.3 [IQR 6.6 to 8.0] ml/kg PBW) (P < .001). In females versus males, use of LTVV increased from 5 to 50% versus from 12 to 78% (difference, –27% [–29% to –25%]; P < .001). The sex difference was mainly driven by patients’ body height and actual body weight (adjusted average causal mediation effect, –30% [–33% to –27%]; P < .001, and 4 [3% to 4%]; P < .001). Conclusions While LTVV is increasingly used in females and males, females continue to receive LTVV less often than males. The sex difference is mainly driven by patients’ body height and actual body weight, and not necessarily by sex. Use of LTVV in females could improve by paying more attention to a correct calculation of VT, i.e., using the correct body height.

We determined the accuracy of distensibility index of inferior vena cava (dIVC) for evaluation of fluid responsiveness in rats with acute respiratory distress syndrome (ARDS) and validated this index for use in rat models. In protocol 1, E. coli lipopolysaccharide was administered in Wistar rats (n=7). After 24h, animals were mechanically ventilated, and stroke volume (SV) and dIVC quantified after blood drainage and subsequent volume expansion (albumin 20%). A receiver operating characteristic (ROC) curve was plotted to determine the optimal dIVC cutoff. In protocol 2, rats (n=10) were divided into fluid-responders (SV increase >5%) and nonresponders (SV increase