Spontaneous Breathing in Early Acute Respiratory Distress Syndrome: Insights From the Large Observational Study to UNderstand the Global Impact of Severe Acute Respiratory FailurE Study

OBJECTIVES: To describe the characteristics and outcomes of patients with acute respiratory distress syndrome with or without spontaneous breathing and to investigate whether the effects of spontaneous breathing on outcome depend on acute respiratory distress syndrome severity. DESIGN: Planned secondary analysis of a prospective, observational, multicentre cohort study. SETTING: International sample of 459 ICUs from 50 countries. PATIENTS: Patients with acute respiratory distress syndrome and at least 2 days of invasive mechanical ventilation and available data for the mode of mechanical ventilation and respiratory rate for the 2 first days. INTERVENTIONS: Analysis of patients with and without spontaneous breathing, defined by the mode of mechanical ventilation and by actual respiratory rate compared with set respiratory rate during the first 48 hours of mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Spontaneous breathing was present in 67% of patients with mild acute respiratory distress syndrome, 58% of patients with moderate acute respiratory distress syndrome, and 46% of patients with severe acute respiratory distress syndrome. Patients with spontaneous breathing were older and had lower acute respiratory distress syndrome severity, Sequential Organ Failure Assessment scores, ICU and hospital mortality, and were less likely to be diagnosed with acute respiratory distress syndrome by clinicians. In adjusted analysis, spontaneous breathing during the first 2 days was not associated with an effect on ICU or hospital mortality (33% vs 37%; odds ratio, 1.18 [0.92-1.51]; p = 0.19 and 37% vs 41%; odds ratio, 1.18 [0.93-1.50]; p = 0.196, respectively ). Spontaneous breathing was associated with increased ventilator-free days (13 [0-22] vs 8 [0-20]; p = 0.014) and shorter duration of ICU stay (11 [6-20] vs 12 [7-22]; p = 0.04). CONCLUSIONS: Spontaneous breathing is common in patients with acute respiratory distress syndrome during the first 48 hours of mechanical ventilation. Spontaneous breathing is not associated with worse outcomes and may hasten liberation from the ventilator and from ICU. Although these results support the use of spontaneous breathing in patients with acute respiratory distress syndrome independent of acute respiratory distress syndrome severity, the use of controlled ventilation indicates a bias toward use in patients with higher disease severity. In addition, because the lack of reliable data on inspiratory effort in our study, prospective studies incorporating the magnitude of inspiratory effort and adjusting for all potential severity confounders are required

Identifying associations between diabetes and acute respiratory distress syndrome in patients with acute hypoxemic respiratory failure: an analysis of the LUNG SAFE database

Background: Diabetes mellitus is a common co-existing disease in the critically ill. Diabetes mellitus may reduce the risk of acute respiratory distress syndrome (ARDS), but data from previous studies are conflicting. The objective of this study was to evaluate associations between pre-existing diabetes mellitus and ARDS in critically ill patients with acute hypoxemic respiratory failure (AHRF). Methods: An ancillary analysis of a global, multi-centre prospective observational study (LUNG SAFE) was undertaken. LUNG SAFE evaluated all patients admitted to an intensive care unit (ICU) over a 4-week period, that required mechanical ventilation and met AHRF criteria. Patients who had their AHRF fully explained by cardiac failure were excluded. Important clinical characteristics were included in a stepwise selection approach (forward and backward selection combined with a significance level of 0.05) to identify a set of independent variables associated with having ARDS at any time, developing ARDS (defined as ARDS occurring after day 2 from meeting AHRF criteria) and with hospital mortality. Furthermore, propensity score analysis was undertaken to account for the differences in baseline characteristics between patients with and without diabetes mellitus, and the association between diabetes mellitus and outcomes of interest was assessed on matched samples. Results: Of the 4107 patients with AHRF included in this study, 3022 (73.6%) patients fulfilled ARDS criteria at admission or developed ARDS during their ICU stay. Diabetes mellitus was a pre-existing co-morbidity in 913 patients (22.2% of patients with AHRF). In multivariable analysis, there was no association between diabetes mellitus and having ARDS (OR 0.93 (0.78-1.11); p = 0.39), developing ARDS late (OR 0.79 (0.54-1.15); p = 0.22), or hospital mortality in patients with ARDS (1.15 (0.93-1.42); p = 0.19). In a matched sample of patients, there was no association between diabetes mellitus and outcomes of interest. Conclusions: In a large, global observational study of patients with AHRF, no association was found between diabetes mellitus and having ARDS, developing ARDS, or outcomes from ARDS. Trial registration: NCT02010073. Registered on 12 December 2013

Epidemiology and patterns of tracheostomy practice in patients with acute respiratory distress syndrome in ICUs across 50 countries

Background: To better understand the epidemiology and patterns of tracheostomy practice for patients with acute respiratory distress syndrome (ARDS), we investigated the current usage of tracheostomy in patients with ARDS recruited into the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG-SAFE) study. Methods: This is a secondary analysis of LUNG-SAFE, an international, multicenter, prospective cohort study of patients receiving invasive or noninvasive ventilation in 50 countries spanning 5 continents. The study was carried out over 4 weeks consecutively in the winter of 2014, and 459 ICUs participated. We evaluated the clinical characteristics, management and outcomes of patients that received tracheostomy, in the cohort of patients that developed ARDS on day 1-2 of acute hypoxemic respiratory failure, and in a subsequent propensity-matched cohort. Results: Of the 2377 patients with ARDS that fulfilled the inclusion criteria, 309 (13.0%) underwent tracheostomy during their ICU stay. Patients from high-income European countries (n = 198/1263) more frequently underwent tracheostomy compared to patients from non-European high-income countries (n = 63/649) or patients from middle-income countries (n = 48/465). Only 86/309 (27.8%) underwent tracheostomy on or before day 7, while the median timing of tracheostomy was 14 (Q1-Q3, 7-21) days after onset of ARDS. In the subsample matched by propensity score, ICU and hospital stay were longer in patients with tracheostomy. While patients with tracheostomy had the highest survival probability, there was no difference in 60-day or 90-day mortality in either the patient subgroup that survived for at least 5 days in ICU, or in the propensity-matched subsample. Conclusions: Most patients that receive tracheostomy do so after the first week of critical illness. Tracheostomy may prolong patient survival but does not reduce 60-day or 90-day mortality. Trial registration: ClinicalTrials.gov, NCT02010073. Registered on 12 December 2013

Virtual Patient Modeling and Prediction Validation for Pressure Controlled Mechanical Ventilation

Abstract: Respiratory failure patients in the intensive care unit (ICU) require mechanical ventilation (MV) to support breathing and tissue oxygenation. Optimizing MV care is problematic. Significant patient variability confounds optimal MV settings and increase the risk of lung damage due to excessive pressure or volume delivery, which in turn can increase length of stay and cost, as well as mortality. Model-based care using in silico virtual patients can significantly affect ICU care, personalizing delivery and optimising care. This research presents a virtual patient model for pressure-controlled MV, an increasingly common mode of MV delivery, based on prior work applied to volume-controlled MV. This change necessitates predictions of flow and thus volume, instead of pressure, as the unspecified variable. A model is developed and validated using clinical data from five patients (N=5) during a series of PEEP (positive end expiratory pressure) changes in a recruitment maneuver (RM), creating a total of 242 predictions. Peak inspiratory volume, a measure of risk of lung damage, errors were 56 [26-9]ml. (10.6[5.3-19.1]ml. (10.6[5.3-19.1%) for predictions of PEEP changes from 2-16cmlH@), Model fitting errors were all lower than 5%. Accurate predictions validate the model, and its potential to both personalise and optimise care

Noninvasive Ventilation of Patients with Acute Respiratory Distress Syndrome: Insights from the LUNG SAFE Study

Rationale: Noninvasive ventilation (NIV) is increasingly used in patients with acute respiratory distress syndrome (ARDS). The evidence supporting NIV use in patients with ARDS remains relatively sparse. Objectives: To determine whether, during NIV, the categorization of ARDS severity based on the PaO2/FIO2Berlin criteria is useful. Methods: TheLUNGSAFE(Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure) study described the management of patients with ARDS. This substudy examines the current practice of NIV use in ARDS, the utility of the PaO2/FIO2ratio in classifying patients receiving NIV, and the impact of NIV on outcome. MeasurementsandMain Results:Of2,813 patients with ARDS,436 (15.5%) were managed with NIV on Days 1 and 2 following fulfillment of diagnosticcriteria.Classification of ARDS severity based on PaO2/FIO2ratio was associated with an increase in intensity of ventilatory support, NIV failure, and intensive care unit (ICU) mortality. NIV failure occurred in 22.2% of mild, 42.3% of moderate, and 47.1% of patients with severe ARDS. Hospital mortality in patients with NIV success and failure was 16.1% and 45.4%, respectively. NIV use was independently associated with increased ICU (hazard ratio, 1.446 [95% confidence interval, 1.159-1.805]), but not hospital, mortality. In a propensity matched analysis, ICU mortality was higher in NIV than invasively ventilated patients with a PaO2/FIO2lower than 150 mm Hg. Conclusions:NIV was used in 15% of patients with ARDS,irrespective of severity category. NIV seems to be associated with higher ICU mortality in patients with a PaO2/FIO2lower than 150 mm Hg

Outcomes of Patients Presenting with Mild Acute Respiratory Distress Syndrome: Insights from the LUNG SAFE Study

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: Hospital mortality in acute respiratory distress syndrome is approximately 40%, but mortality and trajectory in "mild" acute respiratory distress syndrome (classified only since 2012) are unknown, and many cases are not detected WHAT THIS ARTICLE TELLS US THAT IS NEW: Approximately 80% of cases of mild acute respiratory distress syndrome persist or worsen in the first week; in all cases, the mortality is substantial (30%) and is higher (37%) in those in whom the acute respiratory distress syndrome progresses BACKGROUND:: Patients with initial mild acute respiratory distress syndrome are often underrecognized and mistakenly considered to have low disease severity and favorable outcomes. They represent a relatively poorly characterized population that was only classified as having acute respiratory distress syndrome in the most recent definition. Our primary objective was to describe the natural course and the factors associated with worsening and mortality in this population. METHODS: This study analyzed patients from the international prospective Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) who had initial mild acute respiratory distress syndrome in the first day of inclusion. This study defined three groups based on the evolution of severity in the first week: "worsening" if moderate or severe acute respiratory distress syndrome criteria were met, "persisting" if mild acute respiratory distress syndrome criteria were the most severe category, and "improving" if patients did not fulfill acute respiratory distress syndrome criteria any more from day 2. RESULTS: Among 580 patients with initial mild acute respiratory distress syndrome, 18% (103 of 580) continuously improved, 36% (210 of 580) had persisting mild acute respiratory distress syndrome, and 46% (267 of 580) worsened in the first week after acute respiratory distress syndrome onset. Global in-hospital mortality was 30% (172 of 576; specifically 10% [10 of 101], 30% [63 of 210], and 37% [99 of 265] for patients with improving, persisting, and worsening acute respiratory distress syndrome, respectively), and the median (interquartile range) duration of mechanical ventilation was 7 (4, 14) days (specifically 3 [2, 5], 7 [4, 14], and 11 [6, 18] days for patients with improving, persisting, and worsening acute respiratory distress syndrome, respectively). Admissions for trauma or pneumonia, higher nonpulmonary sequential organ failure assessment score, lower partial pressure of alveolar oxygen/fraction of inspired oxygen, and higher peak inspiratory pressure were independently associated with worsening. CONCLUSIONS: Most patients with initial mild acute respiratory distress syndrome continue to fulfill acute respiratory distress syndrome criteria in the first week, and nearly half worsen in severity. Their mortality is high, particularly in patients with worsening acute respiratory distress syndrome, emphasizing the need for close attention to this patient population

Resolved versus confirmed ARDS after 24 h: insights from the LUNG SAFE study

Purpose: To evaluate patients with resolved versus confirmed ARDS, identify subgroups with substantial mortality risk, and to determine the utility of day 2 ARDS reclassification. Methods: Our primary objective, in this secondary LUNG SAFE analysis, was to compare outcome in patients with resolved versus confirmed ARDS after 24\ua0h. Secondary objectives included identifying factors associated with ARDS persistence and mortality, and the utility of day 2 ARDS reclassification. Results: Of 2377 patients fulfilling the ARDS definition on the first day of ARDS (day 1) and receiving invasive mechanical ventilation, 503 (24%) no longer fulfilled the ARDS definition the next day, 52% of whom initially had moderate or severe ARDS. Higher tidal volume on day 1 of ARDS was associated with confirmed ARDS [OR 1.07 (CI 1.01\u20131.13), P = 0.035]. Hospital mortality was 38% overall, ranging from 31% in resolved ARDS to 41% in confirmed ARDS, and 57% in confirmed severe ARDS at day 2. In both\ua0resolved and confirmed\ua0ARDS, age, non-respiratory SOFA score, lower PEEP and P/F ratio, higher peak pressure and respiratory rate were each\ua0associated with mortality. In confirmed ARDS, pH and the presence of immunosuppression or neoplasm were also associated\ua0with mortality. The increase in area under the receiver operating curve for ARDS reclassification on day 2 was marginal. Conclusions: ARDS, whether resolved or confirmed at day 2, has a high mortality rate. ARDS reclassification at day 2 has limited predictive value for mortality. The substantial mortality risk in severe confirmed ARDS suggests that complex interventions might best be tested in this population. Trial Registration: ClinicalTrials.gov NCT02010073. \ua9 2018, Springer-Verlag GmbH Germany, part of Springer Nature and ESICM

ESICM LIVES 2016: part two : Milan, Italy. 1-5 October 2016.

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