Pathophysiology
According to the recently suggested definition, sepsis represents a "life-threatening organ dysfunction caused by a dysregulated host response to infection [Singer et al. JAMA 2016]. This updated definition emphasizes the primacy of the non-homeostatic host response to infection, its potential lethality, as well as the need for urgent recognition and treatment. The traditional concept of sepsis as a syndrome caused by uncontrolled injurious inflammation has thus been replaced by the current view of a multifaceted host response, entailing not only sustained inflammation, but also prolonged immune suppression [van der Poll Crit Care 2016, Hotchkiss et al. Nat Rev Immunol 2013].
Sepsis is one of the leading causes of morbidity and mortality worldwide, and the true burden of disease arising from this clinical syndrome remains unknown. Current estimates of 30 million sepsis cases and 6 million deaths per year are based on extrapolation of data on hospital-treated sepsis in high-income countries and, therefore, are most likely underestimated [Fleischmann et al. Am J Respir Crit Care Med 2016]. Long-term consequences of sepsis are increasingly recognized as a condition referred to as persistent critical illness. It may last for months and is characterized by organ dysfunction, dysfunctional host response to repeated infections, slow or even permanent cognitive decline, and loss of overall sense of well-being [Andersson et al. Annu Rev Immunol 2011, Angus JAMA 2010]. Sepsis is frequently followed by a reduced duration of healthy life expectancy, even if the patient's overall lifespan is preserved.