Daily Ards Research Analysis
Across ARDS care, a large binational cohort found no association between ECMO center volume and 6‑month death or disability, suggesting coordinated regional networks may offset traditional volume–outcome effects. In COVID‑19 ARDS, high-sensitivity troponin T on the day of extubation independently predicted extubation failure. In neonatal RDS, a meta-analysis of 26 RCTs indicates surfactant plus budesonide lowers BPD risk and resource use, though overall certainty is mostly low.
Summary
Across ARDS care, a large binational cohort found no association between ECMO center volume and 6‑month death or disability, suggesting coordinated regional networks may offset traditional volume–outcome effects. In COVID‑19 ARDS, high-sensitivity troponin T on the day of extubation independently predicted extubation failure. In neonatal RDS, a meta-analysis of 26 RCTs indicates surfactant plus budesonide lowers BPD risk and resource use, though overall certainty is mostly low.
Research Themes
- ECMO organization and long-term outcomes
- Biomarkers for extubation readiness in ARDS
- Pharmacotherapy to prevent BPD in neonatal RDS
Selected Articles
1. Hospital-level volume in extracorporeal membrane oxygenation cases and death or disability at 6 months.
In a binational registry-embedded cohort (n=1,232), ECMO center volume (>30 vs ≤30 cases/year) was not associated with death or new disability at 6 months across VV-, VA-, and ECPR-ECMO after multivariable adjustment. Sensitivity analyses, including exclusion of inter-hospital transfers, confirmed the null association, implicating coordinated regional care and training.
Impact: Provides high-quality, long-term, patient-centered outcomes that challenge the assumption that higher ECMO volume necessarily yields better results. Informs regionalization, transfer policies, and training strategies.
Clinical Implications: Health systems should prioritize coordinated networks, standardized protocols, and inter-hospital transfers/training over rigid volume thresholds when organizing ECMO services and benchmarking outcomes.
Key Findings
- No difference in 6‑month death or new disability between high- and low-volume centers for VV-ECMO (OR 1.09, 95% CI 0.65–1.83; p=0.744).
- No difference for VA-ECMO (OR 1.10, 95% CI 0.66–1.84; p=0.708) or ECPR (OR 1.38, 95% CI 0.37–5.08; p=0.629).
- Findings were consistent across sensitivity analyses, including exclusion of transferred patients; total n=1,232 (663 high-volume, 569 low-volume).
Methodological Strengths
- Registry-embedded, multicenter binational cohort with pre-specified 6‑month patient-centered outcome.
- Multivariable analyses across ECMO subgroups with sensitivity analyses including transfer exclusions.
Limitations
- Observational design leaves potential residual confounding.
- Generalizability may be limited to regions with coordinated ECMO networks (Australia/New Zealand).
Future Directions: Prospective multicenter studies to identify which components of coordinated networks (e.g., protocols, simulation training, transfer timing) drive outcome equivalence; incorporation of patient-reported outcomes and cost-effectiveness.
OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) is a high-risk procedure with significant morbidity and mortality and there is an uncertain volume-outcome relationship, especially regarding long-term functional outcomes. The aim of this study was to examine the association between ECMO centre volume and long-term death and disability outcomes. DESIGN SETTING AND PARTICIPANTS: This is a registry-embedded observational cohort study. Patients were included if they were enrolled in the binational ECMO registry (EXCEL). The exclusion criteria included patients on ECMO for heart/lung transplants. Data included demographics, clinical information on their first ECMO run, and six-month outcomes obtained by telephone interview. The primary outcome was death or new disability at six months. A multivariable analysis was conducted using hospitals' annual ECMO volume. High-volume centres were defined as having >30 ECMO cases annually, and analyses were run on ECMO subgroups of veno-venous (VV), veno-arterial (VA), and extracorporeal cardiopulmonary resuscitation (ECPR). RESULTS: Of 1232 patients, 663 patients were cared for on ECMO at high-volume centres and 569 patients at low-volume centres. There was no difference in six-month death or new disability between high- and low-volume ECMO centres in VV-ECMO [OR: 1.09 (0.65-1.83), p = 0.744], VA-ECMO [OR: 1.10 (0.66-1.84), p = 0.708], and ECPR-ECMO [OR: 1.38 (0.37-5.08), p = 0.629]. This finding was persistent in all sensitivity analyses, including exclusion of patients who were transferred between high- and low-volume centres. CONCLUSION: There was no difference in death or disability at six months between high- and low-volume centres in Australia and New Zealand, possibly due to the current model of coordinated care that includes patient transfers and training between high- and low-volume ECMO centres in our region.
2. The prognostic role of cardiac and inflammatory biomarkers in extubation failure in patients with COVID-19 acute respiratory distress syndrome.
Among 297 extubated C-ARDS patients, 21.5% failed extubation. On the day of extubation, Hs‑TnT, NT‑proBNP, and PCT were associated with failure in univariable analyses; only Hs‑TnT remained independently associated after adjusting for age, ventilation days, and SOFA (adjusted OR 1.38, 95% CI 1.02–1.90). Combined elevation of Hs‑TnT and PCT identified a 46% failure risk vs 13% when both were normal.
Impact: Identifies a readily available cardiac biomarker (Hs‑TnT) that independently stratifies extubation risk in C‑ARDS, enabling more objective liberation decisions.
Clinical Implications: Consider incorporating Hs‑TnT into extubation readiness assessments in C‑ARDS, alongside clinical variables; patients with elevated Hs‑TnT (± elevated PCT) may benefit from enhanced monitoring, optimization, or delayed extubation.
Key Findings
- Extubation failure occurred in 21.5% of 297 C‑ARDS patients.
- On extubation day, Hs‑TnT (OR 1.72), NT‑proBNP (OR 1.24), and PCT (OR 1.38) were associated with failure in univariable analyses.
- After multivariable adjustment, only Hs‑TnT remained independently associated (adjusted OR 1.38, 95% CI 1.02–1.90). Combined elevated Hs‑TnT (≥14 ng/mL) and PCT (≥0.25 ng/mL) conferred a 46% failure risk vs 13% when both normal.
Methodological Strengths
- Clearly defined endpoint (reintubation or death within 7 days) and adjustment for key clinical confounders (age, ventilation duration, SOFA).
- Real-world single-center cohort with standardized biomarker measurements on the day of extubation.
Limitations
- Single-center retrospective design limits generalizability and causal inference.
- Focused on C‑ARDS; applicability to non-COVID ARDS requires validation.
Future Directions: Prospective multicenter validation and integration of Hs‑TnT with clinical indices and physiologic weaning tests to build multivariable risk models; assessment of biomarker-guided extubation strategies.
BACKGROUND: Extubation failure is associated with an increased morbidity, emphasizing the need to identify factors to further optimize extubation practices. The role of biomarkers in the prediction of extubation failure is currently limited. The aim of this study was to investigate the prognostic value of cardiac (N-terminal pro-B-type natriuretic peptide (NT-proBNP), High-sensitivity Troponin T (Hs-TnT)) and inflammatory biomarkers (Interleukin-6 (IL-6) and Procalcitonin (PCT)) for extubation failure in patients with COVID-19 Acute Respiratory Distress Syndrome (C-ARDS). MATERIALS AND METHODS: In this single-center retrospective cohort study, patient characteristics and laboratory measurements were extracted from electronic medical records. Patients were eligible for inclusion if they were extubated after mechanical ventilation. The primary endpoint was extubation failure, defined as the need for reintubation or death within the next seven days after extubation, regardless of whether post-extubation respiratory support was used. Uni- and multivariable logistic regression was performed to investigate the association between biomarkers and extubation failure. Biomarkers were log RESULTS: Of the 297 patients included, 21.5% experienced extubation failure. In univariable analysis, NT-proBNP (OR 1.24, 95% CI 1.06-1.47), Hs-TnT (OR 1.72, 95% CI 1.37-2.19) and PCT (OR 1.38, 95% CI 1.16-1.65) measured on the day of extubation were significantly associated with extubation failure. After multivariable adjustment for clinical variables (age, duration of mechanical ventilation, SOFA score), Hs-TnT was the only biomarker that was independently associated with extubation failure (adjusted OR 1.38, 95% CI 1.02-1.90). Patients with both elevated Hs-TnT (≥ 14 ng/mL) and elevated PCT (≥ 0.25 ng/mL) carried the highest risk of extubation failure (46%), while in patients with normal Hs-TnT and PCT values, only 13% experienced extubation failure. CONCLUSIONS: Hs-TnT, NT-proBNP and PCT measured on the day of extubation are associated with extubation failure in mechanically ventilated patients with C-ARDS. Since Hs-TnT is the only biomarker that is independently associated with extubation failure, Hs-TnT could offer additional objective measures for assessing readiness for extubation. Future studies should focus on an integrative approach of biomarkers combined with relevant clinical factors to predict extubation failure.
3. Efficacy of pulmonary surfactant with budesonide in premature infants: A systematic review and meta-analysis.
Across 26 RCTs (n=2,701), adding budesonide to pulmonary surfactant reduced bronchopulmonary dysplasia (RR 0.61) and shortened ventilation days (−2.21), oxygen days (−5.86), and hospital stay (−5.61) versus surfactant alone, without short-term adverse events. Overall certainty was mostly low to very low by GRADE, with moderate certainty supporting reductions in moderate-to-severe BPD.
Impact: Synthesizes a large RCT evidence base suggesting a widely available steroid added to surfactant may reduce BPD and resource use in preterm infants, informing practice while highlighting the need for higher-quality trials.
Clinical Implications: Consider budesonide with surfactant for high-risk preterm infants in settings with protocols and monitoring, while recognizing the low certainty and prioritizing enrollment in ongoing high-quality trials and long-term safety follow-up.
Key Findings
- 26 RCTs (n=2,701) compared PS+budesonide vs PS alone.
- PS+budesonide reduced BPD incidence (RR 0.61; 95% CI 0.51–0.73).
- Shortened mechanical ventilation (MD −2.21 days), oxygen requirement (MD −5.86 days), and hospital stay (MD −5.61 days); no increase in short-term adverse events; overall evidence certainty mostly low to very low.
Methodological Strengths
- Comprehensive multi-database search with random-effects meta-analysis and GRADE assessment.
- Large aggregate sample size across randomized trials enabling precise estimates for key clinical outcomes.
Limitations
- Overall evidence certainty rated mostly low to very low due to study quality and heterogeneity.
- Limited data on long-term neurodevelopmental outcomes and standardized dosing/administration protocols.
Future Directions: Large pragmatic multicenter RCTs with standardized dosing/administration, stratification by BPD risk, and long-term neurodevelopmental and safety outcomes; implementation studies in diverse care settings.
Pulmonary surfactant (PS) is one of the main treatment for neonates with respiratory distress syndrome (RDS). Budesonide has recently been studied as an additional treatment in such cases, but there is limited evidence supporting this. This study was implemented to determine the efficacy of PS combined with budesonide in premature infants. To achieve this, we conducted a systematic review and meta-analysis of randomized controlled trials by searching PubMed, Scopus, Embase, and the Cochrane Library from inception until July 12, 2024. We utilized a random-effects model to calculate the risk ratio and mean differences (MDs) with 95% confidence intervals (CIs) for the clinical outcomes of PS with budesonide versus PS alone. We used the GRADE approach to assess the quality of the evidence. We included 26 randomized controlled trials with a total of 2701 patients in the analysis. Treatments of PS with budesonide and PS alone were compared in all trials. PS with budesonide reduced bronchopulmonary dysplasia (BPD) incidence (risk ratio, 0.61; 95% CI, 0.51, 0.73), duration of mechanical or invasive mechanical ventilation (MD, -2.21 days; 95% CI, -2.72, -1.71), duration requiring oxygen (MD, -5.86 days; 95% CI, -8.44, -3.29), and hospitalization time (MD, -5.61 days; 95% CI, -8.65, -2.56). These results were based on low to very low evidence certainty. Only moderate-to-severe BPD or severe BPD showed a significant reduction when PS was used in conjunction with budesonide, a finding supported by moderate evidence certainty. Our study showed that the administration of PS with budesonide significantly improved respiratory outcomes, including the incidence of BPD, duration of mechanical or invasive mechanical ventilation, duration requiring oxygen, and hospitalization time in preterm infants, without short-term adverse drug events. However, the evidence certainty was mostly low to very low.