Abstract
Background Current incidence and outcome of patients with acute hypoxaemic respiratory failure requiring mechanical ventilation in the intensive care unit (ICU) are unknown, especially for patients not meeting criteria for acute respiratory distress syndrome (ARDS).
Methods An international, multicentre, prospective cohort study of patients presenting with hypoxaemia early in the course of mechanical ventilation, conducted during four consecutive weeks in the winter of 2014 in 459 ICUs from 50 countries (LUNG SAFE). Patients were enrolled with arterial oxygen tension/inspiratory oxygen fraction ratio ≤300 mmHg, new pulmonary infiltrates and need for mechanical ventilation with a positive end-expiratory pressure of ≥5 cmH2O. ICU prevalence, causes of hypoxaemia, hospital survival and factors associated with hospital mortality were measured. Patients with unilateral versus bilateral opacities were compared.
Findings 12 906 critically ill patients received mechanical ventilation and 34.9% with hypoxaemia and new infiltrates were enrolled, separated into ARDS (69.0%), unilateral infiltrate (22.7%) and congestive heart failure (CHF; 8.2%). The global hospital mortality was 38.6%. CHF patients had a mortality comparable to ARDS (44.1% versus 40.4%). Patients with unilateral-infiltrate had lower unadjusted mortality, but similar adjusted mortality compared to those with ARDS. The number of quadrants on chest imaging was associated with an increased risk of death. There was no difference in mortality comparing patients with unilateral-infiltrate and ARDS with only two quadrants involved.
Interpretation More than one-third of patients receiving mechanical ventilation have hypoxaemia and new infiltrates with a hospital mortality of 38.6%. Survival is dependent on the degree of pulmonary involvement whether or not ARDS criteria are reached.
Abstract
Patients with hypoxaemic respiratory failure represent more than one-third of patients requiring mechanical ventilation and their mortality often exceeds 40%. Adjusting for severity, mortality is similar whether it is unilateral or bilateral (as in ARDS). https://bit.ly/2VshdWc
Introduction
Acute hypoxaemic respiratory failure is a leading cause of admission and need for mechanical ventilation in intensive care units (ICU). Studies have usually focused on patients meeting the criteria for acute respiratory distress syndrome (ARDS) [1–3]. There are limited data on hypoxaemic patients who do not fulfil the definition of ARDS [4–6]. A large prospective observational study in Sweden, Denmark and Iceland examined patients with acute respiratory failure (ARF) requiring mechanical ventilation regardless of the level of inspiratory oxygen fraction (FiO2), and found a mortality rate ∼40% with or without ARDS >20 years ago [5].
Hypoxaemic patients without ARDS can have cardiac failure or fluid overload, or only unilateral infiltrates on chest imaging. These patients are excluded from epidemiological studies addressing ARDS, and exploring this population is important. First, the definition of ARDS is subject to variations into clinicians' interpretations such as the relative contribution of heart failure or fluid overload [7], and/or the analysis of chest radiographs for the diagnosis of bilateral pulmonary infiltrates [8–10]. Previous studies have shown that bilateral involvement in community-acquired pneumonia is an independent risk factor for mortality [11, 12]. Understanding the differential impact of unilateral versus bilateral airspace disease is important, because they may overlap with ARDS. In addition, it is essential to determine whether these patients can benefit from lung protective approaches like those used for patients with ARDS [13, 14]. Although the underlying biological mechanisms may differ across these different groups, the symptomatic management of the lungs, e.g. ventilator settings, sedation, proning, could be comparable. Therefore, understanding the behaviour of hypoxaemic “non-ARDS” ventilated patients might optimise the management strategy of these acutely hypoxaemic critically ill patients and may help to better understand the limits of the current ARDS definition.
The Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) is the most recent and largest international prospective cohort of hypoxaemic mechanically ventilated patients with new infiltrates [1]. In a pre-specified analysis, we set out to describe the global burden and compare the different subgroups of hypoxaemic patients with new infiltrates: those who fulfil the criteria for the Berlin definition of ARDS; patients whose failure was entirely explained by cardiac failure or fluid overload as declared by clinicians; and patients with unilateral infiltrate upon chest imaging.
Materials and methods
Study design
LUNG SAFE (ClinicalTrials.gov identifier NCT02010073) was a prospective multicentre observational study conducted in 459 ICUs from 50 different countries. All participating ICUs obtained ethics committee approval and patient consent or ethics committee waiver of consent, depending on local regulations. National coordinators and site investigators were responsible for obtaining ethics committee approval and for ensuring data integrity and validity. Participating centres screened all newly admitted patients for four consecutive winter weeks (February–March 2014 in the northern hemisphere, June–August 2014 in the southern hemisphere). A total of 4499 patients had acute hypoxaemic respiratory failure defined by arterial oxygen tension (PaO2)/FiO2 ratio ≤300 mmHg, new pulmonary infiltrates on chest imaging and requirement of ventilator support with a positive end-expiratory pressure (PEEP) ≥5 cmH2O. The number of quadrants involved (chest radiograph or computed tomography (CT) scan) was reported by clinicians. The detailed methods and design of LUNG SAFE have been described previously [1]; some results of this study have been reported in abstract form [15].
Participants and definitions
Patients were divided into three groups, as follows. 1) ARDS: patients fulfilling the Berlin criteria for ARDS [4]; 2) congestive heart failure (CHF): patients in whom respiratory failure was considered by clinicians to be fully explained by cardiac failure or fluid overload; 3) unilateral-infiltrate: patients fulfilling Berlin definition for ARDS criteria, except that they presented with only unilateral infiltrates on chest imaging.
To ensure homogeneity in the analysis, we kept patients with early onset (first 48 h post-ICU admission) for meeting criteria, not treated with extracorporeal membrane oxygenation (ECMO) in the first 48 h, and not admitted to another ICU for >2 days before being transferred to the participating ICU.
Statistical analyses
Continuous variables are reported as mean±sd or median (interquartile range (IQR)), and categorical variables as n (%). Comparisons of proportions were made using Chi-squared and Fisher exact tests. Three groups were compared (unilateral-infiltrate, ARDS and CHF), and continuous variables were compared using ANOVA or Kruskal–Wallis test, as appropriate. We included geo-economic grouping in multivariable analyses, using the 2016 World Bank country classification [16]. When global comparisons were statistically significant, pairwise comparisons adjusting for multiple testing were performed using the Tukey or Benjamini–Hochberg method.
Prognostic risk factors from prior literature and variables found to be associated in bivariate analysis with a p-value ≤0.20 were entered in stepwise (forward and backward) multivariable logistic regression analyses with significance α levels ≤0.05 for retention.
As basic analysis of chest imaging (quadrants involved) was an important focus, this component was introduced in mortality models either 1) considering bilateral opacities as a dichotomous variable; or 2) considering the number of quadrants involved as an ordinal variable. To better examine the specific impact of bilateral versus unilateral opacities, mortality analyses were repeated restricting the population to patients having two quadrants involved whether they were unilateral (i.e. non-ARDS) or bilateral (i.e. ARDS).
Multicollinearity was evaluated with variance inflation factors for each variable and ruled out if the variance inflation factor was <4 (relatively conservative). The results are shown as odds ratios with 95% confidence intervals. Models' performance was assessed using the Hosmer–Lemeshow goodness-of-fit test statistic. We used a Kaplan–Meier analysis to estimate the likelihood of hospital mortality or invasive ventilation discontinuation within 90 days of onset of ARF.
No statistical power calculation was conducted before the study, and sample size was based on available data. For all numerical variables, outliers were assessed and corrected by contacting site investigators if needed. The remaining outliers were plausible values that were kept in the analysis. No assumptions were made for missing data, and we followed the Strengthening the Reporting of Observational Studies in Epidemiology recommendations [17]. Statistical analyses were done with R (version 3.5.5, http://cran.r-project.org, accessed August 2019). All p-values were two-sided, and values <0.05 were deemed statistically significant. Data are presented unadjusted unless specifically stated. We assumed that patients discharged alive from hospital before 90 days were alive on day 90.
Results
Prevalence and outcomes of hypoxaemic patients under mechanical ventilation
29 144 patients were admitted to participating ICUs during the LUNG SAFE study and 12 906 patients received mechanical ventilation. Among them, 4499 patients (15.5% of the total admissions, and 34.9% of hypoxaemic patients requiring mechanical ventilation) fulfilled our criteria for hypoxaemia. The 4499 patients with acute hypoxaemia under mechanical ventilation represented 0.63 cases per ICU bed over 4 weeks.
3834 (>85%) patients had data available in the first 2 days (figure 1). Patients receiving noninvasive ventilation or under early ECMO are shown in figure 1, but they were not included in the subsequent analysis. Most patients (n=3176; 83%) received invasive ventilation, comprising 2193 (69.0%) who fulfilled all the Berlin criteria for ARDS, 261 (8.2%) with CHF and 722 (22.7%) with only unilateral-infiltrate, of whom 143 (19.8% of the latter group) developed full ARDS criteria (bilateral images) later during their ICU stay. The global hospital mortality of these patients was 38.6%.
Flowchart of the patients screened and included in the analysis. ARDS: acute respiratory distress syndrome; CHF: congestive heart failure; NIV: noninvasive ventilation; ECMO: extracorporeal membrane oxygenation; ICU: intensive care unit.
Patients with CHF
Patients with CHF were older, presented more frequent comorbidities such as diabetes, chronic renal failure or chronic cardiac failure (New York Heart Association class 3 or 4), and less frequently COPD or immunocompromised status compared to patients with ARDS (table 1 and supplementary table E1). Many baseline characteristics were similar to patients with ARDS (Sequential Organ Failure Assessment (SOFA) score, arterial pH, PaO2/FiO2 ratio), but ventilatory parameters indicated lower arterial carbon dioxide tension, PEEP and peak inspiratory pressure (PIP) (tables 1 and 2). They received higher tidal volumes, lower respiratory rates and lower standardised minute ventilation (table 2). Mortality was 44.1%, not different from mortality of patients with ARDS (40.4%). Survivors of CHF had shorter durations of mechanical ventilation, length of stay in the ICU and in the hospital than ARDS (supplementary table E1).
Baseline and outcomes of all patients and separated by population category
Ventilatory management and outcomes by population category
Patients with unilateral-infiltrate
Characteristics
Compared to patients with ARDS, the 722 patients with unilateral-infiltrate had many similar characteristics. COPD was more frequent, but other comorbidities did not differ (table 1 and supplementary table E1). The three main risk factors for hypoxaemia were similar in patients with unilateral-infiltrate and with ARDS, namely pneumonia, gastric aspiration and extrapulmonary sepsis. Aspiration was more frequent in patients in unilateral-infiltrate while pneumonia and extrapulmonary sepsis rates were more prevalent in ARDS.
Patients with unilateral-infiltrate had lower baseline respiratory and systemic illness severity than patients with ARDS, lower SOFA and nonpulmonary SOFA scores, and higher arterial pH, PaO2/FiO2 ratio and lower PIP (table 1). Plateau pressure and driving pressure (reported in only 31.1% of the patients) were lower in patients with unilateral-infiltrate than in ARDS (table 2, supplementary table E1 and figure 2).
Boxplots of respiratory parameters at day 1 according to the population category (unilateral-infiltrate versus acute respiratory distress syndrome (ARDS)). p-values are results of t-test comparisons. Outliers appear as dots. a) Tidal volume; b) positive end-expiratory pressure (PEEP); c) peak inspiratory pressure; d) plateau pressure; e) driving pressure. Data available for 912 (31.2%) patients in d) and e); f) respiratory rate; g) standardised minute ventilation; h) inspiratory oxygen fraction (FiO2). PBW: predicted body weight.
Management
Patients with unilateral-infiltrate received higher tidal volumes, but lower PEEP, FiO2, respiratory rate and standardised minute ventilation than patients with ARDS (table 2 and figure 2).
“Protective” ventilation, defined as receiving tidal volume <8 mL·kg−1 predicted body weight and a plateau pressure <30 cmH2O (when available) was delivered at a similar rate in patients with unilateral-infiltrate and in patients with ARDS (63% versus 67%, p=0.250; supplementary figure E1). The use of adjunctive therapies was low in the whole population, but was higher in patients with ARDS than in unilateral-infiltrate patients (supplementary table E2).
Unadjusted outcomes
Overall, unadjusted ICU and hospital mortality were lower in patients with unilateral-infiltrate than in patients with ARDS (26% versus 35% and 35% versus 40%) (table 2, supplementary table E1 and figure 3a) and patients with unilateral-infiltrate had more invasive-ventilation-free days than patients with ARDS (table 2). In an analysis confined to survivors, ICU stay was shorter in patients with unilateral-infiltrate than in patients with ARDS, but hospital length of stay was similar.
a) Probability of discontinuing mechanical ventilation and of hospital survival in patients with unilateral-infiltrate versus acute respiratory distress syndrome (ARDS); b) probability of discontinuing mechanical ventilation and of hospital survival in patients with two quadrants and unilateral-infiltrate versus two quadrants and ARDS. Solid lines represent the probability of hospital survival and dotted lines represent the probability of mechanical ventilation discontinuation. p-values are the results of log-rank tests.
Impact of the number of quadrants involved (patients without CHF)
Risk factors for death in unilateral-infiltrate and ARDS
Comparison of survivors versus nonsurvivors is shown in supplementary table E3. Multivariable analysis of the factors contributing to outcome in these patients with ARDS or unilateral-infiltrate adjusting on main confounders demonstrated that the presence of bilateral opacities on the chest imaging (i.e. ARDS) was an independent risk factor for death (supplementary table E4). A similar model adjusting on the same confounders using the number of quadrants involved instead of the bilateral opacities characteristics showed that having three or four involved quadrants was significantly associated with a higher risk of hospital mortality. Independent risk factors for mortality included age, immunocompromised status, chronic liver failure, higher extrapulmonary SOFA score, concomitant cardiac failure, medical indication or trauma, location in a middle-income country, higher respiratory rate and peak inspiratory pressure and lower pH. Conversely, higher body mass index, higher PEEP and drug overdose as the cause of respiratory failure were associated with better outcomes (supplementary table E4). The multivariable analysis of factors associated with hospital mortality restricted to patients with unilateral-infiltrate found similar results, although with less significant variables (supplementary table E5).
Patients with infiltrates in only two quadrants of chest radiograph
Out of 1094 patients with two quadrant infiltrates on chest radiography, 172 (16%) had unilateral opacities (unilateral-infiltrate), while 922 (84%) had bilateral opacities (ARDS) (table 3). Unilateral-infiltrate patients had more immunosuppression, gastric aspiration and contusions and less extrapulmonary sepsis, but most of other patients' characteristics, gas exchange variables and ventilator management were identical. The unadjusted mortality rates and other outcomes were similar between groups (figure 3b). In a multivariable analysis adjusting on the same covariates as the model performed for the whole population, the presence of bilateral (versus unilateral) opacities was not associated with mortality (supplementary table E6).
Demographics, illness severity, management and outcomes of patients with unilateral infiltrate and with acute respiratory distress syndrome (ARDS) with two quadrants involved on chest radiography
Development of ARDS in patients presenting initially with unilateral-infiltrate
Of patients with unilateral-infiltrate on day 1 and 2, 143 (20%) subsequently developed ARDS. Patients who developed bilateral infiltrates were more severely ill than patients who never developed ARDS as evidenced by lower PaO2/FiO2 ratio in the first 2 days, higher haemodynamic SOFA score, lower pH and higher PIP. Patients who developed ARDS had similar mortality rates, but longer stays and duration of mechanical ventilation (supplementary table E7). In multivariable analyses adjusting for age, SOFA score, pH and PaO2/FiO2 ratio, only PIP was associated with the evolution towards ARDS (supplementary table E8).
Discussion
The LUNG SAFE study shows that slightly more than a third of patients requiring mechanical ventilation in the participating ICU have PaO2/FiO2 ratio ≤300 mmHg. Patients with CHF receiving mechanical ventilation have a mortality rate comparable to patients with ARDS. Patients with unilateral-infiltrate have lower severity of illness than patients with ARDS and the extent of the infiltrates on the chest imaging is associated with mortality. The outcome of patients with two-quadrant involvement on the chest radiograph is similar whether the distribution is bilateral (i.e. qualifying them for ARDS) or unilateral. Importantly, in patients with unilateral-infiltrate, peak pressure is the only independent risk factor for developing ARDS.
More than 15% of all admissions and more than one-third of patients who received ventilation in this large international observational study display hypoxaemia with new infiltrates. They have a high mortality rate. This condition as a whole has an important impact on healthcare systems worldwide, greater than ARDS alone [1, 18, 19]. While the subgroup with ARDS is well characterised and studied [1, 4], the population not fulfilling ARDS criteria is underappreciated as a clinical entity, and incidence and outcomes have not been often reported to date [5, 6, 20, 21]. The lack of consensual definition and the heterogeneity of this group are potential explanations. In addition, ARDS is considered as an archetypal condition in the critically ill and has dominated the research agenda [22–26].
Few data are available for this category of patients. In a prospective study in Sweden, Denmark, and Iceland, Luhr et al. [5] examined the prevalence and 90-day mortality of ARF, defined as intubation and mechanical ventilation ≥24 h, as well as acute lung injury (ALI) and ARDS based on American–European consensus definition [5]. They did not use any oxygenation criteria for ARF, making comparisons difficult with our data: they included 1231 ARF patients, 287 ALI patients and 221 ARDS patients. 90-day mortality was 41% for all ARF, 42% for ALI and 41% for ARDS. The severity of illness and any chronic disease (except COPD) was more important for mortality and outcome than the definitions of ARDS if the patient was invasively ventilated >24 h (defined as ARF). Vincent et al. [6] reported the results of a sub-study to validate the sequential organ failure assessment score looking at patients having PaO2/FiO2 <200 mmHg and mechanical ventilation. They reported a prevalence of 54% with an ICU mortality of 34%. In the present study the number of quadrants seems to be a strong and noteworthy marker of severity of illness independent of whether it is defined as ARDS. This was an unexpected finding given the low reproducibility of radiographic imaging in intensive care [27]. However, the classification based on the number of quadrants with alveolar consolidation is ultra-simple and may have a better reproducibility than more specific description of the type of infiltrates. This classification was one of the cardinal features of the Lung Injury Score, used for many years [28]. In our study, patients presenting with ARDS and unilateral-infiltrate had quite similar profiles.
Comorbidities and main reasons for hypoxaemia were comparable, although patients with aspiration were more frequent in unilateral injury. Patients with unilateral-infiltrate received slightly higher tidal volumes and lower PEEP than patients with ARDS. After adjustment, a similarly high mortality in patients with unilateral-infiltrate was observed compared to patients with ARDS and the same number of quadrants involved. This suggests that the extent of lung involvement is the predominant factor influencing outcome, rather than the bilateral characteristic. There was a stepwise increase in mortality when the number of quadrants involved increased from two to four, and patients with two quadrants, whether unilateral or bilateral, had the same outcomes. Therefore, a very simple approach using quadrants confirmed previous findings (such as the general impact of unilateral versus bilateral on outcome), but also found an association between the number of quadrants and outcome, which has a biological rationale. The number of quadrants involved may grossly reflect the amount of nonaerated lung. Therefore, the important point raised by our study is not to emphasise the importance of the chest radiograph, but conversely to suggest that it may be debatable to continue keeping the current definition of the need for bilateral infiltrates for defining ARDS.
Regarding the ARDS definition, our data confirm that patients with unilateral-infiltrate are not fundamentally different in terms of poor outcome from patients with ARDS [5]. They also have similar underlying risk factors, comorbidity profiles and are managed similarly. Importantly, peak pressure was the only risk factor for developing secondary ARDS in patients with unilateral-infiltrate. This reinforces the need for a protective ventilation in these patients. The need of subdividing these patients into ARDS and unilateral-infiltrate, at least based on the current clinical criteria, can be re-discussed depending on what is studied. Given the lack of knowledge regarding this condition, unilateral patients might be enrolled in studies of ARDS, perhaps with stratification based on the number of quadrants involved to understand if similar management approaches should be used. The pathophysiology or biological mechanisms differ, but the management may not be so different regarding, for instance, the ventilation of a baby lung. High PIP was the main risk factor for developing ARDS in patients with unilateral-infiltrate. The poor outcomes of this population justify further research.
Physiological studies looking at unilateral versus bilateral injury are needed to understand the impact of ventilator settings. For instance, the respective effects of PEEP or large tidal volumes in the presence of asymmetrical injury is an important question to address. Our data suggest that the same ventilator parameters seem to influence outcome in unilateral or bilateral lung injury. The failure of current clinical criteria to meaningfully subgroup hypoxaemic patients underlines the need to explore alternative classification approaches, including phenotyping based on biological/immunological profiles [29, 30], if specific treatments can be applied according to these phenotypes [31]. In our study, the basic clinical classification of the number of quadrants involved, although probably imperfect, had a strong prognostic value. Re-examining the impact of the number of quadrants may help to determine whether this parameter could be included as a severity criterion in the ARDS definition or for a definition including all hypoxaemic patients.
Patients with CHF receive a different therapeutic management approach compared to other types of respiratory failure. Although data are scarce, mechanical ventilation has always been associated with a poor prognosis [32, 33]. CHF patients had a shorter duration of support but a similar mortality to patients with ARDS, again in line with Luhr et al. [5]. One study compared outcomes of patients with cardiogenic pulmonary oedema to patients with ARDS [34]. In this retrospective study, authors found a four-fold increased risk of hospital mortality for patients with ARDS as compared to patients with cardiogenic pulmonary oedema, but definitions differed from ours (limited to need for mechanical ventilation and a PEEP of ≥5 cmH2O). This population of patients with cardiac failure may need more specific research attention. One could question the accuracy of the clinical classification of CHF by investigators in LUNG SAFE. Differentiating ARDS from pure cardiac failure can be challenging [7, 35, 36], especially since the Berlin definition clearly states that patients could present with ARDS and concomitant heart failure [4]. Patients were classified as CHF in the present study when hypoxaemia was fully explained by cardiac failure or fluid overload per the treating clinician. This analysis reflects clinical practice and the way patients are enrolled in or excluded from clinical trials.
Our study has the limitations of an observational design with the risk of unmeasured confounding factors. Regarding quality of data collection, all numerical variables were checked, outliers were detected and queries to confirm their values were sent to investigators. This ensured quality of our dataset and explains the low numbers of missing data, mostly reflecting lack of clinicians' monitoring of certain variables (e.g. plateau pressure). Both the results of chest radiographs and CT scans were used by clinicians for the diagnosis of ARDS and the number of quadrants, but the images were not systematically validated or reviewed by independent radiologists. For performing the Kaplan–Meier curves, we considered hospital discharge to be equal to outcome at 90 days, which is a simplification. Some epidemiological data suggest that hospital outcome and 90-day mortality are very similar for this population. Patients classified in the CHF group were patients for which the clinicians considered that the respiratory failure was fully explained by cardiac failure or fluid overload. Patients with respiratory infection and concomitant fluid overload were considered in the ARDS or the unilateral-infiltrate groups. It is known that chest radiography appearance can worsen after fluid administration. We do not have this granularity of information as this is the case in all trials in ARDS. In general, we don't have systematic validation of the chest radiograph by independent radiologists.
Conclusion
Mechanically ventilated patients with hypoxaemia and new infiltrate represent a high global burden of illness, affecting one-third of the patients receiving ventilation in the ICU with a mortality close to 40%. Patients with unilateral-infiltrate have a high mortality comparable to patients with ARDS of similar severity. Regarding outcome, the global extent of lung involvement seems more important than the unilateral versus bilateral distribution of the lung opacities. These findings emphasise the need for greater attention to patients with unilateral-infiltrate in future studies.
Supplementary material
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Footnotes
This article has an editorial commentary: https://doi.org/10.1183/13993003.00043-2021
This study is registered as a clinical trial with ClinicalTrials.gov identifier NCT02010073. Requests for data sharing can be submitted to the steering committee of the LUNG SAFE group.
This article has supplementary material available from erj.ersjournals.com
LUNG SAFE Steering Committee: Antonio Pesenti, John G. Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F. McAuley, Marco Ranieri, Gordon Rubenfeld, B. Taylor Thompson, Hermann Wrigge and Arthur S. Slutsky. LUNG SAFE Executive Committee: John G. Laffey, Giacomo Bellani, Tài Pham and Eddy Fan. LUNG SAFE national coordinators: Argentina: Fernando Rios; Australia/New Zealand: Frank Van Haren; Belgium: Thierry Sottiaux and Pieter Depuydt; Bolivia: Fredy S. Lora; Brazil: Luciano Cesar Azevedo; Canada: Eddy Fan; Chile: Guillermo Bugedo; China: Haibo Qiu; Colombia: Marcos Gonzalez; Costa Rica: Juan Silesky; Czech Republic: Vladimir Cerny; Denmark: Jonas Nielsen; Ecuador: Manuel Jibaja; France: Tài Pham; Germany: Hermann Wrigge; Greece: Dimitrios Matamis; Guatemala: Jorge Luis Ranero; India: Pravin Amin; Iran: S.M. Hashemian; Ireland: Kevin Clarkson; Italy: Giacomo Bellani; Japan: Kiyoyasu Kurahashi; Mexico: Asisclo Villagomez; Morocco: Amine Ali Zeggwagh; The Netherlands: Leo M. Heunks; Norway: Jon Henrik Laake; Philippines: Jose Emmanuel Palo; Portugal: Antero do Vale Fernandes; Romania: Dorel Sandesc; Saudi Arabia: Yaasen Arabi; Serbia: Vesna Bumbasierevic; Spain: Nicolas Nin and Jose A. Lorente; Sweden: Anders Larsson; Switzerland: Lise Piquilloud; Tunisia: Fekri Abroug; UK: Daniel F. McAuley and Lia McNamee; Uruguay: Javier Hurtado; USA: Ed Bajwa; Venezuela: Gabriel Démpaire. LUNG SAFE site investigators (by country): Albania: UHC Mother Theresa, Tirana: Hektor Sula and Lordian Nunci; University Hospital Shefqet Ndroqi, Tirana: Alma Cani. Argentina: Clinica de Especialidades, Villa Maria: Alan Zazu; Hospital Julio C. Perrando, Resistencia: Christian Dellera and Carolina S. Insaurralde; Sanatorio Las Lomas, San Isidro, Buenos Aires: Risso V. Alejandro; Sanatorio de La Trinidad San Isidro, San Isidro: Julio Daldin and Mauricio Vinzio; Hospital Español de Mendoza, Godoy Cruz-Mendoza: Ruben O. Fernandez; Hospital del Centenario, Rosario: Luis P. Cardonnet and Lisandro R. Bettini; San Antonio, Gualeguay, Entre Rios: Mariano Carboni Bisso and Emilio M. Osman; Cemic, Buenos Aires: Mariano G. Setten and Pablo Lovazzano; Hospital Universitrario Austral, Pilar: Javier Alvarez and Veronica Villar; Hospital Por + Salud, Pami Dr Cesar Milstein, Buenos Aires: Norberto C. Pozo and Nicolas Grubissich; Sanatorio Anchorena, Buenos Aires: Gustavo A. Plotnikow and Daniela N. Vasquez; Sanatorio de La Trinidad Mitre, Buenos Aires: Santiago Ilutovich and Norberto Tiribelli; Hospital Luis agomaggiore, Mendoza: Ariel Chena and Carlos A. Pellegrini; Hospital Interzonal General de Agudos, San Martín, La Plata: María G. Saenz and Elisa Estenssoro; Hospital Misericordia, Cordoba: Matias Brizuela and Hernan Gianinetto; Sanatorio Juncal, Temperley: Pablo E. Gomez and Valeria I. Cerrato; Hospital D.F. Santojanni, Buenos Aires: Marco G. Bezzi and Silvina A. Borello; Hospital Alejandro Posadas, Buenos Aires: Flavia A. Loiacono and Adriana M. Fernandez. Australia: St Vincent's Hospital, Sydney: Serena Knowles and Claire Reynolds; St George Public Hospital, Kogarah: Deborah M. Inskip and Jennene J. Miller; Westmead Hospital, Westmead: Jing Kong and Christina Whitehead; Flinders Medical Center, Bedford Park: Shailesh Bihari; John Hunter Hospital, Newcastle: Aylin Seven and Amanda Krstevski; Canberra Hospital, Garran: Helen J. Rodgers and Rebecca T. Millar; Calvary Mater Newcastle, Waratah: Toni E. McKenna and Irene M. Bailey; Cabrini Hospital, Melbourne: Gabrielle C. Hanlon; Liverpool Hospital, Liverpool: Anders Aneman and Joan M. Lynch; Coffs Harbour Health Campus, Coffs Harbour: Raman Azad and John Neal; Sir Charles Gairdner Hospital, Nedlands: Paul W. Woods and Brigit L. Roberts; Concord Hospital, Concord: Mark R. Kol and Helen S. Wong. Austria: General Hospital of Vienna/Medical University of Vienna, Vienna: Katharina C. Riss and Thomas Staudinger. Belgium: Cliniques Universitaires St Luc, Université Catholique de Louvain, Brussels: Xavier Wittebole and Caroline Berghe; Center Hospitalier Universitaire DinantGodinne, Yvoir: Pierre A. Bulpa and Alain M. Dive; Acuut Ziekenhuis Sint Augustinus Veurne, Veurne: Rik Verstraete and Herve Lebbinck; Ghent University Hospital, Ghent: Pieter Depuydt and Joris Vermassen; University Hospitals Leuven, Leuven: Philippe Meersseman and Helga Ceunen. Brazil: Hospital Renascentista, Pouso Alegre: Jonas I. Rosa and Daniel O. Beraldo; Vitoria Apart Hospital, Serra: Claudio Piras and Adenilton M. Rampinelli; Hospital Das Clinicas, São Paulo: Antonio P. Nassar, Jr; Hospital Geral Do Grajaù, São Paulo: Sergio Mataloun and Marcelo Moock; Evangelical Hospital, Cachoeiro de Itapemirim/Espírito Santo: Marlus M. Thompson and Claudio H. Gonçalves; Hospital Moinhos de Vento, Porto Alegre: Ana Carolina P. Antônio and Aline Ascoli; Hospital Alvorada Taguatinga, Taguatinga: Rodrigo S. Biondi and Danielle C. Fontenele; Complexo Hospitalar Mngabeira Tarcisio Burity, Joao Pessoa: Danielle Nobrega and Vanessa M. Sales. Brunei: Raja Isteri Pengiran Anak Saleha Hospital, Bandar Seri Begawan: Ahmad Yazid Bin HJ Abul Wahab, Maizatul Ismail and Suresh Shindhe. Canada: Medical-Surgical Intensive Care Unit of St Michael's Hospital, Toronto: John Laffey and Francois Beloncle; St Joseph's Health Center, Toronto: Kyle G. Davies and Rob Cirone; Sunnybrook Health Sciences Center, Toronto: Venika Manoharan and Mehvish Ismail; Toronto Western Hospital, Toronto: Ewan C. Goligher and Mandeep Jassal; Medical Surgical Intensive Care Unit of the Toronto General Hospital, Toronto: Erin Nishikawa and Areej Javeed; Cardiovascular Intensive Care Unit of St Michael's Hospital, Toronto: Gerard Curley and Nuttapol Rittayamai; Cardiovascular Intensive Care Unit of the Toronto General Hospital, Toronto: Matteo Parotto and Niall D. Ferguson; Mount Sinai Hospital, Toronto: Sangeeta Mehta and Jenny Knoll; Trauma-Neuro Intensive Care Unit of St Michael's Hospital, Toronto: Antoine Pronovost and Sergio Canestrini. Chile: Hospital Clínico Pontificia Universidad Católica de Chile, Santiago: Alejandro R. Bruhn and Patricio H. Garcia; Hospital Militar de Santiago, Santiago: Felipe A. Aliaga and Pamela A. Farías; Clinica Davila, Santiago: Jacob S. Yumha; Hospital Guillermo Grant Benavente, Concepcion: Claudia A. Ortiz and Javier E. Salas; Clinica Las Lilas, Santiago: Alejandro A. Saez and Luis D. Vega; Hospital Naval Almirante Nef, Viña del Mar: Eduardo F. Labarca and Felipe T. Martinez; Hospital Luis Tisné Brousse, Penanolen: Nicolás G. Carreño and Pilar Lora. China: Second Affiliated Hospital of Harbin Medical University, Harbin: Haitao Liu; Nanjing Zhong-da Hospital, Southeast University, Nanjing: Haibo Qiu and Ling Liu; First Affiliated Hospital of Anhui Medical University, Hefei: Rui Tang and Xiaoming Luo; Peking University People's Hospital, Beijing: Youzhong An and Huiying Zhao; Fourth Affiliated Hospital of Harbin Medical University, Harbin: Yan Gao and Zhe Zhai; Nanjing Jiangbei People's Hospital Affiliated to Medical School of Southeast University, Nanjing: Zheng L. Ye and Wei Wang; First Affiliated Hospital of Dalian Medical University, Dalian: Wenwen Li and Qingdong Li; Subei People's Hospital of Jiangsu Province, Yanghzou: Ruiqiang Zheng; Jinling Hospital, Nanjing: Wenkui Yu and Juanhong Shen; Urumqi General Hospital, Urumqi: Xinyu Li; Intensive Care Unit, First Affiliated Hospital of Wanna Medical College, Yijishan Hospital, Wuhu: Tao Yu and Weihua Lu; Sichuan Provincial People's Hospital, Chengdu: Ya Q. Wu and Xiao B. Huang; Hainan Province People's Hospital, Haikou: Zhenyang He; People's Hospital of Jiangxi Province, Nanchang: Yuanhua Lu; Qilu Hospital of Shandong University, Jinan: Hui Han and Fan Zhang; Zhejiang Provincial People's Hospital, Hangzhou: Renhua Sun; First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui: Hua X. Wang and Shu H. Qin; Nanjing Municipal Government Hospital, Nanjing: Bao H. Zhu and Jun Zhao; First Hospital of Lanzhou University, Lanzhou: Jian Liu and Bin Li; First Affiliated Hospital of Chongqing University of Medical Science, Chongqing: Jing L. Liu and Fa C. Zhou; Xuzhou Central Hospital, Xuzhou: Qiong J. Li and Xing Y. Zhang; First People's Hospital of Foshan, Foshan: Zhou Li-Xin and Qiang Xin-Hua; First Affiliated Hospital of Guangxi Medical University, Nanning: Liangyan Jiang; Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai: Yuan N. Gao and Xian Y. Zhao; First Hospital of Shanxi Medical University, Taiyuan: Yuan Y. Li and Xiao L. Li; Shandong Provincial Hospital, Jinan: Chunting Wang and Qingchun Yao; Fujian Provincial Hospital, Fuzhou: Rongguo Yu and Kai Chen; Henan Provincial People's Hospital, Zhengzhou: Huanzhang Shao and Bingyu Qin; Second Affiliated Hospital of Kunming Medical University, Kunming City: Qing Q. Huang and Wei H. Zhu; Xiangya Hospital, Central South University, Changsha: Ai Y. Hang and Ma X. Hua; First Affiliated Hospital of Guangzhou Medical University, Guangzhou: Yimin Li and Yonghao Xu; People's Hospital of Hebei Province, Shijiazhuang: Yu D. Di and Long L. Ling; Guangdong General Hospital, Guangzhou: Tie H. Qin and Shou H. Wang; Beijing Tongren Hospital, Beijing: Junping Qin; Jiangsu Province Hospital, Nanjing: Yi Han and Suming Zhou. Colombia: Fundación Valle del Lili, Cali: Monica P. Vargas. Costa Rica: Hospital San Juan De Dios, San Jose: Juan I. Silesky Jimenez, Manuel A. González Rojas, Jaime E. SolisQuesada and Christian M. Ramirez-Alfaro. Czech Republic: University Hospital of Ostrava, Ostrava: Jan Máca and Peter Sklienka. Denmark: Aarhus Universitetshospital, Aarhus: Jakob Gjedsted and Aage Christiansen; Rigshopitalet: Jonas Nielsen. Ecuador: Hospital Militar, Quito: Boris G. Villamagua and Iguel Llano. France: Clinique du Millenaire, Montpellier: Philippe Burtin and Gautier Buzancais; Center Hospitalier, Roanne: Pascal Beuret and Nicolas Pelletier; Center Hospitalier Universitaire d'Angers, Angers: Satar Mortaza and Alain Mercat; Hôpital Marc Jacquet, Melun: Jonathan Chelly and Sébastien Jochmans; Center Hospitalier Universitaire Caen, Caen: Nicolas Terzi and Cédric Daubin; Henri Mondor Hospital, Créteil: Guillaume Carteaux and Nicolas de Prost; Cochin Hospital, Paris: Jean-Daniel Chiche and Fabrice Daviaud; Hôpital Tenon, Paris: Tài Pham and Muriel Fartoukh; CH Mulhouse-Emile Muller, Mulhouse: Guillaume Barberet and Jerome Biehler; Archet 1 University Hospital, Nice: Jean Dellamonica and Denis Doyen; Hopital Sainte Musse, Toulon: Jean-Michel Arnal and Anais Briquet; Hopital Nord–Réanimation des Détresses Respiratoires et Infections Sévères, Marseille: Sami Hraiech and Laurent Papazian; Hôpital Européen Georges Pompidou, Paris: Arnaud Follin; Louis Mourier Hospital, Colombes: Damien Roux and Jonathan Messika; Center Hospitalier de Dax, Dax: Evangelos Kalaitzis; Réanimation Médicale, Groupe Hospitalier Pitié-Salpêtrière, Paris: Laurence Dangers and Alain Combes; Assistance Publique-Hôpitaux de Paris Ambroise Paré, Boulogne-Billancourt: Siu-Ming Au; University Hospital Rouen, Rouen: Gaetan Béduneau and Dorothée Carpentier; Center Hospitalier Universitaire Amiens, Amiens–Salouel: Elie H. Zogheib and Herve Dupont; Center Hospitalier Intercommunal Robert Ballanger, Aulnay-sousBois: Sylvie Ricome and Francesco L. Santoli; Center Hospitalier René Dubos, Pontoise: Sebastien L. Besset; Center Hospitalier Intercommunal Portes de l'Oise, Beaumont-sur-Oise: Philippe Michel and Bruno Gelée; Archet 2 University Hospital, Nice: Pierre-Eric Danin and Bernard Goubaux; Center Hospitalier Pierre Oudot, Bourgoin Jallieu: Philippe J. Crova and Nga T. Phan; Center Hospitalier Dunkerque, Dunkerque: Frantz Berkelmans; Center Hospitalier de Belfort Montbéliard, Belfort: Julio C. Badie and Romain Tapponnier; Center Hospitalier Emile Muller, Mulhouse: Josette Gally and Samy Khebbeb; Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, Strasbourg: Jean-Etienne Herbrecht and Francis Schneider; Center Hospitalier de Dieppe, Dieppe: PierreLouis M. Declercq and Jean-Philippe Rigaud; Bicetre, Le Kremin–Bicetre: Jacques Duranteau and Anatole Harrois; Center Hospitalier Universitaire Gabriel Montpied, Clermont-Ferrand: Russell Chabanne and Julien Marin; Center Hospitalier Universitaire Estaing, Clermont-Ferrand: Charlene Bigot and Sandrine Thibault; Center Hospitalier Intercommunal Eure-Seine Evreux, Evreux: Mohammed Ghazi and Messabi Boukhazna; Center Hospitalier de Châlons en Champagne, Châlons en Champagne: Salem Ould Zein; CH Beauvais, Beauvais: Jack R. Richecoeur and Daniele M. Combaux; Center Hospitalier Le Mans, Le Mans: Fabien Grelon and Charlene Le Moal; Hôpital Fleyriat, Bourg-en-Bresse: Elise P. Sauvadet and Adrien Robine; Hôpital Saint Louis, Paris: Virginie Lemiale and Danielle Reuter; Service de Pneumologie Pitié-Salpétrière, Paris: Martin Dres and Alexandre Demoule; Center Hospitalier Gonesse, Gonesse: Dany Goldgran-Toledano; Hôpital Croix Rousse, Lyon: Loredana Baboi and Claude Guérin. Germany: St Nikolaus-Stiftshospital, Andernach: Ralph Lohner; Fachkrankenhaus Coswig Gmbh, Coswig: Jens Kraßler and Susanne Schäfer; University Hospital Frankfurt, Frankfurt am Main: Kai D. Zacharowski and Patrick Meybohm; Department of Anesthesia and Intensive Care Medicine, University Hospital of Leipzig, Leipzig: Andreas W. Reske and Philipp Simon; Asklepios Klinik Langen, Langen: HansBernd F. Hopf and Michael Schuetz; Städtisches Krankenhaus Heinsberg, Heinsberg: Thomas Baltus. Greece: Hippokrateion General Hospital of Athens, Athens: Metaxia N. Papanikolaou and Theonymfi G. Papavasilopoulou; Gh Ahepa, Thessaloniki: Giannis A. Zacharas and Vasilis Ourailogloy; Hippokration General Hospital of Thessaloniki, Thessaloniki: Eleni K. Mouloudi and Eleni V. Massa; Hospital General of Kavala, Kavala: Eva O. Nagy and Electra E. Stamou; Papageorgiou General Hospital, Thessaloniki: Ellada V. Kiourtzieva and Marina A. Oikonomou. Guatemala: Hospital General de Enfermedades, Instituto Guatemalteco de Seguridad Social, Ciudad de Guatemala: Luis E. Avila; Centro Médico Militar, Guatemala: Cesar A. Cortez and Johanna E. Citalán. India: Deenanath Mangeshkar Hospital and Research Center, Pune: Sameer A. Jog and Safal D. Sable; Care Institute of Medical Sciences Hospital, Ahmedabad: Bhagyesh Shah; Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow: Mohan Gurjar and Arvind K. Baronia; Rajasthan Hospital, Ahmedabad: Mohammedfaruk Memon; National Institute of Mental Health and Neuro Sciences, Bangalore: Radhakrishnan Muthuchellappan and Venkatapura J. Ramesh; Anesthesiology Unit of the Kasturba Medical College and Department of Respiratory Therapy, School of Allied Health Sciences, Manipal University, Manipal: Anitha Shenoy and Ramesh Unnikrishnan; Sanjeevan Hospital, Pune: Subhal B. Dixit and Rachana V. Rhayakar; Apollo Hospitals, Chennai: Nagarajan Ramakrishnan and Vallish K. Bhardwaj; Medicine Unit of the Kasturba Medical College and Department of Respiratory Therapy, School of Allied Health Sciences, Manipal University, Manipal: Heera L. Mahto and Sudha V. Sagar; G. Kuppuswamy Naidu Memorial Hospital, Coimbatore: Vijayanand Palaniswamy and Deeban Ganesan. Iran: National Research Institute of Tuberculosis and Lung Disease/Masih Daneshvari, Tehran: Seyed Mohammadreza Hashemian and Hamidreza Jamaati; Milad Hospital, Tehran: Farshad Heidari. Ireland: St Vincent's University Hospital, Dublin: Edel A. Meaney and Alistair Nichol; Mercy University Hospital, Cork: Karl M. Knapman and Donall O'Croinin; Cork University Hospital, Cork: Eimhin S. Dunne and Dorothy M. Breen; Galway University Hospital, Galway: Kevin P. Clarkson and Rola F. Jaafar; Beaumont Hospital, Dublin: Rory Dwyer and Fahd Amir; Mater Misericordiae University Hospital, Dublin: Olaitan O. Ajetunmobi and Aogan C. O'Muircheartaigh; Tallaght Hospital, Dublin: Colin S. Black and Nuala Treanor; Saint James's Hospital, Dublin: Daniel V. Collins and Wahid Altaf. Italy: Santa Maria delle Croci Hospital, Ravenna: Gianluca Zani and Maurizio Fusari; Arcispedale Sant'Anna Ferrara, Ferrara: Savino Spadaro and Carlo A. Volta; Ospedale Profili, Fabriano, Ancona: Romano Graziani and Barbara Brunettini; Umberto I. Nocera Inferiore, Nocera Inferiore Salerno: Salvatore Palmese; Azienda Ospedaliera San Paolo–Polo Universitario–Università degli Studi di Milano, Milan: Paolo Formenti and Michele Umbrello; Sant'Anna, San Fermo Della Battaglia, Como: Andrea Lombardo; Spedali Civili Brescia, Brescia: Elisabetta Pecci and Marco Botteri; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca Granda, Ospedale Maggiore Policlinico, Milan: Monica Savioli and Alessandro Protti; University Campus Bio-Medico of Rome, Rome: Alessia Mattei and Lorenzo Schiavoni; Azienda Ospedaliera “Mellino Mellini”, Chiari, Brescia: Andrea Tinnirello and Manuel Todeschini; Policlinico P. Giaccone, University of Palermo, Palermo: Antonino Giarratano and Andrea Cortegiani; Niguarda Cà Granda Hospital, Milan: Sara Sher and Anna Rossi; A. Gemelli University Hospital, Rome: Massimo M. Antonelli and Luca M. Montini; Ospedale “Sandro Pertini”, Rome: Paolo Casalena and Sergio Scafetti; Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione; Istituto Di Ricovero e Cura a Carattere Scientifico; University of Pittsburgh Medical Center, Palermo: Giovanna Panarello and Giovanna Occhipinti; Ospedale San Gerardo, Monza: Nicolò Patroniti and Matteo Pozzi; Santa Maria Della Scaletta, Imola: Roberto R. Biscione and Michela M. Poli; Humanitas Research Hospital, Rozzano: Ferdinando Raimondi and Daniela Albiero; Ospedale Desio-Ao Desio-Vimercate, Desio: Giulia Crapelli and Eduardo Beck; Pinetagrande Private Hospital, Castelvolturno: Vincenzo Pota and Vincenzo Schiavone; Istituto di Ricovero e Cura a Carattere Scientifico San Martino Ist, Genova: Alexandre Molin and Fabio Tarantino; Ospedale San Raffaele, Milano: Giacomo Monti and Elena Frati; Ospedali Riuniti Di Foggia, Foggia: Lucia Mirabella and Gilda Cinnella; Azienda Ospedaliera Luigi Sacco–Polo Universitario, Milano: Tommaso Fossali and Riccardo Colombo; Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Turin: Pierpaolo Terragni and Ilaria Pattarino; Università degli Studi di Pavia-Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia: Francesco Mojoli and Antonio Braschi; Ao Ospedale Civile Legnano, Legnano: Erika E. Borotto; Arnas Ospedale Civico Di Cristina Benfratelli, Palermo: Andrea N. Cracchiolo and Daniela M. Palma; Azienda Ospedaliera Della Provincia Di Lecco–Ospedale “A. Manzoni”, Lecco: Francesco Raponi and Giuseppe Foti; A.O. Provincia Di Lecco–Ospedale Alessandro Manzoni, Lecco: Ettore R. Vascotto and Andrea Coppadoro; Cliniche Universitarie Sassari, Sassari: Luca Brazzi and Leda Floris; Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia: Giorgio A. Iotti and Aaron Venti. Japan: Yokohama City University Hospital, Yokohama: Osamu Yamaguchi and Shunsuke Takagi; Toyooka Hospital, Toyooka City: Hiroki N. Maeyama; Chiba University Hospital, Chiba City: Eizo Watanabe and Yoshihiro Yamaji; Okayma University Hospital, Okayama: Kazuyoshi Shimizu and Kyoko Shiozaki; Japanese Foundation for Cancer Research, Cancer Institute Hospital, Department of Emergency Medicine and Critical Care, Tokyo: Satoru Futami; Ibaraki Prefectural Central Hospital, Kasama: Sekine Ryosuke; Tohoku University Hospital, Sendai-Shi: Koji Saito and Yoshinobu Kameyama; Tokyo Medical University Hachioji Medical Center, Hachioji, Tokyo: Keiko Ueno; Tokushima University Hospital, Tokushima: Masayo Izawa and Nao Okuda; Maebashi Red Cross Hospital, Gunma Maebashi: Hiroyuki Suzuki and Tomofumi Harasawa; Urasoe General Hospital, Urasoe: Michitaka Nasu and Tadaaki Takada; Ohta General Hospital Foundation Ohta Nishinouchi Hospital, Fukushima: Fumihito Ito; Jichi Medical University Hospital, Shimotsuke: Shin Nunomiya and Kansuke Koyama; Mito Kyodo General Hospital, Tsukuba University Hospital Mito Medical Center, Mito: Toshikazu Abe; Sendai City Hospital, Sendai: Kohkichi Andoh and Kohei Kusumoto; Ja Hiroshima General Hospital, Hatsukaichi City, Hiroshima: Akira Hirata and Akihiro Takaba; Yokohama Rosai Hospital, Yokohama: Hiroyasu Kimura; Nagasaki University Hospital, Nagasaki: Shuhei Matsumoto and Ushio Higashijima; Niigata University Medical and Dental Hospital, Niigata: Hiroyuki Honda and Nobumasa Aoki; Mie University Hospital, Tsu, Mie: Hiroshi Imai; Yamaguchi University Hospital, Ube, Yamaguchi: Yasuaki Ogino and Ichiko Mizuguchi; Saiseikai Kumamoto Hospital, Kumamoto City: Kazuya Ichikado; Shinshu University School of Medicine, Matsumoto City: Kenichi Nitta and Katsunori Mochizuki; Kuki General Hospital, Kuki: Tomoaki Hashida; Kyoto Medical Center, Kyoto: Hiroyuki Tanaka; Fujita Health University, Toyoake: Tomoyuki Nakamura and Daisuke Niimi; Rakwakai Marutamachi Hospital, Kyoto: Takeshi Ueda; Osaka University Hospital, Suita City, Osaka Prefecture: Yozo Kashiwa and Akinori Uchiyama. Latvia: Paul Stradins Clinical University Hospital, Riga: Olegs Sabelnikovs and Peteris Oss. Lebanon: Kortbawi Hospital, Jounieh: Youssef Haddad. Malaysia: Hospital Kapit, Kapit: Kong Y. Liew. Mexico: Instituto Nacional de Cancerología, Mexico City: Silvio A. Ñamendys-Silva and Yves D. Jarquin-Badiola; Hospital de Especialidades “Antonio Fraga Mouret” Centro Medico Nacional La Raza Instituto Mexicano del Seguro Social, Mexico City: Luis A. Sanchez-Hurtado and Saira S. Gomez-Flores; Hospital Regional 1° de Octubre, Mexico City: Maria C. Marin and Asisclo J. Villagomez; Hospital General Dr. Manuel Gea Gonzalez, Mexico City: Jordana S. Lemus and Jonathan M. Fierro; Hospital General de Zona No. 1 Instituto Mexicano del Seguro Social Tepic Nayarit, Tepic: Mavy Ramirez Cervantes and Francisco Javier Flores Mejia; Centro Medico Dalinde, Mexico City: Dulce Dector and Alejandro Rojas; Opd Hospital Civil de Guadalajara Hospital Juan I. Menchaca, Guadalajara: Daniel R. Gonzalez and Claudia R. Estrella; Hospital Regional de Ciudad Madero Pemex, Ciudad Madero: Jorge R. Sanchez-Medina and Alvaro Ramirez-Gutierrez; Centro Médico American British Cowdray, Mexico City: Fernando G. George and Janet S. Aguirre; Hospital Juarez de Mexico, Mexico City: Juan A. Buensuseso and Manuel Poblano. Morocco: Mohammed V University, University Teaching Ibn Sina Hospital, Rabat: Tarek Dendane and Amine Ali Zeggwagh; Hopital Militaire D'Instruction Mohammed V, Rabat: Hicham Balkhi; Errazi, Marrakech: Mina Elkhayari and Nacer Samkaoui; University Teaching Hospital Ibn Rushd, Casablanca: Hanane Ezzouine and Abdellatif Benslama; Hôpital des Spécialités de Rabat, Rabat: Mourad Amor and Wajdi Maazouzi. The Netherlands: Tjongerschans, Heerenveen: Nedim Cimic and Oliver Beck; Cwz, Nijmegen: Monique M. Bruns and Jeroen A. Schouten; Rijnstate Hospital, Arnhem: Myra Rinia and Monique Raaijmakers; Radboud Umc, Nijmegen: Leo M. Heunks and Hellen M. Van Wezel; Maastricht University Medical Center, Maastricht: Serge J. Heines and Ulrich Strauch; Catharinaziekenhuis, Eindhoven: Marc P. Buise; Academic Medical Center, Amsterdam: Fabienne D. Simonis and Marcus J. Schultz. New Zealand: Tauranga Hospital, Tauranga: Jennifer C. Goodson and Troy S. Browne; Wellington Hospital, Wellington: Leanlove Navarra and Anna Hunt; Dunedin Hospital, Dunedin: Robyn A. Hutchison and Mathew B. Bailey; Auckland City Hospital, Auckland: Lynette Newby and Colin McArthur; Whangarei Base Hospital, Whangarei: Michael Kalkoff and Alex Mcleod; North Shore Hospital, Auckland: Jonathan Casement and Danielle J. Hacking. Norway: Ålesund Hospital, Ålesund: Finn H. Andersen and Merete S. Dolva; Oslo University Hospital, Rikshospitalet Medical Center, Oslo: Jon H. Laake and Andreas Barratt-Due; Stavanger University Hospital, Stavanger: Kim Andre L. Noremark and Eldar Søreide; Haukeland University Hospital, Bergen: Brit Å. Sjøbø and Anne B. Guttormsen. Peru: Hospital Nacional Edgardo Rebagliati Martins, Lima: Hector H. Leon Yoshido; Clínica Ricardo Palma, Lima: Ronald Zumaran Aguilar and Fredy A. Montes Oscanoa. Philippines: The Medical City, Pasig: Alain U. Alisasis and Joanne B. Robles; Chong Hua Hospital, Cebu: Rossini Abbie B. Pasanting-Lim and Beatriz C. Tan. Poland: Warsaw University Hospital, Warsaw: Pawel Andruszkiewicz and Karina Jakubowska. Portugal: Centro Hospitalar Da Cova Da Beira, Covilhã: Cristina M. Coxo; Hospital Santa Maria, Chln, Lisboa: António M. Alvarez and Bruno S. Oliveira; Centro Hospitalar Trás-Os-Montes E. Alto Douro, Hospital de S. Pedro-Vila Real, Vila Real: Gustavo M. Montanha and Nelson C. Barros; Hospital Beatriz Ângelo, Loures: Carlos S. Pereira and António M. Messias; Hospital de Santa Maria, Lisboa: Jorge M. Monteiro; Centro Hospitalar Médio Tejo–Hospital de Abrantes, Abrantes: Ana M. Araujo and Nuno T. Catorze; Instituto Português de Oncologia de Lisboa, Lisboa: Susan M. Marum and Maria J. Bouw; Hospital Garcia de Orta, Almada: Rui M. Gomes and Vania A. Brito; Centro Hospitalar Do Algarve, Faro: Silvia Castro and Joana M. Estilita; Hospital de Cascais, Alcabideche: Filipa M. Barros; Hospital Prof. Doutor Fernando Fonseca Epe, Amadora: Isabel M. Serra and Aurelia M. Martinho. Romania: Fundeni Clinical Institute, Bucharest: Dana R. Tomescu and Alexandra Marcu; Emergency Clinical County Hospital Timisoara, Timisoara: Ovidiu H. Bedreag and Marius Papurica; Elias University Emergency Hospital, Bucharest: Dan E. Corneci and Silvius Ioan Negoita. Russian Federation: University Hospital, Kemerovo: Evgeny Grigoriev; Krasnoyarsk Regional Hospital, Krasnoyarsk State Medical University, Krasnoyarsk: Alexey I. Gritsan and Andrey A. Gazenkampf. Saudi Arabia: General Intensive Care Unit of Prince Sultan Military Medical City, Riyadh: Ghaleb Almekhlafi and Mohamad M. Albarrak; Surgical Intensive Care Unit of Prince Sultan Military Medical City, Riyadh: Ghanem M. Mustafa; King Faisal Hospital and Research Center, Riyadh: Khalid A. Maghrabi and Nawal Salahuddin; King Fahad Hospital, Baha: Tharwat M. Aisa; Neuro Critical Care Unit, King Abdulaziz Medical City, Riyadh: Ahmed S. Al Jabbary and Edgardo Tabhan; Intensive Care Unit, King Abdulaziz Medical City, Riyadh: Yaseen M. Arabi; Surgical Intensive Care Unit, King Abdulaziz Medical City, Riyadh: Yaseen M. Arabi and Olivia A. Trinidad; Trauma Intensive Care Unit, King Abdulaziz Medical City, Riyadh: Hasan M. Al Dorzi and Edgardo E. Tabhan. Serbia: Clinical Center of Serbia, Belgrade: Vesna Bumbasirevic and Bojan Jovanovic. South Africa: Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg: Stefan Bolon and Oliver Smith. Spain: Hospital Sant Pau, Barcelona: Jordi Mancebo and Hernan Aguirre-Bermeo; Hospital Universitari Bellvitge, L'Hospitalet de Llobregat, Barcelona: Juan C. Lopez-Delgado and Francisco Esteve; Hospital Son Llatzer, Palma de Mallorca: Gemma Rialp and Catalina Forteza; Sabadell Hospital, Centro de Investigación Biomédica en Red Enfermedades Respiratorias, Sabadell: Candelaria De Haro and Antonio Artigas; Hospital Universitario Central de Asturias, Oviedo: Guillermo M. Albaiceta and Sara De Cima-Iglesias; Complejo Hospitalario Universitario A Coruña, A Coruña: Leticia Seoane-Quiroga and Alexandra Ceniceros-Barros; Hospital Universitario Miguel Servet, Zaragoza: Antonio L. RuizAguilar and Luis M. Claraco-Vega; Morales Meseguer University Hospital, Murcia: Juan Alfonso Soler and Maria del Carmen Lorente; Hospital Universitario del Henares, Coslada: Cecilia Hermosa and Federico Gordo; Complejo Asistencial de Palencia, Hospital Rio Carrión, Palencia: Miryam PrietoGonzález and Juan B. López-Messa; Fundación Jiménez Díaz, Madrid: Manuel P. Perez and Cesar P. Perez; Hospital Clínico Universitario Lozano Blesa, Zaragoza: Raquel Montoiro Allue; Hospital Verge de la Cinta, Tortosa: Ferran RocheCampo and Marcos Ibañez-Santacruz; Hospital Universitario 12 de Octubre, Madrid: Susana Temprano; Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid: Maria C. Pintado and Raul De Pablo; Hospital Universitari Germans Trias I Pujol, Badalona: Pilar Ricart Aroa Gómez; Hospital Universitario Arnau de Vilanova de Lleida, Lleida: Silvia Rodriguez Ruiz and Silvia Iglesias Moles; Cst Terrassa, Barcelona: Mª Teresa Jurado and Alfons Arizmendi; Hospital Universitari Mútua Terrassa, Terrassa: Enrique A. Piacentini; Hospital Universitario de Móstoles, Mostoles: Nieves Franco and Teresa Honrubia; Complejo Asistencial de Salamanca, Salamanca: Meisy Perez Cheng and Elena Perez Losada; Hospital General Universitario de Ciudad Real, Ciudad Real: Javier Blanco and Luis J. Yuste; Torrecardenas, Almeria: Cecilia Carbayo-Gorriz and Francisca G. Cazorla-Barranquero; Hospital Universitario Donostia, San Sebastian: Javier G. Alonso and Rosa S. Alda; Hospital Universitario de Torrejón, Madrid: Ángela Algaba and Gonzalo Navarro; Hospital Universitario de La Princesa, Madrid: Enrique Cereijo and Esther Diaz-Rodriguez; Hospital Universitario Lucus Augusti, Lugo: Diego Pastor Marcos and Laura Alvarez Montero; Hospital Universitario Santa Lucia, Cartagena: Luis Herrera Para and Roberto Jimenez Sanchez; Hospital Universitario Severo Ochoa, Leganes, Madrid: Miguel Angel Blasco Navalpotro and Ricardo Diaz Abad; University Hospital of Nuestra Señora de Candelaria, Santa Cruz de Tenerife: Raquel Montiel González and Dácil Parrilla Toribio; Hospital Universitario Marques de Valdecilla, Santander: Alejandro G. Castro and Maria Jose D. Artiga; Hospital Infanta Cristina, Parla, Madrid: Oscar Penuelas; Hospital General de Catalunya, Sant Cugat del Valles: Tomas P. Roser and Moreno F. Olga; San Pedro de Alcántara, Cáceres: Elena Gallego Curto and Rocío Manzano Sánchez; Sant Joan de Reus, Reus: Vallverdu P. Imma and Garcia M. Elisabet; Hospital Joan XXIII, Tarragona: Laura Claverias and Monica Magret; Hospital Universitario de Getafe, Madrid: Ana M. Pellicer and Lucia L. Rodriguez; Hospital Universitario Río Hortega, Valladolid: Jesús Sánchez-Ballesteros and Ángela González-Salamanca; Hospital Arquitecto Marcide, Ferrol, La Coruña: Antonio G. Jimenez and Francisco P. Huerta; Hospital General Universitario Gregorio Marañón, Madrid: Juan Carlos J. Sotillo Diaz and Esther Bermejo Lopez; Hospital General de Segovia, Segovia: David D. Llinares Moya and Alec A. Tallet Alfonso; Hospital General Universitario Reina Sofia, Murcia: Palazon Sanchez Eugenio Luis and Palazon Sanchez Cesar; Complejo Hospitalario Universitario de Albacete, Albacete: Sánchez I. Rafael and Corcoles G. Virgilio; Hospital Infanta Elena, Valdemoro: Noelia N. Recio. Sweden: Sahlgrenska University Hospital, Gothenburg: Richard O. Adamsson and Christian C. Rylander; Karolinska University Hospital, Stockholm: Bernhard Holzgraefe and Lars M. Broman; Akademiska Sjukhuset Uppsala, Uppsala: Joanna Wessbergh and Linnea Persson; Vrinnevisjukhuset, Norrköping: Fredrik Schiöler and Hans Kedelv; Linkoping University Hospital, Linköping: Anna Oscarsson Tibblin and Henrik Appelberg; Skellefteå Lasarett, Skellefteå: Lars Hedlund and Johan Helleberg; Karolinska University Hospital Solna, Stockholm: Karin E. Eriksson and Rita Glietsch; Umeå University Hospital, Umeå: Niklas Larsson and Ingela Nygren; Danderyd Hospital, Stockholm: Silvia L. Nunes and Anna-Karin Morin; Lund University Hospital, Lund: Thomas Kander and Anne Adolfsson. Switzerland: Centre Hospitalier Universitaire Vaudois, Lausanne: Lise Piquilloud; Hôpital Neuchâtelois–La Chaux de-Fonds, La Chaux-de-Fonds: Hervé O. Zender and Corinne Leemann-Refondini. Tunisia: Hopital Taher Sfar Mahdia, Mahdia: Souheil Elatrous; University Hospital Farhat Hached Sousse, Sousse: Slaheddine Bouchoucha and Imed Chouchene; Center Hospitalier Universitaire F. Bourguiba, Monastir: Islem Ouanes; Mongi Slim University Hospital, La Marsa: Asma Ben Souissi and Salma Kamoun. Turkey: Cerrahpasa Medical Faculty Emergency Intensive Care Unit, Istanbul: Oktay Demirkiran; Cerrahpasa Medical Faculty Sadi Sun Intensive Care Unit, Istanbul: Mustafa Aker and Emre Erbabacan; Uludag University Medical Faculty, Bursa: Ilkay Ceylan and Nermin Kelebek Girgin; Ankara University Faculty of Medicine, Reanimation 3rd Level Intensive Care Unit, Ankara: Menekse Ozcelik and Necmettin Ünal; Ankara University Faculty of Medicine, 2nd Level Intensive Care Unit–Postoperative Intensive Care Unit, Ankara: Basak Ceyda Meco; Istanbul Kartal Egitim Ve Arastirma Hastanesi, Istanbul: Onat O. Akyol and Suleyman S. Derman. UK: Papworth Hospital, Cambridge: Barry Kennedy and Ken Parhar; Royal Glamorgan Hospital, Llantrisant: Latha Srinivasa; Royal Victoria Hospital, Belfast: Lia McNamee and Danny McAuley; Jack Steinberg Intensive Care Unit of the King's College, London: Phil Hopkins and Clare Mellis; Frank Stansil Intensive Care Unit of the King's College Hospital, London: Vivek Kakar; Liver Intensive Care Unit of the King's College, London: Dan Hadfield; Christine Brown Intensive Care Unit of the King's College, London: Andre Vercueil; West Suffolk Hospital, Bury St Edmunds: Kaushik Bhowmick and Sally K. Humphreys; Craigavon Area Hospital, Portadown: Andrew Ferguson and Raymond Mckee; Barts Health National Health Service Trust, Whipps Cross Hospital, Leytonstone: Ashok S. Raj and Danielle A. Fawkes; Kettering General Hospital, Foundation National Health Service Trust, Northamptonshire: Philip Watt and Linda Twohey; Barnet General Hospital, Barnet: Rajeev R. Jha, Matthew Thomas, Alex Morton and Varsha Kadaba; Rotherham General Hospital, Rotherham: Mark J. Smith and Anil P. Hormis; City Hospital, Birmingham: Santhana G. Kannan and Miriam Namih; Poole Hospital National Health Service Foundation Trust, Poole: Henrik Reschreiter and Julie Camsooksai; Weston General Hospital, Weston-Super-Mare: Alek Kumar and Szabolcs Rugonfalvi; Antrim Area Hospital, Antrim: Christopher Nutt and Orla Oneill; Aintree University Hospital, Liverpool: Colette Seasman and Ged Dempsey; Northern General Hospital, Sheffield: Christopher J. Scott and Helen E. Ellis; John Radcliffe Hospital, Oxford: Stuart Mckechnie and Paula J. Hutton; St Georges Hospital, London: Nora N. Di Tomasso and Michela N. Vitale; Hillingdon Hospital, Uxbridge: Ruth O. Griffin and Michael N. Dean; Royal Bournemouth and Christchurch National Health Service Foundation Trust, Bournemouth: Julius H. Cranshaw and Emma L. Willett; Guy's and St Thomas' National Health Service Foundation Trust, London: Nicholas Ioannou; Guy's and St Thomas' Severe Respiratory Failure Service, Whittington Hospital, London: Sarah Gillis; Wexham Park Hospital, Slough: Peter Csabi; Western General Hospital, Edinburgh: Rosaleen Macfadyen and Heidi Dawson; Royal Preston Hospital, Preston: Pieter D. Preez and Alexandra J. Williams; Brighton and Sussex University Hospitals National Health Service Trust, Brighton: Owen Boyd and Laura Ortiz-Ruiz de Gordoa; East and North Herts National Health Service Trust, Stevenage: Jon Bramall and Sophie Symmonds; Barnsley Hospital, Barnsley: Simon K. Chau and Tim Wenham; Prince Charles Hospital, Merthyr Tydfil: Tamas Szakmany and Piroska Toth-Tarsoly; University Hospital of South Manchester National Health Service Foundation Trust, Manchester: Katie H. McCalman and Peter Alexander; Harrogate District Hospital, Harrogate: Lorraine Stephenson and Thomas Collyer; East and North Herts National Health Service Trust, Welwyn Garden City: Rhiannon Chapman and Raphael Cooper; Western Infirmary, Glasgow: Russell M. Allan and Malcolm Sim; Dumfries and Galloway Royal Infirmary, Dumfries: David W. Wrathall and Donald A. Irvine; Charing Cross Hospital, London: Kim S. Zantua and John C. Adams; Worcestershire Royal Hospital, Worcester: Andrew J. Burtenshaw and Gareth P. Sellors; Royal Liverpool University Hospital, Liverpool: Ingeborg D. Welters and Karen E. Williams; Royal Alexandra Hospital, Glasgow: Robert J. Hessell and Matthew G. Oldroyd; Morriston Hospital, Swansea: Ceri E. Battle and Suresh Pillai; Frimley Park Hospital, Frimley: Istvan Kajtor and Mageswaran Sivashanmugavel; Altnagelvin Hospital, Derry: Sinead C. Okane and Adrian Donnelly; Buckinghamshire Healthcare National Health Service Trust, High Wycombe: Aniko D. Frigyik and Jon P. Careless; Milton Keynes Hospital, Milton Keynes: Martin M. May and Richard Stewart; Ulster Hospital, Belfast: T. John Trinder and Samantha J. Hagan; University Hospital of Wales, Cardiff: Jade M. Cole; Freeman Hospital, Newcastle upon Tyne: Caroline C. MacFie and Anna T. Dowling. Uruguay: Hospital Español, Montevideo: Javier Hurtado and Nicolás Nin; Cudam, Montevideo: Javier Hurtado; Sanatorio Mautone, Maldonado: Edgardo Nuñez; Sanatorio Americano, Montevideo: Gustavo Pittini and Ruben Rodriguez; Hospital de Clínicas, Montevideo: María C. Imperio and Cristina Santos; Circulo Católico Obreros Uruguay–Sanatorio Juan Pablo II, Montevido: Ana G. França and Alejandro Ebeid; Centro de Asistencia del Sindicato Médico del Uruguay, Montevideo: Alberto Deicas and Carolina Serra. USA: St. Louis University Hospital, St. Louis, Missouri: Aditya Uppalapati and Ghassan Kamel; Beth Israel Deaconess Medical Center, Boston, Massachusetts: Valerie M. Banner-Goodspeed and Jeremy R. Beitler; Memorial Medical Center, Springfield, Illinois: Satyanarayana Reddy Mukkera and Shreedhar Kulkarni; University of Cincinnati Medical Center, Cincinnati, Ohio: John O. Shinn III and Dina Gomaa; Massachusetts General Hospital, Boston, Massachusetts: Christopher Tainter, Jarone Lee and Tomaz MesarJarone Lee; R. Adams Cowley Shock Trauma Center, Baltimore, Maryland: Dale J. Yeatts and Jessica Warren; Intermountain Medical Center, Murray, Utah: Michael J. Lanspa, Russel R. Miller, Colin K. Grissom and Samuel M. Brown; Mayo Clinic, Rochester, Minnesota: Philippe R. Bauer; North Shore Medical Center, Salem, Massachusetts: Ryan J. Gosselin and Barrett T. Kitch; Albany Medical Center, Albany, New York: Jason E. Cohen, Scott H. Beegle and Shazia Choudry; John H. Stoger Hospital of Cook County, Chicago, Illinois: Renaud M. Gueret and Aiman Tulaimat; University of Alabama at Birmingham, Birmingham, Alabama: William Stigler and Hitesh Batra; Duke University Hospital, Durham, North Carolina: Nidhi G. Huff; Iowa Methodist Medical Center, Des Moines, Iowa: Keith D. Lamb and Trevor W. Oetting; Surgical and Neurosciences Intensive Care Unit of the University of Iowa Hospitals and Clinics, Iowa City, Iowa: Nicholas M. Mohr and Claine Judy; Medical Center of Louisiana at New Orleans, New Orleans, Louisiana: Shigeki Saito and Fayez M. Kheir; Tulane University, New Orleans, Louisiana: Fayez Kheir; Critical Care Unit of the University of Iowa Hospitals and Clinics, Iowa City, Iowa: Adam B. Schlichting and Angela Delsing; University of California, San Diego Medical Center, San Diego, California: Daniel R. Crouch and Mary Elmasri; University of California San Diego Thornton Hospital, La Jolla, California: Daniel R. Crouch and Dina Ismail; University Hospital, Cincinnati, Ohio: Kyle R. Dreyer, Thomas C. Blakeman and Dina Gomaa; Tower 3B Medical Intensive Care Unit of Brigham and Women's Hospital, Boston, Massachusetts: Rebecca M. Baro and, Carolina Quintana Grijalba; Tower 8C Burn/Trauma Intensive Care Unit of Brigham and Women's Hospital, Boston, Massachusetts: Peter C. Hou; Tower 8D Surgical Intensive Care Unit of Brigham and Women's Hospital, Boston, Massachusetts: Raghu Seethala; Tower 9C Neurosurgical Intensive Care Unit of Brigham and Women's Hospital, Boston, Massachusetts: Imo Aisiku; Tower 9D Neurological Intensive Care Unit of Brigham and Women's Hospital, Boston, Massachusetts: Galen Henderson; Tower 11C Thoracic Intensive Care Unit of Brigham and Women's Hospital, Boston, Massachusetts: Gyorgy Frendl; Shapiro 6W Cardiac Surgery Intensive Care Unit of Brigham and Women's Hospital, Boston, Massachusetts: Sen-Kuang Hou; Shapiro 9E Coronary Care Unit of Brigham and Women's Hospital, Boston, Massachusetts: Robert L. Owens and Ashley Schomer.
Conflict of interest: T. Pham has nothing to disclose.
Conflict of interest: A. Pesenti reports personal fees from Maquet, Novalung/Xenios, Baxter, Gilead and Boehringer Ingelheim, outside the submitted work.
Conflict of interest: G. Bellani reports grants and personal fees from Draeger Medical, personal fees from Getinge, Hamilton, GE Healthcare, Dimar SRL, Intersurgical and Flowmeter SPA, outside the submitted work.
Conflict of interest: G. Rubenfeld has nothing to disclose.
Conflict of interest: E. Fan reports personal fees from ALung Technologies, Getinge and MC3 Cardiopulmonary, grants, personal fees and non-financial support from Fresenius Medical Care, outside the submitted work.
Conflict of interest: G. Bugedo has nothing to disclose.
Conflict of interest: J.A. Lorente has nothing to disclose.
Conflict of interest: A.D.V. Fernandes has nothing to disclose.
Conflict of interest: F. Van Haren has nothing to disclose.
Conflict of interest: A. Bruhn has nothing to disclose.
Conflict of interest: F. Rios has nothing to disclose.
Conflict of interest: A. Esteban has nothing to disclose.
Conflict of interest: L. Gattinoni has nothing to disclose.
Conflict of interest: A. Larsson reports grants from the Swedish Heart and Lung Foundation, during the conduct of the study.
Conflict of interest: D.F. McAuley reports personal fees from consultancy for GlaxoSmithKline, Boehringer Ingelheim and Bayer, outside the submitted work; in addition, his institution has received funds from grants from the UK NIHR, Wellcome Trust, Innovate UK, NI HSC R&D Division, NI Chest Heart and Stroke, and MRC; is one of four named inventors on a patent US8962032 covering the use of sialic acid-bearing nanoparticles as anti-inflammatory agents issued to his institution, The Queen's University of Belfast (http://www.google.com/patents/US8962032); and is a Director of Research for the Intensive Care Society and NIHR EME Programme Director.
Conflict of interest: M. Ranieri has nothing to disclose.
Conflict of interest: B.T. Thompson reports personal fees from Bayer, Thetis and Novartis, outside the submitted work.
Conflict of interest: H. Wrigge reports personal fees for consultancy from Dräger Medical, personal fees for advisory board work from Liberate Medical, grants and personal fees for lectures from InfectoPharm, personal fees for lectures from MSD and GE, outside the submitted work.
Conflict of interest: L.J. Brochard reports grants from Medtronic Covidien, grants and non-financial support from Fisher Paykel, non-financial support from Air Liquide, Sentec and Philips, other (patent) from General Electric, outside the submitted work.
Conflict of interest: J.G. Laffey reports grants and personal fees from Baxter, grants and non-financial support from Aerogen and Factor Biosciences, outside the submitted work.
Support statement: This work was supported by the European Society of Intensive Care Medicine. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received August 29, 2020.
- Accepted November 21, 2020.
- Copyright ©ERS 2021
References
