Daily Ards Research Analysis

BACKGROUND AND RESEARCH QUESTION: CD14-dependent innate immunity contributes to poor outcomes in COVID-19 pneumonia. We tested the clinical and biological efficacy of a blocking monoclonal antibody to CD14 (IC14) for treatment of severe COVID-19 pneumonia and the utility of a biomarker of CD14 pathway activation in predicting outcome. STUDY DESIGN AND METHODS: We report a preplanned secondary analysis of the I-SPY COVID Trial, which enrolled hospitalized patients with severe COVID-19 pneumonia at 19 medical centers in the U.S. who required high-level respiratory support. Participants were randomized to receive either intravenous IC14 (4 mg/kg on Day 1, then 2 mg/kg on Days 2-4) (N=67) or standard care (N=76). Primary endpoints included time-to-recovery, defined as the first two-day period on ≤6L/min O RESULTS: IC14 treatment did not improve time-to-recovery or 28-day mortality in the overall population, and the trial was stopped due to meeting futility criteria for the time-to-recovery endpoint. However, a predefined sub-group analysis showed that IC14 treatment was associated with a numerical reduction in 28-day mortality in participants with high (above median) baseline presepsin levels (N=47) [Hazard Ratio for mortality (HRm)): 0.52, 95% credible interval (CrI): 0.22-1.22, posterior probability HRm<1 (Pr (HRm<1|Data))=0.93]. IC14 treatment increased plasma sCD14, a pharmacodynamic marker and decreased plasma inflammatory biomarkers, including IL-8, RAGE, VEGF, and presepsin. INTERPRETATION: Although IC14 treatment did not improve overall clinical outcomes, this new secondary analysis shows that IC14 had the expected pharmacodynamic and biological effects, and that baseline plasma presepsin concentrations may identify patients likely to respond to IC14 treatment. Further trials are needed to determine the efficacy of IC14 treatment in acute lung injury and the value of presepsin to identify patients most likely to respond. CLINICAL TRIAL REGISTRATION IF APPLICABLE: Clinicaltrials.gov: NCT04488081.

BACKGROUND: The recruitment-to-inflation (R/I) ratio is a new bedside tool with potential to evaluate lung recruitability by positive end-expiratory pressure (PEEP) but was only validated using pressure-volume curves and the optimal threshold separating low and high recruiters by PEEP is not precisely known. The aim of the study is to evaluate the diagnostic performance of the R/I ratio using computed tomography (CT) as a gold standard in patients with acute respiratory distress syndrome (ARDS). METHODS: This study is a single-center prospective observational study performed on adults ARDS patients under invasive mechanical ventilation. The R/I ratio was measured with the ventilator, and low-dose CT scans were acquired at PEEP 15 and 5 cmH RESULTS: Fifty patients were included, and eight patients were secondarily excluded (7/50 [14%] for suspected air leaks, and 1/50 [2%] for airway opening pressure > 15 cmH CONCLUSIONS: In a population of ARDS patients with low recruitment potential, the R/I ratio had a poor diagnostic performance to predict lung recruitability, but R/I ratio values below 0.57 reliably identified ARDS patients with low recruitability, provided they did not present focal ARDS.

OBJECTIVES: Primary: To evaluate the level of sedation, use, daily doses, and duration of analgosedative drugs in COVID-19 patients on mechanical ventilation (MV) using a standardized protocol, comparing survivors and non-survivors. Secondary: To identify independent predictors of hospital mortality. DESIGN: Retrospective cohort study. SETTING: Medical-surgical ICU. PATIENTS: Adults with SARS-CoV-2 infection requiring invasive MV and continuous infusion of analgosedation and/or neuromuscular blocking agents (NMBAs) for at least 48 h. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Level of sedation, use, daily doses, and duration of analgosedative drugs; hospital mortality and associated factors. RESULTS: Among 198 patients (nurse-to-patient ratio 1:2.4; 65% staff turnover), median global RASS was -4.5. Kaplan-Meier analysis showed lower survival with deeper sedation. Fentanyl (99%) and midazolam (97%) were the most used, followed by NMBAs (81%), propofol and dexmedetomidine (48%). Non-benzodiazepine sedatives were precribed more in survivors (88%) than non-survivors (53%) (p < 0.01). Survivors had more days of fentanyl, midazolam, and dexmedetomidine; no differences in NMBA use or drug doses were observed. Mortality was 63%. Independent predictors of mortality included APACHE II, SOFA CONCLUSIONS: Standardized protocols emphasizing the ACD components of the ABCDEF bundle, along with appropriate use of analgosedation and NMBAs despite limited staffing, effectively supported the management of sedation without significant dose differences between survivors and non-survivors. Sedation level and the use of non-benzodiazepine sedatives were independently associated with better outcomes, highlighting the importance of the light sedation and the ABCDEF bundle.