Project description:The ventilatory care of patients with acute respiratory distress syndrome (ARDS) is evolving as our understanding of physiologic mechanisms of respiratory failure improves. Despite several decades of research, the mortality rate for ARDS remains high. Over the years, we continue to expand strategies to identify and mitigate ventilator-induced lung injury. This now includes a greater understanding of the benefits and harms associated with spontaneous breathing.
Project description:ObjectivesAs coronavirus disease 2019 is a novel disease, treatment strategies continue to be debated. This provides the intensive care community with a unique opportunity as the population of coronavirus disease 2019 patients requiring invasive mechanical ventilation is relatively homogeneous compared with other ICU populations. We hypothesize that the novelty of coronavirus disease 2019 and the uncertainty over its similarity with noncoronavirus disease 2019 acute respiratory distress syndrome resulted in substantial practice variation between hospitals during the first and second waves of coronavirus disease 2019 patients.DesignMulticenter retrospective cohort study.SettingTwenty-five hospitals in the Netherlands from February 2020 to July 2020, and 14 hospitals from August 2020 to December 2020.PatientsOne thousand two hundred ninety-four critically ill intubated adult ICU patients with coronavirus disease 2019 were selected from the Dutch Data Warehouse. Patients intubated for less than 24 hours, transferred patients, and patients still admitted at the time of data extraction were excluded.Measurements and main resultsWe aimed to estimate between-ICU practice variation in selected ventilation parameters (positive end-expiratory pressure, Fio2, set respiratory rate, tidal volume, minute volume, and percentage of time spent in a prone position) on days 1, 2, 3, and 7 of intubation, adjusted for patient characteristics as well as severity of illness based on Pao2/Fio2 ratio, pH, ventilatory ratio, and dynamic respiratory system compliance during controlled ventilation. Using multilevel linear mixed-effects modeling, we found significant (p ≤ 0.001) variation between ICUs in all ventilation parameters on days 1, 2, 3, and 7 of intubation for both waves.ConclusionsThis is the first study to clearly demonstrate significant practice variation between ICUs related to mechanical ventilation parameters that are under direct control by intensivists. Their effect on clinical outcomes for both coronavirus disease 2019 and other critically ill mechanically ventilated patients could have widespread implications for the practice of intensive care medicine and should be investigated further by causal inference models and clinical trials.
Project description:ObjectiveTo determine the incidence and significance of ventilator avoidance in patients with critical coronavirus disease 2019 (COVID-19).MethodsThis prospective observational cohort study evaluated hospital mortality and 1-year functional outcome among critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated acute respiratory distress syndrome (ARDS). The explanatory variable was ventilator avoidance, modeled as 'initial refusal' of intubation (yes/no). Modified Rankin Scale (mRS) scores were obtained from surviving patients (or their surrogates) via phone or email questionnaire.ResultsAmong patients for whom intubation was recommended (n = 102), 40 (39%) initially refused (95% confidence interval [CI] 30%, 49%). The risk of death was 79.3% (49/62) in those who did not initially refuse intubation compared with 77.5% (31/40) in those who initially refused, with an adjusted odds ratio for death of 1.27 (95% CI 0.47, 3.48). The distribution of 1-year mRS scores was not significantly different between groups.ConclusionAmong critically ill patients with COVID-19-associated ARDS, ventilator avoidance was common, but was not associated with increased in-hospital mortality or 1-year functional outcome.
Project description:ObjectivesThere is limited evidence on the impact of protocolized ventilator weaning in pediatric acute respiratory distress syndrome, despite utilization in clinical trials and clinical care. We aimed to determine whether protocolized ventilator weaning shortens mechanical ventilation duration and PICU length of stay in pediatric acute respiratory distress syndrome survivors.DesignSecondary analysis of a prospective pediatric acute respiratory distress syndrome (Berlin definition) cohort from July 2011 to June 2019 analyzed using interrupted time series analysis pre- and postimplementations of a ventilator-weaning pathway. We compared duration of invasive ventilation and PICU length of stay in survivors before and after implementation of a ventilator-weaning pathway. We excluded PICU nonsurvivors and subjects with greater than 100 ventilator days.SettingLarge academic tertiary-care PICU.PatientsChildren with acute respiratory distress syndrome who survived to PICU discharge with less than or equal to 100 days of invasive mechanical ventilation.InterventionsImplementation of a ventilator-weaning pathway on May 2016.Measurements and main resultsOf 723 children with acute respiratory distress syndrome, 132 subjects died and six subjects with ventilation greater than 100 days were excluded. Of the remaining 585 subjects, 375 subjects had acute respiratory distress syndrome prior to pathway intervention and 210 after. Patients in the preintervention epoch were younger, more likely to have infectious acute respiratory distress syndrome, and had increased use of alternative ventilator modes. Pathway adoption was rapid and sustained. Controlling for temporality, pathway implementation was associated with a decrease of a median 3.6 ventilator days (95% CI, -5.4 to -1.7; p < 0.001). There was no change in the reintubation rates. Results were robust to multiple sensitivity analyses adjusting for confounders.ConclusionsVentilator-weaning pathway implementation shortened invasive ventilation duration in pediatric acute respiratory distress syndrome survivors with no change in reintubation. The effect size of this intervention was comparable with those targeted in acute respiratory distress syndrome trials.
Project description:Prone position has been used in acute respiratory distress syndrome (ARDS) patients for more than 40 years in ICU. After having demonstrated its capability to significantly improve oxygenation in a large number of patients, sometimes dramatically, this procedure has been found to prevent ventilator-induced lung injury, the primary concern for the intensivists managing ARDS patients. Over the time, several trials have been done, which regularly improved and refined from each other. At the end, significant improvement in survival has been demonstrated in the most severe ARDS patients, at a threshold of 100-150 mmHg PaO2/FiO2 ratio. The effect of proning on survival cannot be predicted and seems unrelated with both severity of oxygenation impairment and oxygenation response to proning. The rate of complication is declining with the increase in centers expertise. The pressure sores are more frequent in prone and require a special attention. Prone position is a key component of lung protective mechanical ventilation and should be used as a first line therapy in association with low tidal volume and neuromuscular blocking agents in patients with severe ARDS.
Project description:Rationale: Serial measurements of genome-wide transcriptional changes in alveolar macrophages (AMs) in patients with acute respiratory distress syndrome (ARDS) could identify dynamic biologic processes that are associated with clinical outcomes. Objectives: To identify associations between AM transcriptional programs and the composite endpoint of ventilator-free days (VFDs) over the course of ARDS. Methods: We performed unbiased genome-wide transcriptional profiling of AMs purified from bronchoalveolar lavage fluid collected from patients with ARDS. Cells were obtained at baseline (Day 1), Day 4, and Day 8 after ARDS onset. We assessed pathway enrichment in subjects with VFDs > 0 (VFD-Extubated/Alive) versus VFDs = 0 (VFD-Intubated/Dead) at each time point. Measurements and Main Results: We found highly divergent AM transcriptional patterns at all time points between ARDS patients based on their VFD status (FDR < 0.05). “M1-like” and pro-inflammatory gene sets such as IL-6-JAK-STAT signaling were significantly enriched in AMs isolated on Day 1 in VFD-Extubated/Alive versus VFD-Intubated/Dead subjects. In contrast, many of these same gene sets were associated with the VFD-Intubated/Dead subjects on Day 8. In patients who had samples from each time point, we identified multiple AM gene clusters whose temporal expression patterns were associated with VFD status. The relationship between AM expression profiles and VFDs was distinct in subjects with Direct (pulmonary) versus Indirect (extrapulmonary) ARDS. Conclusion: Clinically meaningful outcomes over the course of ARDS are associated with highly distinct AM transcriptional programs. Our findings suggest that interventions targeting the alveolar immune response should be tested within strictly defined time periods.
Project description:Acute respiratory distress syndrome (ARDS) is a heterogeneous form of acute, diffuse lung injury that is characterized by dysregulated inflammation, increased alveolar-capillary interface permeability, and non-cardiogenic pulmonary edema. In the general population, the incidence and mortality associated with ARDS over the last two decades have steadily declined in parallel with optimized approaches to pneumonia and other underlying causes of ARDS as well as increased utilization of multimodal treatment strategies that include lung-protective ventilation. In the cancer settings, significant declines in the incidence and mortality of ARDS over the past two decades have also been reported, although these rates remain significantly higher than those in the general population. Epidemiologic studies identify infection, including disseminated fungal pneumonias, as a major underlying cause of ARDS in the cancer setting. More than half of cancer patients who develop ARDS will not survive to hospital discharge. Those who do survive often face a protracted and often incomplete recovery, resulting in significant long-term physical, psychological, and cognitive sequelae. The residual organ dysfunction and poor functional status after ARDS may delay or preclude subsequent cancer treatments. As such, close collaboration between the critical care physicians and oncology team is essential in identifying and reversing the underlying causes and optimizing treatments for cancer patients with ARDS. This chapter reviews the diagnosis and common causes of ARDS in cancer and gives an update on the general management principles for cancer patients with ARDS in the ICU.
Project description:Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) regulates numerous intracellular signaling pathways involved in inflammation and apoptosis. We hypothesized that genetic variation in MAP3K1 might be associated with outcomes in patients with acute respiratory distress syndrome (ARDS), and that these variants would alter MAP3K1-mediated changes in inflammation and transcriptional regulation. To test this hypothesis, we genotyped single-nucleotide polymorphisms covering linkage disequilibrium bins in MAP3K1 in 306 subjects with ARDS from the ARDSNet FACTT (Fluid and Catheter Treatment Trial) study, and tested for associations between MAP3K1 single-nucleotide polymorphisms and ventilator-free days (VFDs) and mortality. We then validated these associations in a separate cohort of 241 patients with ARDS from Harborview Medical Center (Seattle, WA). We found the variant allele of rs832582 (MAP3K1906Val) was significantly associated with decreased VFDs using multivariate linear regression (-6.1 d, false discovery rate?=?0.06) in the FACTT cohort. In the Harborview Medical Center cohort, subjects homozygous for MAP3K1906Val also had decreased VFDs (-15.1 d, false discovery rate?<?0.01), and increased 28-day mortality (all subjects homozygous for the rare allele died). In whole blood stimulated with various innate immune agonists ex vivo, MAP3K1906Val was associated with increased IL-1?, IL-6, IL-8, monocyte chemoattractant protein 1, and TNF-? production. Transcriptome analysis of whole blood stimulated with Toll-like receptor 4 agonist ex vivo demonstrated enrichment of inflammatory gene sets in subjects homozygous for MAP3K1906Val. Our findings show a robust association between the variant allele of rs832582 (MAP3K1906Val) and decreased VFDs in patients with ARDS and suggest that this variant may predispose individuals to a greater inflammatory response.
Project description:BackgroundThe clinical impact and outcomes of ventilator-associated pneumonia (VAP) have been scarcely investigated in patients with the acute respiratory distress syndrome (ARDS).MethodsPatients admitted over an 18-month period in two intensive care units (ICU) of a university-affiliated hospital and meeting the Berlin criteria for ARDS were retrospectively included. The association between VAP and the probability of death at day 90 (primary endpoint) was appraised through a Cox proportional hazards model handling VAP as a delay entry variable. Secondary endpoints included (i) potential changes in the PaO2/FiO2 ratio and SOFA score values around VAP (linear mixed modelling), and (ii) mechanical ventilation (MV) duration, numbers of ventilator- and vasopressor-free days at day 28, and length of stay (LOS) in patients with and without VAP (median or absolute risk difference calculation). Subgroup analyses were performed in patients with COVID-19-related ARDS and those with ARDS from other causes.ResultsAmong the 336 included patients (101 with COVID-19 and 235 with other ARDS), 176 (52.4%) experienced a first VAP. VAP induced a transient and moderate decline in the PaO2/FiO2 ratio without increase in SOFA score values. VAP was associated with less ventilator-free days (median difference and 95% CI, - 19 [- 20; - 13.5] days) and vasopressor-free days (- 5 [- 9; - 2] days) at day 28, and longer ICU (+ 13 [+ 9; + 15] days) and hospital (+ 11.5 [+ 7.5; + 17.5] days) LOS. These effects were observed in both subgroups. Overall day-90 mortality rates were 35.8% and 30.0% in patients with and without VAP, respectively (P = 0.30). In the whole cohort, VAP (adjusted HR 3.16, 95% CI 2.04-4.89, P < 0.0001), the SAPS-2 value at admission, chronic renal disease and an admission for cardiac arrest predicted death at day 90, while the COVID-19 status had no independent impact. When analysed separately, VAP predicted death in non-COVID-19 patients (aHR 3.43, 95% CI 2.11-5.58, P < 0.0001) but not in those with COVID-19 (aHR 1.19, 95% CI 0.32-4.49, P = 0.80).ConclusionsVAP is an independent predictor of 90-day mortality in ARDS patients. This condition exerts a limited impact on oxygenation but correlates with extended MV duration, vasoactive support, and LOS.