Michael Bauer

Sepsis – changing the paradigm

University Hospital Jena, Department of Anesthesiology and Intensive Care Medicine

Sepsis is the most common preventable cause of death in hospitals. The adoption of the new sepsis definition last year shifted the interest from systemic inflammation (SIRS) to organ dysfunction as the clinical hallmark of an inappropriate host response. Based on a better understanding of the molecular mechanisms, the focus of the new definition is no longer the inflammatory response, but rather the impairment of organ function which results not exclusively from inflammation but also from e.g. metabolic dysfunction. The paradigm thus moves away from the infection and the systemic inflammatory response, and toward that which makes sepsis so dangerous in terms of both disease dynamics and outcome: organ dysfunction. This change of perspective requires novel diagnostic tools to enable early recognition of infected patients with an increased risk of developing sepsis in clinical routine, even outside of the intensive care unit. The new definition also promotes development of new treatment strategies with improved ability to treat sepsis causally. Diagnostic uncertainty is the main driver for delays in therapy, the mis- and overuse of antibiotics, and the failure to identify patients who might benefit from adjunctive therapies. There is a need for new sepsis biomarkers that can aid in therapeutic decision making and add information about screening, diagnosis, risk stratification, and monitoring of the response to therapy. The most promising novel approaches for diagnosis of infection and the ensuing host response consist of light-based (photonic) tools as well as on transcriptomic, proteomic, or metabolic profiling. Novel approaches to sepsis diagnostics promise to transform sepsis from a single syndrome into a group of distinct ‘endophenotypes’ and help in the development of better diagnostic tools and effective adjunctive sepsis therapies.