Heterogeneity in Sepsis: New Biological Evidence with Clinical Applications

Abstract

Since the first consensus definition of sepsis almost three decades ago [1], our understanding of the clinical characteristics that prognosticate the outcome of this complex syndrome has improved [2], resulting in a simpler classification scheme [3]. The existing definitions, however, remain imprecise and the clinical diagnosis of sepsis corresponds poorly with post hoc presence of infection [4]. Furthermore, the outcome of sepsis depends on factors beyond patient signs and symptoms [5], including age [6], the infection source [7], and the timing and appropriateness of therapeutic interventions [8] (Fig. 40.1). There is currently a promising shift from predicting outcome to a pathobiology-driven understanding of the heterogeneity in the host response to sepsis, utilizing novel translational high throughput tools and analytic methods to define distinct host response subgroups. It is now well recog- nized that biological markers improve the classification of sepsis and can facilitate identification of distinct patient subclasses, or endotypes.