Daily Sepsis Research Analysis
Three studies advance sepsis research across prediction, pathophysiology, and clinical management. An externally validated machine learning model predicted progression to septic shock using routine ICU data with transparent SHAP explanations. Untargeted metabolomics mapped dynamic metabolic shifts (notably arginine biosynthesis) in the first ICU week, while an ED cohort showed bacteremia does not worsen hospital outcomes in suspected septic shock.
Summary
Three studies advance sepsis research across prediction, pathophysiology, and clinical management. An externally validated machine learning model predicted progression to septic shock using routine ICU data with transparent SHAP explanations. Untargeted metabolomics mapped dynamic metabolic shifts (notably arginine biosynthesis) in the first ICU week, while an ED cohort showed bacteremia does not worsen hospital outcomes in suspected septic shock.
Research Themes
- Early risk prediction in sepsis
- Metabolic phenotyping and precision nutrition in critical illness
- Clinical impact of bacteremia in suspected septic shock
Selected Articles
1. Early prediction of septic shock in ICU patients using machine learning: development, external validation, and explainability with SHAP.
Using MIMIC-IV for development and eICU-CRD for external validation, a random forest model predicted septic shock progression with AUC 0.785 and balanced accuracy 0.717. SHAP highlighted SOFA, heart rate, creatinine, SAPS II, and OASIS as key contributors, supporting interpretable, data-driven risk stratification in the ICU.
Impact: Provides externally validated, explainable prediction of septic shock from routinely collected ICU data, enabling earlier intervention. The transparent feature attributions facilitate clinician trust and adoption.
Clinical Implications: Could support real-time alerts and targeted monitoring for high-risk sepsis patients, informing timely resuscitation, hemodynamic optimization, and escalation decisions.
Key Findings
- Random forest achieved AUC 0.785, balanced accuracy 0.717, and F1 0.511 for predicting septic shock.
- External validation on eICU-CRD confirmed performance across institutions.
- SHAP identified SOFA, heart rate, creatinine, SAPS II, and OASIS as top predictors.
Methodological Strengths
- External validation using an independent ICU database (eICU-CRD)
- Model interpretability via SHAP and feature selection with LASSO
- Comparison of six ML algorithms with multiple performance metrics
Limitations
- Retrospective observational design limits causal inference and is vulnerable to residual confounding
- Moderate discrimination; generalizability beyond US ICU databases requires prospective validation
Future Directions: Prospective, multi-center impact studies integrating the model into clinical workflows, calibration for local populations, and assessment of alert-to-action timeliness and patient outcomes.
BACKGROUND: Septic shock is a severe and life-threatening complication of sepsis associated with high mortality. Early identification remains challenging due to the heterogeneous clinical presentation of patients, incomplete real-world ICU data, and the dynamic pathophysiological progression of sepsis. This study aimed to develop and externally validate machine learning (ML) models to predict the progression to septic shock in intensive care unit (ICU) patients with sepsis. METHODS: Data were extracted from two large critical care databases: MIMIC-IV (training set) and eICU-CRD (validation set). Variable selection was performed using LASSO regression. Six ML algorithms-random forest (RF), XGBoost, support vector machine, light gradient boosting machine, logistic regression, and naïve Bayes-were trained on the MIMIC-IV dataset and externally validated on the eICU dataset. Model performance was evaluated using AUC, F1 score, sensitivity, specificity, and balanced accuracy. Model interpretability was assessed using SHapley Additive exPlanations (SHAP). RESULTS: A total of 11,383 septic patients were included, of whom 2,259 in the training cohort and 1,212 in the validation cohort developed septic shock. The RF model achieved the best performance, with an AUC of 0.785, balanced accuracy of 0.717, and an F1 score of 0.511. SHAP analysis identified SOFA score, heart rate, creatinine, SAPS II, and OASIS as the most influential predictors. CONCLUSION: The proposed ML model enables early prediction of septic shock using routinely collected ICU data. SHAP-based interpretation enhances transparency and clinical interpretability. This approach may assist in timely risk stratification, support data-driven decision-making, and ultimately improve outcomes in patients with sepsis.
2. Analysis of the time-course change of acute-phase energy metabolism in critically ill patients using untargeted metabolomics.
Prospective serial metabolomics of ICU patients identified dynamic shifts in galactonic acid, ornithine, and L-arginine with pathway-level changes in arginine biosynthesis. Sepsis and non-sepsis profiles diverged, and metabolic trajectories correlated strongly with SOFA scores, suggesting targets for precision nutrition.
Impact: Links early critical illness metabolism to clinical severity with time-resolved data, uncovering arginine pathway alterations that could inform individualized nutrition strategies.
Clinical Implications: Metabolic phenotyping may guide timing and composition of nutrition and rehabilitation in sepsis, with attention to arginine-related pathways.
Key Findings
- Annotated 123 metabolites with significant time-course changes in galactonic acid, ornithine, and L-arginine over ICU days 1–7.
- Pathway analysis showed alterations in the arginine biosynthesis pathway.
- Sepsis vs. non-sepsis exhibited distinct metabolic profiles; creatine phosphate, uric acid, and creatinine were significant markers.
- In sepsis patients, metabolic changes correlated strongly with SOFA scores.
Methodological Strengths
- Prospective daily sampling over the first ICU week
- Untargeted LC/MS metabolomics with multivariate and pathway analyses
- Clinical correlation using SOFA scores
Limitations
- Small single-center case series (n=10) limits generalizability
- Exploratory design without interventional testing or replication
Future Directions: Validate metabolic signatures in larger, multi-center cohorts and test metabolically informed nutrition strategies in adaptive trials.
BACKGROUND AND AIMS: Critically ill patients are believed to experience a dynamic progression of energy metabolism according to the severity and phase of the illness. Although optimizing nutrition and physical therapy to the metabolic profile is recommended for better outcomes, the mechanisms for disease-related metabolic changes remain unclear. This study aimed to elucidate key metabolites and pathways associated with time-course metabolic changes and clinical parameters in acute-phase critically ill patients using untargeted metabolomics. METHODS: We conducted a single-center prospective case series study on critically ill adults expected to require mechanical ventilation for at least 7 days in our intensive care unit. Data collection was started within 48 h of ICU admission, and daily serum samples from day 1 to day 7 were collected. Untargeted metabolomics was performed using liquid chromatography/mass spectrometry. Statistical analyses included principal component analysis, (orthogonal) partial least squares discriminant analysis, and pathway analysis. RESULTS: Ten patients were analyzed during the study period from July 2021 to September 2022. A total of 123 metabolites were annotated by untargeted metabolomics, with significant time-course changes in galactonic acid, ornithine, and l-arginine. Pathway analysis indicated alterations in the arginine biosynthesis pathway. A subgroup analysis showed distinct metabolic profiles for sepsis and non-sepsis patients, with creatine phosphate, uric acid, and creatinine being significant markers. In sepsis patients, metabolic changes strongly correlated with the sequential organ failure assessment (SOFA) score. CONCLUSION: Using untargeted metabolomics, we annotated several metabolites and metabolic pathways strongly associated with time-course changes in the metabolic profile. In addition, it is suggested that nutritional therapy can be optimized according to specific pathophysiology.
3. Comparable Outcomes in Suspected Septic Shock: A Retrospective Study of Emergency Department Patients With and Without Bacteremia.
In 847 ED patients with suspected septic shock (28.7% bacteremic), hospital mortality, length of stay, ICU stay, and intubation rates did not differ by bacteremia status. Gram-positive vs. Gram-negative vs. mixed bacteremia showed no mortality differences.
Impact: Challenges assumptions that bacteremia portends worse outcomes in suspected septic shock, informing risk stratification and resource allocation in the ED.
Clinical Implications: Bacteremia alone may not warrant different early disposition or escalation in suspected septic shock; emphasis should remain on hemodynamic stabilization and source control guided by clinical severity.
Key Findings
- Among 847 suspected septic shock ED patients, 28.7% had bacteremia.
- No significant differences in hospital mortality, hospital LOS, ICU LOS, or intubation between bacteremic and non-bacteremic patients.
- Gram-positive, Gram-negative, and mixed bacteremia were not associated with mortality differences.
Methodological Strengths
- Large single-center cohort with clear operational definition of suspected septic shock
- Comprehensive outcome assessment across mortality, LOS, and respiratory support
Limitations
- Retrospective single-center design with predominantly univariate comparisons
- Potential misclassification of septic shock and residual confounding
Future Directions: Multi-center, adjusted analyses to validate findings and evaluate bacteremia’s role in antibiotic stewardship and disposition decisions.
BACKGROUND: Bacteremia is commonly present in patients with septic shock. Previous studies have found mixed associations between hospital outcomes and the presence of bacteremia in this patient population. OBJECTIVES: The primary aim of this study was to determine whether adult patients who present to the emergency department (ED) with suspected septic shock and who have bacteremia from ED-derived blood cultures have differences in outcomes. Secondary aims included the association of Gram-positive, Gram-negative, and mixed Gram-positive and Gram-negative bacteremia on hospital mortality. Finally, we sought to create a model to predict bacteremia based on ED variables. METHODS: We conducted a retrospective observational analysis at an urban academic center over a 5-year period between 2013 and 2018. Suspected septic shock was defined by the following: blood cultures collected, antibiotics administered, and vasopressors initiated in the ED. Hospital outcomes were compared in those with and without bacteremia. A logistic regression analysis was used to fit a model to best predict the presence of bacteremia based on ED variables. RESULTS: We analyzed 470,558 patient encounters, and 847 were classified as suspected septic shock, meeting inclusion criteria. Two hundred forty-three (28.7%) were categorized as having bacteremia. No statistical differences were detected in univariate comparisons between patients with and without bacteremia in hospital mortality, hospital length of stay, intensive care unit length of stay, or intubation during hospitalization between those with and without bacteremia. Hospital mortality was not associated with bacteremia based on subgroup analysis by Gram stain. CONCLUSIONS: Adult patients who present to the ED with suspected septic shock and have initial blood cultures that result in bacteremia experience hospital outcomes comparable with those without bacteremia.