Daily Sepsis Research Analysis
Analyzed 8 papers and selected 3 impactful papers.
Summary
Across three multicenter studies, new evidence refines how we risk-stratify and manage sepsis. Obesity markedly increases the risk of early sepsis-associated ARDS, antimicrobial delivery delays hinge on distinct workflow bottlenecks that are actionable, and older adults exhibit an early, persistent immune-inflammatory signature linked to mortality.
Research Themes
- Definition-sensitive risk of sepsis-associated ARDS in obesity
- Operational determinants of time-to-antibiotics in community-onset sepsis
- Longitudinal immunophenotyping and prognostication in older adults with sepsis
Selected Articles
1. Obesity and Early Sepsis-Associated Acute Respiratory Distress Syndrome: A Prospective Multicenter Study.
In 1,799 adults with sepsis, obesity independently increased the incidence of early SA-ARDS under both Berlin and HFNC-inclusive definitions, with robust findings after PSM/IPW. A mortality advantage for obesity was observed only under the Berlin definition and disappeared when HFNC patients were included, emphasizing definition-sensitive interpretations of the obesity paradox.
Impact: This prospective multicenter analysis clarifies obesity’s dual role—higher susceptibility without universal survival benefit—across evolving ARDS definitions, informing risk stratification and study design.
Clinical Implications: Screen high-BMI sepsis patients for early respiratory deterioration and consider proactive respiratory support. Interpret survival analyses cautiously across ARDS definitions, and tailor prevention strategies without assuming a protective obesity effect in HFNC-inclusive cohorts.
Key Findings
- Obesity independently increased SA-ARDS incidence under an HFNC-inclusive definition (adjusted OR 5.61, 95% CI 4.56–6.92; AUC 0.700).
- Risk was also higher under the Berlin definition (OR 6.66, 95% CI 5.01–8.91) and among HFNC recipients (OR 5.77, 95% CI 3.85–8.85); results were robust in PSM and IPW analyses.
- No BMI-related survival differences appeared under the HFNC-inclusive definition, whereas obesity was associated with lower 90-day mortality under the Berlin criteria, particularly in older patients with prolonged hospitalization.
Methodological Strengths
- Prospective multicenter cohort with 1,799 sepsis patients and predefined primary/secondary outcomes.
- Robust confounding control using propensity score matching and inverse probability weighting across two ARDS definitions.
Limitations
- Observational design limits causal inference; residual confounding cannot be excluded.
- Generalizability may vary across ICUs and regions; BMI-related misclassification and unmeasured lifestyle factors may bias estimates.
Future Directions: Validate HFNC-inclusive ARDS definitions across settings; test preventive respiratory strategies in high-BMI sepsis; explore mechanistic links between adiposity and lung injury.
PURPOSE: The role of obesity in sepsis-associated acute respiratory distress syndrome (SA-ARDS) remains uncertain, particularly amid evolving diagnostic criteria. We aimed to assess whether obesity differentially influences SA-ARDS incidence and mortality under the Berlin definition versus an expanded framework incorporating high-flow nasal cannula (HFNC). METHODS: This prospective multicenter cohort study included 1,799 adults with sepsis 3.0 from three ICUs. SA-ARDS was diagnosed using (1) Berlin criteria and (2) a new definition integrating HFNC. The primary outcome was incidence of SA-ARDS. Secondary outcomes included 28- and 90-day mortality in SA-ARDS patients. RESULTS: Obesity was independently associated with elevated SA-ARDS incidence under the new definition (adjusted OR 5.61, 95% CI 4.56-6.92; AUC = 0.700), with even higher risk in ARDS patients under Berlin criteria (OR 6.66, 95% CI 5.01-8.91) and HFNC recipients (OR 5.77, 95% CI 3.85-8.85). These associations remained robust in PSM and IPW analyses. However, in ARDS patients of the new definition (including HFNC patients), no survival differences were observed across BMI categories. However, under the Berlin definition, obesity patients had significantly lower 90-day mortality than underweight and normal-weight patients, particularly in the elderly and those with prolonged hospital stays (P < 0.05). CONCLUSIONS: Obesity independently increased SA-ARDS risk across both diagnostic frameworks. However, the mortality benefit (Berlin definition) was absent when using the expanded criteria incorporating HFNC. This indicates obesity drives susceptibility but confers no universal survival advantage in new ARDS cohorts.
2. Identifying Rate-Limiting Steps in the Antimicrobial Workflow for Community-Onset Sepsis.
In 3,623 patients with community-onset sepsis, time-to-antibiotics varied by workflow sequence, with the shortest times when antimicrobials were administered before culture collection. Distinct rate-limiting steps emerged by group, indicating that concurrent ordering and targeted process fixes can meaningfully shorten delivery times.
Impact: This large, prospective, multicenter study isolates modifiable bottlenecks in antimicrobial delivery, yielding immediately actionable targets for sepsis quality improvement.
Clinical Implications: Adopt concurrent ordering of antimicrobials and blood cultures to reduce time-to-antibiotics. Tailor process improvements to the identified rate-limiting step in each workflow (e.g., accelerate order-to-administration logistics in Group A; expedite initial prescribing in Group B).
Key Findings
- Median time from time zero to antimicrobial administration was 63.5 min (Group C), 87.0 min (Group A), and 115.0 min (Group B).
- Rate-limiting steps differed by workflow: prescription-to-administration (Group A), time-zero-to-prescription (Group B), and culture prescription-to-collection (Group C).
- Septic shock was associated with shorter intervals overall, except that prescription-to-administration time remained unchanged.
Methodological Strengths
- Prospective multicenter design with a large sample (n=3,623) and granular, workflow-defined timestamps.
- Comparative analysis across predefined step-sequences enabling identification of modifiable bottlenecks.
Limitations
- Observational design without direct linkage to patient-centered outcomes (e.g., mortality or length of stay).
- Potential misclassification of time zero and limited generalizability to non-Korean healthcare systems.
Future Directions: Test EHR-embedded concurrent ordering, pharmacy logistics accelerators, and protocolized culture-collection pathways in stepped-wedge or cluster RCTs to confirm outcome benefits.
OBJECTIVES: To characterise time intervals preceding antimicrobial administration in community-onset sepsis and identify rate-limiting steps. METHODS: In this multicentre prospective observational study of patients with community-onset sepsis in South Korea (June 2020-December 2023), the antimicrobial workflow was defined by five time points: time zero, blood culture prescription and collection, and antimicrobial prescription and administration. Patients were categorised into three groups by step sequence, and four key intervals were analysed. RESULTS: Among 3,623 patients (mean age 74.3 ± 13.0 years; 56.6% male), 1,838 (50.7%) were assigned to Group A (antimicrobials and cultures prescribed before culture collection), 1,517 (41.9%) to Group B (cultures obtained before antimicrobial prescription), and 268 (7.4%) to Group C (antimicrobials given before culture collection). Median time from time zero to administration was shortest in Group C (63.5 min), then Group A (87.0 min) and Group B (115.0 min). The rate-limiting step differed by group: prescription-to-administration in Group A, time-zero-to-prescription in Group B, and culture prescription-to-collection in Group C. Septic shock was associated with shorter intervals overall, except prescription-to-administration, which was unchanged. CONCLUSIONS: Rate-limiting steps in antimicrobial delivery differ by clinical workflow. Early concurrent prescription of antimicrobials and blood cultures was associated with shorter time to antimicrobial administration.
3. Longitudinal immune-inflammatory profiles and mortality in older adults with sepsis: a multicentre prospective cohort study.
Among 1,851 older adults across health, nonsevere infection, and sepsis, sepsis featured reduced cellular immune markers with elevated cytokines. These signatures were detectable on ICU day 1, persisted longitudinally, and day-1 biomarkers were associated with in-hospital mortality, supporting early immunophenotypic risk stratification.
Impact: This large, multicenter cohort provides longitudinal immunophenotyping in older sepsis, linking early immune patterns to mortality and bridging pathophysiology with prognostication.
Clinical Implications: Consider early immune monitoring in older sepsis patients to inform prognosis and tailor supportive or immunomodulatory strategies pending interventional validation.
Key Findings
- Sepsis in older adults was associated with lower circulating cellular immune markers (e.g., lymphocytes and T cells) and higher cytokine levels compared with nonsevere infection and healthy controls.
- These immune-inflammatory separations were evident on ICU day 1 and remained observable with available follow-up measurements through day 7.
- Day-1 biomarkers were associated with in-hospital mortality based on Cox regression, suggesting prognostic utility.
Methodological Strengths
- Prospective multicenter cohort spanning healthy controls, nonsevere infection, and sepsis with comprehensive immune profiling.
- Use of multivariable regression and linear mixed-effects models for adjusted cross-sectional and longitudinal analyses.
Limitations
- Observational design precludes causal inference and is subject to residual confounding.
- Potential missingness in scheduled longitudinal measurements and limited generalizability beyond ICU settings.
Future Directions: Derive and validate parsimonious immune signatures for bedside risk stratification and test targeted immunomodulatory interventions in older sepsis populations.
BACKGROUND: Older adults are at high risk of sepsis, but the immune-inflammatory features distinguishing sepsis from nonsevere infection and their prognostic relevance remain incompletely defined. We aimed to characterize immune-inflammatory profiles across the older adult infection spectrum and evaluate their longitudinal association with in-hospital mortality. METHODS: In this multicentre prospective observational cohort, 1,851 participants aged ≥ 60 years were enrolled, including healthy controls, patients with nonsevere infection, and patients with sepsis. Immune-cell subsets, cytokines, complement components, and routine laboratory indices were assessed. Adjusted cross-sectional comparisons were performed using multivariable linear regression. Among patients with sepsis, model-estimated longitudinal profiles from intensive care unit (ICU) day 1 to day 7 were analysed using linear mixed-effects models among available scheduled measurements, and day-1 biomarkers associated with in-hospital mortality were evaluated using Cox regression. RESULTS: The cohort included 524 healthy controls, 511 patients with nonsevere infection, and 816 patients with sepsis. Across the infection spectrum, sepsis was characterized by progressively lower circulating lymphocyte, T-cell, cluster of differentiation 8 (CD8 CONCLUSIONS: In older adults, sepsis was associated with an adjusted circulating immune-inflammatory pattern characterized by lower cellular immune markers and higher cytokine levels. This separation was evident on ICU day 1 and remained observable among patients with available follow-up measurements. Given the observational design, these associations should not be interpreted as causal.