Sepsis Phenotypes and Treatment Approaches

Understanding Sepsis Phenotyping

The American Thoracic Society defines sepsis as a clinically observable syndrome characterized by dysregulated host response to infection with organ dysfunction 1, 3
The Society of Critical Care Medicine defines subphenotype as distinct subgroups within sepsis based on shared measurable properties that can be reliably discriminated from each other 1, 4
The European Society of Intensive Care Medicine defines endotype as subphenotypes with distinct pathobiological mechanisms that may predict specific treatment responses 1, 3
The Infectious Diseases Society of America defines treatable trait as clinical characteristics/biomarkers indicating underlying mechanisms that respond to specific interventions (e.g., hyperinflammation) 1, 4

Machine learning models analyzing >25 routinely measured clinical parameters in electronic health data consistently identify four distinct sepsis subphenotypes, which demonstrate differential mortality and treatment responses 1

The American College of Chest Physicians recommends using validated 3-4 variable classifiers using readily available clinical data to reliably identify subphenotypes with differential mortality and treatment responses 2
The Society of Critical Care Medicine suggests that respiratory system compliance in ARDS patients can identify subgroups with differential response to low tidal volume ventilation 5, 2
The European Society of Intensive Care Medicine states that SOFA score quantifies organ dysfunction severity and serves as a prognostic indicator 2

The American Thoracic Society notes that clinical severity criteria alone achieve prognostic enrichment but generally fail to enrich for treatment response 1, 4, 2
The Infectious Diseases Society of America reports that ARDS subphenotypes show divergent responses to PEEP strategies, fluid therapy, simvastatin, and activated protein C 1, 5
The Society of Critical Care Medicine states that AKI subphenotypes in sepsis demonstrate different responses to vasopressin versus norepinephrine 5

The American College of Chest Physicians recommends initiating immediate treatment for sepsis using standard criteria, including administering broad-spectrum antibiotics within 1 hour 6
The Society of Critical Care Medicine suggests calculating SOFA score for severity stratification and documenting number and type of organ failures 2
The European Society of Intensive Care Medicine recommends measuring respiratory system compliance for mechanically ventilated patients 5, 2

The Infectious Diseases Society of America advises against using biomarkers to escalate or intensify antibiotic therapy, as procalcitonin and similar markers should only guide de-escalation, not escalation 7
The American College of Chest Physicians notes that delaying antibiotics for phenotyping is not recommended, as the one-hour antibiotic target supersedes all classification considerations 7, 6