Daily Sepsis Research Analysis
Three high-impact studies reshape sepsis care: a multinational RCT shows personalized resuscitation targeting capillary refill time improves a hierarchical composite outcome in early septic shock; a global effort updates and validates the SOFA-2 organ dysfunction score across 3.3 million ICU encounters; and an RCT finds sodium bicarbonate does not reduce 90-day mortality in severe acidemia with AKI but lowers kidney replacement therapy use.
Summary
Three high-impact studies reshape sepsis care: a multinational RCT shows personalized resuscitation targeting capillary refill time improves a hierarchical composite outcome in early septic shock; a global effort updates and validates the SOFA-2 organ dysfunction score across 3.3 million ICU encounters; and an RCT finds sodium bicarbonate does not reduce 90-day mortality in severe acidemia with AKI but lowers kidney replacement therapy use.
Research Themes
- Personalized resuscitation and bedside physiology in septic shock
- Modernizing organ dysfunction scoring (SOFA-2) for critical illness and sepsis
- Acid-base therapy in severe acidemia with AKI: mortality vs organ support
Selected Articles
1. Personalized Hemodynamic Resuscitation Targeting Capillary Refill Time in Early Septic Shock: The ANDROMEDA-SHOCK-2 Randomized Clinical Trial.
In 1467 patients within 4 hours of septic shock, a CRT-targeted personalized resuscitation protocol achieved a win ratio of 1.16 versus usual care (95% CI 1.02-1.33; P=0.04) for a hierarchical composite of death, duration of vital support, and hospital stay. Benefits were driven mainly by shorter duration of vital support, with similar mortality proportions between groups.
Impact: This large, multinational RCT provides pragmatic evidence that bedside physiology-guided resuscitation using capillary refill time can improve patient-centered composite outcomes in early septic shock.
Clinical Implications: Implementing CRT-guided personalized resuscitation, including structured assessment of pulse pressure, diastolic pressure, fluid responsiveness, and bedside echocardiography, may reduce time on vasopressors and organ support in early septic shock. Protocolized training and workflow integration are required.
Key Findings
- Win ratio 1.16 (95% CI 1.02-1.33; P=0.04) favoring CRT-PHR for the hierarchical composite outcome at 28 days.
- Individual pairwise wins: death 19.1% vs 17.8%; duration of vital support 26.4% vs 21.1%; length of hospital stay 3.4% vs 3.2% (CRT-PHR vs usual care).
- Trial enrolled 1501 patients; 1467 analyzed across 86 centers in 19 countries; effect mainly driven by shorter duration of vital support.
Methodological Strengths
- Multinational, multicenter randomized design with protocolized CRT-guided algorithms.
- Hierarchical composite analyzed via win ratio with APACHE II stratification, enhancing clinical relevance and statistical efficiency.
Limitations
- Open-label pragmatic design with potential performance bias.
- Primary benefit driven by duration of vital support; mortality difference was small.
Future Directions: Evaluate mortality effects and implementation strategies, including automation of CRT assessment, and test CRT-PHR within sepsis subphenotypes and resource-limited settings.
2. Sodium Bicarbonate for Severe Metabolic Acidemia and Acute Kidney Injury: The BICARICU-2 Randomized Clinical Trial.
Among 627 analyzed patients with pH ≤7.20 and moderate–severe AKI, sodium bicarbonate did not change 90-day mortality (62.1% vs 61.7%; P=.91) but reduced kidney replacement therapy use (35% vs 50%; absolute difference −15.5%). No significant differences were observed in other secondary outcomes or adverse events.
Impact: Provides definitive, contemporary RCT evidence guiding acid-base therapy in critically ill patients, clarifying that routine bicarbonate does not improve survival despite reducing dialysis use.
Clinical Implications: For severe acidemia with AKI, bicarbonate infusion to target pH ≥7.30 should not be expected to reduce mortality, though it may reduce the need for kidney replacement therapy. Decisions should balance dialysis avoidance with lack of survival benefit.
Key Findings
- 90-day all-cause mortality was similar with bicarbonate vs control (62.1% vs 61.7%; P=.91).
- Kidney replacement therapy was less frequent with bicarbonate (35% vs 50%; absolute difference −15.5%).
- Open-label RCT across 43 ICUs; no significant differences in other secondary outcomes or adverse events.
Methodological Strengths
- Randomized multicenter design with clinically relevant primary endpoint and adequate follow-up.
- Robust secondary and safety assessments including KRT, organ support, and infections.
Limitations
- Open-label design may introduce performance bias.
- Findings generalize to severe acidemia with AKI; not powered for sepsis-only subgroup effects.
Future Directions: Identify subgroups that may derive survival benefit (e.g., profound hyperkalemia, specific sepsis phenotypes), and evaluate bicarbonate strategies integrated with RRT timing and fluid stewardship.
3. Development and Validation of the Sequential Organ Failure Assessment (SOFA)-2 Score.
SOFA-2 revised variables and thresholds across brain, respiratory, cardiovascular, liver, kidney, and hemostasis systems to reflect contemporary practice, achieving AUROC 0.79 (vs 0.77 for SOFA-1). Predictive validity persisted through ICU day 7. Gastrointestinal and immune domains were not incorporated due to insufficient data and content validity.
Impact: Modernizes the foundational organ dysfunction score central to sepsis definition and clinical research, using 3.34 million encounters across diverse settings with external validation.
Clinical Implications: SOFA-2 offers updated thresholds and variables aligned with current organ support, enabling more accurate risk stratification, benchmarking, and eligibility criteria for trials and sepsis surveillance.
Key Findings
- SOFA-2 improved predictive performance (AUROC 0.79; 95% CI 0.76-0.81) compared with SOFA-1 (AUROC 0.77; 95% CI 0.74-0.81).
- Updated variables and thresholds across six organ systems; integrated contemporary organ support treatments and alternative measures for low-resource settings.
- External validation across six cohorts (n≈1.24 million) confirmed performance; gastrointestinal and immune domains were not included.
Methodological Strengths
- Modified Delphi consensus integrated with federated, multi-country EHR analysis for development and validation.
- Extensive internal and external validation across over 3.3 million ICU encounters.
Limitations
- Observational data with potential residual confounding; only modest AUROC improvement vs SOFA-1.
- Gastrointestinal and immune dysfunction were not included due to data and validity constraints.
Future Directions: Prospective validation, integration into sepsis definitions and clinical workflows, evaluation of responsiveness to therapy, and development of GI/immune modules when data mature.