Search

RATIONALE: Noisy ventilation with variable Vt may improve respiratory function in acute lung injury. OBJECTIVES: To determine the impact of noisy ventilation on respiratory function and its biological effects on lung parenchyma compared with conventional protective mechanical ventilation strategies. METHODS: In a porcine surfactant depletion model of lung injury, we randomly combined noisy ventilation with the ARDS Network protocol or the open lung approach (n = 9 per group). MEASUREMENTS AND MAIN RESULTS: Respiratory mechanics, gas exchange, and distribution of pulmonary blood flow were measured at intervals over a 6-hour period. Postmortem, lung tissue was analyzed to determine histological damage, mechanical stress, and inflammation. We found that, at comparable minute ventilation, noisy ventilation (1) improved arterial oxygenation and reduced mean inspiratory peak airway pressure and elastance of the respiratory system compared with the ARDS Network protocol and the open lung approach, (2) redistributed pulmonary blood flow to caudal zones compared with the ARDS Network protocol and to peripheral ones compared with the open lung approach, (3) reduced histological damage in comparison to both protective ventilation strategies, and (4) did not increase lung inflammation or mechanical stress. CONCLUSIONS: Noisy ventilation with variable Vt and fixed respiratory frequency improves respiratory function and reduces histological damage compared with standard protective ventilation strategies. [ABSTRACT FROM AUTHOR]

Background: Pressure ulcers account for a substantial fraction of hospital-acquired pathology, with consequent morbidity and economic cost. Treatments are largely focused on preventing further injury, whereas interventions that facilitate healing remain limited. Intermittent electrical stimulation (IES) increases local blood flow and redistributes pressure from muscle-bone interfaces, thus potentially reducing ulcer progression and facilitating healing., Methods: The Pressure Injury Treatment by Intermittent Electrical Stimulation (PROTECT-2) trial will be a parallel-arm multicenter randomized trial to test the hypothesis that IES combined with routine care reduces sacral and ischial pressure injury over time compared to routine care alone. We plan to enroll 548 patients across various centers. Hospitalized patients with stage 1 or stage 2 sacral or ischial pressure injuries will be randomized to IES and routine care or routine care alone. Wound stage will be followed until death, discharge, or the development of an exclusion criteria for up to 3 months. The primary endpoint will be pressure injury score measured over time., Discussion: Sacral and ischial pressure injuries present a burden to hospitalized patients with both clinical and economic consequences. The PROTECT-2 trial will evaluate whether IES is an effective intervention and thus reduces progression of stage 1 and stage 2 sacral and ischial pressure injuries., Trial Registration: ClinicalTrials.gov NCT05085288 Registered October 20, 2021., (© 2024. The Author(s).)

Background: Pregnancy is associated with an increased risk of pulmonary aspiration during general anaesthesia, but the incidence of this complication is not well defined., Methods: We performed a retrospective database review in a tertiary care university hospital to determine the incidence of pulmonary aspiration in pregnant patients undergoing endotracheal intubation, with and without Rapid Sequence Induction (RSI), as well as face-mask ventilation and supraglottic airway devices. We included Patients in the 2 nd or 3 rd trimester of pregnancy and immediate postpartum undergoing surgical procedures. The primary endpoint was the occurrence of pulmonary aspiration., Results: Data from 2,390 patients undergoing general anaesthesia for cerclage of cervix uteri, manual removal of retained placenta, repair of obstetric laceration, or postpartum bleeding were retrospectively evaluated. A supraglottic airway device or face-mask ventilation was used in 1,425/2,390 (60%) of patients, while 638/2,390 (27%) were intubated. RSI was used in 522/638 (82%) of patients undergoing tracheal intubation, or 522/2,390 (22%) of the entire cohort. In-depth review of the charts, including 54 patients who had been initially classified as "possible pulmonary aspiration" by anaesthetists, revealed that this adverse event did not occur in the cohort., Conclusions: In conclusion, in this obstetric surgery patient population at risk for pulmonary aspiration, supraglottic airway devices were used in approximately 60% of cases. Yet, no aspiration event was detected with either a supraglottic airway or endotracheal intubation., (© 2024. The Author(s).)

Objective: Benefit or harm of higher positive end expiratory pressure (PEEP) for acute respiratory distress syndrome (ARDS) is controversial. We aimed to assess the impact of higher levels of PEEP in patients with ARDS under a Bayesian framework. Design: Systematic review and Bayesian meta-analysis of randomised clinical trials comparing higher to lower PEEP in adult patients with ARDS. Data sources: MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials from 1996 to 1 March 2020. Review methods: We extracted data from high quality randomised clinical trials comparing higher to lower levels of PEEP in adult patients, using low tidal volume in both arms, and conducted a Bayesian meta-analysis using aggregate data from these studies. Results : Eight clinical trials including 3703 patients (n = 1833 for higher PEEP, n = 1870 for lower PEEP) were included. Under a minimally informative prior, the posterior probability of benefit with higher PEEP was 65% (relative risk, 0.97 [95% credible interval, 0.78-1.14]). In patients with moderate-to- severe ARDS, the posterior probability of benefit with higher PEEP was 77% (relative risk, 0.94 [95% credible interval, 0.77-1.13]). Down-weighting studies that employed a maximum recruitment strategy by 100% increased the posterior probability of benefit to 92% under a minimally informative prior. Conclusions: The probability of benefit or harm from routine use of higher PEEP for patients with ARDS ranges from 27% to 86%, and from 14% to 73% depending on one's prior, suggesting continued uncertainty and equipoise regarding the benefit of PEEP If data from trials using a maximum recruitment strategy is discounted to some extent because of uncertainty over the appropriateness of this approach, the available evidence suggests that higher PEEP could be beneficial for moderate-to-severe ARDS. However, well powered randomised clinical trials are needed to confirm these findings., Competing Interests: Ary Serpa Neto has received personal fees from Dräger outside of the submitted work. Marcelo Gama de Abreu has received grants and personal fees from Drägerwerk and GlaxoSmithKline, and personal fees from GE Healthcare outside of the submitted work. Ewan Goligher has received travel reimbursement and speaker honoraria from Getinge outside of the submitted work., (© 2021 College of Intensive Care Medicine of Australia and New Zealand.)

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

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 T  = 6 ml/kg, PEEP = 3 cmH 2 O) for 1 h. Nonventilated animals (n = 4) were used for molecular biology analyses. CF-PSV compared with LF-PSV: (1) decreased the diffuse alveolar damage score (10 [7.8-12] vs. 25 [23-31.5], p = 0.006), mainly due to edema in axial and alveolar parenchyma; (2) increased birefringence for occludin and claudin-4 in lung tissue and expression of zonula-occludens-1 and metalloproteinase-9 in lung. LF compared with CF reduced neutrophil gelatinase-associated lipocalin and interleukin-6 expression in the kidneys in PSV and PCV. In conclusion, CF compared with LF combined with PSV yielded less lung epithelial cell damage in the current model of ALI. However, LF compared with CF resulted in less kidney injury markers, regardless of the ventilatory strategy., (© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

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

Background: Hydroxyethyl starch (HES) solutions are used for volume therapy to treat hypovolemia due to acute blood loss and to maintain hemodynamic stability. This study was requested by the European Medicines Agency (EMA) to provide more evidence on the long-term safety and efficacy of HES solutions in the perioperative setting., Methods: PHOENICS is a randomized, controlled, double-blind, multi-center, multinational phase IV (IIIb) study with two parallel groups to investigate non-inferiority regarding the safety of a 6% HES 130 solution (Volulyte 6%, Fresenius Kabi, Germany) compared with a crystalloid solution (Ionolyte, Fresenius Kabi, Germany) for infusion in patients with acute blood loss during elective abdominal surgery. A total of 2280 eligible patients (male and female patients willing to participate, with expected blood loss ≥ 500 ml, aged > 40 and ≤ 85 years, and ASA Physical status II-III) are randomly assigned to receive either HES or crystalloid solution for the treatment of hypovolemia due to surgery-induced acute blood loss in hospitals in up to 11 European countries. The dosing of investigational products (IP) is individualized to patients' volume needs and guided by a volume algorithm. Patients are treated with IP for maximally 24 h or until the maximum daily dose of 30 ml/kg body weight is reached. The primary endpoint is the treatment group mean difference in the change from the pre-operative baseline value in cystatin-C-based estimated glomerular filtration rate (eGFR), to the eGFR value calculated from the highest cystatin-C level measured during post-operative days 1-3. Further safety and efficacy parameters include, e.g., combined mortality/major post-operative complications until day 90, renal function, coagulation, inflammation, hemodynamic variables, hospital length of stay, major post-operative complications, and 28-day, 90-day, and 1-year mortality., Discussion: The study will provide important information on the long-term safety and efficacy of HES 130/0.4 when administered according to the approved European product information. The results will be relevant for volume therapy of surgical patients., Trial Registration: EudraCT 2016-002162-30 . ClinicalTrials.gov NCT03278548., (© 2022. The Author(s).)

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies., Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality., Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42·4% vs 44·2%; absolute difference -1·69 [-9·58 to 6·11] p=0·67; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5-8] vs 6 [5-8] cm H 2 O; p=0·0011). ICU mortality was higher in MICs than in HICs (30·5% vs 19·9%; p=0·0004; adjusted effect 16·41% [95% CI 9·52-23·52]; p<0·0001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0·80 [95% CI 0·75-0·86]; p<0·0001)., Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status., Funding: No funding., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The aim of this analysis is to determine geo-economic variations in epidemiology, ventilator settings and outcome in patients receiving general anesthesia for surgery., Methods: Posthoc analysis of a worldwide study in 29 countries. Lower and upper middle-income countries (LMIC and UMIC), and high-income countries (HIC) were compared. The coprimary endpoint was the risk for and incidence of postoperative pulmonary complications (PPC); secondary endpoints were intraoperative ventilator settings, intraoperative complications, hospital stay and mortality., Results: Of 9864 patients, 4% originated from LMIC, 11% from UMIC and 85% from HIC. The ARISCAT score was 17.5 [15.0-26.0] in LMIC, 16.0 [3.0-27.0] in UMIC and 15.0 [3.0-26.0] in HIC (P = .003). The incidence of PPC was 9.0% in LMIC, 3.2% in UMIC and 2.5% in HIC (P < .001). Median tidal volume in ml kg - 1 predicted bodyweight (PBW) was 8.6 [7.7-9.7] in LMIC, 8.4 [7.6-9.5] in UMIC and 8.1 [7.2-9.1] in HIC (P < .001). Median positive end-expiratory pressure in cmH 2 O was 3.3 [2.0-5.0]) in LMIC, 4.0 [3.0-5.0] in UMIC and 5.0 [3.0-5.0] in HIC (P < .001). Median driving pressure in cmH 2 O was 14.0 [11.5-18.0] in LMIC, 13.5 [11.0-16.0] in UMIC and 12.0 [10.0-15.0] in HIC (P < .001). Median fraction of inspired oxygen in % was 75 [50-80] in LMIC, 50 [50-63] in UMIC and 53 [45-70] in HIC (P < .001). Intraoperative complications occurred in 25.9% in LMIC, in 18.7% in UMIC and in 37.1% in HIC (P < .001). Hospital mortality was 0.0% in LMIC, 1.3% in UMIC and 0.6% in HIC (P = .009)., Conclusion: The risk for and incidence of PPC is higher in LMIC than in UMIC and HIC. Ventilation management could be improved in LMIC and UMIC., Trial Registration: Clinicaltrials.gov , identifier: NCT01601223., (© 2022. The Author(s).)

Background: It is unknown whether lung-protective ventilation is applied in burn patients and whether they benefit from it. This study aimed to determine ventilation practices in burn intensive care units (ICUs) and investigate the association between lung-protective ventilation and the number of ventilator-free days and alive at day 28 (VFD-28)., Methods: This is an international prospective observational cohort study including adult burn patients requiring mechanical ventilation. Low tidal volume ( V T ) was defined as V T  ≤ 8 mL/kg predicted body weight (PBW). Levels of positive end-expiratory pressure (PEEP) and maximum airway pressures were collected. The association between V T and VFD-28 was analyzed using a competing risk model. Ventilation settings were presented for all patients, focusing on the first day of ventilation. We also compared ventilation settings between patients with and without inhalation trauma., Results: A total of 160 patients from 28 ICUs in 16 countries were included. Low V T was used in 74% of patients, median V T size was 7.3 [interquartile range (IQR) 6.2-8.3] mL/kg PBW and did not differ between patients with and without inhalation trauma ( p  = 0.58). Median VFD-28 was 17 (IQR 0-26), without a difference between ventilation with low or high V T ( p  = 0.98). All patients were ventilated with PEEP levels ≥5 cmH 2 O; 80% of patients had maximum airway pressures <30 cmH 2 O., Conclusion: In this international cohort study we found that lung-protective ventilation is used in the majority of burn patients, irrespective of the presence of inhalation trauma. Use of low V T was not associated with a reduction in VFD-28., Trial Registration: Clinicaltrials.gov NCT02312869. Date of registration: 9 December 2014., (© The Author(s) 2021. Published by Oxford University Press.)

Background: The scientific working group for "Anaesthesia in thoracic surgery" of the German Society of Anaesthesiology and Intensive Care Medicine (DGAI) has performed an online survey to assess the current standards of care and structural properties of anaesthesia workstations in thoracic surgery., Methods: All members of the European Society of Anaesthesiology (ESA) were invited to participate in the study., Results: Thoracic anaesthesia was most commonly performed by specialists/board-certified anaesthetists and/or senior/attending physicians. Across Europe, the double lumen tube (DLT) was most commonly chosen as the primary device for lung separation (461/ 97.3%). Bronchial blockers were chosen less frequently (9/ 1.9%). Throughout Europe, bronchoscopy was not consistently used to confirm correct double lumen tube positioning. Respondents from Eastern Europe (32/ 57.1%) frequently stated that there were not enough bronchoscopes available for every intrathoracic operation. A specific algorithm for difficult airway management in thoracic anaesthesia was available to only 18.6% (n = 88) of the respondents. Thoracic epidural analgesia (TEA) is the most commonly used form of regional analgesia for thoracic surgery in Europe. Ultrasonography was widely available 93,8% (n = 412) throughout Europe and was predominantly used for central line placement and lung diagnostics., Conclusions: While certain "gold standards "are widely met, there are also aspects of care requiring substantial improvement in thoracic anaesthesia throughout Europe. Our data suggest that algorithms and standard operating procedures for difficult airway management in thoracic anaesthesia need to be established. A European recommendation for the basic requirements of an anaesthesia workstation for thoracic anaesthesia is expedient and desirable, to improve structural quality and patient safety., (© 2021. The Author(s).)

Background: We hypothesized that a decrease in frequency of controlled breaths during biphasic positive airway pressure (BIVENT), associated with an increase in spontaneous breaths, whether pressure support (PSV)-assisted or not, would mitigate lung and diaphragm damage in mild experimental acute respiratory distress syndrome (ARDS)., Materials and Methods: Wistar rats received Escherichia coli lipopolysaccharide intratracheally. After 24 hours, animals were randomly assigned to: 1) BIVENT-100+PSV0%: airway pressure (Phigh) adjusted to VT = 6 mL/kg and frequency of controlled breaths (f) = 100 bpm; 2) BIVENT-50+PSV0%: Phigh adjusted to VT = 6 mL/kg and f = 50 bpm; 3) BIVENT-50+PSV50% (PSV set to half the Phigh reference value, i.e., PSV50%); or 4) BIVENT-50+PSV100% (PSV equal to Phigh reference value, i.e., PSV100%). Positive end-expiratory pressure (Plow) was equal to 5 cmH2O. Nonventilated animals were used for lung and diaphragm histology and molecular biology analysis., Results: BIVENT-50+PSV0%, compared to BIVENT-100+PSV0%, reduced the diffuse alveolar damage (DAD) score, the expression of amphiregulin (marker of alveolar stretch) and muscle atrophy F-box (marker of diaphragm atrophy). In BIVENT-50 groups, the increase in PSV (BIVENT-50+PSV50% versus BIVENT-50+PSV100%) yielded better lung mechanics and less alveolar collapse, interstitial edema, cumulative DAD score, as well as gene expressions associated with lung inflammation, epithelial and endothelial cell damage in lung tissue, and muscle ring finger protein 1 (marker of muscle proteolysis) in diaphragm. Transpulmonary peak pressure (Ppeak,L) and pressure-time product per minute (PTPmin) at Phigh were associated with lung damage, while increased spontaneous breathing at Plow did not promote lung injury., Conclusion: In the ARDS model used herein, during BIVENT, the level of PSV and the phase of the respiratory cycle in which the inspiratory effort occurs affected lung and diaphragm damage. Partitioning of inspiratory effort and transpulmonary pressure in spontaneous breaths at Plow and Phigh is required to minimize VILI., Competing Interests: The authors have declared that no competing interests exist.

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., Competing Interests: Ary Serpa Neto reported receiving personal fees from Dräger outside of the submitted work. Marcelo Gama de Abreu reported receiving grants and personal fees from Drägerwerk AG and GlaxoSmithKline and receiving personal fees from GE Healthcare outside of the submitted work. No other disclosures were reported. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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)., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-21-764). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Background: It is uncertain whether the association of the intraoperative driving pressure (ΔP) with postoperative pulmonary complications (PPCs) depends on the surgical approach during abdominal surgery. Our primary objective was to determine and compare the association of time-weighted average ΔP (ΔP TW ) with PPCs. We also tested the association of ΔP TW with intraoperative adverse events., Methods: Posthoc retrospective propensity score-weighted cohort analysis of patients undergoing open or closed abdominal surgery in the 'Local ASsessment of Ventilatory management during General Anaesthesia for Surgery' (LAS VEGAS) study, that included patients in 146 hospitals across 29 countries. The primary endpoint was a composite of PPCs. The secondary endpoint was a composite of intraoperative adverse events., Results: The analysis included 1128 and 906 patients undergoing open or closed abdominal surgery, respectively. The PPC rate was 5%. ΔP was lower in open abdominal surgery patients, but ΔP TW was not different between groups. The association of ΔP TW with PPCs was significant in both groups and had a higher risk ratio in closed compared to open abdominal surgery patients (1.11 [95%CI 1.10 to 1.20], P <  0.001 versus 1.05 [95%CI 1.05 to 1.05], P <  0.001; risk difference 0.05 [95%CI 0.04 to 0.06], P <  0.001). The association of ΔP TW with intraoperative adverse events was also significant in both groups but had higher odds ratio in closed compared to open abdominal surgery patients (1.13 [95%CI 1.12- to 1.14], P <  0.001 versus 1.07 [95%CI 1.05 to 1.10], P <  0.001; risk difference 0.05 [95%CI 0.030.07], P <  0.001)., Conclusions: ΔP is associated with PPC and intraoperative adverse events in abdominal surgery, both in open and closed abdominal surgery., Trial Registration: LAS VEGAS was registered at clinicaltrials.gov (trial identifier NCT01601223 ).

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

Remote imaging photoplethysmography (iPPG) senses the cardiac pulse in outer skin layers and is responsive to mean arterial pressure and pulse pressure in critically ill patients. Whether iPPG is sufficiently sensitive to monitor cutaneous perfusion is not known. This study aimed at determining the response of iPPG to changes in cutaneous perfusion measured by  Laser speckle imaging (LSI). Thirty-seven volunteers were engaged in a cognitive test known to evoke autonomic nervous activity and a Heat test. Simultaneous measurements of iPPG and LSI were taken at baseline and during cutaneous perfusion challenges. A perfusion index (PI) was calculated to assess iPPG signal strength. The response of iPPG to the challenges and its relation to LSI were determined. PI of iPPG significantly increased in response to autonomic nervous stimuli and to the Heat test by 5.8% (p = 0.005) and 11.1% (p < 0.001), respectively. PI was associated with LSI measures of cutaneous perfusion throughout experiments (p < 0.001). iPPG responses to study task correlated with those of LSI (r = 0.62, p < 0.001) and were comparable among subjects. iPPG is sensitive to autonomic nervous activity in volunteers and is closely associated with cutaneous perfusion.

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.

Patients undergoing emergency surgery may present with the acute respiratory distress syndrome (ARDS) or develop this syndrome postoperatively. The incidence of ARDS in the postoperative period is relatively low, but the impact of ARDS on patient outcomes and healthcare costs is relevant Aakre et.al (Mayo Clin Proc 89:181-9, 2014).The development of ARDS as a postoperative pulmonary complication (PPC) is associated with prolonged hospitalisation, longer duration of mechanical ventilation, increased intensive care unit length of stay and high morbidity and mortality Ball et.al (Curr Opin Crit Care 22:379-85, 2016). In order to mitigate the risk of ARDS after surgery, the anaesthetic management and protective mechanical ventilation strategies play an important role. In particular, a careful integration of general anaesthesia with neuraxial or locoregional techniques might promote faster recovery and reduce opioid consumption. In addition, the use of low tidal volume, minimising plateau pressure and titrating a low-moderate PEEP level based on the patient's need can improve outcome and reduce intraoperative adverse events. Moreover, perioperative management of ARDS patients includes specific anaesthesia and ventilator settings, hemodynamic monitoring, moderately restrictive fluid administration and pain control.The aim of this review is to provide an overview and evidence- and opinion-based recommendations concerning the management of patients at risk of and with ARDS who undergo emergency surgical procedures.

Background: Conflicting data have reported beneficial effects of crystalloids, hyper-oncotic albumin (20%ALB), and iso-oncotic albumin (5%ALB) in critically ill patients. Although hyper-oncotic albumin may minimize lung injury, recent studies have shown that human albumin may lead to kidney damage proportional to albumin concentration. In this context, we compared the effects of Ringer's lactate (RL), 20%ALB, and 5%ALB, all titrated according to similar hemodynamic goals, on pulmonary function, lung and kidney histology, and molecular biology in experimental acute lung injury (ALI)., Methods: Male Wistar rats received Escherichia coli lipopolysaccharide intratracheally (n = 24) to induce ALI. After 24 h, animals were anesthetized and randomly assigned to receive RL, 20%ALB, or 5%ALB (n = 6/group) to maintain hemodynamic stability (distensibility index of inferior vena cava < 25%, mean arterial pressure > 65 mmHg). Rats were then mechanically ventilated for 6 h. Six animals, which received neither ventilation nor fluids (NV), were used for molecular biology analyses., Results: The total fluid volume infused was higher in RL compared to 5%ALB and 20%ALB (median [interquartile range], 10.8[8.2-33.2] vs. 4.8[3.6-7.7] and 4.3[3.9-6.6] mL, respectively; p = 0.02 and p = 0.003). B-line counts on lung ultrasound (p < 0.0001 and p = 0.0002) and serum lactate levels (p = 0.01 and p = 0.01) were higher in RL than 5%ALB and 20%ALB. Diffuse alveolar damage score was lower in 5%ALB (10.5[8.5-12]) and 20%ALB (10.5[8.5-14]) than RL (16.5[12.5-20.5]) (p < 0.05 and p = 0.03, respectively), while acute kidney injury score was lower in 5%ALB (9.5[6.5-10]) than 20%ALB (18[15-28.5], p = 0.0006) and RL (16 [15-19], p = 0.04). In lung tissue, mRNA expression of interleukin (IL)-6 was higher in RL (59.1[10.4-129.3]) than in 5%ALB (27.0[7.8-49.7], p = 0.04) or 20%ALB (3.7[7.8-49.7], p = 0.03), and IL-6 protein levels were higher in RL than 5%ALB and 20%ALB (p = 0.026 and p = 0.021, respectively). In kidney tissue, mRNA expression and protein levels of kidney injury molecule (KIM)-1 were lower in 5%ALB than RL and 20%ALB, while nephronectin expression increased (p = 0.01 and p = 0.01), respectively., Conclusions: In a rat model of ALI, both iso-oncotic and hyper-oncotic albumin solutions were associated with less lung injury compared to Ringer's lactate. However, hyper-oncotic albumin resulted in greater kidney damage than iso-oncotic albumin. This experimental study is a step towards future clinical designs.

After publication of the original article [1], the authors have notified us that two of the collaborator first and last names have been inverted in the "PROTHOR Investigators" table.

Background: Perioperative anaemia leads to impaired oxygen supply with a risk of vital organ ischaemia. In healthy and fit individuals, anaemia can be compensated by several mechanisms. Elderly patients, however, have less compensatory mechanisms because of multiple co-morbidities and age-related decline of functional reserves. The purpose of the study is to evaluate whether elderly surgical patients may benefit from a liberal red blood cell (RBC) transfusion strategy compared to a restrictive transfusion strategy., Methods: The LIBERAL Trial is a prospective, randomized, multicentre, controlled clinical phase IV trial randomising 2470 elderly (≥ 70 years) patients undergoing intermediate- or high-risk non-cardiac surgery. Registered patients will be randomised only if Haemoglobin (Hb) reaches ≤9 g/dl during surgery or within 3 days after surgery either to the LIBERAL group (transfusion of a single RBC unit when Hb ≤ 9 g/dl with a target range for the post-transfusion Hb level of 9-10.5 g/dl) or the RESTRICTIVE group (transfusion of a single RBC unit when Hb ≤ 7.5 g/dl with a target range for the post-transfusion Hb level of 7.5-9 g/dl). The intervention per patient will be followed until hospital discharge or up to 30 days after surgery, whichever occurs first. The primary efficacy outcome is defined as a composite of all-cause mortality, acute myocardial infarction, acute ischaemic stroke, acute kidney injury (stage III), acute mesenteric ischaemia and acute peripheral vascular ischaemia within 90 days after surgery. Infections requiring iv antibiotics with re-hospitalisation are assessed as important secondary endpoint. The primary endpoint will be analysed by logistic regression adjusting for age, cancer surgery (y/n), type of surgery (intermediate- or high-risk), and incorporating centres as random effect., Discussion: The LIBERAL-Trial will evaluate whether a liberal transfusion strategy reduces the occurrence of major adverse events after non-cardiac surgery in the geriatric population compared to a restrictive strategy within 90 days after surgery., Trial Registration: ClinicalTrials.gov (identifier: NCT03369210 ).

Background: Mechanical ventilation (MV) is a life-saving technology that restores or assists breathing. Like any treatment, MV has side effects. In some patients it can cause diaphragmatic atrophy, injury, and dysfunction (ventilator-induced diaphragmatic dysfunction, VIDD). Accumulating evidence suggests that VIDD makes weaning from MV difficult, which involves increased morbidity and mortality., Methods and Analysis: This paper describes the protocol of a randomized, controlled, open-label, multicenter trial that is designed to investigate the safety and effectiveness of a novel therapy, temporary transvenous diaphragm pacing (TTVDP), to improve weaning from MV in up to 88 mechanically ventilated adult patients who have failed at least two spontaneous breathing trials over at least 7 days. Patients will be randomized (1:1) to TTVDP (treatment) or standard of care (control) groups. The primary efficacy endpoint is time to successful extubation with no reintubation within 48 h. Secondary endpoints include maximal inspiratory pressure and ultrasound-measured changes in diaphragm thickness and diaphragm thickening fraction over time. In addition, observational data will be collected and analyzed, including 30-day mortality and time to discharge from the intensive care unit and from the hospital. The hypothesis to be tested postulates that more TTVDP patients than control patients will be successfully weaned from MV within the 30 days following randomization., Discussion: This study is the first large-scale clinical trial of a novel technology (TTVDP) aimed at accelerating difficult weaning from MV. The technology tested provides the first therapy directed specifically at VIDD, an important cause of delayed weaning from MV. Its results will help delineate the place of this therapeutic approach in clinical practice and help design future studies aimed at defining the indications and benefits of TTVDP., Trial Registration: ClinicalTrials.gov, NCT03096639 . Registered on 30 March 2017.

Background: Ischemic stroke causes brain inflammation, which we postulate may result in lung damage. Several studies have focused on stroke-induced immunosuppression and lung infection; however, the possibility that strokes may trigger lung inflammation has been overlooked. We hypothesized that even focal ischemic stroke might induce acute systemic and pulmonary inflammation, thus altering respiratory parameters, lung tissue integrity, and alveolar macrophage behavior., Methods: Forty-eight Wistar rats were randomly assigned to ischemic stroke (Stroke) or sham surgery (Sham). Lung function, histology, and inflammation in the lung, brain, bronchoalveolar lavage fluid (BALF), and circulating plasma were evaluated at 24 h. In vitro, alveolar macrophages from naïve rats (unstimulated) were exposed to serum or BALF from Sham or Stroke animals to elucidate possible mechanisms underlying alterations in alveolar macrophage phagocytic capability. Alveolar macrophages and epithelial and endothelial cells of Sham and Stroke animals were also isolated for evaluation of mRNA expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α., Results: Twenty-four hours following ischemic stroke, the tidal volume, expiratory time, and mean inspiratory flow were increased. Compared to Sham animals, the respiratory rate and duty cycle during spontaneous breathing were reduced, but this did not affect lung mechanics during mechanical ventilation. Lungs from Stroke animals showed clear evidence of increased diffuse alveolar damage, pulmonary edema, and inflammation markers. This was associated with an increase in ultrastructural damage, as evidenced by injury to type 2 pneumocytes and endothelial cells, cellular infiltration, and enlarged basement membrane thickness. Protein levels of proinflammatory mediators were documented in the lung, brain, and plasma (TNF-α and IL-6) and in BALF (TNF-α). The phagocytic ability of macrophages was significantly reduced. Unstimulated macrophages isolated from naïve rats only upregulated expression of TNF-α and IL-6 following exposure to serum from Stroke rats. Exposure to BALF from Stroke or Sham animals did not change alveolar macrophage behavior, or gene expression of TNF-α and IL-6. IL-6 expression was increased in macrophages and endothelial cells from Stroke animals., Conclusions: In rats, focal ischemic stroke is associated with brain-lung crosstalk, leading to increased pulmonary damage and inflammation, as well as reduced alveolar macrophage phagocytic capability, which seems to be promoted by systemic inflammation.

Introduction: Robotic-assisted surgery (RAS) has emerged as an alternative minimally invasive surgical option. Despite its growing applicability, the frequent need for pneumoperitoneum and Trendelenburg position could significantly affect respiratory mechanics during RAS. AVATaR is an international multicenter observational study aiming to assess the incidence of postoperative pulmonary complications (PPC), to characterise current practices of mechanical ventilation (MV) and to evaluate a possible association between ventilatory parameters and PPC in patients undergoing RAS., Methods and Analysis: AVATaR is an observational study of surgical patients undergoing MV for general anaesthesia for RAS. The primary outcome is the incidence of PPC during the first five postoperative days. Secondary outcomes include practice of MV, effect of surgical positioning on MV, effect of MV on clinical outcome and intraoperative complications., Ethics and Dissemination: This study was approved by the Institutional Review Board of the Hospital Israelita Albert Einstein. The study results will be published in peer-reviewed journals and disseminated at international conferences., Trial Registration Number: NCT02989415; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In experimental acute respiratory distress syndrome (ARDS), random variation of tidal volumes ( V T ) during volume controlled ventilation improves gas exchange and respiratory system mechanics (so-called stochastic resonance hypothesis). It is unknown whether those positive effects may be further enhanced by periodic V T fluctuation at distinct frequencies, also known as deterministic frequency resonance. We hypothesized that the positive effects of variable ventilation on lung function may be further amplified by periodic V T fluctuation at specific frequencies. In anesthetized and mechanically ventilated pigs, severe ARDS was induced by saline lung lavage and injurious V T (double-hit model). Animals were then randomly assigned to 6 h of protective ventilation with one of four V T patterns: (1) random variation of V T (WN); (2) P 04 , main V T frequency of 0.13 Hz; (3) P 10 , main V T frequency of 0.05 Hz; (4) VCV, conventional non-variable volume controlled ventilation. In groups with variable V T , the coefficient of variation was identical (30%). We assessed lung mechanics and gas exchange, and determined lung histology and inflammation. Compared to VCV, WN, P 04 , and P 10 resulted in lower respiratory system elastance (63 ± 13 cm H 2 < 0.05). Cycle-by-cycle analysis of lung mechanics suggested intertidal recruitment/de-recruitment in P 2 O/L, 48.4 ± 21 cm H 2 O/L, and 45.1 ± 5.9 cm H 2 O/L respectively, P < 0.05 all), but only P 10 improved PaO 2 /F I O 2 after 6 h of ventilation (318 ± 96 vs. 445 ± 110 mm Hg, P < 0.05). Cycle-by-cycle analysis of lung mechanics suggested intertidal recruitment/de-recruitment in P 10 . Lung histologic damage and inflammation did not differ among groups. In this experimental model of severe ARDS, periodic V T fluctuation at a frequency of 0.05 Hz improved oxygenation during variable ventilation, suggesting that deterministic resonance adds further benefit to variable ventilation.

Introduction: Current evidence on epidemiology and outcomes of invasively mechanically ventilated intensive care unit (ICU) patients is predominantly gathered in resource-rich settings. Patient casemix and patterns of critical illnesses, and probably also ventilation practices are likely to be different in resource-limited settings. We aim to investigate the epidemiological characteristics, ventilation practices and clinical outcomes of patients receiving mechanical ventilation in ICUs in Asia., Methods and Analysis: PRoVENT-iMIC (study of PRactice of VENTilation in Middle-Income Countries) is an international multicentre observational study to be undertaken in approximately 60 ICUs in 11 Asian countries. Consecutive patients aged 18 years or older who are receiving invasive ventilation in participating ICUs during a predefined 28-day period are to be enrolled, with a daily follow-up of 7 days. The primary outcome is ventilatory management (including tidal volume expressed as mL/kg predicted body weight and positive end-expiratory pressure expressed as cm H 2 O) during the first 3 days of mechanical ventilation-compared between patients at no risk for acute respiratory distress syndrome (ARDS), patients at risk for ARDS and in patients with ARDS (in case the diagnosis of ARDS can be made on admission). Secondary outcomes include occurrence of pulmonary complications and all-cause ICU mortality., Ethics and Dissemination: PRoVENT-iMIC will be the first international study that prospectively assesses ventilation practices, outcomes and epidemiology of invasively ventilated patients in ICUs in Asia. The results of this large study, to be disseminated through conference presentations and publications in international peer-reviewed journals, are of ultimate importance when designing trials of invasive ventilation in resource-limited ICUs. Access to source data will be made available through national or international anonymised datasets on request and after agreement of the PRoVENT-iMIC steering committee., Trial Registration Number: NCT03188770; Pre-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Tidal volume (V T ) has been considered the main determinant of ventilator-induced lung injury (VILI). Recently, experimental studies have suggested that mechanical power transferred from the ventilator to the lungs is the promoter of VILI. We hypothesized that, as long as mechanical power is kept below a safe threshold, high V T should not be injurious. The present study aimed to investigate the impact of different V T levels and respiratory rates (RR) on lung function, diffuse alveolar damage (DAD), alveolar ultrastructure, and expression of genes related to inflammation [interleukin (IL)-6], alveolar stretch (amphiregulin), epithelial [club cell secretory protein (CC)16] and endothelial [intercellular adhesion molecule (ICAM)-1] cell injury, and extracellular matrix damage [syndecan-1, decorin, and metalloproteinase (MMP)-9] in experimental acute respiratory distress syndrome (ARDS) under low-power mechanical ventilation. Twenty-eight Wistar rats received Escherichia coli lipopolysaccharide intratracheally. After 24 h, 21 animals were randomly assigned to ventilation (2 h) with low mechanical power at three different V T levels ( n = 7/group): (1) V T = 6 mL/kg and RR adjusted to normocapnia; (2) V T = 13 mL/kg; and 3) V T = 22 mL/kg. In the second and third groups, RR was adjusted to yield low mechanical power comparable to that of the first group. Mechanical power was calculated as [(Δ[Formula: see text]/Est, L )/2]× RR (ΔP, L = transpulmonary driving pressure, Est, L = static lung elastance). Seven rats were not mechanically ventilated (NV) and were used for molecular biology analysis. Mechanical power was comparable among groups, while V T gradually increased. ΔP, L and mechanical energy were higher in V T = 22 mL/kg than V T = 6 mL/kg and V T = 13 mL/kg ( p < 0.001 for both). Accordingly, DAD score increased in V T = 22 mL/kg compared to V T = 6 mL/kg and V T = 13 mL/kg [23(18.5-24.75) vs. 16(12-17.75) and 16(13.25-18), p < 0.05, respectively]. V T = 22 mL/kg was associated with higher IL-6, amphiregulin, CC16, MMP-9, and syndecan-1 mRNA expression and lower decorin expression than V T = 6 mL/kg. Multiple linear regression analyses indicated that V T was able to predict changes in IL-6 and CC16, whereas ΔP, L predicted pHa, oxygenation, amphiregulin, and syndecan-1 expression. In the model of ARDS used herein, even at low mechanical power, high V T resulted in VILI. V T control seems to be more important than RR control to mitigate VILI.

Background: The majority of critically ill patients do not suffer from acute respiratory distress syndrome (ARDS). To improve the treatment of these patients, we aimed to identify potentially modifiable factors associated with outcome of these patients., Methods: The PRoVENT was an international, multicenter, prospective cohort study of consecutive patients under invasive mechanical ventilatory support. A predefined secondary analysis was to examine factors associated with mortality. The primary endpoint was all-cause in-hospital mortality., Results: 935 Patients were included. In-hospital mortality was 21%. Compared to patients who died, patients who survived had a lower risk of ARDS according to the 'Lung Injury Prediction Score' and received lower maximum airway pressure (P max ), driving pressure (ΔP), positive end-expiratory pressure, and FiO 2 levels. Tidal volume size was similar between the groups. Higher P max was a potentially modifiable ventilatory variable associated with in-hospital mortality in multivariable analyses. ΔP was not independently associated with in-hospital mortality, but reliable values for ΔP were available for 343 patients only. Non-modifiable factors associated with in-hospital mortality were older age, presence of immunosuppression, higher non-pulmonary sequential organ failure assessment scores, lower pulse oximetry readings, higher heart rates, and functional dependence., Conclusions: Higher P max was independently associated with higher in-hospital mortality in mechanically ventilated critically ill patients under mechanical ventilatory support for reasons other than ARDS. Trial Registration ClinicalTrials.gov (NCT01868321).

Background: Transfusion of blood products and mechanical ventilation with injurious settings are considered risk factors for postoperative lung injury in surgical Patients., Methods: A systematic review and individual patient data meta-analysis was done to determine the independent effects of peri-operative transfusion of blood products, intra-operative tidal volume and airway pressure in adult patients undergoing mechanical ventilation for general surgery, as well as their interactions on the occurrence of postoperative acute respiratory distress syndrome (ARDS). Observational studies and randomized trials were identified by a systematic search of MEDLINE, CINAHL, Web of Science, and CENTRAL and screened for inclusion into a meta-analysis. Individual patient data were obtained from the corresponding authors. Patients were stratified according to whether they received transfusion in the peri-operative period [red blood cell concentrates (RBC) and/or fresh frozen plasma (FFP)], tidal volume size [≤7 mL/kg predicted body weight (PBW), 7-10 and >10 mL/kg PBW] and airway pressure level used during surgery (≤15, 15-20 and >20 cmH 2 O). The primary outcome was development of postoperative ARDS., Results: Seventeen investigations were included (3,659 patients). Postoperative ARDS occurred in 40 (7.2%) patients who received at least one blood product compared to 40 patients (2.5%) who did not [adjusted hazard ratio (HR), 2.32; 95% confidence interval (CI), 1.25-4.33; P=0.008]. Incidence of postoperative ARDS was highest in patients ventilated with tidal volumes of >10 mL/kg PBW and having airway pressures of >20 cmH 2 O receiving both RBC and FFP, and lowest in patients ventilated with tidal volume of ≤7 mL/kg PBW and having airway pressures of ≤15 cmH 2 O with no transfusion. There was a significant interaction between transfusion and airway pressure level (P=0.002) on the risk of postoperative ARDS., Conclusions: Peri-operative transfusion of blood products is associated with an increased risk of postoperative ARDS, which seems more dependent on airway pressure than tidal volume size., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: Quantitative lung computed tomography (CT) provides fundamental information about lung aeration in critically ill patients. We tested a scanning protocol combining reduced number of CT slices and tube current, comparing quantitative analysis and radiation exposure to conventional CT., Methods: In pigs, CT scans were performed during breath hold in a model of lung injury with three different protocols: standard spiral with 180 mAs tube current-time product (Spiral180), sequential with 20-mm distance between slices and either 180 mAs (Sequential180) or 50 mAs (Sequential50). Spiral scans of critically ill patients were collected retrospectively, and subsets of equally spaced slices were extracted. The agreement between CT protocols was assessed with Bland-Altman analysis., Results: In 12 pigs, there was good concordance between the sequential protocols and the spiral scan (all biases ≤1.9%, agreements ≤±6.5%). In Spiral180, Sequential180 and Sequential50, estimated dose exposure was 2.3 (2.1-2.8), 0.21 (0.19-0.26), and 0.09 (0.07-0.10) mSv, respectively (p < 0.001 compared to Spiral180); number of acquired slices was 244 (227-252), 12 (11-13) and 12 (11-13); acquisition time was 7 (6-7), 23 (21-25) and 24 (22-26) s. In 32 critically ill patients, quantitative analysis extrapolated from 1-mm slices interleaved by 20 mm had a good concordance with the analysis performed on the entire spiral scan (all biases <1%, agreements ≤2.2%)., Conclusions: In animal CT data, combining sequential scan and low tube current did not affect significantly the quantitative analysis, with a radiation exposure reduction of 97%, reaching a dose comparable to chest X-ray, but with longer acquisition time. In human CT data, lung aeration analysis could be extrapolated from a subset of thin equally spaced slices.

Lung ischemia-reperfusion injury remains a major complication after lung transplantation. Variable ventilation (VV) has been shown to improve respiratory function and reduce pulmonary histological damage compared to protective volume-controlled ventilation (VCV) in different models of lung injury induced by endotoxin, surfactant depletion by saline lavage, and hydrochloric acid. However, no study has compared the biological impact of VV vs. VCV in lung ischemia-reperfusion injury, which has a complex pathophysiology different from that of other experimental models. Thirty-six animals were randomly assigned to one of two groups: (1) ischemia-reperfusion (IR), in which the left pulmonary hilum was completely occluded and released after 30 min; and (2) Sham, in which animals underwent the same surgical manipulation but without hilar clamping. Immediately after surgery, the left (IR-injured) and right (contralateral) lungs from 6 animals per group were removed, and served as non-ventilated group (NV) for molecular biology analysis. IR and Sham groups were further randomized to one of two ventilation strategies: VCV ( n = 6/group) [tidal volume (V T ) = 6 mL/kg, positive end-expiratory pressure (PEEP) = 2 cmH 2 O, fraction of inspired oxygen (FiO 2 ) = 0.4]; or VV, which was applied on a breath-to-breath basis as a sequence of randomly generated V T values ( n = 1200; mean V T = 6 mL/kg), with a 30% coefficient of variation. After 5 min of ventilation and at the end of a 2-h period (Final), respiratory system mechanics and arterial blood gases were measured. At Final, lungs were removed for histological and molecular biology analyses. Respiratory system elastance and alveolar collapse were lower in VCV than VV (mean ± SD, VCV 3.6 ± 1.3 cmH 2 0/ml and 2.0 ± 0.8 cmH 2 0/ml, p = 0.005; median [interquartile range], VCV 20.4% [7.9-33.1] and VV 5.4% [3.1-8.8], p = 0.04, respectively). In left lungs of IR animals, VCV increased the expression of interleukin-6 and intercellular adhesion molecule-1 compared to NV, with no significant differences between VV and NV. Compared to VCV, VV increased the expression of surfactant protein-D, suggesting protection from type II epithelial cell damage. In conclusion, in this experimental lung ischemia-reperfusion model, VV improved respiratory system elastance and reduced lung damage compared to VCV.

Background: The aim of this investigation was to compare ventilation at different levels of positive end-expiratory pressure (PEEP) with regard to clinical important outcomes of intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) at onset of ventilation., Methods: Meta-analysis of randomized controlled trials (RCTs) comparing a lower level of PEEP with a higher level of PEEP was performed. The primary outcome was in-hospital mortality., Results: Twenty-one RCTs (1393 patients) were eligible. PEEP ranged from 0 to 10 cmH 2 O and from 5 to 30 cmH 2 O in the lower PEEP and the higher PEEP arms of included RCTs, respectively. In-hospital mortality was not different between the two PEEP arms in seven RCTs (risk ratio [RR] 0.87; 95% confidence interval [CI] 0.62-1.21; I 2  = 26%, low quality of evidence [QoE]), as was duration of mechanical ventilation in three RCTs (standardized mean difference [SMD] 0.68; 95% CI -0.24 to 1.61; I 2  = 82%, very low QoE). PaO 2 /FiO 2 was higher in the higher PEEP arms in five RCTs (SMD 0.72; 95% CI 0.10-1.35; I 2  = 86%, very low QoE). Development of ARDS and the occurrence of hypoxemia (2 RCTs) were lower in the higher PEEP arms in four RCTs and two RCTs, respectively (RR 0.43; 95% CI 0.21-0.91; I 2  = 56%, low QoE; RR 0.42; 95%-CI 0.19-0.92; I 2  = 19%, low QoE). There was no association between the level of PEEP and any hemodynamic parameter (four RCTs)., Conclusion: Ventilation with higher levels of PEEP in ICU patients without ARDS at onset of ventilation was not associated with lower in-hospital mortality or shorter duration of ventilation, but with a lower incidence of ARDS and hypoxemia, as well as higher PaO 2 /FiO 2 . These findings should be interpreted with caution, as heterogeneity was moderate to high, the QoE was low to very low, and the available studies prevented us from addressing the effects of moderate levels of PEEP.