Daily Ards Research Analysis

PURPOSE: Acute respiratory failure is the leading reason for intensive care unit (ICU) admission among critically ill patients with cancer. We aimed to describe the clinical characteristics, risk factors, and outcomes of patients with cancer and acute respiratory distress syndrome (ARDS) and to evaluate associations of venovenous extracorporeal membrane oxygenation (ECMO) with outcomes in the subgroup with severe ARDS. METHODS: We conducted a multinational, prospective, observational cohort study of patients with cancer and ARDS in 13 countries in Europe and North America. The primary endpoint was 90-day mortality. RESULTS: Among 715 included patients, 73.4% had hematologic malignancies and 26.6% solid tumors; 31.2% had undergone hematopoietic stem-cell transplantation (168 allogeneic). ICU, hospital, and 90-day mortality rates were 55.3%, 70.9%, and 73.2%, respectively. By multivariate analysis, independent predictors of higher 90-day mortality were older age, peripheral vascular disease, severe ARDS at inclusion, acute kidney injury, and ICU admission as a time-limited trial (vs. full code). Conversely, lymphoma was associated with lower 90-day mortality. Among the 322 patients (45.7%) with severe ARDS at inclusion, 90-day mortality was 82.2%; with no difference between patients who received ECMO (n = 58, 18%) and those who did not (82.6% vs. 80.7%, P = 0.89). This finding remained unchanged in a double-adjusted overlap- and propensity-weighted Cox mixed-effects model (adjusted hazard ratio, 1.12; 95% confidence interval 0.65-1.94; P = 0.69). CONCLUSION: Patients with cancer and ARDS, particularly severe forms, experience high 90-day mortality, irrespective of ECMO use. These findings suggest a need for nuanced ICU goals-of-care discussions and raise concerns about the generalizability of ECMO guidelines to this population.

BACKGROUND: Endotheliopathy and coagulopathy are known complications of COVID-19, with a significant association with mortality. Although dexamethasone is the standard of care for patients with severe COVID-19, its precise mode of action remains elusive. We aim to investigate the functional consequences of dexamethasone treatment on COVID-19-associated procoagulant endotheliopathy. METHODS: First, during the 7 days after hospitalization, we measured several endothelial and coagulopathy biomarkers in a prospective cohort of patients with COVID-19 with acute respiratory distress syndrome (ARDS) who were either treated or not with both dexamethasone and therapeutic UFH (unfractionated heparin). Second, we developed an in vitro thrombin generation assay on cultured human endothelial cells to measure the ability of stimulated endothelial colony-forming cells to activate coagulation in normal plasma, which is expressed as an endogenous thrombin potential (ETP). RESULTS: Among the cohort of 44 ARDS COVID-19 patients, 23 patients treated with dexamethasone and therapeutic UFH had significantly decreased von Willebrand Factor, Ang-2 (angiopoietin-2), soluble E-selectin, and d-dimer levels over 7 days. To differentiate the effect of UFH and dexamethasone on endotheliopathy, we used the thrombin generation assay and showed that endothelial colony-forming cell stimulation with dexamethasone but not UFH-in addition to a cocktail of proinflammatory cytokines (to mimic the cytokine storm of severe COVID-19)-significantly decreased ETP in comparison to proinflammatory cytokines only. Moreover, in another cohort of 331 patients with COVID-19 of varying severity, the endothelial colony-forming cell stimulation with the plasma of 87 ARDS patients showed significantly higher ETP (1260 nmol/L per minute [interquartile range, 1140-1260]) compared with 75 non-ARDS patients (1024 nmol/L per minute [interquartile range, 915-1200]; CONCLUSIONS: Our data suggest that dexamethasone protects against COVID-19 endothelium-induced coagulopathy. These findings are in line with the decreased prevalence of venous thrombosis among hospitalized patients with COVID-19 treated with dexamethasone.

BACKGROUND: Preterm birth is the leading cause of childhood mortality, with respiratory distress syndrome as the predominant aetiology. Initiating continuous positive airways pressure (CPAP) immediately after birth may reduce CPAP failure, the need for ventilation, and surfactant use. In low-resource settings, without ventilation or surfactant, immediate CPAP could significantly reduce preterm mortality. We explored the experiences, perceptions, and acceptability of immediate CPAP among parents, caregivers, and healthcare workers in a Ugandan hospital. METHODS: This qualitative study (April 2023-April 2024) was nested in a pilot randomised controlled trial of immediate delivery room CPAP for very low birthweight infants (VLBW, < 1500 g) at a government hospital in Uganda. Data were collected through 12 key informant interviews and focus group discussions with 36 healthcare workers, and 37 parents and caregivers of enrolled infants. We applied deductive framework analysis using the Theoretical Framework of Acceptability (TFA) and coded transcripts using Nvivo 12. RESULTS: Regarding affective attitude, healthcare workers, mothers and caregivers expressed positive feelings towards immediate CPAP. For perceived effectiveness, healthcare workers described immediate CPAP as a prophylactic intervention that reduces the severity of complications and shortens hospital stays, while mothers and caregivers believed it expands the infant's lungs and increases chances of survival. Concerning burden, healthcare workers highlighted that successful implementation depends on a committed neonatal team, multidisciplinary team collaboration, adequate staffing, active maternal involvement, and the availability of sufficient CPAP machines. Opportunity costs were evident where limited staffing forced healthcare workers to choose between prioritising the mother or the infant. Under ethicality, cultural beliefs, religious views, and fear were identified as influential factors in decision making around immediate CPAP. Regarding intervention coherence, healthcare workers, mothers, and caregivers demonstrated a good understanding of the purpose and process of immediate CPAP. Finally, self-efficacy was linked to the availability of adequate staff, training, and necessary equipment to confidently engage in the intervention. CONCLUSIONS: Immediate CPAP was found to be acceptable among healthcare workers and mothers/caregivers. Successful implementation requires adequate staff training, comprehensive health education, adequate human resources, and sufficient availability of CPAP machines. TRIAL REGISTRATION: Study is registered on Pan African Clinical Trials Registry (PACTR) PACTR202208462613789. Registered 08/08/2022. https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=23888 .