Rationale for sequential extracorporeal therapy (SET) in sepsis.

Area of Science:

• Critical care medicine
• Nephrology
• Immunology

Background:

• Sepsis and septic shock significantly contribute to morbidity and mortality in critically ill patients.
• The clinical progression involves microbial invasion, immune response, organ damage, and dysfunction.
• Each stage presents potential therapeutic targets, including extracorporeal interventions.

Purpose of the Study:

• To explore the potential of extracorporeal therapies in managing sepsis and septic shock.
• To outline a sequential approach for applying extracorporeal therapies at different stages of sepsis progression.
• To suggest appropriate endpoints for trials evaluating extracorporeal therapies in sepsis.

Main Methods:

• Review of sepsis pathophysiology and potential extracorporeal intervention points.
• Categorization of extracorporeal therapies based on targets: pathogen removal, endotoxin adsorption, cytokine clearance, and organ support.
• Discussion of specific techniques including affinity binders, polymyxin B hemoperfusion, cytokine hemoadsorption, and various organ support modalities.

Main Results:

• Extracorporeal therapies can target specific molecules like pathogens, endotoxins, and cytokines at various stages of sepsis.
• Techniques include pathogen/endotoxin removal, non-specific cytokine adsorption, and comprehensive organ support (respiratory, cardiac, renal).
• The application sequence and timing of these therapies are crucial for efficacy.

Conclusions:

• Extracorporeal therapies offer a multi-faceted approach to sepsis management by targeting distinct pathophysiological steps.
• Future trials should focus on achieving specific therapeutic actions rather than solely on mortality endpoints.
• Optimizing the use of extracorporeal therapies requires a precise understanding of sepsis progression and targeted intervention.