Daily Sepsis Research Analysis
Three impactful sepsis studies stood out today: a multicenter prospective cohort identified an extracellular vesicle coagulolytic balance (EV-CLB) that independently predicts 90-day mortality in septic shock; an updated meta-analysis of RCTs found no mortality benefit of continuous versus intermittent meropenem infusion, though clinical cure and ICU length of stay improved; and a large multicenter analysis showed children with prearrest sepsis have markedly worse in-hospital cardiac arrest outco
Summary
Three impactful sepsis studies stood out today: a multicenter prospective cohort identified an extracellular vesicle coagulolytic balance (EV-CLB) that independently predicts 90-day mortality in septic shock; an updated meta-analysis of RCTs found no mortality benefit of continuous versus intermittent meropenem infusion, though clinical cure and ICU length of stay improved; and a large multicenter analysis showed children with prearrest sepsis have markedly worse in-hospital cardiac arrest outcomes without differences in intra-arrest diastolic blood pressure.
Research Themes
- Coagulation–fibrinolysis imbalance biomarkers in septic shock
- Beta-lactam dosing strategies (continuous vs intermittent infusion) in sepsis
- Pediatric sepsis and resuscitation outcomes after in-hospital cardiac arrest
Selected Articles
1. The Procoagulant and Fibrinolytic Balance of Extracellular Vesicles Predicts Mortality in Septic Shock Patients.
In a multicenter prospective cohort of 225 septic shock patients, the extracellular vesicle coagulolytic balance (EV-CLB)—the ratio of TF-dependent thrombin to uPA-dependent plasmin generation—was significantly higher in non-survivors and independently predicted 90-day mortality. EV-CLB outperformed individual EV procoagulant or fibrinolytic measures and correlated with SAPS II and lactate, with notable prognostic strength in Gram-negative and intra-abdominal/urinary infections.
Impact: Introduces a mechanistically anchored, EV-based composite biomarker with independent prognostic value in septic shock, potentially enabling phenotype-guided therapy addressing coagulation–fibrinolysis imbalance.
Clinical Implications: EV-CLB may support early risk stratification and guide individualized strategies (e.g., anticoagulation or antifibrinolytic modulation), though technical standardization of EV assays is needed before clinical adoption.
Key Findings
- EV-CLB at 24 h was higher in non-survivors vs survivors (median 2.78 vs 0.97 a.u., p<0.001).
- Survivors showed a significant EV-CLB decrease from H0 to H48, unlike non-survivors.
- EV-CLB independently predicted day-90 mortality after adjusting for severity and comorbidities.
- EV-CLB correlated better with SAPS II and lactate than individual EV procoagulant or fibrinolytic measures.
- Subgroup analyses showed strong prognostic value in peritonitis, biliary/urinary infections, and Gram-negative sepsis.
Methodological Strengths
- Multicenter prospective design with predefined primary outcome (day-90 mortality).
- Multivariable Cox modeling adjusting for severity markers and comorbidities; trial registered (NCT02062970).
Limitations
- Observational design limits causal inference regarding coagulation/fibrinolysis modulation.
- EV measurement standardization and technical complexity may impede near-term clinical translation.
Future Directions: Validate EV-CLB in external cohorts, standardize assays, and test EV-CLB–guided anticoagulation/antifibrinolytic strategies in adaptive trials.
2. Continuous vs. intermittent meropenem infusion in critically ill patients with sepsis: a systematic review and meta-analysis of randomized controlled trials with trial sequential analysis.
Across five RCTs (n=1,075), continuous meropenem infusion did not reduce all-cause mortality versus intermittent dosing (RR 0.89, 95% CI 0.75–1.04) but was associated with shorter ICU length of stay, higher clinical cure rates, and shorter meropenem duration. Findings refine dose–administration strategies by highlighting a lack of survival benefit while suggesting potential workflow or PK/PD advantages.
Impact: Provides updated, RCT-only evidence with trial sequential analysis, correcting earlier impressions of survival benefit from continuous infusion and guiding antibiotic administration policies.
Clinical Implications: Intermittent meropenem dosing remains appropriate when targeting mortality endpoints; continuous infusion may be reserved for PK/PD optimization or resource considerations given improved cure and ICU LOS but requires individualized assessment.
Key Findings
- Five RCTs (n=1,075) showed no mortality reduction with continuous infusion vs intermittent dosing (RR 0.89; 95% CI 0.75–1.04).
- Continuous infusion was associated with shorter ICU length of stay.
- Higher clinical cure rates and shorter meropenem therapy duration were observed with continuous infusion.
- Trial sequential analysis supports the conclusion of no mortality benefit to date.
Methodological Strengths
- Meta-analysis restricted to randomized controlled trials with trial sequential analysis.
- Pre-registered systematic review (PROSPERO CRD42024528380) and multi-database search.
Limitations
- Heterogeneity in dosing regimens and infusion protocols across RCTs.
- Mortality may be underpowered for subgroup effects; limited number of trials.
Future Directions: Large pragmatic RCTs focusing on high MIC pathogens and PK/PD target attainment, with patient-centered outcomes (mortality, organ support-free days).
3. Outcomes, Characteristics, and Physiology of In-Hospital Cardiac Arrest in Children With Sepsis.
Among 1,129 pediatric IHCAs, prearrest sepsis (16.3%) was associated with markedly reduced survival to discharge with favorable neurologic outcome (28.3% vs 58.4%; adjusted RR 0.54, 95% CI 0.43–0.68). Despite worse outcomes and higher vasoactive needs, intra-arrest diastolic blood pressures were similar between sepsis and non-sepsis groups.
Impact: Provides multicenter, adjusted evidence that pediatric sepsis dramatically worsens IHCA outcomes without differences in intra-arrest DBP, informing prevention, resuscitation planning, and postarrest care priorities.
Clinical Implications: Children with prearrest sepsis represent a high-risk IHCA phenotype warranting aggressive prevention, early deterioration detection, and enhanced postarrest hemodynamic support; DBP targets during CPR may not need sepsis-specific modification.
Key Findings
- Prearrest sepsis present in 16.3% (184/1129) of pediatric IHCAs.
- Favorable neurologic survival markedly lower with sepsis (28.3% vs 58.4%; adjusted RR 0.54, 95% CI 0.43–0.68).
- Sepsis patients had longer CPR durations and more frequent epinephrine and bicarbonate use.
- Average diastolic blood pressure during CPR did not differ between sepsis and non-sepsis groups.
- Postarrest, sepsis survivors had higher vasoactive requirements, more hypotension, and higher early mortality.
Methodological Strengths
- Large multicenter cohort with prospectively designed data capture and adjusted analyses.
- Clinically meaningful outcomes including favorable neurologic survival and intra-arrest physiology.
Limitations
- Secondary analysis; exposure to sepsis was not randomized and residual confounding is possible.
- Lack of granular infection source/pathogen data to explain physiologic differences.
Future Directions: Develop sepsis-specific IHCA prevention bundles and test postarrest hemodynamic strategies in randomized or adaptive trials for this high-risk phenotype.