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Potentially modifiable factors contributing to outcome from acute respiratory distress syndrome: the LUNG SAFE study
Purpose
To improve the outcome of the acute respiratory distress syndrome (ARDS), one needs to identify potentially modifiable factors associated with mortality.
Methods
The large observational study to understand the global impact of severe acute respiratory failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients with severe respiratory failure, conducted in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across five continents. A pre-specified secondary aim was to examine the factors associated with outcome. Analyses were restricted to patients (93.1 %) fulfilling ARDS criteria on day 1–2 who received invasive mechanical ventilation.
Results
2377 patients were included in the analysis. Potentially modifiable factors associated with increased hospital mortality in multivariable analyses include lower PEEP, higher peak inspiratory, plateau, and driving pressures, and increased respiratory rate. The impact of tidal volume on outcome was unclear. Having fewer ICU beds was also associated with higher hospital mortality. Non-modifiable factors associated with worsened outcome from ARDS included older age, active neoplasm, hematologic neoplasm, and chronic liver failure. Severity of illness indices including lower pH, lower PaO
2
/FiO
2
ratio, and higher non-pulmonary SOFA score were associated with poorer outcome. Of the 578 (24.3 %) patients with a limitation of life-sustaining therapies or measures decision, 498 (86.0 %) died in hospital. Factors associated with increased likelihood of limitation of life-sustaining therapies or measures decision included older age, immunosuppression, neoplasia, lower pH and increased non-pulmonary SOFA scores.
Conclusions
Higher PEEP, lower peak, plateau, and driving pressures, and lower respiratory rate are associated with improved survival from ARDS.
Trial Registration: ClinicalTrials.gov NCT02010073.
Journal Article
Lucky you : a novel
\"In Erika Carter's fierce and darkly funny debut novel, Lucky You, three women in their early twenties find themselves aimlessly adrift in the Arkansas college town they've stuck around in too long. Ellie, Chloe and Rachel are friends (sort of), waitresses at the same dive bar. Each is becoming unmoored in her own way: Ellie obliterates all feeling with alcohol and self-destructive acts of sexual promiscuity; Chloe pulls out patches of her hair and struggles to keep incipient mental illness at bay; changeable Rachel has fallen under the sway of a messianic boyfriend with whom she's agreed to live off-grid for a year in order to return to \"health,\" and she asks Ellie and Chloe to join them in \"The Project\". In a remote, rural house in the Ozarks, nearly undone by boredom and the brewing tension between them, each tries to solve the conundrum of being alive. By turns funny, knowing and hauntingly sad, Lucky You is a study in damage and detachment, a fearless portrait of three women at a crucial point in their lives. With startling exactitude and wickedly deadpan humor, it lays bare the emotional core of its characters with surgical precision. The writing is deft and controlled, as natural and unforced as breath -- which makes it impossible to look away\" -- Provided by publisher.
Book
Acute Respiratory Distress Syndrome Subphenotypes Respond Differently to Randomized Fluid Management Strategy
Abstract
Rationale
We previously identified two acute respiratory distress syndrome (ARDS) subphenotypes in two separate randomized controlled trials with differential response to positive end-expiratory pressure.
Objectives
To identify these subphenotypes in a third ARDS cohort, to test whether subphenotypes respond differently to fluid management strategy, and to develop a practical model for subphenotype identification.
Methods
We used latent class analysis of baseline clinical and plasma biomarker data to identify subphenotypes in FACTT (Fluid and Catheter Treatment Trial; n = 1,000). Logistic regression was used to test for an interaction between subphenotype and treatment for mortality. We used stepwise modeling to generate a model for subphenotype identification in FACTT and validated its accuracy in the two cohorts in which we previously identified ARDS subphenotypes.
Measurements and Main Results
We confirmed that a two-class (two-subphenotype) model best described the study population. Subphenotype 2 was again characterized by higher inflammatory biomarkers and hypotension. Fluid management strategy had significantly different effects on 90-day mortality in the two subphenotypes (P = 0.0039 for interaction); mortality in subphenotype 1 was 26% with fluid-liberal strategy versus 18% with fluid-conservative, whereas mortality in subphenotype 2 was 40% with fluid-liberal strategy versus 50% in fluid-conservative. A three-variable model of IL-8, bicarbonate, and tumor necrosis factor receptor-1 accurately classified the subphenotypes.
Conclusions
This analysis confirms the presence of two ARDS subphenotypes that can be accurately identified with a limited number of variables and that responded differently to randomly assigned fluid management. These findings support the presence of ARDS subtypes that may require different treatment approaches.
Journal Article
Early Neuromuscular Blockade in the Acute Respiratory Distress Syndrome
This trial revisited research conducted about a decade ago that showed a survival benefit with early neuromuscular blockade in patients with acute respiratory distress syndrome. The new trial did not show a benefit with neuromuscular blockade with respect to overall survival or other clinical outcomes.
Journal Article
Lower or Higher Oxygenation Targets for Acute Hypoxemic Respiratory Failure
Even though supplemental oxygen is used for the treatment of patients with hypoxemic respiratory failure, the most effective oxygenation targets are not known. In this randomized trial, a lower oxygenation target did not result in lower mortality than a higher target.
Journal Article
Esophageal and transpulmonary pressure in the clinical setting: meaning, usefulness and perspectives
Purpose
Esophageal pressure (Pes) is a minimally invasive advanced respiratory monitoring method with the potential to guide management of ventilation support and enhance specific diagnoses in acute respiratory failure patients. To date, the use of Pes in the clinical setting is limited, and it is often seen as a research tool only.
Methods
This is a review of the relevant technical, physiological and clinical details that support the clinical utility of Pes.
Results
After appropriately positioning of the esophageal balloon, Pes monitoring allows titration of controlled and assisted mechanical ventilation to achieve personalized protective settings and the desired level of patient effort from the acute phase through to weaning. Moreover, Pes monitoring permits accurate measurement of transmural vascular pressure and intrinsic positive end-expiratory pressure and facilitates detection of patient–ventilator asynchrony, thereby supporting specific diagnoses and interventions. Finally, some Pes-derived measures may also be obtained by monitoring electrical activity of the diaphragm.
Conclusions
Pes monitoring provides unique bedside measures for a better understanding of the pathophysiology of acute respiratory failure patients. Including Pes monitoring in the intensivist’s clinical armamentarium may enhance treatment to improve clinical outcomes.
Journal Article
Stability of ARDS subphenotypes over time in two randomised controlled trials
RationaleTwo distinct acute respiratory distress syndrome (ARDS) subphenotypes have been identified using data obtained at time of enrolment in clinical trials; it remains unknown if these subphenotypes are durable over time.ObjectiveTo determine the stability of ARDS subphenotypes over time.MethodsSecondary analysis of data from two randomised controlled trials in ARDS, the ARMA trial of lung protective ventilation (n=473; patients randomised to low tidal volumes only) and the ALVEOLI trial of low versus high positive end-expiratory pressure (n=549). Latent class analysis (LCA) and latent transition analysis (LTA) were applied to data from day 0 and day 3, independent of clinical outcomes.Measurements and main resultsIn ALVEOLI, LCA indicated strong evidence of two ARDS latent classes at days 0 and 3; in ARMA, evidence of two classes was stronger at day 0 than at day 3. The clinical and biological features of these two classes were similar to those in our prior work and were largely stable over time, though class 2 demonstrated evidence of progressive organ failures by day 3, compared with class 1. In both LCA and LTA models, the majority of patients (>94%) stayed in the same class from day 0 to day 3. Clinical outcomes were statistically significantly worse in class 2 than class 1 and were more strongly associated with day 3 class assignment.ConclusionsARDS subphenotypes are largely stable over the first 3 days of enrolment in two ARDS Network trials, suggesting that subphenotype identification may be feasible in the context of clinical trials.
Journal Article
Mechanical power normalized to predicted body weight as a predictor of mortality in patients with acute respiratory distress syndrome
Purpose
Protective mechanical ventilation based on multiple ventilator parameters such as tidal volume, plateau pressure, and driving pressure has been widely used in acute respiratory distress syndrome (ARDS). More recently, mechanical power (MP) was found to be associated with mortality. The study aimed to investigate whether MP normalized to predicted body weight (norMP) was superior to other ventilator variables and to prove that the discrimination power cannot be further improved with a sophisticated machine learning method.
Methods
The study included individual patient data from eight randomized controlled trials conducted by the ARDSNet. The data was split 3:1 into training and testing subsamples. The discrimination of each ventilator variable was calculated in the testing subsample using the area under receiver operating characteristic curve. The gradient boosting machine was used to examine whether the discrimination could be further improved.
Results
A total of 5159 patients with acute onset ARDS were included for analysis. The discrimination of norMP in predicting mortality was significantly better than the absolute MP (
p
= 0.011 for DeLong’s test). The gradient boosting machine was not able to improve the discrimination as compared to norMP (
p
= 0.913 for DeLong’s test). The multivariable regression model showed a significant interaction between norMP and ARDS severity (
p
< 0.05). While the norMP was not significantly associated with mortality outcome (OR 0.99; 95% CI 0.91–1.07;
p
= 0.862) in patients with mild ARDS, it was associated with increased risk of mortality in moderate (OR 1.11; 95% CI 1.02–1.23;
p
= 0.021) and severe (OR 1.13; 95% CI 1.03–1.24;
p
< 0.008) ARDS.
Conclusions
The study showed that norMP was a good ventilator variable associated with mortality, and its predictive discrimination cannot be further improved with a sophisticated machine learning method. Further experimental trials are needed to investigate whether adjusting ventilator variables according to norMP will significantly improve clinical outcomes.
Journal Article
Mechanical Ventilation Guided by Esophageal Pressure in Acute Lung Injury
Positive end-expiratory pressure (PEEP) is used to improve oxygenation in patients with acute lung injury or the acute respiratory distress syndrome. In this pilot trial, the investigators show that adjusting PEEP with the use of measurements of esophageal pressure to estimate transpulmonary pressure leads to improved oxygenation as compared with the conventional approach to ventilator management.
Patients with acute lung injury or ARDS were randomly assigned to mechanical ventilation directed either by esophageal-pressure measurements or according to standard-of-care recommendations. The use of esophageal pressures to estimate the transpulmonary pressure significantly improved oxygenation and respiratory-system compliance.
Recent changes in the practice of mechanical ventilation have improved survival in patients with the acute respiratory distress syndrome (ARDS), but mortality remains unacceptably high. Whereas low tidal volumes are clearly beneficial in patients with ARDS, how to choose a positive end-expiratory pressure (PEEP) is uncertain.
1
–
4
Ideally, mechanical ventilation should provide sufficient transpulmonary pressure (airway pressure minus pleural pressure) to maintain oxygenation while minimizing repeated alveolar collapse or overdistention leading to lung injury.
5
In critical illness, however, there is marked variability among patients in abdominal and pleural pressures
6
,
7
; thus, for a given level of PEEP, transpulmonary pressures . . .
Journal Article