Conceptual Model of Sepsis as a Dysregulated Host Response: Depicting Directionality of Immunologic and Metabolic Dysregulation.

Abstract

Background Mortality from Sepsis continues to remain high in hospitalized patients worldwide. Previously, the conceptual model of sepsis was based on the systemic inflammatory immune response syndrome, an adaptive model. In 2016, a new definition of sepsis was proposed as a dysregulated host response to infection, however until now, no model has been proposed elucidating what immunologic mechanisms are dysregulated. Aim We sought to propose a new model of sepsis to elucidate evidence-based immunologic and metabolic mechanisms which are dysregulated in sepsis. Methods Evidence in the literature comparing and contrasting sepsis before and after the 2016 consensus definition of sepsis was reviewed for themes. Themes from research published post 2016, were described connecting immunologic and metabolic mechanisms in sepsis. This information further informed earlier research that has been published by the primary author. Results A new conceptual model of sepsis was developed to elucidate the current definition of sepsis as a dysregulated host response, incorporating themes uncovered in sepsis research post 2016. Conclusion The model proposed here supports clinicians in applying the current definition of sepsis to a physiological model. This can benefit clinicians by offering new ways of recognizing sepsis, and researchers by recommending a physiologic model to advance sepsis research. Keywords: Sepsis, sepsis model, immunologic dysregulation, metabolic dysregulation