Weekly Ards Research Analysis
This week’s ARDS literature emphasizes pragmatic negative randomized evidence against routine extracorporeal CO2 removal (ECCO2R), mechanistic advances identifying the STING–Drp1–GSDMD mitochondrial axis as a druggable pathway in sepsis-related lung injury, and pragmatic corticosteroid comparisons in COVID-19 with implications for ICU resource use. Several observational and methodological studies sharpen risk stratification (DIC, CKRT, nutrition status) and introduce quantitative diagnostics (CT
Summary
This week’s ARDS literature emphasizes pragmatic negative randomized evidence against routine extracorporeal CO2 removal (ECCO2R), mechanistic advances identifying the STING–Drp1–GSDMD mitochondrial axis as a druggable pathway in sepsis-related lung injury, and pragmatic corticosteroid comparisons in COVID-19 with implications for ICU resource use. Several observational and methodological studies sharpen risk stratification (DIC, CKRT, nutrition status) and introduce quantitative diagnostics (CT-derived focal index, S/F ratio) to personalize ventilatory strategies.
Selected Articles
1. Methylprednisolone pulse therapy compared with intravenous dexamethasone for severe COVID-19 patients: a randomized clinical trial.
Double-blind RCT (n=300) showed no difference in mortality or mechanical ventilation need between dexamethasone and pulse methylprednisolone in hospitalized COVID-19 patients, but dexamethasone was associated with a significantly shorter ICU length of stay. These pragmatic findings inform steroid selection and resource utilization.
Impact: High-quality, blinded head-to-head RCT directly informs corticosteroid choice in severe COVID-19 and impacts ICU bed utilization decisions.
Clinical Implications: Favor dexamethasone as default for hospitalized severe COVID-19 needing respiratory support unless specific indications for pulse steroids exist; expect similar hard outcomes but potential ICU-stay benefits with dexamethasone.
Key Findings
- No significant difference in mortality: 12.6% (dexamethasone) vs 15.3% (methylprednisolone); RR 0.82, P=0.50.
- No significant difference in mechanical ventilation need: 16.6% vs 21.3%; RR 0.78, P=0.30.
- ICU length of stay shorter with dexamethasone (9.5 vs 11.3 days; P<0.001).
2. Extracorporeal carbon dioxide removal for the treatment of acute hypoxaemic respiratory failure: the REST RCT.
A multicenter pragmatic RCT (n≈412) found ECCO2R-facilitated ultra-low tidal volume ventilation did not reduce 90-day mortality, conferred no short- or long-term patient benefit, increased costs, and had potential device-related harms; the trial was stopped early for futility.
Impact: Provides definitive randomized, pragmatic evidence discouraging routine ECCO2R adoption and guiding resource and device deployment decisions in acute hypoxemic respiratory failure/ARDS.
Clinical Implications: Do not routinely use ECCO2R outside trials for hypoxemic respiratory failure/ARDS; prioritize conventional lung-protective ventilation, and restrict ECCO2R to well-designed clinical studies targeting specific subgroups if justified.
Key Findings
- No reduction in 90-day mortality with ECCO2R vs standard care (41.5% vs 39.5%; RR 1.05, 95% CI 0.83–1.33).
- No short- or long-term secondary outcome benefits; higher costs and possible device complications.
- Trial stopped early for futility; enrollment challenges and site inexperience noted.
3. Inhibition of STING-induced mitochondrial Drp1/N-GSDMD-mediated MtDNA release alleviates Sepsis-induced lung injury.
Preclinical mechanistic work identifies a macrophage STING–N‑GSDMD–mtDNA positive feedback loop and STING-dependent Drp1–N‑GSDMD coupling via mitochondrial calcium that promotes pyroptosis and lung injury; disulfiram (a GSDMD inhibitor) disrupted mitochondrial N‑GSDMD localization and reduced injury in models, highlighting druggable nodes.
Impact: Identifies a previously unrecognized mitochondrial mechanism linking innate immune sensing to pyroptosis and single out STING/GSDMD/Drp1–Ca2+ coupling as translational therapeutic targets for sepsis-related lung injury and ARDS.
Clinical Implications: Supports prioritizing biomarker validation (STING/GSDMD) in ARDS cohorts and early-phase trials of GSDMD/STING modulators (with careful safety assessment) as a targeted alternative to non-specific immunosuppression.
Key Findings
- Macrophage STING–N‑GSDMD–mtDNA positive feedback loop drives inflammation and pyroptosis in LPS and COVID-19 ARDS models.
- STING promotes mitochondrial Ca2+–dependent Drp1–N‑GSDMD interaction linking fission to membrane permeabilization.
- Disulfiram inhibited mitochondrial N‑GSDMD anchoring and reduced mitochondrial permeabilization and lung injury in models.