Daily Sepsis Research Analysis
Three impactful papers advance sepsis research across definitions, risk stratification, and infection-related obstetric care. An open-source EHR workflow reveals only fair-to-moderate agreement among major sepsis case criteria, a new sepsis-focused R-NEWS improves mortality prediction in ED patients, and a meta-analysis of twin previable PPROM quantifies high infection risks and suggests selective reduction may reduce maternal morbidity.
Summary
Three impactful papers advance sepsis research across definitions, risk stratification, and infection-related obstetric care. An open-source EHR workflow reveals only fair-to-moderate agreement among major sepsis case criteria, a new sepsis-focused R-NEWS improves mortality prediction in ED patients, and a meta-analysis of twin previable PPROM quantifies high infection risks and suggests selective reduction may reduce maternal morbidity.
Research Themes
- Sepsis case identification and definitional heterogeneity
- Early risk stratification in suspected sepsis in the ED
- Infection risks and management strategies in high-risk obstetrics
Selected Articles
1. Sepsis and septic shock case identification from electronic health records: an open-source workflow and comparison of cohorts by criteria.
An open-source end-to-end EHR workflow identified over 300,000 sepsis and 59,000 septic shock cases across 25 sites using CDC ASE, Sepsis-3, and ICD criteria. Agreement between criteria was only fair to moderate, and patients meeting both CDC ASE and Sepsis-3 were sicker with higher in-hospital mortality.
Impact: This work provides scalable, transparent infrastructure to build sepsis cohorts and demonstrates substantial definitional heterogeneity across widely used criteria.
Clinical Implications: Retrospective cohort identification for research, quality improvement, and benchmarking should apply multiple criteria or harmonize definitions to mitigate misclassification and selection bias.
Key Findings
- Developed and released open-source code for an EHR workflow implementing CDC ASE, Sepsis-3, and ICD-based criteria.
- Identified 302,112 sepsis and 59,043 septic shock patients across 25 EDs/hospitals (2012–2024).
- Only 35% (sepsis) and 45% (shock) met multiple criteria among those meeting at least one.
- Highest agreement was between CDC ASE and Sepsis-3 (sepsis κ=0.39, Jaccard=0.31; shock κ=0.53, Jaccard=0.37).
- Patients meeting both CDC ASE and Sepsis-3 were more severely ill with higher in-hospital mortality.
Methodological Strengths
- Large, multi-site EHR dataset with transparent, reusable open-source code
- Systematic comparison using Cohen's kappa and Jaccard indices; restriction to first sepsis encounter
Limitations
- Retrospective design and reliance on EHR/documentation may cause misclassification
- Single health system; generalizability to other EHRs and regions uncertain
Future Directions: External implementation across diverse health systems, prospective validation, and impact evaluation of cohort definition choices on research/QI outcomes.
BACKGROUND: Deploying clinical criteria to identify patients with sepsis from the electronic health record is challenging. We sought to build an open-source data workflow for sepsis and septic shock case identification using three distinct criteria and assess the identified cohorts. METHODS: We developed a workflow from raw data queries through case identification using the Centers for Disease Control and Prevention Adult Sepsis Event (CDC ASE), Sepsis-3, and International Classification of Diseases criteria. The workflow was then applied to patient encounters between 2012 and 2024 across 25 emergency departments and hospitals in an integrated health system. Separate cohorts of sepsis and septic shock patients by criteria were derived, restricted to a patient's first sepsis encounter, and compared. Pairwise agreement was evaluated with Cohen's kappa (κ) and Jaccard index. RESULTS: Our programming code for the complete workflow is available on a public platform. We identified 302,112 patients with sepsis and 59,043 with septic shock who met one or more of the three criteria. Multiple criteria were satisfied for only 35% of patients meeting at least one sepsis criterion and 45% of patients meeting at least one septic shock criterion. Pairwise agreement was the highest between CDC ASE and Sepsis-3 criteria for both sepsis (κ = 0.39, Jaccard index = 0.31) and septic shock (κ = 0.53, Jaccard index = 0.37). Characteristics and outcomes of patients differed across cohorts identified with the three criteria. Patients meeting both CDC ASE and Sepsis-3 criteria for sepsis and septic shock were more severely ill and had high in-hospital mortality incidence. CONCLUSIONS: Our open-source workflow is useful for individuals seeking to build and analyze sepsis and septic shock cohorts. Agreement between case criteria was fair to moderate. Clinicians, researchers, and quality improvement practitioners who identify patient cohorts with sepsis and septic shock retrospectively should consider applying multiple criteria.
2. Respiratory National Early Warning Score for 28-day mortality prediction in suspected sepsis patients in the emergency department.
In a prospective ED cohort of 1,348 adults with suspected sepsis, a five-variable R-NEWS emphasizing respiratory parameters outperformed NEWS, qSOFA, and SIRS for 7- and 28-day mortality prediction (AUC 0.76 and 0.72). Calibration was good, and internal validation supported robustness, but external validation is needed.
Impact: Provides a practical, sepsis-oriented modification of NEWS that improves short-term mortality prediction using readily available clinical parameters.
Clinical Implications: R-NEWS can support early triage, escalation decisions, and resource allocation for suspected sepsis in ED settings when used alongside clinical judgment.
Key Findings
- Developed a five-parameter R-NEWS emphasizing respiratory function (RR, supplemental O2, SBP, HR, GCS).
- Demonstrated higher discrimination than NEWS, qSOFA, and SIRS (28-day AUC 0.72; 7-day AUC 0.76).
- Good calibration (Hosmer–Lemeshow p=0.474) and consistent internal bootstrapping validation.
- High-risk R-NEWS (≥7) associated with 28-day mortality of 28.9% vs. 3.9% in low-risk (≤3).
Methodological Strengths
- Prospective cohort with predefined predictors and multivariable model development
- Internal validation via bootstrapping and head-to-head comparison with established scores
Limitations
- Single-center study; generalizability uncertain
- No external or impact analysis; AUCs moderate and may require recalibration elsewhere
Future Directions: External, multicenter validation with impact analyses on triage decisions and patient outcomes; evaluation of dynamic updates and integration into clinical workflows.
BACKGROUND: Most early warning scores were derived in heterogeneous acutely ill populations and are not specifically tailored to patients with suspected sepsis in the emergency department (ED). In sepsis, respiratory rate (RR) is frequently elevated as part of the pathophysiologic response, suggesting that sepsis-focused tools may require recalibrated RR thresholds. We therefore aimed to develop and evaluate the Respiratory National Early Warning Score (R-NEWS), a sepsis-oriented modification emphasizing respiratory parameters, to improve prediction of 28- and 7-day mortality among ED patients with suspected sepsis. METHODS: We conducted a prospective cohort study in the ED of Thammasat University Hospital, enrolling adults with suspected sepsis and excluding those with cardiac arrest or do-not-resuscitate orders. Multivariable backward stepwise logistic regression identified significant predictors of 28-day mortality, which were then used to construct the R-NEWS scoring system. Predictive performance was evaluated and compared with NEWS, qSOFA, and SIRS using the area under the receiver operating characteristic curve (AuROC). RESULTS: A total of 1,348 patients were analyzed; 28-day mortality was 13.4%. Five independent predictors were identified: respiratory rate, need for supplemental oxygen, systolic blood pressure, heart rate, and Glasgow Coma Scale. R-NEWS demonstrated good calibration (Hosmer-Lemeshow p = 0.474) and higher discrimination than NEWS, qSOFA, and SIRS. The AuROC of R-NEWS was 0.72 (95% CI, 0.68, 0.76) for 28-day mortality and 0.76 (95% CI, 0.71, 0.81) for 7-day mortality. Internal validation using bootstrapping yielded consistent results. High-risk R-NEWS (≥ 7) was associated with a 28-day mortality of 28.9%, compared with 3.9% in the low-risk group (≤ 3). CONCLUSION: R-NEWS, a simplified five-parameter score emphasizing respiratory function, demonstrated favorable performance for predicting short- and intermediate-term mortality in ED patients with suspected sepsis. Used alongside clinical judgment, R-NEWS may aid early risk stratification and sepsis management. External, multicenter validation and prospective evaluation are warranted before widespread implementation.
3. Previable PROM in twins: A systematic review and meta-analysis.
Across 286 twin pregnancies with previable PPROM, infection-related morbidity was substantial (maternal sepsis 7.8%, septic shock 1.6%). Selective reduction prolonged latency, increased gestational age and birthweight, and reduced clinical chorioamnionitis and neonatal death versus expectant management, though two-infant survival to discharge was not achieved.
Impact: Quantifies maternal infection risks, including sepsis and septic shock, in a rare high-risk obstetric condition and compares outcomes of two management strategies.
Clinical Implications: Counseling for twin previable PPROM should include explicit discussion of maternal sepsis risk and the trade-offs of selective reduction, which may reduce infectious morbidity while precluding two-infant survival to discharge.
Key Findings
- Included 45 studies totaling 286 twin pregnancies with previable PPROM.
- Maternal infection burden: clinical chorioamnionitis 33.5%, maternal sepsis 7.8%, septic shock 1.6%.
- Selective reduction vs. expectant management: longer latency (15.0±8.4 vs. 8.3±5.7 weeks) and higher GA at delivery (31.6±7.7 vs. 24.4±4.4 weeks), all P<0.001.
- Selective reduction associated with lower clinical chorioamnionitis (19.1% vs. 40.3%, P=0.008) and neonatal death (3.6% vs. 17.1%, P=0.033).
- Two-infant survival to discharge was 0% after selective reduction vs. 25.7% with expectant management.
Methodological Strengths
- Comprehensive multi-database search with pooled analyses and management-strategy subgrouping
- Focus on rare twin previable PPROM with explicit maternal infection outcomes
Limitations
- Predominantly observational data (case reports/series and cohorts) with likely heterogeneity and bias
- Potential publication bias; limited standardized definitions and reporting
Future Directions: Prospective registries and standardized reporting to better quantify maternal sepsis risk and to refine selection criteria for selective reduction in twin previable PPROM.
BACKGROUND: Previable prelabor rupture of membranes (PROM) in twin pregnancies is a rare but high-risk condition associated with substantial neonatal mortality and maternal morbidity. Management options include expectant management and selective reduction, though guidance is limited and based primarily on singleton data. Emerging reports suggest selective reduction may improve outcomes for the unaffected co-twin by prolonging latency and reducing maternal complications. OBJECTIVES: To evaluate maternal, obstetric, and neonatal outcomes in twin pregnancies complicated by previable PROM before 24 weeks of gestation, and to compare outcomes following expectant management and selective reduction. SEARCH STRATEGY: A comprehensive literature search was conducted in Medline, Embase, and Web of Science for studies published between January 1990 and September 2024. SELECTION CRITERIA: Eligible studies included case reports, case series, and cohort studies, reporting outcomes of twin pregnancies with previable prelabor rupture of membranes (PPROM) managed either expectantly or by selective reduction of the affected twin. DATA COLLECTION AND ANALYSIS: Data on maternal, obstetric, and neonatal outcomes were extracted and pooled for analysis. Subgroup analyses were performed based on management strategy: selective reduction versus expectant management. MAIN RESULTS: A total of 45 studies were included, comprising 286 twin pregnancies with previable PROM. Selective reduction was performed in 16.4% (n = 47) of the pregnancies. Across the entire cohort, no infant was discharged home alive in 32.0% of the pregnancies, one infant in 51.6%, and two infants in only 16.4%. Clinical chorioamnionitis occurred in 33.5%, maternal sepsis in 7.8%, septic shock in 1.6%, and hysterectomy in 0.8%. Compared to expectant management, selective reduction was associated with longer latency (15.0 ± 8.4 vs. 8.3 ± 5.7 weeks), higher gestational age at delivery (31.6 ± 7.7 vs. 24.4 ± 4.4 weeks), and higher birth weight (2663.6 ± 703.9 vs. 1251.3 ± 773.0 g) of the co-twin, all P < 0.001. Following selective reduction compared to expectant management, the discharge home of one live infant was more common (66.0% vs. 33.8%, P < 0.001), yet the discharge of two infants was not possible (0.0% vs. 25.7%, P < 0.001). Following selective reduction, clinical chorioamnionitis and neonatal death were lower (19.1% vs. 40.3%, P = 0.008 and 3.6% vs. 17.1%, P = 0.033, respectively). CONCLUSIONS: Twin pregnancies with PPROM are associated with high maternal and neonatal risks. Selective reduction may improve outcomes for the unaffected twin and reduce maternal morbidity. These findings underscore the need for individualized, multidisciplinary counseling and highlight the critical gaps in evidence guiding management in this rare clinical scenario.