Daily Ards Research Analysis
Early prone positioning in invasively ventilated COVID-19 ARDS is associated with reduced 28- and 90-day mortality, underscoring the importance of timing. A large EHR-based cohort identifies serum anion gap as an independent prognostic marker in ARDS and suggests furosemide may be beneficial in patients with the highest anion gap. In neonates, a refined thoracic ultrasound score outperforms traditional LUS in late preterm infants for predicting surfactant need.
Summary
Early prone positioning in invasively ventilated COVID-19 ARDS is associated with reduced 28- and 90-day mortality, underscoring the importance of timing. A large EHR-based cohort identifies serum anion gap as an independent prognostic marker in ARDS and suggests furosemide may be beneficial in patients with the highest anion gap. In neonates, a refined thoracic ultrasound score outperforms traditional LUS in late preterm infants for predicting surfactant need.
Research Themes
- Time-sensitive interventions in ARDS (prone positioning within 48 hours)
- Prognostication and phenotype-guided therapy in ARDS using routine labs (anion gap)
- Point-of-care ultrasound for neonatal respiratory management (surfactant prediction)
Selected Articles
1. Effect of early and later prone positioning on outcomes in invasively ventilated COVID-19 patients with acute respiratory distress syndrome: analysis of the prospective COVID-19 critical care consortium cohort study.
In a global prospective cohort of 3131 invasively ventilated COVID-19 patients, prone positioning within 48 hours of starting IMV was associated with lower 28- and 90-day mortality compared with never being proned. Proning initiated after 48 hours showed no significant association with mortality.
Impact: This study clarifies the time-sensitive nature of prone positioning benefits in COVID-19 ARDS using a large, prospective, multinational dataset. It provides practice-relevant evidence to prioritize early proning.
Clinical Implications: ICUs should prioritize initiating prone positioning within 48 hours of IMV in eligible COVID-19 ARDS patients and monitor timing as a quality metric. Later initiation appears unlikely to improve survival; protocols should focus on early screening and logistics to avoid delays.
Key Findings
- Among 3131 patients, 33% were proned within 48 h, 20% after 48 h, and 47% were never proned.
- Early proning (≤48 h) was associated with lower 28-day mortality (HR 0.82; 95% CI 0.68–0.98; p=0.03) and 90-day mortality (HR 0.81; 95% CI 0.68–0.96; p=0.02) versus never proned.
- Proning after 48 h was not associated with reduced 28-day (HR 0.93; p=0.47) or 90-day mortality (HR 0.95; p=0.59).
Methodological Strengths
- Prospective, multinational cohort with large sample size (N=3131)
- Clear exposure definition by timing (≤48 h vs >48 h) and time-to-event analyses
Limitations
- Observational design susceptible to residual confounding and selection bias for proning
- Generalizability to non-COVID ARDS is uncertain
Future Directions: Conduct randomized or pragmatic cluster trials to test early versus delayed/no proning and evaluate physiological responsiveness and safety across ARDS phenotypes, including non-COVID etiologies.
BACKGROUND: Prone positioning of patients with COVID-19 undergoing invasive mechanical ventilation (IMV) is widely used, but evidence of efficacy remains sparse. The COVID-19 Critical Care Consortium has generated one of the largest global datasets on the management and outcomes of critically ill COVID-19 patients. This prospective cohort study investigated the association between prone positioning and mortality and in particular focussed on timing of treatment. METHODS: We investigated the incidence, demographic profile, management and outcomes of proned patients undergoing IMV for COVID-19 in the study. We compared outcomes between patients prone positioned within 48 h of IMV to those (i) never proned, and (ii) proned only after 48 h. RESULTS: 3131 patients had data on prone positioning, 1482 (47%) were never proned, 1034 (33%) were proned within 48 h and 615 (20%) were proned only after 48 h of commencement of IMV. 28-day (hazard ratio 0.82, 95% confidence interval [CI] 0.68, 0.98, p = 0.03) and 90-day (hazard ratio 0.81, 95% CI 0.68, 0.96, p = 0.02) mortality risks were lower in those patients proned within 48 h of IMV compared to those never proned. However, there was no evidence for a statistically significant association between prone positioning after 48 h with 28-day (hazard ratio 0.93, 95% CI 0.75, 1.14, p = 0.47) or 90-day mortality (hazard ratio 0.95, 95% CI 0.78, 1.16, p = 0.59). CONCLUSIONS: Prone positioning is associated with improved outcomes in patients with COVID-19, but timing matters. We found no association between later proning and patient outcome.
2. A Refined Score, Namely Thoracic Ultrasound Score, to Predict the Need for Surfactant in Preterm Neonates: A Prospective, Multicenter, Observational Study.
In a prospective multicenter cohort of preterm neonates (N=170), the thoracic ultrasound score (TUS) correlated with oxygenation similarly to LUS but showed superior prediction of surfactant need in infants with GA ≥34 weeks (AUC 0.971 vs 0.797; p=0.02). Performance was comparable to LUS in GA <34 weeks.
Impact: This study introduces a refined ultrasound score that specifically addresses a known limitation of LUS in late preterm infants, potentially improving early, noninvasive decision-making for surfactant therapy.
Clinical Implications: TUS may be adopted to guide early surfactant decisions in preterm neonates, particularly GA ≥34 weeks, potentially reducing unnecessary intubations or delayed therapy. Implementation requires standardized scanning protocols and operator training.
Key Findings
- Preterm neonates (N=170): 58 received surfactant vs 112 did not; GA and birth weight were lower in the treated group.
- TUS and LUS correlated with oxygenation metrics: S/F ratio (r = -0.670 and r = 0.615) and OSI (r = 0.524 and r = 0.423), all p < 0.001.
- In GA ≥34 weeks, TUS outperformed LUS for predicting surfactant need (AUC 0.971 vs 0.797; p=0.02); in GA <34 weeks, performance was similar (AUC 0.956 vs 0.952).
Methodological Strengths
- Prospective, multicenter design with standardized imaging within 3 hours of life
- Stratified ROC analyses by gestational age with objective oxygenation correlates (S/F, OSI)
Limitations
- Moderate sample size and potential operator dependence of ultrasound assessments
- Clinical impact on hard outcomes (e.g., intubation rates, LOS) not tested in interventional trials
Future Directions: External validation in independent cohorts and randomized implementation studies to test whether TUS-guided protocols improve clinical outcomes and resource use.
INTRODUCTION: Lung ultrasound score (LUS) is used to predict the need for surfactant in preterm neonates. Its performance is lower in neonates with a gestational age (GA) ≥ 34 weeks. We developed a score, thoracic ultrasound score (TUS), to overcome the shortcomings of LUS. OBJECTIVES: To assess the feasibility and diagnostic accuracy of TUS to evaluate oxygenation and predict the need for surfactant administration, compared to LUS. MATERIALS AND METHODS: This was a prospective, multicenter, observational study. Preterm neonates in noninvasive ventilation with GA between 24 + 0 and 36 + 6 weeks were assessed for eligibility. Lung ultrasound were performed within 3 h of life, and TUS and LUS were calculated. RESULTS: Fifty-eight neonates who received surfactant were compared with 112 neonates who did not receive surfactant: GA 30.2 ± 3.1 weeks versus 32.6 ± 2.3 weeks, (p < 0.001), and birth weight 1466 ± 674 g versus 1725 ± 519 g, (p = 0.006), respectively. TUS and LUS showed a similar association with S/F ratio (r = -0.670 and r = 0.615) and OSI (r = 0.524 and r = 0.423), all p < 0.001. In neonates with GA < 34 weeks, the AUC (95% CI) was similar: 0.956 (0.923-0.989) versus 0.952 (0.921-0.984). In neonates with GA ≥ 34 weeks, the AUC (95% CI) of TUS was superior to LUS: 0.971 (0.914-1.000) versus 0.797 (0.639-0.980), p = 0.02. CONCLUSION: Compared to LUS, TUS showed a similar association with the oxygenation status and a superior ability to predict the need for surfactant in neonates with GA ≥ 34 weeks. The latter was similar in neonates with GA < 34 weeks.
3. Anion gap predicting 90-Day mortality and guiding furosemide use in ARDS.
Using MIMIC-IV data on 11,227 ARDS patients, higher serum anion gap independently predicted 90-day mortality. Furosemide use was associated with reduced mortality only in the highest anion gap quartile, suggesting potential benefit in a high–anion gap phenotype.
Impact: This large-scale analysis elevates a readily available lab (anion gap) as a prognostic biomarker in ARDS and generates a testable hypothesis for phenotype-guided diuretic therapy.
Clinical Implications: In ARDS, routinely assess and trend anion gap to inform risk stratification. Consider conservative fluid strategy and cautious furosemide use in patients with very high anion gap while awaiting prospective validation; avoid overinterpreting causality given potential confounding.
Key Findings
- Retrospective cohort of 11,227 ARDS patients from MIMIC-IV (v2.2).
- Elevated anion gap independently associated with higher 90-day mortality (adjusted HR 1.23; 95% CI 1.10–1.37; p<0.001).
- Furosemide showed a protective association only in the highest anion gap quartile (Q4: adjusted HR 0.57; 95% CI 0.50–0.65; p<0.001), with no significant effect in Q2–Q3.
Methodological Strengths
- Very large sample size with robust multivariable Cox models
- Dose–response evaluation using restricted cubic splines and stratified subgroup analyses
Limitations
- Retrospective EHR-based study with potential residual confounding and ARDS misclassification
- Confounding by indication likely for furosemide; fluid balance and hemodynamic data may be limited
Future Directions: Prospective validation and randomized trials of diuretic strategies guided by anion gap or metabolic phenotype to establish causality and refine patient selection.
The objective of this study was to investigate whether serum anion gap (AG), which may serve as an indicator for multiple organic dysfunctions in the condition of hypoxia, could be utilized as a reliable prognostic marker for short-term mortality and a potential therapeutic target in patients with acute respiratory distress syndrome (ARDS). A retrospective cohort study was conducted using data from the Medical Information Mart for Intensive Care (MIMIC-IV) electronic database (version 2.2), including 11,227 confirmed patients with ARDS. Multivariate Cox proportional hazards analysis revealed a significant association between elevated AG levels and all-cause mortality. After adjusting for confounding factors, elevated AG levels were strongly correlated with 90-day mortality [adjusted hazard ratio (HR) 1.23; 95% confidence interval (CI) 1.10-1.37; P < 0.001]. Restricted cubic splines and Kaplan-Meier curves demonstrated an increased risk of all-cause mortality with higher AG levels. Subgroup analysis results emphasized the significance of furosemide as a pivotal therapeutic option, which was further supported by subsequent Kaplan-Meier curves and Cox proportional hazards analysis showing its protective effects in patients with elevated serum AG levels. Even after adjusting for relevant confounding factors, furosemide continued to exhibit a significant protective effect in the group with the highest AG level (Q4: adjusted HR 0.57; 95% CI 0.50-0.65; P < 0.001); however, no significant protective effect was observed in the intermediate level groups (Q2 and Q3). In summary, this research demonstrated a significant association between heightened serum AG levels and increased mortality risk among ARDS patients, which was mitigated by administration of furosemide.