Daily Ards Research Analysis

OBJECTIVE: The "REstricted vs. Liberal positive end-expiratory pressure in patients without Acute Respiratory Distress Syndrome (ARDS)" (RELAx) trial compared lower vs. higher positive end-expiratory pressures (PEEP) in invasively ventilated critically ill patients without ARDS, concluding non-inferiority of lower PEEP in frequentist analysis. This study aimed to perform a Bayesian re-analysis of RELAx to assess probabilities of clinically meaningful differences between lower and higher PEEP. DESIGN: A post hoc Bayesian analysis of RELAx data. SETTING: RELAx was a non-inferiority multicenter trial conducted between October 2017 and March 2019 in eight ICUs. PATIENTS: The trial included 980 ICU patients expected to require invasive mechanical ventilation greater than or equal to 24 hours for reasons other than ARDS. All patients included in the original analysis entered the Bayesian re-analysis. INTERVENTIONS: Participants were randomized to the lowest possible PEEP between 0 and 5 cm H2O or to a higher PEEP of 8 cm H2O. MEASUREMENTS AND MAIN RESULTS: The primary outcome was ventilator-free days at day 28 (VFD-28). Secondary outcomes were 28-day mortality and ventilation duration. The odds ratio for higher VFD-28 with lower PEEP was 1.08 (95% credible intervals, 0.87-1.35), with consistent estimates across priors and with a probability of superiority ranging from 75% to 78%. For 28-day mortality and duration of ventilation, the probability of benefit of the lower-PEEP strategy ranged from 72% to 89%, and from 11% to 28%, respectively. In patients admitted for other reasons than cardiac arrest or intubated for other reasons than respiratory failure, probabilities of benefit with lower PEEP exceeded 90%. CONCLUSIONS: Although the probability of benefit in the overall population was modest, the analysis suggested a higher probability of benefit in selected subgroups, particularly patients admitted for other reasons than cardiac arrest or intubated for other reasons than respiratory failure. These findings highlight potential heterogeneity of treatment effect and support further investigations.

IMPORTANCE: In preterm neonates supported with continuous positive airway pressure (CPAP), early caffeine administration and less invasive surfactant administration (LISA) results in a lower frequency of endotracheal intubation. It is unknown whether this regimen improves outcomes at a corrected age of 2 years in this population. OBJECTIVE: To determine whether LISA improves neurodevelopmental impairment (NDI) and pulmonary outcomes at a corrected age of 2 years. DESIGN, SETTING, AND PARTICIPANTS: This prespecified secondary analysis and follow-up of a randomized clinical trial was performed at 3 academic medical centers in California. Participants included infants born at gestational ages ranging from 24 weeks 0 days to 29 weeks 6 days with follow-up assessments available. Follow-up visits occurred from May 2, 2022, to April 3, 2025. INTERVENTIONS: Infants received intravenous caffeine by 2 hours of life followed by either less invasive surfactant administration (intervention group) or CPAP without initial surfactant administration (control group). MAIN OUTCOMES AND MEASURES: The primary outcome was the composite of death or moderate to severe NDI at a corrected age of 2 years, as measured by the Bayley Scales of Infant Development (BSID). Secondary outcomes included components of the BSID composite; the third edition of the Ages and Stages Questionnaire (ASQ-3); developmental screening; pulmonary outcomes of bronchodilator use, oral and/or inhaled corticosteroid use, or hospitalizations with respiratory diagnoses after discharge; and results of an autism screen. RESULTS: Of 180 randomized infants, 147 (81.7%) had follow-up assessments available (74 in the LISA group and 73 in the CPAP group); 75 infants (51.0%) were male. The mean (SD) gestational age at the time of the Bayley assessment was 24.6 (1.5) months corrected age for the LISA group and 24.7 (2.2) months corrected age for the CPAP group. The mean (SD) chronological age for the ASQ-3 was 28.1 (2.4) months for both groups. Death or moderate to severe NDI occurred in 17 of 74 children (23.0%) in the LISA group and 23 of 70 (32.9%) in the control group (odds ratio [OR], 1.56 [95% CI, 0.77-3.17]; P = .22). On the screening ASQ-3, infants in the LISA group had no statistically significant differences in rates of typical development (22 of 69 [31.9%] vs 12 of 67 [17.9%]; OR, 0.47 [95% CI, 0.21-1.04]; P = .06) and scores indicating possible delay (43 of 69 [62.3%] vs 47 of 67 [70.1%]; OR, 1.42 [95% CI, 0.70-2.90]; P = .34) compared with the control group. Children in the LISA group were more likely to have a mean (SD) fine motor z score in the reference range (-0.59 [1.10] vs -1.00 [1.01]; P = .03). There were no differences between the LISA and CPAP groups in bronchodilator use, oral and/or inhaled corticosteroid use, or postdischarge hospitalizations with respiratory diagnoses. CONCLUSIONS AND RELEVANCE: In this secondary analysis of a randomized clinical trial of preterm infants supported with CPAP, early caffeine administration plus LISA did not reduce the incidence of death or moderate to severe NDI noted on the BSID. Infants who received LISA were more likely to have a fine motor domain score in the reference range on ASQ-3 developmental screen. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04209946.

Sepsis affects around 50 million people annually and is a significant contributor to acute respiratory distress syndrome (ARDS), leading to high morbidity and mortality. Sepsis-induced ARDS is the leading cause of ARDS globally and has worse outcomes compared to other causes, with mortality rates up to 40% in severe instances. Geographic variability in ARDS prevalence is notable, with rates of 27% among septic patients in China, 6-7% in Western countries, and up to 31% in sub-Saharan African Intensive Care Units, highlighting significant disparities in disease burden and outcomes. Management of sepsis-induced ARDS generally necessitates mechanical ventilation, yet extended ventilatory support can lead to negative outcomes. Weaning from ventilation is complicated by the inflammatory response and multiorgan dysfunction seen in sepsis. Traditional weaning predictors, like the rapid shallow breathing index, show inadequate sensitivity and specificity, indicating a requirement for more effective predictive tools. Recent studies have identified several biomarkers, including Pancreatic Stone Protein, soluble receptor for advanced glycation end-products, and soluble urokinase plasminogen activator receptor, as promising tools for enhancing the prediction of mechanical ventilation outcomes in sepsis-induced ARDS. Despite the identification of multiple biomarkers, a major clinical gap remains: there is currently no consensus on their routine use to guide weaning, largely due to inconsistent findings, heterogeneity in study designs, and limited large-scale validation. This review explores the role of circulating and respiratory biomarkers in improving outcomes for patients with sepsis-induced ARDS, particularly in predicting successful mechanical ventilation weaning. It appraises the evidence surrounding these biomarkers against traditional weaning indices and identifies gaps in existing research. The review emphasizes the strengths and limitations of current studies, suggesting that validated biomarker-guided strategies could significantly enhance clinical management by reducing ventilation duration, preventing extubation failures, and improving survival rates in this vulnerable patient group.