Daily Sepsis Research Analysis

OBJECTIVE: The Sepsis-3 consensus statement emphasised the need for data-based approaches to organ failure assessment and use the Sequential Organ Failure Assessment (SOFA) for this purpose. We aimed to develop a framework for a data-driven update to the SOFA score for patients with sepsis. DESIGN: Systematic analysis of potential markers of organ dysfunction in a retrospective, observational study. SETTING: Intensive care units from three tertiary hospital centres in the United States, the Netherlands, and Austria were included in the study. PARTICIPANTS: 28 100 American, 5339 Dutch, and 2450 Austrian patients with suspected sepsis were included in this study. MEASUREMENTS AND MAIN RESULTS: We assessed 56 organ function variables. We applied area under curve maximisation procedures to optimise the predictive power for mortality. We chose the most predictive biomarker for existing organ dysfunction domains and added a metabolic domain. We compared the area under the receiver operating characteristic curve and the area under the precision recall curve of the data-driven approach against the current SOFA system. The novel approach outperformed the current SOFA in all domains and databases (the area under the receiver operating characteristic curve: for US patients: 0.766 vs. 0.727, mortality: 10.7%; for Dutch patients: 0.70 vs. 0.653, mortality: 22.0%; for Austrian patients: 0.704 vs. 0.665, mortality: 22.0%; all p < 0.01 for the best performing score). The precision-recall curve confirmed such observations. CONCLUSIONS: We developed and validated a framework for a data-driven update to the SOFA to identify and classify organ dysfunction in suspected septic patients. This framework can be used to revise the SOFA score and its application to the identification and classification of sepsis.

PURPOSE: Machine learning has shown promise to detect useful subgroups of patients with sepsis from gene expression and protein data. This approach has rarely been deployed in metabolomic datasets. Metabolomic data are of interest as they capture effects from the genome, proteome, and environmental. We aimed to discover metabolic sub-phenotypes of septic shock, examine their temporal stability and association with clinical outcome. METHODS: Analysis was performed in two double-blind randomized trials in septic shock (LeoPARDS (1402 samples from 470 patients) and VANISH (493 samples from 173 patients)). Patients were included soon after the onset of shock and had serum collected at up to four time points. Metabolic clusters were identified from 474 metabolites using k-means clustering in LeoPARDS and predicted in VANISH with an elastic net classifier. RESULTS: Three sub-phenotypes were found. The main determinants of cluster membership were lipid species, especially lysophospholipids. Low lysophospholipid sub-phenotypes were associated with higher circulating cytokine levels. Persistence of low lysophospholipid sub-phenotypes was associated with higher mortality compared to the high lysophospholipid sub-phenotype (LeoPARDS: cluster 2 odds ratio 3.66 (95% CI 1.88-7.20), p = 0.0001, cluster 3 2.49 (1.29-4.81), p = 0.006; VANISH: cluster 2 4.13 (1.17-15.61), p = 0.03), cluster 3 3.22 (1.09-9.92), p = 0.04, vs cluster 1). We found no heterogeneity of treatment effect for any of the trial interventions by baseline metabolic sub-phenotype. CONCLUSION: Three metabolic subgroups exist in septic shock which evolve over time. Persistence of low lysophospholipid sub-phenotypes is associated with mortality. Monitoring these subgroups could help identify patients at risk of poor outcome and direct novel therapies such as lysophospholipid supplementation. REGISTRATION: Clinicaltirals.gov Identifiers, VANISH: ISRCTN 20769191, LeoPARDS: ISRCTN12776039.

OBJECTIVE: This European Society of Intensive Care Medicine (ESICM) guideline provides evidence-based recommendations on the volume of early resuscitation fluid for adult critically ill patients. METHODS: An international panel of experts developed the guideline, focusing on fluid resuscitation volume in adult critically ill patients with circulatory failure. Using the PICO format, questions were formulated, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was applied to assess evidence and formulate recommendations. RESULTS: In adults with sepsis or septic shock, the guideline suggests administering up to 30 ml/kg of intravenous crystalloids in the initial phase, with adjustments based on clinical context and frequent reassessments (very low certainty of evidence). We suggest using an individualized approach in the optimization phase (very low certainty of evidence). No recommendation could be made for or against restrictive or liberal fluid strategies in the optimization phase (moderate certainty of no effect). For hemorrhagic shock, a restrictive fluid strategy is suggested after blunt trauma (moderate certainty) and penetrating trauma (low certainty), with fluid administration for non-traumatic hemorrhagic shock guided by hemodynamic and biochemical parameters (ungraded best practice). For circulatory failure due to left-sided cardiogenic shock, fluid resuscitation as the primary treatment is not recommended. Fluids should be administered cautiously for cardiac tamponade until definitive treatment and guided by surrogate markers of right heart congestion in acute pulmonary embolism (ungraded best practice). No recommendation could be made for circulatory failure associated with acute respiratory distress syndrome. CONCLUSIONS: The panel made four conditional recommendations and four ungraded best practice statements. No recommendations were made for two questions. Knowledge gaps were identified, and suggestions for future research were provided.