A clinical guide to assess the immune response to sepsis: from bench to bedside - Critical Care Science (CCS)

Over the last decade, there has been a remarkable expansion in our knowledge regarding the intricate pathological mechanisms underlying sepsis. This quintessential medical disorder, defined as a life-threatening, complex syndrome resulting from a dysregulated host immune response to infection, has prompted ongoing updates to diagnostic criteria and sepsis management and resulted in increased awareness among healthcare professionals. The global burden of sepsis highlights the disease’s importance as a major health concern and a leading contributor to mortality and critical illness worldwide.

It is widely acknowledged that the physiological derangements observed in patients with sepsis, culminating in severe multiple organ failure, predominantly stem from a combination of conflicting inflammatory and anti-inflammatory signaling pathways. However, substantial research has shown that patients with sepsis exhibit only a transient hyperinflammation phase and swiftly transition to an immunosuppressed state.⁽⁾ This biological duality has become increasingly apparent due to the increased risk of mortality (40 – 80%) and hospital-acquired infections among a significant proportion of patients with sepsis.⁽⁾ This has driven the current literature to focus increasingly on the downregulated mechanisms of immune function and concurrent septic immunoparalysis. While direct and comprehensive evidence linking mortality risk, infection risk, and intensive care unit (ICU) complications to this immunosuppressed state has not been reported, increasing evidence suggests that immunoparalysis independently contributes to poor ICU prognoses and higher mortality rates. Modulating immunoparalysis may be crucial to increase survivability in severely ill patients with sepsis.

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