Daily Sepsis Research Analysis
Three studies reshape sepsis care: a multicenter target trial emulation suggests corticosteroid effects depend on predicted organ dysfunction trajectories; a meta-analysis of RCTs indicates critical care ultrasonography may reduce mortality and fluid balance; and an RCT-only meta-analysis finds sepsis early warning systems do not improve mortality or key process outcomes, challenging current screening recommendations.
Summary
Three studies reshape sepsis care: a multicenter target trial emulation suggests corticosteroid effects depend on predicted organ dysfunction trajectories; a meta-analysis of RCTs indicates critical care ultrasonography may reduce mortality and fluid balance; and an RCT-only meta-analysis finds sepsis early warning systems do not improve mortality or key process outcomes, challenging current screening recommendations.
Research Themes
- Precision stratification of immunomodulatory therapy in sepsis
- Ultrasound-guided fluid management in critical care
- Reappraisal of sepsis screening effectiveness
Selected Articles
1. Multicenter target trial emulation to evaluate corticosteroids for sepsis stratified by predicted organ dysfunction trajectory.
Using a two-stage machine learning pipeline to subphenotype and predict organ dysfunction trajectories, the authors emulated a target trial across multiple cohorts of sepsis, pneumonia, and ARDS. The association between corticosteroid use and 28-day mortality differed by predicted trajectory and across cohorts, suggesting treatment effect heterogeneity aligned with pathobiology.
Impact: Introduces a pragmatic precision-medicine framework to tailor steroids by predicted organ dysfunction trajectories, potentially reconciling mixed trial results.
Clinical Implications: Clinicians should consider that corticosteroid benefit may depend on dynamic organ dysfunction trajectories; future protocols could incorporate early trajectory prediction to guide steroid use.
Key Findings
- Two-stage ML (subphenotyping then prediction) classified patients by organ dysfunction trajectory.
- Target trial emulation showed that corticosteroid–28-day mortality associations varied by predicted trajectory.
- Heterogeneous effects were observed across cohorts of sepsis, pneumonia, and ARDS.
Methodological Strengths
- Multicenter retrospective design with target trial emulation
- Advanced ML subphenotyping and prospective-style stratification
Limitations
- Observational emulation subject to residual confounding and misclassification
- Generalizability and implementation require prospective validation
Future Directions: Prospective, randomized trials stratified by predicted trajectories to test steroid efficacy; integration of trajectory prediction tools into clinical decision support.
2. The Effect of Early Warning Systems for Sepsis on Mortality: A Systematic Review and Meta-analysis.
Across 7 randomized trials (n=3409), sepsis early warning systems did not significantly reduce mortality, time to antibiotics, or length of stay; overall evidence certainty was low. The authors call for reconsideration of guideline recommendations that endorse universal sepsis screening.
Impact: Provides RCT-only evidence that challenges widely adopted screening policies, with potential to redirect quality-improvement resources.
Clinical Implications: Hospitals should critically appraise sepsis screening alerts and prioritize interventions with proven benefit; future trials should standardize alert logic and link to actionable protocols.
Key Findings
- Pooled mortality OR with early warning systems: 0.84 (95% CI 0.60–1.18), not significant.
- Time to antibiotics 0.08 hours faster (95% CI −0.44 to 0.28), not significant.
- Length of stay −0.27 days (95% CI −1.21 to 0.66), not significant; overall evidence graded low.
Methodological Strengths
- Restricted to randomized controlled trials with comprehensive database search
- Risk of bias and certainty assessed using Cochrane tool and GRADE; PROSPERO-registered
Limitations
- Low certainty due to bias and imprecision; heterogeneity of alert systems and workflows
- Limited reporting of downstream actions following alerts
Future Directions: Design pragmatic RCTs with standardized alert logic, integration with protocolized care, and patient-centered outcomes; evaluate targeted vs universal screening.
3. Critical Care Ultrasonography for Volume Management: A Systematic Review, Meta-Analysis, and Trial Sequential Analysis of Randomized Trials.
Across 17 RCTs (n=1765), CCUS-guided fluid management may reduce mortality (RR 0.79) and lower cumulative fluid balance within 72 hours, with uncertain effects on ventilation duration, ICU LOS, vasopressor use, AKI, and RRT due to low/very low certainty.
Impact: Synthesizes randomized evidence supporting ultrasound-guided hemodynamic management, quantifying mortality benefit and early fluid stewardship.
Clinical Implications: Incorporate CCUS into fluid decision-making algorithms, emphasizing training and protocolization while acknowledging low certainty and heterogeneity.
Key Findings
- 17 RCTs, 1765 patients: mortality RR 0.79 (95% CI 0.67–0.95).
- Reduced cumulative fluid balance up to 72 hours (MD −0.72 L; 95% CI −1.5 to +0.07 L).
- Uncertain effects on MV duration, ICU LOS, vasopressor use, AKI, and RRT (very low certainty).
Methodological Strengths
- RCT限定の統合、重複独立抽出、ランダム効果モデル
- Cochrane改変ツールとGRADEによるバイアス・確実性評価
Limitations
- Low certainty due to imprecision and indirectness; heterogeneous CCUS protocols and clinician expertise
- Outcome definitions and follow-up timing varied across trials
Future Directions: Large, pragmatic RCTs with standardized CCUS protocols and training, evaluating patient-centered outcomes and cost-effectiveness.