Daily Ards Research Analysis
Analyzed 10 papers and selected 3 impactful papers.
Summary
A Bayesian re-analysis of the RELAx RCT suggests lower PEEP is likely non-inferior and may be beneficial for selected non-ARDS ICU patients, underscoring heterogeneity of treatment effect. A prespecified 2-year follow-up of an RCT in preterm neonates found early caffeine plus LISA did not reduce death or moderate–severe neurodevelopmental impairment but improved fine motor screening scores. A meta-analysis reports ~20% incidence of BPD-associated pulmonary hypertension and highlights key modifiable and perinatal risk factors.
Research Themes
- Personalized mechanical ventilation and PEEP strategies in ICU
- Long-term neurodevelopment after less invasive surfactant administration in preterm neonates
- Risk stratification for BPD-associated pulmonary hypertension
Selected Articles
1. Effect of a Lower Vs. Higher Positive End-Expiratory Pressure Strategy on Clinically Relevant Outcomes in ICU Patients Without Acute Respiratory Distress Syndrome: Bayesian Re-analysis of the REstricted Vs. Liberal Positive End-Expiratory Pressure in Patients Without Acute Respiratory Distress Syndrome (RELAx) Randomized Clinical Trial.
A Bayesian re-analysis of the multicenter RELAx RCT (n=980) found that lower PEEP likely yields similar or better ventilator-free days by day 28 versus higher PEEP, with modest overall probability of benefit and stronger signals in prespecified clinical subgroups. Results emphasize heterogeneity of treatment effect in non-ARDS ICU patients and support individualized PEEP strategies.
Impact: Introduces probabilistic evidence on lower PEEP strategies using Bayesian methods, informing personalized ventilation beyond frequentist non-inferiority conclusions.
Clinical Implications: For invasively ventilated non-ARDS ICU patients, lower PEEP may be reasonable and potentially beneficial, particularly in select subgroups, supporting individualized PEEP titration rather than uniform high PEEP.
Key Findings
- Lower PEEP showed an odds ratio of 1.08 (95% CrI 0.87–1.35) for higher VFD-28 with a 75–78% probability of superiority.
- Probability of benefit with lower PEEP was 72–89% for 28-day mortality and 11–28% for ventilation duration.
- In patients admitted for reasons other than cardiac arrest or intubated for non-respiratory failure, probability of benefit exceeded 90%.
- Findings point to heterogeneity of treatment effect across patient subgroups.
Methodological Strengths
- Bayesian re-analysis with consistency across priors enables probabilistic interpretation of benefit
- Large multicenter RCT dataset (n=980) with prespecified outcomes in the parent trial
Limitations
- Post hoc nature of the re-analysis; not a new randomized comparison
- Findings apply to non-ARDS patients and to the tested PEEP targets (0–5 vs 8 cmH2O), which may limit generalizability
Future Directions: Prospective Bayesian-informed RCTs to validate subgroup benefits and integrate physiologic phenotyping for PEEP titration.
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.
2. Two-Year Outcomes of Less Invasive Surfactant Administration Among Preterm Neonates: A Secondary Analysis of a Randomized Clinical Trial.
In preterm infants randomized to early caffeine plus LISA versus CPAP alone, the composite of death or moderate–severe NDI at 2 years did not differ significantly, though fine motor domain scores on ASQ-3 were more often within the reference range in the LISA group. Pulmonary medication use and respiratory hospitalizations after discharge were similar between groups.
Impact: Provides well-powered, prespecified long-term follow-up data after a widely adopted neonatal respiratory intervention, including important negative results and domain-specific developmental signals.
Clinical Implications: LISA may not reduce the composite of death or moderate–severe NDI at 2 years, but potential fine motor benefits warrant consideration in shared decision-making; long-term neurodevelopment should remain a key outcome in neonatal respiratory care.
Key Findings
- Death or moderate–severe NDI at 2 years: 23.0% (LISA) vs 32.9% (control); P=0.22 (not significant).
- ASQ-3 typical development rates trended higher with LISA (31.9% vs 17.9%; P=0.06).
- Fine motor z score more often within reference range with LISA (mean -0.59 vs -1.00; P=0.03).
- No differences in postdischarge bronchodilator or steroid use, or respiratory hospitalizations.
Methodological Strengths
- Prespecified secondary analysis with standardized neurodevelopmental assessments (BSID, ASQ-3)
- Multicenter randomized trial cohort with high follow-up rate (81.7%)
Limitations
- Secondary analysis may be underpowered for some outcomes; P-values indicate non-significance on primary composite
- Conducted at three centers in California, which may limit generalizability
Future Directions: Larger multicenter follow-ups to confirm domain-specific developmental benefits and to evaluate respiratory health trajectories into childhood.
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.
3. [A Meta analysis of risk factors for pulmonary hypertension related to bronchopulmonary dysplasia in preterm infants].
Across 15 observational studies (n=4,561), the pooled incidence of BPD-associated PH in preterm infants was approximately 20%. Risk increased with hemodynamically significant PDA, longer mechanical ventilation, SGA, severe BPD, PDA requiring ligation, oligohydramnios, ventilator-associated pneumonia, and neonatal respiratory distress syndrome.
Impact: Quantifies BPD-PH burden and consolidates multiple perinatal and respiratory risk factors, supporting targeted surveillance in high-risk preterm infants.
Clinical Implications: NICUs should prioritize echocardiographic screening for BPD-PH among infants with hemodynamically significant PDA, prolonged ventilation, severe BPD, SGA, and other identified risk factors to enable earlier intervention.
Key Findings
- Pooled incidence of BPD-associated pulmonary hypertension in preterm infants was approximately 20%.
- Risk factors included hemodynamically significant patent ductus arteriosus, longer mechanical ventilation, small for gestational age (SGA), and severe BPD.
- Additional risk markers: PDA requiring surgical ligation, oligohydramnios, ventilator-associated pneumonia, and neonatal respiratory distress syndrome.
Methodological Strengths
- Comprehensive multi-database search across Chinese and international sources
- Meta-analytic synthesis of cohort and case-control studies with explicit software (Stata 15.0)
Limitations
- Based on observational studies, subject to residual confounding
- Heterogeneity in study designs and definitions may affect pooled estimates; PRISMA adherence and heterogeneity metrics not detailed in the abstract
Future Directions: Prospective, standardized echocardiographic screening studies to refine risk prediction models and evaluate targeted preventive strategies for BPD-PH.
OBJECTIVES: To systematically evaluate the incidence and risk factors of pulmonary hypertension (PH) associated with bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: Cohort and case-control studies on the incidence and risk factors of PH complicating BPD (hereinafter referred to as BPD-PH) in preterm infants, published from database inception to July 2024, were retrieved from China National Knowledge Infrastructure, Wanfang Data, VIP Database, Chinese Biomedical Literature Database, PubMed, Web of Science, Embase, MEDLINE, and Cochrane Library. Meta analysis was performed using Stata 15.0 software. RESULTS: A total of 15 studies involving 4 561 preterm infants were included. Meta analysis results showed that the overall incidence of BPD-PH in preterm infants was 20.1% (95% CONCLUSIONS: The overall incidence of BPD-PH in preterm infants is relatively high. Hemodynamically significant patent ductus arteriosus, mechanical ventilation duration, SGA, severe BPD, patent ductus arteriosus requiring surgical ligation, oligohydramnios, ventilator-associated pneumonia, and respiratory distress syndrome can increase the risk of PH in preterm infants with BPD, and clinical monitoring should prioritize BPD infants with these high-risk factors.